BACKGROUND Human mutations in the gonadotropin-releasing hormone receptor (GnRHR) gene cause normosmic idiopathic hypogonadotropic hypogonadism (IHH). At least 19 different mutations have been identified in this G-protein-coupled receptor, which consist mostly of missense mutations. OBJECTIVES To identify and determine the frequency of mutations in the coding region of the gonadotropin-releas...

Federal University of São Paulo (UNIFESP), São Paulo SP, Brazil: Department of Neurology and Neurosurgery; Department of Endocrinology; Department of Ophthalmology. The association between cerebellar ataxia and hypogonadism was first described by Gordon Holmes in 1907. It represents a highly heterogenous syndrome with insidious onset. The hypogonadism of most patients with Gordon Holmes syndrom...

OBJECTIVE The underlying genetic etiology of hypogonadotropic hypogonadism (HH) is heterogeneous. Fibroblast growth factor signaling is pivotal in the ontogeny of gonadotropin-releasing hormone neurons. Loss-of-function mutations in FGFR1 gene cause variable HH phenotypes encompassing pubertal delay to idiopathic HH (IHH) or Kallmann syndrome (KS). As FGFR1 mutations are common, recognizing mut...

Primary adrenal insufficiency is defined by the impaired synthesis of adrenocortical hormones due to an intrinsic disease of the adrenal cortex. Determining its etiology is crucial to allow adequate long-term management and genetic counseling. We report the case of a male adolescent that presented in the neonatal period with adrenal crisis and received replacement therapy for primary adrenal in...

Response Dr Jolobe's report of an 85-year-old woman with a history of stroke, primary hypothyroidism, and low gonadotropin levels appears to conform to the findings we described in a study of postmenopausal women with stroke. The presence of primary hypothyroidism in his patient is in contrast to findings in our group, in which thyroid function was normal. The fact that hypogonadotropic hypogon...

Kallmann syndrome (KS) is a disease clinically characterized by the association of hypogonadotropic hypogonadism and anosmia or hyposmia, for which three modes of transmission have been described: X-linked, autosomal recessive and autosomal dominant. The KAL-1 gene, responsible for the X-linked form of the disease, has been isolated and its intron-exon organization determined. In this study, tw...

In this study, we describe a patient with a phenotype of complete hypogonadotropic hypogonadism who presented primary failure of pulsatile GnRH therapy, but responded to exogenous gonadotropin administration. This patient bore a novel point mutation (T for A) at codon 168 of the gene encoding the GnRH receptor (GnRH-R), resulting in a serine to arginine change in the fourth transmembrane domain...

Ultrasound assessment of ovarian volume, follicular size, and uterine growth was undertaken in 40 normal premenarcheal girls aged 6 months to 14 years. Ovarian follicles were detected from 6 months of age and increased in size and number, so that after the age of 8.5 years there was a progressive increase in the incidence of 'megalocystic' appearance. Eight girls with idiopathic precocious pube...

Idiopathic hypogonadotropic hypogonadism is a rare disease that is characterized by delayed/absent puberty and/or infertility due to an insufficient stimulation of an otherwise normal pituitary-gonadal axis by gonadotrophin-releasing hormone (GnRH) action. Because reduced or normal luteinizing hormone (LH)/follicle-stimulating hormone (FSH) levels may be observed in the affected patients, the t...