Full Chapter Endocrine Emergencies Recognition and Treatment Contemporary Endocrinology 2Nd Edition Chaim Vanek PDF

Endocrine Emergencies: Recognition
and Treatment (Contemporary

Endocrinology) 2nd Edition Chaim
Vanek
Visit to download the full and correct content document:
https://textbookfull.com/product/endocrine-emergencies-recognition-and-treatment-co
ntemporary-endocrinology-2nd-edition-chaim-vanek/
More products digital (pdf, epub, mobi) instant
download maybe you interests ...
Endocrine Emergencies Recognition and Treatment Lynn

Loriaux And Chaim Vanek
https://textbookfull.com/product/endocrine-emergencies-
recognition-and-treatment-lynn-loriaux-and-chaim-vanek/
Endocrine and metabolic medical emergencies a clinician

s guide Second Edition Matfin
https://textbookfull.com/product/endocrine-and-metabolic-medical-
emergencies-a-clinician-s-guide-second-edition-matfin/
Endocrine Disrupting Chemicals induced Metabolic

Disorders and Treatment Strategies 3rd Edition Ilan
Kapoor
https://textbookfull.com/product/endocrine-disrupting-chemicals-
induced-metabolic-disorders-and-treatment-strategies-3rd-edition-
ilan-kapoor/
Islamophobia and Psychiatry: Recognition, Prevention,

and Treatment H. Steven Moffic
https://textbookfull.com/product/islamophobia-and-psychiatry-
recognition-prevention-and-treatment-h-steven-moffic/
Emergencies in Supportive and Palliative Care 2nd
Edition Currow
https://textbookfull.com/product/emergencies-in-supportive-and-
palliative-care-2nd-edition-currow/
Pediatric Endocrinology and Inborn Errors of Metabolism

2nd Edition Kyriakie Sarafoglou
https://textbookfull.com/product/pediatric-endocrinology-and-
inborn-errors-of-metabolism-2nd-edition-kyriakie-sarafoglou/
Arrhythmia Recognition The Art of Interpretation 2nd

Edition Garcia
https://textbookfull.com/product/arrhythmia-recognition-the-art-
of-interpretation-2nd-edition-garcia/
Acne Scars: Classification And Treatment 2nd Edition

Antonell Tosti
https://textbookfull.com/product/acne-scars-classification-and-
treatment-2nd-edition-antonell-tosti/
Endocrinology and Systemic Diseases Piero Portincasa
https://textbookfull.com/product/endocrinology-and-systemic-
diseases-piero-portincasa/
Contemporary Endocrinology
Series Editor: Leonid Poretsky
Lynn Loriaux
Chaim Vanek
Editors
Endocrine
Emergencies
Recognition and Treatment
Second Edition
Series Editor
Leonid Poretsky
Division of Endocrinology
Lenox Hill Hospital
New York, NY, USA
More information about this series at http://www.springer.com/series/7680

Lynn Loriaux • Chaim Vanek
Editors
Endocrine Emergencies
Recognition and Treatment
Second Edition
Editors
Lynn Loriaux Chaim Vanek
Department of Medicine Department of Medicine
Oregon Health and Science University Oregon Health and Science University
Portland, OR Portland, OR
USA USA
ISSN 2523-3785 ISSN 2523-3793 (electronic)

ISBN 978-3-030-67454-0 ISBN 978-3-030-67455-7 (eBook)
https://doi.org/10.1007/978-3-030-67455-7
© Springer Nature Switzerland AG 2021

This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part of
the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation,
broadcasting, reproduction on microfilms or in any other physical way, and transmission or information
storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology
now known or hereafter developed.
The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication
does not imply, even in the absence of a specific statement, that such names are exempt from the relevant
protective laws and regulations and therefore free for general use.
The publisher, the authors and the editors are safe to assume that the advice and information in this book
are believed to be true and accurate at the date of publication. Neither the publisher nor the authors or the
editors give a warranty, expressed or implied, with respect to the material contained herein or for any
errors or omissions that may have been made. The publisher remains neutral with regard to jurisdictional
claims in published maps and institutional affiliations.
This Springer imprint is published by the registered company Springer Nature Switzerland AG
The registered company address is: Gewerbestrasse 11, 6330 Cham, Switzerland
Series Editor Foreword
Endocrine emergencies are too important to be left exclusively to endocrinologists.

For this reason, the second edition, edited by Drs. Lynn Loriaux and Chaim Vanek,
is of immense value for all practicing physicians regardless of their specialty. In this
monograph, a stellar group of authors addresses in detail a variety of endocrine
conditions that need to be recognized early and managed urgently.
The topics include not only the diagnoses that are traditionally considered to be
endocrine emergencies (e.g., those of acute hormonal insufficiency or excess), but
also a number of dangerous infectious complications that may afflict patients with
endocrine disease, particularly with diabetes (e.g., necrotizing soft tissue infections,
mucormycosis, emphysematous cholecystitis, and pyelonephritis).
In summary, this book authored by an outstanding multidisciplinary writing crew
(in addition to endocrinologists—both adult and pediatric—the contributing authors
include gynecologists, infectious disease specialists, and nephrologists) represents
an invaluable tool for all students and practitioners of medicine.
New York, NY, USA Leonid Poresky
v
Preface
Medical emergencies in the field of endocrinology encompass thyroid, adrenal,

pituitary, and other hormonal systems. These “endocrine emergencies” require spe-
cific interventions, beyond normal resuscitation protocols, within 2 to 24 hours to
successfully care for a patient. The purpose of this book is to detail the management
of endocrine, diabetic, and metabolic emergencies by consensus of experts in the
field. We believe that this book will bring the topic areas up to date, set a standard
for diagnosis and treatment in each category, and comprehensively cover the area
for the practicing clinician.
Each chapter begins with a Précis that presents, in concentrated form, what the
physician needs to know to begin the evaluation and emergency treatment of known
endocrine emergencies, such as facial pain in a patient with poorly controlled dia-
betes (mucormycosis), or the extreme urgency of a patient presenting with fever and
generalized lymphadenopathy (adrenal insufficiency).
This is followed by an extended discussion of disease pathophysiology that can
be read after initial treatment has begun. Extended discussions will reveal why
David bested Goliath with a stone (pituitary apoplexy), explain paroxysms of palpi-
tations and diaphoresis after consuming gruyere cheese with merlot (pheochromo-
cytoma), and how to elicit “main d’accoucheur” sign for the assessment of acute
hypocalcemia.
This revised edition has new updates in the evaluation and management of adre-
nal insufficiency, hypercalcemia, hyperchylomicronemia, and edits in the recogni-
tion/care of other endocrine emergencies.
Portland, OR, USA Lynn Loriaux

Chaim Vanek
vii
Contents
1 Acute Adrenal Insufficiency�� 1

Lynn Loriaux
2 Diabetic Ketoacidosis and Hyperosmolar Hyperglycemic
Syndrome�� 9
Beatrice C. Lupsa and Silvio E. Inzucchi
3 Hypoglycemia �� 27
Philip E. Cryer
4 Necrotizing Soft Tissue Infections�� 37
J. Stone Doggett and Brian Wong
5 Malignant (Necrotizing) Otitis Externa �� 43
6 Mucormycosis�� 51
7 Emphysematous Cholecystitis�� 59
8 Emphysematous Pyelonephritis�� 65
9 Thyrotoxic Crisis: Thyroid Storm�� 71
John J. Reyes-Castano and Kenneth Burman
10 Myxedema Coma �� 93
Ines Donangelo and Glenn D. Braunstein
11 Acute Suppurative Thyroiditis�� 103
ix
x Contents
12 Hyponatremia: SIADH�� 109

Raghav Wusirika and David H. Ellison
13 Diabetes Insipidus�� 123
Raghav Wusirika and David H. Ellison
14 Pheochromocytoma Hypertensive Crisis �� 137
Vitaly Kantorovich and Karel Pacak
15 Hypocalcemia �� 147
Robert Klein and Chaim Vanek
16 Hypercalcemia�� 159
Robert Klein and Chaim Vanek
17 Pituitary Apoplexy �� 173
Pouyan Famini and Shlomo Melmed
18 Ovarian Hyperstimulation Syndrome (OHSS) �� 209
Robert L. Barbieri
19 Ambiguous Genitalia in the Newborn�� 223
Selma F. Witchel and Walter L. Miller
20 Porphyrias: Acute Manifestations�� 239
Akshata Moghe and Karl E. Anderson
21 Acute Pancreatitis Due to Hyperchylomicronemia�� 257
P. Barton Duell
Index�� 277
Contributors
Karl E. Anderson, MD Preventive Medicine and Population Health, University of

Texas Medical Branch, Galveston, TX, USA
Robert L. Barbieri, MD Department of Obstetrics and Gynecology, Brigham and
Women’s Hospital, Harvard Medical School, Boston, MA, USA
Glenn D. Braunstein, MD Medicine/Endocrinology, Cedars-Sinai Medical
Center, Los Angeles, CA, USA
Kenneth Burman, MD Endocrine Sections, Georgetown University Medical
Center/MedStar Washington Hospital Center, Washington, DC, USA
Philip E. Cryer, MD Barnes-Jewish Hospital, St. Louis, MO, USA
J. Stone Doggett, MD Division of Infectious Disease, Oregon Health and Science
University, Portland, OR, USA
Ines Donangelo, MD Department of Medicine, David Geffen School of Medicine,
University of California Los Angeles, Los Angeles, CA, USA
P. Barton Duell, MD Division of Endocrinology, Diabetes, and Clinical Nutrition,
Oregon Health and Science University, Portland, OR, USA
David H. Ellison, MD Nephrology and Hypertension, Oregon Health and Science
Pouyan Famini, MD Division of Endocrinology, Diabetes, and Metabolism,
Cedars-Sinai Medical Center, Los Angeles, CA, USA
Silvio E. Inzucchi, MD Section of Endocrinology, Yale University School of
Medicine, Yale-New Haven Hospital, New Haven, CT, USA
Vitaly Kantorovich, MD Division of Endocrinology and Metabolism, University
of CT Health Center, Farmington, CT, USA
Robert Klein, MD Division of Endocrinology, Diabetes and Clinical Nutrition,
xi
xii Contributors
Lynn Loriaux, MD, PhD Department of Medicine, Oregon Health and Science
Beatrice C. Lupsa, MD Section of Endocrinology, Yale University School of
Medicine, Yale-New Haven Hospital, New Haven, CT, USA
Shlomo Melmed, MD Division of Endocrinology, Diabetes, and Metabolism,
Cedars-Sinai Medical Center, Los Angeles, CA, USA
Walter L. Miller, MD Department of Pediatrics, Center for Reproductive Sciences,
University of California, San Francisco, San Francisco, CA, USA
Akshata Moghe, MD, PhD University of Pittsburgh Medical Center,
Pittsburgh, PA, USA
Karel Pacak, MD, PhD, Dsc Eunice Kennedy Shriver National Institute of Child
Health and Human Development, National Institutes of Health, Bethesda, MD, USA
John J. Reyes-Castano, MD Section of Endocrine, Medstar Washington Hospital
Center, Washington, DC, USA
Chaim Vanek, MD Division of Endocrinology, Diabetes and Clinical Nutrition,
Selma F. Witchel, MD Division of Pediatric Endocrinology, UPMC Children’s
Hospital of Pittsburgh, University of Pittsburgh, Pittsburgh, PA, USA
Brian Wong, MD Division of Infectious Disease, Oregon Health and Science
Raghav Wusirika, MD Division of Nephrology, Oregon Health and Science
Chapter 1
Acute Adrenal Insufficiency
Lynn Loriaux
Précis
1. Clinical setting: Shock resistant to volume and vasopressor resuscitation

2. Diagnosis:
(a) History: Important complaints include weight loss, syncope, hypoglycemia,
fatigue, and unexplained abdominal pain. Recent supraphysiological gluco-
corticoid steroid treatment or recent history of pituitary or hypothalamic dis-
ease. Adrenal surgery, abdominal trauma, unexplained flank pain associated
with anticoagulation, and bleeding diathesis syndromes increase the likeli-
hood of primary adrenal failure. Medications that interfere with glucocorti-
coid synthesis, secretion, and action are ketoconazole, etomidate, and
mifepristone (RU-486).
(b) Physical examination: Fever, orthostatic hypotension, hyperpigmentation of
the skin, vitiligo, and lymphadenopathy. Calcification of auricular cartilage
(“petrified ear”) is a sign of adrenal insufficiency.
(c) Laboratory values: A total plasma cortisol of less than 20 μg/dL, hyponatre-
mia, hypoglycemia, relative lymphocytosis, eosinophilia, prerenal azotemia,
and mild to moderate anion gap metabolic acidosis are common.
(d) Imaging: Abnormalities of the hypothalamus/pituitary gland and abnormali-
ties of adrenal size. Bilaterally small adrenal glands can be the result of
autoimmune adrenal destruction or adrenal suppression. Large adrenal
glands are caused by infection, infarction, infiltration, and hemorrhage.
3. Treatment: In addition to the standard treatment for shock, the treatment for
acute adrenal insufficiency is an intravenous replacement of hydrocortisone in a
L. Loriaux (*)
Department of Medicine, Oregon Health and Science University, Portland, OR, USA
e-mail: loriauxl@ohsu.edu
© Springer Nature Switzerland AG 2021 1

L. Loriaux, C. Vanek (eds.), Endocrine Emergencies, Contemporary Endocrinology,
https://doi.org/10.1007/978-3-030-67455-7_1
2 L. Loriaux
dose that replicates the plasma cortisol levels associated with critical illness. The
standard dose is 50 mg hydrocortisone intravenously every 6 h until the crisis is
past. If the pretreatment plasma cortisol is greater than 20 μg/dL, the cortisol
administration can be discontinued when the crisis resolves. If the pretreatment
cortisol level is less than 20 μg/dL, the intravenous dose of hydrocortisone should
be reduced to an oral dose of 12–15 mg/m2/day until the diagnosis of adrenal
insufficiency can be confirmed or excluded. It can require 12 h following the first
dose of hydrocortisone before the first therapeutic effects are clinically manifest.
Acute Adrenal Insufficiency
There are two forms of acute adrenal insufficiency. Primary (Addison’s disease)
adrenal insufficiency is associated with destruction of both adrenal glands.
Autoimmunity, infection, infiltration, infarction, and hemorrhage are common eti-
ologies. Both cortisol and aldosterone are deficient. Secondary acute adrenal insuf-
ficiency is associated with ACTH deficiency caused by hypothalamic or pituitary
dysfunction. Only cortisol is deficient. Aldosterone secretion, regulated by the
renin–angiotensin system, is normal in secondary adrenal insufficiency.
Thomas Addison (1790–1860) was born in Longbenton Village, 4 miles north-
east of Newcastle upon Tyne, England. He went to medical school at the University
of Edinburgh and graduated with a thesis on syphilis and “hydra guram” (G = hydra-
guros = “silver water” = mercury). He went to London, became an expert on sexu-
ally transmitted disease, was licensed by the London College of Physicians in 1819,
and opened a practice. On March 15, 1849, at a meeting of the South London
Medical Society, Addison presented his observations on a group of anemic patients
with a unique hyperpigmentation of the skin:
“The discoloration pervades the whole surface of the body, but is most manifest
on the face, neck, shoulders, and extremities.” The condition was uniformly fatal.
All patients that had postmortem examinations revealed destructive lesions of the
adrenal glands [1–3].
The clinical syndrome defined by lack of cortisol and aldosterone was first
described by Lipsett and Pearson:
“We have withdrawn cortisone from adrenalectomized patients in the attempt to
maintain them without any steroid hormone administration. It soon became appar-
ent that this was not possible. When cortisone was withdrawn, clinical collapse
developed promptly. Within 24 h of cortisone withdrawal, the patient complained of
malaise, lethargy, anorexia, and weakness. At 48 h, the patient noted giddiness in
the upright position and such profound weakness that he was unwilling to leave the
bed. At 72 h, the patient was usually unable to take food, and nausea, vomiting, diar-
rhea, and stupor frequently ensued. The blood pressure fell but not to shock levels
as long as the patient remained horizontal. The patient developed a gaunt and ashen
appearance, the skin was cold and gray, the pulse weak, and it appeared that death
would soon follow. Administration of cortisone at this time brought about dramatic
clinical improvement usually within 12 h, so that the patient was ready to eat and to
ambulate, and he felt well” [4, 5] (Fig. 1.1).
1 Acute Adrenal Insufficiency 3
Effect of withdrawal of cortisone
In adrenal ectomized man
1.8.0 65 103346
Prostate Co
Cortisone
Acetate P.O
MGS/Day
100
50
0
MEQ/ L
135
130
Serum
125 sodium
120
MEQ/ 24 HR
0
25
Urinary
50 sodium
75
Liters/ day
3 Urinary
volume
2
1
0
Kg
60
59
58
57
56
Cells /mm3
400
Cosinophiles
300
200
100
0
1 2 3 4 5 6 7 8 9 10
Fig. 1.1 The syndrome of acute glucocorticoid deficiency produced in an adrenalectomized per-
son. (Reproduced from Pearson et al. [4], 543–544; 1956)
4 L. Loriaux
Adrenal crisis is characterized by cardiovascular collapse unresponsive to the

administration of catecholamines. The catecholamine resistance is caused by the
failure of catecholamine receptor biosynthesis [6, 7]. Without glucocorticoid, cate-
cholamine receptor biosynthesis fails at transcription.
The Adrenal Response to Stress
The first to investigate the response of the adrenal gland to critical illness was Melby
and Spink in 1958 [8]. These investigators measured plasma cortisol in 20 patients
with sepsis and in 13 normal control subjects. Plasma cortisol in septic patients was
elevated, 63 ± 30 μg/dL, compared to 13 ± 4 in normal subjects.
The concept that the “stress induced rise in cortisol is needed to survive stress”
has been addressed in two studies. The first was done by Udelsman et al. [9] using
rhesus monkeys. Udelsman studied three groups of adult male monkeys. All were
adrenalectomized. All were treated with replacement doses of cortisol and fludro-
cortisone. The fourth group underwent a “sham adrenalectomy.” One day before a
planned surgical stress, cholecystectomy, the replacement glucocorticoid dose was
changed to “ten times normal” in group one, “normal” in group two, and “1/10
normal” in group three. Group 4 underwent a “sham cholecystectomy.” In groups 1
and 2, there were no changes in blood pressure, heart rate, or electrolytes. The group
3 animals, however, did not do well. Three of the nine animals died in the periopera-
tive period. The authors contend that:
The physiologically replaced group was hemodynamically indistinguishable from either
the supraphysiological replaced or sham-adrenalectomy-placebo group, both before and
after cholecystectomy. The mortality rates were identical in the supraphysiological and
physiologically replaced groups (14 %) and were not significantly different from those in
the sham-adrenalectomy-placebo group. In contrast, the sub-physiologically replaced mon-
keys developed marked hemodynamic instability, with significant reduction (P < 0.05) in
mean systemic blood pressure, cardiac index, systemic vascular resistance index, and left
ventricular stroke work index. Surgical stress amplified this instability and resulted in a 30
% perioperative mortality rate (P < 0.05) when compared with that in the sham-
treated group).
These findings demonstrate that, at minimum, physiologic glucocorticoid

replacement is both necessary and sufficient for primates to tolerate surgical stress.
The second study was published by Kehlet and Binder in 1973 [10]. One hun-
dred and four patients chronically treated with glucocorticoid were studied. All had
an elective surgical procedure. Seventy-four operations such as colectomy and sple-
nectomy were classified as major surgical procedures. The remainder was classified
as minor procedures. Fourteen normal individuals underwent minor surgery and
served as control subjects. Glucocorticoid therapy was removed 36 hours before the
scheduled operation. The operations were done without any glucocorticoid supple-
mentation. Blood pressure and heart rate were measured every 5 min during the
operation, and plasma cortisol measurements were made at 1, 4, 7, 12, and 14 hours
after the beginning of the surgical procedure. Glucocorticoid treatment was reiniti-
ated 72 hours after the procedures. In the major surgery group, 37 of 74 patients had
a subnormal cortisol response to surgery with hypotension in 18 of 74 patients, but
all recovered without an urgent need for glucocorticoids.
The lesson from these studies is that the most important thing the physician can
do to prevent acute adrenal insufficiency during stress in patients at risk for adrenal
insufficiency (known/presumed Addison’s or secondary insufficiency from chronic
steroid usage) is to ensure that adequate glucocorticoid is “on board” 2 to 12 hours
before the stress is introduced. One hundred milligrams of hydrocortisone will suf-
fice, and the patient should be returned to their regular hydrocortisone dose once in
stable postoperative recovery. The routine doubling or tripling of glucocorticoids
dosages for several days after surgical procedures is unnecessary.
The Cortrosyn® Stimulation Test
The diagnosis of adrenal insufficiency has rested upon the interpretation of the
Cortrosyn® (synthetic ACTH—adrenocorticotropic hormone) stimulation test.
Cortrosyn® is the first 24 of the 39 amino acids in the full ACTH peptide. A 250-μg
intravenous dose of Cortrosyn® is followed by plasma cortisol measurements at
fixed intervals of 30 and 60 min. The minimum normal Cortrosyn® stimulated
value is 18–20 μg/dL at 60 minutes [11]. An additional measure of normal response
has been the magnitude of the rise of plasma cortisol in response to Cortrosyn®. A
delta change between the basal and stimulated levels of less than 5–9 μg/dL, depend-
ing on the report, is considered an abnormal response to the Cortrosyn® stimulation
test. However, since the delta change is inversely related to the basal cortisol con-
centration [12, 13], this criterion is now rarely applied.
There are several clinical situations that can complicate the interpretation of the
Cortrosyn® test. The first is the acute loss of adrenocorticotropic hormone (ACTH)
secretion. For example, acute pituitary stalk resection from surgery or trauma will
not reliably result in abnormal values in the Cortrosyn® test for up to 12 days,
reflecting time for the adrenal glands to atrophy after ACTH hormone stimulation is
acutely withdrawn [14]. Second, circulating cortisol is bound to cortisol-binding
globulin (CBG) (70%) and albumin (20%). Ten percent of circulating cortisol is
free, i.e., not protein bound. At a total cortisol level of 20 μg/dL, 4 μg of cortisol is
bound to 4 g of albumin. If the plasma albumin level is reduced to 2 g/dL, only 2 μg
of cortisol will be albumin bound, and the total plasma cortisol level will fall by
2 μg/dL. This will alter the “cut-off” value [15] (Fig. 1.2). It is common for critically
ill patients to have reduced circulating albumin levels. The result is an increased
number of false-positive tests (failing to stimulate to 18–20 μg/dL) in the critically
ill. This same concept applies to changes in CBG concentrations which cause even
bigger changes in total plasma cortisol. A measurement of free cortisol levels is
helpful in this scenario.
6 L. Loriaux
Bound to corticosteroid-
24 binding globulin
Cutoff for
23 cosyntropin
Bound to albumin stimulation
22 test
Free
21
20
19
18
17
16
Plasma cortisol level (mg/dl)
15
14
13
12
11
10
9
8
5
4
0
Normal Stressed Stressed with
hypoalbuminemia
Circulating Plasma Cortisol Levels in a Normal Person, A
Stress Person, and a Stresses Person with Hypoalbuminemia.
Approximately 10 percent of cortisol is present in the free
(bioactive) state, unbound to protein; 20 percent is loosely
bound to albumin; and 70 percent is tightly bound to cortisol-
binding globulin. Binding to cortisol-binding globulin is nearly
saturated at plasma cortisol levels in the range of 15 to 18mg
per deciliter (413.8 to 496.6 nmol per liter). With stress and
hypoalbuminemia, the maximal total cortisol measurement will
fall below that in persons with a normal albumin concentration
and, often, below the traditional cutoff level for the co-
syntropin stimulating test, even though the level of free,
bioactive cortisol is the same in these two groups and is
appropriate for the clinical situtation. To convert values to
nanomoles per liter, multiply by 27.6
Fig. 1.2 The effects of hypoalbuminemia on the Cortrosyn® stimulation tests. (Reprinted from
Loriaux [15])
∆ cortisol max fast 60 min. p.j.l n mol/1
400
10 mg ACTH (77%) 30 mg ACTH

20 mg ACTH (94%)
300
100 mg CRH (76%)
5 mg ACTH (60%)
200 30 mg CRH (53%)
100
2.5 mg ACTH (12%)
50 100 150 200 250 300 350
Peak ACTH levels ng/t
Fig. 1.3 The correlation between maximum serum cortisol and dose of human ACTH. Note the
serum ACTH levels at the Vmax, plateaued portion of the curve
All of the baseline clinical data that we depend upon to interpret the Cortrosyn®
stimulation test were determined with a Cortrosyn® dose of 250 μg. This is a maxi-
mally stimulating dose that is well out on the Vmax (maximum velocity), plateaued
portion of the dose response curve (Fig. 1.3). If the Cortrosyn® dose is reduced so
that it is on the rapidly rising part of the curve, the coefficient of variation of the test
increases, and the results are less precise [16]. A 1-μg ACTH stimulation test has
been proposed as better than the 250 μg test for identifying patients with what is
thought to be a partially functioning pituitary gland [16]. However, this author
strongly advises against the use of the 1-μg dose as it will lead to incorrectly identi-
fying patients as having adrenal insufficiency. Furthermore, Cortrosyn® is approved
by the US Food and Drug Administration (FDA) at only 250 μg dose for the evalu-
ation of adrenal insufficiency.
Conclusion
The diagnosis of acute adrenal insufficiency is a clinical one: shock poorly respon-
sive to volume and vasopressor therapy. All patients with this syndrome should be
treated with 200 mg of hydrocortisone given in 50 mg intravenous boluses at 6-hour
intervals. Treatment should be continued until the hypotension is resolved. Twelve
hours after the initiation of glucocorticoids, the patient will have a vigorous diuresis
of the fluids given at an initial resuscitation; serum osmolality must be closely
8 L. Loriaux
monitored. Intravenous desmopressin (DDAVP) is useful to prevent excessive water

loss [17].
When can the cortisol be discontinued? The most useful tool in making this deci-
sion is the total plasma cortisol measured before glucocorticoid treatment is initi-
ated. Patients with values over 20 μg/dL can have the hydrocortisone discontinued
over a few days. Those with total plasma cortisol levels less than 20 μg/dL should
have the dose reduced over a period of several days to an oral replacement dose of
12–15 mg/m2 and kept at that dose until primary or secondary adrenal insufficiency
can be excluded with a Cortrosyn® test.
High-dose steroids for several days are used in serious infections to treat the
inflammatory component of the immune response; this is a separate clinical situa-
tion from acute adrenal crisis [18].
References
1. Pearce JMS. Thomas Addison (1793 – 1860). J R Soc Med. 2004;97:297.

2. Addison T. Chronic suprarenal insufficiency, usually due to tuberculosis of suprarenal capsule.
London Med Gazette. 1849;43:717–8.
3. Addison T. On the constitutional and local effects of disease of the supra-renal capsules.
London: Samuel Highley; 1855.
4. Pearson OH, et al. Clinical and metabolic studies of bilateral adrenalectomy for advanced
cancer in man. Surgery. 1953;34:543–56.
5. Lipsett MB, Pearson OH. Pathophysiology and treatment of adrenal crisis. N Engl J Med.
1956;254:511–4.
6. Davies AO, Lefkowitz RJ. Regulation of B-Adrenergic receptors by steroid hormones. Annu
Rev Physiol. 1984;46:119–30.
7. Collins S, Bolanowski MA, Caron MG, Lefkowitz RJ. Genetic regulation of B-Adrenergic
receptors. Annu Rev Physiol. 1989;51:203–15.
8. Melby JC, Spink WW. Comparative studies in adrenal cortisol function and cortisol metabolism
in healthy adults and in patients with shock due to infection. J Clin Invest. 1958;37:1791–7.
9. Udelsman R, Loriaux DL, Chrousos GP. Reevaluation of the role of glucocorticoids in surgical
stress. Surg Forum. 1985;36:18–20.
10. Kehlet H, Binder CH. Adrenocortical function and clinical course during and after surgery in
glucocorticoid treated patients. Br J Anesth. 1973;45:1043–8.
11. Kehlet H, et al. Short ACTH test in assessing hypothalamic-pituitary-adrenocortical function.
Br Med J. 1976;7:249–51.
12. May ME, Carey RM. Rapid adrenocorticotropic hormone test in practice. Am J Med.
1985;79:679–84.
13. Speckart PF, Nicolloff JT, Bethune JE. Screening for adrenocortical insufficiency with
Cosyntropin® (synthetic ACTH). Arch Intern Med. 1971;128:761–3.
14. Hjortrup A, Kehlet H, Lindholm J, Stentaft P. Value of the 30-minute adrenocorticotropin
(ACTH) test in demonstrating hypothalamic-pituitary-adrenocortical insufficiency after acute
ACTH deprivation. J Clin Endocrinol Metab. 1983;57:668–70.
15. Loriaux L. Glucocorticoid therapy in the intensive care unit. N Engl J Med. 2004;350:1601.
16. Oelker W. Dose response aspects in the clinical assessment of the HPA axis, and the low-dose
adrenocorticotropin tests. Eur J Endocrinol. 1998;135:27–33.
17. Thomson AE, Brownell EG, Cuming GR. Water diuresis in adrenal cortical insufficiency. Ann
Intern Med. Original Research: 1960, May 1.
18. Sterne JA. Association between Administration of systemic corticosteroids and mortal-
ity among critically ill patients with COVID-19. A meta-analysis. JAMA. Published online
September 2, 2020. https://doi.org/10.1001/jama.2020.17023.
Chapter 2
Diabetic Ketoacidosis and Hyperosmolar
Hyperglycemic Syndrome
Beatrice C. Lupsa and Silvio E. Inzucchi
Précis
1. Clinical setting: Any altered state of well-being in the context of significant

hyperglycemia in a patient with type 1 (DKA) or advanced type 2 diabetes mel-
litus (DKA or HHS), particularly during acute illness, may signify one of these
diabetic emergencies.
2. Diagnosis:
(a) History: Most patients with diabetic ketoacidosis (DKA) or with hyperos-
molar hyperglycemic state (HHS) will have a history of diabetes and a his-
tory of altered insulin dose, infection, and significant medical “stress.”
Antecedent symptoms of polyuria and polydipsia, lassitude, blurred vision,
and mental status changes may predominate the clinical picture. With DKA,
abdominal pain and tachypnea are often present.
(b) Physical examination usually reveals an altered sensorium, signs of volume
contraction/dehydration (tachycardia, hypotension, dry mucous membranes,
“tenting” of the skin), and, in DKA, the odor of acetone in the breath.
(c) Laboratory evaluation: The diagnostic criteria for DKA include blood glu-
cose above 250 mg/dL, arterial pH < 7.30, serum bicarbonate <15 mEq/l,
and moderate degree of ketonemia and/or ketonuria. Patients with HHS
present with extreme hyperglycemia (blood glucose >600 mg/dL), increased
osmolality (>320 mOsm/kg), and profound dehydration/volume contraction.
The laboratory evaluation of a patient with hyperglycemic emergency should
include measurement of blood glucose and hemoglobin A1c, arterial blood
gases, serum electrolytes, ketones and osmolality, renal function, and
B. C. Lupsa (*) · S. E. Inzucchi

Section of Endocrinology, Yale University School of Medicine, Yale-New Haven Hospital,
New Haven, CT, USA
e-mail: beatrice.lupsa@yale.edu
© Springer Nature Switzerland AG 2021 9

L. Loriaux, C. Vanek (eds.), Endocrine Emergencies, Contemporary Endocrinology,
https://doi.org/10.1007/978-3-030-67455-7_2
10 B. C. Lupsa and S. E. Inzucchi
u rinalysis. A workup for sepsis or other precipitating causes should be initi-

ated if indicated.
3. Treatment
(a) DKA
1. Fluid: Estimated fluid deficit is 5–7 liters. Correct with normal saline, 2 L
in the first 2 hours, the remainder over the next 22 hours.
2. Insulin: IV bolus of 0.1 U/Kg regular insulin followed by an intravenous
infusion of 0.1 U/kg/h. The goal is to reduce plasma glucose by 50–75 mg/
dL/h. Initial target plasma glucose is 200–250 mg/dL. Once achieved,
reduce insulin rate and provide dextrose to “clamp” the plasma glucose
until the acidosis/anion gap is resolved.
3. Acid/base: pH will climb with plasma expansion and insulin administra-
tion. Use small amounts of sodium bicarbonate only for severe acidemia
(pH < 6.9).
4. Electrolytes: Close monitoring and correction of serum potassium are
critical. (If serum potassium <3.5, correct hypokalemia before any insulin
is given.)
5. Search for cause: Seek to determine underlying precipitant, such as treat-
ment nonadherence, infection, and myocardial infarction.
(b) HHS
1. Fluid: Estimated fluid deficits typically larger than in DKA (7–9 liters or
100–200 ml/kg). Correction/maintenance of plasma volume with normal
saline is critical in older patients. Correct rate depends on blood pressure,
other signs of volume contraction, and any history of underlying cardio-
vascular disease, especially heart failure.
2. Insulin: Should be initiated after initial saline plasma expansion. IV bolus
of 0.1 U/Kg regular insulin followed by an intravenous infusion of 0.1 U/
kg/h. The goal is to reduce plasma glucose by 50–75 mg/dL/h. Target
plasma glucose is 250–300 mg/dL.
3. Acid/base: By definition, no major deficits related to HHS itself.
4. Electrolytes: Derangements not as common as in DKA, but monitoring is
still required.
5. Serum osmolality correction should not exceed 3 mOsm/Kg/hr.
Introduction
Diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic syndrome (HHS)

are two acute and life-threatening complications of diabetes requiring prompt rec-
ognition and aggressive therapy to optimize clinical outcomes. Although they share
certain features, DKA and HHS differ clinically according to the degree of
2 Diabetic Ketoacidosis and Hyperosmolar Hyperglycemic Syndrome 11
Table 2.1 Diagnostic criteria for diabetic ketoacidosis (DKA) and hyperosmolar state (HHS)
DKA
Mild Moderate Severe HHS
Plasma glucose (mg/dL) >250 >250 >250 >600
Arterial pH 7.25– 7.00–7.24 <7.00 >7.30
7.30
Serum bicarbonate (mEq/L) 15–18 10 to <15 <10 >18
Urine ketonesa Positive Positive Positive None (small)
Serum ketonesa Positive Positive Positive None (small)
Effective serum osmolality (mOsm/ Variable Variable Variable >320
kg water)b
Anion gapc >10 >12 >12 Variable but usually
normal
Mental status Alert Alert/ Stupor/ Stupor/coma
drowsy coma
Adapted from Kitabchi et al., Diabetes Care, 2001 [1]
a
Nitroprusside reaction method
b
Calculation: 2 [measured Na (mEq/L)] + glucose (mg/dL)/18
c
Calculation: Na+ − (Cl− + HCO3 −), in mEq/L
hyperglycemia and the presence of ketoacidosis. The fundamental difference

between the two conditions is that a small residual amount of insulin prevents sig-
nificant ketosis and acidosis in HHS. Descriptive definitions of DKA and HHS and
the criteria for classification of the severity of the former are shown in Table 2.1.
Patients with DKA present with hyperglycemia, ketonemia, and metabolic aci-
dosis secondary to absolute or profound relative insulin deficiency. HHS is charac-
terized by a greater severity of plasma glucose elevation, marked increase of plasma
osmolality, absent or mild ketosis, and altered mental status. In HHS, residual insu-
lin secretion minimizes ketone body production but is not able to control hypergly-
cemia. The older terms “hyperglycemic hyperosmolar nonketotic coma” and
“hyperglycemic hyperosmolar nonketotic state” have been replaced with the term
“hyperglycemic hyperosmolar syndrome (or state)” to reflect the fact that different
levels of mentation and ketosis may indeed be present.
Most patients with DKA have type 1 diabetes, which is associated with absolute
insulin deficiency. Patients with advanced or severe type 2 diabetes can also be at
risk during acute illnesses. HHS occurs almost exclusively in type 2 diabetes
patients, who continue to demonstrate some degree of insulin secretion.
Pathogenesis
The events leading to DKA and HHS are shown in Fig. 2.1. In DKA, absent or
severely reduced insulin concentrations, increased insulin-counterregulatory hor-
mones (cortisol, glucagon, growth hormone, and catecholamines), and peripheral
Insulin deficiency
Pancreas
Absolute Relative
↑↑↑Counterregulatory hormones
Adipose tissue
↑ Lipolysis Muscle
Absent or minimal ketosis
↑ Aminoacids ↓ Glucose utilization

↑ FFA & Glycerol to liver
Liver
Ketone body production
↓ Glucose utilization
↓ Alkali reserve ↑ Gluconeogenesis
↑ Glycogenolysis
Ketoacidosis
Hyperglycemia
Triacylglycerol
Osmotic diuresis
Hyperlipidemia Dehydration Hyperosmolality
HHS
DKA
Fig. 2.1 Schematic overview of the pathogenesis of diabetic ketoacidosis and hyperosmolar
hyperglycemic syndrome. (Adapted from Kitabchi et al., Diabetes Care, 2001 [1]). DKA diabetic
ketoacidosis, FFA free fatty acids, HHS hyperosmolar hyperglycemic syndrome
insulin resistance result in hyperglycemia and ketosis. Hyperglycemia evolves

through decreased glucose utilization by peripheral tissues and accelerated hepatic
gluconeogenesis and glycogenolysis [1–4]. Due to increased lipolysis and decreased
lipogenesis, abundant circulating free fatty acids are converted to ketone bodies
(beta-hydroxybutyrate, acetoacetate, and acetone) by the liver. Beta-hydroxybutyrate
and acetoacetate are two relatively strong acids. At a physiological pH, these two
ketoacids dissociate completely, and the excess hydrogen ions bind bicarbonate,
resulting in decreased serum [HCO3 −] concentrations. Ketones thus circulate in the
anionic form, leading to the development of the anion gap metabolic acidosis that
characterizes DKA. Hyperglycemia-induced osmotic diuresis also leads to dehydra-
tion, hyperosmolality, electrolyte losses, and subsequent decreased plasma volume
and glomerular filtration. With decline in renal function, glycosuria and ketonuria
are attenuated, further exacerbating hyperglycemia, hyperosmolality, and ketoaci-
dosis. Activation of the sympathoadrenal system further counteracts insulin action,
heightening all of these features.
HHS is also caused by a reduction in the net effective action of circulating insulin
and an increase in counterregulatory hormones, leading to hyperglycemia and
hyperosmolality. The key difference between HHS and DKA is that insulin levels in
HHS are inadequate to control hyperglycemia but generally sufficient to prevent
significant ketosis and, as a result, acidosis.
Recent studies have shown that patients in hyperglycemic crisis also exhibit a
severe proinflammatory state characterized by elevated cytokine (tumor necrosis
factor-α (alpha), interleukin-β (beta), −6, and −8), C-reactive protein, reactive oxy-
gen species, lipid peroxidation, and plasminogen activator inhibitor-1 [5].
New-onset type 1 diabetes (and, in some circumstances, type 2) can present with
DKA. The most common precipitating factors are omission of insulin or inadequate
insulin coverage especially during some other acute illnesses (e.g., gastroenteritis,
influenza), severe infections, myocardial infarction, stroke, pancreatitis, or major
surgery. Insulin pump malfunction, psychiatric illness, eating disorders, and drug
abuse can also be associated with DKA. Administration of medications such as
corticosteroids, conventional and atypical antipsychotic drugs, thiazide diuretics,
and beta-blockers has also been reported to promote the development of DKA.
HHS is seen exclusively in type 2 diabetes and can sometimes be its initial pre-
sentation. Infection is the major precipitating factor (pneumonia, pyelonephritis,
etc.) occurring in about 50% of the patients. Other acute illnesses such as myocar-
dial infarction and stroke, which cause the release of counterregulatory hormones,
and intra-abdominal processes, including acute pancreatitis, can be the stimulus for
HHS. Medications associated with DKA also have been associated with
HHS. Nonetheless, in about 20% of patients presenting with hyperglycemic crisis,
there is no obvious cause—likely due to an abrupt increased insulin requirement for
some unidentifiable reason, with superimposed effects of gluco-toxicity, which
describes the phenomenon of worsening beta-cell secretion of insulin caused by
hyperglycemia itself.
Diagnosis
History and Physical Examination
DKA and HHS are medical emergencies that require urgent recognition and treat-
ment. The initial approach to these patients should include a rapid but thorough
history and physical examination with special focus on patency of airways, mental
status, state of hydration, cardiovascular and renal integrity, and potential sources of
infection.
The development of DKA is usually relatively acute, occurring in less than
24–48 h, whereas HHS usually evolves over several days to weeks. The typical
symptoms of unrestrained hyperglycemia in both syndromes include polyuria, poly-
dipsia, blurred vision, fatigue, weakness, and weight loss. DKA patients usually
present with vomiting and abdominal pain probably due to delayed gastric empty-
ing and ileus caused by electrolyte abnormalities and/or acidosis.
Physical findings include poor skin turgor, tachycardia, and hypotension. In

DKA, there may be a fruity odor to the breath (from ketosis) as well as rapid, regu-
lar, and deep respirations (Kussmaul breathing), the latter representing an effort to
mitigate the impact of metabolic acidosis by inducing a compensatory respiratory
alkalosis. Patients with HHS can present with focal neurological signs (hemiparesis,
hemianopsia) and seizures. Mental status can vary from alertness to lethargy and
coma. Serum osmolality is the most important determinant of mental status in
HHS. In particular, obtundation and coma may be seen when the effective osmolal-
ity exceeds 330 mOsm/kg [6].
Even though infection is a common precipitating factor for hyperglycemic cri-
ses, the body temperature can be misleadingly normal or low due to peripheral
vasodilation.
Laboratory Findings
The easiest and most urgent laboratory tests are determination of blood glucose by
finger stick and urinalysis with reagent strips for ketones and glucose allowing for
the detection or at least the strong suspicion of these hyperglycemic crises before
the patient is seen. These can be done by the patient at home.
The initial laboratory evaluation of a patient with DKA or HHS should include
measurement of blood glucose, arterial blood gases, renal function, serum electro-
lytes, ketones, serum osmolality, complete blood count with differential, and uri-
nalysis. A workup for sepsis should be initiated by obtaining blood and urine
cultures and a chest X-ray if clinically indicated. Additional tests include EKG and
determination of the hemoglobin A1c level, the latter to assess for chronicity and
degree of hyperglycemia (Table 2.2).
Table 2.2 Initial laboratory evaluation for DKA and HHS

Infectious disease
Metabolic evaluation evaluationa Othersa
Glucose CBC with Electrocardiogram
differential
Serum ketones Chest X-ray Urine toxicology
panel
Electrolytes (monovalent and divalent: Na+, K+, Urine culture Pregnancy test
Cl−, HCO3 −, Ca2+, PO4 3−, Mg2+)
Serum osmolality Blood cultures
Blood urea nitrogen (BUN) and creatinine Viral nasal swab
Arterial blood gases (ABG)
Liver function tests
Amylase and lipase
Hemoglobin A1c
Urinalysis
If clinically indicated
a
The diagnostic criteria for DKA include blood glucose above 250 mg/dL, arterial
pH < 7.30, serum bicarbonate <15 mEq/L, and moderate degree of ketonemia and/
or ketonuria (Table 2.1) [1]. Hyperglycemia is a key diagnostic criteria of DKA;
however, 10% of DKA patients will have a glucose level below 250 mg/dL [7],
sometimes due to insulin administration before getting to the hospital decreased
nutritional intake and decreased gluconeogenesis due to recent ethanol consump-
tion or advanced liver disease [8, 9].
Accumulation of ketones results in an anion gap metabolic acidosis. The anion
gap is calculated by subtracting the major measured anions (chloride and bicarbon-
ate) from the major measured cation (sodium). In the older literature, a level above
14–15 mEq/L was thought to be consistent with an increased anion gap metabolic
acidosis. However, most laboratories currently measure sodium and chloride using
ion-specific electrodes. The plasma chloride level measured by this method is usu-
ally 2–6 mEq/L higher than with prior analytical methods. Therefore, using the
ion-specific technique, an anion gap of >10–12 mEq/L would suggest the presence
of an anion gap acidosis [10, 11]. Arterial blood gases support the diagnosis with the
presence of acidemia.
Important laboratory features of DKA are ketonemia and ketonuria. The ratio
between the two main ketoacids, beta-hydroxybutyrate and acetoacetate, depends
on the prevailing redox state. In high redox states, such as DKA (as well as lactic
acidosis), beta-hydroxybutyrate predominates. Assessment of ketone status is usu-
ally performed with the nitroprusside reaction, which provides a semiquantitative
measurement of acetoacetate and acetone. However, the nitroprusside reaction does
not detect beta-hydroxybutyrate, thus underestimating the severity of ketoacidosis.
If available, direct measurement of serum beta-hydroxybutyrate can be helpful in
establishing the diagnosis.
Patients with HHS present with extreme hyperglycemia (blood glucose >600 mg/
dL), increased osmolality (>320 mOsm/kg), and profound dehydration/volume con-
traction. The effective serum osmolality is calculated as follows: 2 [measured Na
(mEq/L)] + glucose (mg/dL)/18, with normal value being 290 ± 5 mOsm/kg (blood
urea nitrogen, which enters the equation for total serum osmolality, is not included
here as it is freely diffusible across cell membranes and is therefore not considered
an “effective osmole”). Usually in HHS, the anion gap is normal, and serum bicar-
bonate level is over 20 mEq/L. However, some patients can present with mild aci-
dosis, due to the accumulation of ketone bodies in low concentration and/or lactate
resulting from generalized hypoperfusion.
Both DKA and HHS are associated with large fluid and electrolyte deficits
(Table 2.3). The development of dehydration and electrolyte depletion is the result
of hyperglycemia, insulin deficiency, and, in DKA, keto-anion excretion.
Hyperglycemia causes an osmotic diuresis. During severe hyperglycemia the
renal threshold of glucose and ketones is exceeded. The osmotic effect of glycosuria
results in impaired water and sodium chloride reabsorption in the proximal tubule
and loop of Henle [12]. Insulin deficiency itself may further contribute to fluid and
electrolyte losses because insulin stimulates salt and water resorption in the proxi-
mal and distal nephron and phosphate reabsorption in the proximal tubule. Ketoacid
Table 2.3 Typical deficits of water DKA HHS

and electrolytes in DKA and HHS
Total water (L) 6 8
Water (mL/kg)a 100 100–200
Na+ (mEq/kg) 7–10 5–13
Cl− (mEq/kg) 3–5 5–15
K+ (mEq/kg) 3–5 4–6
PO4 3− (mmol/kg) 5–7 3–7
Mg2+ (mEq/kg) 1–2 1–2
Ca2+ (mEq/kg) 1–2 1–2
Adapted from Kitabchi et al., Diabetes Care, 2006 [29]
a
Per kilogram of body weight
excretion exacerbates solute diuresis by causing urinary cation excretion in the form
of sodium, potassium, and ammonium salts.
The severity of dehydration is greater in HHS than in DKA likely due to more
gradual and longer duration of metabolic decompensation and decreased fluid
intake. Also, nausea and vomiting (in DKA) and fever, when present, can further
contribute to dehydration.
Serum sodium concentration is markedly decreased because of intracellular
water shifting to the extracellular compartment in order to equilibrate hyperosmo-
lality. Usually the admission sodium is factitiously low because of the hyperglyce-
mia and hyperlipidemia. The corrected sodium can be calculated by adding 1.6 mEq
to the reported sodium value for every 100 mg of glucose over 100 mg/dL. As a
result, a normal or high-measured serum sodium in this setting actually indicates a
severe state of dehydration, as is often the case in patients presenting with HHS.
The patient’s serum potassium may be initially elevated due to an extracellular
shift of potassium caused by insulin deficiency, acidemia, and hypertonicity, which
is falsely reassuring as the total body potassium stores are probably depleted. A low
or low-normal potassium level suggests severe total body potassium depletion.
Patients with uncontrolled hyperglycemia are usually in a negative phosphate
balance because of phosphaturia caused by osmotic diuresis and the shift of phos-
phate out of the cell in the setting of acidosis.
Leukocytosis around 10,000–15,000 mm3 is a common finding in DKA and may
not be the result of an infection. This is attributed to stress and elevation in stress
hormones. However, leukocytosis above 25,000 mm3 suggests a septic process and
should trigger further evaluation.
Hyperamylasemia has been reported in patients with DKA. It is not always asso-
ciated with pancreatitis. The origin of amylase in DKA is usually a non-pancreatic
tissue such as the salivary glands. Measuring a lipase level can be useful in the dif-
ferential diagnosis; however, lipase also can be elevated in the absence of pancreati-
tis [13]. The mechanisms of increased amylase and lipase levels in DKA are not
well defined.
Moderate hypertriglyceridemia is common during episodes of DKA [14]. The
deficiency of insulin activates lipolysis in adipose tissue releasing increased free
fatty acids, which accelerates the formation of very-low-density lipoprotein (VLDL)
in the liver. In addition, reduced activity of lipoprotein lipase in peripheral tissue

decreases the removal of VLDL from the plasma, resulting in hypertriglyceridemia.
Severe hypertriglyceridemia and hypertriglyceridemia-induced pancreatitis leading
to DKA or HHS are well recognized [15]. Severe hypertriglyceridemia may falsely
lower serum glucose (pseudo-normoglycemia) [16] and serum sodium (pseudohy-
ponatremia) [17] in laboratories using volumetric testing and dilution samples with
ion-specific electrodes.
Differential Diagnosis
DKA must be differentiated from other conditions that present with ketoacidosis
and anion gap metabolic acidosis. Starvation and alcoholic ketoacidosis are not
typically associated with hyperglycemia above 200 mg/dL, and, usually, the bicar-
bonate level is greater than 18 mEq/L. Other causes of an anion gap metabolic aci-
dosis include lactic acidosis, acute renal failure, and the ingestion of methanol,
ethylene glycol, paraldehyde, and salicylate. The origin of the anion gap can usually
be ascertained by assessing the ketone concentrations in the plasma. HHS is diffi-
cult to confuse with other conditions, given its narrowly defined diagnostic criteria.
Overlap syndromes with features of both DKA and HHS, however, can be encoun-
tered in the clinical practice. These may occur in patients with a slower development
of ketoacidosis and, as a result, more protracted urinary losses of free water, result-
ing in hyperosmolality.
Treatment
The therapeutic goals of DKA and HHS management include restoration of volume
status, correction of hyperglycemia and ketoacidosis (in DKA), correction of elec-
trolyte abnormalities, treatment of precipitating factors, and prevention of the com-
plications of DKA and HHS. Adequate intravenous (IV) access is essential with two
larger bore IV peripheral lines or a central line. A suggested protocol for the man-
agement of patients with DKA and HHS is summarized in Fig. 2.2.
Fluid Therapy
In the emergency room, fluid resuscitation is critical for intravascular, interstitial,

and intracellular volume and restoration of renal perfusion. The average fluid loss is
approximately 5–7 L in DKA and 7–9 L in HHS (Table 2.3). The IV fluid adminis-
tration replaces the fluid and electrolyte deficiencies while simultaneously reducing
plasma glucose concentrations and counterregulatory hormones, partially through
Fig. 2.2 Suggested protocol for management of adult patients with diabetic ketoacidosis and
hyperosmolar hyperglycemic syndrome. (Adapted from Kitabchi et al., Diabetes Care, 2009 [18]).
BG blood glucose, DKA diabetic ketoacidosis, HHS hyperosmolar hyperglycemic syndrome, hr
hour, H2O water, IV intravenously, KCl potassium chloride, NaCl sodium chloride, mEq/L milli-
equivalents per liter, SC subcutaneous
dilution but also through volume expansion and resultant expansion of plasma vol-
ume. IV fluids should be administered before starting insulin in HHS, especially in
older patients with tenuous cardiovascular status, in order to preserve vascular vol-
ume (see below).
Normal saline is generally given in the first hour at a rate of 15–20 mL/kg body
weight/h or 1–1.5 L in the first hour, although care is required in older patients with
underlying cardiovascular disease. After initial stabilization, if the corrected serum
sodium is normal or elevated, normal saline can be changed to half-normal saline at
a rate of ~250–500 mL/h. If the corrected sodium is low, normal saline can be con-
tinued at a similar rate. Fluid replacement should correct the estimated deficit in the
first 24 h, with 50% of fluid resuscitation in the first 8–12 h. In patients with HHS,
the change in serum osmolality should not exceed 3 mOsm/kg water/h.
The response to fluid resuscitation is judged by monitoring hemodynamic param-
eters (blood pressure and heart rate), clinical exam, urinary output, and laboratory
values. In patients with renal or cardiac compromise, fluid resuscitation should be
conducted with caution to avoid fluid overload.
Once the serum glucose is 200–250 mg/dL in DKA, the insulin infusion rate
should be reduced to 1–2 U/h, and 5% dextrose should be added to the IV fluids
Table 2.4 Suggested algorithm for clamping the blood glucose using dextrose-containing IV
fluids and IV insulin in DKA
Serum glucose IV fluid Insulin infusion
200–250 mg/dL in Change to D50.45%NS Reduce insulin drip to 1–2 U/hb,c
DKA 100–200 mL/ha,b
100 mL/h 1 U/h
200 mL/h 2 U/h
If serum glucose Do not reduce IV fluids Minor increases in insulin infusion rate
increases (~0.5–1 U/h)d
If serum glucose Increase IV fluids Do not decrease insulin infusion rate
decreases
a
Provides 5–10 g of carbohydrates per hour
b
Alternative is 0.02–0.05 U/kg/h
c
Give insulin IV 1 U/h for every 5 g of dextrose IV/h
d
Highly insulin-resistant patients who require large amounts of IV insulin may need as much as
5–10 U of insulin/h. Accordingly, insulin dose adjustments may need to be more aggressive. The
insulin dose can likely be reduced gradually as hyperglycemia improves
(this is termed the “glucose-insulin clamp” by some authorities). This technique

will prevent hypoglycemia but will allow continuation of insulin administration suf-
ficient in amount to resolve the ketoacidosis in DKA (i.e., to close the anion gap). A
proposed algorithm for clamping the serum glucose using dextrose-containing IV
fluids and IV insulin is outlined in Table 2.4.
Due to concerns that lowering the serum glucose too fast in HHS might promote
the development of cerebral edema, some authorities recommend adding 5% dex-
trose to the IV fluids when the serum glucose is 250–300 mg/dL until the patient is
mentally alert [18]. In the majority of HHS cases, serum osmolality and mental
status are normalized by the time the hyperglycemia is corrected; thus the “glucose
clamp” will not often be necessary. Indeed, a simple lowering of the insulin infusion
rate without the addition of dextrose can be sufficient, even in cases where the men-
tal status remains abnormal.
Insulin Therapy
The only contraindication to insulin therapy is a current serum potassium below

3.5 mEq/L as insulin will worsen the hypokalemia by shifting the potassium into
the cells.
The administration of continuous intravenous infusion of regular insulin is the
preferred route as it has short half-life, is easy to titrate, and has a rapid onset and
short duration of action. The insulin dose is similar in DKA and HHS. However, as
mentioned before, initial volume expansion with crystalloid is recommended (at
least 1 L) in the more profoundly dehydrated and older HHS patients. This recom-
mendation is to protect the plasma volume; once insulin is administered, the conse-
quent fall in circulating glucose concentrations will lead to an intracellular shift of
Another random document with
no related content on Scribd:
connected with the home-surroundings and members of the family is
not so important as the character of the delusions; and the influence
of the relatives is often most salutary, even when the patient has
most distressing thoughts concerning them or even when he is too
insane to be always sure of their identity. If the insanity arises in a
violent emotional shock, and home sights and surroundings recall
and arouse the mental pain, as is the rule in such cases, recovery
usually depends upon removal from home. The matter of suicide
where there are means of proper watching does not influence me in
my decision, as I think that the dangers of self-destruction are fully
as great in asylums as outside with sufficient care, whereas the
stimulus to the patient to kill himself from both insane and sane
motives is greater the more he is surrounded with depressing
influences. On the other hand, it not seldom happens that the
diversity of sights in the hospital, the routine, the varied events of the
day, the amusements, the walks, the drives, even the discomforts
and annoyances, serve to distract the patient's mind from his
delusions better than the same result can be accomplished under
the pleasant influences at home, while a natural feeling of self-
respect prevents those who have power of self-control from giving
way to their impulses before strangers, especially when they know
that such conduct will take them to a lower ward with less agreeable
associates.
There is no doubt, however, that home-treatment of the insane in the

majority of cases is synonymous with neglect of all those minute
attentions to details that make the difference between recovery and
chronic mental disease. Home-associations often act upon the
insane mind like frequent passive motion to a diseased or fractured
hip; the relatives of the insane patient oftener than not share with
him a common inheritance of an unstable mental organization, and
will not be judicious in their treatment of him, or they cannot be
subjected to the risk of becoming insane themselves in taking care of
an insane brother or parent; and it is seldom that a private house
away from home can be converted into a hospital, as it must be for
the treatment of an insane person. One of the greatest difficulties in
the home-treatment of the insane is during the many months of slow
convalescence, when it is difficult to prevent a too early resumption
of cares or work or methods of life prejudicial to complete restoration
to health; so that in that stage of the disease, if in no other, removal
from the familiar and usual surroundings of the patient will usually be
quite necessary. The small private hospitals, with all their many and
obvious advantages, always have been, and inevitably must be,
chiefly devoted to wealthy patients who wish for a home where they
can have medical supervision, rather than curative institutions for
any large number of persons; and there is not enough going on in
them to sufficiently occupy the attention of certain curable patients
who must be removed from home, although they are well adapted to
those who need quiet and seclusion chiefly. The larger hospitals,
with their large staff of skilled officers and nurses, and with all their
appliances for recreation or rest, amusements or occupation,
discipline or gentle support, must be our chief means for treating the
insane. They are indispensable for a large number of the insane who
are of such unstable mental equilibrium that a little over-exertion or a
trifling deviation from a carefully regulated routine throws them off
their balance; and they must be used, temporarily at least, for many
of the incurable or partially curable insane who need a place and an
opportunity to learn self-control and self-management. Enormous
advances have been made in the construction and management of
hospitals for the insane, more especially in the last fifteen years. We
see it everywhere. But the greatest need, of opportunities to combine
advantages of the asylum treatment with the benefits of home-
comforts, to place sick people where the influences surrounding
them will be healthy, and where there are not so many harmful as
well as useless restrictions upon liberty, and so many morbid
associations, is as yet entirely unfilled in this country. The question of
the best, or even of an improved, organization for our insane
asylums is too wide a subject to be discussed here. That our present
system tends to make the medical staff narrow if they are appointed
to their duties without previous broad training and experience or for
political reasons, is a self-evident proposition; and yet there are
manifest objections to just such a visiting staff as is customary in
general hospitals.
As Maudsley says, squalor in an attic with liberty is better than being
locked up in a palace with luxury. Many of the insane share that
feeling with their sane brothers. To not a few it makes the difference
between recovering their mental health and lapsing into incurable
dementia. Many would voluntarily consent to remain in places less
distasteful to them. If we could separate them into classes, as Mr.
Mould10 has done in England by buying or hiring ordinary dwellings
one or two miles even from his asylum, we could have separate
houses with open doors or shut, as the case demands, for those who
require them, and reserve the associated halls and large buildings
for a different class. Mr. Mould has not applied his own system to
those cases which need it the most, the curable insane, except to a
very moderate degree.
10 Presidential Address at the Annual Meeting of the British Medico-Psychological
Society, October, 1880.
It is not often that the physician is called, or his advice heeded if

given, in the early stages of mental disease, and the first symptoms
are by no means easy to differentiate from the less harmful results of
mental strain. If there be, however, sufficient loss of equilibrium to
suggest the question of beginning insanity, it is of course better to
take the safer way and recommend removal of all sources of
irritation, and to advise rest, sleep, simple food, attention to the
general laws of health, outdoor life, and change of scene for a
sufficient length of time to restore the mental poise, avoiding
narcotics and sedatives as far as possible, and keeping the patient
with a safe adviser or within easy reach of one. In many cases,
especially of young persons, this may involve a radical change in
their choice of a profession and whole plans of life. If the question of
marriage comes up in these cases before the physician as to
preventing further developments of threatened disorder, it can only
be said that what may be well for the individual is not always best for
society. A few years' delay will usually give time for the question to
settle itself.
When insanity has actually appeared the same rules should govern
its management as in other diseases. If, like smallpox and
diphtheria, it is a great source of danger to others, the patient should
be put in a safe place; if, like typhoid fever arising from bad drainage,
its cure depends upon the removal of a given cause, the patient
must leave the infected locality or have the cause displaced; if, like
rheumatism in a damp cellar, it can be treated successfully only
under different conditions, the patient must be removed; and if
poverty or other conditions prevent the best possible treatment, the
next best practicable plan must be followed.
The first question which comes up in the care of the insane is with
regard to removal from home and commitment to an asylum; and
here a great many points must be taken into consideration. It is not
always that a home can be accommodated to the use of an insane
member of the family. There are not many in which there can be
proper quiet and seclusion without depriving the patient of that
abundance of fresh air and outdoor exercise which is so often
required in treatment. Frequently those nearest to him irritate him to
the last degree, or he has some aversion or delusion in regard to
them rendering their presence injurious. If the delusions and
impulses of a patient are not such as to endanger the lives of the
household, his violence and excitement and uneasiness or
melancholia may make life simply intolerable to his relatives, or his
exactions may be exhausting to their strength and his constant
presence a means of making still others insane. His noise may
disturb a whole neighborhood. His vagaries may require control, his
indecencies concealment, his enfeeblement help more than can be
sufficiently given outside of a hospital, his general condition more
judicious care than his friends can command, and his example may
have a pernicious effect upon children growing up with an insane
diathesis. In many people a long time insane much of their vicious
conduct is due to habit or to tendencies which they cannot or will not
control without the steady, kind discipline which cannot be got at
home.
A man with delusions by virtue of which he thinks that some one is
plotting to ruin or kill him is apt to commit murder; a mother who
believes that the world is going to ruin and her children to torture
may be expected to put herself and them out of misery; a demented
woman chops off her infant's head because its cries disturb her; and
the maniac's delirium or epileptic's fury drives him into any horrible
act. Such people need to be watched always by some person or
persons fully able to prevent their doing harm, which in many cases
can only be done, with any reasonable degree of liberty to the
patient, in a hospital for the insane. If the danger is obviated by
removal of certain persons—children, for instance—or if watching by
nurses serves the purpose, and there are no Other objections to
such a course, there are cases in which the chances of cure are
more if the patient remains at home whenever the disease pursues
an acute course. Most of the insane, however, have passed the
curable stage; the majority need the moral support and freedom from
responsibility or the regular life and regimen of a hospital; and a
large proportion of the cases following a subacute or chronic course
must be removed from home. The expense attendant upon the safe
treatment of mental disease in a private house is entirely beyond the
means of most families, just as they cannot send their consumptives
to Colorado or France, and so the hospital becomes a necessity.
Except in dangerous cases, however, the hospital should never be
hastily decided upon. A little delay does not diminish the patient's
chances of recovery, and may show that the attack is only transient,
whereas removal to a strange place might aggravate the disease
and increase its duration. It is particularly important not to choose an
unfavorable time to commit an insane person to an asylum, and
thereby add to discouraging conditions already existing an additional
source of despair at a time when every influence should be as
elevating and cheering as possible. In most cases, especially if there
is a suicidal or homicidal tendency, it is best, when removal to an
asylum has been decided to be necessary, not to argue the question
with the patient, but to explain why it must be done, and then do it
without delay.
The law provides the methods of commitment to asylums. They are
so different in the different States that they cannot be discussed
here.11 The one rule holds good everywhere, however—that it is far
better to use force than deception in sending the insane from home
to asylums, and that the cases are very few in treating the insane in
or out of asylums where deception is either justifiable or wise. A
second safe rule is that a person of unsound mind is always a
source, immediate or remote, of more or less danger.
11 An abstract of the various laws may be found in the appendix to the American
edition of Clouston's Clinical Lectures on Mental Diseases.
Commitment to an asylum means so much that safeguards against

improper action should provide careful examination of the case by
competent physicians, as little restraint as is required by safety, good
medical treatment in the hospital, thorough supervision by
experienced persons on the part of the state, safe-keeping of the
dangerous patients, and easy removal of those who have recovered
or who may be sent out to their own advantage. In too many States
confinement in an asylum means that two physicians, or even one,
who may know little or much of insanity, think it best, and removal
depends upon the word of one man, the superintendent. Once in the
asylum, the best practice of the present day should be followed—
namely, to allow free communication and visits from friends until it is
shown that they do harm, to multiply cheerful and natural influences
to the last degree, to furnish rest, exercise, occupation, or recreation
as each case requires, and to remove all that is morbid and
disagreeable so far as that can be done. A permanent removal from
the hospital should be insisted upon as soon as it is safe to complete
the convalescence at home or elsewhere, and an abundance of
fresh air, indoors and out, should be supplied as the best curative
agent from first to last. Arguing, moralizing, cheering up, rigid
restraint, disciplining, sedative drugs simply for quieting patients, and
still more bleeding and blistering, are for the most part things of the
past. Mechanical restraint is all but abolished in the best hospitals,
and is used only so far as it is considered the best medical
treatment. A prison-like appearance of the wards has been found to
be not only quite unnecessary, but harmful.
In many cases of insanity I make the question of removal to a large

hospital one of circumstances and of money. If separation from the
influences under which the disease occurs is necessary, and that
cannot be secured at home, I usually select, as the case demands
and opportunity is afforded, a private house with good nurses, a
small private hospital, or an insane asylum where the general
influences are the healthiest, where the medical treatment is in
accordance with the best modern principles, and where the
construction of the hospital is most nearly adapted to the
requirements of the present day. Accessibility to visits of friends and
the family physician where they help in the cure, and remoteness
from them when they do harm, are also points to be considered. In
many cases where the illness is of long duration a change of scene
and association will prove of great service, even from one hospital to
another. The permanent settling down into the routine of hospitalism
is especially to be avoided. Of course there are cases, or rather
conditions, in which a change would be detrimental to the last
degree.
The associations, surroundings, and influences brought to bear upon

the patient—what has been called the moral treatment—are of the
first importance in the treatment of mental disease, and diet and
hygiene come next. Medicines are of use in properly selected cases.
The appetite must often be stimulated, the digestion regulated, and
various painful symptoms must be relieved, so far as possible,
without a resort to internal sedatives and narcotics. Rest and sleep
are essential to recovery, but every effort should be made to obtain
them by judicious regulation of outdoor exercise and of quiet as each
case requires, abundant non-stimulating food frequently given, fresh
air, tonics, baths, and removal of sources of irritation. Stimulants will
sometimes be needed to prevent excessive exhaustion. Seclusion in
a room darkened or not is useful in some conditions of excitement,
and not seldom distressing symptoms are relieved by the simple
presence of another person or by the absence of certain individuals.
Drugs of sufficient strength and in such quantity as to produce quiet
or sleep should be used only when absolutely necessary, and then
for as short a time as possible. Their prolonged use is open to many
manifest objections in all persons, and particularly in those suffering
from mental disorders, inasmuch as with them large doses, if any,
are commonly given, and it is very difficult often, in the impaired
state of mind of the patient, to get indications of symptoms which
contraindicate the use of a particular drug or to learn when it is
producing harmful effects. Tonics are often indicated, but should be
used with discrimination, as some of them, especially those affecting
the cerebral circulation, frequently produce disagreeable results.
After apparent recovery there should be a long period of after-

treatment, which in most cases will be best met in rest or travel.
In the various forms of mental disease, through concentration of the

mind on various delusions and by excess or deficiency in mental
activity, the ordinary symptoms of physical disturbance or disease,
independent of the insanity, are so much modified as to be often
overlooked. It goes without saying that intercurrent diseases and
distressing symptoms should be treated on the principles generally
applicable to those conditions, so far as that can be done without
aggravating the insanity. The usual treatment of pneumonia, for
instance, may in an insane person provoke such determined
opposition or so excite or aggravate delusions that, so far as the
disease of the lungs is concerned, it may be better to let it take its
chance, with good general care, including food, warmth, etc.
The conditions of cerebral hyperæmia require cold applications to

the head, the wet pack, prolonged warm baths, a non-stimulating
diet, and quiet. If the condition is acute and of short duration, rest in
bed is useful, provided it can be secured without force. For
prolonged mental excitement from cerebral hyperæmia it will be
usually better to equalize the circulation by that motor activity which
is characteristic of the disease, and to allow free exercise in the open
air, keeping within the limits of exhaustion. My experience has not
justified the use of bleeding, except, possibly, in acute delirium
(mania peracuta). It is difficult to limit the action of blisters, and they
often irritate the patient so much as to do more harm than good.
Persistent refusal of food is usually due to delirium or delusions, and
should be met with a resort to feeding with the stomach-tube before
the point of exhaustion is reached if the tact of a skilled nurse fails of
success. Mechanical restraint increases the cerebral hyperæmia,
and there are few homes or general hospitals where it must not be
used if there is excessive violence or delirium, making the insane
asylum in those cases a necessity. Objectionable as it is, however,
mechanical restraint is less harmful than the continued use of large
doses of sedative drugs, as is so often the practice, in order to keep
patients quiet enough to remain at home.
Ergot, hydrate of chloral, and opiates, which sometimes must be

given by the rectum or stomach-tube, are sometimes advisable for a
short time, but must be used with great caution. Milder sedatives,
especially the bromides, serve a temporary use in the less violent
cases; but less sleep will often serve if secured by quiet, abundant
liquid food, and general measures, and in exhaustion by alcoholic
stimulants.
Menorrhagia is very common in the maniacal states. It usually

requires no special treatment, unless so great as to produce
exhaustion. Amenorrhœa is commonly conservative, and then
demands only general treatment; if it causes evident disturbance of
the cerebral circulation, the ordinary methods, including electricity,
massage, and local use of leeches, should be used.
Galvanism is sometimes useful, applied to the head, in cases of

mental torpor and stupor. That and the faradic current, used with
great care, act as powerful tonics to the general nervous and
muscular system.
Insomnia is often the chief manifestation of the insane taint, in which

case drugs are, for the most part, worse than useless. In all forms of
sleeplessness it is better to try malt, cod-liver oil, beer, food,
massage, baths, exercise, rest, etc. before resorting to narcotics and
sedatives. Camphor, hyoscyamus, cannabis indica, the valerianates,
bromides, codeia are much less objectionable than chloral,
morphine, and opium.
Where masturbation is simply an evidence of loss of self-control, it is

met best by constant watching, and gradually, as the mental state
improves, arranging the daily life so as to develop the feeling of self-
respect. Where it depends upon local paræsthesia, opium and
camphor and cold bathing are indicated.
Constipation is a troublesome symptom, especially in the states of

mental depression. When a full, laxative diet, cod-liver oil, and malt
do not correct it, small doses of laxatives given frequently act better
than the occasional use of purgatives.
There is a class of cases which are best treated by educating the

patients as one would educate a child.
In the general care of the insane it is the duty of the state to see that
they have all the rights of the citizen which are consistent with their
proper and safe treatment, including the benefits of property and
estate. There certainly should be in all countries, as in England,
officers whose duty it is to see that this is done. For a large number
of people with defective or diseased brains, who are now allowed to
wander about committing crimes and serving repeated sentences in
reformatories, houses of correction, and prisons, an enlightened
public policy would find the best, and in the end the cheapest,
treatment to consist in keeping them under supervision and control
as unsound members of society.
The more particular treatment of the insane differs in the various

mental diseases, varying as it necessarily must according to different
conditions. Its prevention is not an easy problem. Many of the
external causes of insanity seem inevitable in our complex
civilization: it would be impossible to widely regulate marriages, even
if we knew how; those people predisposed to insanity are usually too
self-confident and self-willed to receive advice; and moderation in all
things, healthful occupation, temperate habits, good digestion, and,
above all, out-of-door life, seem as much like a sarcasm if suggested
to many of the toilers as a waste of words if recommended to the idle
and luxurious, while the parents who have transmitted to their
children unstable or diseased brains generally impair what chances
they have in life by vicious training.
Where syphilis, drunkenness, and other marked sources of mental

degeneration do not obtain, simple food, plenty of sleep, avoidance
of extremes of heat and cold, plain dressing, baths, good digestion,
out-of-door life, fresh air, careful attention to slight disorders or
injuries of the brain and nervous system, guidance against too much
study and too much excitement or dissipation, development of
character and moral force, intellectual and physical training,
avoidance of too much emotional, sentimental, or even artistic
culture, careful watchfulness during the period of adolescence,
occupation without overwork, healthful recreation, a contented or
philosophical mind, and suitable marriages, would produce the
strong wills and healthy organisms needed to combat the tendencies
of modern life. Such a course would undoubtedly make many a child
with an hereditary predisposition to insanity become a healthy parent
of children in whom the same treatment would soon eliminate the
family taint. The character should be strengthened to learn to
overcome difficulties rather than evade them. There are cases in
which such a course can be adopted, and where the physician's
advice may be of untold benefit to generations.
There are many crises in life when the mind totters and seems ready
to fall, which the physician is more likely to recognize than any other
person. Sometimes the odds are too heavy to fight against, but often
there is a transient mental disturbance in such critical cases, or an
incipient insanity, according as the indications are met with wisdom
and patience or with neglect, indifference, and lack of judgment. The
treatment called for is of the person rather than of the mental state,
and in all forms of mental disease success in treatment depends
very materially upon the personality of the physician, who must
adapt himself also to the personality of the patient.
In about one-fourth of the cases of insanity there is no hereditary
predisposition to the disease, and its prevention can be most
hopefully looked for in attention to the general laws of health, the
observance of which tends to secure immunity from all diseases. In
the remaining cases—three times as many, in round numbers—the
most hopeful course is in abstaining from marriage altogether or in
the avoidance of unwise marriages; and it is an encouraging fact that
many people in the community now take that conscientious view of
the matter, although if they decide what to do without competent
advice they are liable to err in the opposite direction of exaggerating
their morbid tendencies, and so increasing their unhealthy
predisposition. There are certain groups of physical and mental
manifestations which the experienced physician recognizes as signs
of tendencies which only await favorable conditions—a sufficient
exciting cause—in the indulgence in drink or other excesses, in the
exclusive search for wealth or fame, in the absence of healthy
occupation, in mental wear and worry, in over-excitement, in the
various conditions of ill-health, to develop into actual insanity. This
physiognomy of temperament suggests to the observant physician a
warning against excess of all kinds, and a recommendation for that
course in life which promises the greatest likelihood of preserving a
quiet mind and a healthy body and of securing a rational
employment. Too much work is less dangerous to most people than
too little.
States of Mental Defect and Degeneration.12
12 Compare Moreau's La Psychologie morbide and Morel's Traité des Dégénérences

physiques, intellectuelles, et morales de l'Éspèce humaine.
MICROCEPHALISM, CRETINISM, INTELLECTUAL IDIOCY, MORAL IDIOCY,

INTELLECTUAL IMBECILITY, MORAL IMBECILITY (under which Westphal,
Spitzka, and others place moral insanity) are really names for
different degrees of similar defects, for the most part hereditary and
congenital or resulting from disease or injury in infancy and early
childhood, as distinguished from dementia, which is the result of later
destructive mental or brain diseases. Idiots and the demented insane
are sometimes so alike in their mental condition that, if young
persons, they can be definitely distinguished one from the other only
by a knowledge of the previous history of the case. Idiocy has its
origin at or before birth or soon after, and terminal dementia seldom
before puberty, commonly after maturity. In the United States
census, where there is a doubt in the matter, the individual is classed
as an idiot if the mental disorder occurred before the age of twelve in
girls and fourteen in boys, and as insane (demented) if above that
age.
The microcephalic brain may be as small as one-fifth the normal

size, due chiefly to intra-uterine conditions for the most part
unknown. Of course that means complete idiocy. The brains of other
idiots differ in size and development. The mental condition in all is
similar. Idiocy with the small or large or asymmetrical brain is
classified, practically rather than scientifically, by Shuttleworth, as
follows:
A. Congenital or Developmental13 Cases.—1, Microcephalic, with

small heads: forehead and occiput defective; 2, hydrocephalic; 3,
plagiocephalic, with distorted heads: features in an oblique plane; 4,
scaphocephalic, with keel-like distortion of forehead; 5, scrofulous
cases; 6, Mongol type; 7, cretinoid cases, with stunted bodies:
irregularly expanded heads and enlarged thyroid glands; 8, syphilitic
cases; 9, primary neurotic, with body well developed: signs of
irregular nervous action; 10, sensorial idiocy, with two or more
senses deficient (e.g. sight and hearing); 11, mixed cases.
13 Developmental conveniently includes those cases which, though of intra-uterine
origin, become more pronounced as physical development proceeds.
B. Non-Congenital, Acquired, or Accidental.—1, Traumatic; 2, post-

febrile; 3, hydrocephalic; 4, hypertrophic, with large square-built
heads; 5, eclampsic; 6, epileptic; 7, paralytic; 8, idiocy by
deprivation: loss of two or more senses in infancy (e.g. sight and
hearing); 9, emotional idiocy, with no bodily deformity: shrinking,
scared expression; 10, toxic idiocy, with no bodily deformity:
malnutrition.14
14 “The Physical Features of Idiocy,” Liverpool Medico-Chirurgical Journal, July, 1883.
From the creature of deformed limbs and ape-like movements,

incapable of articulate speech, even in monosyllables, or
systematized ideas, leading a purely vegetative life, unclean, and
with the instincts of a wild beast, up to moderate mental or moral
imbecility, there are endless varieties of defects and monstrosities in
mind, character, morals, and instincts, differing according to the
profoundness of the disorder of the brain (hydrocephalus, atrophy,
sclerosis, inflammation of the brain substance or membranes, injury
from compression, blows, falls, convulsions, etc.), the extent of the
defect in the brain development, the amount of the degenerative
hereditary taint, or, in the case of cretinism, the importance of the
endemic as well as the congenital influences.
In some of the higher planes of imbecility a considerable degree of

intellectual brightness, or even talent, is often observed, and every
variety of mental and moral perversion or simple reckless brutality.
Training often does a great deal to bring many of these unfortunate
creatures within the bounds of good behavior, but their care oftener
falls within the province of the medical superintendent in an asylum
or the teacher than to the physician in general practice. They are
easily led astray by others, and commit all sorts of motiveless crimes
or with a trivial or disproportionate motive, and with blind disregard of
consequences or inability to comprehend them. In the gallery, at
Washington, of photographs of counterfeiters and of passers of
counterfeit money, the faces of the latter show conclusively that they
belong to the intellectually weak-minded or imbecile class. Their own
amusement, gratification, or impulse is so far the basis of their
conduct that only a minority are harmless if not more or less
constantly watched. Fortunately, a great portion—unfortunately, not
all—of the idiots are sterile, but many of the mentally and morally
weak-minded, with striking congenital defects which no training can
fully remedy, propagate their species indefinitely for the benefit of our
prisons and asylums.
Intellectual idiocy and marked intellectual imbecility are so common

as to constitute 1 in 650 of our population. Less noticeable
intellectual imbecility is quite frequent in the large class of
troublesome and perverse children and youth of both sexes,
commonly called weak-minded.
Moral imbecility, which cannot be corrected by education, is less

common.
Moral idiocy is rare. It consists in such an absence of the moral

sense that it cannot be aroused. It is sometimes associated with
sufficient intellectual powers to make deliberate action and
premeditation quite possible. Such persons are monstrosities, who,
for the safety of the community, must be kept shut up for life like wild
beasts.
The fact should be remembered, from a medico-legal point of view,

that the defective in mind are quite liable to short attacks of simple
mania and mental depression and to epilepsy, both of the obvious
type and of the obscure or masked form, so that their degrees of
responsibility, or rather of irresponsibility, vary from time to time. As a
rule, a good physical organization and a general condition denoting
healthy circulation and nutrition mark the better brains, and
constitute important elements in forming a prognosis in regard to the
possibility of educating imbecile and feeble-minded children up to the
point of reasonably good behavior and ability to at least partly take
care of themselves. The simpler their lives and the more purely
routine or imitative their work, the less their defect is noticed. Many
can wheel a barrow as well as any one.
THE INSANE TEMPERAMENT (Insane Diathesis, Neuro-psychopathische

Constitution) is an exaggeration of the nervous temperament. It is
closely allied to insanity and the neuroses, and at the critical periods
of life is very apt to develop into one of them. It is congenital or due
to early interference with the normal development of the brain by
injury or disease. It shows itself in childhood and infancy by irregular
or disturbed sleep, irritability, apprehension, strange ideas, great
sensitiveness to external impressions, high temperature, delirium, or
convulsions from slight causes, disagreeable dreams and visions,
romancing, intense feeling, periodic headache, muscular twitchings,
capricious appetite, and great intolerance of stimulants and
narcotics. At puberty developmental anomalies are often observed in
girls, and not seldom perverted sexual instincts in both sexes. During
adolescence there are often excessive shyness or bravado, always
introspection and self-consciousness, and sometimes abeyance or
absence of the sexual instinct, which, however, is frequently of
extraordinary intensity. The imitative and imaginative faculties may
be quick. The affections and emotions are strong. Vehement dislikes
are formed, and intense personal attachments result in extraordinary
friendships, which not seldom swing suddenly around to bitter enmity
or indifference. The natural home associations and feelings easily
become disturbed or perverted. The passions are unduly a force in
the character, which is commonly said to lack will-power. The
individual's higher brain-centres are inhibited, and he dashes about
like a ship without a rudder, fairly well if the winds are fair and the
seas calm, but dependent upon the elements for the character and
time of the final wreck. Invention, poetry, music, artistic taste,
philanthropy, intensity, and originality are sometimes of a high order
among these persons, but desultory, half-finished work and
shiftlessness are much more common. With many of them
concentrated, sustained effort is impossible, and attempts to keep
them to it result disastrously. Their common sense, perception of the
relations of life, executive or business faculty, and judgment are
seldom well developed. The memory is now and then phenomenal.
In later life there is a ready reaction to external circumstances, even
to the weather, by which the individual is usually a little exhilarated or
somewhat depressed. All sorts of vaso-motor disturbances are
common and create distressing symptoms. Such people are said to
be on the border-line between sanity and insanity. They are apt to be
self-conscious, egoistic, suspicious, and morbidly conscientious;
they easily become victims of insomnia, neurasthenic,
hypochondriacal, neurotic, hysterical, or insane, and they offend
against the proprieties of life or commit crimes with less cause or
provocation than other persons. At the same time that many of them
are among the most gifted and attractive people in their community,
the majority are otherwise, and possess an uncommon capacity of
making fools of themselves, being a nuisance to their friends and of
little use to the world. Many of them get fairly well through life if their
lives are tolerably easy or especially well regulated; if not, even they
seldom escape further disturbance during the period of growing old.
Their mortality-rate, especially from pulmonary consumption, is high.
The prognosis is usually stated as unfavorable, largely, perhaps,
because proper treatment is seldom pursued. If such children could
be placed in the hands of judicious and experienced physicians from
earliest years, much better results would undoubtedly be got and the
downward tendency might be stopped. In the critical physiological
periods of life, and under the influence of mental worry with physical
strain, there is danger of breaking down. At the senile dissolution
some of them lose much of their lifelong peculiarities, and as the
mind fails in force and activity become more like other people. After
the climacteric there may be also great improvement.
TREATMENT should consist in the general principles of mental

hygiene, especially in training the mind to self-control and to avoid
introspection—in a word, in maintaining health and in having healthy
occupation. The earlier in life it begins, the better. It is well for such
persons, unless of uncommon gifts in some direction, as many are,
to obtain quiet, routine positions in life, and to avoid its wearing
responsibilities as much as possible. The question of marriage is a
difficult one for the physician if he is called upon for advice. Of
course the risk often can be estimated only approximately, even after
knowing both parties, who will heed medical counsel implicitly if it
happens to coincide with their own notions. The further propagation
of the neuro-psychopathic constitution in the world involves much
entirely uncompensated misery, as well as genius, enthusiasm, and
originality, the compensation for which is estimated by society in one
way as regards Burns, Byron, De Quincey, Carlyle, Goldsmith, John
Howard, and Frederick the Great's father, and in another when
considering the inmates of jails and almshouses and the destroyers
of home peace. Maudsley thinks that one such poet as Shelley
justifies the risks of marriage in the insane diathesis, and Savage
considers the neuro-psychopathic constitution a useful element in
society; while Clouston holds that the world would be better off to
lose the few ill-balanced geniuses, the hundreds of impracticable,
unwise talented men and women, and the thousands of people who
cannot get on, shiftless, given to drink, idle, improvident, and
unpractical, to get rid of the insane diathesis, especially if we shall
find a middle course and learn to apply the laws of heredity so as to
save the best and eliminate the unsound. It is to this class probably
that Pinel refers in saying that what he calls moral insanity is largely
a matter of bad education. It is undoubtedly true that judicious
training in very many cases would limit, if not prevent, the further
development of the morbid element and strengthen the healthy side,
so as to prevent actual insanity.
CONSTITUTIONAL AFFECTIVE MENTAL DISEASE is a further development

of the congenital or hereditary predisposition to nervous or mental
disease, with more or less of the marks of the neuro-psychopathic
constitution. It is of two forms, the depressed and the mildly
exhilarated, in neither case amounting to simple melancholia or mild
mania. Sometimes the two forms are seen in a single member or in
different members of one family where mental degeneration has
begun. The frequent association of pulmonary consumption with
these cases is possibly, in part, due to malnutrition in those persons
living under the influence of more or less perpetual gloom, and to
exposure and over-exertion in those who are constantly unnaturally
excited, sleeping too little and driving their alert brains to the extent
of exhaustion. Misanthropists, communists, iconoclasts of all kinds,
enthusiasts and reformers, useful people and worse than useless,
common nuisances, criminals, saints, and heroes, are found among
them. Undoubtedly, in the case of criminals the tyranny of their
organization deprives the intellect of much of the proper inhibitory
power over the passions and evil tendencies, and yet with sufficient
motive they can hold themselves considerably in check.
The PROGNOSIS is not favorable. At the critical periods of life, after
severe diseases or injuries and with undue mental or physical strain,
there is danger of further progress of the disease into more
pronounced types; and this result is often the only way of satisfying
the community that what they called meanness or wickedness was
only disease. The progress of the disease is commonly very slow. It
often seems like simple progressive development of character,
except for the fact, generally overlooked, that it advances often in a
different direction to what would be natural, and is independent of
normal development. The subsidence of habitual severe headache
not seldom marks a sharp advance in the severity of the mental
symptoms.
The TREATMENT is hygienic. It must begin early in life, and be devoted

especially to avoidance of mental overwork, to healthy occupation, to
simple habits, and to a wise mental training.
MORAL INSANITY (Insanity of Action, Affective Insanity, l'Insanite

morale, Moralisches Irresein, Folie raisonnante, Folie lucide, Manie
sans délire of Pinel), the general moral mania of Ray, is
distinguished by that writer from partial moral mania (instinctive
mania, manie raisonnante of Pinel, la folie impulsive, impulsive
insanity, emotional insanity, impulsives Irresein), which includes
suicidal insanity, homicidal insanity, dipsomania, pyromania,
kleptomania, erotomania, nymphomania, satyriasis (aidoiomania),
animal impulse, perverted sexual instinct (conträre
Sexualempfindung, la sensation sexuelle contraire), and topophobia,
if that disease be classed among the insanities.
Moral insanity is seldom seen in the insane asylum until the disease
has passed over into pronounced mental enfeeblement or delusional
insanity. Purely moral insanity—“an uncontrollable violence of the
emotions and instincts”—is probably as rare as purely intellectual
insanity. Moral insanity is attended with some mental impairment,
just as moral perversion is part of intellectual insanity. Indeed, I have
heard patients complain as much of the degradation of character in
their insanity as of any symptoms referable directly to the intellect.
The term is not a fortunate one, but, like the expression moral
treatment of the insane, it is in quite general use. It is recognized by
all the authorities on mental disease, whatever may be their opinions
as to the limitations of responsibility in it. It is especially to it that we
can apply the words of the Autocrat of the Breakfast-Table, that the
worst forms of insanity are those to which the asylum shuts its doors.
It is marked by moral perversion, change of character and action,
and so little intellectual impairment as to be easily overlooked by one
not familiar with morbid mental phenomena.
Mild simple mania ending in recovery has been described as moral

insanity even by Pinel and Pritchard, and is so miscalled rather
generally at the present day. Moral deterioration is observed after
fevers or physiological periods of life, following slight and moderate
cerebral hemorrhages or injuries to the back and head, affecting the
brain, mental strain, etc., which, in persons of the neuro-
psychopathic constitution, now and then end in permanent change of
character. A similar but curable mental state is the frequent
beginning of more pronounced insanity, and often remains the sole
evidence of unsoundness of mind even after the patient is thought
well enough to be discharged from the asylum.
Although moral insanity is probably a common cause of young

persons of both sexes being led into lives of licentiousness,
wickedness, and crime, it is to be carefully differentiated from
deliberate yielding to temptation and following lives of vice until a
strong enough motive is offered for doing better or a punishment is
made sufficient to be deterrent.
Moral insanity is essentially a very slowly progressive and incurable

disease, starting in congenital or acquired mental deterioration, and
with its symptoms. It usually ends, after long years of wretchedness
to the individual and misery to his friends, in more general insanity,
slowly advancing dementia, death by intercurrent disease or
accident, or in suicide. It is a most distressing disease in the young,
who are punished by parents and teachers in succession, sent about
from one school to another, boarded with friends or with

Full Chapter Endocrine Emergencies Recognition and Treatment Contemporary Endocrinology 2Nd Edition Chaim Vanek PDF

Uploaded by

Document Information

Original Title

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Full Chapter Endocrine Emergencies Recognition and Treatment Contemporary Endocrinology 2Nd Edition Chaim Vanek PDF

Uploaded by

Copyright:

Available Formats

Endocrine Emergencies: Recognition

and Treatment (Contemporary

Endocrine Emergencies Recognition and Treatment Lynn

Endocrine and metabolic medical emergencies a clinician

Endocrine Disrupting Chemicals induced Metabolic

Islamophobia and Psychiatry: Recognition, Prevention,

Pediatric Endocrinology and Inborn Errors of Metabolism

Arrhythmia Recognition The Art of Interpretation 2nd

Acne Scars: Classification And Treatment 2nd Edition

Endocrinology and Systemic Diseases Piero Portincasa

More information about this series at http://www.springer.com/series/7680

ISSN 2523-3785 ISSN 2523-3793 (electronic)

© Springer Nature Switzerland AG 2021

Endocrine emergencies are too important to be left exclusively to endocrinologists.

New York, NY, USA Leonid Poresky

Medical emergencies in the field of endocrinology encompass thyroid, adrenal,

Portland, OR, USA Lynn Loriaux

1 Acute Adrenal Insufficiency�������������������������������������������������������������������� 1

12 Hyponatremia: SIADH���������������������������������������������������������������������������� 109

Karl E. Anderson, MD Preventive Medicine and Population Health, University of

1. Clinical setting: Shock resistant to volume and vasopressor resuscitation

© Springer Nature Switzerland AG 2021 1

Acute Adrenal Insufficiency

Effect of withdrawal of cortisone

In adrenal ectomized man

Adrenal crisis is characterized by cardiovascular collapse unresponsive to the

The Adrenal Response to Stress

These findings demonstrate that, at minimum, physiologic glucocorticoid

The Cortrosyn® Stimulation Test

∆ cortisol max fast 60 min. p.j.l n mol/1

10 mg ACTH (77%) 30 mg ACTH

2.5 mg ACTH (12%)

50 100 150 200 250 300 350

Peak ACTH levels ng/t

monitored. Intravenous desmopressin (DDAVP) is useful to prevent excessive water

1. Pearce JMS. Thomas Addison (1793 – 1860). J R Soc Med. 2004;97:297.

Beatrice C. Lupsa and Silvio E. Inzucchi

1. Clinical setting: Any altered state of well-being in the context of significant

B. C. Lupsa (*) · S. E. Inzucchi

© Springer Nature Switzerland AG 2021 9

u­ rinalysis. A workup for sepsis or other precipitating causes should be initi-

Diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic syndrome (HHS)

hyperglycemia and the presence of ketoacidosis. The fundamental difference

↑ Aminoacids ↓ Glucose utilization

Hyperlipidemia Dehydration Hyperosmolality

insulin resistance result in hyperglycemia and ketosis. Hyperglycemia evolves

History and Physical Examination

Physical findings include poor skin turgor, tachycardia, and hypotension. In

Table 2.2 Initial laboratory evaluation for DKA and HHS

Table 2.3 Typical deficits of water DKA HHS

in the liver. In addition, reduced activity of lipoprotein lipase in peripheral tissue

In the emergency room, fluid resuscitation is critical for intravascular, interstitial,

(this is termed the “glucose-insulin clamp” by some authorities). This technique

The only contraindication to insulin therapy is a current serum potassium below

There is no doubt, however, that home-treatment of the insane in the

It is not often that the physician is called, or his advice heeded if

Commitment to an asylum means so much that safeguards against

In many cases of insanity I make the question of removal to a large

The associations, surroundings, and influences brought to bear upon

After apparent recovery there should be a long period of after-

In the various forms of mental disease, through concentration of the

The conditions of cerebral hyperæmia require cold applications to

Ergot, hydrate of chloral, and opiates, which sometimes must be

New York, NY, USA Leonid Poresky

Portland, OR, USA Lynn Loriaux

1 Acute Adrenal Insufficiency�� 1

12 Hyponatremia: SIADH�� 109

Acute Adrenal Insufficiency

The Adrenal Response to Stress

The Cortrosyn® Stimulation Test

u rinalysis. A workup for sepsis or other precipitating causes should be initi-

History and Physical Examination