SUN-440 - Secondary Adrenal Insufficiency with Cushingoid Features Associated with Medroxyprogesterone Acetate Use

Medroxyprogesterone acetate (MPA) is a widely used contraceptive agent in women of reproductive age. Cushingoid features and secondary adrenal insufficiency (AI) are rare but potentially serious adverse effects.

An 18-year-old female with no significant past medical history presented with bilateral temporal headaches accompanied by peripheral visual field loss. Further history revealed progressive weight gain, easy bruising, moon facies, proximal muscle weakness, anxiety, and prominent violaceous striae, prompting endocrine evaluation. Initial biochemical testing demonstrated an undetectable morning serum cortisol level (0 µg/dL) with a suppressed adrenocorticotropic hormone (ACTH) concentration (4.2 pg/mL). A standard 250-µg cosyntropin stimulation test showed an inadequate cortisol response, with serum cortisol levels of 2 µg/dL at both 30 and 60 minutes, suggesting adrenal insufficiency. The remainder of the pituitary hormone axes were intact. Pituitary MRI revealed no abnormalities. The only medication identified was a two-year history of MPA used for contraception. The patient was initiated on physiologic glucocorticoid replacement therapy, which was subsequently tapered and discontinued following recovery of the hypothalamic–pituitary–adrenal (HPA) axis. Follow-up laboratory testing demonstrated normalization of ACTH (28.7 pg/mL) and serum cortisol (15.3 µg/dL).

MPA is a synthetic 17α-hydroxyprogesterone derivative and a potent progesterone receptor (PR) agonist. Its long-acting parenteral formulation is commonly utilized as a contraceptive method. While progesterone lacks intrinsic glucocorticoid activity, the 6α-methylation of MPA confers glucocorticoid-like properties, which may lead to dysregulation of the HPA axis. In rare and severe cases activation of glucocorticoid pathways can suppress ACTH secretion via negative feedback mechanisms. This suppression results in low ACTH and cortisol levels, leading to secondary AI, while simultaneous glucocorticoid receptor activation may produce Cushingoid features, as observed in this patient. The extent of MPA’s impact on the HPA axis remains incompletely understood, with existing literature demonstrating considerable variability. Experimental animal models have shown that prolonged exposure to MPA may result in adrenal atrophy and undetectable cortisol levels, suggesting significant HPA axis suppression. Nonetheless, other studies have reported no measurable effects on adrenal or pituitary function.

The presence of Cushingoid features accompanied by suppressed plasma cortisol and ACTH levels should prompt clinicians to evaluate for exogenous MPA exposure. This consideration is warranted not only in patients receiving high dose MPA therapy but also in those using standard contraceptive dosing. Recognition and careful discontinuation are essential to prevent adrenal crisis.

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