Endocrine Abstracts

Introduction: Klinefelter syndrome (KS) is the most common genetic form of male hypogonadism, despite becoming evident only after puberty. The syndrome is characterized by a primary gonadal defect, which results in small testes due to hyalinization of the seminiferous tubules, low to low normal range of serum testosterone levels and elevated serum gonadotrophins. Paradoxically, a few cases have been described, presenting with hypogonadotropism.

Case-report: A 52-year-old male was referred to the endocrinology outpatient’s department due to obesity grade 3 (BMI 55.6 kg/m², Height 1.80 m, Weight 180 kg). He had past history of hypertension, schizophrenia and chronic venous insufficiency and was polimedicated, namely with fluoxetine, risperidone, biperiden and haloperidol. There was no history of visual disturbances or anosmia, but the patient complained of diminished olfaction. Physical examination revealed sparse facial hair, gynecomastia, central obesity, small, soft testes, and the penile length was 5 cm. Laboratory evaluation showed normal levels of gonadotrophins (FSH 6.5 U/l; LH 4.8 U/l), despite low total (31.7 ng/dl) and free (1.5 pg/ml) serum testosterone. Estradiol level was low (E2<10 pg/ml) and prolactin level was within normal range (9.4 ng/ml). The remaining anterior pituitary hormonal profile was normal, and the pituitary MRI did not display any lesion. A diagnosis of hypogonadism hypogonadotropic was assumed and the patient started testosterone replacement therapy responding positively, with improved virilization and a weight loss of about 35 kg in 6 months. Posteriorly, a LHRH test was performed, which showed subnormal FSH and LH responses. Initially, a Kallmann Syndrome was hypothesized, however genetic test came back negative, and surprisingly peripheral karyotyping revealed a 47 XXY pattern, confirming a Klinefelter syndrome.

Conclusion: Only a few cases of Klinefelter Syndrome presenting with hypogonadism hypogonadotropic have been reported in the past. The pathophysiology remains unknown, although it has been suggested that this occurred due to exhaustion of the gonadotrophs as a result of prolonged hypersecretion. The use of psychotropic drugs has been associated with hypogonadotropism, however this is mainly through hyperprolactinemia. Additionally, male obesity secondary hypogonadism has been described, although usually associated with high estradiol levels, and an improvement after weight loss has also been reported. Since these factors could not explain the hypogonadotropism, and a pituitary tumor was also excluded, the case reported might represent a rare variant of KS.