Endocrine Abstracts

JOINT1121

Congenital Hypogonadotropic Hypogonadism is caused by conditions affecting the hypothalamus or pituitary gland, leading to altered or absent secretion of GnRH (gonadotropin-releasing hormone) or inadequate biosynthesis of pituitary gonadotropins (FSH and LH). The disease can be categorized into two groups: two-thirds of patients present with hypogonadotropic hypogonadism associated with anosmia, defined as “Kallmann syndrome,” while the remaining one-third exhibit congenital hypogonadotropic hypogonadism with normal olfactory function, termed “idiopathic.” An alteration in the prokineticin system (PROK1 and PROK2) is among the various causes of hypogonadotropic hypogonadism. Specifically, PROK2 is predominantly expressed in the central nervous system, where it prompts the migration of GnRH-secreting neurons. Loss-of-function mutations in this protein or its receptor (PROKR2) have been associated in literature with the onset of hypogonadotropic hypogonadism, even in the absence of olfactory dysfunction. A 44-year-old male patient was referred to our outpatient clinic following recent pathological rib fractures, without a family history of fragility fractures or osteoporosis. Blood tests revealed normal phosphate-calcium metabolism, however the gonadal profile showed low levels of testosterone and gonadotropins, documenting hypogonadotropic hypogonadism. The patient reported no symptoms commonly associated with hypogonadism such as difficulties with ejaculation or nocturnal/morning erections). Despite this, a scrotal ultrasound revealed testicles smaller than expected for his age and a physical examination detected mild gynecomastia. The patient reported no change in his sense of smell. The densitometry scan revealed the presence of osteoporosis at the radial site (Z-score -2.4) and reduced bone mass at the lumbar vertebral site (Z-score -1.7). The Trabecular Bone Score (TBS) showed a markedly reduced value (TBS L1-L4: 1.012). X-rays of the dorsal and lumbar spine revealed osteoporotic fractures in the D11 and D12 vertebrae. An MRI of the pituitary gland with contrast showed no abnormalities. Genetic analysis identified a heterozygous mutation in exon 3 of the PROKR2 gene, classified as a variant of uncertain significance for hypogonadotropic hypogonadism. After confirming normal haematocrit and PSA levels, therapy with testosterone gel was initiated for hypogonadotropic hypogonadism resulting in a progressive normalization of testosterone levels. For osteoporosis associated with fragility fractures, intravenous infusion of zoledronic acid was administered and vitamin D supplementation therapy was started. In conclusion, hypogonadism should be considered in the evaluation of male patients presenting with osteoporosis, especially at a young age, to ensure accurate diagnosis and management of the condition and its associated complications.