• PMID: 15001585
• Gene Name: AR
• Condition: Partial androgen insensitivity syndrome (PAIS)
• Association: Using clinical, molecular, and genetic studies, the patient was found to have partialandrogen insensitivity syndrome (PAIS) caused by a novel mutation (Ser(740)Cys) in the ligand-binding domain of the androgen receptor. Subsequent studies of the patient c
• Mutation: Ser(740)Cys
• Population size: 1
• Population details: 1 hypogonadotropic hypogonadism
• Sex: Male
• Infertility type: Male infertility
• Other associated phenotypes: Partial androgen insensitivity syndrome (PAIS)

Acute stress masking the biochemical phenotype of partial androgen insensitivity syndrome in a patient with a novel mutation in the androgen receptor

Pitteloud N, Villegas J, Dwyer AA, Crowley WF Jr, McPhaul MJ, Hayes FJ.

Hypogonadism has traditionally been classified as either hypogonadotropic or hypergonadotropic based on serum gonadotropin levels. However, when hypothalamic suppression of GnRH secretion occurs, it can mask an underlying hypergonadotropic state. In this report we document the unusual case of a 61-yr-old man with androgen insensitivity and coincidental functional hypogonadotropic hypogonadism (HH). Although functional HH is not a well-recognized entity in the male, major stress has been reported to cause transient suppression of the hypothalamic-pituitary-gonadal axis in men. The patient in question was noted to have undervirilization, minimal pubertal development, hypogonadal testosterone, and low gonadotropin levels consistent with congenital HH during a hospital admission for myocardial infarction. However, the patient had also had surgery for hypospadias, a clinical feature not typically part of the phenotypic spectrum of congenital HH. We therefore hypothesized that the combination of acute stress and chronic glucocorticoid administration for temporal arteritis induced transient HH in a patient with a disorder of sexual differentiation in whom gonadotropin levels would have otherwise been elevated. Using clinical, molecular, and genetic studies, the patient was found to have partial androgen insensitivity syndrome (PAIS) caused by a novel mutation (Ser(740)Cys) in the ligand-binding domain of the androgen receptor. Subsequent studies of the patient confirmed the characteristic gonadotropin and sex steroid abnormalities of PAIS. We describe for the first time a patient with PAIS presenting with a reversible hypogonadotropic biochemical profile triggered by an acute illness and corticosteroid therapy. This case highlights the necessity for caution when interpreting gonadotropin levels during acute stress. FAU - Pitteloud, Nelly AU - Pitteloud N AD - Reproductive Endocrine Unit, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts 02114, USA. FAU - Villegas, Jacob AU - Villegas J FAU - Dwyer, Andrew A AU - Dwyer AA FAU - Crowley, William F Jr AU - Crowley WF Jr FAU - McPhaul, Michael J AU - McPhaul MJ