An Adult With Hair Loss! a Rare Case of Non-Classical 3β Hydroxysteroid Dehydrogenase (3β HSD) Deficiency

Introduction: Congenital adrenal hyperplasia (CAH) is the most frequent cause of adrenal insufficiency and ambiguous genitalia in newborn. Unlike 21-hydroxylase and 11β- hydroxylase deficiencies, classical 3β hydroxysteroid dehydrogenase (3β HSD) deficiency affects steroid biosynthesis in both the adrenals and the gonads. We present a rare case of suspected 3β HSD in an adult with hair loss. Case: 33 years old with female with no PMH/prior pregnancies was referred to endocrinology for low testosterone, male pattern hair loss and decreased libido for 2 years. At onset of symptoms, she was following an intensive exercise regimen for weight loss and was using Oxandrolone for 2 months to promote muscle mass. She now reports increased axillary and pubic hair growth but loss of scalp hair as well as fatigue. Menarche was at 14 years. Menstrual cycles are regular but with hypomenorrhea. Physical examination showed normal BP, signs of male pattern hair loss on scalp. light terminal hair growth over abdomen, middle thighs and around areola but without galactorrhea. Labs remarkable for normal sodium and potassium, A1c 5.2%, ACTH of 7.2, Cortisol of 8.2 (5–25 µg/dl), TSH of 1.43 (0.5–5.0 mIU/L), Free T4 of 1.28 (0.8–1.8 ng/dl), Estrone 102 (17–200 pg/ml), Normal DHEA 133, Total testosterone <3 (8–60 ng/dl), Free testosterone 0.4 (0.3–1.9 ng/dL), LH 7 (1.0–18.0 mIU/mL), FSH 9.6 (2.0–12.0 mIU/mL), Estradiol 45.9 (15–350 pg/mL),low 17-hydroxyprogesterone of 11 (<80 ng/dL), DHEA-S of 88 (31–228 µg/dL), low Androstenedione of 28 (80–240 ng/dL) and Dihydrotestosterone 6.3 (normal). MRI brain revealed a normal pituitary gland, slightly enlarged for age. Co-syntropin stimulation test has been delayed due to the pandemic. Discussion: 3β HSD converts delta-5 steroids (pregnenolone, 17-hydroxypregnenolone, DHEA, androstenediol) to delta-4 steroids (progesterone, 17-hydroxyprogesterone, androstenedione, testosterone) respectively. Delta-4 steroids were low in our patient. Increased ratio of delta 5 steroids: delta 4 is characteristic of 3β HSD. Most cases of 3β HSD deficiency present as neonates with hyponatremia, hyperkalemia, and ambiguous genitalia but a non-salt wasting form has occasionally been described in older patients. The non-classical form often manifests as menstrual irregularities and hirsutism along with possible male pattern hair loss of varying degrees in women. The normal levels of estradiol and estrone are likely due to peripheral conversion of androstenedione by aromatase. 3β HSD deficiency is usually treated with steroids which helps resolve most symptoms. References: Simard J, Rheaume E, Mebarki F, Sanchez R, New MI, Morel Y, Labrie F. Molecular basis of human 3 beta-hydroxysteroid dehydrogenase deficiency. J Steroid Biochem Mol Biol. 1995 Jun;53(1–6):127–38.