Abstract
Patients with either an autoimmune thyroid disease or thyroid nodules exhibit an increased incidence of celiac sprue. 1 Total thyroidectomy in the setting of celiac sprue poses an increased risk of postoperative hypocalcemia because of a characteristic malabsorption of calcium and magnesium. 2 Hypocalcemia secondary to celiac sprue is independent of the well-described risk of hypoparathyroidism after total thyroidectomy. 3
Celiac sprue is a chronic condition in which there is a characteristic mucosal lesion of the small intestine that impairs nutrient absorption by the involved bowel. 4,5 Intestinal absorption and associated symptoms normalize with the adoption of a gluten-free diet. Nonetheless, chronic calcium and magnesium malabsorption coupled with an associated vitamin D insensitivity may exacerbate postoperative hypocalcemia after total thyroidectomy despite dietary precautions and normal parathyroid function. 2,6
We present an illustrative case of total thyroidectomy for papillary thyroid carcinoma in a patient with Hashimoto's thyroiditis and celiac sprue. Total thyroidectomy in this setting must be undertaken with heightened attention to the risk of postoperative hypocalcemia because of chronic malabsorption of calcium and magnesium.
CASE REPORT
A 32-year-old woman with a history of Hashimoto's thyroiditis presented to the gastroenterology clinic with complaints of episodic abdominal distention, foul-smelling diarrhea, upper and lower extremity bone pain, and chronic fatigue. Duodenal biopsy demonstrated widening and flattening of the villi with an increased amount of chronic inflammatory cells and lymphoid aggregates within the lamina propria. Bone mineral density assessment with dual energy x-ray absorptiometry (DEXA) was consistent with osteopenia. The diagnosis of celiac sprue was confirmed, and the patient instituted a gluten-free diet.
One month later, the patient presented to the endocrinology clinic. Her gastrointestinal distress had greatly diminished, but she continued to complain of intermittent bone pain. Examination revealed an incidental nodule of the inferior left thyroid lobe. Thyroid-stimulating hormone and total serum calcium levels were within normal limits. Cervical ultrasound confirmed a 6-mm solid nodule at the left lateral aspect of the thyroid isthmus. Fine needle aspirate of the mass revealed atypical epithelial cells suggestive of papillary carcinoma in a background of chronic thyroiditis.
The patient underwent total thyroidectomy with preservation of the parathyroid glands. Intraoperative frozen section examination of the left thyroid lobe confirmed the diagnosis of papillary thyroid carcinoma. Final pathologic examination revealed a 6-mm unifocal papillary carcinoma in a background of Hashimoto's thyroiditis. The patient was placed on oral calcium carbonate 500 mg twice daily and calcitriol 0.25 $mUg once daily and was discharged in stable condition 1 day after her operation.
On the fourth day after her operation, progressive circumoral paresthesias, facial twitching, and tingling of the hands and feet developed in the patient. A positive Chvostek's sign was elicited. Ionized calcium and magnesium concentrations were 3.7 mg/dL (reference range, 4.6 to 5.4 mg/dL) and 1.3 mg/dL (reference range, 1.3 to 1.9 mg/dL), respectively. The patient was admitted to the hospital and received intravenous calcium gluconate and magnesium sulfate. Her symptoms resolved over the next 3 days, and she was discharged in stable condition with an ionized calcium concentration of 4.2 mg/dL and intact parathormone concentration of 4 pg/mL (reference range, 10 to 65 pg/mL). She began a regimen of oral calcium gluconate 1000 mg 4 times daily, calcitriol 1.5 $mUg twice daily, and a gluten-free diet.
After radioablation of residual thyroid bed tissue with 100 mCi iodine-131, the patient continued to report symptoms of chronic fatigue and occasional circumoral tingling. By the 6-month follow-up, the patient reported resolution of gastrointestinal distress, paresthesias, and bone pain. Concentrations of ionized calcium and intact parathormone were 5.1 mg/dL and 13 pg/mL, respectively. Duodenal biopsy revealed chronic inflammation with no villous atrophy seen.
DISCUSSION
The absorption of calcium occurs predominantly in the duodenum and jejunum. 2 Regulation of this process is dependent on the activated form of vitamin D, 1$aL,25-(OH)2D3. 2 Vitamin D absorption in turn is dependent on adequate bile salt uptake in the distal ileum. 2
The characteristic mucosal lesion of celiac sprue leads to malabsorption of calcium, magnesium, vitamin D, and bile salts in the small bowel. 4,5 Parathyroid hormone production attempts to correct the resulting serum hypocalcemia by increasing bone turnover and renal reabsorption. 2 Inadequately corrected hypomagnesemia, however, can suppress both the secretion and the systemic effects of parathyroid hormone. 6
Hypocalcemia can persist even with correction of the intestinal malabsorptive disorder. 2 The “hungry bone syndrome” describes the condition where calcium is preferentially deposited in bone despite persistent serum hypocalcemia. 2
Calcium regulation can be further disrupted in the setting of thyroid surgery. Transient hypocalcemia can occur in as many as 17% of postthyroidectomy patients, whereas permanent surgical hypoparathyroidism occurs in up to 8% of patients. 3 The patient in the case report presented with postoperative hypocalcemia despite oral supplementation of calcium and vitamin D. Further investigation revealed signs of malabsorption in addition to a transient serum hypoparathyroidism. Aggressive parenteral supplementation of calcium and magnesium was required to normalize serum calcium. Long-term oral supplementation of calcium and vitamin D together with a strict gluten-free diet may be required in patients with celiac sprue who are undergoing total thyroidectomy. 2,5
Physicians should raise the question of celiac sprue in all patients with autoimmune thyroid disease and gastrointestinal symptoms. 1 Because of the potential for severe postoperative hypocalcemia, screening for celiac sprue may be indicated in patients with autoimmune thyroid disease who plan to undergo total thyroidectomy.