PANCE Exam: Endocrine Review Questions & Answers

DISEASES OF THE THYROID GLAND

Question: At what cervical level is the thyroid located?
It is located at the level of the fourth cervical vertebra.

Question: What are the etiologies associated with a GOITER?
Graves or Hashimoto disease
Oral contraceptives or other medications
Infection
Tumors
Environmental (iodine deficiency)
Receptor defects (resistance to thyroxin)

Question: Which medications are commonly found to result in sporadic goiters?
Oral contraceptives, lithium, amiodarone, and iodide-containing asthma inhalers.

Question: What are the main etiologies for elevated thyroid-binding globulin (TBG) levels?
- Pregnancy
- Infancy
- Estrogens (oral contraceptives/HRT)
- Heroin

Question: What is thyrotoxicosis?
A hypermetabolic state occurring secondary to excess circulating thyroid hormone.

Question: What are the etiologies for thyrotoxicosis?
- Thyroid hormone overdose
- Thyroid hyperfunction
- Thyroid inflammation

What is the most common cause of hyperthyroidism?
Grave disease (toxic diffuse goiter).

Question: What is a thyrotropin receptor stimulating antibody (TSH receptor antibodies)?
An antibody commonly found in Grave disease, which binds to the TSH receptor leading to thyroid stimulation, excessive thyroid hormone production, and goiter.

Question: Which HLA is associated with Grave disease?
HLA-DR3. The association of this HLA type represents a sevenfold relative risk for Grave disease.

Question: Is Grave disease more common in men than in women?
Women are affected five times more often than men.

Question: What are the classical signs and symptoms of Grave disease?
Emotional lability, autonomic hyperactivity, exophthalmos, tremor, increased appetite, weight loss, diarrhea, and a goiter in nearly all affected individuals.

Question: How is Grave disease confirmed by laboratory testing?
Increased free T3 and T4 levels with decreased TSH. Frequently, thyroid peroxidase and TSH receptor stimulating antibodies are present.

Question: What treatment options exist for patients with Grave disease?
Patients can be managed medically with propylthiouracil (PTU) or methimazole, surgically with a subtotal thyroidectomy, or with radioiodine therapy (RAI).

Question: Which of the treatment options for Grave disease is considered definitive?
Radioactive iodine therapy is the definitive treatment of choice.

Question: What drug blocks the uptake of radioactive iodine and should be stopped prior to radioactive iodine scanning or therapy?
Potassium iodine.

Question: What are the three largest concerns with surgical management of Grave disease?

1. Hyper- or hypothyroidism depending on the amount of tissue removed

2. Vocal cord paralysis

3. Hypoparathyroidism

Question: What is the most common precipitant of thyroid storm?
Infections (usually pulmonary).

Question: What signs and symptoms are helpful for diagnosing thyroid storm?
History of hyperthyroidism, widened pulse pressure, tachycardia, hypertension, a palpable goiter, tachycardia, fever/hyperthermia, diaphoresis, increased CNS activity (tremors), emotional lability, delirium or coma, and heart failure.

How do you manage acute thyrotoxicosis (thyroid storm)?
- Support and hydration.
- IV propylthiouracil 1 g to block thyroid production and effects.
- Propranolol at 10 mg/kg IV over 10 to 15 minutes for hypertension and cardiac arrhythmias.
- Lugol iodide, five drops PO every 8 hours or sodium iodide 125 to 250 mg/dl IV over 24 hours will stop thyroxine production.
- Oral dexamethasone at 0.2 mg/kg or oral hydrocortisone 5 mg/kg is another measure that can be taken to further reduce peripheral conversion of T4 to T3.

Question: What is the most common cause of non-iatrogenic hypothyroidism?
Autoimmune Hashimoto thyroiditis.

Question: What are the clinical manifestations of acquired hypothyroidism?
Cold intolerance, constipation, low-pitched voice, menstrual irregularities, mental and physical slowing, dry skin, coarse brittle hair, and decreased energy level with increased need for sleep.

Question: How can primary hypothyroidism be distinguished from secondary hypothyroidism?
Primary hypothyroidism (source is thyroid): TSH levels are high, free T4 and T3 levels are low, and possible presence of antibodies.
Secondary hypothyroidism (source is pituitary): TSH levels are low or normal, free T4 and T3 levels are low, and no antibodies.

Question: What drugs may worsen hypothyroidism?
Propranolol and phenothiazine.

Question: What is the recommended treatment for hypothyroidism?
Thyroxine (T4) hormone replacement.

Question: When initiating thyroid hormone replacement therapy, what is the recommended replacement dose?
1 to 2 μg/kg/day. The initial dose should take into account patient’s age, weight, and cardiac status. Average starting dose is typically 50 μg. Dosage adjustments are made in increments of 25 to 50 μg until at therapeutic level.

Question: What is the recommended monitoring of thyroid hormone replacement therapy?
The therapy should be monitored using serum TSH and plasma-free T4 levels: Initially, every 4 to 6 weeks until at therapeutic dose, every 6 months thereafter, and at 4 to 6 weeks following any adjustment in dose.

Question: What are the hallmark clinical features of myxedema coma?
Hypothermia (75%), bradycardia, and coma.

Question: What is the recommended treatment for myxedema coma?
Thyroxine (T4) administered as an IV bolus at dose of 50 to 100 μg every 6 to 8 hours until replete thyroid hormone reserves and then followed by oral dosing. Triiodothyronine (T3) is NOT recommended in the treatment of myxedema coma.
Supportive measures, correction of hypothermia, ventilatory support, and hydration with normal saline are also indicated.

What is the most common clinical manifestation of lymphocytic thyroiditis?
The appearance of a goiter.

Question: Of hypothyroid, euthyroid, and hyperthyroid, which is the most common presentation of patients with lymphocytic thyroiditis?
The majority will be euthyroid. However, many patients will eventually become hypothyroid, while only a few will manifest the symptoms of hyperthyroidism.

Question: What is DeQuervain disease?
A subacute, nonsuppurative thyroiditis. Its clinical manifestations involve a tender thyroid, fever, and chills, usually remitting within several months.

Question: What is the etiology of DeQuervain thyroiditis?
Most likely due to a viral infection such as mumps or Coxsackie virus.

Question: Which types of nodules are more likely to be malignant on a thyroid scan, hot or cold?
Cold. This procedure should not be considered confirmatory. Cysts and benign adenomas can also read as cold. Some types of thyroid cancers will read as “warm” and thus be dismissed. Use caution when interpreting results.

Question: What test should be performed to distinguish a benign cystic nodule from a malignant nodule?
Fine needle aspiration biopsy and cytological evaluation.

Question: What is a solitary thyroid nodule most likely to be?
A nodular goiter (50%). Other possibilities to consider include carcinoma (20%), adenoma (20%), cyst (5%), or thyroiditis (5%).

Question: If fine needle aspiration of a thyroid nodule reveals parafollicular cells, what type of carcinoma should be suspected?
Medullary carcinoma of the thyroid.

Question: What combination of disorders account for multiple endocrine neoplasia type IIA?
Medullary carcinoma of the thyroid, adrenal medullary hyperplasia or pheochromocytoma, and hyperparathyroidism.

Question: Define sick euthyroid syndrome:
Altered thyroid function in the setting of an acute nonthyroidal illness; no true thyroid dysfunction is present; often seen in critically ill patients.

What changes in thyroid function are seen in a sick euthyroid syndrome?
Most common change is a fall in plasma T3 levels typically due to decrease in the deiodinase activity, which converts T4 to T3 in the peripheral tissue.
Also seen is low plasma total T4 concentrations. This is due to decrease in binding of T4 to thyroid binding globulin.
Finally, plasma TSH levels can be both suppressed (due to high levels of corticosteroids in setting of critical illness) or elevated in response to drops in circulating T4 and T3.


DISEASES OF THE PARATHYROID GLAND

Question: What is the most common cause of hypercalcemia?
Hyperparathyroidism. This condition accounts for 60% of ambulatory hypercalcemic patients.

Question: Is the pituitary gland responsible for parathyroid regulation?
No. Unlike the thyroid gland, the parathyroids are not regulated by the pituitary gland, but rather, by circulating calcium levels.

Question: What is pseudohypoparathyroidism?
An autosomal recessive disorder characterized by kidneys’ unresponsiveness to PTH, shortened fourth and fifth metacarpals and metatarsals, and short stature, all occurring without evidence of parathyroid dysfunction.

Question: What other mineral must be considered in a patient who appears hypocalcemic?
Magnesium. Giving calcium in the setting of low magnesium will not correct the problem. However, magnesium administration will correct both calcium and magnesium levels.

Question: What is the difference between primary and secondary hyperparathyroidism?
In primary hyperparathyroidism, the defect is in the parathyroid gland, (i.e., an adenoma or hyperplasia). While in secondary hyperparathyroidism, the elevated PTH is a physiologic response to a low calcium level, usually a result of renal disease.

Question: What are the diagnostic laboratory findings seen in hyperparathyroidism?
Elevated serum calcium and elevated intact PTH with concomitant decreased phosphorous levels.

Question: What is von Recklinghausen disease?
Hyperparathyroidism, leading to cystic changes in bone due to osteoclastic resorption with fibrous replacement, thus forming nonneoplastic “brown tumors.”

What are the clinical features of hypercalcemic crisis?
Anorexia
Belly pain
Coma
Delirium
Emesis
Fatigue/weakness

Question: What is a positive Chvostek sign?
Facial grimacing as a result of repeated contractions of the facial muscles when percussion (with the tip of index or middle finger) is applied to the facial nerve (at the top of the cheek just below the zygomatic bone in front of the ear). Chvostek maneuver generally indicates hypocalcemia. It may be present in approximately 10% to 30% of normal individuals.

Question: What is Trousseau sign and when is it exhibited?
A carpal spasm induced when the blood pressure cuff on the upper arm maintains an above-systolic pressure for approximately 3 minutes. Fingers become spastically extended at the interphalangeal joints and flexed at the metacarpophalangeal joints. It is typically present in latent tetany because of hypocalcemia, hypomagnesemia, severe alkalosis, and strychnine poisoning.

Question: Which is a more reliable physical examination finding of hypocalcemia, Trousseau sign or Chvostek sign?
Trousseau sign; 10% of normal people have a positive Chvostek sign, and studies reveal approximately 29% of hypocalcaemia may result in a false negative Chvostek sign; therefore, this test a poor discriminator. On the other hand, Trousseau sign is relatively specific for hypocalcaemia—94%of hypocalcaemic patients display a positive sign, comparedwith 1% of normocalcaemic people.

Question: What is the most common cause of hyperparathyroidism?
Parathyroid adenoma (85%).

Question: What are the treatment options for hyperparathyroidism?
Definitive treatment is surgical resection (parathyroidectomy).
Medical management (reserved for patients meeting the criteria): Modest intake of calcium (1000 mg/day) and vitamin D (400–600 IU/day). Theoretically, low calcium intake can stimulate PTH production, and therefore, it is not recommended; 25% of medically observed patients develop indications for surgery.

Question: What are the criteria for medical management of hyperparathyroidism?
- Serum calcium level elevated only mildly.
- No previous episode of life-threatening hypercalcemia.
- Normal renal status (i.e., creatinine clearance of >70% without nephrolithiasis or nephrocalcinosis).
- T score above –2.5 at lumbar spine, hip, and forearm.
- Asymptomatic.

What are the recommendations for the management and monitoring of a patient status post-parathyroidectomy?
Immediate postoperative management focuses on establishing the success of the surgery and monitoring the patient for complications such as symptomatic hypocalcemia, bleeding, vocal cord paralysis, and laryngospasm. The serum calcium concentration typically reaches a nadir within 24 to 36 hours after surgery. The serum PTH level is in the normal range within 30 hours. The patient should maintain a low-calcium diet until the serum calcium concentration is normal.


DISEASES OF THE ADRENAL GLAND

Question: What are the zones of the adrenal cortex?
The adrenal cortex makes up 80% to 90% of the adrenal gland. The three zones from outer to inner include zona glomerulosa, zona fasciculate, and zona reticularis.

Question: What products are produced by the adrenal medulla?
The adrenal medulla consists of 10% to 20% of the adrenal gland. It is derived from neuroectodermal cells of the sympathetic ganglia and is the source of catecholamine hormones (epinephrine and norepinephrine).

Question: What hormones are produced by the adrenal cortex?
Mineralocorticoids, glucocorticoids, and androgenic sex steroids.

Question: What is the major glucocorticoid produced by the adrenal cortex? How is it regulated?
Cortisol. It is regulated by the signals from the pituitary gland (specifically adrenocorticotropic hormone [ACTH]).

Question: What is the major mineralocorticoid? How is it regulated?
Aldosterone. It is regulated by ACTH from the pituitary and by the renin angiotensin system.

Question: What is the major sex androgen produced by the adrenal cortex?
Dehydroepiandrosterone (DHEA). It is regulated by ACTH from the pituitary and circulating levels of testosterone and estrogens.

Question: What controls the release of adrenocorticotropic hormone (ACTH) from the pituitary?
Directly: Corticotropin-releasing hormone (CRH) from the hypothalamus, circulating cortisol levels, and antidiuretic hormone (ADH) otherwise known as vasopressin.
Indirectly: Circulating ACTH levels.

Question: What are the actions of cortisol (glucocorticoids)?
Majorly affects protein, glucose, and fat metabolism. It strongly inhibits the entire process of inflammation and immune response. It inhibits muscle proteolysis and increases hepatic conversion of liberated amino acids into glucose (for storage as glycogen). It inhibits collagen synthesis, thereby reducing bone formation, connective tissue, and muscle mass. It increases arteriolar tone (through decreased endothelial permeability).

What are the actions of aldosterone (mineralocorticoids)?
Major regulator of sodium, potassium, and fluid balance. It acts on the renal tubule to increase sodium reabsorption and concomitant expansion of extracellular fluid, which results in maintenance of blood pressure. In turn, renal excretion of H+ and K+ occur, resulting in lowered plasma potassium concentrations.

Question: What are the actions of dehydroepiandrosterone (DHEA)?
DHEA is a precursor steroid to testosterone and estradiol. In women, it supplies 50% of androgenic hormone requirement (while the remainder comes from the ovaries). After menopause, the adrenal cortex is the sole source of estrogens in women. In men, DHEA is negligible since the majority of the testosterone is produced from the testes.

Question: What is the definition of adrenal insufficiency?
Inadequate function of the adrenal gland due to disease, destruction, or surgical removal of the adrenal cortices.

Question: What are the etiologies of primary adrenal insufficiency?
- Acute, abrupt onset:
- Adrenal hemorrhage (i.e., anticoagulation therapy)
- Thrombosis (as seen in meningococcal disease)
- Disseminated infection (i.e., sepsis)
- Antiphosphoid syndrome
- Slow, insidious progression:
- Autoimmune disease (Addison disease)
- Infection (i.e., TB, coccidiomycosis, blastomycosis, histoplasmosis)
- Metastatic carcinoma (most common lung, breast, kidney)
- Lymphoma
- AIDS (CMV, Kaposi sarcoma, etc.)

Question: What is the most common cause of primary adrenal insufficiency?
Failure of the adrenal cortex due to autoimmune process (also known as Addison disease).

Question: What are the causes of secondary adrenal insufficiency?
- Sheehan syndrome (postpartum pituitary necrosis)
- Bleeding into a pituitary macroadenoma
- Head trauma

Question: What are the common clinical manifestations of adrenal insufficiency?
Fatigue, lethargy, anorexia, weight loss, hyperpigmentation, hyponatremia, and hyperkalemia are common. Depression, dizziness, orthostatic hypotension, nausea and vomiting, diarrhea, generalized abdominal pain, WBC changes (i.e., lymphocytosis, eosinophilia), and normocytic, normochromic anemia are also significant manifestations.

What are the clinical features of Addison disease (explain using the name as a mnemonic)?
Anorexia
Diarrhea
Dehydration
Increased K+
Skin pigmentation
Orthostatic hypotension
Na level is abnormal

Question: What characteristic electrolyte imbalances are associated with primary adrenal insufficiency?
Hyperkalemia, hyponatremia, hypoglycemia, azotemia (if volume depletion is present), and a mild metabolic acidosis.

Question: Are orthostatic hypotension and electrolyte abnormalities more common in primary or secondary adrenal insufficiency?
Primary, because of the aldosterone deficiency and hypovolemia.

Question: What are the most specific signs of primary adrenal insufficiency?
Hyperpigmentation of the skin and mucosal membranes due to high ACTH levels as a consequence of cortisol feedback and salt craving.

Question: What is the most common cause of secondary adrenal insufficiency and adrenal crisis?
Iatrogenic adrenal suppression from prolonged steroid use. Rapid withdrawal of steroids may lead to collapse and death.

Question: Which hormone secretion is NOT impaired by secondary adrenal insufficiency?
Aldosterone. Aldosterone secretion is more dependent upon angiotensin II than corticotrophin-releasing hormone signals from the pituitary gland. Aldosterone deficiency is not a problem in hypopituitarism.

Question: Besides serum cortisol levels and plasma ACTH, what are the three tests used to evaluate adrenal insufficiency?
1. Corticotropin stimulation test
2. Insulin-induced hypoglycemia
3. Metyrapone test

Question: How is a corticotropin (ACTH) stimulation test performed to rule out adrenal insufficiency?
After a baseline ACTH and cortisol level are obtained, 250 μg of Cosyntropin is given IV (or IM). Cortisol levels are obtained at 30 and 60 minutes postinjection. Adrenal function is thought to be normal if the cortisol level drawn at 30 or 60 minutes is ≥18 μg/dL and there are raises of minimum of >7 mg/dL above baseline.

Are imaging studies of the adrenal glands necessary in primary adrenal insufficiency?
Yes. In cases other than autoimmune or adrenal myeloneuropathy, a CT scan of the adrenal should be performed to aid in the differential diagnosis. Enlarged glands with/without calcifications in patients with TB are a sign of active disease and warrant anti-infective therapy. Enlargement also occurs in other fungal infections, lymphoma, cancer, and AIDS. A biopsy by CT guidance may also be helpful.

Question: What is the daily replacement of hydrocortisone for a stabilized patient with adrenal insufficiency?
Hydrocortisone 15 mg in the morning and 10 mg in the afternoon. This matches the two-third a.m., one-third p.m. normal circadian release of cortisol physiologically. The dose should be the smallest possible to alleviate clinical symptoms yet prevent weight gain and osteoporosis. Measurements of urinary cortisol may help determine the appropriate dosing.

Question: What accounts for the almost immediate effect of cortisol on blood pressure in patients with adrenal insufficiency?
Cortisol exerts a permissive effect on catecholamine vascular responsitivity and a vital role in the maintenance of vascular tone, vascular permeability, and distribution of body water within the vascular compartment.

Question: What added precautions should be taken by all patients with adrenal insufficiency?
They should wear a medic alert bracelet, carry a card detailing their medications, and double or triple their dose of hydrocortisone when they have surgery or sustain injury/illness. They should secure ampules of glucocorticoids for self-injection or suppositories when vomiting or unable to take oral steroids.

Question: What is the amount of increased cortisol production that accompanies surgery?
It depends upon the surgery; 85% above baseline for up to 2 days postlaparotomy and 35% above baseline for more minor procedures involving joints, breasts, or neck.

Question: Which drugs can increase the metabolism of cortisol?
Phenytoin, phenobarbital, and Rifampin.

Question: What symptoms should increase the suspicion of adrenal insufficiency in the critically ill?
Unexplained circulatory instability, high fever without cause, unresponsive to antibiotics, hypoglycemia, hyponatremia, hyperkalemia, neutropenia, eosinophilia, unexplained mental status changes, disparate anticipated severity of disease, and the actual state of the patient.

Question: What are the adverse effects of using excessive dosing when replacing cortisol production during times of stress?
Catabolic effects on muscle, impaired wound healing, antagonizing insulin, and the effects on glucose metabolism as well as the anti-inflammatory effect on any active infection.

Question: What are the current dosing recommendations for stress doses in patients with suspected adrenal insufficiency?
- Minor stress: 25 mg/day
- Moderate stress: 50 to 75 mg/day
- Major stress: 100 to 150 mg/day

Two weeks after a myocardial infarction, a patient takes warfarin and has sudden onset of hypotension, right flank pain, right CVA pain, epigastric pain, fever, nausea, and vomiting. What is the most likely etiology?
Adrenal gland hemorrhage (adrenal apoplexy).

Question: What is the Waterhouse-Fredrickson syndrome?
Septicemia secondary to meningococcemia with associated bilateral adrenal gland hemorrhage. The patient will have a petechial rash, purpura, shaking, chills, a severe headache, and other signs of acute adrenal insufficiency.

Question: What are the causes of acute adrenal crisis?
Major stress such as surgery, severe injury, myocardial infarction, or any other acute illness in a patient with primary or secondary adrenal insufficiency.

Question: What are the principal signs and symptoms of adrenal crisis? The most common cause is withdrawal of steroids:
Abdominal pain, hypotension, and shock.

Question: What is the protocol for emergent steroid replacement in adrenal crisis?
Treat by administering hydrocortisone; 100 mg IV bolus and 100 mg added to the first liter of D5 0.9 NS. Additional 50 to 100 mg IV q8h until stable.

Question: What are the two main causes of death during an adrenal crisis?
Circulatory collapse and hyperkalemia-induced arrhythmias.

Question: Name four conditions that can be attributed to adrenocortical overstimulation:
Cushing syndrome, hyperaldosteronism, adrenogenital syndrome, and feminization.

Question: What is Cushing disease?
Pituitary adenoma leading to increased ACTH secretion with resultant bilateral adrenal hyperplasia and elevated cortisol levels.

Question: How is Cushing disease different from Cushing syndrome?
Cushing syndrome is elevated cortisol levels from various causes, including paraneoplastic syndromes, primary adrenal tumors, and exogenous use of cortisol, whereas Cushing disease is specifically the elevation in cortisol levels due to ACTH-secreting pituitary adenomas (it is a subset of Cushing syndrome).

Question: What clinical manifestations are common to all patients with Cushing syndrome?
Moon facies, buffalo hump, obesity, hypertrichosis, hypertension, growth retardation, easy bruising, purple striae on the hips and abdomen, and amenorrhea in women.

What is the differential diagnosis for hypercortisolism state?
- Pseudo-Cushing syndrome: major depressive disorder, alcohol excess.
- Hypercortisolism without Cushing syndrome: obesity, stress, trauma, acute illness, pregnancy, hyperthyroidism, drug induced (i.e., psychotropic medications).
- Metabolic syndrome and/or polycystic ovary syndrome may mimic Cushing syndrome with similar signs and symptoms.

Question: What is the recommended SCREENING test for suspected Cushing syndrome?
Dexamethasone suppression test: abnormal is plasma cortisol >5 μg/dL at 8 a.m. after 1 mg dexamethasone ingested 11 p.m. day before.

Question: What is the recommended CONFIRMATORY test for hyperfunctioning adrenal status?
24-hour urine cortisol levels: abnormal level in adult man is >10 mg/24 hours, in adult woman is >8 mg/24 hours, in elderly people slightly lower, and in pediatric patients depends on age but significantly lower.

Question: What is considered the definitive treatment for Cushing syndrome?
Surgical resection, or if nonoperable etiology, then treat the underlying cause.

Question: What are the clinical manifestations of primary hyperaldosteronism (Conn syndrome)?
Hyperplasia of the zona glomerulosa leading to hypertension, sodium and water retention, hypokalemia, and decreased serum renin levels.

Question: What are the hallmarks of polyglandular autoimmune disease type I?
Autoimmune hypoparathyroidism, autoimmune adrenalitis (Addison disease), and chronic mucocutaneous candidiasis.

Question: What is a pheochromocytoma?
Catecholamine-producing tumor of the neurochromaffin cells. Most arise from the adrenal medulla but extra-adrenal masses may occur at anatomical regions containing sympathetic ganglia.

Question: What are the classic signs and symptoms of pheochromocytomas?
Paroxysmal episodes of hypertension, autonomic hyperactivity, and headaches lasting for 20 to 30 minutes. Concomitant underlying hypertension between episodes may be present. Abdominal mass present on examination or imaging.

Question: When is the peak incidence of pheochromocytoma?
Third or fourth decade. However, it can occur from infancy to old age. Familial pheochromocytomas typically occur earlier in life and are bilateral.

Question: What laboratory tests help make the diagnosis of pheochromocytoma?
An increased total 24-hour urinary catecholamines and their metabolites (i.e., epinephrine, norepinephrine, metanephrine, and VMA). Clonidine suppression test can also be administered in an inpatient setting.

Which class of antihypertensive drugs are recommended for the temporary treatment of pheochromocytoma-associated hypertension?
Alpha-adrenergic blocking agents such as phenoxybenzamine and prazosin.

Question: How do you manage a hypertensive crisis in a patient with a pheochromocytoma?
1 mg of IV phentolamine or 0.5 to 0.8 mg/kg/min of sodium nitroprusside.

Question: What is the treatment of choice for pheochromocytoma (intra-adrenal or extra-adrenal)?
Surgical resection.


DISEASES OF THE PITUITARY GLAND

Question: What is the radiologic study of choice to assess the pituitary or hypothalamic gland when hormonal abnormalities have been established?
MRI with analysis of the sagittal and coronal sections. A CT scan can be helpful if bony invasion is suspected.

Question: What is the most common type of pituitary tumor?
Prolactinomas.

Question: What are the common presenting signs of a prolactinoma?
Headache, visual field impairment (typically bitemporal hemianopsia), amenorrhea, and galactorrhea.

Question: What is the most common presenting symptom of a prolactinoma in a woman?
Secondary amenorrhea.

Question: What is the differential diagnosis for hyperprolactinemia?
Hyperprolactinemia can be caused by pituitary adenomas, hypothyroidism, or drugs, such as reserpine, methyldopa, phenothiazine, or oral contraceptives.

Question: What is the serum prolacting level in hyperprolactinemia?
50 ng/mL (typically > 200 ng/mL in prolactinoma).

Question: What two options exist for the treatment of prolactinomas?
Bromocriptine and surgery via a transsphenoidal approach.

Question: What is diabetes insipidus?
A lack of ADH secretion, which results in an inability to concentrate the urine despite functioning kidneys.

Compare and contrast CENTRAL diabetes insipidus from NEPHROGENIC diabetes insipidus:


Question: What is the danger of rigorously hydrating a patient who has hypernatremia due to diabetes insipidus?
Cerebral edema, seizures, and death.

Question: What is the typically response to the administration of ADH in a patient with central diabetes insipidus?
Response to exogenous ADH is typically a 50% increase in urine osmolality.

Question: What should the clinician consider if the patient with diabetes insipidus continues to diurese despite repeated doses of DDAVP (ADH)?
The patient most probably has nephrogenic diabetes insipidus owing to unresponsive kidney receptors for ADH, irrespective of whether the ADH is endogenous or exogenous.

Question: If nephrogenic diabetes insipidus is assumed, what further pharmacological treatment may be helpful?
Thiazide diuretics have a paradoxical effect and may work in decreasing fluid losses.

Question: What is the definition for SIADH?
Syndrome of inappropriate antidiuretic hormone. There is an excessive release of ADH, resulting in a dilutional hyponatremia and hyposmolar state.

Question: What key laboratory results are expected with SIADH?
Low serum sodium levels and high urine sodium levels in the setting of normovolemia and normal renal, thyroid, and adrenal function. It is the most common cause of normovolemic hyponatremia.

What is the treatment for SIADH?
Treatment of severe symptomatic hyponatremia includes a loop diuretic, such as furosemide, and the simultaneous infusion of small boluses of 3% saline over 4 hours or normal saline. If hyponatremia is corrected too rapidly, neurologic sequelae may result.

Question: What is the hormone abnormality in acromegaly?
Excessive growth hormone.

Question: What are the clinical manifestations of acromegaly?
Coarse facial features, enlarged tongue, enlargement of the distal extremities, and hypogonadism.

Question: What are the clinical manifestations of primary hypogonadism?
Failure of development of the secondary sexual characteristics with abnormally small penis and testes.

Question: What is hypogonadotropic hypogonadism?
Decreased levels of gonadotropins (FSH and LH) from the pituitary, which results in inadequate estrogen, progesterone, and/or testosterone production despite functioning ovaries or testes.

Question: How is the diagnosis of primary hypogonadism made?
The levels of FSH and LH are abnormally elevated for the corresponding age. Testosterone levels remain low and show little response to the administration of hCG.


DIABETES MELLITUS

Question: What is the most common cause of hypoglycemia seen in the emergency department?
An insulin reaction in a diabetic patient.

Question: What are the key predisposing factors to hypoglycemia in diabetic patients on insulin?
Exercise, poor oral intake, worsening renal function, and medications are the key predisposing factors to consider.

Question: What principal hormone protects the human body from hypoglycemia?
Glucagon.

Question: What are the neurologic signs and symptoms associated with hypoglycemia?
Hypoglycemia may produce mental and neurologic dysfunction. Neurologic manifestations can include paresthesias, cranial nerve palsies, transient hemiplegia, diplopia, decerebrate posturing, and clonus.

Question: Which is the most common type of hypoglycemia in children?
Ketotic hypoglycemia. This condition usually develops in boys between 18 months and 5 years of age. Attacks typically arise from caloric deprivation. These attacks may be episodic and are more frequent in the morning and during periods of illness.

In the first 2 years of life, what is the most common cause of drug-induced hypoglycemia?
Salicylates.
Between ages 2 and 8 years, alcohol is the most likely cause.
Between ages 11 and 30 years, insulin and sulfonylureas are the primary causes.

Question: What drugs potentiate the hypoglycemic effects of sulfonylurea?
Salicylates, alcohol, sulfonamides, phenylbutazone, and bishydroxycoumarin.

Question: How is sulfonylurea-induced hypoglycemia treated?
IV glucose alone may be insufficient. It may require diazoxide, 300 mg slow IV over 30 minutes, repeated q4h.

Question: What are the classifications of impaired glucose regulation from normal to diabetes?

A1C is not yet recommended for diagnosis (although it may be in the future).

Question: How is the etiology of type 1 DM different from type 2 DM?
Type 1 DM is associated with human leukocyte antigens (HLA), autoimmunity, and or islet cell antibodies.
Type 2 DM usually involves a genetic mutation resulting in inactive pancreatic and liver enzymes as well as insulin receptor defects leading to resistance.

Question: What etiologies are responsible for secondary DM?
Exocrine pancreatic diseases such as cystic fibrosis, pancreatic cancer, and Cushing disease.

Question: What are the main signs and symptoms of diabetes mellitus?
Patient presents with classic symptoms of polyuria (increased urination), polydipsia (increased thirst), and polydysplasia (increased appetite despite increased caloric intake). Other symptoms include fatigue, blurry vision, menstrual irregularities, delayed wound healing, or recurrent infections. In type 1 DM, typically, weight loss is seen. In type 2 DM, typically, weight gain is seen (obesity). Many cases of type 2 DM are asymptomatic.

What are the diagnostic criteria for diabetes mellitus according to the World Health Organization?
1. Symptoms of DM and a casual plasma glucose 200 mg/dL or higher. (Symptoms include polyuria, polydipsia, and unexplained weight loss.)
OR
2. Fasting plasma glucose 126 mg/dL or higher on two separate occasions.
OR
3. 2-hour plasma glucose is 200 mg/dL or greater during an oral glucose tolerance test (performed with glucose load of 75 g glucose).

Question: What is the significance of the HgbA1C?
It represents the fraction of hemoglobin that has been nonenzymatically glycosylated. It provides an accurate estimation of the relative blood glucose level over the preceding 8 to 12 weeks.

Question: What are the two main side effects of uncontrolled diabetes mellitus on the retina?
Diabetic retinopathy and neovascularization.

Question: What are the main side effects of uncontrolled diabetes mellitus on the nervous system?
Peripheral polyneuropathy, gastrointestinal autonomic neuropathy (i.e., gastroparesis and diabetic enteropathy), genitourinary autonomic neuropathy (i.e., erectile dysfunction and bladder incontinence), and cardiovascular autonomic neuropathy (i.e., resting tachycardia, exercise intolerance, and orthostatic hypotension).

Question: Describe the classic presentation of diabetic peripheral polyneuropathy:
Progressive peripheral nerve damage resulting in “stocking and glove” distribution of pain, numbness, tingling, and decreased sensation.

Question: What is the main side effect of uncontrolled diabetes mellitus on the renal system? How is it prevented?
Diabetic nephropathy. Prevention includes glycemic control and angiotensin inhibition with antihypertensive agents (either angiotension converting enzyme inhibitor [ACE-I] or angiotensin receptor blocker [ARB]).

Question: What is the earliest manifestation of diabetic nephropathy?
An increase in albumin excretion (microalbuminuria).

Question: What are the key factors predisposing diabetics to soft tissue infections?
Microvascular disease, poor wound healing, and trauma often masked by neuropathy.

Question: What is the Somogyi effect?
A hyperglycemic event that results from an overzealous response by counter regulatory hormones during a period of hypoglycemia.

Question: What is the Dawn phenomenon?
A term used to describe an abnormal early-morning (usually between 4 and 8 a.m.) increase in blood sugar in patients with diabetes. The dawn phenomenon is more common in people with type 1 diabetes than with type 2 diabetes.

Which ethnic groups are most at risk for diabetes mellitus?
Hispanics: Prevalence is 1.7 to 2.4 times higher than in non-Hispanics and the death rate is twice as high.
Native Americans: Prevalence is 2.6 to 4.0 times higher than in nonnative Americans and the death rate is also twice as high.
Reasons for the high rate of disease in these groups is attributed to increased incidence of obesity and hyperinsulinemia.

Question: What is the recommended first-line oral hyperglycemic agent in type 2 diabetes (as long as not contraindicated)?
Metformin.

Question: What is the formula for calculating the initial total daily amount of insulin necessary for type 1 diabetic patient?
0.5 U × wt (kg).

Question: What is the optimal formula used for dosing insulin in a type 1 diabetic patient?
50% basal insulin and 50% bolus insulin.

Question: What are the onset time, peak, and duration of regular insulin?
Onset: 0.5 to 1 hour
Peak: 2 to 3 hours
Total duration: 3 to 6 hours

Question: What are the onset time, peak, and duration of NPH insulin?
Onset: 2 to 4 hours
Peak: 6 to 12 hours
Total duration: 10 to 16 hours

Question: What are the onset time, peak, and duration of glargine insulin?
Onset: 1 to 2 hours
Peak: plateau release, no peak
Duration: 20 to 24 hours

Question: What is the appropriate mixture of regular and intermediate acting insulin in a twice daily insulin injection regimen?
Two-third of the dose should be given 30 minutes prior to breakfast; the remaining one-third given 30 minutes prior to dinner. Both injections should be two-third intermediate acting and one-third regular (short acting) insulin.

Question: What are the ideal blood glucose and HgbA1C levels for a diabetic patient?
Premeal glucose: 80 to 120 mg/dL
2 hours postprandial: 100 to 160 mg/dL
Bedtime glucose: 100 to 140 mg/dL
HbA1c: <7% (some experts are recommending <6.5%)

Which common medications are likely to worsen glucose control in a diabetic patient?
Thiazide diuretics, beta-blockers, steroids, estrogens, dilantin, cyclosporin, and diazoxide.

Question: What are the common causes of abdominal pain, nausea, and vomiting in a diabetic patient?
Diabetic gastroparesis, gallbladder disease, pancreatitis, and, perhaps, ischemia bowel.

Question: What are some agents used to treat severe diabetic gastroparesis?
Cisapride and metoclopramide are the key agents. Erythromycin has also been tried in very severe cases.

Question: What medications are likely to lead to acute hyperkalemia in a diabetic patient?
NSAIDs, ACE inhibitors, beta-blockers, potassium-sparing diuretics, and salt substitutes (these are usually potassium salts).

Question: Which gastrointestinal condition should be considered in a diabetic patient with diffuse abdominal pain, bloody stools, and a high serum lactate?
One should strongly consider ischemic or necrotic bowel.

Question: What is the most desirable agent used to treat severe hyperglycemia in pregnancy?
Multiple injections of insulin.

Question: What are the major adverse effects of intravenous radiocontrast dye given to diabetic patients?
Acute tubular necrosis is well known. One should also watch for worsening of CHF, precipitation of angina pectoris, and hemodynamic compromise.

Question: What side effect of propranolol may of be of concern to a diabetic patient?
Hypoglycemia. Beta-blockers can also retard recovery from insulin-induced hypoglycemia. This latter effect is presumably due to diminished or absent early warning signs. Studies showed that the effects on glucose metabolism may be less prominent with beta-1 selective drugs.

Question: What are the signs and symptoms of diabetic ketoacidosis (DKA)?
- Nausea/vomiting with abdominal pain
- Hyperventilation (Kussmaul respirations)
- Hypotension/shock
- Polyuria, polydipsia, and weight loss

Question: What do profound polyuria and dehydration in DKA reflect?
Severe osmotic diuresis caused by glycosuria.

What laboratory findings are expected with DKA?
- Elevated serum glucose (typically >250 mg/dL but less than 800 mg/dL in DKA).
- Elevated serum ketoacids (β-hydroxybutyrate, acetoacetate) and natural ketone (acetone).
- Ketonuria and glucosuria are present.
- Serum osmolality is greater than 320 to 330 mOsm/kg.
- Serum bicarbonate levels, pCO2, and pH are decreased, leading to a metabolic acidosis with increased anion gap.
- Hyponatremia and variable potassium levels (may be elevated but can be normal).
- Elevated white blood cell (WBC) count.

Question: What is the major mechanism of hyponatremia in DKA patients?
Dilution of sodium due to shifting of water out of the cells into the vascular space.

Question: What is the most important initial step in treating DKA?
Volume replacement, with the first liter administered over about 60 minutes.

Question: Outline the basic treatment including fluid replacement for DKA:
- Start with normal saline (the total deficit may be 5–10 L), followed by potassium (100–200 mEq) in the first 12 to 24 hours.
- Prescribe insulin: 5 to 10 U bolus followed by 5 to 10 U/h. Change replacement fluids to D5W when the glucose falls below 200 mg/dL and keep at rate of 150 to 200 mL/h.
- Administer sodium bicarbonate (100 mmol diluted) if pH <6.9.

Question: Why should caution be used in administering bicarbonate therapy during DKA?
Because of risk of paradoxical CSF acidosis, cardiac arrhythmias, decreased oxygen delivery to tissue, and fluid and sodium overload.

Question: What major insults are likely to lead to DKA in an otherwise controlled diabetic patient?
Always look for infection (even a minor one), cardiac ischemia, medications, and lack of compliance with insulin and diet.

Question: What is the possible adverse effect seen during very rapid correction of severe hyperglycemia?
Cerebral edema.

Question: What are the key features of nonketotic hyperosmolar coma?
Hyperosmolality, hyperglycemia, and dehydration. Blood sugar levels should be >800 mg/dL, serum osmolality should be >350 mOsm/kg, and serum ketones should be negative.

Question: What are the key factors leading to hypernatremia in a patient with nonketogenic hyperosmolar coma?
Profound dehydration with greater losses of water than of salts as well as impaired thirst.

Question: Besides the typical presentation seen with hyperglycemia emergency, what unique focal neurologic signs may be present in a patient with nonketotic hyperosmolar coma?
Hemisensory deficits or perhaps hemiparesis. 10% to 15% of these patients will have a seizure.

Outline the recommended treatment for nonketotic hyperosmolar coma:
- Administer fluids (patients can be as much as 12-L deficient). Give normal saline until adequate blood pressure and urinary output established.
- Administer potassium (10–15 mEq/h).
- Administer insulin (only about 5–10 U).
- Add D5W replacement fluids when blood glucose level drops below 200 mg/dL.

Question: What is the drug of choice for a patient with nonketotic hyperosmolar coma and who experiences a seizure?
The drugs of choice for this seizure disorder are lorazepam (Ativan) or diazepam (Valium). Phenobarbital is also appropriate. Phenytoin is contraindicated in patients with hyperglycemic, hyperosmolar, nonketotic coma.

Question: What is the overall mortality rate of nonketotic hyperosmolar coma?
Approximately 50%.


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