A 43-year-old woman comes to the office to discuss amenorrhea. She began having irregular menses 2 years ago, and her last menstrual period was 9 months ago. Family history is unremarkable. Laboratory studies show an increased serum prolactin level, a normal TSH level, and an undetectable β-hCG concentration. Serum calcium is normal. MRI reveals a 6-mm pituitary adenoma. The patient refuses medical and surgical therapy as she is happy about not having menstrual periods. If left untreated, this patient is at greatest risk of developing which of the following?
Prolactinoma | |
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This patient's small pituitary adenoma with an elevated prolactin level and secondary amenorrhea is consistent with a prolactin-secreting adenoma (prolactinoma). High levels of prolactin suppress GnRH secretion from the hypothalamus, leading to reduced secretion of LH (and to a lesser extent FSH) and subsequent hypogonadism. Nonsecretory ("nonfunctioning") adenomas can also cause mild hyperprolactinemia due to pressure on the stalk, but these tumors primarily cause mass-effect symptoms (eg, hypopituitarism, headache, bitemporal hemianopsia) due to pressure on surrounding structures.
Estrogen maintains bone mass in premenopausal women. Low estrogen levels lead to increased production of inflammatory cytokines (especially IL-1 and tumor necrosis factor–alpha), increasing expression of the receptor activator of nuclear factor kappa B ligand (RANKL) and resulting in increased osteoclast activity. Loss of estrogen, whether from menopause, ovulatory dysfunction, or surgical removal of the ovaries, increases the risk of bone loss and osteoporosis.
(Choice A) Adenomas are associated with pituitary apoplexy (hemorrhage into the pituitary). However, this occurs more commonly with large adenomas and is not typically associated with strokes located in the cortex.
(Choice B) Multiple endocrine neoplasia (MEN) type 1 is characterized by pituitary adenomas, hyperparathyroidism, and endocrine tumors of the pancreas. Gastrin-secreting pancreatic tumors are common and may lead to recurrent peptic ulcers (Zollinger-Ellison syndrome). However, almost all patients with MEN type 1 have hyperparathyroidism with hypercalcemia.
(Choice D) Early menopause (age <40) is associated with an increased risk of cardiovascular events, but the effect of the prolactinoma-induced low estrogenic state on cardiovascular risk in older women is unclear.
(Choice E) Excess growth hormone secretion from a somatotroph pituitary adenoma can lead to diabetes mellitus due to increased insulin resistance in peripheral tissues. However, adults typically present with acromegaly.
Educational objective:
Hyperprolactinemia suppresses secretion of GnRH, which leads to reduced estrogen in women. Low estrogen levels are a risk factor for accelerated bone loss.