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.