A 41-year-old woman comes to the physician with an 8-month history of amenorrhea. Multiple home pregnancy tests during this time have been consistently negative. She has mild dyspareunia and blurred vision but no headaches, galactorrhea, hot flashes, or weight change. The patient's past medical and family histories are unremarkable. She takes no medications, including over-the-counter drugs. She does not use alcohol, tobacco, or intravenous drugs. Physical examination is unremarkable. Basic metabolic panel and complete blood count are within normal limits. Her hormone profile shows a prolactin level of 50 ng/mL (normal 5-20 ng/mL). Serum luteinizing hormone level is undetectable, follicle-stimulating hormone is low normal, and the α-subunit is markedly increased. Serum thyroid-stimulating hormone, testosterone, and insulin-like growth factor 1 are normal. Magnetic resonance imaging of the pituitary shows a 2-cm pituitary tumor with suprasellar extension. What is the most appropriate next step in management of this patient?

Question

A 41-year-old woman comes to the physician with an 8-month history of amenorrhea.  Multiple home pregnancy tests during this time have been consistently negative.  She has mild dyspareunia and blurred vision but no headaches, galactorrhea, hot flashes, or weight change.  The patient's past medical and family histories are unremarkable.  She takes no medications, including over-the-counter drugs.  She does not use alcohol, tobacco, or intravenous drugs.  Physical examination is unremarkable.  Basic metabolic panel and complete blood count are within normal limits.  Her hormone profile shows a prolactin level of 50 ng/mL (normal 5-20 ng/mL).   Serum luteinizing hormone level is undetectable, follicle-stimulating hormone is low normal, and the α-subunit is markedly increased.  Serum thyroid-stimulating hormone, testosterone, and insulin-like growth factor 1 are normal.  Magnetic resonance imaging of the pituitary shows a 2-cm pituitary tumor with suprasellar extension.  What is the most appropriate next step in management of this patient?

Quizplus · Accepted Answer

Explanation: This patient has amenorrhea and hypogonadism with suppressed luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels but increased α-subunits. This is strongly suggestive of a nonfunctioning pituitary adenoma, which usually arises from the gonadotropin-secreting cells (gonadotrophs) in the pituitary gland. Normal gonadotrophs secrete LH and FSH (which are dimeric hormones consisting of a common α-subunit and a different β-subunit), but the dysfunctional cells in most gonadotroph adenomas secrete primarily just the common α-subunit. The clinical symptoms of α-subunit overproduction are usually minimal ("nonfunctioning" adenoma), and the diagnosis is not apparent until the adenoma is large enough to cause headaches or visual disturbances due to mass effect. The preferred therapy for most nonfunctioning pituitary adenomas is trans-sphenoidal surgery, which can provide rapid relief of the associated neurologic symptoms. Patients may also regain their normal gonadal function after resection. Radiation (field therapy or stereotactic radiation) may be used as adjuvant therapy in patients with incompletely resected adenomas. However, radiation is not first-line therapy as its onset of action is too slow, it can damage surrounding neurologic tissues, and it can lead to delayed hypopituitarism in many cases (Choice D). (Choice A) Dopaminergic medications such as cabergoline are the preferred treatment for prolactin-secreting adenomas (prolactinomas), but they have no significant effect on gonadotropin-secreting adenomas. Large nonfunctioning pituitary adenomas that compress the pituitary stalk may block the normal hypothalamic inhibition of prolactin secretion, leading to a mild increase in prolactin levels. This does not indicate the presence of a prolactinoma, which usually is associated with a much larger increase in prolactin levels (>200 ng/mL). (Choice B) Patients with amenorrhea due to a pituitary adenoma may be treated with estrogen and progesterone to restore menses and relieve hypogonadal symptoms. These would not address the underlying tumor, however, and would not relieve symptoms related to mass effect. (Choice C) Octreotide, a somatostatin analogue, acts on somatostatin receptors in the pituitary to inhibit release of growth hormone. It is sometimes used in growth hormone-producing adenomas (acromegaly) but has minimal benefits in nonfunctioning adenomas. Educational objective: Nonfunctioning pituitary adenomas generally arise from gonadotropin-secreting cells of the pituitary gland. Patients usually present with hypogonadism and low gonadotropin levels; serum α-subunit levels are characteristically increased. Large tumors may cause symptoms directly through mass effect on local tissues. The primary treatment modality is trans-sphenoidal surgery. References: Non-functioning pituitary adenomas. (http://www.ncbi.nlm.nih.gov/pubmed/19945027)

A 41-Year-Old Woman Comes to the Physician with an 8-Month