A 33-year-old woman presents to the clinic complaining of an absence of menses for the pas… — USMLE Step 2 CK

A $33$ -year-old woman presents to the clinic complaining of an absence of menses for the past $9$ months. Her previously regular $28$ -day menstrual cycles stopped completely, although she did experience a single episode of light vaginal spotting one week ago. Over the past year, the patient has also developed profound fatigue, cold intolerance, constipation, and occasional mild morning headaches. She recently noticed a spontaneous milky discharge from both breasts. She takes no medications and has no significant past medical history. Vital signs show a blood pressure of $110/70$ mm Hg and a heart rate of $56$ /min. Body mass index is $24$ kg/m $^2$ . Physical examination reveals dry skin and delayed relaxation of the deep tendon reflexes. Visual fields are full to confrontation. Pelvic examination is unremarkable.

Laboratory results are as follows:

Test	Result	Reference Range
Urine beta-hCG	Negative	Negative
Serum prolactin	$52$ ng/mL	$4$ - $23$ ng/mL
Free T4	$0.6$ ng/dL	$0.9$ - $1.7$ ng/dL
Thyroid-stimulating hormone (TSH)	$1.2$ $\mu$ U/mL	$0.4$ - $4.2$ $\mu$ U/mL
Follicle-stimulating hormone (FSH)	$3.5$ mIU/mL	$4.7$ - $21.5$ mIU/mL (follicular)

Which of the following is the most likely diagnosis?

Nonfunctioning pituitary adenomaAnswer
B
Autoimmune thyroiditis
C
Polycystic ovary syndrome
D
Endometrial adenocarcinoma
E
Normal physiologic changes of pregnancy

Answer

Nonfunctioning pituitary adenoma

The correct diagnosis is a nonfunctioning pituitary adenoma. This patient presents with secondary amenorrhea, symptoms of hypothyroidism (fatigue, cold intolerance, bradycardia, delayed reflexes), and galactorrhea. Her laboratory evaluation confirms central hypothyroidism (low free T4 with an inappropriately normal TSH) and central hypogonadism (low/normal FSH in the setting of prolonged amenorrhea). Furthermore, her serum prolactin is mildly elevated. This specific pattern is the hallmark of a pituitary macroadenoma. The adenoma exerts a mass effect that compresses the normal thyrotrophs and gonadotrophs, leading to decreased TSH and FSH/LH secretion. Concurrently, the mass compresses the pituitary stalk (infundibulum). Because prolactin secretion is normally under tonic inhibition by hypothalamic dopamine, stalk compression prevents dopamine from reaching the anterior pituitary. This loss of inhibition causes a mild to moderate elevation in prolactin (typically under

100

ng/mL), a phenomenon known as the 'stalk effect.'

Step-by-Step Solution

Evaluate the patient's presenting symptoms and vital signs.

The patient has secondary amenorrhea, galactorrhea, fatigue, cold intolerance, constipation, and bradycardia with delayed deep tendon reflexes.

This constellation of symptoms points to involvement of multiple endocrine axes, specifically the gonadal, lactotroph, and thyroid pathways.

Analyze the laboratory results to determine the primary level of endocrine dysfunction.

Free T4 is low, but TSH is inappropriately normal (central hypothyroidism). FSH is low-normal despite prolonged amenorrhea (central hypogonadism). Prolactin is mildly elevated (

52

ng/mL).

Primary gland failures (e.g., ovaries or thyroid) would result in highly elevated stimulating hormones (FSH or TSH) due to a lack of negative feedback. The lack of elevation indicates a central (pituitary or hypothalamic) failure.

Synthesize the laboratory pattern with the anatomical pathways.

The combined central hypothyroidism, central hypogonadism, and mild hyperprolactinemia indicate a mass lesion in the pituitary.

A nonfunctioning macroadenoma compresses normal pituitary tissue (lowering TSH, FSH, and LH) and compresses the pituitary stalk. Stalk compression prevents hypothalamic dopamine from reaching the lactotrophs, leading to a loss of inhibition and a resulting mild 'stalk effect' hyperprolactinemia (typically

30

100

ng/mL).

Key Concept

Evaluation of secondary amenorrhea with concurrent central hypothyroidism and stalk effect hyperprolactinemia.

Estimated Time:1m 15s

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