Vitamin D Levels Predict Hypocalcemia After Thyroid Cancer Treatment

Preoperative vitamin D deficiency (VDD) is associated with postoperative symptomatic hypocalcemia in patients with thyroid cancer undergoing total thyroidectomy (TT) plus central compartment neck dissection (CCND), according to an oral presentation by Kee-Hyun Nam, MD, PhD, at the 2014 American Thyroid Association (ATA) Annual Meeting.

"Although some studies have reported that preoperative vitamin D deficiency is a risk factor for hypocalcemia after total thyroidectomy in patients with nontoxic multinodular goiter or Graves' disease, the association between VDD and postoperative hypocalcemia in thyroid cancer patients undergoing TT plus central compartment neck dissection remains unclear,” explained Nam, of the department of surgery at Severance Hospital, Yonsei University Health System in Seoul, South Korea. “We evaluated whether preoperative vitamin D deficiency was associated with postoperative symptomatic hypocalcemia."

According to World Health Organization (WHO) criteria, vitamin D levels below 10 ng/mL are defined as deficient, and vitamin D levels below 20 ng/mL are defined as insufficient. The prevalence of vitamin D insufficiency in Korea is high, affecting 47.3% of males and 64.5% of females. The results of a retrospective study conducted by Nam's institution found that, using these definitions, 25.7% of patients (104/404) had vitamin D deficiency and 52.0% of patients (210/404) had vitamin D insufficiency.

To determine whether or not there was, in fact, an association between preoperative vitamin D deficiency and the development of postoperative hypocalcemia, this study prospectively collected data from 267 consecutive thyroid cancer patients who underwent TT with CCND between September 2012 and May 2014. Patients were categorized by preoperative vitamin D levels as either deficient (<10 ng/mL) or not deficient (≥10 ng/mL). Symptomatic hypocalcemia was defined as the presence or signs or symptoms such as muscle cramps or spasms and a serum calcium level less than 8.2 mg/dL.

Overall, patients with thyroid cancer exhibited a high prevalence of vitamin D deficiency or insufficiency (25% and 52%, respectively). Preoperative vitamin D deficiency was associated with a significant increase in the rate of postoperative symptomatic hypocalcemia in patients with thyroid cancer undergoing total thyroidectomy with CCND (43.8% vs 30.4%, P = .043).

Postoperative serum parathyroid hormone (PTH) level is still the main predictor of postoperative hypocalcemia, based on a positive correlation between postoperative PTH and calcium level. Compared with patients without vitamin D deficiency, those with vitamin D deficiency were significantly more likely to develop symptomatic hypocalcemia in cases of postoperative intact parathyroid hormone (iPTH) levels less than 15 pg/mL (77.5% vs 53.2, P = .008). In an effort to identify an appropriate preoperative vitamin D threshold level, the investigators found that preoperative vitamin D levels greater than 20 ng/mL reduced the risk of symptomatic hypocalcemia by 72% (P = .003).

"In conclusion, vitamin D deficiency is significantly associated with postoperative, symptomatic hypocalcemia in thyroid cancer patients undergoing TT plus CCND. In fact, vitamin D deficiency could predict symptomatic hypocalcemia in cases of postoperative iPTH levels <15 pg/mL,” said Nam. “We suggest that preoperative supplementation of oral vitamin D be considered as a way to minimize postoperative symptomatic hypocalcemia in thyroid cancer patients with preoperative vitamin D deficiency."

Postoperative hypocalcemia is the most common complication after TT, with transient hypocalcemia occurring in about 30% to 50% of patients and permanent hypocalcemia, lasting 6 months or longer, occurring in 0.5% to 2% of patients. In addition to uncomfortable symptoms, postoperative hypocalcemia also results in longer hospital stays and ongoing laboratory tests.

The parathyroid glands control calcium levels. Vitamin D₃ is a principal regulator of both PTH secretion and the proliferation of parathyroid cells. The parathyroid glands have both vitamin D and calcium sensing receptors that together work as a part of a negative-feedback system. Patients with vitamin D deficiency absorb less calcium from the gastrointestinal tract, making them more reliant on PTH-mediated bone and nephron resorption of calcium. Temporary reduction of PTH secretion after TT predisposes patients with vitamin D deficiency to develop more marked hypocalcemia than those with normal vitamin D levels.

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