Vitamin D Supplements for Hypocalcemia in Thyroid Cancer

Nancy A Melville

November 06, 2014

SAN DIEGO — Preoperative vitamin D deficiency significantly increases the risk for postoperative hypocalcemia in thyroid-cancer patients undergoing total thyroidectomy and central compartment neck dissection (CCND), according to new research presented here at the 2014 Annual Meeting of the American Thyroid Association.

While vitamin D deficiency has been previously linked to postoperative hypocalcemia following total thyroidectomy in Graves' disease and nontoxic multinodular goiter patients, the role of the deficiency in thyroid-cancer patients has been less explored.

"We found that vitamin D deficiency is significantly associated with postoperative symptomatic hypocalcemia in thyroid-cancer patients undergoing total thyroidectomy with CCND," said first author Dr Kee-Hyun Nam (Severance Hospital, Seoul, Korea).

"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," Dr Nam added.

Asked to comment, Dr John D Casler (Mayo Clinic Jacksonville, Florida) said the study helps shed light on the complicated roles of vitamin D and parathyroid-hormone [PTH] levels in postthyroidectomy hypocalcemia.

Both this study and a poster he presented appear to confirm that low postoperative PTH levels are predictive of hypocalcemia, with the suggestion that vitamin D supplementation may play a role in alleviating this.

"I thought [Dr Nam's] paper was excellent," he added. "It provided yet another piece of evidence regarding the interconnectivity of vitamin D, serum calcium, and parathyroid hormone [PTH]."

Low PTH Strongest Predictor, but Vitamin D Status Is Key, Too

Dr Nam and colleagues studied 267 thyroid-cancer patients who underwent a total thyroidectomy and CCND; 73 were defined as vitamin D deficient preoperatively (vitamin D level of less than 10 ng/mL), and the remaining 194 were not (vitamin D level of 10 ng/mL or higher).

The rate of postoperative symptomatic hypocalcemia (defined as serum calcium levels of less than 8.2 mg/dL along with symptoms or signs of hypocalcemia) was higher in the group that was vitamin D deficient preoperatively than in the group that was not (43.8% vs 30.4%; P = .043).

Low postoperative serum parathyroid-hormone level (less than 15 pg/mL) was the strongest predictor of hypocalcemia based on the need for IV calcium infusion (P < .001). But preoperative vitamin D deficiency was also a predictive factor for symptomatic hypocalcemia (P = .007), with an odds ratio of 3.00.

And those with low postoperative parathyroid-hormone levels had significantly higher rates of symptomatic hypocalcemia if they were also vitamin D deficient (77.5% vs 53.2% in the nondeficient group; P = .008).

The known interactions between vitamin D and PTH help explain the possible mechanisms leading to hypocalcemia, Dr Nam explained.

"Parathyroid glands control calcium levels, and vitamin D3 is a principal regulator of both parathyroid secretion and the proliferation of parathyroid cells," he said.

Patients who are vitamin D deficient meanwhile absorb less calcium from the gut, making them more reliant on parathyroid-mediated bone resorption of calcium.

As there is often a temporary reduction of PTH secretion after total thyroidectomy, this "predisposes vitamin D deficient patients to more marked hypocalcemia than in individuals with normal vitamin D levels," Dr Nam explained.

Vitamin D deficiency could therefore predict symptomatic hypocalcemia in cases of low postoperative PTH levels — a normal preoperative vitamin D level of 20 ng/mL or greater was associated with as much as a 72% reduced risk for symptomatic hypocalcemia compared with those with vitamin D deficiency (P = .003) in the study, he and his colleagues note.

Calcium Supplementation Based on Parathyroid-Hormone Levels

Dr Casler meanwhile coauthored a separate poster presentation at the meeting describing his clinic's own experience in tackling postthyroidectomy hypocalcemia.

They implemented a protocol in 2013 whereby calcium supplementation with Citracal (Bayer HealthCare) and Rocaltrol (Roche) was given as deemed appropriate based on 1-hour postoperative serum PTH levels (whereby patients were stratified as at low, medium, and high risk for hypocalcemia).

The patients were given the oral calcium with or without vitamin D supplementation;  serum calcium levels were checked weekly, and calcium/vitamin D support was withdrawn as indicated, Dr Casler explained

They reviewed 66 patients treated under the new protocol and compared them with 130 thyroidectomies prior to the implementation; there were 11 episodes of hypocalcemia in the new protocol group (16.6%) compared with 27 in the preprotocol group (20.7%).

Hypocalcemia occurred in 42.8% of preprotocol cases in which parathyroid glands were noted in the pathology specimen compared with only 29.4% of similar cases in the protocol group. Four patients in the preprotocol group were readmitted to the hospital for severe hypocalcemia, but there were no readmissions in the postprotocol group.

"We were hoping for an improvement in our postop patients but were surprised to see how dramatically postop care improved," Dr Casler said. "Emergency-department visits went to zero."

"Our study confirms that postoperative PTH level less than 10 pg/mL is a predictor of hypocalcemia following total thyroidectomy (P < .05). This study adds a risk stratification to postop management and standardizes management in our institution."

The next steps in terms of research, he added, will be to further evaluate the role of vitamin D deficiency in the equation.

"We are preparing a study that will assess the impact of treatment for vitamin D deficiency on the incidence of postoperative hypocalcemia in thyroidectomy patients," he concluded.

Dr Nam and coauthors and Dr Casler reported they have relevant financial relationships.

2014 Annual Meeting of the American Thyroid Association; October 31, 2014; San Diego, CA. Abstracts 14 and 58.

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