Endocrine Abstracts

JOINT400

Hypogonadotropic hypogonadism is a rare endocrine disorder secondary to congenital or acquired diseases affecting the hypothalamus or pituitary gland. The congenital form is caused by alterations in genes that fuel the development and migration of GnRH-secreting neurons or interfere with the physiology of the hypothalamic-pituitary axis. It can be classified into Kallmann Syndrome (associated with anosmia) or normosmic congenital isolated hypogonadism (associated with normosmia). Congenital forms are characterized by micropenis, cryptorchidism, eunuchoid proportions and delayed puberty in males and by primary amenorrhea in females. Acquired forms may result from numerous functional or organic causes impairing the physiology of the hypothalamic-pituitary region, manifesting as erectile dysfunction, reduced libido and infertility in males and secondary amenorrhea in females. In this prospective study 31 patients (23 females and 8 males) were recruited at the Department of Endocrinology in Pisa for disorders related to hypogonadotropic hypogonadism. For each patient, medical history and clinical characteristics (pubertal development stage, signs or symptoms of estrogen or androgen deficiency) were evaluated. Ultrasound of the pelvis (to assess uterine and ovarian size and structure) and scrotum (to evaluate testicular location and size) was performed. Hormonal profiles, bone densitometry, brain and sella turcica MRI (to check for hypoplasia or absence of olfactory bulbs), olfactory tests (if anosmia was present) and genetic analysis of genes associated with hypogonadotropic hypogonadism were conducted. In 18 female patients (all with secondary amenorrhea) and one male patient, hypothalamic-pituitary axis dysfunction was suspected to have a functional cause (associated with significant weight loss, severe emotional stress or excessive physical exercise). Brain MRI of one female patient with primary amenorrhea revealed a triventricular hydrocephalus, while two patients were found to have an “empty sella.” One patient presented with a markedly reduced pituitary gland size. Four patients exhibited anosmic congenital hypogonadism or Kallmann Syndrome, associated with various mutations in the KISS1R gene and hypoplasia or aplasia of the olfactory bulbs. Two patients were found to have normosmic congenital hypogonadism, linked to mutations in the GnRHR gene and the CHD7 gene respectively. Finally, one male patient presented with hypogonadism in the context of Hartsfield Syndrome, associated with a mutation in the FGFR1 gene. Most of our patients showed impaired bone mineral density. In conclusion, hypogonadotropic hypogonadism is a rare endocrine disorder with various clinical manifestations. Its diagnosis requires careful integration of clinical, biochemical, instrumental, and genetic investigations to determine its etiology, enabling appropriate treatment of the condition.