FD/MAS: Scoliosis is a complication of FD/MAS; risk factors and long-term outcomes are unknown. Bisphosphonates are used; however, the effect on scoliosis is unkown. To assess this, Cobb angles were measured, and variables associated with scoliosis progression identified. Of 138 subjects, 84 (61%) had scoliosis, including 55 (65%) classified as mild (Cobb angle >10 to 30 degrees), 11 (13%) as moderate (>30 to 45 degrees), and 18 (22%) as severe (>45 degrees). Total skeletal disease burden was highly associated with scoliosis severity (p<0.0001). Endocrinopathies associated with scoliosis included fibroblast growth factor 23 (FGF23)-mediated hypophosphatemia (p<0.001) and hyperthyroidism (p<0.001). Bone turnover markers, including osteocalcin and NTX-telopeptides, were associated with severe scoliosis (p<0.01). Associations were identified between Cobb angle and functional metrics, including leg length discrepancy (p<0.01), hip range of motion (p<0.05), and strength of the gluteus medius and maximus (p<0.01). Longitudinal analyses were conducted in 69 subjects who had serial radiographs over a median 4.9-year period (range, 0.9 to 14.7 years). Twenty-two subjects were treated with bisphosphonates; there was no difference in Cobb angle progression compared to untreated subjects (0.10 versus 0.53 degrees/year, p=0.36). Longitudinal data was available for 10 of 12 subjects treated with spinal fusion; one had instrumentation failure, but in nine subjects Cobb angles were stable with 6.1 years of follow-up (range, 0.9 to 14.7 years). Two fatalities from scoliosis-associated restrictive lung disease occurred in subjects managed non-operatively. Scoliosis occurs frequently in patients with polyostotic FD,and may be potentially fatal. The primary risk factor for progressive scoliosis is total skeletal disease burden. Treatable features that contribute to scoliosis progression include leg length discrepancy, FGF23-mediated hypophosphatemia, and hyperthyroidism. Current data do not support routine use of bisphosphonates to prevent progression of spinal curvature. Spinal fusion is frequently effective in providing long-term stability, and may be lifesaving. We investigated potential mechanisms of hearing loss in FD/MAS. Individuals underwent clinical, biochemical, computed tomographic, audiologic, and otolaryngologic evaluations. Conductive hearing loss was hypothesized to be associated with narrowing of the external auditory canal (EAC), FD involving the epitympanum, and FD crowding the ossicular chain. Sensorineural hearing loss was hypothesized to be associated with FD affecting the internal auditory canal (IAC) and otic capsule. Of the 130 study participants with craniofacial FD who were evaluated, 116 (89.2%) had FD that involved the temporal bone (median age, 19.6 years; range, 4.6-80.3 years; 64 female 55.2%), whereas 14 (10.8%) had craniofacial FD that did not involve the temporal bone. Of the 183 ears with temporal bone FD, hearing loss was identified in 41 ears (22.4%) and was conductive in 27 (65.9%), sensorineural in 12 (29.3%), and mixed in 2 (4.9%). Hearing loss was mild and nonprogressive in most participants. Whereas EACs were narrower in ears with FD (mean difference MD, 0.33 mm; 95% CI, 0.11-0.55 mm), this finding was associated with conductive hearing loss in only 4 participants. Fibrous dysplasia crowding of the ossicles was associated with conductive hearing loss (odds ratio OR, 5.0; 95% CI, 2.1-11.6). The IAC length was not different between ears with and without FD (MD, -0.37; 95% CI, -0.95 to 0.211); however, canals were elongated in ears with sensorineural hearing loss (MD, -1.33; 95% CI, -2.60 to -0.07). Otic capsule involvement was noted in 4 participants; 2 had sensorineural hearing loss. Both MAS-associated growth hormone excess (OR, 3.1; 95% CI, 1.3-7.5) and neonatal hypercortisolism (OR, 11; 95% CI, 2.5-55) were associated with an increased risk of hearing loss. Hearing loss in craniofacial FD is common and mild to moderate in most individuals. It typically arises from FD crowding of the ossicular chain and elongation of the IAC, whereas EAC stenosis and otic capsule invasion are less common causes. Individuals with craniofacial FD should undergo otolaryngologic evaluation and monitoring, including assessment to identify those with high-risk features. Mineral Homeostasis: hPTH therapy can effectively manage hypocalcemia in hypoparathyroidism. However, little is known about its ability to decrease the renal comorbidities: nephrocalcinosis (NC), nephrolithiasis (NL), and renal insufficiency. Urinary citrate (Ucit) promotes the solubility of urinary calcium (UCa); hypocitraturia is a risk factor for NC/NL. Twenty-four-hour UCa, Ucit, and UCa/Ucit were determined in 31 hypoparathyroid subjects receiving hPTH 1-34 therapy for up to 5 years. Before hPTH 1-34, the geometric least squares mean UCa was 346mg/day (normal <250) and Ucit was 500mg/day (normal 250-1190); UCa/Ucit was 0.67mg/mg. After 6 months of hPTH 1-34, UCa decreased (238, p<0.001), but with a greater decrease in Ucit (268, p<0.001), increasing UCa/Ucit, which became significant over time (p<0.001). After stopping hPTH 1-34 and resuming conventional therapy (follow-up; FU), compared to the last measures on hPTH 1-34, Ucit rose to 626 (p<0.001), reducing UCa/Ucit to 0.44, (p<0.05); UCa also rose (273), but was still lower than baseline (p<0.05). Daily hPTH 1-34 dose did not correlate with UCa, but was inversely related to Ucit, and directly related to UCa/Ucit (p<0.01). Mean blood bicarbonate decreased significantly on hPTH 1-34 and remained lower than baseline at FU (p<0.01). Mean eGFR increased on hPTH 1-34 (86 to 96mL/min/1.73m2 , p<0.001) and returned to baseline at FU. On renal imaging, 6 subjects did not have NC/NL, 8 had NC/NL prior to hPTH 1-34 that remained unchanged, and 16 developed new-onset (n=10) or progressive (n=6) NC/NL while on hPTH 1-34. Our data demonstrate that treatment with subcutaneous hPTH 1-34 may have an untoward effect of hypocitraturia and high UCa/Ucit ratio that may increase renal morbidity. With increasing use of PTH therapy in hypoparathyroidism, close monitoring and exploration for treatment of hypocitraturia seem warranted. Published 2018. This article is a U.S. Government work and is in the public domain in the USA. Tumor removal results in cure in TIO. However, because of high perioperative comorbidity, either from tumor location or host factors, surgery is sometimes not an option. Tumor destruction via cryoablation may be an effective option for inoperable PMTs. Three subjects with a confirmed diagnosis of TIO were studied. All three underwent cryoablation of suspected PMTs rather than surgery due to significant medical comorbidities or challenging anatomical location. Subject 3 had tumor embolization 24 hours prior to cryoablation because of the size and hypervascularity of the tumor. The success of the tumor cryoablation was defined by normalization of serum phosphate and FGF23. Cryoablation resulted in a rapid decrease in plasma intact FGF23 by 24 hours postprocedure in all three subjects (0, 2, and 9pg/mL, respectively) with normalization of blood phosphate by postprocedure day 3. Three-day renal tubular reabsorption of phosphate increased to 76%, 94%, and 95.2%, respectively; 1, 25(OH)2 vitamin D increased to 84, 138, and 196pg/ml, respectively. All three had dramatic clinical improvement in pain and weakness. Two subjects tolerated the procedure well with no complications; one had significant prolonged procedure-related localized pain. Although surgery remains the treatment of choice, cryoablation may be an effective, less invasive, and safe treatment for patients with difficult to remove tumors or who are poor surgical candidates.
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