No abstract

Kallmann syndrome, a form of idiopathic hypogonadotropic hypogonadism, is characterized by developmental abnormalities of the reproductive system and abnormal olfaction. Despite association of certain genes with idiopathic hypogonadotropic hypogonadism, the genetic inheritance and expression are complex and incompletely known. In the present study, seven Kallmann syndrome pedigrees in an ethnic Han Chinese population were screened for genetic mutations. The exons and intron-exon boundaries of 19 idiopathic hypogonadotropic hypogonadism (idiopathic hypogonadotropic hypogonadism)-related genes in seven Chinese Kallmann syndrome pedigrees were sequenced. Detected mutations were also tested in 70 sporadic Kallmann syndrome cases and 200 Chinese healthy controls. In pedigrees 1, 2, and 7, the secondary sex characteristics were poorly developed and the patients' sense of smell was severely or completely lost. We detected a genetic mutation in five of the seven pedigrees: homozygous KAL1 p.R191ter (pedigree 1); homozygous KAL1 p.C13ter (pedigree 2; a novel mutation); heterozygous FGFR1 p.R250W (pedigree 3); and homozygous PROKR2 p.Y113H (pedigrees 4 and 5). No genetic change of the assayed genes was detected in pedigrees 6 and 7. Among the 70 sporadic cases, we detected one homozygous and one heterozygous PROKR2 p.Y113H mutation. This mutation was also detected heterozygously in 2/200 normal controls and its pathogenicity is likely questionable. The genetics and genotype-phenotype relationships in Kallmann syndrome are complicated. Classical monogenic inheritance does not explain the full range of genetic inheritance of Kallmann syndrome patients. Because of stochastic nature of genetic mutations, exome analyses of Kallmann syndrome patients may provide novel insights.

Hypopituitarism is a clinical syndrome caused by reduced production of adenohypophyseal hormones. The clinical manifestations of senile hypopituitarism are more complicated and a delay in diagnosis and treatment may lead to rapid development of pituitary crisis. Therefore, clinicians should be alerted to senile hypopituitarism. For patients with hyponatremia, hypoglycemia and unexplained coma, an evaluation of pituitary function should be performed. Hormone replacement therapy for patients with confirmed hypopituitarism should be standardized and unauthorized dose reduction or withdrawal is not allowed.

Hypopituitarism is a clinical syndrome caused by reduced production of adenohypophyseal hormones. The clinical manifestations of senile hypopituitarism are more complicated and a delay in diagnosis and treatment may lead to rapid development of pituitary crisis. Therefore, clinicians should be alerted to senile hypopituitarism. For patients with hyponatremia, hypoglycemia and unexplained coma, an evaluation of pituitary function should be performed. Hormone replacement therapy for patients with confirmed hypopituitarism should be standardized and unauthorized dose reduction or withdrawal is not allowed.