Pituitary & Calcium Disorders

Prolactinoma and acromegaly

Prolactinoma is the most common pituitary adenoma. Prolactin suppresses GnRH, so women present with galactorrhea, amenorrhea, and infertility, while men present with low libido and erectile dysfunction, often later and with larger tumors. A large tumor adds headache and bitemporal hemianopsia from chiasmal compression. A prolactin above 250 ng/mL strongly suggests a prolactinoma. First exclude pregnancy, hypothyroidism (TRH stimulates prolactin), and dopamine-antagonist drugs (antipsychotics, metoclopramide). A nonfunctioning macroadenoma that compresses the stalk raises prolactin only modestly (the "stalk effect").

Dopamine agonists shrink prolactinomas. They are first-line even for large macroadenomas: cabergoline (preferred, better tolerated) or bromocriptine normalizes prolactin and shrinks the tumor. Reserve transsphenoidal surgery for drug-resistant tumors or acute visual compromise not responding to medication.

Acromegaly is GH excess, usually from a somatotroph adenoma, after the growth plates fuse: enlarging hands, feet, and jaw, coarse features, sweating, hypertension, diabetes, carpal tunnel syndrome, sleep apnea, and cardiomyopathy. Before fusion, GH excess causes gigantism. Screen with serum IGF-1, a stable integrated marker (random GH fluctuates). Confirm with an oral glucose tolerance test in which GH fails to suppress, then obtain a pituitary MRI. Cardiovascular disease is the leading cause of death.

Hypopituitarism

Causes. Mass lesions, Sheehan syndrome (postpartum pituitary infarction after hemorrhage, often first noticed as failure to lactate), pituitary apoplexy (hemorrhage into an adenoma with sudden severe headache, visual loss, and shock), and radiation. Target hormones are low with low or inappropriately normal trophic hormones.

Cortisol before thyroxine. Replace each deficient hormone, but always give glucocorticoid (hydrocortisone) BEFORE levothyroxine. Starting levothyroxine first raises metabolic demand and cortisol clearance, which can trigger an adrenal crisis in a cortisol-deficient patient. Mineralocorticoid is not needed because aldosterone is renin-driven, and levothyroxine is titrated to free T4 because TSH is unreliable.

Pituitary apoplexy is an emergency: give stress-dose glucocorticoids at once and involve neurosurgery for visual compromise.

Water balance: diabetes insipidus and SIADH

Central diabetes insipidus is ADH deficiency (head trauma, pituitary surgery, tumors): polyuria, dilute urine, hypernatremia, and high serum osmolality. On a water deprivation test the urine fails to concentrate, then CONCENTRATES after desmopressin. Treat with desmopressin (DDAVP).

Nephrogenic diabetes insipidus is renal resistance to ADH: urine does NOT concentrate even after desmopressin. Causes are lithium, hypercalcemia, and hypokalemia. Treat by removing the cause, plus thiazide diuretics, a low-salt/low-protein diet, and amiloride for lithium-induced disease (it blocks lithium entry through collecting-duct sodium channels). Thiazides raise serum lithium levels, so amiloride is preferred if lithium continues, and lithium levels must be watched if a thiazide is used.

SIADH is excess ADH causing euvolemic hyponatremia with concentrated urine (urine osmolality >100), low serum osmolality, and elevated urine sodium. Causes are small cell lung cancer, CNS disease, drugs (SSRIs, carbamazepine), surgery, and pain. It is a diagnosis of exclusion, so rule out hypothyroidism and adrenal insufficiency. Treat with fluid restriction and salt tablets, hypertonic saline if severe, and vaptans or demeclocycline for chronic cases.

Correct chronic hyponatremia slowly, less than 8 mEq/L in 24 hours, to avoid osmotic demyelination (central pontine myelinolysis). Normal saline can worsen SIADH, because the kidney excretes the salt and keeps the water.

Hypercalcemia

Measure the PTH. Confirm true hypercalcemia first (correct for albumin or measure ionized calcium). The two most common causes are primary hyperparathyroidism (outpatients) and malignancy (inpatients). HIGH or inappropriately normal PTH means primary hyperparathyroidism; LOW PTH points to malignancy (PTHrP, osteolytic metastases, myeloma), vitamin D excess, or granulomatous disease such as sarcoidosis, whose macrophages make calcitriol.

Primary hyperparathyroidism is usually a single adenoma (~85%): high calcium, LOW phosphate, and high or inappropriately normal PTH with elevated urine calcium. It causes stones, bones, abdominal groans, and psychiatric overtones. Parathyroidectomy is indicated if symptomatic or meeting criteria: calcium >1 mg/dL above normal, age <50, osteoporosis (T-score ≤ −2.5) or vertebral fracture, eGFR <60 mL/min, nephrolithiasis or nephrocalcinosis, or hypercalciuria (>250 mg/day in women, >300 mg/day in men) (2022 Fifth International Workshop). Sestamibi scan or ultrasound localizes the adenoma before surgery but does not make the diagnosis.

High urinary calcium distinguishes primary hyperparathyroidism from familial hypocalciuric hypercalcemia, which has LOW urine calcium and needs no surgery.

Beyond the sequence. Avoid loop diuretics unless the patient is volume-overloaded, and treat the underlying cause; glucocorticoids help in granulomatous disease and vitamin D excess.

Hypocalcemia

Tetany and long QT. Hypocalcemia causes perioral numbness, tetany, Chvostek sign (facial twitch on tapping the facial nerve), Trousseau sign (carpal spasm with a BP cuff), prolonged QT, and seizures. Causes are post-thyroidectomy hypoparathyroidism, vitamin D deficiency, hypomagnesemia, and chronic kidney disease. Check albumin first, because low albumin lowers total but not ionized calcium.

Treatment. Give IV calcium gluconate for symptomatic cases; otherwise oral calcium plus vitamin D (calcitriol when PTH or kidney function is missing), and correct magnesium.

Low magnesium both impairs PTH release and causes end-organ PTH resistance, so hypocalcemia will not correct until magnesium is repleted.