Diagnosis of female 17α-hydroxylase deficiency after gonadectomy: a case report

Abstract

Background 17α-Hydroxylase deficiency is a recessively inherited autosomal disease caused by mutations in the CYP17A1 gene. It is a rare disease and accounts for approximately 1% of congenital adrenal cortex hyperplasias. Inhibition of 17α-hydroxylase causes low levels of cortisol and high levels of adrenocorticotropic hormone in the blood as well as excessive levels of mineralocorticoids that lead to hypertension and hypokalemia. Usually, the female patients are diagnosed with abnormality of the genitalia or extra genitalia, primary amenorrhea, or hypertension in puberty. We report a case of a 29-year-old woman who had undergone gonadectomy in her childhood due to complete androgen insensitivity syndrome and was diagnosed with 17α-hydroxylase deficiency in adulthood. Case presentation Our patient was a Japanese female diagnosed with androgen insensitivity syndrome, and both gonadectomy and episioplasty were performed at the age of 11 years at the University of Tsukuba Hospital. Thereafter, she was transferred to our hospital at the age of 21 years for vaginoplasty. At the age of 25 years, she presented with hypertension followed by complicated hypokalemia at the age of 28 years. The captopril loading test and adrenocorticotropic hormone loading test of her adrenal steroidogenesis revealed primary aldosteronism. After sufficient genetic counseling, a genetic test was performed that identified her as having CYP17A1 gene mutation. Conclusions The differential diagnosis of disorders of sex development can be difficult at a young age without complete expression of the phenotype. However, diagnosis at a later age would change the treatment and prognosis of the disease; therefore, a genetic examination should be considered.

Novel mutations of the CYP17A1 gene cause disorders of sex development in two-chromosome karyotype 46,XY infants and a literature review: A case report

“…Therefore, patients often seek medical attention during puberty without gonad development, severe hypertension or electrolyte disturbances. At the same time, it is also easily diagnosed as androgen-insensitivity syndrome, primary aldosteronism and other diseases [33]. The current treatment plan for 17α-OHD patients is to administer supplementary physiological doses of glucocorticoids, oestrogen or androgen.…”

Clinical Features of Unrecognized Congenital Adrenal Hyperplasia due to 17α-hydroxylase Deficiency Since Adolescence: A Case Report

“…This mutation has been described in earlier reports from both Japan and New Zealand in patients with similar phenotypes and both 46,XY and 46,XX karyotypes. 5 - 7 Structural and functional studies of the mutant protein with cos-1 cells lines have shown that this deletion alters the protein folding, thus reducing the activity of 17α-hydroxylase (<37%) and 17,20 lyase (<8%) compared to the wildtype protein resulting in partial combined 17α-hydroxylase/17,20 lyase deficiency. 7 Based on the guidelines of the American College of Human Genetics released in 2015, the identified mutation is classified as pathogenic.…”

Genetic diagnosis and clinical analysis of 17α-hydroxylase/17, 20-lyase deficiency combined with type 2 diabetes mellitus: A case report

“…As a result, the notable feature of patients with 17OHD are low blood levels of cortisol, androgen, estrogen and a compensatory high adrenocorticotropic hormone (ACTH) levels. [5,6] Excessive levels of ACTH stimulate the 11-deoxycorticosterone (DOC) and corticosterone production, which have powerful mineralocorticoid activity, leading to extracellular volume expansion, hypertension, and hypokalemia. [5][6][7] Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder, and is characterized by chronic hyperglycemia resulting from defects in insulin secretion and/or insulin action.…”

“…[5,6] Excessive levels of ACTH stimulate the 11-deoxycorticosterone (DOC) and corticosterone production, which have powerful mineralocorticoid activity, leading to extracellular volume expansion, hypertension, and hypokalemia. [5][6][7] Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder, and is characterized by chronic hyperglycemia resulting from defects in insulin secretion and/or insulin action. [8] The risk for T2DM and insulin resistance have been shown to be increased in CAH but has been mainly been blamed on supraphysiological glucocorticoid replacement, even though high androgens in poorly treated 21 hydroxylase deficiency probably also increase the risk for glycemic disturbances.…”

“…[5,6] Excessive levels of ACTH stimulate the 11-deoxycorticosterone (DOC) and corticosterone production, which have powerful mineralocorticoid activity, leading to extracellular volume expansion, hypertension, and hypokalemia. [5–7]…”