Isolated adrenocorticotropin deficiency presenting as primary infertility

Area of Science:

• Reproductive Endocrinology
• Neuroendocrinology

Background:

• Primary infertility and amenorrhea are common complaints, often investigated for polycystic ovary syndrome or hypothalamic dysfunction.
• Endocrine evaluation typically focuses on the hypothalamic-pituitary-gonadal axis, but other pituitary hormones can be involved.

Observation:

• A 31-year-old female presented with a 2-year history of amenorrhea and infertility, showing low estradiol and progesterone with decreased LH pulsatility.
• Impaired cortisol responses to hypoglycemic stress and short Synacthen test, but normal response to prolonged Synacthen test, suggested adrenal insufficiency.
• Corticotropin-releasing factor (CRF) testing revealed an inadequate ACTH response, confirming isolated ACTH deficiency.

Findings:

• Hydrocortisone therapy initiated for isolated ACTH deficiency resulted in an ovulatory menstrual cycle.
• Amenorrhea recurred upon steroid dose reduction, resolving with normalized steroid replacement, indicating a direct link between cortisol levels and the hypothalamic-pituitary-gonadal axis.
• Steroid treatment significantly increased gonadotropin pulsatility (LH and FSH), restoring normal menstrual function.

Implications:

• Isolated ACTH deficiency is a rare, treatable cause of hypogonadism and infertility in women.
• This case underscores the critical role of adequate cortisol levels in maintaining normal reproductive function via the hypothalamo-pituitary gonadal axis.
• Highlights the importance of considering secondary adrenal insufficiency in cases of unexplained infertility and amenorrhea.