Overview
Severe steroid 21-hydroxylase deficiency is not directly addressed in the provided abstracts; however, the summaries focus on severe 17 alpha-hydroxylase deficiency, a related disorder characterized by impaired cortisol and sex steroid synthesis, leading to hypertension, hypokalemia, sexual infantilism, and pseudohermaphroditism 123456.Diagnosis
Clinical Presentation: Absent or delayed puberty, hypertension, hypokalemia, and pseudohermaphroditism 12456.
Biochemical Tests: Elevated levels of 11-deoxycorticosterone, corticosterone, and ACTH; low levels of cortisol, 17-hydroxyprogesterone, and sex steroids 14.
Genetic Analysis: Identification of mutations in the P450c17 gene, such as point mutations (e.g., Arg440His) or deletions affecting enzyme activity 123.
Functional Assays: Demonstration of absent 17 alpha-hydroxylase and 17,20-lyase activities in cell cultures 123.Management
Glucocorticoid Therapy: Dexamethasone to control hypertension, electrolyte imbalances, and to induce secondary sexual characteristics 45.
Sex Hormone Replacement: Estrogen therapy for female pseudohermaphrodites to promote secondary sexual development 4.
Monitoring: Regular assessment of blood pressure, electrolytes, and response to therapy; long-term follow-up for complications like malignant hypertension 5.Special Populations
Pediatrics: Early diagnosis and intervention are crucial to prevent long-term complications such as hypertension and osteoporosis 14.
Comorbidities: Hypokalemic myopathy can occur and requires specific management alongside endocrinological treatment 6.Key Recommendations
Genetic Testing for P450c17 Mutations: Essential for confirming the diagnosis and understanding the specific defect (Evidence: Moderate 123).
Initiate Dexamethasone Therapy: To manage hypertension and electrolyte imbalances, with dose adjustments based on clinical response (Evidence: Moderate 45).
Consider Sex Hormone Replacement: Particularly estrogen for female pseudohermaphrodites to support pubertal development (Evidence: Moderate 4).
Long-term Monitoring: Regular follow-up to detect and manage complications like malignant hypertension and secondary complications (Evidence: Expert opinion 5).References
1 Fardella CE, Hum DW, Homoki J, Miller WL. Point mutation of Arg440 to His in cytochrome P450c17 causes severe 17 alpha-hydroxylase deficiency. The Journal of clinical endocrinology and metabolism 1994. link
2 Fardella CE, Zhang LH, Mahachoklertwattana P, Lin D, Miller WL. Deletion of amino acids Asp487-Ser488-Phe489 in human cytochrome P450c17 causes severe 17 alpha-hydroxylase deficiency. The Journal of clinical endocrinology and metabolism 1993. link
3 Yanase T, Kagimoto M, Matsui N, Simpson ER, Waterman MR. Combined 17 alpha-hydroxylase/17,20-lyase deficiency due to a stop codon in the N-terminal region of 17 alpha-hydroxylase cytochrome P-450. Molecular and cellular endocrinology 1988. link90110-4)
4 Fraser R, Brown JJ, Mason PA, Morton JJ, Lever AF, Robertson JI et al.. Severe hypertension with absent secondary sex characteristics due to partial deficiency of steroid 17 alpha-hydroxylase activity. Journal of human hypertension 1987. link
5 Morimoto I, Maeda R, Izumi M, Ishimaru T, Nishimori I, Nagataki S. An autopsy case of 17 alpha-hydroxylase deficiency with malignant hypertension. The Journal of clinical endocrinology and metabolism 1983. link
6 Yazaki K, Kuribayashi T, Yamamura Y, Kurihara T, Araki S. Hypokalemic myopathy associated with 17 alpha-hydroxylase deficiency: a case report. Neurology 1982. link