The role of fibroblast growth factor 23 for hypophosphatemia and abnormal regulation of vitamin D metabolism in patients with McCune?Albright syndrome

Abstract

McCune-Albright syndrome (MAS) is sometimes complicated by hypophosphatemia and abnormally low levels of 1,25(OH)(2)D in the presence of hypophosphatemia. Recently, fibroblast growth factor 23 (FGF-23) was reported as a phosphaturic and a causal factor of abnormal vitamin D metabolism. This abnormal phosphate and vitamin D metabolism is well known to be found in oncogenic and X-linked hypophosphatemia. We furthermore reported increased circulating plasma FGF-23 levels in patients with oncogenic and X-linked hypophosphatemia. To determine whether FGF-23 may be involved in the pathogenesis of MAS, we measured plasma FGF-23 levels in six MAS patients. As a control for hypophosphatemia, we also investigated the plasma FGF-23 levels in two patients with hereditary hypophosphatemic rickets with hypercalciuria (HHRH). We also investigated the correlation of plasma FGF-23 levels with serum phosphate and 1,25(OH)(2)D levels after short-term pamidronate therapy in three MAS patients. Plasma FGF-23 levels were significantly increased in patients with MAS compared to normal controls, whereas they were not increased in HHRH patients. Serum phosphate levels of the MAS patients were significantly lower than those observed in normal controls. Plasma FGF-23 levels showed significant negative correlation with serum phosphate concentrations. In three MAS patients, pamidronate therapy decreased plasma FGF-23 levels, which showed significant negative correlation with serum 1,25(OH)(2)D concentrations. These data suggested that FGF-23 is a possible causal factor for hypophosphatemia and abnormal vitamin D metabolism in MAS.

Anti-FGF-23 neutralizing antibodies ameliorate muscle weakness and decreased spontaneous movement of Hyp mice

“…(1)(2)(3)(4) 2 D levels. (7) However, excess actions of FGF-23 cause hypophosphatemic rickets/ osteomalacia, including X-linked hypophosphatemic rickets/ osteomalacia (XLH), (8,9) autosomal dominant and recessive hypophosphatemic rickets/osteomalacia (ADHR and ARHR), (10)(11)(12) tumor-induced rickets/osteomalacia (TIO), (8,9) hypophosphatemic rickets/osteomalacia associated with McCune-Albright syndrome/fibrous dysplasia, (13,14) and hypophosphatemic diseases caused by intravenous administration of iron polymaltose. (15,16) Hypophosphatemic rickets/osteomalacia usually has been treated by oral phosphate and active vitamin D 3 .…”

Fibroblast Growth Factor-23 (FGF23) in Patients with Transient Hypoparathyroidism: Its Important Role in Serum Phosphate Regulation

“…Therefore, phosphate homeostasis is sometimes disturbed in favor of maintaining calcium homeostasis in clinical settings. A new class of phosphate regulating factor, fibroblast growth factor-23 (FGF23), has been discovered through studies of phosphate-wasting disorders such as X-linked hypophosphatemia [1,2], autosomal dominant hypophosphatemic rickets [3], tumor-induced osteomalacia [4][5][6][7], and McCune-Albright syndrome [8,9]. FGF23 plays an important role in phosphate homeostasis via regulation of type IIa sodium-phosphate cotransporter and 1α-hydroxylase of 25-hydroxyvitamin D [10].…”

Severe arterial hypertension: a possible complication of McCune-Albright syndrome

“…The decrease in guanosine triphosphatase (GTPase) activity due to this mutation results in increases in cyclic adenosine 3′,5′-monophosphate (cAMP) levels in endocrine organs and leads to increases in the activity of Gsα proteinassociated hormones, including luteinizing hormone (LH), thyroid-stimulating hormone (TSH), adrenocorticotropin (ACTH), and growth hormone-releasing hormone (GHRH) [13]. In addition to hormonal action, the overproduction of interleukin-6 and fibroblast growth factor (FGF)-23 caused by the increased cAMP synthesis due to the activating mutation of Gsα protein is involved in increases in bone resorption and in hypophosphatemia, respectively, as we have previously reported [22,23].…”