ODP035 Congenital Adrenal Hyperplasia secondary to 3 beta hydroxydehydrogenase deficiency: Case study and review of literature
Authors: Alkhaddo Jamil , Jaiswal Gayatri , Tipu Ali 
Published: November 2022

Introduction

Congenital Adrenal Hyperplasia (CAH) results from one of the five steroidogenic hormonal deficiencies in adrenal steroid synthesis pathway, most commonly caused by 21-hydroxylase deficiency (21-OHD). 3β-hydroxysteroid dehydrogenase (3βHSD) deficiency (def) is very rare cause of CAH, accounting for less than 0.5% of the CAH cases, associated with disorder of sexual development (DSD) and steroidogenesis. We present a case of salt wasting CAH secondary to 3βHSD-def with focus on the management compared with 21-OHD.

Case

53yr white female who was diagnosed with salt wasting CAH at birth, started on hydrocortisone replacement. She had oophorectomy at age of 11 due to hemorrhagic changes in ovaries. She was placed on oral contraceptives for most of her life. Her family history is significant for CAH in all of her 3 sisters, with oldest sister having pubic hair at age of 2 with frequent illnesses, triggering extensive workup and was subsequently diagnosed with CAH. Two brothers were also diagnosed with CAH with complete scrotum bifurcation at birth. Her family was subsequently diagnosed with 3βHSD deficiency. Patient's ACTH, Renin, 17-Hydroxyprogesterone (17-OHP) levels have been fluctuating due to skipping of hydrocortisone doses on occasions. Her sleep pattern remains disturbed, going to bed 3-4 AM and waking up at 2-3 PM.

Discussion

3βHSD deficiency is very rare cause of CAH with prevalence less than 1 in million cases at birth. First cases were reported by Bongiovanni in 1962. It is autosomal recessive disorder affecting both the sexes. 3βHSD is expressed in adrenal glands and gonadal tissues, where it catalyzes conversion of pregnenolone, 17-hydroxypregnenolone (17OHPreg) and dehydroepiandrosterone (DHEA) into aldosterone, cortisol and androstenedione respectively. Patient with salt-wasting 3βHSD def need mineralocorticoids, glucocorticoids along with sex steroid replacements. Clinical presentation varies with different degrees of salt wasting, incomplete masculinization in males and virilization in females, depending on the severity of the gene mutation. Elevated 17-OHPreg and its ratio with cortisol along with elevated Δ-5 steroids is used for diagnosis with confirmation through genetic testing, compared with 17-OHP levels which are mainly used for 21-OHD diagnosis. Management is challenging with glucocorticoid and mineralocorticoid replacement therapy with risk of under-/over-replacement, some requiring higher doses compared with other forms of CAH. There is higher risk of long term complication such as obesity, reduced adult height, infertility, osteoporosis, TARTs. Compared with 21-OHD, patients with complete 3βHSD def may need sex steroid replacement at puberty including testosterone (males) and cyclic estrogen-progesterone therapy (females). Timing of hydrocortisone should be individualized as higher doses in the morning or evening showed no substantial differences affecting sleep rating, daily activity score, nocturnal BP. DHEA is a useful marker for the adequacy of the therapy along with clinical monitoring.

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