In rare cases, sequence variants of the NR5A1/SF-1 gene may result in POI, or in various disorders of gonadal development (DGD) or adrenal insufficiency.
NR5A1 mutations lead to several phenotypes, including sex reversal, spermatogenesis failure, premature ovarian failure and adrenocortical insufficiency.
Novel Heterozygous Mutations of NR5A1 and Their Functional Characteristics in Patients with 46,XY Disorders of Sex Development without Adrenal Insufficiency.
This is the first study searching for NR5A1 mutations in oriental patients from the Middle East and Arab region with XY DSD and no adrenal insufficiency, revealing a frequency similar to that in European patients (6.5-15%).
NR5A1 mutations have been identified in patients with various forms of 46,XY disorders of sex development (DSD), including complete gonadal dysgenesis with or without adrenal insufficiency, mild testicular dysgenesis with ambiguous external genitalia or female external genitalia with clitoromegaly, and penoscrotal hypospadias.
More recently, heterozygous NR5A1 mutations have been identified in a substantial proportion of patients with 46,XY disorders of sex development (46,XY DSD) without adrenal insufficiency.
The spectrum of phenotypes associated with mutations in steroidogenic factor 1 (SF-1, NR5A1, Ad4BP) includes severe penoscrotal hypospadias in 46,XY males without adrenal insufficiency.
Initially, mutations of SF-1/Ad4BP gene (NR5A1) in humans were identified in two 46, XY female patients with adrenal insufficiency and gonadal dysgenesis.
Previous studies have identified three human subjects with mutations in SF-1 causing adrenocortical insufficiency with varying degrees of gonadal dysfunction.
These SF-1 knockout mice lacked adrenal glands and gonads, causing adrenocortical insufficiency and sex reversal of their internal and external genitalia.
We describe a phenotypically and genotypically normal girl, with signs and symptoms of adrenal insufficiency and no apparent defect in ovarian maturation, bearing a heterozygote G-->T transversion in exon 4 of the NR5A1 gene that leads to the missense R255L in the SF-1 protein.
Patients were divided into 3 groups according to the serum cortisol response to the rapid ACTH test; those with a peak serum cortisol level of <15 μg/dL were defined as the adrenal insufficiency (AI) probable group, ≥15 μg/dL and <18 μg/dL as the AI suspected group, and ≥18 μg/dL as the non-AI group.
<b>ABSTRACT</b><b>Objective:</b> To evaluate the performance of morning serum cortisol (MSC) compared to a 10 μg ACTH stimulation test in the diagnosis of adrenal insufficiency (AI).
In both groups, none of the patients who had sufficient preoperative ACTH without hydrocortisone supplementation (n=15) showed hypocortisolism in the immediate postoperative measurement.
Primary AI is defined by the inability of the adrenal cortex to produce sufficient amounts of glucocorticoids and/or mineralocorticoids despite normal or increased adrenocorticotropin hormone (ACTH).