Diseases of the Adrenal

glands
 Adrenal insufficiency
• Adrenal insufficiency is a failure by the
adrenal gland to output enough steroid
hormones.
• Severe or chronic cases, (named also
Addison's disease), is a common cause of
adrenal failure.
• Adrenal gland failure may cause an
Addisonian crisis
Adrenal insufficiency symptoms
• Fatigue • Infertility
• Weakness • Alopecia
• Anorexia • Acute confusional state
• Nausea • Cutaneous pigmentation
• Vomiting • Mucosal pigmentation
• Hypotension
• Weight loss
• Hypoglycaemia
• Abdominal pain
 Lab Studies:
• CT scan
– A CT scan of the abdomen may show hemorrhage in
the adrenals, calcification of the adrenals, or
metastasis.
– In cases of secondary adrenal insufficiency, a head
CT scan may show destruction of the pituitary (ie,
empty sella syndrome) or a pituitary mass lesion.
• ECG: Elevated peaked T waves may indicate
hyperkalemia.
• Sodium level low (plasma or serum)
• Chloride level low (plasma or serum)
• Potassium level raised (plasma or serum)
• Hypoglycaemia
• Cortisol level low (plasma or serum)
• Osmolarity low (plasma)
• Sodium level raised (urine)
• Potassium level low (urine)
 Emergency Department Care:
Maintain airway, breathing, and circulation.
• Employ coma protocol (ie, glucose, thiamine,
naloxone).
• Use aggressive volume replacement therapy
(dextrose 5% in normal saline solution [D5NS]).
• Correct electrolyte abnormalities as follows:
• Use dextrose 50% as needed for hypoglycemia.
• Administer hydrocortisone 100 mg IVP q6h.
interference with testing of cortisol levels.
• Administer fludrocortisone acetate
(mineralocorticoid) 0.1 mg qd.
• Always treat the underlying problem that
precipitated the crisis.
 Treatment
• Cortisol is replaced orally with hydrocortisone tablets
(25-75 mg), a synthetic glucocorticoid, taken once or
twice a day (5-15 mg).
• If aldosterone is also deficient, it is replaced with oral
doses of a mineralocorticoid called fludrocortisone
acetate (Florinef), which is taken once a day.
• Patients receiving aldosterone replacement therapy are
usually advised by a doctor to increase their salt intake.
• Because patients with secondary adrenal insufficiency
normally maintain aldosterone production, they do not
require aldosterone replacement therapy.
 «Cushing's Syndrome»
• In 1932, a physician by the name of Harvey Cushing
described eight patients with
• central body obesity,
• glucose intolerance,
• hypertension,
• excess hair growth,
• osteoporosis,
• kidney stones,
• menstrual irregularity,
• and emotional liability.
• It is now known that these symptoms are the result of
excess production of cortisol by the tumor of adrenal
glands.
 "Cushings Disease"
• When a pituitary tumor secretes too much
ACTH (Adrenal Cortical Tropic Hormone),
it simply causes the otherwise normal
adrenal glands to produce too much
cortisol.
• This type of Cushings syndrome is termed
"Cushings Disease"
 Symptoms of Cushing's syndrome
• Obesity - with fat around the 'trunk' rather than arms and legs.
• Facial puffiness, and the face often looks 'redder' than usual.
• Diabetes.
• Facial hair in women.
• High blood pressure.
• Muscle weakness.
• Purple/pink stretch marks may appear - similar to those seen on
some pregnant women.
• Aches and pains - particularly backache.
• Mood swings - such as being more irritable, depressed, or anxious
than usual.
• Lack of sex drive (libido).
• Periods may become irregular, or stop, in women.
• Osteoporosis ('brittle bones').
• Oedema ('water retention') around ankles.
 Laboratory abnormalities in Cushing
syndrome
• 4 methods are accepted for the diagnosis of Cushing syndrome:
ü urinary free cortisol levels higher than 1500 mcg/24 h.
ü low-dose dexamethasone suppression test,
ü evening serum and salivary cortisol level,
ü and dexamethasone–corticotropin-releasing hormone test.
• A plasma ACTH level is undetectable in patients with ACTH-
independent Cushing syndrome.
• Imaging Studies
ü Imaging studies for Cushing syndrome should be performed after the
biochemical evaluation has been performed.
ü An abdominal CT scan is recommended if a primary adrenal problem is
suspected. The presence of an adrenal mass larger than 4-6 cm raises
the possibility that the mass is an adrenal carcinoma.
ü If a pituitary source of excess ACTH is suspected, patients should
undergo a contrast-enhanced magnetic resonance imaging (MRI) study
of the pituitary.
 Treatment of Cushing's syndrome
• Surgery to remove one or both tumor of
adrenal glands is an option.
• This stops the body making any cortisol
from adrenal glands.
• Patients after Surgery to remove of both
adrenal glands will need lifelong
replacement therapy of certain hormones.
 Conn Syndrome
• Conn syndrome is characterized by increased
aldosterone secretion from the adrenal glands,
suppressed plasma renin activity (PRA),
hypertension, and hypokalemia. It was first
described in 1955 by J.W. Conn in a patient who
had an aldosterone-producing adenoma ).
• Currently, primary hyperaldosteronism,
especially Conn syndrome, seems to be the
most common form of secondary hypertension.
 Symptoms
• Few symptoms are specific, and mostly they
result from hypokalemia and alkalosis.
Aldosterone, by inducing renal distal tubular
reabsorption of sodium, enhances secretion of
potassium and hydrogen ions, causing
hypernatremia, hypokalemia, and alkalosis.
• Patients with severe hypokalemia report fatigue,
muscle weakness, cramping, headaches, and
palpitations. They can also have polydipsia and
polyuria from hypokalemia-induced nephrogenic
diabetes insipidus.
 Lab Studies
• Routine laboratory studies can show hypernatremia,
hypokalemia, and metabolic alkalosis
• Almost 20% of patients have impaired glucose tolerance
however, diabetes mellitus is rare.
• Typically, renin levels are suppressed to less than 1
ng/mL/h in patients with primary hyperaldosteronism,
and levels do not stimulate above 2 ng/mL/h with
diuretics and upright posture.
• The most commonly used confirmatory test is a 24-hour
urine aldosterone level obtained after 3 days of salt
loading. The patient can be instructed to maintain a
sodium intake of at least 200 mEq/d for 3 days.
• A 24-hour aldosterone excretion rate of greater than 14
mcg (with a concomitant 24-h urine sodium >200 mEq)
is diagnostic of primary hyperaldosteronism.
 Imaging Studies
• CT scanning
– Once the diagnosis of primary hyperaldosteronism is
confirmed, the next step is to differentiate the
subtypes and to identify surgically curable disease.
For practical purposes, this means distinguishing
between an adrenal adenoma and bilateral
hyperplasia.
– Scanning with iodine I 131 iodocholesterol (NP-59, a
precursor of aldosterone): This has also been used to
detect unilateral functional adrenal lesions. In
experienced hands, NP-59 scanning has a sensitivity
of 88%. However, this procedure is not widely
available, requires careful patient preparation, is very
expensive, and rarely detects lesions larger than 1.5
cm.
– MRI: MRI is not more sensitive than CT scanning.
 Treatment
• Surgery is the main therapy for Conn syndrome. A
laparoscopic adrenalectomy is favored, when possible.
• Medical therapy is administered to patients with
persistent hypertension postoperatively, poor surgical
candidates, and those who refuse surgery.
• A sodium-restricted diet (<80 mEq or <2 g of sodium per
d), maintenance of ideal body weight, and regular
aerobic exercise contribute substantially to the success
of pharmacologic treatment.
• Frequently, hypertension and hypokalemia can be
controlled with a potassium-sparing agent (first-step
agent) such as spironolactone.
• Second-step agents include thiazides diuretics, ACE
inhibitors, calcium channel antagonists, and angiotensin
II blockers.
The diseases of the pituitary gland
and hypothalamus
The pituitary gland, or hypophysis, is an endocrine gland
about the size of a pea that sits in a small, bony cavity (sella
turcica) at the base of the brain.
 Major hormones secreted
Secretory cells Hormone Target Effect
Adrenocorticotro Adrenal Secretion of
Corticotrophs pic hormone gland glucocorticoids
(ACTH)
Follicle- Ovaries, Growth of reproductive
Gonadotrophs stimulating Testes system
hormone (FSH)
Luteinizing Ovaries, Sex hormone production
Gonadotrophs hormone (LH) Testes
Growth hormone Liver, Promotes growth; lipid &
Somatotrophs (GH) adipose carbohydrate
tissue metabolism
Lactotrophs Prolactin (PRL) Ovaries, Secretion of estrogens /
(Mammotrophs) mammary progesterone; milk
glands production
Thyroid- Thyroid Secretion of thyroid
Thyrotrophs stimulating gland hormones
hormone (TSH)
 Pathology
Condition Direction Hormone

Acromegaly overproduction growth hormone

Growth underproduction growth hormone

hormone
deficiency
Syndrome of overproduction vasopressin
inappropriate
antidiuretic
hormone
 Condition Direction Hormone

Diabetes underproduction vasopressin

insipidus

Sheehan underproduction prolactin

syndrome

Pituitary overproduction any pituitary

adenoma hormone

Hypopituitarism underproduction any pituitary

hormone
 Diabetes insipidus
• Diabetes insipidus (DI) is a disease
characterized by excretion of large amounts of
severely diluted urine, which cannot be
reduced when fluid intake is reduced.
• It denotes inability of the kidney to concentrate
urine.
• DI is caused by a deficiency of antidiuretic
hormone (ADH), or by an insensitivity of the
kidneys to that hormone.
 Signs and symptoms
• Excessive urination
• Extreme thirst (especially for cold water)
• Symptoms of diabetes insipidus are quite similar to those of
untreated diabetes mellitus, with the distinction that the urine
is not sweet and there is no hyperglycemia (elevated blood
glucose). Blurred vision is a rarity.
• The extreme urination continues throughout the day and the
night.
• In children, DI can interfere with appetite, eating, weight gain,
and growth as well. They may present with fever, vomiting, or
diarrhea.
• Adults with untreated DI may remain healthy for decades as
long as enough water is drunk to offset the urinary losses.
However, there is a continuous risk of dehydration.
 Diagnosis
• Blood glucose, bicarbonate and calcium need to be tested.
• Electrolytes can show substantial derangement;
- hypernatremia is common in severe cases.
• Urinalysis shows low electrolyte levels, and measurement of
urine osmolarity (or specific gravity) is generally low.
• A fluid deprivation test helps determine whether DI is caused by
- excessive intake of fluid
- a defect in ADH production
- a defect in the kidneys' response to ADH
• This test measures changes in body weight, urine output, and
urine composition when fluids are withheld. Sometimes
measuring blood levels of ADH during this test is also
necessary.
 Treatment
• Central DI and gestational DI respond to desmopressin.
• In dipsogenic DI, desmopressin is not usually an option.
• 3 groups of nonhormonal drugs are useful in reducing polyuria:
various diuretics, primarily thiazides; ADH-releasing drugs, such
as chlorpropamide, carbamazepine, and clofibrate; and
prostaglandin inhibitors, which are modestly effective.
• Desmopressin will be ineffective in nephrogenic DI. Instead, the
diuretic hydrochlorothiazide (HCT or HCTZ) or indomethacin
can improve NDI;
• chlorpropamide, carbamazepine, and clofibrate can reduce or
eliminate the need for vasopressin in some patients with partial
CDI. None are effective in NDI.
• Prostaglandin inhibitors (indomethacin 0.5 to 1.0 mg/kg po tid,
although most NSAIDs are effective) may reduce urine volume,
but generally by no more than 10 to 25%, perhaps by
decreasing renal blood flow and GFR.
 Information sources:
1. Endocrinology: Textbook / Ed. by prof. Petro M. Bodnar. – Vinnytsia: Нова
Книга, 2017. – 327 р.
2. Contemporary Aspects of Endocrinology / A. Diamanti – Kandarakis. –
2011. – 478p.
3. Eear Book of Endocrinology / M. Schott. – 2012. – 408 p.
4. Hot topics in Endocrine and Related Disease / M. Fedele. – 2013. – 274 p.
5. Williams Textbook of Endocrinology, 14th Edition / S. Melted, R. Koenig, C.
Rosen, R. Auchus, A. Goldfine / 2019. – 1792 p.
6. Harrison`s principles of internal medicine, 20th Edition / J. L. Jameson,
A.S. Fauci, D.L. Kasper, S.L. et all. – 2018. – Р. 4048.
7. http://406.dsma.dp.ua/
8. https://www.endocrinology.org/
9. https://www.ese-hormones.org/
10. European Society of Cardiology. https://www.escardio.org/
 Topic lecture questions:
1. Please, list etiological factors of Addisons’ disease

2. Please, define diagnostical criteria for Cushing

syndrome

3. Please, list laboratory criteria for Conn syndrome

4. What is a first-line treatment for symptomatical arterial

hypertension caused by pheochromocytoma?

5. Please, list key points for treatment patients with

Diabetes insipidus