Rare types of congenital adrenal hyperplasia: report of five children with 11β-hydroxylase deficiency including pathogenic and novel CYP11B1 variants.
Bala A, Banerjee S, et al. • Archives of endocrinology and metabolism • 2026
Five children with 11β-hydroxylase deficiency showed phenotypic variability, a median 2-year diagnostic delay, and management challenges including post-treatment central precocious puberty, with two novel CYP11B1 variants identified and hydrocortisone alone resolving hypertension in only one of three hypertensive patients.
Key Findings
Results
11β-hydroxylase deficiency (11β-OHD) was associated with a median diagnostic delay of 2 years across the five reported cases.
Five children were included in this case series report.
The median diagnostic delay was 2 years from symptom onset to confirmed diagnosis.
The delay underscores challenges in distinguishing 11β-OHD from other forms of congenital adrenal hyperplasia, particularly 21-hydroxylase deficiency.
Early differentiation from 21-hydroxylase deficiency was described as critical to prevent hypertension-related morbidity.
Results
Two novel CYP11B1 variants were identified in two unrelated patients with 11β-OHD.
The study identified pathogenic and novel variants in the CYP11B1 gene across the five cases.
Two of the five patients carried previously unreported (novel) CYP11B1 variants.
The two patients with novel variants were unrelated to each other.
Genetic profiling was part of the comprehensive clinical, hormonal, and genetic characterization of each patient.
Results
Hydrocortisone replacement therapy resolved hypertension in only one of three hypertensive patients, with the remaining two requiring additional spironolactone.
Three of the five children presented with hypertension, consistent with accumulation of 11-deoxycorticosterone, a potent mineralocorticoid.
Hydrocortisone monotherapy was sufficient to normalize blood pressure in one hypertensive patient.
Two hypertensive patients required spironolactone in addition to hydrocortisone for blood pressure management.
This finding highlights management challenges beyond standard glucocorticoid replacement in 11β-OHD.
Results
Post-treatment central precocious puberty was identified as a management complication in this cohort.
Central precocious puberty developed in at least one patient following initiation of treatment.
This complication was specifically highlighted as a management challenge in the context of 11β-OHD.
Post-treatment central precocious puberty has been described as a known complication of glucocorticoid treatment in congenital adrenal hyperplasia when bone age is significantly advanced prior to treatment.
The finding emphasizes the need for monitoring pubertal development after treatment initiation.
Background
11β-OHD leads to impaired cortisol synthesis, causing increased ACTH stimulation, accumulation of steroid precursors diverted to androgen synthesis, and accumulation of 11-deoxycorticosterone resulting in hyporeninemic hypokalemic hypertension.
11β-OHD is caused by biallelic pathogenic variants in the CYP11B1 gene.
The enzymatic block results in cortisol deficiency and consequent ACTH excess.
Excess steroid precursors are shunted into androgen biosynthesis pathways.
Accumulated 11-deoxycorticosterone acts as a potent mineralocorticoid, producing the characteristic triad of hyporeninemia, hypokalemia, and hypertension.
The hormonal profile was described as playing a crucial role in diagnosis.
Results
The clinical presentation of the five children demonstrated significant phenotypic variability.
The authors specifically emphasized phenotypic variability as a key observation across the five cases.
Phenotypic variability in 11β-OHD can complicate clinical recognition and timely diagnosis.
The combination of clinical, hormonal, and genetic profiling was used to characterize the full spectrum of presentation.
Not all hypertensive patients responded equally to standard hydrocortisone treatment, further illustrating variable disease expression.
What This Means
This research reports on five children diagnosed with a rare hormonal disorder called 11β-hydroxylase deficiency (11β-OHD), a form of congenital adrenal hyperplasia (CAH). In this condition, the adrenal glands cannot properly make cortisol due to a faulty gene (CYP11B1), which causes a buildup of other hormones — some of which act like male sex hormones and others that raise blood pressure. The study found that it took a median of 2 years after symptoms appeared for these children to receive the correct diagnosis, and that the children showed a wide variety of symptoms, making recognition difficult. Two of the five patients had gene variants that had never been reported before in medical literature.
Management of 11β-OHD proved challenging in this group. Three of the five children had high blood pressure, but the standard treatment (hydrocortisone, a steroid replacement) only brought blood pressure back to normal in one of them — the other two also needed a blood pressure medication called spironolactone. Additionally, at least one child developed a complication called central precocious puberty (early puberty triggered by the brain) after starting treatment, which is a known but important side effect to monitor. These findings highlight that treating 11β-OHD is not straightforward and requires close, individualized follow-up.
This research suggests that 11β-OHD can look very different from patient to patient and is frequently confused with the more common form of CAH (21-hydroxylase deficiency). Distinguishing between the two early is important because 11β-OHD specifically causes high blood pressure, and delayed or incorrect treatment can lead to serious cardiovascular complications. Identifying the specific genetic mutation can help confirm the diagnosis and may guide treatment decisions, particularly in cases where standard therapy is not fully effective.
Bala A, Banerjee S, George A, Srivastava P, Kumar M, Kc N, et al.. (2026). Rare types of congenital adrenal hyperplasia: report of five children with 11β-hydroxylase deficiency including pathogenic and novel CYP11B1 variants.. Archives of endocrinology and metabolism. https://doi.org/10.20945/2359-4292-2026-0073