SAT-431 - Dual Gland Failure: Linking Primary Ovarian Insufficiency and Adrenal Insufficiency

Premature ovarian insufficiency (POI) and primary adrenal insufficiency (PAI) are rare conditions that may coexist as part of autoimmune endocrinopathies. Early recognition is critical to prevent long-term morbidity. Although 21-hydroxylase antibodies are recommended in the evaluation of POI, seronegativity does not exclude evolving adrenal insufficiency.
A 34-year-old woman with antiphospholipid syndrome, class I obesity, and major depressive disorder presented with secondary amenorrhea. Menarche occurred at age 11 with regular menses. She had two prior uncomplicated full-term pregnancies. At age 22, after placement of a non-hormonal intrauterine device (IUD), she developed progressive amenorrhea. Menses did not resume after IUD removal at age 34. She reported fatigue and anxiety but no hyperpigmentation, hypotension, or gastrointestinal symptoms. Examination was unremarkable aside from elevated BMI.
Initial evaluation revealed low estradiol ( < 24 mIU/mL), elevated FSH (18.9 mIU/mL) and LH (31.6 mIU/mL), with normal prolactin and TSH. As required for POI diagnosis, gonadotropins and estradiol were repeated, confirming persistently elevated FSH (63 mIU/mL) and hypoestrogenism. Anti-Müllerian hormone was low (0.544 ng/mL). Pregnancy, chromosomal abnormalities, fragile X premutation, and 21-hydroxylase antibodies were excluded. POI was diagnosed and hormone replacement therapy initiated.
Prior outside testing showed elevated ACTH (185 pg/mL) with low-normal cortisol. Repeat testing demonstrated rising ACTH (232 pg/mL) with low cortisol (9.6 µg/dL). ACTH stimulation testing showed inadequate cortisol response (peak 12.2 µg/dL). DHEA was low, while renin and aldosterone were normal, indicating preserved mineralocorticoid function; therefore, fludrocortisone was not indicated. Hydrocortisone replacement was initiated.
PAI occurs in approximately 2–10% of women with POI. While adrenal antibodies have high specificity, their sensitivity is limited. In this seronegative patient, markedly elevated ACTH served as a key predictor of primary adrenal insufficiency and justified further testing.
POI and PAI may develop even after prior successful pregnancies, with POI presenting in the 20s or late 30s. This case underscores the importance of repeating gonadotropins to confirm POI and maintaining a high index of suspicion for adrenal insufficiency. Elevated ACTH warrants comprehensive adrenal evaluation, even in antibody-negative patients.

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