If confirmed in future studies, the findings may help clinicians adjust their vitamin D recommendations, suggest lifestyle changes to lose weight, or consider early therapy with parathyroid hormone (PTH) for overweight patients, the researchers said.
Their study, “Body mass index predicts resistance to active vitamin D in patients with hypoparathyroidism,” was published in the journal Endocrine.
Chronic hypoparathyroidism mostly results from accidental damage of the parathyroid glands, responsible for producing PTH, during surgery to remove the thyroid.
Low levels of PTH lead to abnormally low calcium levels in the blood, a condition termed hypocalcemia.
Primary treatment to raise calcium levels normally consists of calcium and calcitriol supplements. However, doctors prescribe doses of calcitriol (activated vitamin D) on a case-by-case basis, reflecting the significant variability in the amount of supplementation needed to correct calcium insufficiency and provide clinical improvements.
In fact, many patients respond poorly to conventional therapy or need marked dose increases, risking side effects and poor adherence to treatment.
So far, clinicians have no way of predicting resistance to conventional treatment, which has hampered patient follow-up and the decision about whether to increase dose.
In an effort to identify predictors of resistance to calcitriol treatment, researchers from Italy and the U.S. followed 71 patients newly diagnosed with hypoparathyroidism (68 post-surgical, three due to autoimmune disease). The investigators evaluated demographic, clinical, and anthropometric characteristics (body shape and composition such as height and weight) at diagnosis and looked for relationships between these characteristics and resistance to treatment with calcitriol.
Patients were followed for at least one year and were on stable treatment with calcium and calcitriol for six months or more. Resistance to conventional therapy was defined as needing at least one microgram of calcitriol daily.
Results revealed no differences in age, sex, and disease duration between the 24 treatment-resistant patients and the 47 who experienced a better response.
Then, the researchers grouped patients according to their BMI: normal weight (under 25 Kg/m2), overweight (25 to 29.9 Kg/m2); obesity class I (30 to 34.9 Kg/m2), class II (35 to 39.9 Kg/m2), and class III (at least 40 Kg/m2).
In this analysis, the team found that BMI was significantly higher in patients resistant to calcitriol — 28 versus 25 kg/m2. Further tests revealed that BMI was independently associated with resistance to conventional therapy.
No significant differences in daily supplementation of calcium were observed between BMI groups.
Among the 24 treatment-resistant patients, 79% were obese and 21% had a normal BMI.
“This is the first study showing that elevated BMI at diagnosis, a variable not related to the disease per se, can predict calcitriol resistance in [hypoparathyroidism],” the researchers wrote.
Patients who weigh more seem to require higher doses of calcitriol, which might be explained by the accumulation of vitamin D in adipose tissue (fat), the team added.
Although larger studies are needed to confirm these observations, these findings may guide clinicians to adapt calcitriol doses to BMI and help patients reduce weight by advising changes in their lifestyle.
If changes to calcitriol doses and lifestyle are not effective, particularly in overweight or obese patients, doctors may consider add-on therapy with low-dose Natpara (Natpar in Europe), a lab-made version of PTH hormone, the scientists wrote. Natpara is a treatment for adults with chronic hypoparathyroidism not controlled well with conventional therapy.