ESPE Abstracts

Background: TARTs mostly occur in congenital adrenal hyperplasia due to 21-hydroxylase deficiency, but were described in other forms of CAH. Elevated ACTH levels, may play a role in TARTs development. Here we describe the first child with undetected CYP11A1 deficiency who presented with TART.

Case description: An 11 year old boy noticed left sided scrotal enlargement, without further complaints. Ultrasound showed a hydrocele and in both testis a testicular mass near the mediastinum testis with a heterogenous hypo-isoechogenic aspect, with symmetric focal hyperemia and microcalcifications. TARTS were considered and he was referred to the pediatric endocrinologist. At the age of 1 year he had a febral convulsion, hypoglycemia and hepatomegaly. Metabolic investigation was normal and hepatic enlargement resolved spontaneously. Puberty started early at the age of 11 years. He had diffuse hyperpigmentation. During illnesses, he often vomited and was more severely ill than other children. Normal male genital development, Tanner stage: P4, G4, testis 12 ml.

Laboratory results at age 11 years: normal sodium and potassium, increased ACTH (798 ng/l), basal cortisol 185 nmol/l, normal renin concentration, low adrenal steroids. ACTH-stimulation test: no increase in cortisol, or other adrenal steroids. LH and FSH were moderately increased (LH 11,9 U/l, FSH 13,67 U/l) and testosteron was moderately increased for his age (8,16 nmol/l). Karyotype 46XY. Adrenals were not seen on ultrasound, bone age was 1,5 years advanced. Whole Exome Sequencing for disorders in sexual development/adrenal disease showed two compound heterozygous variants in CYP11A1. The pathogenic variant c.835del p.(lle279fs) leads to a premature stopcodon in CYP11A1 protein. The second variant c.940G>A p.(Glu314Lys) is a variation with unknown significance but has been described as pathogenic together with the c.835deletion. Both parents are carrier of one of the mutations The patient is treated with hydrocortisone, ACTH concentration has decreased, on ultrasound TARTS are slightly smaller. Cytochrome P450 side-chain cleavage enzyme (CYP11A1) facilitates the first step of steroidogenesis. Patients present with adrenal insufficiency and disorder of sex development in 46XY individuals. Milder CYP11A1 deficient patients present with isolated adrenal insufficiency or isolated glucocorticoid deficiency and normal male genital development. On ultrasound, adrenals are invisible or normal in size. Sufficient androgens must have been synthesized for appropriate masculinization and pubertal development. Although fertility may be compromised due to TARTs and due to CYP11A1deficiency.

Conclusion: TARTs can be a presenting symptom of CAH due to CYP11A1 deficiency.