Endocrine · USMLE Step 1

USMLE Endocrine

Hormone axes, classic endocrine pathologies, and their hallmark lab findings.

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What is the primary negative feedback regulator of the HPA axis?
Cortisol (glucocorticoid) inhibits CRH release from the hypothalamus and ACTH from the pituitary.
What hormone stimulates cortisol production by the adrenal zona fasciculata?
ACTH (adrenocorticotropic hormone) from the anterior pituitary
Which hormones comprise the HPG axis?
GnRH (hypothalamus), FSH and LH (anterior pituitary), testosterone or estrogen/progesterone (gonads)
What is the rate-limiting enzyme in thyroid hormone synthesis?
Thyroid peroxidase (TPO), which catalyzes iodine incorporation and coupling of tyrosine residues
TSH primarily stimulates the release of which thyroid hormones?
T4 (thyroxine) and T3 (triiodothyronine) from thyroid follicular cells
Which thyroid hormone is more biologically active: T3 or T4?
T3 (triiodothyronine) is 3-5 times more potent than T4
What is the classic triad of Cushing's syndrome?
Central obesity with fat redistribution (moon facies, buffalo hump), proximal muscle weakness, purple stretch marks
In Cushing's syndrome, what is the expected 24-hour urine free cortisol compared to normal?
Significantly elevated (normal is less than 50-100 mcg/24 hr; Cushing's typically greater than 250 mcg/24 hr)
What is the dexamethasone suppression test used for?
The low-dose dexamethasone suppression test screens for and confirms hypercortisolism by testing whether cortisol is suppressible. Once Cushing's syndrome is confirmed, plasma ACTH (not the DST) distinguishes ACTH-dependent from ACTH-independent causes; the high-dose dexamethasone suppression test then differentiates pituitary Cushing's disease (cortisol suppresses) from ectopic ACTH secretion (cortisol does not suppress) among ACTH-dependent causes.
In Cushing's syndrome, plasma ACTH is elevated in which type(s)?
ACTH-dependent types: pituitary adenoma (Cushing's disease) and ectopic ACTH secretion (small cell lung cancer)
What are the classic electrolyte abnormalities in primary adrenal insufficiency (Addison's disease)?
Hyponatremia, hyperkalemia, and hypoglycemia
How does the morning plasma cortisol differ between Addison's disease and normal?
In Addison's disease, morning cortisol is severely low (typically less than 3 mcg/dL), whereas normal is 10-20 mcg/dL
In Addison's disease, what is the expected ACTH level?
ACTH is markedly elevated (often greater than 1000 pg/mL) due to loss of negative feedback from cortisol
What is the classic presentation of primary hypothyroidism?
Cold intolerance, weight gain, fatigue, bradycardia, dry skin, and delayed deep tendon reflexes
In primary hypothyroidism, TSH is elevated and free T4 is low. Why does TSH rise?
Loss of negative feedback from T4 (and T3) leads to unopposed TRH and TSH secretion

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