What is the most common cause of congenital adrenal hyperplasia and how will this manifest in females?
- Major cause: 21-hydroxylase (P450C21) deficiency
- manifests as pseudohermaphroditism in females (ambiguous genitalia but internal organs are normal)
- androgens and progesterone are increased, while glucocorticoids and mineralocorticoids are decreased (salt wasting, hypovolemia, hypotension)
What are symptoms of hypocalcemia and what endocrine should you always check when you suspect hypocalcemia?
- symptoms: numbness, tingling, muscle spasms
- check PTH levels!
- damage to the PTH (primary) usually occurs via autoimmune damage, surgical excision of thyroid, or DiGeorge syndrome - serum PTH and calcium levels will be LOW
- if there is end organ resistance to PTH (pseudohypoPTH), usually due to a mutation in receptors that makes them unable to produce cAMP, the serum PTH will be high while calcium will be low
Patient presents with several kidney stones. What workup would you want to do, and what are you suspecting?
- check calcium levels! High calcium and low phosphate can lead to deposition of stones
- also check PTH levels - with stones, we suspect hyperparathyroidism, which can be due to PTH adenoma, hyperplasia, or carcinoma
- look for other symptoms, such as depression, memory issues, nausea (increased gastric acid secretion), and osteitis fibrosa cystica
High calcium, high PTH, and a mass with sheets of neoplastic chief cells in a rich capillary network?
- parathyroid adenoma (most common cause of hyperparathyroidism)
- can be associated with MEN1
Describe the steps in which chronic renal failure (the most common cause) can lead to secondary hyperparathyroidism
1) renal insufficiency leads to decreased phosphate excretion
2) increased serum phosphate binds free calcium
3) decreased free calcium stimulates PTH release (all 4 glands - will see hyperplasia equally)
- labs will show increased PTH, decreased serum calcium, increased serum phosphate, and increased alkaline phosphatase
- secondary hyperparathyroidism can also be caused by vit D deficiency, malabsorption, Fanconi syndrome, and renal tubular acidosis
- take home points: check calcium and phosphate levels to distinguish between primary and secondary causes of PTH
Differentiate between MEN1, MEN2a, MEN2b
MEN1: pituitary adenoma, primary hyperparathyroidism, and islet cell tumor of pancreas
MEN2a: medullary thyroid carcinoma, pheochromocytoma, primary hyperparathyroidism
MEN2b: same as 2a, but develops earlier and usually without PTH involvement
MEN2 syndromes associated with RET mutation
Neuroblastomas are the most common extra cranial solid neoplasms of childhood. 1/3 of these are adrenal. Describe the pathogenesis and symptoms
- may occur with NF1, Beckwith-Wiedemann syndrome, and Hirschsprung disease
- amplification of N-myc occurs
- abdominal mass with small blue cells and Homer Wright rosettes
- since affects adrenal medulla, urinary excretion of catecholamines and metabolites are elevated
What are the symptoms of Cushing syndrome? What should be the first question you ask your patient if you suspect this?
- emotional disturbance, moon facies, osteoporosis, upper truncal obesity, thin and wrinkled skin, amenorrhea, muscle weakness, pupura, skin ulcers
- all due to excess production of cortisol from zona fasciculata of adrenal cortex
- ask them about exogenous corticosteroids, which are the most common cause of Cushing syndrome
What is Cushing disease? How can you test to diagnose this?
- Excess cortisol due to pituitary tumors that secrete ACTH
- use the dexamethasone suppression test: if you administer and cortisol levels go down, you know the source is the pituitary
Describe primary chronic adrenal insufficiency (Addison disease)
- most commonly due to autoimmune destruction of adrenal glands
- weakness, weight loss, GI disturbances, hypotension, hyponatremia, hyperkalemia, hyperpigmentation
Tumor of chromaffin cells of adrenal medulla
- secretes catecholamines –> HTN resistant to therapy (headaches, blurry vision, tachycardia, sweating)
- increased serum metanephrines and urinary VMA
- associated with MEN2, von Hippel-Lindau, NF1