Endocrine Abstracts

Background: Patients with Klinefelter’s syndrome (KS) present a high prevalence of osteopenia, osteoporosis and fragility fractures. Several factors may contribute to skeletal fragility, e.g. hypogonadism, derangements in vitamin D metabolism, reduced testicular secretion of Insulin-like Factor 3. However, phosphate metabolism has never been investigated.

Methods: A retrospective analysis was conducted to investigate prevalence and characteristics of hypophosphatemia (HypoP, serum phosphate ≤2.7 mg/dl) among adult KS patients followed-up at a tertiary endocrinology center in Milan, Italy. Among 100 patients, 86 had at least one phosphate assessment and were included in the analysis. HypoP was defined as recurrent/persistent if confirmed in ≥2 assessments. Moreover, 36 KS patients (age 32 [26–43] years) were consecutively enrolled in a cross-sectional study and compared to 32 male healthy controls (age 29 [26–40], P=0.49). Blood and urine parameters of phosphate metabolism, including tubular resorption of phosphate (TmP/GFR), were assessed in both groups. Hip, femoral neck and lumbar spine bone mineral density (BMD) was evaluated in KS patients by dual-energy X-ray absorptiometry.

Results: In the retrospective analysis, 20 out of 86 (23%) patients presented mild-moderate HypoP in at least one assessment. HypoP was recurrent/persistent in 9 patients (10%). No apparent causes of HypoP were identified. Patients with HypoP were older (43 [40–53] vs 31 [26–46] years, P<0.001) and had a greater phosphate urinary loss (TmP/GFR 3 [2.7-3.7] vs 2.4 [2.2-2.9] mg/dl, P=0.002) than patients with normal phosphate, but prevalence of low BMD was similar (5/21 vs 14/66, P=0.9). In the cross-sectional study, KS patients displayed lower testosterone concentrations than controls (4.8 [3.4–5.6] vs 5.1 [4.6–7.2] ng/ml, P=0.03), but comparable levels of phosphate (3.4 [0.7] vs 3.6 [0.6], P=0.18), 25OH-vitamin-D, parathyroid hormone and alkaline phosphatase. HypoP was observed in 7/36 KS (19%) and 3/32 controls (9%, not-significant). However, KS patients displayed a statistical trend for greater urinary phosphate excretion (TmP/GFR 2.9 [2.6–3.3] vs 3.3 [2.9–3.8], P=0.07). Phosphate metabolism parameters were not associated to testosterone concentrations or BMD. TmP/GFR correlated inversely with 25OH-vitamin-D (r=-0.34, P=0.046).

Conclusion: Persistent/recurrent, unexplained hypoP can be observed in 10% of KS patients. In KS a trend to increased urinary phosphate excretion is observed. However, these mild derangements in phosphate metabolism are not associated with BMD. Interestingly, the finding that phosphate urinary excretion is associated with 25OH-vitamin-D may suggest a role for FGF-23. This phosphatonin, indeed, inhibits both renal 1alpha-hydroxilaton of 25OH-vitamin-D and tubular resorption of phosphate, and should be evaluated in further studies.