Relative aldosterone insufficiency after glucocorticoid replacement in 17α-hydroxylase/17,20-lyase deficiency — ASN Events
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Relative aldosterone insufficiency after glucocorticoid replacement in 17α-hydroxylase/17,20-lyase deficiency (#453)

Xin Pan 1 2 , Fuye Yang 3 , Xiaoxiao Song 2
  1. Endocrinology, The First People's Hospital of Xiaoshan District, Hangzhou, ZHEJIANG, China
  2. Endocrinology, The Second Affiliated Hospital Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
  3. Nephrology, The Second Affiliated Hospital Zhejiang University School of Medicine, Hangzhou, Zhejiang, China

Aims

17α-hydroxylase/17,20-lyase deficiency (17OHD), a rare form of congenital adrenal hyperplasia (CAH), is caused by biallelic CYP17A1 mutations [1]. Marked clinical heterogeneity often delays diagnosis, compromising prognosis [1]. This study reports a 40-year-old woman presenting with renal impairment who was diagnosed with 17OHD, highlighting clinical features and treatment complexities to raise awareness of standardized management.

Methods

Comprehensive endocrine evaluation, adrenal imaging, and karyotyping were performed. Whole-exome sequencing identified compound heterozygous CYP17A1 mutations, confirmed by Sanger sequencing in both parents.

Results

A 40-year-old phenotypic female with untreated hypertension and primary amenorrhea presented to nephrology with foamy urine, renal impairment, and incidentally detected hypokalemia. Refractory hypertension (five antihypertensives including spironolactone) and persistent hypokalemia prompted endocrine referral. Physical examination revealed sexual infantilism. Laboratory findings showed hypergonadotropic hypogonadism, low cortisol (8 AM: 18.0 nmol/L; elevated ACTH (8 AM: 94.1 pg/mL), suppressed renin and aldosterone, and high-turnover bone loss. Abdominal CT showed bilateral adrenal hyperplasia with absent uterus. Karyotype analysis revealed 46,XX. Whole-exome sequencing (Figure 1) identified compound heterozygous CYP17A1 mutations, confirmed by Sanger sequencing in both parents. She was diagnosed with 17OHD and started on dexamethasone 0.375 mg nightly. Blood pressure and potassium improved with declining ACTH, but hyperkalemia occurred after 1 months. This reflected relative aldosterone insufficiency: dexamethasone suppressed ACTH and 11-deoxycorticosterone (DOC) synthesis, while chronic renin–angiotensin–aldosterone system suppression from prior DOC excess had downregulated zona glomerulosa CYP11B2, preventing timely aldosterone compensation [2,3]. Reduced renal function further impaired potassium excretion [4]. Fludrocortisone replacement normalized potassium, confirming relative aldosterone deficiency.

Conclusion

This case highlights that hereditary adrenal disorders should be suspected in patients with sexual infantilism, hypertension, and hypokalemia regardless of age. 17OHD replacement requires dynamic monitoring of electrolytes and hormones to balance glucocorticoid and mineralocorticoid doses. Early diagnosis, standardized treatment, and long-term organ protection are crucial for prognosis.

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