What is the most likely diagnosis in a 30-year-old woman with three years of infertility, previously 45‑day menstrual cycles now six months of amenorrhea, elevated thyroid‑stimulating hormone, hyperprolactinemia, and low‑normal follicle‑stimulating hormone and luteinizing hormone?

Diagnosis: Primary Hypothyroidism with Secondary Hyperprolactinemia

The most likely diagnosis is primary hypothyroidism (Option A), which is causing secondary hyperprolactinemia and subsequent anovulatory infertility. 1, 2, 3

Diagnostic Reasoning

Primary Hypothyroidism is the Unifying Diagnosis

• TSH is markedly elevated at 9.2 μIU/L (normal 0.4-5.0), confirming primary hypothyroidism and making this the correct answer 1, 2
• Prolactin is significantly elevated at 140 ng/mL (normal <25 ng/mL), but this is secondary to the hypothyroidism rather than a primary prolactinoma 1, 2
• Hyperprolactinemia occurs in 43% of women with frank primary hypothyroidism due to compensatory hypersecretion of thyrotropin-releasing hormone (TRH), which directly stimulates prolactin release 1, 2
• Treating the hypothyroidism alone typically normalizes prolactin levels and restores regular menses and fertility without requiring dopamine agonist therapy 1, 3

Why the Other Options Are Incorrect

Hypopituitarism (Option B) is excluded because:

• FSH (5.3 IU/L) and LH (7.2 IU/L) are within normal follicular phase ranges (5-20 IU/L and 5-22 IU/L respectively), not suppressed 4
• TSH is elevated, not low—hypopituitarism would show low or inappropriately normal TSH with low thyroid hormones 2

Primary hyperprolactinemia/prolactinoma (Option C) is less likely because:

• While prolactin is elevated at 140 ng/mL, this level is consistent with stalk effect or secondary causes rather than a prolactinoma, which typically produces levels >4,000 mU/L (approximately >190 ng/mL) 1, 2
• The elevated TSH indicates primary hypothyroidism is the driving pathology 1, 2
• Primary hypothyroidism can cause pituitary hyperplasia that mimics a prolactinoma on imaging, making thyroid evaluation mandatory before assuming a pituitary tumor 2, 3

PCOS (Option D) is unlikely because:

• While oligomenorrhea and infertility occur in PCOS, hyperprolactinemia itself suppresses gonadotropin secretion via kisspeptin inhibition, making it impossible to distinguish PCOS from hyperprolactinemia-induced anovulation until prolactin normalizes 1
• The markedly elevated TSH and prolactin point to hypothyroidism as the primary etiology 1, 2
• PCOS typically shows LH/FSH ratio >2; this patient has a ratio of 1.36 (7.2/5.3) 4, 1

Clinical Management Algorithm

Immediate Steps

1. Initiate levothyroxine replacement therapy for the primary hypothyroidism 1, 3
2. Recheck TSH, free T4, and prolactin in 6-8 weeks after starting thyroid replacement 1
3. Do NOT start dopamine agonist therapy until thyroid function is normalized and prolactin remains elevated 1, 2

Expected Outcomes

• Prolactin levels should normalize within weeks to months of achieving euthyroid state 1, 3
• Menstrual cycles typically resume once prolactin normalizes 1, 3
• Fertility is often restored without additional intervention—the case report demonstrates pregnancy occurring within one month of starting levothyroxine 3
• Any pituitary enlargement on imaging should resolve within approximately one year of thyroid replacement 3

Critical Pitfalls to Avoid

• Never assume a prolactinoma without first excluding hypothyroidism—TSH and free T4 must be measured immediately in all patients with hyperprolactinemia 1, 2
• Do not order pituitary MRI until after confirming persistent hyperprolactinemia following treatment of hypothyroidism 1
• Avoid starting bromocriptine or cabergoline in patients with medication-correctable secondary hyperprolactinemia 1, 2
• Remember that prolactin levels of 100-200 ng/mL are more consistent with secondary causes (hypothyroidism, medications, stalk effect) rather than prolactinomas, which typically exceed 200-250 ng/mL 1, 2