Phenotypic Spectrum and Diagnostic Challenges in Non-21-Alfa-Hydroxylase Deficiency Congenital Adrenal Hyperplasia: A Case Series from a Tertiary care Centre

Authors

  • Shriraam Mahadevan Professor and Head of the Department of Endocrinology and Metabolism, Sri Ramachandra Institute of Higher Education and Research (Deemed to be University), Chennai, India Author
  • Anand Sheya Department of Endocrinology and Metabolism, Sri Ramachandra Institute of Higher Education and Research (Deemed to be University), Chennai, India Author
  • Vasireddy Nayana Tara Department of Endocrinology and Metabolism, Sri Ramachandra Institute of Higher Education and Research (Deemed to be University), Chennai, India Author
  • Asha Ranjan Assistant Professor, Department of Endocrinology and Metabolism, Sri Ramachandra Institute of Higher Education and Research (Deemed to be University), Chennai, India Author
  • Adlyne Reena Asirvatham Professor, Department of Endocrinology and Metabolism, Sri Ramachandra Institute of Higher Education and Research (Deemed to be University), Chennai, India Author
  • Sai Namratha Gogineni Department of Endocrinology and Metabolism, Sri Ramachandra Institute of Higher Education and Research (Deemed to be University), Chennai, India Author

DOI:

https://doi.org/10.47363/JPRRR/2025(7)177

Keywords:

Non-21-OHD CAH, Congenital Adrenal Hyperplasia, Genetic Disorders, Young Hypertension

Abstract

Purpose: Congenital adrenal hyperplasia (CAH) is an autosomal recessive disorder caused by enzyme deficiencies in adrenal steroidogenesis, with 21-hydroxylase deficiency (21-OHD) being the most common. However, rarer forms such as 11β-hydroxylase (11β-OHD), 3β-hydroxysteroid dehydrogenase type 2 (3β-HSD2), 17α-hydroxylase (17α-OHD), and steroidogenic acute regulatory protein (StAR) deficiency present diagnostic challenges due to variable phenotypes. This study describes the clinical, biochemical, and genetic profiles of non-21OHD CAH cases at a tertiary care centre.

Methods: A retrospective review of 87 CAH patients from 2008 to 2022 identified 13 cases of non-21OHD CAH. Clinical, biochemical, imaging and genetic data were analysed. The diagnosis was confirmed by hormonal assays and next-generation sequencing (NGS)-based genetic analysis.

Results: Among the 13 cases, six patients had 11β-OHD, primarily presenting with precocious puberty, hypertension, and hyperpigmentation, with elevated ACTH, 17-OHP, and suppressed renin levels. Three patients with 3β-HSD2 deficiency were diagnosed in early infancy following salt-wasting crises. 17α-OHD was diagnosed in three adolescent females presenting with primary amenorrhea, tall stature, hypertension, and elevated gonadotropins.One case of StAR deficiency was diagnosed at 45 days of life, presenting with adrenal crisis and severe adrenal insufficiency.

Conclusion: Non-21OHD CAH presents diagnostic challenges due to its varied clinical spectrum. Hypertension and hypokalemia are key differentiators for 11β-OHD and 17α-OHD, while steroid profiling (LC-MS) aids in diagnosing 3β-HSD2 deficiency. However, the most crucial aspect is the early diagnosis, which is a significant factor in preventing complications like hypertensive cardiomyopathy and adrenal crises. 

Author Biographies

  • Shriraam Mahadevan, Professor and Head of the Department of Endocrinology and Metabolism, Sri Ramachandra Institute of Higher Education and Research (Deemed to be University), Chennai, India

    Professor and Head of the Department of Endocrinology and Metabolism, Sri Ramachandra Institute of Higher Education and Research (Deemed to be University), Chennai, India

  • Anand Sheya, Department of Endocrinology and Metabolism, Sri Ramachandra Institute of Higher Education and Research (Deemed to be University), Chennai, India

    Department of Endocrinology and Metabolism, Sri Ramachandra Institute of Higher Education and Research (Deemed to be University), Chennai, India

  • Vasireddy Nayana Tara, Department of Endocrinology and Metabolism, Sri Ramachandra Institute of Higher Education and Research (Deemed to be University), Chennai, India

    Department of Endocrinology and Metabolism, Sri Ramachandra Institute of Higher Education and Research (Deemed to be University), Chennai, India

  • Asha Ranjan, Assistant Professor, Department of Endocrinology and Metabolism, Sri Ramachandra Institute of Higher Education and Research (Deemed to be University), Chennai, India

    Assistant Professor, Department of Endocrinology and Metabolism, Sri Ramachandra Institute of Higher Education and Research (Deemed to be University),Chennai, India

  • Adlyne Reena Asirvatham, Professor, Department of Endocrinology and Metabolism, Sri Ramachandra Institute of Higher Education and Research (Deemed to be University), Chennai, India

    Professor, Department of Endocrinology and Metabolism, Sri Ramachandra Institute of Higher Education and Research (Deemed to be University), Chennai, India

  • Sai Namratha Gogineni, Department of Endocrinology and Metabolism, Sri Ramachandra Institute of Higher Education and Research (Deemed to be University), Chennai, India

    Department of Endocrinology and Metabolism, Sri Ramachandra Institute of Higher Education and Research (Deemed to be University), Chennai, India

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Published

2025-04-28

Issue

Vol. 7 No. 8 (2025): Volume 7 Issue 8

Section

Articles