X-linked hypophosphatemia (XLH) is the most common monogenetic cause of chronic hypophosphatemia, characterized by rickets and osteomalacia. Disease manifestations and treatment of XLH patients in... Show moreX-linked hypophosphatemia (XLH) is the most common monogenetic cause of chronic hypophosphatemia, characterized by rickets and osteomalacia. Disease manifestations and treatment of XLH patients in the Netherlands are currently unknown. Characteristics of XLH patients participating in the Dutch observational registry for genetic hypophosphatemia and acquired renal phosphate wasting were analyzed. Eighty XLH patients, including 29 children, were included. Genetic testing, performed in 78.8% of patients, showed a PHEX mutation in 96.8%. Median (range) Z-score for height was - 2.5 (- 5.5; 1.0) in adults and - 1.4 (- 3.7; 1.0) in children. Many patients were overweight or obese: 64.3% of adults and 37.0% of children. All children received XLH-related medication e.g., active vitamin D, phosphate supplementation or burosumab, while 8 adults used no medication. Lower age at start of XLH-related treatment was associated with higher height at inclusion. Hearing loss was reported in 6.9% of children and 31.4% of adults. Knee deformities were observed in 75.0% of all patients and osteoarthritis in 51.0% of adult patients. Nephrocalcinosis was observed in 62.1% of children and 33.3% of adults. Earlier start of XLH-related treatment was associated with higher risk of nephrocalcinosis and detection at younger age. Hyperparathyroidism longer than six months was reported in 37.9% of children and 35.3% of adults. This nationwide study confirms the high prevalence of adiposity, hearing loss, bone deformities, osteoarthritis, nephrocalcinosis and hyperparathyroidism in Dutch XLH patients. Early start of XLH-related treatment appears to be beneficial for longitudinal growth but may increase development of nephrocalcinosis. Show less
High plasma fibroblast growth factor 23 (FGF23) and low potassium intake have each been associated with incident hypertension. We recently demonstrated that potassium supplementation reduces FGF23... Show moreHigh plasma fibroblast growth factor 23 (FGF23) and low potassium intake have each been associated with incident hypertension. We recently demonstrated that potassium supplementation reduces FGF23 levels in pre-hypertensive individuals. The aim of the current study was to address whether 24-h urinary potassium excretion, reflecting dietary potassium intake, is associated with FGF23, and whether FGF23 mediates the association between urinary potassium excretion and incident hypertension in the general population. At baseline, 4194 community-dwelling individuals without hypertension were included. Mean urinary potassium excretion was 76 (23) mmol/24 h in men, and 64 (20) mmol/24 h in women. Plasma C-terminal FGF23 was 64.5 (54.2-77.8) RU/mL in men, and 70.3 (56.5-89.5) RU/mL in women. Urinary potassium excretion was inversely associated with FGF23, independent of age, sex, urinary sodium excretion, bone and mineral parameters, inflammation, and iron status (St. beta -0.02, p < 0.05). The lowest sex-specific urinary potassium excretion tertile (HR 1.18 (95% CI 1.01-1.37)), and the highest sex-specific tertile of FGF23 (HR 1.17 (95% CI 1.01-1.37)) were each associated with incident hypertension, compared with the reference tertile. FGF23 did not mediate the association between urinary potassium excretion and incident hypertension. Increasing potassium intake, and reducing plasma FGF23 could be independent targets to reduce the risk of hypertension in the general population. Show less
In patients with sporadic PHPT, the rate of persistence after initial PTx is 7% and that of recurrence none. In the case of persistent PHPT, the sensitivity of the widely used, non-invasive Tc99m... Show moreIn patients with sporadic PHPT, the rate of persistence after initial PTx is 7% and that of recurrence none. In the case of persistent PHPT, the sensitivity of the widely used, non-invasive Tc99m-MIBI-SPECT imaging technique is decreased and is significantly lower than that of the invasive technique of selective venous sampling for PTH. Chronic excess of PTH has a catabolic effect on bone, leading to mineral depletion of bone. Patients with pre-operative radiological signs of severe PTH-associated bone disease are at risk of developing hungry bone syndrome after surgery, which may be prevented by pre-operative treatment with bisphosphonates and 1,25(OH)2D. PTH inhibits sclerostin production and stimulates FGF23 production, presumably to counterbalance its own actions on bone and on 1,25(OH)2D, resulting in novel feedback loops. In contrast to sporadic PHPT, recurrent PHPT does occur in patients with parathyroid carcinoma. In these patients, downregulation of CASR, HRPT2/CDC73 mutations and global loss of parafibromin are strong negative determinants of the disease-free survival and overall survival. Recent progresses in surgical and medical treatment of patients with parathyroid carcinoma have made it possible to secure longer survival, even in patients with tumors demonstrating 2 of the 3 identified molecular negative prognostic factors. Show less
