Endocrine Abstracts

JOINT1333

Case description: In 2014, a 25-year-old patient was referred with unfulfilled desire to conceive, oligomenorrhoea, pronounced hirsutism since age 17, and clitoromegaly. A transvaginal ultrasound revealed bilateral ovarian lesions (left 4x2x1.5 cm; right 2x2 cm) later confirmed through MRI, as well as enlarged adrenal glands. Diastolic blood pressure was elevated and laboratory testing showed normal electrolytes and low cortisol (82 nmol/l[80-638]), however the patient had no signs of hypocortisolism. Further evaluation showed: testosterone 12.1 nmol/l[0.3-1.7], DHEA-sulfate 3.99 µmol/l[1.7-9.7], androstendione° >35.0 nmol/l[2.0-9.0], aldosterone 47 pmol/l[32-654], renin 0.6 ng/l[1.7-23.9], 17-OH-progesterone (stimulated) 19.4 nmol/l[<43], 11-desoxycortisol° >180 nmol/l[<12], ACTH 2008.0 pg/ml[<46.0]. We diagnosed congenital adrenal hyperplasia (CAH) with 11-β-hydroxylase deficiency and ovarian adrenal rest tumors (OARTs). Whole exome sequencing did not reveal a pathogenic variant. Due to active mineralocorticoid and glucocorticoid precursors, no substitution was required. Treatment with glucocorticoids was initiated to control androgen excess and restore menstruation. Subsequently she became pregnant spontaneously in 2017. After delivery, glucocorticoids were discontinued; nevertheless she became pregnant a second time and now has two healthy sons. In 2021, the patient presented with severe fatigue and low blood pressure of 92/61 mmHg (heart rate 69/min). Androgens were almost unmeasurable and cortisol very low: cortisol 20 nmol/l, ACTH 1107.0 ng/l, DHEA-sulfate 0.14 µmol/l, androstendione° <1.05 nmol/l, 17-OH-progesterone 1.6 nmol/l, 11-desoxycortisol° 10.2 nmol/l, sodium 140 mmol/l, potassium 3.9 mmol/l. She was diagnosed with an Addisonian crisis and substituted with hydrocortisone. 21-hydroxylase antibodies were positive (1.2 U/ml[<0.4]), suggesting autoimmune Addison’s disease, however further autoimmunological testing (ANA, IgG, IgM, IgA, complement CH50, C3/C4, B-cell and T-cell-subpopulations) was negative. In 2022, aged 32 years, the patient presented with premature ovarian failure (cessation of menstruation, hot flashes, estradiol 26.5 pmol/l[114-1959], LH 48.1 IU/l[<95.6], FSH 21.8 IU/l[1.7-21.5]) and hormone replacement was started. Surprisingly, the OARTs regressed and had not been detectable in imaging since 2019.

Discussion: This case raises the question of whether the concurrence of CAH, Addison’s disease, and premature ovarian failure in this patient is coincidental or indicative of a potential underlying connection. A case report (Sigrid Aslaksen et al., 2019) documented a patient with CAH with mutation in 3β-hydroxysteroid dehydrogenase and subsequent Addison’s disease and premature ovarian failure. We hypothesize that prolonged ACTH stimulation could have led to progressive depletion or dysfunction of ACTH-dependent tissue. This is supported by the finding that the mineralocorticoid steroid synthesis, regulated by the Renin-Angiotensin-Aldosterone system rather than ACTH, remained intact.