PARADOX Study Quantifies Clinical, Social, and Economic Burden of Hypoparathyroidism

Hypothyroidism is a rare endocrine disorder caused by insufficient or absent parathyroid hormone, leading to hypocalcemia and hyperphosphatemia. Its causes are varied, ranging from congenital to acquired. Patients with hypoparathyroidism experience a range of short-term symptoms and long-term complications; however, information on the overall burden of illness and morbidity associated with hypoparathyroidism is limited.

To assess the clinical, social, and economic implications of hypoparathyroidism from the affected patients' perspective, the study authors—Bart L. Clarke, MD; James Sanders, and Hjalmar Lagast, MD—conducted the Patients' Attitudes and Responses About Hypoparathyroidism Toleration Explored (PARADOX) study in patients using standard symptomatic management therapy. The study authors concluded that “despite the current standard of treatment (oral calcium and active vitamin D), patients with hypoparathyroidism have a high burden of illness and experience a broad spectrum of symptoms, with multifaceted effects on their lives.”

The results of the PARADOX study were presented at the 83rd Annual Meeting of the American Thyroid Association, in San Juan, Puerto Rico, on October 18, 2013. “To our knowledge, this is the largest and most comprehensive study conducted to assess the impact of disease in patients with hypoparathyroidism,” the authors stated.

The PARADOX Web-based survey consisted of a questionnaire that was filled out by adult US patients who had been diagnosed with hypoparathyroidism for six months or more, had low-serum calcium or were using medication for management of low-serum calcium at screening, and were not diagnosed with pseudohypoparathyroidism or pseudopseudohypoparathyroidism. The patient population had had hypoparathyroidism for an average of 13 years. Eligible participants answered questions regarding demographics, diagnosis, and management; initial perceptions of hypoparathyroidism at diagnosis; current symptoms, perceptions, and therapy; acute episodes and comorbidities; and impact of disease on employment, personal and social life, and well-being.

Seventy-nine percent of the 374 patients surveyed described the severity of their condition as moderate to severe, and most of the cases occurred as a result of a surgical event. Participants were asked to indicate which of 38 symptoms associated with hypoparathyroidism (organized into three domains: physical, cognitive, and emotional) they had experienced in the last 12 months while taking current standard management therapies. The top symptoms reported by more than 50% of patients were fatigue (82%), muscle pain or cramping (78%), paresthesia (76%), tetany (70%), joint or bone pain (67%), pain or weakness in extremities (53%), brain fog or mental lethargy (72%), inability to focus or concentrate (65%), memory loss or forgetfulness (61%), sleep disturbances (57%), anxiety, fear, and inner unrest (59%), and feelings of sadness and depression (53%).

Participants were also asked to select comorbidities experienced from a provided list of six medical conditions. Comorbidities were experienced by 69% of the patients. The most frequently reported comorbidities were cardiac arrhythmias and kidney stones.

Participants reported visiting a mean of six physicians before and after diagnosis and visiting their current managing physician (endocrinologist, 72%; primary care physician, 21%) four times per year on average. Some of the participants' perceptions and attitudes at diagnosis reflect that most of them felt unprepared to deal with and manage their hypoparathyroidism (56%) and understood that hypoparathyroidism was not a very serious condition (41%), or that it was a relatively easy condition to manage (33%). After diagnosis, participants reported that they perceived that most physicians do not understand hypoparathyroidism (79%) and that they were concerned about the long-term complications of their hypoparathyroidism medications (75%). Moreover, 63% of participants stated that hypoparathyroidism is harder to control and to deal with compared to what the physician initially told them to expect, and that controlling their hypoparathyroidism turned out to be harder than they expected (60%). These perceptions and attitudes, among others, were measured on a 7-point Likert scale.

The survey concluded that, despite current management regimens, 72% of patients experienced more than 10 symptoms in the 12 months preceding the survey, for a mean of 13 hours per day. Also, 79% reported hospital or emergency room visits due to hypoparathyroidism (the annualized rate for them in both acute-episode settings exceeded the national average for the general population: 0.8 vs. 0.4 for emergency room visits and 1.3 vs. 0.6 for hospital days). In addition, 45% reported significant interference with daily life, including the inability to perform some household activities (85%) and disease-associated change in employment status (20%).