Combination of Klinefelter Syndrome and Acromegaly

Abstract

Klinefelter syndrome (KS) is the most common chromosomal aneuploidy in male population, which demonstrates an unusual association with acromegaly. We herein present a rare case involving the confirmation of KS 2 years after surgical treatment for acromegaly.A 27-year-old man presented with an acromegalic appearance. Endocrinological examination revealed a high growth hormone (GH) concentration, low testosterone concentration, and high follicle-stimulating hormone and luteinizing hormone concentration. Brain imaging revealed a 9 × 6 × 7− mm sellar low-density nodule suggestive of a microadenoma. Trans-sphenoidal surgery was undertaken, and immunohistochemistry revealed GH positivity. Two years after surgery, the patient underwent examination for infertility. He presented with diminished pubic hair, and small and firm testes. Hormonal assay revealed hypergonadotrophic hypogonadism on the basis of decreased serum total testosterone (<0.2 ng/mL), and elevated luteinizing hormone (14.71 mIU/mL) and follicle-stimulating hormone (21.8 mIU/mL). A chromosomal karyotype examination showed 47,XXY, confirming the diagnosis of KS. Replacement therapy with oral testosterone undecanoate was begun. Brain imaging showed no delayed enhancement in the saddle region of the pituitary gland, but the concentration of plasma insulin-like growth factor maintained a high level. The patient's GH concentration was not significantly suppressed by the GH glucose suppression test. In this consideration, he was referred for postoperative somatostatin analogue treatment to control GH hypersecretion.The misdiagnosis or delayed diagnosis of KS is mainly because of substantial variations in clinical presentation and insufficient professional awareness of the syndrome itself. As the simultaneous occurrence of KS and acromegaly is rare, and the association between them remains unclear, we suggest that complete pituitary hormonal screening and conventional pituitary MRI should be essential for patients with KS to screen for pituitary tumor.

Pseudoacromegaly—A challenging entity in the endocrine clinic: A systematic review

“…These findings support the relevance of endocrine specialists in the management of pseudoacromegaly patients, where adequate assessment of GH/IGF‐1 axis is crucial to conclusively rule out (or diagnose) acromegaly 53–55 . Endocrinologists must ensure that every pseudoacromegaly case have a normal GH/IGF‐1 axis before assuming a certain condition as the cause of acromegaloid features, 56,57 as acromegaly may coexist with other pseudoacromegaly disorders, as reported in Seip‐Berardinelli syndrome, 58 Tatton‐Brown‐Rahman syndrome, 59 pachydermoperiostosis, 60 and Klinefelter syndrome, 61 or in families with both GH‐related pituitary and non‐pituitary gigantism 62 . Endocrine specialists are also important to avoid erroneous diagnosis of acromegaly, 17–20 and prevent inadequate pituitary surgery in pseudoacromegaly cases with pituitary incidentalomas 14,17 …”

Central hypogonadism in Klinefelter syndrome: report of two cases and review of the literature

“…Finally, it has to be mentioned that, besides these rare cases, germ cell tumours [51][52][53][54], craniopharyngioma [55] and pituitary adenomas [56][57][58][59] have been reported in Klinefelter syndrome as causes of acquired hypopituitarism; therefore, an exhaustive diagnostic workup is always recommended in presence of HH to exclude organic diseases of the sellar region.…”

A Chinese Case of X-Linked Acrogigantism and Systematic Review

“…There are still no cases of gigantism in patients with trisomy X syndrome and Klinefelter syndrome, as well as no acromegaly in trisomy X syndrome patients. However, 2 cases of Klinefelter syndrome accompanied by acromegaly drew our interest [39,40]. Whether their conditions are related to their increased GPR101 gene, copy numbers remain unknown and need further study.…”