Endocrine Abstracts

JOINT2902

Klinefelter’s syndrome is the most common genetic form of male hypogonadism. However, the overt phenotype does not become apparent until after puberty. During childhood and even early puberty, pituitary-gonadal function is relatively normal in 47XXY subjects. Clinical manifestations of androgens deficiency may vary and it’s related to the degree of decreased testosterone production and androgens alterations. Thus there are patients with no secondary sexual development; others cannot be distinguished from healthy individuals. Even though many of the undiagnosed causes are due to failure to recognize Klinefelter syndrome, the majority of missed diagnoses are due to minimally abnormal phenotype of Klinefelter syndrome.

Case Report: A 65-year-old male was diagnosed in May 2023 with multinodular goiter and bilateral macronodular adrenal hyperplasia based on CT findings, later on confirmed with ACTH-independent Cushing’s syndrome (basal cortisol=16.10 ug/dl, ACTH=1.50 pg/ml, cortisol after 2x2DXM=18.18 ug/dl), with secondary diabetes mellitus HbA1c=6.9% and hypertension. At that time primary hypogonadism was diagnosed: testosterone=1.08 ng/ml, FSH=31.54 mIU/ml, LH=25.26 mIU/ml. He underwent laparoscopic left adrenalectomy on November 2023 with significant clinical improvement, normalization of blood pressure and remission of diabetes (Hba1c= 5.7%). Although post-operatively patient had an apparent normalization of adrenocortical function, he presented adrenocortical insufficiency (ACTH=4 pg/ml, cortisol 8AM=4.87ug/dl) requiring initiation of low-dose hydrocortisone replacement therapy. He was also found with primary hypogonadism, (testosterone=1.05 ng/ml, FSH=36.81mUI/ml, LH=40.27mUI/ml). He reported a history of surgical single testis, but had never undergone further investigation for gonadal dysfunction. Karyotyping was performed given the biochemical findings and clinical suspicion, confirmed the result-47XXY, diagnostic of Klinefelter syndrome. The patient’s long undiagnosed hypogonadism together with Cushing’s syndrome had likely contributed to his osteoporosis (DXA L₁-L₄T score=-4.0 DS). Management was done by administration of ibandronate and transdermic testosterone.

Conclusions: This case illustrates the complications that can arise from the association between Cushing’s disease and delayed diagnosis of hypogonadism. One reason for the delayed diagnosis of Klinefelter’s syndrome was that hypogonadism, is a feature common to both Klinefelter’s and Cushing’s syndrome, which masked it’s recognition. The overlapping metabolic and hormonal clutter in Cushing’s syndrome can hide clinical presentation of Klinefelter’s syndrome, leading to delayed recognition and treatment of osteoporosis, but in the absence of fractures, most likely to have a positive outcome and improvement in bone mineral density. Rapid approach of Klinefelter in older patients may improve long-term results by addressing associated metabolic, cardiovascular and bone complications.