MON-529 Body Mass Index Predicts Resistance To Active Vitamin D In Patients With Hypoparathyroidism

Abstract

Persistent hypoparathyroidism (PH) is a severe disease mostly occurring as a surgical complication of total thyroidectomy. Calcium and calcitriol are the most common and low cost therapies. However, several patients (pts) do not achieve control of the disease under this conventional therapy or need heavy up-titration, with high risk of poor compliance and side effects. Recently, human recombinant PTH (rhPTH) has been introduced in clinical practice and is indicated, due to its elevated cost, only in PH pts “resistant” to conventional therapy. Surprisingly, no predictor of risk of resistance has yet been identified: this could be of paramount importance to guide ad hoc follow-up and clinical management of PH. To this end, in this retrospective study we evaluated the anthropometric characteristics assessed at the diagnosis of PH, in 84 consecutive pts (79 with post-surgical, 5 with autoimmune PH). All pts were followed-up for at least one year, and were under stable conventional treatment with active vitamin D analog and calcium from at least six months. In keeping with recent literature, we defined as resistant to conventional therapy those pts in need to take 1 µg of calcitriol daily or more. We found no difference in age (57±13 vs 56±13 yrs., p=NS), sex (F/M: 48/9 vs 23/4, p=NS), and disease duration (7 IQ: 4-13 vs 11 IQ: 7-17 yrs.; p=NS), between non-resistant and resistant groups, respectively. Conversely, body mass index (BMI) was higher in resistant pts (28±5 vs 25±5 kg/m2, p=0.017). Furthermore, logistic regression analysis showed that BMI was independently associated with resistance to conventional therapy (OR 1.13, 95% CI 1.02-1.26; p=0.02), in face of similar serum calcium levels obtained by therapy (8.7 vs 8.9 mg/dl, p=NS). After categorizing the pts according to BMI, we observed that three quarters of pts non-resistant to active vitamin D (23/31) were normal weight, compared to 8/31 obese pts (p=0.0001); whereas proportion of obese among resistant was more than double (6/25) vs non-resistant pts (5/47). This is the first study showing that elevated BMI at diagnosis, a variable not related to the disease per se but casually occurring, can predict active vitamin D resistance in PH. This finding is in agreement with evidences of reduced expression of vitamin D receptor in adipose tissue. Moreover, the lipophilic nature of vitamin D may be associated with a greater proportion of stored vs circulating vitamin D in obese pts. If the predictive power of BMI will be confirmed by larger studies, our data may help clinicians in three ways: 1. Adapt from the beginning the active vitamin D dose, and the schedule of eventual dose escalation, to BMI; 2. Advise towards lifestyle modifications, never previously recommended by guidelines in this setting, leading to weight loss in PH; 3. If body weight reduction is not obtained, consider an earlier switch to rhPTH in overweight/obese PH pts resistant to active vitamin D.