What is the most likely diagnosis in a postmenopausal woman with low thyroid‑stimulating hormone, normal free thyroxine, elevated estradiol, and suppressed follicle‑stimulating hormone and luteinizing hormone?

Most Likely Diagnosis: Estrogen-Secreting Ovarian Tumor

The combination of suppressed FSH/LH with elevated estradiol in a postmenopausal woman is pathognomonic for an estrogen-secreting ovarian neoplasm, most commonly a granulosa cell tumor, until proven otherwise. The low TSH with normal free T4 represents secondary central hypothyroidism from the underlying ovarian pathology affecting pituitary function.

Diagnostic Reasoning

Why This Cannot Be Normal Menopause

• Postmenopausal women should have elevated FSH and LH (typically >40 mIU/mL) with low estradiol (<25-30 pg/mL) due to loss of ovarian follicular function and absence of negative feedback 1, 2, 3.
• The presence of high estradiol with suppressed gonadotropins directly contradicts the expected postmenopausal hormonal profile and indicates an autonomous source of estrogen production 4, 1.
• In true menopause, FSH rises first and remains elevated, while this patient demonstrates the opposite pattern 5.

The Ovarian Tumor Hypothesis

• Estrogen-secreting ovarian tumors (granulosa cell tumors, thecomas) produce sufficient estradiol to suppress the hypothalamic-pituitary-gonadal axis, resulting in inappropriately low FSH and LH despite postmenopausal status 4.
• These tumors are most common in postmenopausal women and often present with hormonal abnormalities before causing mass effect symptoms 4.
• The elevated estradiol provides negative feedback to the pituitary, suppressing gonadotropin release—exactly the pattern seen here 4, 1.

The Central Hypothyroidism Component

• Low TSH with normal free T4 indicates central (secondary) hypothyroidism, suggesting pituitary or hypothalamic dysfunction 4.
• This pattern is consistent with hypophysitis or pituitary dysfunction, which can occur when the hypothalamic-pituitary axis is disrupted by severe hormonal imbalances 4.
• The combination of gonadotropin suppression and TSH suppression suggests global anterior pituitary dysfunction rather than isolated thyroid disease 6.

Critical Diagnostic Workup Required

Immediate Imaging

• Obtain transvaginal ultrasound and pelvic MRI immediately to identify ovarian masses, as estrogen-secreting tumors are often small and easily missed on physical examination 4.
• If imaging is negative for ovarian pathology, proceed to MRI of the sella turcica to evaluate for pituitary adenoma or other sellar masses that could cause both central hypothyroidism and gonadotropin suppression 4.

Confirmatory Hormone Testing

• Repeat FSH, LH, and estradiol measurements to confirm the pattern, as single measurements can occasionally be misleading 1, 2.
• Measure inhibin B and anti-Müllerian hormone (AMH), which are often markedly elevated in granulosa cell tumors and can serve as tumor markers 4.
• Check morning ACTH and cortisol to assess for additional pituitary hormone deficiencies if hypophysitis is suspected 4.

Rule Out Exogenous Estrogen

• Obtain detailed medication history including over-the-counter supplements, compounded hormones, and topical estrogen preparations that the patient may not recognize as hormone therapy 4, 2.
• Exogenous estrogen would similarly suppress FSH/LH but is far less likely to cause central hypothyroidism unless there is concurrent pituitary pathology 4.

Common Pitfalls to Avoid

• Do not assume this is "atypical menopause" or perimenopause—the hormonal pattern is incompatible with any phase of normal ovarian senescence 1, 3, 5.
• Do not treat the low TSH as primary hyperthyroidism—the normal free T4 excludes this diagnosis and indicates central pathology 4.
• Do not delay imaging while waiting for repeat labs—estrogen-secreting tumors can be malignant (granulosa cell tumors have malignant potential) and require prompt surgical evaluation 4.
• Do not overlook small ovarian masses—these tumors are often <5 cm and may appear benign on imaging but are functionally active 4.

Alternative Diagnoses (Less Likely)

If Imaging Shows Pituitary Pathology

• Hypophysitis or pituitary adenoma could theoretically cause both central hypothyroidism and hypogonadotropic hypogonadism, but would not explain the elevated estradiol 4.
• Pituitary pathology typically causes low estradiol, not high, making this diagnosis incompatible with the clinical picture 4.

Critical Illness or Severe Stress

• Critically ill postmenopausal women can develop suppressed gonadotropins with inappropriately low FSH/LH for their menopausal state 6.
• However, this is accompanied by low estradiol and low free T4 (sick euthyroid syndrome), not the high estradiol and normal T4 seen here 6.

Next Steps in Management

• Refer urgently to gynecologic oncology if ovarian mass is identified, as surgical excision is both diagnostic and therapeutic 4.
• Refer to endocrinology if pituitary pathology is found, for management of central hypothyroidism and evaluation of other pituitary hormone axes 4.
• Do not initiate thyroid hormone replacement until the underlying cause is identified, as treating central hypothyroidism without addressing the primary pathology can mask important diagnostic clues 4.