Pass Critical Care Endocrine Frcem Resources

Dr Ali Ragab (www.facebook.com/groups/pass.critical.
care/)
Pass Critical Care

Essential ICU study notes
Endocrine
Dr. Ali Ragab
1
Dr Ali Ragab (www.facebook.com/groups/pass.critical.care/)
Table of Contents
DIABETIC KETOACIDOSIS (DKA) ............................................................................................... 3
ALCOHOLIC KETOACIDOSIS (AKA).......................................................................................... 11
HYPERGLYCEMIA IN CRITICALLY ILL PATIENT ......................................................................... 13
HYPERGLYCEMIC HYPEROSMOLAR SYNDROME .................................................................... 16
HYPOGLYCEMIA .................................................................................................................... 18
DIABETES INSIPIDUS ............................................................................................................. 23
MYXEDEMA COMA ............................................................................................................... 26
THYROID STORM .................................................................................................................. 30
SICK EUTHYROID SYNDROME ................................................................................................ 34
ADRENAL FAILURE ................................................................................................................ 35
HYPOPITUITARY COMA......................................................................................................... 40
2
DIABETIC KETOACIDOSIS (DKA)

Definition
• DKA = hyperglycemia + metabolic acidosis + ketosis.
Common triggers for DKA

• Discontinuation/missing insulin therapy.
• Infection.
• New onset of DM.
• Major stressors à infection – MI – trauma.
• Medication à high-dose glucocorticoid therapy.
Pathophysiology
Hyperglycemia
• Total or near-total insulin deficiency à inability of glucose to enter
cells + ↑ hepatic glucose production à hyperglycemia à osmotic
diuresis à loss of free water and depletion of electrolytes.
Ketonemia or ketonuria
• ↓ Insulin à ↓ glucose entry into cells à adipose tissue releases free
fatty acids (lipolysis) à metabolized by the liver to acetoacetate and
β–hydroxybutyrate.
Metabolic acidosis
• ↑ Ketones production à H+ accumulation à metabolic acidosis.
Clinical manifestations
• GIT à nausea – vomiting – abdominal pain – polyphagia.
• Respiratory à Kussmaul’s respiration – acetone breath odor.
• Circulatory à dehydration – orthostatic hypotension – tachycardia.
• Urinary à polydipsia – polyuria.
• CNS à DCL – drowsiness – coma.
Diagnosis
3
Hyperglycemia
• Plasma glucose >200 mg/dL or known DM.
Metabolic acidosis
• pH <7.30 – HCO3 <15 mEq/L – base excess < −10.
• Metabolic alkalosis may be associated with severe vomiting (rare).
Serum anion gap
• Estimate of the quantity of serum unmeasured anions (e.g. albumin –
lactate – drugs – alcohol – ketones).
Serum anion gap = (Na + K) − (CL + HCO3)
• Patients with DKA usually present with serum anion gap >20 mEq/L.
Ketonemia and ketonuria
• Ketonemia (≥ 3 mmol/L) or significant ketonuria (> ++ on dipstick).
Increased serum levels of Ketone bodies
• Acetoacetate + β–hydroxybutyrate + Acetone.

BOHB: AcAc ratio
• Normally BOHB: AcAc ratio is 3: 1.

• Acidosis increases ratio to 6: 1 or even 12: 1.
Short come of dip-testing methods
• Some dip-testing methods only check for AcAc and acetone but not
BOHB which can be the main ketone body found in urine initially.
• Captopril can also give false positive test for urinary acetone.
Serum ketones and creatinine level
• Serum ketones may interfere with some creatinine assays and give
falsely high readings.
• If in doubt à measure capillary ketones (ketonemia >3 mmol/L)
Serum sodium concentration
4
• Usually decreases due to osmotic effect of hyperglycemia.

• Serum Na decreases by 1.6 mEq/L for every 100 mg/dL increase in
glucose level above 100 mg/dL.
Potassium concentration
• Initial hyperkalemia due to acidosis (despite low total body K).
• As insulin is given à shift of potassium into cells à hypokalemia.
Renal
• ↑ BUN (due to prerenal azotemia).
• AcAc can interfere with some creatinine assays.
Hematology
• ↑ Hematocrit and hemoglobin.
• ↑ TLC with left shift (in the absence of infection).
Lipids
• ↑ Serum triglyceride (reverses with insulin therapy).
Serum amylase
• ↑ Serum amylase (up to × 10) (even in absence of pancreatitis).
Other investigations
• Chest radiograph and ECG.
• Patient (>40 years) à consider cardiac markers even if asymptomatic.
Initial Laboratory Values in DKA and HHS

Value DKA HHS
Mild Moderate Severe
BG (mg/dL) >250 >250 >250 >600
Arterial pH 7.25–7.30 7.00–7.24 <7.00 >7.30
HCO3 (mEq/L) 15–18 10–14 <10 >15
5
Urine/serum Positive Positive Positive Trace

Ketones
Osmolarity <320 <320 <320 330–380
(mOsm/L)
Anion gap >10 >12 >12 <12
Mental state Alert Alert/drowsy Stupor/coma Stupor/coma
Na (mmol/L) 125–135 125–135 125–135 135–145
Severe DKA
• If ≥1 of the following features is present à transfer to ICU for
monitoring and CVC.
Criteria of severe DKA

• Blood ketones > 6 mmol/L.
• Venous HCO3 < 5 mmol/L.
• Venous/arterial pH < 7.00.
• K < 3.5 mmol/L on admission.
• GCS < 12.
• O2 saturation <92% on air (assuming no respiratory disease).
• SBP < 90 mmHg.
• Pulse >100 or < 60 bpm.
• Anion gap above 16.
Management of DKA
Fluid replacement à 0.9% saline (replacement fluid of choice)
• Typical fluid deficit à 100 mL / kg.
• Rate of fluid replacement
o 1000 mL over 1 hour (faster if SBP < 90 mmHg) then
o 1000 mL over 2 hours then
o 1000 mL over 8 hours.
6
Bicarbonate
• Bicarbonate may increase risk of cerebral edema (not recommended).
Indication
• pH ≤ 7.0 + respiratory depression or severe hypotension unresponsive

to aggressive fluid replacement.
• When pH ≥ 7.1 à stop infusion.
Administration
• Two ampules (2 x 50 mEq) + 1000 mL D5W.
Glucose
• If glucose <250 mg/dL à start 10% glucose at 125 mL/h to run
alongside saline (Avoid hypoglycemia).
Potassium
• Typical deficit = 3-5 mEq/kg.
• Typical infusion rate = 20 mEq/h (40 mEq/h in severe hypokalemia).
• Don’t add K to the 1st bag; thereafter add K according to most recent
VBG result.
Serum K (mmol/L) Amount of KCl to add per liter of IV fluid

>5.5 Nil
3.5–5.5 40 mmol
<3.5 higher doses
Phosphate
• Insulin infusion à ¯ phosphate concentration within 4-6 hours.
Manifestations of severe hypophosphatemia
• Neurologic disturbances – arthralgias – muscle weakness with

respiratory failure – rhabdomyolysis – liver dysfunction.
7
Administration
• 5 mL K phosphate ampule in severe hypophosphatemia (<1.0 mg/dL).
Insulin therapy
Infusion
• 50 U soluble insulin + 50 mL 0.9% saline à infuse at 0.1 unit/kg/h.

• Continue patient’s regular long-acting insulin at usual doses/times.
• Consider long-acting insulin in newly diagnosed DM type 1.
• Start insulin IVI when fluid and electrolyte correction are underway.
Goal of therapy
• ↓ Blood ketones by 0.5 mmoL/L/h.

• ↑ Venous HCO3 by 3 mmoL/L/h.
• ↓ Blood glucose by 50-75 mg/dL/h.
• If not achieving à ↑ insulin IVI by 1 U/h until target rates achieved.
Continue fixed rate insulin until
• Ketones < 0.6 mmoL/L.

• Venous pH > 7.30.
• Venous HCO3 > 18 mmoL/L.
• Do not rely on urinary ketones to indicate resolution — they stay
positive after DKA resolved.
Find and treat infection/cause for DKA

• If precipitating cause is left untreated à DKA may recur.
Complications
Electrolyte disturbances
• Hypokalemia – hypomagnesemia – hypophosphatemia.
Recurrence of DKA during hospital stay
8
Causes of recurrent DKA during hospital stay
• Stopping insulin early.

• Severe infection.
• Severe contra-insulin state (e.g. Cushing syndrome).
• Medications (e.g. glucocorticoids).
Cerebral edema
• See below.
Persistent hypotension
Causes of persistent hypotension
• Rapid falling of blood glucose à fluid shifts à ↓ BP.

• Other causes à bleeding – severe acidosis – arrhythmia – MI – cardiac
tamponade – sepsis – adrenal insufficiency.
Renal complications
• Postrenal obstruction – atonic bladder – ATN due to pyelonephritis.
Thromboembolism
• Thrombosis of cerebral vessels and stroke (uncommon).
Hyperchloremic metabolic acidosis

• Hyperchloremic metabolic acidosis with normal anion gap frequently
develops after therapy and corrects spontaneously.
Cerebral edema in DKA

Clinical features
• Headache – DCL.
• Sudden deterioration in mental status after initial improvement.
• Bradycardia – hypertension – papilledema.
Risk factors
9
• Rapid decline in BG.
Management
• Initiate treatment as soon as cerebral edema is clinically suspected.
Mannitol
• 0.5-1 gm/kg IV over 20 min.

• Repeat if there is no initial response in 30 min to 1 hour.
Hypertonic saline (3%)
• 5-10 mL/kg over 30 min.

• Alternative to mannitol (if there is no initial response to mannitol).
↓ Fluid administration
• ↓ Rate of fluid administrated by one-third.
Hyperventilation
• Hyperventilation to PCO2 < 22 mmHg has been associated with poor

outcomes and is not recommended.
Other measures
• Elevate the head of the bed.

• Intubation for airway protection and impending respiratory failure.
Obtain CT brain
• After treatment is initiated.

• Obtain brain CT to rule out thrombosis or hemorrhage.
10
ALCOHOLIC KETOACIDOSIS (AKA)

Definition
• Complex acid-base disorder that occurs in chronic alcoholics.
• Usually appears 1-3 days after period of heavy binge drinking.
Pathophysiology
• Ethanol ingestion (large quantity) à ↓ gluconeogenesis but not
glycogenolysis à hypoglycemia (when glycogen stores are exhausted)
à ↓ insulin levels à release of free fatty acids from adipose tissue à
formation of ketone bodies.
Clinical features
• Nausea – vomiting – abdominal pain.
• Electrolyte abnormalities (↓ Na – ↓ K – ↓ PO4 – ↓ Mg).
• Hypoglycemia.
• Occurs typically in alcohol abusers but can occur after binge drinking
in adults or accidental ingestion in children.
Laboratory
• Hypoglycemia (can be as low as 20 mg/dL).
• Anion gap acidosis (arterial pH < 7.20).
• Both ketoacids and lactate contribute to the unmeasured anion pool.
Ketoacids + hypoglycemia
• Ketoacids in hypoglycemic patient excludes hyperinsulinemia as the
cause of hypoglycemia.
Management
Fluids and electrolytes
• Rehydration with IV fluids.
• Electrolytes replacement as indicated.
11
Glucose
• Correct hypoglycemia with D50W.
Glucose and fluids administration à ↑ insulin à ↓ lipolysis and free fatty

acid release à rapidly reverses the condition.
Thiamine
• Parenteral thiamine (100 mg) to prevent Wernicke encephalopathy.
12
HYPERGLYCEMIA IN CRITICALLY ILL PATIENT

Definition
• Hyperglycemia = FBG > 126 mg/dL OR any RBG >200 mg/dL.
Etiology
Type 1 diabetes (insulin dependent)
• Autoimmune destruction of insulin producing β cells of pancreas à
absolute insulin deficiency.
Type 2 diabetes (non-insulin-dependent)
• Relative insulin deficiency due to defects in both insulin action and
insulin secretion à can be treated with diet ± oral agents ± insulin
(insulin is the most appropriate during acute illness).
Drug induced
• Catecholamines – glucocorticoids.
Other causes
• Gestational diabetes.
• Pancreatectomy.
• Stress hyperglycemia.
• Nutritional support (e.g. TPN – continuous enteral tube feeding).
Diagnosis
Bedside blood glucose monitoring
• Fasting blood glucose > 126 mg/dL or any RBG >200 mg/dL.
• Less accurate at blood glucose extremes à verified with laboratory.
• Do not delay therapy awaiting confirmatory laboratory results.
Management
Target blood glucose concentration
• Recommended BG level à 140-180 mg/dL.
13
Insulin-infusion Protocol
• Start insulin infusion if 2 consecutive BG values are >180 mg/dL.
• 0.1 U/kg IV push; then IVI at 0.1 U/kg/h.
• Measure blood glucose level q1-2h during insulin therapy.
• Goal à ↓ BG by 50-75 mg/dL/h.
• If this goal is not achieved à double insulin infusion rate.
Transitioning to subcutaneous insulin

Criteria for transitioning
• Stable IV insulin dose and glucose within target range for 6 hours.
• IV regular insulin should be continued for 2-3 hours after the first
subcutaneous insulin is injected.
Calculate insulin requirement
• Establish 24-hour insulin requirement.

• Give 50% as basal insulin and plan 50% as prandial insulin.
• Correction bolus can be added for BG above 150.
Oral agents
Oral hypoglycemic agents should not be used in the ICU
• Metformin (Glucophage) à risk of lactic acidosis.

• Thiazolidinediones (Actos) à risk of congestive heart failure.
Special considerations
Hyperglycemia and surgery
• Patient prepared for urgent surgery or during surgery à treat with SC

short-acting insulin or continuous IVI insulin.
Hyperalimentation and hyperglycemia
14
• Add ≤ 50% of anticipated total insulin requirement for duration of

feeding to parenteral nutrition formulations.
• Additional insulin should be administered by IVI or SC injection.
• If large insulin dose is required à ↓ carbohydrates administration.
15
HYPERGLYCEMIC HYPEROSMOLAR SYNDROME

Definition and etiology
• Severe hyperglycemia + hyperosmolarity + dehydration.
• Typically seen in elderly type II diabetic patients.
Pathophysiology
Relative insulin deficiency = enough insulin to inhibit ketone body
formation but not enough to prevent glycogenolysis and gluconeogenesis
• ↓ Insulin à ↑ BG à osmotic diuresis à fluid and electrolyte losses.
Clinical features
• Hyperglycemia à thirst – polyuria.
• Dehydration à hypotension – tachycardia.
• CNS à lethargy – confusion – seizures – coma.
Diagnosis
• Hyperglycemia à usually >600 mg/dL.
• Hyperosmolarity à usually >350 mOsm/kg.
• Serum ketones à usually normal or slightly elevated.
• ABG à pH > 7.30 (no acidosis); serum HCO3 >15.
• BUN à usually elevated (prerenal azotemia is common).
Management
Correction of hypovolemia
• Fluid deficit = 100-200 mL/kg.
• In the first 2 hours à give 1-2 L of 0.9% saline.
• Patient requires 6-8 L of fluids during the first 12 hours.
Type of crystalloids
• Normal saline à even in hypernatremia to expand extracellular fluid.
16
• ½ normal saline à switch to ½ normal saline once patient stabilizes.
Hemodynamic monitoring
• Hemodynamic monitoring is advised during aggressive rehydration

in elderly person with heart disease.
Electrolyte management
Potassium replacement
• Started as soon as urine flow has been established.

• Insulin therapy à rapid fall in serum K.
• Check serum K frequently and monitor ECG.
Insulin therapy
• HHS à more sensitive to insulin than DKA.
o Initial bolus is not recommended.
o Start at 0.05 U/kg/h.
• Maintain BG near 250 mg/dL for the first 24 hours.
• Rapid fall in BG à rapid osmotic shifts à ↓ BP and cerebral edema.
• Delay insulin in HHS until at least 1 liter of normal saline infused.
Management of the underlying cause

• Infection.
• Stress à e.g. MI or trauma.
• Anxiolytics and sedatives à ↓ response to thirst.
• Diuretics à prerenal azotemia.
• Steroids à hyperglycemia.
• Endocrinal diseases à hypothyroidism or apathetic thyrotoxicosis.
17
HYPOGLYCEMIA
Definition
• No specific BG level defines hypoglycemia (Typically <50 mg/dL).
Whipple triad defines hypoglycemia best

1. Documentation of low glucose concentration.
2. Concurrent symptoms of hypoglycemia.
3. Resolution of symptoms after administration of glucose.
Etiology
Excess insulin
• Intensive insulin therapy and insulin overdose.
Oral medications
Sulfonylurea à augment insulin secretion
• Hypoglycemia in young à in the setting of drug overdoses.

• Hypoglycemia in elderly à in the setting of starvation superimposed
on liver or kidney impairment.
Antidiabetic agents à promote normoglycemia via other mechanisms
• Metformin – thiazolidinediones – alpha glucosidase inhibitors.

• When given as monotherapy they seldom cause hypoglycemia.
Insulinomas/hyperinsulinemia
• Insulin-secreting pancreatic islet cell tumors.
• Paraneoplastic hypoglycemia à tumors secreting insulin-like GF.
• Gastric bypass surgery à postprandial hypoglycemia.
• Autoimmune à anti-insulin receptor antibodies in Hodgkin’s disease.
Deficiencies in counterregulatory hormones

• Adrenal disease (↓ glucocorticoid à hypoglycemia).
18
• Hypopituitarism (↓ GH – ↓ cortisol – ↓ thyroid hormone).

• Glucagon deficiency (rare cause of hypoglycemia).
Inadequate production of endogenous glucose

• Severe hepatic dysfunction.
• Chronic renal insufficiency.
Alcohol induced hypoglycemia

• Ethanol à ↓ gluconeogenesis.
Drugs
• Beta blockers à ↓ gluconeogenesis and mask adrenergic symptoms.
• Salicylates à hypoglycemia in children but rarely in adults.
Sepsis
• Sepsis has occasionally been implicated in hypoglycemia.
Clinical presentation
Adrenergic symptoms (autonomic nervous system activity)
• Palpitations – sweating – anxiety – tremor – tachycardia.
Neuroglycopenic symptoms (decreased activity of CNS)

• Dizziness – headache – clouding of vision – mental dullness – fatigue
– confusion – seizures – coma.
Laboratory
Blood glucose concentration
• BG level <50 mg/dL + symptoms of hypoglycemia.
Ketonuria
• ↓ Glucose à ↓ insulin levels à lipolysis and ketogenesis.
• Hypoglycemia + ketonuria is unlikely to be due to high insulin.
19
Detection of drugs and toxins

Oral agent abuse
• Test serum and urine for sulfonylureas.
Detection of insulin injection abuse
• Obtain simultaneous insulin and C-peptide during hypoglycemia.

• Insulin and C-peptide are co-secreted by β-cells (C-peptide is not
present in commercial insulin).
Insulinomas
Radiology
• Insulinomas are often small and difficult to visualize radiographically.
Immune-reactive insulin/glucose ratio
• Suspected insulinoma à obtain fasting immune-reactive insulin and

glucose (mg/dL) à if IRI/glucose ratio is > 0.3 à insulin may be
inappropriately high.
Pro-insulin
• Pro-insulin >30% of insulin concentration à insulinoma.
ECG abnormalities
• T wave flattening – ↑ QT interval – ST segment depression – ↓ HR.
Other
• Check hepatic and renal function.
• Suspected adrenal insufficiency à cosyntropin test.
Management
Glucose
Bolus glucose administration
20
• IV 50 mL of D50W over 3-5 min.

• Cooperative patients à PO carbohydrates (e.g. glucose tablets).
Glucose infusion
• Indication à hypoglycemia not due to exogenous short- or

intermediate- acting insulin (D5W or D10W).
• Maintain target BG level >100 mg/dL (monitor BG every 1-3 hours).
• Meals should be provided if the patient can eat.
When to stop glucose infusion?
• Discontinue infusion à measure BG q15min à if patient is unable to

maintain BG >50 mg/dL or if the patient becomes symptomatic à
start glucose therapy again.
Hypoglycemia due to sulfonylurea?
• Admit to hospital because the ½ life of these drugs >24 hours.

• Sulfonylurea overdose may require 2-3 days of IV glucose therapy.
• Glucose infusions are continued while such patients are asleep.
• Somatostatin analog octreotide à ↓ insulin secretion (may be helpful).
Glucagon
• Glucagon 1 mg IV/IM (will not work in malnourished patients).
• Most effective in patients with ample liver glycogen stores.
Agents that block insulin secretion

• If hypoglycemia is due to insulinoma or nesidioblastosis à add drugs
that inhibit insulin secretion (diazoxide and octreotide).
Prevent drug absorption and increase elimination

• Activated charcoal à adsorbs sulfonylureas.
• Urinary alkalinization à enhance sulfonylurea excretion.
• Charcoal hemoperfusion à indicated in RF and massive overdose.
21
Steroids
• Glucocorticoids à ↑ gluconeogenesis + ↓ insulin action.
• Indication à in refractory hypoglycemia of obscure etiology.
22
DIABETES INSIPIDUS
Definition
Passage of large volumes (>3 L/day) of dilute urine due to impaired water
resorption by the kidney due to
• Cranial DI à ↓ ADH secretion from posterior pituitary.

• Nephrogenic DI à ↓ response of the kidney to ADH.
Etiology
Causes of cranial DI
• Infection à meningoencephalitis.
• Infiltration à histiocytosis – sarcoidosis.
• Inflammatory à autoimmune hypophysitis.
• Tumor à craniopharyngioma – metastases – pituitary tumor.
• Trauma à temporary if distal to pituitary stalk.
• Congenital à defects in ADH gene.
• Vascular à hemorrhage.
• Surgery à Hypophysectomy.
• Idiopathic.
Causes of nephrogenic DI
• Inherited.
• Metabolic à low potassium – high calcium.
• Drugs à lithium – demeclocycline.
• Chronic renal disease.
• Post-obstructive uropathy.
Gestational DI
• ↑ placental production of vasopressinase.
• Variant of central or nephrogenic DI developing during pregnancy.
Symptoms
23
• Polyuria – polydipsia – dehydration.

• Symptoms of hypernatremia.
Investigations
Hallmark of DI = dilute urine + hypertonic plasma.
Serum and urine osmolalities

Serum osmolality
𝐠𝐥𝐮𝐜𝐨𝐬𝐞 𝐦𝐠/𝐝𝐋 𝐁𝐔𝐍 𝐦𝐠/𝐝𝐋
Posm = 2 x (Na + k) + 𝟏𝟖
+ 𝟐.𝟖
• Normal plasma osmolality à 285-295 mOsm/kg and urine can be

concentrated to more than twice this concentration.
Urine osmolality
• In central DI à urine osmolarity is <200 mOsm/L.

• In nephrogenic DI à urine osmolarity is between 200-500 mOsm/L.
In diabetes insipidus
• ↑ Plasma osmolality + ↓ urine osmolality (U/P ratio < 2/1).
8–hour Water deprivation test

Diagnosis of DI is confirmed by urinary response to fluid restriction
• Failure of urine osmolarity to increase by > 30 mOsm/L in the 1st few

hours of complete fluid restriction à DI.
• Fluid losses can be excessive during fluid restriction in DI (particularly
central DI) à monitor fluid restriction carefully.
Once diagnosis of DI is confirmed à vasopressin (5U IV)
• In central DI à urine osmolality ↑ by ≥50% immediately.

• In nephrogenic DI à urine osmolality is unchanged.
Management
24
Cranial DI
• MRI (head) + test anterior pituitary function.
Desmopressin (synthetic analogue of ADH)
• Usual dose à 2-5U of aqueous vasopressin SC q4-6h.

• Serum Na à monitor during vasopressin therapy because water
intoxication and ↓ Na can occur if central DI begins to resolve.
Nephrogenic DI
• Treatment of the underlying cause.
• If persistent à try bendroflumethiazide 5 mg PO/24h.
• NSAIDS à inhibition of prostaglandin synthase (prostaglandins
locally inhibit the action of ADH) à ↓ urine volume.

• IV fluids to keep up with urine output.
• If pNa ≥ 170 à use 0.9% saline (↓ Na by <12 mmol/L per day).
• Use of 0.45% saline can be dangerous.
25
MYXEDEMA COMA
Definition
• Severe longstanding hypothyroidism.
Clinical features of myxedema coma

Neurological features
• Sleepy – lethargic – ↓ mood – ↓ memory – dementia – ataxia –
neuropathy – reflexes relax slowly.
CVS
• ↓ HR – ↓ BP – CHF – pericardial effusion.
General
• Face à round puffy face.
• Extremities à non-pitting edema – cold.
• Skin à dry thin hair/skin.
• Hoarse voice.
• ↑ Weight.
• Goiter.
GIT
• Constipation – ileus.
Muscles
• Myopathy – myalgia – cramps – weakness.
Etiology
Primary autoimmune hypothyroidism
Primary atrophic hypothyroidism
• Diffuse lymphocytic infiltration of thyroid à atrophy (no goiter).
26
Hashimoto’s thyroiditis
• Goitre due to lymphocytic and plasma cell infiltration.

• May be hypothyroid or euthyroid.
• Initial period of hyperthyroid (Hashitoxicosis) – rare.
• Autoantibody titres are very high.
Other causes of primary hypothyroidism
• Iodine deficiency.
• Surgery à post-thyroidectomy.
• Drug à antithyroid drugs – amiodarone – Li – iodine – radioiodine.
Secondary hypothyroidism
• Not enough TSH due to hypopituitarism (very rare).
Investigations
Thyroid function tests
Primary hypothyroidism
• Serum free T4 à ↓ (<5 pmol/L).

• Serum TSH à ↑ (>50 mU/L).
• Serum T3 à should not be requested (inaccurate for hypothyroidism).
Secondary hypothyroidism
• Serum free T4 à undetectable.

• Serum TSH à low – normal – slightly elevated (range of 5–8 mU/L).
Respiratory function tests

• Hypoventilation à type II respiratory failure (↓ PO2 + ↑ PCO2).
Chest X-ray
• Pleural effusion – cardiomegaly – pericardial effusion.
27
ECG
• Sinus bradycardia + low voltage complexes.
Other investigations
• Serum Na à ↓ <130 mmol/L (often <120 mmol/L).
• Anemia à normochromic macrocytic.
• ↓ eGFR.
• ↑ Serum creatine kinase.
• Hypercholesterolemia.
Treatment
Supportive treatment
• Hypoventilation à assisted ventilation.
• Hypotension à hemodynamic support.
• Hypoglycemia à IV glucose.
• Hyponatremia à water restriction or hypertonic saline.
• Hypothermia à passive rewarming.
Treatment of the cause

• Treat underlying infection and other illnesses (if present).
Thyroid hormone replacement

• T3 (liothyronine) 5-20 mcg q4-12h IV slowly until sustained
improvement (2-3 days) then levothyroxine 50 mcg q24h PO.
Hydrocortisone
• Hydrocortisone 100 mg/8h IV — vital if pituitary hypothyroidism.
Minimize/avoid (sedatives – hypnotics – narcotics)

• Due to ↑ duration of action and ↑ obtundation.
Active heating
28
• Active warming (blankets and fluids) may be needed for hypothermia.

• Rewarming rate should not exceed 0.5°C/h until core temperature is
raised to approximately 31 °C.
Complications
• High mortality (60%) despite optimal treatment.
• Hypotonia of GIT.
• Urinary retention due to hypotonic bladder.
29
THYROID STORM
Definition
• Life-threatening hypermetabolic state due to ↑↑ thyroid hormone.
Etiology
• Hyperthyroidism (most common).
Graves’ disease
• Circulating IgG à bind to and activate G-protein-coupled thyrotropin
receptors à thyroid enlargement and ↑ hormone production (react
with orbital autoantigens).
Toxic multinodular goiter
• Seen in elderly and in iodine-deficient areas (nodules that secrete
thyroid hormones).
Toxic adenoma
• There is solitary nodule producing T3 and T4.
Ectopic thyroid tissue

• Metastatic follicular thyroid cancer.
• Struma ovarii (ovarian teratoma with thyroid tissue).
Exogenous
• Iodine excess (food contamination and contrast media).
• Levothyroxine excess à ↑ T4 + ↓ T3 + ↓ thyroglobulin.
Others
• De Quervain’s thyroiditis à self-limiting post-viral painful goiter.
• Drugs à amiodarone – lithium.
• Postpartum.
• TB (rare).
Precipitating factors
30
• Recent thyroid surgery or radioiodine – infection – MI – trauma.
Pathophysiology
• Increased T4 and T3 levels.
• Precipitating factor à inhibition of thyroid hormone binding to
plasma proteins à ↑ free hormone concentrations in the already
elevated free hormone pool à thyroid storm.
Clinical features
• General à T (>38. 5°C) – sweating – vasodilatation – dehydration.
• CVS à HR – arrhythmias – CHF.
• CNS à Delirium – agitation – tremor – coma – death.
• GIT à vomiting – diarrhea – hepatomegaly – splenomegaly – jaundice.
Differential diagnosis
• Sepsis – neuroleptic malignant syndrome – malignant hyperthermia –
acute mania with lethal catatonia.
Diagnosis
• Do not wait for test results if urgent treatment is needed.
• Do TSH + free T4 + free T3.
• Confirm with technetium uptake if possible.
Treatment
Treat precipitating factors
• Treat suspected infection.

• Correct à dehydration – electrolyte disturbances – hypoglycemia.
Institute cooling techniques

• Fever à tepid sponging ± paracetamol.
31
• Avoid aspirin (ASA à displaces T4 from binding protein).

• Dantrolene à ¯ pyrexia due to extreme muscle activity.
Sedation
• Control agitation à e.g. chlorpromazine 50 mg PO/IM (monitor BP).
High dose beta-blockers

Mainstay of treatment à ↓ peripheral effects of T3 and T4 + ↓ T + ↓ HR +
↓ HTN + ↓ tremor
• If no contraindication + good COP à propranolol 60 mg q4–6h PO or

1 mg over 10 min IV (may need repeating every few hours).
• In asthma or poor COP à give ultra-short-acting β-blocker e.g. IV
esmolol (propranolol has caused cardiac arrest in thyroid storm).
• Consider diltiazem if β-blockers contraindicated.
Anti-thyroid drugs
Antithyroid drugs block T4 synthesis and should be given immediately
• Propylthiouracil is preferred because it blocks T4 to T3 conversion.

• Carbimazole 15-25 mg q6h PO; after 4 hours give Lugol’s solution 0.3
mL q8h PO well diluted in water for 7-10 days to block thyroid.
White cell suppression occurs with both drugs and therapy is stopped if sore
throat develops.
Continuing treatment
• After 5 days à ↓ carbimazole to 15 mg q8h then à adjust carbimazole.

• After 10 days stop propranolol and iodine.
Corticosteroids
• Hydrocortisone 100 mg q6h IV or dexamethasone 2 mg q6h PO.
• Prevent peripheral conversion of T4 to T3.
Orally administered ion-exchange resins
32
• Colestipol or cholestyramine à trap hormone in the intestine and

prevent recirculation.
Remove thyroid hormones from the circulation

• Plasmapheresis or peritoneal dialysis.
Complications
• Mortality rate à 10-20%.
• Ophthalmopathy in Graves’ disease.
• After definitive therapy for hyperthyroidism (surgery or radioactive
iodine) à hypothyroidism is the most common result.
33
SICK EUTHYROID SYNDROME

Definition
• Thyroid hormones abnormalities in critically ill patients not due to
intrinsic thyroid or pituitary disease.
Thyroid hormones changes

• Initially ↓ free T3 then ↓ TSH.
• Severe illness à ↓ free T4.
• With recovery à TSH may overshoot and become transiently high.
Pathophysiology
• Cytokines (TNFα – IL1 – IL6) à reproduce many of features of sick
euthyroid syndrome.
Abnormalities include alterations in

• Peripheral transport and metabolism of thyroid hormone.
• Regulation of TSH secretion.
• Thyroid function itself.
Investigations
• Initially à ↓ free T3.
• Then à ↓ TSH.
• Finally à ↓ free T4.
Treatment
• Treat the underlying disease.
• Thyroid hormone replacement worsens outcomes.
• Thyroid function tests normalize once patient is well (initially with
transient ↑ TSH).
34
ADRENAL FAILURE
Definition
• Failure of the adrenal cortex to produce normal amounts of
glucocorticoid and mineralocorticoid hormones.
Causes of adrenal insufficiency

Adrenal gland destruction
• Autoimmune à Addison’s disease.
• Infection à TB – fungal – histoplasmosis – HIV.
• Infiltration à tumor – leukemia – amyloidosis.
• Hemorrhage à anticoagulation – septicemia.
• Surgery à adrenalectomy.
Secondary (reduced pituitary ACTH secretion)

• Pituitary damage à adenoma – trauma.
• Pituitary infarction à postpartum hemorrhage.
• Pituitary hemorrhage à anticoagulation.
• Sudden exogenous steroid withdrawal.
Rarely hypothalamic (reduced ACTH synthesis)

• Hypothalamic destruction à tumor – granuloma.
Drugs
• Inhibit steroid production à ketoconazole.
• Increase hepatic metabolism à rifampicin – phenytoin.
Relative adrenal insufficiency

• Critical illness.
Precipitating factors
• Infection – trauma – surgery – missed medication.
35
Pathophysiology
Adrenal cortex
1. Zona glomerulosa à aldosterone.
2. Zona fasciculata à cortisol.
Aldosterone
Action of aldosterone
• Controlled mainly by à renin-angiotensin system.

• Action on distal renal tubule
o Reabsorption of Na.
o Secretion of K and H.
Aldosterone deficiency results in
• Na loss + water loss + ↑ reabsorption of K à ↓ plasma volume and

dehydration à ↑ BUN and plasma renin activity.
Glucocorticoids
Action of glucocorticoids
• ↑ Gluconeogenesis.
• Protein wasting.
• ↓ ACTH release through hypothalamic and pituitary actions.
• Maintain blood pressure.
Excess glucocorticoids
• Mineralocorticoid receptors à Na reabsorption + K and H excretion.

• Hypocalcemia and osteoporosis.
• Lymphopenia + eosinopenia + leukocytosis à ↓ host defenses.
Low plasma cortisol
• ↓ Cortisol levels à ↑ ACTH and β-lipotropin à ↑ melanocyte-

stimulating hormone à skin hyperpigmentation.
36
• Orthostatic hypotension.
• Frank shock in crisis.
• Hypoglycemia and increased sensitivity to insulin.
Clinical manifestations
• Shock à ↓ BP – ↑ HR – ↓ UOP – confusion – coma.
• Muscle à weakness – myalgias.
• Mood à depression – psychosis.
• GIT à nausea/vomiting – abdominal pain – diarrhea/constipation.
• Skin à pigmented palmar creases and buccal mucosa (↑ ACTH).
• Fever.
Investigations
Adrenal function tests
Short ACTH stimulation test (Synacthen test)
• Do plasma cortisol before and ½-hour after tetracosactide 250 mcg IM.
• If 30 min cortisol level >550 nmol/L à Addison’s is excluded.
• Steroid drugs may interfere with assays.
• In pregnancy and contraceptive pill à cortisol levels may be
reassuring but falsely high (due to ↑ cortisol-binding globulin).
ACTH level
• In Addison’s à 9am ACTH level is high (>300 ng/L).

• In secondary causes à low.
21–Hydroxylase adrenal autoantibodies
• Positive à autoimmune disease in >80%.
Routine investigations
• Renal à ↓ Na – ↑ K – ↑ Ca – uremia.
• CBC à eosinophilia – anemia.
37
• BG level à ↓ glucose (due to ↓ cortisol).
CT scan of the adrenal glands

• TB – histoplasma – metastatic disease – adrenal hemorrhage.
Treatment
Addisonian crisis
Replacement therapy
• Hydrocortisone 100 mg q6h for 48 hours.

• Mineralocorticoid (e.g. fludrocortisone) is only needed in PAI.
• Stress à cortisol levels tenfold à high-dose hydrocortisone (or
dexamethasone) may be needed.
Treat hypotensive shock
• Aggressive fluid therapy à e.g. 4-5 L of 0.9% NS over 12-24 h.

• Provide inotropic support (if required).
Other therapies
• Hyperkalemia à fluid and steroids.

• Hypoglycemia à glucose supplements.
• Infection à antibiotics.
Less severe Addison’s disease

Oral therapy from the onset
• Cortisol à hydrocortisone 20 mg AM + 10 mg PM.

• Mineralocorticoid à fludrocortisone 0.1–0.2 mg/day.
• In Addison’s disease à therapy is lifelong and must never be stopped.
Intercurrent stress
For minor surgery
38
• Single oral or IV/IM hydrocortisone 100 mg may be adequate.
For major procedures requiring general anesthesia
• Hydrocortisone 100 mg q6h (IV) until oral medication can be restarted.
39
HYPOPITUITARY COMA
Definition
• DCL due to decompensated chronic hypophyseal failure.
Etiology
• Pituitary infarction (e.g. postpartum).
• Pituitary apoplexy.
• SAH.
Presentation
Suspect when
• Hypothermia – refractory hypotension – septic signs without fever.
• Short stature – loss of axillary/pubic hair – gonadal atrophy.
Clinical feature
• Headache – ophthalmoplegia – DCL – ↓ BP – hypothermia –
hypoglycemia – signs of hypopituitarism.
Tests
• Cortisol – ACTH.
• T4 – TSH.
• Glucose.
• CT/MRI (pituitary fossa).
Treatment
Waiting for lab confirmation may be fatal.
Cortisol
• Hydrocortisone à 100 mg IV q6h.
Liothyronine
• Liothyronine à 10 mcg q12h PO or slowly IV.
• Only after hydrocortisone therapy.
40
Surgery
• Indication à pituitary apoplexy.
41

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DIABETIC KETOACIDOSIS (DKA)

Common triggers for DKA

• Acetoacetate + β–hydroxybutyrate + Acetone.

• Normally BOHB: AcAc ratio is 3: 1.

Short come of dip-testing methods

• Usually decreases due to osmotic effect of hyperglycemia.

Initial Laboratory Values in DKA and HHS

Urine/serum Positive Positive Positive Trace

Criteria of severe DKA

• pH ≤ 7.0 + respiratory depression or severe hypotension unresponsive

• Two ampules (2 x 50 mEq) + 1000 mL D5W.

Serum K (mmol/L) Amount of KCl to add per liter of IV fluid

Manifestations of severe hypophosphatemia

• Neurologic disturbances – arthralgias – muscle weakness with

• 5 mL K phosphate ampule in severe hypophosphatemia (<1.0 mg/dL).

• 50 U soluble insulin + 50 mL 0.9% saline à infuse at 0.1 unit/kg/h.

• ↓ Blood ketones by 0.5 mmoL/L/h.

Continue fixed rate insulin until

• Ketones < 0.6 mmoL/L.

Find and treat infection/cause for DKA

Recurrence of DKA during hospital stay

Causes of recurrent DKA during hospital stay

• Stopping insulin early.

• Rapid falling of blood glucose à fluid shifts à ↓ BP.

Hyperchloremic metabolic acidosis

Cerebral edema in DKA

• Rapid decline in BG.

• 0.5-1 gm/kg IV over 20 min.

Hypertonic saline (3%)

• 5-10 mL/kg over 30 min.

• ↓ Rate of fluid administrated by one-third.

• Hyperventilation to PCO2 < 22 mmHg has been associated with poor

• Elevate the head of the bed.

• After treatment is initiated.

ALCOHOLIC KETOACIDOSIS (AKA)

Glucose and fluids administration à ↑ insulin à ↓ lipolysis and free fatty

HYPERGLYCEMIA IN CRITICALLY ILL PATIENT

Transitioning to subcutaneous insulin

Calculate insulin requirement

• Establish 24-hour insulin requirement.

• Metformin (Glucophage) à risk of lactic acidosis.

• Patient prepared for urgent surgery or during surgery à treat with SC

Hyperalimentation and hyperglycemia

• Add ≤ 50% of anticipated total insulin requirement for duration of

HYPERGLYCEMIC HYPEROSMOLAR SYNDROME

• ↓ Insulin à ↑ BG à osmotic diuresis à fluid and electrolyte losses.

• Normal saline à even in hypernatremia to expand extracellular fluid.

• ½ normal saline à switch to ½ normal saline once patient stabilizes.

• Hemodynamic monitoring is advised during aggressive rehydration

• Started as soon as urine flow has been established.

Management of the underlying cause

Whipple triad defines hypoglycemia best

• Hypoglycemia in young à in the setting of drug overdoses.

Antidiabetic agents à promote normoglycemia via other mechanisms

• Metformin – thiazolidinediones – alpha glucosidase inhibitors.