# Two Distinct Endocrine Conditions in a Single Pediatric Patient: Congenital Adrenal Hyperplasia and Type 1 Diabetes Mellitus

## TL;DR

A teenage girl with a rare adrenal condition also developed type 1 diabetes, suggesting a possible genetic link between the two.

## Contribution

The paper presents a rare case of coexisting NCCAH and T1DM, suggesting a potential shared genetic susceptibility.

## Key findings

- The patient had NCCAH due to a CYP21A2 mutation and later developed T1DM with positive autoantibodies.
- The CYP21A2 gene's location in the MHC may explain the coexistence of these two conditions.
- The case emphasizes the need for thorough evaluation and follow-up in patients with endocrine disorders.

## Abstract

Non-classical congenital adrenal hyperplasia (NCCAH) is an autosomal recessive disorder most commonly caused by partial 21-hydroxylase deficiency, typically presenting with late-onset hyperandrogenism. Type 1 diabetes mellitus (T1DM) is an autoimmune disease characterized by the destruction of pancreatic beta cells, although its coexistence with NCCAH, as described in the literature, is rare.

We report an adolescent girl previously diagnosed with NCCAH at six years of age, identified due to premature adrenarche, elevated 17-hydroxyprogesterone and androstenedione, genetically confirmed by a homozygous CYP21A2 c.1683G>T p.(Arg561Leu) pathogenic variant. During adolescence, she exhibited progression of hyperandrogenism, requiring glucocorticoid therapy. At 16 years of age, she presented to the emergency department with polydipsia, polyuria, weight loss, and recurrent fungal infections. Laboratory evaluation revealed hyperglycemia (435 mg/dL), a glycated hemoglobin (HbA1c) of 11.5%, without ketoacidosis, and positivity for anti-GAD65 and anti-islet cell antibodies, establishing the diagnosis of T1DM.

This case highlights important diagnostic and clinical considerations when hereditary endocrine diseases coexist with autoimmune diseases. Although NCAAH is not autoimmune, the location of CYP21A2 within the major histocompatibility complex (MHC)--a genomic region rich in immunoregulatory genes--may contribute to a shared genetic susceptibility background in a subset of patients.The coexistence of NCCAH and T1DM is uncommon but may be partially explained by the location of the CYP21A2 gene within the major histocompatibility complex (MHC), a genomic region associated with autoimmune susceptibility. Shared immunogenetic mechanisms may therefore contribute to the concurrent occurrence of these conditions, despite NCCAH not being classically autoimmune. This case highlights the importance of a thorough etiological evaluation in patients with hyperandrogenism, as well as the need for ongoing clinical follow-up, considering the possibility, albeit rare, of the development of other pathologies.