Hypoparathyroidism can frequently result in postsurgical hypocalcemia, which usually responds to treatment. But a patient recently seen by a team of NYU Langone endocrinologists failed to respond to optimal treatment with calcium carbonate, calcitriol, and hydrochlorothiazide, initially puzzling them. Brenda Dorcely, MD, a postdoctoral fellow at NYU Langone, and Loren Wissner Greene, MD, clinical professor in the Department of Medicine, successfully uncovered the etiology of the patient’s recalcitrant hypocalcemia despite only one other case cited in recent literature. The case was subsequently presented as a poster at the 89th Annual Meeting of the American Thyroid Association, in Chicago, in October 2019.

Iatrogenic Injury Resulted in Transfer to NYC Health + Hospitals/Bellevue

The patient was a 60-year-old man who underwent emergent tracheostomy and direct laryngoscopy and bronchoscopy with biopsy after presenting to a hospital in the Bronx, New York, with a 4-month history of voice changes, 10-pound weight loss, and difficulty breathing for 1 week. He had a visible neck mass on the right side that extended from his larynx and protruded through his neck. The patient’s history also included HIV, herpes simplex, chronic obstructive pulmonary disorder, and cigarette smoking.

Initial pathology revealed invasive squamous cell carcinoma, and the patient had surgery that resulted in inadvertent injury of the thoracic duct and parathyroid glands. He was subsequently transferred to Manhattan’s NYC Health + Hospitals/Bellevue, a large tertiary care center with the ability to handle a complex revision. At Bellevue, the patient received total laryngectomy, total thyroidectomy, direct laryngoscopy, and bilateral neck dissections.

Postsurgical Hypocalcemia Remained Unresolved Despite Treatment

On postoperative day 1 of his second surgery, the patient had a corrected serum calcium level of 7.6 mg/dL (ref 8.0–10.2), magnesium of 1.2 mg/dL (ref 1.3–1.9), and phosphorus of 5.3 mg/dL (ref 2.7–4.5). His parathyroid hormone was less than 6.3 pg/mL, and his 25-hydroxyvitamin D level was 13.1 ng/mL. Dr. Dorcely and Dr. Greene were consulted to manage the patient’s hypocalcemia.

Hypocalcemia secondary to postsurgical hypoparathyroidism is a common complication of extensive neck surgery. Dr. Dorcely and Dr. Greene initially treated the patient with the standard regimen of oral calcium carbonate, 12 g (elemental) daily; calcitriol, 0.50 mcg (1,25 vitamin D) daily; and hydrochlorothiazide, 12.5 mg (to increase renal calcium resorption) daily via percutaneous endoscopic gastrostomy. But hypocalcemia persisted despite treatment. “His calcium kept dropping, and we had to keep sending him back to the ICU for calcium infusions,” Dr. Dorcely says. “He required recurrent management with intravenous calcium gluconate just to maintain his serum calcium levels, even at the low levels where they stood.”

Dr. Dorcely and Dr. Greene were baffled by another finding: the patient did not have any of the typical symptoms of hypocalcemia despite a serum calcium level of 6.5 mg/dL. Hypocalcemia is associated with tetany, characterized by neuromuscular irritability. Some symptoms associated with hypocalcemia are mild, such as perioral numbness, paresthesia of the hands and feet, and muscle cramps. But severe symptoms include carpopedal spasm, laryngospasm, and focal or generalized seizures that are unrelated to tetany. Hypocalcemia may also be associated with QT interval prolongation and potentially fatal ventricular arrhythmias. “None of the clinical findings of hypocalcemia were present. We were scratching our heads,” Dr. Greene says.

A Confluence of Contributing Factors

Hypocalcemia due to postsurgical hypoparathyroidism usually responds to treatment. The patient’s course suggested another etiology, but the cause was not immediately evident. A collaborative review of the patient’s postoperative course ultimately revealed several contributing factors, including a thoracic duct chyle leak, a rare complication of neck surgery.

Chyle is a milky substance consisting of fat droplets in lymphatic fluid. Characteristics associated with a thoracic duct chyle leak include visible accumulation of chyle on the surface of the neck. In addition to supraclavicular erythema, lymphedema, or a palpable fluid collection and a creamy or milky drain output, patients may have a sudden increase in drain output, particularly after an enteral feeding. A biochemical assay of drain output typically reveals chylomicrons, a triglyceride level of more than 100 mg/dL, and a higher triglyceride level in the drainage effluent than in serum. Leakage of the lipid-laden fluid results in loss of calcium and other electrolytes, in addition to fat-soluble vitamins such as vitamin D.

Compounding the patient’s resistance to treatment for his hypocalcemia was administration of octreotide, a somatostatin used after ENT surgery to control or seal chyle leaks. Calcium carbonate requires acidity for absorption, but octreotide inhibits gastrin secretion and decreases secretion of gastric acid by parietal cells. Octreotide also decreases gastric motility, which may impair delivery of calcium to the small intestine for absorption.

A Change of Treatment Leads to a Successful Outcome

Unlike calcium carbonate, calcium citrate does not require acidity for absorption, so a change of treatment improved the patient’s response. As the chyle leak resolved, octreotide was discontinued, further resolving the patient’s hypocalcemia. His calcium level gradually rose, and the hypocalcemia resolved. At the patient’s discharge, his serum calcium level was 9.5 mg/dL, and he was discharged on a regimen of oral calcium citrate, calcitriol (1,25 vitamin D), and cholecalciferol (25 OH vitamin D).

“It’s a very rare case to have all these things happening at once,” Dr. Dorcely says. “To have parathyroid effects, to have the thoracic duct chyle leak occurring, and then, on top of it, to have the octreotide working against our objective.” Endocrinologists use octreotide to treat hypercalcemia. “We usually don’t think of octreotide as drug for a chyle leak, as it is not used that way in the context of endocrinology,” Dr. Dorcely says.

This case is unusual in that the chyle leak and its treatment contributed to the recalcitrance of a not-unexpected hypocalcemia secondary to hypoparathyroidism. “We present this case often because it needs to be on the radar of endocrinologists,” Dr. Greene says. “This rare set of circumstances can come together, and the consequence can be disastrous if not properly appreciated and addressed.”