Appeal type: Experimental/Investigational
Decision: Upheld Decision of Health Plan

Nature of Statutory Criteria/Case Summary: An enrollee has requested reimbursement for a parathyroid allotransplant procedure. Hypoparathyroidism describes underactive parathyroid gland function, which results in deficiency of parathyroid hormone (PTH) production. The role of PTH is to regulate blood calcium levels. Without adequate PTH production, calcium levels decline, resulting in hypocalcemia, which causes variable symptoms including muscle cramps, a tingling sensation around the mouth or in the extremities, weakness, seizures, brain fog, irregular heartbeats, and in some cases, deposits of soft tissue calcium in the brain, kidney, joint, eyes, skin and blood vessels. Long-term uncontrolled hypoparathyroidism may lead to skeletal abnormalities that can affect bone strength, leading to a higher risk of bone fractures. Brandi and colleagues report that conventional treatment of hypoparathyroidism included calcium supplements, magnesium supplements, vitamin D analogs, and in some cases phosphate binders, thiazide diuretics, and recombinant human (rh) PTH therapy.  However, treatment requires a fine balance between improving levels of calcium in the blood and avoiding excess levels of calcium in the urine, or hypercalciuria. The authors further note that the six goals of chronic management therapy of hypoparathyroidism are, (1) to prevent signs and symptoms of hypocalcemia; (2) to maintain the serum calcium concentration slightly below normal (i.e., no more than 0.5 mg/dL below normal) or in the low normal range; (3) to maintain the calcium-phosphate product to below 55 mg2/dL2 (4.4 mmol2/L2); (4) to avoid hypercalciuria; (5) to avoid hypercalcemia; and (6) to avoid renal (nephrocalcinosis/nephrolithiasis) and other extra skeletal calcifications. Mannstadt and colleagues report that achieving these goals with the available oral therapies, such as high-dose oral calcium and active vitamin D, can be challenging, in particular due to restrictions on the option to prescribe recombinant PTH. Parathyroid allotransplantation involves the implantation of donor parathyroid tissue into the recipients skeletal muscle. The goal of the transplant is restoration of normal physiologic parathyroid function. There is significant heterogeneity in parathyroid tissue harvest, processing, and transplantation technique, donor tissue origin, use of induction and maintenance immunosuppressive regimens, and recipient patient characteristics and graft survival. One drawback to parathyroid allotransplantation is the potential need for life-long immunosuppression. Kim and colleagues report that the optimal technique and role of immunosuppression in parathyroid allotransplantation remain unclear. Immunosuppressant medications may carry significant risk and require frequent monitoring. Currently, parathyroid allotransplant as an option to treat hypoparathyroidism is not incorporated into guidelines in the United States on treatment of hypoparathyroidism. In a systematic review of 24 published studies of parathyroid allotransplant, Kim and colleagues found that amongst 177 patients without a history of previous transplant, the pooled graft survival rate was 29.9%. In a review of case studies, Parameswaran and colleagues reported a mean allograft survival of 41% at follow-up of one year. The authors noted the widely variable surgical techniques and immunosuppression regimens as challenges in comparing case reports, concluding that the long-term benefit and harms of allotransplantation are still unclear due to the clinical and statistical heterogeneity observed among the studies. While hypoparathyroidism may be a challenging condition to treat due to limited medical therapies that, in some cases, may not adequately control the condition, given the lack of randomized controlled trials and data supporting improved outcomes with parathyroid allotransplantation, the service at issue was not likely to be more beneficial for treatment of hypoparathyroidism than the available standard therapy. Therefore, the parathyroid allotransplant procedure was not likely to have been more beneficial for treatment of the patients condition than any available standard therapy.Findings:  Three of the three physician reviewers found the parathyroid allotransplant procedure at issue was not likely to have been more beneficial for treatment of the patients medical condition than any available standard therapy.Final Result: The reviewers determined that the service at issue was not likely to have been more beneficial for treatment of the patients medical condition than any available standard therapy. Therefore, the Health Plans denial should be upheld. Credentials/Qualifications: Physician reviewers 1, 2, and 3 are board certified in internal medicine with sub-specialty certification in endocrinology, diabetes, and metabolism and are actively practicing. The reviewers are experts in the treatment of the enrollees medical condition and knowledgeable about the proposed treatment through recent or current actual clinical experience treating those with the same or a similar medical condition.