ESPE Abstracts

Background: 11β-hydroxylase deficiency (11βOHD) is a rare form of congenital adrenal hyperplasia (CAH), caused by biallelic mutations in the CYP11B1 gene. Clinical manifestations include cortisol deficiency, ambiguous genitalia in females, and hypertension. The clinical manifestations sometimes similar to those of 21-hydroxylase deficiency, and can cause confusion especially in limited settings. We presented three patients initially diagnosed as 21-OHD, in order to highlight the outcomes in case of misdiagnosis and important findings on the way to diagnosis.

Cases: Patient 1: A two days old boy, with hypotension and hyponatremia consulted to us. Family history revealed that his sister and cousin diagnosed with CAH. External genitalia was normal. Patient was on a limited setting without access to a laboratory that can measure adrenal steroids other than 17-OHP. ACTH and 17-OHP was elevated. Hidrocortisone treatment was initiated with preliminary diagnosis of 21-OHD. Patient 2(Sister, 3^5/12 yrs): Medical history revealed ambiguous genitalia at birth, subsequently undergoing genitoplasty with a diagnosis of 21-OHD. Medical records revealed hypokalemia over the previous year. Physical examination was normal, except hypertension. Echocardiography revealed left ventricular hypertrophy (LVH). 11-deoxycortisol level was found to be elevated. Fludrocortisone treatment was discontinued. Patient 3 (Cousin, 12^5/12 yrs) : He had diagnosed with 21-OHD, during evaluation for premature adrenarche at the age of 1 year. He was diagnosed with hypertension and LVH nine months prior to referral. Physical examination revealed gynecomastia and scrotal ultrasonography revealed TART. 11-deoxycortisol levels were elevated, with low potassium levels. On the basis of clinical and laboratory findings, 11-OHD suspected. A homozygous pathogenic mutation was detected in the CYP11B1 gene (NM_000497.3: c.372delG) by DNA sequence analysis, confirming CYP11 deficiency.

Discussion: 11βOHD, a rare form of CAH, can present with symptoms similar to 21-OHD, leading to misdiagnosis. We report three cases highlighting the challenges of diagnosing 11βOHD in resource-limited settings. All patients initially received a diagnosis of 21-OHD, and treated with hydrocortisone and fludrocortisone due to limited ability to measure adrenal steroids beyond 17-OHP. Delays resulted in complications such as exacerbated hypertension with use of mineralocorticoids and left ventricular hypertrophy. Elevated 11-deoxycortisol, gynecomastia (not typical in 21-OHD), and later onset of hypokalemia-hypertension emerged as crucial differentiating features. This case series emphasizes the importance of vigilance for 11βOHD in patients with suggestive symptoms, even in limited settings, to ensure early diagnosis and prevent long-term complications.