A 31-year-old woman comes to the clinic due to an 18-month history of inability to conceiv… — USMLE Step 2 CK

A $31$ -year-old woman comes to the clinic due to an $18$ -month history of inability to conceive. She and her partner have been having regular, unprotected intercourse. Her menstrual periods, previously regular, now occur every $50$ to $60$ days. The patient also reports a $5\text{-kg}$ ( $11\text{-lb}$ ) weight gain, sluggishness, and increased sensitivity to cold over the past year. Her BMI is $28\ \text{kg/m}^2$ . Vital signs show a temperature of $36.1^\circ\text{C}$ ( $97.0^\circ\text{F}$ ) and a pulse of $56\text{/min}$ . Physical examination reveals an enlarged, firm, and non-tender thyroid gland, as well as bilateral milky discharge from the nipples. A urine pregnancy test is negative.

Laboratory results:
Thyroid-stimulating hormone (TSH): $22.5\ \mu\text{U/mL}$ (Normal: $0.4$ – $4.0\ \mu\text{U/mL}$ )
Free thyroxine (T4): $0.5\ \text{ng/dL}$ (Normal: $0.9$ – $1.7\ \text{ng/dL}$ )
Prolactin: $68\ \text{ng/mL}$ (Normal: $4$ – $23\ \text{ng/mL}$ )

Which of the following is the most likely pathophysiologic mechanism responsible for this patient's infertility?

Increased hypothalamic thyrotropin-releasing hormone secretionAnswer
B
Autonomous proliferation of pituitary lactotroph cells
C
Insulin resistance leading to excessive ovarian androgen production
D
Decreased dopamine delivery to the pituitary via the tuberoinfundibular pathway
E
Autoimmune-mediated destruction of ovarian follicles

Answer

Increased hypothalamic thyrotropin-releasing hormone secretion

The patient's clinical presentation (weight gain, fatigue, cold intolerance, bradycardia, goiter) and laboratory findings (high TSH, low free T4) are diagnostic of primary hypothyroidism. Primary thyroid failure results in a lack of negative feedback on the hypothalamus, leading to increased secretion of thyrotropin-releasing hormone (TRH). TRH not only stimulates thyrotrophs to release TSH but also stimulates lactotrophs in the anterior pituitary to secrete prolactin. The resulting hyperprolactinemia inhibits the pulsatile release of gonadotropin-releasing hormone (GnRH), which in turn decreases luteinizing hormone (LH) and follicle-stimulating hormone (FSH) secretion, leading to anovulation, oligomenorrhea, and infertility.

Step-by-Step Solution

Analyze the clinical presentation and vital signs.

The patient has weight gain, fatigue, cold intolerance, bradycardia, and an enlarged thyroid gland.

These findings are classic signs of hypothyroidism, which requires laboratory confirmation.

Evaluate the laboratory results.

TSH is markedly elevated (

22.5\ \mu\text{U/mL}

) and free T4 is decreased (

0.5\ \text{ng/dL}

). Prolactin is moderately elevated (

68\ \text{ng/mL}

High TSH with low T4 confirms primary hypothyroidism. The elevated prolactin links the thyroid dysfunction to her galactorrhea and infertility.

Connect the endocrine pathways to explain the hyperprolactinemia and infertility.

Primary hypothyroidism causes decreased T4, removing negative feedback on the hypothalamus and increasing TRH production. Elevated TRH stimulates both thyrotrophs (releasing TSH) and lactotrophs (releasing prolactin).

High prolactin inhibits the pulsatile release of GnRH, leading to decreased LH and FSH, anovulation, oligomenorrhea, and infertility.

Key Concept

Primary hypothyroidism causes hyperprolactinemia because the resulting lack of negative feedback increases TRH secretion from the hypothalamus, which directly stimulates lactotrophs to release prolactin. Hyperprolactinemia subsequently suppresses GnRH pulsatility, leading to anovulatory infertility.

Estimated Time:1m 30s

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