Abstract
Background: Hereditary hypophosphatemic rickets is a debilitating disease with multiple skeletal abnormalities. Children exhibit rickets and growth failure, while adults exhibit bone pain, enthesopathy, HTN, and arthritis. Gene mutations involving renal phosphate reabsorption(PHEX, FGF23, SLC34A3) leads to renal phosphate wasting. Modes of inheritance include X-linked dominant (most common), autosomal dominant, and autosomal recessive. High dose oral phosphate supplements along with calcitriol are the mainstay of treatment. This can lead to complications of secondary hyperparathyroidism. Clinical Case: An 81-year-old Caucasian woman with PMH of X-linked dominant hypophosphatemic rickets (XLH), secondary osteoarthritis of both knees, HTN, and neuropathy was seen in the Endocrinology clinic. She was diagnosed with XLH 47 years ago and was taking calcitriol 0.5 mcg daily along with a phosphate supplement of 250 mg, 2 tablets 5 times a day. She underwent multiple corrective orthopedic procedures and bilateral knee replacements. On exam, she had short stature (height of 149.9 cm), arthritic changes of bilateral hand joints, and dentures. Starting in 2015, there was a rise in PTH to 101 pg/ml (normal 18.4-80 pg/ml). Over the next 4 years her PTH continued to rise to 182.6 pg/ml, 244.4 pg/ml, 350.6 in 2016, 2017, and 2019 respectively. A 24-hour urine collection revealed a calcium level of 175 mg (normal 100-250 mg/24 hours) and a phosphorus level of 2191 mg (normal 900-1300 mg/24 hours). In December of 2018, she developed hypercalcemia with a serum calcium level of 10.9 mg/dl(normal 8.5-10.5 mg/dl). We then tapered off calcitriol and decreased the phosphate supplements to TID. Despite these measures, her PTH continued to rise, but phosphorus remained normal. A Sestamibi scan showed hyperplasia of all four parathyroid glands, and a DXA scan showed normal bone mineral density. Serum alkaline phosphatase was normal. We decreased her phosphate supplements to BID and started cinacalcet at 30 mg BID. Conclusion: This case illustrates the challenges of primary and secondary hyperparathyroidism when treating XLH. It is proposed that an increased oral phosphate load transiently lowers ionized calcium in serum, which then stimulates PTH secretion. Increased mineralization of bone is another possible explanation of this phenomenon. Persistent parathyroid stimulation can cause hyperplasia of parathyroid glands, nephrocalcinosis, hypertension, and renal failure. Early identification, temporary discontinuation of oral phosphate, and an increase of calcitriol will lower PTH. The FDA approved burosumab for the treatment of XLH in 2018. Future studies are needed to see if burosumab therapy prevents the above complications associated with traditional treatment.