Endocrine Abstracts

Deficiencies in the early stages of steroid production often lead to the development of female external genitalia in individuals with both 46XX and 46XY chromosomal patterns. Consequently, they are frequently overlooked when diagnosing primary adrenal insufficiency in cases where male external genitalia are present. Here, we present the case of a 4-year-old boy born from a third-degree consanguineous marriage, exhibiting normal male external genitalia, who displayed hyperpigmentation from the age of 2. He presented with decompensated shock and hypoglycemia, with noticeable hyperpigmentation on his face, lips, hands, and knuckles. Further investigation confirmed primary adrenal insufficiency, marked by a low cortisol level of 213nmol/l during hypoglycemia and a high ACTH level of 112.5 pmol/l(1.5-13.9 pmol/l), along with low sodium (127nmol/l) and normal potassium (4.7nmol/l). Initially, familial glucocorticoid deficiency was considered due to the absence of salt wasting and normal male external genitalia. The child was treated with hydrocortisone replacement, and plasma renin activity was assessed to evaluate mineralocorticoid activity, revealing elevated levels of 12.2ng/ml/hr(1.9-5.2ng/ml/hr). Subsequent clinical exome sequencing identified a compound heterozygous mutation in exon 1 and exon 5 of the CYP11A1 gene. In the past, it was commonly observed that 46XY children with CYP11A1 deficiency would typically present in the neonatal period with female external genitalia and primary adrenal insufficiency, which includes both glucocorticoid and mineralocorticoid deficiencies. However, recent studies have documented cases where children with CYP11A1 defects displayed normal male external genitalia. In our case, the boy was treated with hydrocortisone (15 mg/m2/day), and during follow-up, fludrocortisone (100 mg/day) was also introduced. 3 months later, we observed a reduction in pigmentation, and the ACTH levels dropped to 140pg/ml. The report underscores the existence of atypical CYP11A1 deficiency, characterised by primary adrenal insufficiency alongside typical male external genitalia in 46,XY individuals. This case emphasises the challenge of diagnosing primary adrenal insufficiency, particularly in scenarios where the presentation deviates from the classical norm, such as in 46XY individuals with CYP11A1 deficiency. This case represents the second documented instance with a similar presentation in India, underscoring the necessity for heightened awareness among healthcare practitioners, to facilitate early identification and appropriate management of such cases.