Endocrinology

Question 1

What are the common symptoms and signs of hyperthyroidism?

Answer 1

Symptoms: Nervousness, anxiety, irritability, insomnia, heat intolerance, sweating, palpitations, tremors, weight loss with increased appetite, fatigue, weakness, emotional lability, and diarrhea.

Signs: Enlarged thyroid gland, warm skin, thyroid “stare”- lid lag, exophthalmos, proptosis, ophthalmoplegia (Graves disease), pretibial myxedema (Graves disease), tremor, tachycardia, and atrial fibrillation.

• Check TSH when patients come to the hospital with new-onset atrial fibrillation

Question 2

What are the most common causes of hyperthyroidism? 9

Answer 2

1. Graves disease - diffusely enlarged thyroid gland, (+) thyroid-stimulating antibodies, exophthalmos, proptosis, ophthalmoplegia, and pretibial myxedema
2. Toxic Multinodular Goiter - lumpy thyroid, “hot” nodules on thyroid nuclear scan
3. Adenoma - single hot nodule on thyroid nuclear scan
4. Subacute thyroiditis - viral infection with a tender, painful thyroid gland
5. Factitious hyperthyroidism - self-medication with thyroid hormone
6. Amidarone - can cause hyper- or hypothyroidism
7. TSH-producing pituitary tumor
8. Thyroid carcinoma
9. Struma ovarii

Question 3

Describe the classic laboratory pattern of hyperthyroidism.

Answer 3

TSH level = low (unless the patient has a TSH-secreting tumor)

Triiodothyronine (T3) and thyroxine (T4) are increased

Question 4

How is hyperthyroidism treated?

Answer 4

Short term/stabilizing treatment

• Propylthiouracil (PTU) and methimazole/carbimazole can be used as suppressive agents.
• Beta blockers are used in the setting of thyroid storm.
• Iodine can also suppress the thyroid gland but is rarely used for this purpose clinically.

Definitive treatment (both will require thyroid hormone replacement for life)

• Radioactive iodine ablation
• Surgery in pregnant patients

Question 5

What are the symptoms and signs of hypothyroidism?

Answer 5

Symptoms: Weakness, lethargy, fatigue, cold intolerance, weight gain with anorexia, constipation, loss of hair, hoarseness, menstrual irregularity (menorrhagia is classic), myalgias and arthralgias, memory impairment, and dementia.

• Always rule out hypothyroidism as a cause of dementia.

Signs: Bradycardia; dry, coarse, cold, and pale skin; periorbital and peripheral edema; coarse, thin hair; thick tongue; slow speech; decreased reflexes; hypertension; carpal tunnel syndrome and paresthesias; vitiligo, pernicious anemia, and diabetes (remember the autoimmune association between these three conditions and Hashimoto disease); and coma (severe disease).

• In children, congenital hypothyroidism may occur (mental, motor, and growth retardation).

Question 6

What are the common causes of hypothyroidism? 7

Answer 6

1. Hashimoto thyroiditis - histology shows lymphocytes + anti-thyroid ab + anti-microsomal ab, non-tender goiter
2. Iatrogenic - usually after treatment for hyperthyroidism
3. Iodine deficiency
4. Amiodarone
5. Lithium
6. Secondary hypothyroidism - due to pituitary or hypothalamic failure (decreased TSH)
7. Sheehan syndrome - hypopituitarism caused by pituitary necrosis from blood loss and hypovolemic shock during and after childbirth

Question 7

Describe the laboratory findings in hypothyroidism.

Answer 7

• Elevated TSH (unless caused by secondary causes)
• Decreased T3 and T4
• antithyroid and antimicrosomal antibodies (if Hashimoto thyroiditis)
• hypercholesterolemia, and anemia (which may be because of chronic disease or coexisting pernicious anemia)

Question 8

Why is free T4 (or free T4 index) better than total T4 for measuring thyroid hormone activity?

Answer 8

Free T4 (free T4 index) - measures the active form of thyroid hormone, as many conditions cause a change in the amount of thyroid-binding globulin (TBG), thus changing total T4 levels in the absence of hypo- or hyperthyroid symptoms

• Examples that increase TBG: pregnancy, estrogen therapy, and oral contraceptive pills
• Examples that decrease TBG: nephrotic syndrome, cirrhosis, and corticosteroids

T3 resin uptake is an older test that is not likely to appear on Step 2, but if you are asked, it should rise or fall in the same way as free T4.

Question 9

How is hypothyroidism treated?

Answer 9

With T4 or thyroxine.

T3 should not be used

Question 10

What is sick euthyroid syndrome?

Answer 10

Any illness that cause a temporary derangement in thyroid function tests that resemble hypothyroidism: TSH ranges from normal to mildly elevated, and serum T4 ranges from normal to mildly decreased.

Question 11

What are the symptoms and signs of Cushing syndrome (increased corticosteroids)?

Answer 11

Symptoms: weight gain, easy bruising, acne, hirsutism, emotional lability, depression, psychosis, weakness, menstrual changes, sexual dysfunction, insomnia, and memory loss.

Signs: Buffalo hump, truncal and central obesity with wasting of extremities, round plethoric facies, purplish skin striae, acne, hirsutism, weakness (especially of the proximal muscles), hypertension, depression, psychosis, peripheral edema, poor wound healing, glucose intolerance or diabetes, osteoporosis, and hypokalemic metabolic alkalosis (because of mineralocorticoid effects of certain corticosteroids). Growth may be stunted in children.

Question 12

What are 4 common causes of Cushing syndrome?

Answer 12

1. iatrogenic - steroids
2. Cushing’s disease (pituitary adenoma that secretes ACTH
3. Ectopic ACTH (small cell lung cancer)
4. adrenal adenomas/carcinomas

Question 13

How is Cushing syndrome diagnosed?

Answer 13

24-hour measurement of free cortisol in urine (cortisol is abnormally elevated)

or

dexamethasone suppression test (cortisol levels are not appropriately suppressed several hours after administration of dexamethasone)

ACTH levels

• ACTH is elevated in Cushing disease (get MRI to look for pituitary adenoma) or small cell lung cancer (should also see weight loss, hemoptysis with lung mass on chest radiograph in patients with small cell lung cancer)
• ACTH is decreased in adrenal adenomas (get CT/MRI to look for adrenal tumor)

note: Random cortisol level is an inappropriate test because of wide interpatient and intrapatient variations

Question 14

What are the symptoms and signs of hypoadrenalism (Addison disease)?

Answer 14

Symptoms: Anorexia, weight loss, weakness, apathy.

Signs: Hypotension, hyperkalemia, hyponatremia, hyperpigmentation (only if the pituitary is functioning because of melanocyte stimulating hormone), nausea and vomiting, diarrhea, abdominal pain, mild fever, hypoglycemia, acidosis, eosinophilia, and shock.

Question 15

What is the most common type of hypoadrenalism?

Answer 15

Secondary (iatrogenic) hypoadrenalism

• due to steroids (may take up to 1 year for the adrenals to secrete the appropriate amount of corticosteroids in response to stress)
  
  • Watch for the classic post-op patient who crashes (hypotension, shock, and hyperkalemia) shortly after surgery and has a history of a disease requiring steroid therapy within the past year.
• Assess ACTH (high) and cortisol levels (low), but do not wait for the results to give steroids. The patient may die.
• Give prophylactic stress doses of corticosteroids in the setting of an illness, operation, or other stressor to prevent an adrenal crisis.

Question 16

What are the other causes of hypoadrenalism?

Answer 16

1. autoimmune (idiopathic) disease - patients may have coexisting autoimmune diseases, such as hypothyroidism, pernicious anemia, vitiligo, diabetes, or hypoparathyroidism
2. metastatic cancer (esp. lung cancer)
3. infection (TB, fungal, opportunistic infections in AIDs and other immunocompromised states)
4. ketoconazole
5. pituitary/hypothalamic failure

Question 17

How is hypoadrenalism diagnosed?

Answer 17

ACTH stimulation test - baseline cortisol is measured, ACTH given, and cortisol is measured again at 1 hour; expected cortisol to double baseline. If inappropriate, then this indicates hypoadrenalism. Do NOT withhold treatment to make a diagnosis if the patient is crashing

Question 18

Define hirsutism.

What are common causes of it?

Answer 18

male hair growth pattern in women or prepubescent children

common causes depend on the presence of virulization (clitoral enlargement, deepening of the voice, temporal balding) accompanying the hirsutism:

• - virulization -> think PCOS (Stein-Leventhal syndrome), Cushing Syndrome, Drugs (minoxidil, phenytoin, cyclosporine)
• + virulization -> think androgen-secreting ovarian tumor (ex: Sertoli-Leydig cell tumor, arrhenoblastoma) or adrenal source (CAH, Cushing syndrome, or adrenal tumor)

Question 19

What causes virilization in children?

How should these patients be managed?

Answer 19

In female neonates, think congenital adrenal hyperplasia (classic example is a female infant born with ambiguous genitalia or a male child with precocious puberty)

• usually due to 21-hydroxylase deficiency (21-hydroxylase is involved in the production of both aldosterone and cortisol, children develop signs of hypoadrenalism, with salt-wasting, hypotension, hyperkalemia, hyponatremia, hypoglycemia, acidosis, and nausea and vomiting).
  
  • Labs: abnormally high levels of serum 17-hydroxyprogesterone or urinary 17-ketosteroids, decreased free cortisol

Management: give corticosteroids to prevent death, but think about a testosterone-secreting gonadal neoplasm in older children

Question 20

What are the symptoms and signs of hyperparathyroidism?

Answer 20

same as hypercalcemia (“bones, stones, groans, and psychiatric overtones”)

1˚ (parathyroid gland etiology): serum Ca is high, PO4 is normal-low, PTH is increased

2˚ (renal failure): serum Ca is low, PTH is increased

3˚ (autonomous/unregulated parathyroid function resulting in excess PTH secretion; develops after a long period of 2˚/persistent parathyroid stmiulation): serum Ca is high, PTH is increased

Question 21

What causes hyperparathyroidism?

What are the 3 etiologies and how do you differentiate between them?

Answer 21

1˚ (parathyroid gland etiology: parathyroid adenoma, hyperplasia, or carcinoma): serum Ca is high, PO4 is normal-low, PTH is increased

• confirm wiht a nuclear medicine scan

2˚ (renal failure, CKD): serum Ca is low, PTH is increased

3˚ (autonomous/unregulated parathyroid function resulting in excess PTH secretion; develops after a long period of 2˚/persistent parathyroid stmiulation): serum Ca is high, PTH is increased

Question 22

What are the signs and symptoms of hypoparathyroidism?

Answer 22

Same as those for hypocalcemia (tetany, prolonged QT interval on ECG).

Labs: Calcium is low, phosphorus is high, and PTH is low

Question 23

What causes hypoparathyroidism? 2 big ones

Answer 23

Most common cause is iatrogenic: accidental removal or damage during thyroid surgery (watch for tetany after thyroid surgery)

Other is genetic: DiGeorge Syndrome (children with congenital absence of thyroid/parathyroid glands, tetany in the first 48 hours of life, immunodeficiency, cardiac anomalies, and midline facial defects.)

Question 24

What are the symptoms and signs of hypercalcemia?

Answer 24

Symptoms

• Bones - resorption with osteomalacia and osteitis fibrosa cystica
• Stones - renal stones
• Groans - N/V, ileus, PUD, constipation, pancreatitis
• Psychiatric overtones - emotional liability, delirium, depression, and/or psychosis

Signs: Shortened QT interval (wants to go faster), weakness, polyuria, bone changes and kidney stones on KUB/CT, and renal failure.

Question 25

What causes hypercalcemia? 2 What is the first test you should order?

Answer 25

1. **hyperparathyroidism** 2. **malignancy** * **​**multiple myeloma or lung squamous cell carcinoma (PTH-rp) 1. **genetics** * Familial hypocalciuric hypercalcemia (high serum Ca with low urine Ca) 1. **other** * Vitamin A/D intoxication * sarcoidosis * granulomatous disease * excess Ca intake (milk-alkali syndrome) **get PTH -** helps differentiate hyperparathyroidism (high PTH) from other causes of hypercalcemia such as malignancy, vitamin D intoxication, or thiazide diuretic use (all low PTH).

Question 26

What are the symptoms and signs of hypocalcemia?

Answer 26

**Symptoms**: paresthesias (the classic pattern is perioral or distal extremities), muscle aches, dementia, depression, and psychosis. **Signs**: ***Prolonged QT on ECG***, tetany, ***Chvostek sign*** (tetany elicited by tapping on the facial nerve to cause facial muscle contraction), ***Trousseau sign*** (carpopedal spasm caused by inflation of a blood pressure cuff or application of a tourniquet), dementia, depression, psychosis, seizures, and papilledema.

Question 27

What causes hypocalcemia? What is the first step in management for any patient who presents with hypocalcemia?

Answer 27

* Hypoparathyroidism (usually after thyroid gland surgery) * Pseudohypoparathyroidism (genetic end-organ unresponsiveness to PTH; normal PTH levels, shortened metacarpal bones, short stature, and mental retardation) * DiGeorge syndrome * Vitamin D deficiency (osteomalacia, rickets) * Renal failure of any cause and certain renal tubular problems * Acute pancreatitis (one of the Ranson criteria) * Secondary to hypomagnesemia * Hypoproteinemia of any cause may lead to low levels of total serum calcium, but levels of ionized calcium (the active form) are normal. ln any patient with low serum calcium, the first step is to determine whether the serum albumin level is decreased. If it is, no treatment is required and no symptoms will develop.

Question 28

What specific problems are caused by obesity?

Answer 28

Increase: overall mortality (at any age) Increases the risk for: * insulin resistance and diabetes * HTN * hypertriglyceridemia * CAD * gallstones * sleep apnea and hypoventilation * osteoarthritis * thromboembolism * varicose veins * cancer (especially endometrial cancer)

Question 29

# Define precocious puberty and pseudoprecocious puberty. How is one different than the other? What is the next step in management if this is suspected?

Answer 29

**True precocious puberty -** activation of the hypothalamic-pituitary axis with sexual maturation *before 8 yo* in *females and before 9 yo in males*. * usually idiopathic, but can be caused by CNS lesions * causes testicular or ovarian enlargement **In pseudo- precocious puberty** - secondary sex characteristics develop prematurely because of high circulating levels of androgen or estrogen. * does _not_ cause testicular or ovarian enlargement, All patients with suspected precocious puberty should undergo a **GnRH stimulation test, where if a dose of GnRH produces the typical pubertal response of increased FSH and LH, true precocious puberty is diagnosed**. If this is the case, **get brain MRI** to rule out CNS disease (e.g., hamartomas, tumors, cysts, trauma) as the cause.

Question 30

What causes pseudoprecocious puberty? 4

Answer 30

* exogenous hormones * adrenal tumors * congenital adrenal hyperplasia (21-hydroxylase deficiency) * McCune-Albright syndrome in females (ovarian cysts, pseudoprecocious puberty, polyostotic fibrous dysplasia of bone, and café au lait spots)

Question 31

How is precocious puberty treated? What are the consequences of untreated cases?

Answer 31

_Treatment:_ * **treat underlying disorders** * For true idiopathic precocious puberty, treatment with **long-acting GnRH agonists** is indicated to suppress the pituitary-hypothalamic axis and to delay the onset of puberty until an appropriate age. Because premature puberty causes premature fusion of growth plates in the bone and can cause **serious social problems** for affected children, treatment is indicated.

Question 32

What is the difference between a primary and secondary endocrine disorder?

Answer 32

1˚ - problem is in the gland, the hypothalamic-pituitary axis is functioning appropriately 2˚ - the dysfunction is outside of the gland; the hypothalamic-pituitary axis is NOT functioning appropriately

Question 33

What are the symptoms and signs of primary hyperaldosteronism (Conn syndrome)? What are the causes?

Answer 33

Symptoms: Weakness and edema. Signs: HTN, hypokalemia, hypernatremia, and edema. caused by an aldosterone-secreting adrenal neoplasm

Question 34

What causes secondary hyperaldosteronism?

Answer 34

anything that causes low perfusion of the kidney (-\> high renin) * congestive heart failure * renal artery stenosis (bruit) * dehydration * nephrotic syndrome * cirrhosis

Question 35

Give the classic clinical description of a pheochromocytoma. How is it diagnosed? 2 How is it managed?

Answer 35

clinical picture: wild swings in blood pressure (with some measurements dangerously high), tachycardia, postural hypotension, headaches, sweating, flushing, dizziness, mental status changes, and/or a feeling of impending doom (like a panic attack) Diagnosis: * **Plasma collection for metanephrines, homovanillic acid, and/or vanillylmandelic acid** (catecholamine breakdown products) * **Abdominal CT** if the levels are high Managed: * Surgical tumor removal after stabilization with alpha and then ß-blockers. * Start alpha blockade with phenoxybenzamine 10-14 days preoperatively to render the body less sensitive to catecholamine surges. Initiate a beta blocker only after adequate alpha blockade. If beta blockade is started prematurely, unopposed alpha stimulation could precipitate a hypertensive crisis.

Question 36

Define diabetes insipidus (DI). What are the two types?

Answer 36

DI is a lack of ADH (vasopressin) effect in the body, resulting in the production of inappropriately dilute urine, up to 25 L of urine/day, resulting in dehydration and hypernatremia. Two types: * central - lack of ADH production by the posterior pituitary; usually idiopathic, but can be caused by trauma, neoplasm, sarcoid/granulomatous disease * nephrogenic - kidney unresponsiveness to ADH, usually due to medications (lithium, demeclocycline)

Question 37

What causes central DI?

Answer 37

**central -** lack of ADH production by the posterior pituitary; usually idiopathic, but can be caused by trauma, neoplasm, sarcoid/granulomatous disease *(compare to...)* **nephrogenic -** kidney unresponsiveness to ADH, usually due to medications (lithium, demeclocycline)

Question 38

What causes nephrogenic DI?

Answer 38

nephrogenic - kidney unresponsiveness to ADH, usually due to medications (lithium, demeclocycline) *(compare to...)* central - lack of ADH production by the posterior pituitary; usually idiopathic, but can be caused by trauma, neoplasm, sarcoid/granulomatous diseas

Question 39

What diagnostic test can reveal whether DI is central or nephrogenic? How are these conditions treated?

Answer 39

Give the patient a dose of ADH, and measure urine osmolarity - \> if central DI, urine osmolarity increases with ADH challenge * trmt: ADH replacement - \> if nephrogenic DI, urine remains inappropriately dilute * trmt: stop offending drug and giving a thiazide diuretic (has paradoxical effect of decreasing urine output)

Question 40

# Define the syndrome of inappropriate antidiuretic hormone secretion (SIADH). In what patient is this suspected? How is it diagnosed?

Answer 40

SIADH: ADH is released inappropriately. Suspect in patients with hyponatremia, low serum osmolarity, high urine osmolarity, low electrolyte values, but is euvolemic

Question 41

What causes SIADH? 4 main categories

Answer 41

1. **CNS**: Stroke, hemorrhage, infection, trauma. 2. **Medications**: Narcotics, oxytocin (in pregnant patients), chlorpropamide, antiepileptic agents. 3. **Trauma:** *Pain is a powerful stimulus for ADH*. Watch for the postoperative patient who is receiving fluids (and often narcotics) and has pain. 4. **Lung problems**: Simple pneumonia or ADH-secreting small cell lung cancer

Question 42

How is SIADH treated?

Answer 42

**Stop IV fluids and restrict PO fluid intake**. ## Footnote Do ***_not_*** give hypertonic saline unless the patient has active seizures. May cause brainstem damage or central pontine myelinolysis from rapid correction of Na level. **Demeclocycline** is sometimes used to treat SIADH if water restriction fails because it induces nephrogenic DI, which allows the patient to eliminate free water.