Endocrinology Questions 2021

1. Acromegaly and gigantism. Clinical symptoms, laboratory and physical findings.

Diagnosis. Treatment.
• Acromegaly - a condition in which benign pituitary adenomas lead to an excess secretion
of growth hormone (GH) and insulin-like growth factor 1 (IGF-1).
• In adults, whose epiphyseal plates are closed, the disease causes enlarged hands and feet,
coarsened facial features and pathological growth of internal organs.
• If the condition occurs in children, before epiphyseal plate closure, it is known as
gigantism.
• Etiology: Benign growth hormone-secreting pituitary adenomas
• Clinical features:
• Tumor effects: Headache, vision loss (bitemporal hemianopsia), cranial nerve
palsies, Oligomenorrhea, secondary amenorrhea, galactorrhea, vaginal atrophy,
Erectile dysfunction, decreased libido, decreased testicular volume,
• Soft tissue effects: Doughy skin texture, hyperhidrosis, Deepening of the voice,
macroglossia with fissures, obstructive sleep apnea.
• Skeletal effects: Coarsening of facial features slowly progressing with age,
enlarged nose, forehead and jaw, (macrognathia) with diastema (enlarged between
the incisors), Widened hands, fingers and feet, Painful arthropathy (ankles, hips,
knees).
• Diagnostics:
• Serum IGF-1 concentration
• Elevated IGF-1 level: acromegaly suspected; conduct oral glucose tolerance
test (OGTT)
• Normal IGF-1 level: acromegaly ruled out.
• OGTT with baseline GH and measure GH after 2 hours: the most specific test.
• If GH suppressed: acromegaly ruled out
• If GH not suppressed: confirmed acromegaly; conduct pituitary MRI to
determine the source of excess GH.
• MRI – imaging modality of choice, usually shows a visible mass confirming GH-
secreting pituitary adenoma. If normal à screen for an extrapituitary cause (e.g.,
CT scan of chest and abdomen, measure GHRH).

Treatment:
• Surgery:
o Transsphenoidal adenectomy (preferred method)
o Surgical debulking (in patients with parasellar disease and inoperable
tumors)
• Medication:
o Somatostatin analogs (e.g., octreotide, lanreotide)
o Dopamine agonists (e.g., cabergoline): reduce tumor size and GH secretion
o GH receptor antagonists (e.g., pegvisomant).

• Radiotherapy:
o Conventional fractionated radiotherapy
o Stereotactic radiosurgery (e.g., Gamma Knife, CyberKnife)
• Follow-up:
o Assessing IGF-1 and random GH level 12 weeks after surgery and then
annually
 o Annual hormonal testing for hypopituitarism
o Performing MRI at least 12 weeks after surgery.

Gigantism

• Rare disorder characterized by abnormal linear growth during childhood due

to growth hormone excess while epiphyseal growth plates are still open.
• Clinical features:
o Tall stature
o Increased growth of distal limbs (i.e., hands, feet, fingers, toes)
o Tumor mass symptoms: headache, visual changes, features of
hypopituitarism.
o Progressive microencephaly
o Coarse facial features, frontal bossing, prognathism (soft tissue effects
are less common).
o Obesity.
• Diagnosis:
o Increased Serum IGF-1
o Increased GH after oral glucose tolerance test confirms pituitary
gigantism.
o After a biochemical diagnosis is established:
§ MRI: pituitary mass
§ CT if MRI is negative: exclude other GH- secreting tumors
(e.g., pancreas, adrenal)
• Treatment:
o Transsphenoidal surgery: pituitary adenoma excision
o Medical therapy:
§ Somatostatin analogs (e.g., octreotide)
§ GH receptors antagonists (e.g., pegvisomant).

2. Diabetes insipidus. Vasopressin sensitive diabetes insipidus. Nephrogenic diabetes insipidus.

Diagnosis. Treatment.
• Diabetes insipidus (DI) is a condition in which the kidneys are unable to concentrate
the urine.
• Vasopressin sensitive diabetes insipidus (Central DI), the most common form of
diabetes insipidus, is caused by insufficient levels of circulating antidiuretic
hormone (ADH).
Types:
o Primary (1/3 of cases)
§ Most cases are idiopathic
§ Autoimmune etiology of primary CDI has been suggested.
o Secondary (2/3 of cases)
§ Brain tumor (especially craniopharyngioma) and cerebral metastasis
(e.g., lung cancer).
§ Neurosurgery
§ Traumatic brain injury
§ Pituitary ischemia (e.g., Sheehan syndrome)
§ Infection (e.g., meningitis)
• Nephrogenic DI is characterized by defective renal ADH receptors in the kidneys.
o Rare: caused by defective ADH receptors in the distal tubule and collecting
ducts
o Types:
§ Hereditary (mutation in ADH receptor): very rare
§ Acquired: Adverse effect of medications (lithium, demeclocycline),
Hypokalemia, hypercalcemia, renal disease (e.g., Autosomal
dominant polycystic kidney disease).

• Clinical features:
o Polyuria with diluted urine
o Nocturia à restless sleep, daytime sleepiness
o Polydipsia (excessive thirst)
o Severe dehydration (altered mental status, lethargy, seizures, coma) in cases
of low water intake and hypotension.
• Diagnosis:

• Treatment:
 - Central DI:
o Desmopressin: synthetic vasopressin without
vasoconstrictive effects
§ Administration: intranasal, subcutaneous, or oral.
§ Important side effects: hyponatremia.
§ Other indications besides central DI include
Hemophilia A, Von Willebrand disease.
o Alternative medication: Chlorpropamide.
- Nephrogenic diabetes insipidus
o Discontinuation of the causative agent (e.g., lithium,
demeclocycline) in medication induced NDI
o Thiazide diuretics
o NSAIDs (e.g., indomethacin)
o Amiloride: indicated in patients with lithium-induced NDI.

3. Cushing's syndrome and Cushing's disease. Nelson's disease. Symptoms. Clinical features,
laboratory findings, diagnosis, differential diagnosis. Treatment.
• Cushing syndrome, or hypercortisolism, is an endocrine disorder that is most often
caused iatrogenically by exogenous administration of glucocorticoids.
• Less commonly, Cushing can result from endogenous overproduction of cortisol.

Clinical features:
• Skin:
o Thin, easily bruisable skin with ecchymoses
o Stretch marks (classically purple abdominal striae)
o Hirsutism
o Acne
o If secondary hypercortisolism: often hyperpigmentation.
o Delayed would healing
o Flushing of the face.

• Neuropsychological: lethargy, depression, sleep disturbance, psychosis.

 • Musculoskeletal:
o Osteopenia, osteoporosis, pathological fractures, avascular necrosis of the femoral
head.
o Muscle atrophy/weakness.

• Endocrine and metabolic:

o Insulin resistance à hyperglycemia à mild polyuria in the case of severe
hyperglycemia.
o Dyslipidemia
o Weight gain characterized by central obesity, moon facies, and buffalo hump
o Decreased libido (male)
o Decreased libido, virilization, and/or irregular menstrual cycles (e.g., amenorrhea)
(female)
o Growth delay in children

• Other features:
o Secondary hypertension (≈90% of cases)
o Increased susceptibility to infection (due to immunosuppression)
o Peptic ulcer disease
o Cataracts

Diagnosis:
General lab findings:
• Hypernatremia, hypokalemia, metabolic alkalosis
• Hyperglycemia: due to stimulation of gluconeogenesis enzymes (e.g., glucose-6-
phosphatase) and inhibition of glucose uptake in peripheral tissue.
• Hyperlipidemia (hypercholesterolemia and hypertriglyceridemia)
• Leukocytosis (neutrophilic predominantly), eosinopenia.

Screening for hypercortisolism:

• Increased 24-hour urine cortisol (> 3 times the normal value i.e., >400 microgram/24 h)
• Increased early morning serum cortisol levels (> 50 nmol/L) following a low dose-
dexamethasone suppression test.
• Increased midnight salivary cortisol (> 4 nmol/L)
• Increased serum cortisol (> 7.5 microgram/dL)

Hormone analysis:
1. Serum ACTH
o Low (<5 pg/mL): suspect primary hypercortisolism (adrenal adenoma, carcinoma)
o Normal or elevated (>20 pg/mL): suspect secondary hypercortisolism
2. If secondary hypercortisolism is suspected, one of the following tests may be used to
differentiate between Cushing disease and ectopic ACTH production
o High dose dexamethasone suppression test
§ Adequate suppression of cortisol levels to less than 50% of baseline = Cushing
syndrome.
§ No suppression = ectopic ACTH production.
o Corticotropin Releasing Hormone stimulation test
§ ACTH and cortisol levels increase further: Cushing syndrome
§ No increase in ACTH or cortisol levels: ectopic ACTH production.
Imaging to localize tumor:
• CT and/or MRI of the abdomen: for adrenal tumors.
• CT and/or MRI of the skull: if Cushing disease is suspected.
• Other tests: if ectopic ACTH production suspected:
- Chest x-ray and/or CT
- Abdominal CT
- Pelvic CT
- Thyroid ultrasound

Treatment:
Exogenous Cushing syndrome:
• Consider lowering the dose of glucocorticoids
• Consider the use of alternatives to glucocorticoids (e.g., azathioprine)

Endogenous Cushing syndrome:

• Inoperable disease (e.g., inoperable adrenal carcinomas): drugs to suppress cortisol
synthesis (e.g., metyrapone, mitotane)
• Operable disease: Surgical therapy is the treatment of choice
o Adrenocortical tumor: laparoscopic or open adrenalectomy
o Pituitary adenoma: transsphenoidal resection of the pituitary adenoma.
o ACTH – secreting ectopic tumor: resection of the ectopic foci (e.g., bronchial carcinoid).

Nelson syndrome (post adrenalectomy syndrome):

• Etiology: bilateral adrenalectomy in patients with a previously undiscovered pituitary
adenoma
• Clinical features: headaches, bitemporal hemianopia (mass effect), cutaneous
hyperpigmentation
• Diagnostics:
o High levels of beta-MSH and ACTH
o Pituitary adenoma on MRI confirms the diagnosis
• Treatment: surgery (e.g., transsphenoidal resection) and/or pituitary radiation therapy.

4. Primary hyperaldosteronism. Symptoms, clinical features. Diagnosis, differential diagnosis.

Treatment.
• Also sometimes referred as Conn syndrome, is an excess of aldosterone caused by
autonomous overproduction, usually at the adrenal cortex.
• Etiology: due to adrenal hyperplasia or adrenal adenoma.
• Clinical features/Symptoms:
o Hypertension
§ Sustained systolic BP > 150 mmHg or diastolic > 100 mm Hg over three
measurements on 3 different days.
§ Systolic BP > 140 mmHg or diastolic > 90 mmHg and resistant to 3-drug
therapy with an adrenergic inhibitor, a vasodilator, and a diuretic.
o Features of hypokalemia:
§ Fatigue
§ Muscle weakness, cramping
§ Headaches
 § Paresthesia in severe cases
§ Polyuria and polydipsia
§ Palpitations
§ Constipation

• Absence of significant edema (due to aldosterone escape)

Diagnosis:
• Plasma aldosterone concentration to plasma renin activity (PAC/PRA ratio) – aldosterone
is increased, and renin is decreased in primary hyperaldosteronism.
• Oral sodium loading test (high sodium diet (5000 mg) or oral sodium chloride tablets 2 g
taken 3 times daily) for 3 days.
- In healthy individuals: RAAS is physiologically suppressed
- In primary hyperaldosteronism: failure to suppress aldosterone
secretion
• Saline infusion test: infusion of 2 L of normal saline over 4 hours. Same results as in Oral
sodium loading test.
• Fludrocortisone suppression test: administration of fludrocortisone 0.1 mg every 6 h for a
duration of 4 days without simultaneous replacement of sodium chloride and potassium.
Same results as Oral sodium test
• Captopril suppression test: single dose of captopril 25-50 mg is taken, and PRA and PAC
are measured 2 hours later.
• Imaging: adrenal CT
• Adrenal venous sampling

Differential diagnosis: Secondary hyperaldosteronism, Pseudohyperaldosteronism.

Treatment:
Bilateral adrenal hyperplasia:
• Pharmacotherapy: aldosterone receptor antagonist
o Eplerenone
o Spironolactone

Unilateral autonomous aldosterone secretion (e.g., adenoma)

• Surgery: adrenalectomy
o Prior to surgery, hypokalemia should be corrected with spironolactone and
potassium supplementation
o Following surgery: monitor for hyperkalemia.

• Pharmacotherapy: Aldosterone receptor antagonist may be considered in patients who are

poor surgical candidates.

5. Primary adrenocortical insufficiency - Addison's disease. Acute adrenocortical

insufficiency. Etiology, pathogenesis. Symptoms. Clinical features. Diagnosis.
Differential diagnosis. Treatment.
• Adrenal insufficiency is the decreased production of adrenocortical hormones
(glucocorticoids, mineralocorticoids and adrenal androgens) and is classified as primary,
secondary and tertiary.
• Primary adrenal insufficiency (Addison disease) is caused by a disorder of the adrenal
glands. The most frequent cause of primary adrenal insufficiency is autoimmune
adrenalitis.
• Secondary adrenal insufficiency is the result of decreased ACTH (adrenocorticotropic
hormone), and tertiary adrenal insufficiency is the result of decreased production of CRH
(corticotropin-releasing hormone) by the hypothalamus.

• Pathophysiology:

• Clinical signs:
• Diagnosis:
• Acute adrenal insufficiency: Make a clinical diagnosis and defer detailed
testing until after empiric glucocorticoids are given (see “Adrenal crisis”).
• Chronic adrenal insufficiency: Use stepwise endocrine testing in all patients.
1. Morning cortisol [13]
2. Morning ACTH
3. ACTH stimulation test
• Primary adrenal insufficiency: Screen
for hypoaldosteronism and hypoandrogenism.

• Primary adrenal insufficiency (routine lab test)

o BMP
Na ↓, K ↑, Ca ↑
§
§ Normal anion gap metabolic acidosis
§ Hypoglycemia
§ Creatinine ↑, BUN ↑
o CBC: mild anemia, lymphocytosis, eosinophilia
o Thyroid function abnormalities
[15]

• Secondary adrenal insufficiency: potentially only ↓ Na or hypoglycemia

• Treatment:
• Primary adrenal insufficiency: replacement
for hypocortisolism, hypoaldosteronism, and hypoandrogenism
o Glucocorticoids
o Mineralocorticoids
o Androgens (as needed)
• Secondary/tertiary adrenal insufficiency: replacement
for hypocortisolism and hypoandrogenism
o Glucocorticoids
o Androgens (as needed)
o Replacement of other hormones if there is
concomitant hypopituitarism
 • Underlying causes: Identify and treat reversible conditions in all patients.

Steroid replacement
• Glucocorticoids:
• Agents
o Hydrocortisone
o Cortisone acetate
o Prednisolone
• Considerations
o The total daily replacement dose should be given in divided doses, with
the highest dose given in the morning to mimic diurnal fluctuations.
o Educate patients about increasing their glucocorticoid dose according
to outpatient sick day rules.
o Side effects may arise due to overtreatment (see “Cushing syndrome”).

Mineralocorticoids
• Agent: fludrocortisone (a synthetic mineralocorticoid with
mostly mineralocorticoid and limited glucocorticoid effects) [18]
• Considerations
o Side effects are analogous to glucocorticoids (e.g., hyperpigmentation).
Additional side effects include:
§ Worsening of preexisting heart failure
§ Edema

Androgens [18]
Consider treatment in anatomically female patients with low libido, depressive symptoms,
and low energy levels.
• Agent: DHEA

• Acute adrenocortical insufficiency is an acute, severe glucocorticoid deficiency that

requires immediate emergency treatment.

• Precipitating factors :
• Stress in patients with underlying adrenal insufficiency e.g.: [17]

o Gastrointestinal illness (most common)

o Other infections
o Perioperative period
o Physical stress or pain
o Psychological stress
 • Sudden discontinuation of glucocorticoids after
prolonged glucocorticoid therapy
• Bilateral adrenal hemorrhage or infarction (e.g., Waterhouse-Friderichsen
syndrome)
• Pituitary apoplexy

• Signs and symptoms:

• Hypotension, shock
• Impaired consciousness, coma
• Fever
• Vomiting, diarrhea
• Severe abdominal pain (which can resemble peritonitis)

• Treatment:
• The 5 S’s of adrenal crisis treatment are Salt (0.9% saline), Sugar (50%
dextrose), Steroids (100 mg hydrocortisone IV once, then 200 mg over 24
hours), Support (normal saline to correct hypotension and electrolyte
abnormalities), and Search (for the underlying disorder)

6. Pheochromocytoma. Symptoms. Clinical features. Laboratory findings. Diagnosis and

differential diagnosis. Principles of treatment.

• A pheochromocytoma is a catecholamine-secreting tumor that typically develops in the

adrenal gland.
• Etiology: Majority are benign, unilateral, catecholamine producing tumors, that rarely
produce other hormones such as EPO.
- Tumors arise from Chromaffin cells, which are derived from the
neural crest.
- Localization: ≈90% adrenal medulla, ≈10% extra-adrenal in
sympathetic ganglia.
- 25% of pheochromocytomas are hereditary (germline mutations):
MEN 2A, MEN 2B, Von Hippel-Lindau disease.
• Clinical features:
- Episodic hypertension
- Paroxysmal
§ Throbbing headache
§ Diaphoresis
§ Heart palpitations, tachycardia
§ Pallor
§ Abdominal pain and nausea
§ Anxiety
- Weight loss due to increased basal metabolism
- Hyperglycemia
 - Signs of polycythemia if EPO is secreted

• Diagnosis:
o Best initial test: plasma free metanephrines test
- Examples: homovanillic acid, vanillylmandelic acid
- High sensitivity
o Confirmatory test: metanephrines and catecholamines in 24-hour urine (high
specificity)
o Clonidine suppression test (rarely used)
o Genetic testing if MEN2A, MEN2B or VHL suspected.
o Immunohistochemical staining: positive for chromogranin, synaptophysin.
o Other diagnostic tests:
- 24-hour ambulatory blood pressure monitoring
- Adrenal/abdominal CT or MRI (after positive biochemistry tests to
localize tumor)
- Scintigraphy

• Differential diagnosis:
- Endocrine: Hyperthyroidism, Hypoglycemia, Menopause
- Cardiovascular: Heart failure, Arrythmias, Ischemic heart disease
- Neurological: Migraine, Stroke, Meningioma
- Miscellaneous: Porphyria, Panic disorder, Anxiety disorder, Drug-
induced (e.g., Monoamine oxidase inhibitors).
• Treatment:
o Preoperative blood pressure management: combined alpha-adrenergic and beta-
adrenergic blockade
- First, a non-selective irreversible alpha-blocker is given:
Phenoxybenzamine blocks alpha-1 and alpha-2 adrenoreceptors
equally and irreversibly.
- After sufficient alpha-adrenergic, blockade, a beta-blocker
(amlodipine) may be started for additional blood pressure control
and control of tachyarrhythmias.
o Laparoscopic tumor resection (adrenalectomy): treatment of choice
- No-touch technique
- Open surgical resection is reserved for large or invasive tumors.
o Prognosis and follow up
o Inoperable disease:
- Benign pheochromocytoma: primary therapy with
phenoxybenzamine
- Malignant pheochromocytoma: Metaiodobenzylguanidine (MIBG)
therapy.
- Otherwise, palliative treatment (chemotherapy, tumor
embolization).
7. Multiple endocrine neoplasia. MEN – 1 and MEN - 2. Clinical features. Laboratory findings.
Diagnosis. Treatment.
• Multiple endocrine neoplasia (MEN) is a term used to describe 3 autosomal dominant
syndromes that are associated with certain hormone-producing neoplasias.
• MEN1 is caused by an altered menin protein expression and presents with primary
hyperparathyroidism, often in association with endocrine pancreatic tumors and/or
pituitary adenomas.
• MEN2A and MEN2B are caused by mutated RET proto-oncogene and both present with
medullary thyroid carcinoma and sometimes pheochromocytoma.
8. Nonketotic, hyperglycemic, hyperosmolar diabetic coma. Symptoms. Clinical features.
Laboratory findings. Basic principles of treatment.
• Nonketotic hyperglycinemia is rare, genetic, metabolic disorder caused by a defect in the
enzyme system that breaks down the amino acid glycine, resulting in an accumulation of
glycine in the body’s tissue and fluids. There is a classical form and a variant of NKH.
• Symptoms:
- The severe classic form of NKH typically presents in the first week
of life with low muscle tone, lethargy, seizures, coma and apnea
requiring ventilator support. Severe developmental delay.
- The ventilator is typically needed for a period of 10-20 days before
the apnea resolves.
- Individuals with attenuated classic NKH can present in the neonatal
period or later in infancy, and they present with low muscle tone,
lethargy and seizures. Developmental delay, they can often walk
and achieve various motor skills.
- For variant type of NKH symptoms are spasticity of balance,
problems with optic nerve, heart weakness, seizures.

• Diagnosis:
- CSF and plasma glycine levels are used
- Molecular analysis is an excellent confirmatory test.
- Brain MRI (specific patterns of changes are seen)
- Prenatal diagnosis is available when familial mutations are known.

• Treatment:
- There is no curative treatment for NKH.
 - Sodium benzoate is used to reduce serum glycine levels (reduces
seizures and improves alertness).
- Dextromethorphan is commonly used to reduce seizures and
improve alertness.

• Diabetic hyperosmolar syndrome is a serious condition caused by extremely high blood

sugar levels.
• This condition most commonly occurs in people with type 2 diabetes. It’s often triggered
by illness or infection.
• Symptoms:
- Blood sugar level of 600 mg/dl or 33.3 mmol/L or higher.
- Excessive thirst
- Dry mouth
- Increased urination
- Warm, dry skin
- Fever
- Drowsiness, confusion
- Hallucinations
- Vision loss
- Convulsions
- Coma.

• Etiology:
- Illness or infection
- Not following a diabetes treatment plan or having an inadequate
treatment plan
- Certain medications, such as diuretics.
• Diagnosis:
- Physical and mental status exam
- Medical history
- CBC, urine analysis, bacterial culture for infection, creatinine and
GFR
- ECG.
• Treatment:
- I/V fluids to treat dehydration
- Insulin I/V to lower blood glucose.
- Potassium and sometimes sodium phosphate replacement given
I/V to help the cells function correctly.

9. Hyperandrogenism. Causes. Symptoms. Clinical features. Diagnosis. Treatment.

• Definition: a state of excess androgen levels that causes symptoms such as growth of facial
hair, deepening of the voice and male-pattern baldness.
• Causes:
• Symptoms:
• Virilization: the male appearance of male secondary to sexual characteristics in
female individual
 - Hirsutism: excessive male pattern hair growth (e.g., chin, upper lip, mid-sternum,
abdomen, back, buttocks)
- Male-pattern hair loss
- Acne
- Increased muscle mass
- Voice deepening
- Clitoromegaly
• Diagnostics:
• Lab tests to identify hyperandrogenemia
- increased serum total testosterone
- decreased Sex hormone binding globulin
- free androgen index
• Investigate for the underlying cause

• Treatment:
• Medication to suppress or block androgen and manage symptoms of virilization
- Oral contraceptive pill
- Antiandrogen drugs (e.g., spironolactone, finasteride)
• Treat underlying cause (e.g., surgery for androgen-secreting tumors).

10. Disorders of calcium metabolism. Causes of hypocalcemia and hypercalcemia. Clinical

features. Diagnosis. Treatment.
• Hypocalcemia is a state of low serum calcium levels (total Ca2+ < 8.5 mg/dL) or
ionized Ca2+ <4.65 mg/dL).
• Severe hypocalcemia: total serum calcium concentration ≤ 7.5 mg/dL or ionized
(free) calcium concentration < 3.6 mg/dL
• Etiology:
- Hypoparathyroidism
- Vitamin D deficiency
- Chronic kidney disease
- Hyperphosphatemia
- Medications: loop diuretics, calcitonin, bisphosphonates
• Symptoms:
- Neurological:
§ Tetany – paresthesia (tingling or pin and needles sensation),
spasms (carpopedal spasm) and cramps, Stiffness, myalgia.
§ Seizures
- Cardiovascular:
§ Congestive heart failure
§ Hypotension
§ Cardiac arrhythmias
- Manifestations of chronic hypocalcemia:
§ Emotional instability, depression, confusion, hallucinations.
§ Cataracts, calcification of the cornea
§ Dental enamel hypoplasia
§ Osteomalacia.
• Diagnostics:
 - Confirm true hypocalcemia (measure total and ionized calcium and
check serum albumin and calculate correct calcium)
- Evaluate other electrolyte abnormalities (BMP, serum phosphate
and magnesium).
- Serum intact PTH
- Alkaline phosphatase, Amylase, 25-hydroxyvitamin D (calcidiol)
- Urine studies: 24-hour urinary excretion of calcium and magnesium
- ECG – showing prolonged QT interval, AV block
- Fundoscopy: possible findings à papilledema.

• Treatment:
- Calcium supplementation
§ Severe and/or symptomatic hypocalcemia à I/V calcium
supplementation: calcium gluconate or calcium chloride.
o Continuous cardiac monitoring
§ Mild and/or chronic hypocalcemia à oral calcium
supplementation: calcium citrate, calcium carbonate.

• Hypercalcemia refers to high serum calcium levels (total Ca > 10.5 mg/dL or
ionized Ca2+ > 5.25 mg/dL).
• The most common causes of hypercalcemia are primary hyperparathyroidism and
malignancy involving paraneoplastic production of parathyroid hormone-related
protein.
• Other causes are Medications (thiazide diuretics, excess vitamin D),
Thyrotoxicosis, Milk alkali syndrome, Adrenal insufficiency.
• Clinical features:
- Nephrolithiasis
- Bone pain, arthralgia, myalgias, fractures
- Constipation
- Abdominal pain
- Nausea and vomiting
- Anorexia
- Peptic ulcer disease
- Pancreatitis
- Polyuria
• Classification:
- Mild hypercalcemia (total calcium 10.5-12 mg/dL or ionized
calcium 5.25-8 mg/dL)
- Moderate hypercalcemia (total calcium 12-14 mg/dL or ionized
calcium 8-10 mg/dL)
- Severe hypercalcemia (total calcium >14 mg/dL or ionized calcium
> 10 mg/dL).
• Diagnostics:
- Confirm true hypercalcemia: measure ionized calcium or calculate
corrected calcium using total calcium and serum albumin.
 - Measure serum intact PTH to determine the etiology of
hypercalcemia.
- Serum calcium (total calcium, ionized calcium)
- Other lab studies: albumin, BMP, Alkaline phosphatase, CBC
- ECG findings – Bradycardia, Arrhythmias.
• Treatment:
- Severe hypercalcemia à I/V fluid therapy with 0.9% NaCl, initiate
pharmacotherapy: calcitonin, bisphosphonates, denosumab, treat
any complications, consider hemodialysis for refractory life-
threatening hypercalcemia.
- Mild hypercalcemia à follow calcium levels and monitor for the
development of symptoms.

11. Type 1 diabetes mellitus. Features, causes, general principles of therapy.

• Type 1 DM is the result of an autoimmune response that triggers the destruction of
insulin-producing beta cells in the pancreas, and results in absolute insulin deficiency.
• Etiology: Autoimmune Beta cell destruction in genetically susceptible individuals
§ HLA association. HLA-DR3 and HLA-DR4 positive patients are 4-6 times
more likely to develop type 1 diabetes.
§ Associated with other autoimmune conditions such as Hashimoto thyroiditis,
Type A gastritis, Celiac disease
• Clinical features:

Diagnosis – a single blood test, and also Anti-GAD antibodies, C-peptide, Urine analysis.
Treatment:

12. Type 2 diabetes mellitus. Features, causes, general principles of therapy.

 • Type 2 diabetes is characterized by insulin resistance (insufficient response of
peripheral cells to insulin) and pancreatic beta cell dysfunction (impaired insulin
secretion), resulting in relative insulin deficiency.
• Etiology: Hereditary and environmental factors, associated with metabolic syndrome.
• Clinical features:

Diagnosis: a single blood glucose test, and also Anti-GAD antibodies, C-peptide, Urine
analysis.

Treatment:
HbA1C target for adults: < 7% (53 mmol/mol)

13. Prolactinoma. Etiology, clinical features, diagnosis, therapy.

• A usually benign prolactin-producing tumor of the anterior pituitary gland.
• Etiology: medications, other pituitary tumors, an underactive thyroid gland, ongoing
irritation to the chest, pregnancy, breast-feeding.
• Symptoms: galactorrhea, amenorrhea, gynecomastia, loss of libido (due to
hyperprolactinemia) and/or headaches, bitemporal hemianopia because of compression
of the optic chiasm (due to mass effect).
• Diagnosis:

• Therapy:
o Surgery management (transsphenoidal hypophysectomy- removal of pituitary
tissue under micro or endoscopic guidance) – first line treatment for:
§ Secretory adenomas (excluding prolactinomas)
§ Symptomatic non-secretory adenomas
o Pharmacotherapy:
- Prolactinomas: first-line treatment for symptomatic patients and those
with macroadenoma.
- Secretory adenomas: patients who are unsuitable for surgery.
- Prolactinomas: Dopamine agonists (cause adenoma to shrink)
§ First line: cabergoline
§ Second-line: bromocriptine
- ACTH-secreting tumor
§ Somatostatin analogs
- GH-secreting tumor
§ Somatostatin analogs + cabergoline
- TSH-secreting tumor: somatostatin analog.
14. Hypothyroidism. Thyroiditis. Symptoms, clinical features, diagnosis, differential diagnosis.
Treatment.
• Hypothyroidism is a condition in which the thyroid gland is underactive, resulting in
deficiency of the thyroid hormones triiodothyronine (T3) and thyroxine (T4).
• Thyroiditis is the swelling or inflammation of the thyroid gland and can lead to over-or
under production of thyroid hormone.
- Thyrotoxic phase
- Hypothyroid phase
- Euthyroid phase
o Types of thyroiditis:
- Hashimoto’s thyroiditis
- Silent thyroiditis or painless thyroiditis
- Postpartum thyroiditis
- Radiation- induced thyroiditis
- Subacute thyroiditis or de Quervain’s thyroiditis
- Acute thyroiditis or supportive thyroiditis
- Drug-induced thyroiditis
o Symptoms:
- Hyperthyroid phase: Being worried, feeling irritable, trouble sleeping, fast
heart rate, fatigue, unplanned weight loss, increased sweating and heat
tolerance, anxiety and nervousness, tremors.
- Hypothyroidism: fatigue, unexpected weight gain, constipation, depression,
dry skin, difficulty performing physical exercise, decreased mental ability to
concentrate and focus.
o Diagnostics:
- Thyroid function test (measures the amounts of hormones in the blood –
TSH, T3 and T4)
- Thyroid antibody tests (measure thyroid antibodies that include antithyroid
antibodies)
- Erythrocyte sedimentation rate (indicates inflammation by measuring how
fast red blood cells fall)
- Ultrasound (evaluates the anatomy of the thyroid gland).
- Radioactive iodine uptake (measures how much radioactive iodine is
absorbed by the thyroid gland).
o Treatment:
- Beta blockers in case of palpitations
- In case of inflammation medications such as aspirin or ibuprofen

• Etiology of hypothyroidism:
o Congenital hypothyroidism:
- Sporadic – thyroid hypoplasia, dysplasia or ectopy, thyroid aplasia, iodine
deficiency.
- Hereditary – Dyshormogenetic goiter
o Acquired hypothyroidism:
- Primary hypothyroidism – Hashimoto thyroiditis, Postpartum thyroiditis, De
Quervain thyroiditis, Iatrogenic (e.g., post thyroidectomy, radioiodine therapy,
 antithyroid medication e.g., amiodarone, lithium). Nutritional – iodine deficient
regions, Riedel thyroiditis, Wolff-Chaikoff effect.
- Secondary hypothyroidism: pituitary disorders (e.g., pituitary adenoma) à TSH
deficiency.
- Tertiary hypothyroidism: hypothalamic disorders à TRH deficiency.

• Clinical features:
o General symptoms: Fatigue and decreased physical activity, Cold intolerance,
Decreasing sweating, Hair loss, brittle nails and cold dry skin, Weight gain (despite
poor appetite), Constipation, Bradycardia, Hypothyroid myopathy, myalgia,
stiffness, cramps, Woltman sign (a delayed relaxation of the deep tendon reflexes),
Carpel tunnel syndrome.
o Symptoms related to generalized myxedema: Doughy skin texture, puffy
appearance, Dyspnea, Hoarse voice, difficulty articulating words, Pretibial and
preorbital edema, Myxedema coma.
o Symptoms of hyperprolactinemia: Abnormal menstrual cycle (secondary
amenorrhea or menorrhagia), galactorrhea, decreased libido, erectile dysfunction,
delayed ejaculation and infertility in men.
o Further symptoms: Impaired cognition, somnolence, depression, Hypertension,
Goiter.
o For Congenital hypothyroidism:
- Postpartum symptoms: umbilical hernia, prolonged neonatal jaundice,
hypotonia, decreased activity, hoarse cry, macroglossia, poor feeding
- Congenital iodine deficiency syndrome.
• Diagnostics:
o Congenital hypothyroidism:
- Neonatal screening to measure TSH levels 24-48 hours after birth required
by law.
- Increased TSH levels indicate congenital hypothyroidism.
o Acquired hypothyroidism
- Basic diagnostic strategy

- Further diagnostic considerations:

§ Antibody testing- Tg Ab (thyroglobulin) and TPO Ab (thyroid
peroxidase), TRAb (TSH receptor)
§ Radioactive iodine uptake test: measure exogenous uptake of iodine
by the thyroid, decreased uptake indicates hypothyroidism.
 § Ultrasound of the thyroid gland: e.g., to assess size, structure or
blood flow.
§ Associated conditions – Hypercholesterolemia, hyperlipidemia,
increased creatine kinase, mild anemia, possibly hyponatremia
• Differential diagnosis:
o Euthyroid sick syndrome
o Thyroid hormone resistance
o Riedel thyroiditis
o Hashimoto thyroiditis
• Treatment:
o Drugs:
- L-thyroxine (levothyroxine, a synthetic form of T4): peripherally converted
to T3 (biologically active) and rT3 (biologically inactive).
- Liothyronine: synthetic form of T3
o General principles:
- Lifelong replacement
- Prompt initiation
o Special considerations:
- Children with congenital hypothyroidism: normalization of thyroid hormone
levels within 2-3 weeks is vital.
- Pregnant women with preexisting hypothyroidism: levothyroxine dose must
be increased but should be reduced to pre-pregnancy levels after delivery.
- Anorexia patients: synthetic thyroid hormones are sometimes misused to
achieve weight loss.
- Elderly patients or patients with preexisting cardiovascular conditions:
initiate levothyroxine with a lower dose and gradually increase the dose.
- L-thyroxine replacement in subclinical hypothyroidism if:
§ TSH > 10 mU/L
§ TSH 7.0-9.9 mU/L in asymptomatic patients > 70 years.
§ TSH above the upper limit of normal to 6.9 mU/L in symptomatic
patients < 70 years.

15. Hyperthyroidism. Etiology, pathogenesis, clinical features, diagnosis. Treatment options,

selection of treatment.
• Definition: a condition characterized by the overproduction of thyroid hormones by
the thyroid gland; can cause thyrotoxicosis.
• Etiology:
o Hyperfunctioning of the thyroid gland
- Grave’s disease
- Toxic multinodular goiter
- Toxic adenoma
- TSH-producing pituitary adenoma
o Destruction of the thyroid gland:
- Thyroiditis (Subacute granulomatous thyroiditis (de Quervain
thyroiditis) and Subacute lymphocytic thyroiditis (Postpartum
thyroiditis)).
- Drug induced thyroiditis (e.g., amiodarone, lithium)
 - Contrast-induced thyroiditis
- Hashitoxicosis
- Radiation thyroiditis
o Exogenous thyrotoxicosis
o Ectopic (extrathyroidal) hormone production – Struma ovarii.
• Pathogenesis:
o Disorders of the thyroid gland à excess production of T3/T4 à
compensatory decrease of TSH.
o Thyrotropic adenoma à increased TSH levels à increased T3/T4 levels.
o Other causes of thyrotoxicosis:
- Excess intake/ectopic production of thyroid hormone à increased
levels of circulating T3/T4 à compensatory decrease of TSH.
- Trigger à inflammation of the thyroid gland à cellular damage and
destruction à inappropriate release of T3/T4.

• Clinical features:
o General: Heat intolerance, Excessive sweating because of increased
cutaneous blood flow, Weight loss despite increased appetite, Frequent
bowel movements (because of intestinal hypermotility), Weakness and
fatigue, Onycholysis, Pretibial myxedema.
o Eyes: Lid lag (spasm of the smooth muscle of the levator palpebrae sup), Lid
retraction (“staring look”), Grave’s ophthalmopathy (exophthalmos, edema
of the preorbital tissue).
o Goiter: diffuse smooth, nontender goiter: often audible bruit.
o Cardiovascular: Tachycardia, palpitations and irregular pulse, Hypertension
(systolic pressure increased and diastolic decreased), Abnormal heart rhythm
including atrial fibrillation, Chest pain.
o Musculoskeletal: Fine tremor of the outstretched fingers, Hyperthyroid
myopathy (dysfunction of muscle fibers), Osteopathy – osteoporosis due to
direct effect of T3 on osteoclastic bone resorption.
o Endocrinological: Female (oligo/amenorrhea, anovulatory infertility,
dysfunction of uterine bleeding), Male (gynecomastia, decreased libido,
infertility, erectile dysfunction).
o Neuropsychiatric system: anxiety, emotional instability, depression,
restlessness, Insomnia, Hyperreflexia.
• Diagnosis:
o Thyroid function tests:
- TSH level – typically low
- Free T4 and total T3 levels – typically both are elevated.
o Routine lab studies:
- CBC – leukocytosis and/or mild anemia
- BMP – Hyperglycemia, Mild hypercalcemia.
- Liver chemistry – mildly elevated ALAT, ASAT, ALP and bilirubin
- Serum cholesterol: decreased total cholesterol, LDL and HDL.
- ESR – typically elevated.
o ECG:
- Tachycardia
 - Atrial fibrillation
- LBBB and ECG findings of LVH
o TSH receptor antibody
o Nuclear medicine thyroid scan and radioactive iodine uptake measurement
o Thyroid ultrasound with Doppler

• Treatment options:
o Symptomatic therapy:
- Treatment of hyperadrenergic symptoms: beta blockers (first line)
- Treatment options:
§ First line – propranolol
§ Alternatives – atenolol or metoprolol
§ Severe thyrotoxicosis or thyroid storm treated in ICU: esmolol.
- If contraindications to beta blockers, e.g., severe asthma, consider
calcium channel blockers: verapamil or diltiazem.
o Definitive therapy for hyperthyroidism and thyrotoxicosis
- For Grave’s disease there are 3 options: antithyroid drugs
(methimazole in most patients), Radioactive iodine ablation
(contraindicated in pregnant/breastfeeding women, children <5 years
old) and surgery (contraindicated in pregnant women).