Left-Shifted Relation Between Calcium and Parathyroid Hormone in Graves' Disease

Abstract

BACKGROUND: Patients with Graves' disease (GD) have disturbances in calcium regulation with manifestations such as postoperative hypocalcemia. We have investigated the thyroid as well as the parathyroid function in detail. MATERIALS AND METHOD: A series of patients undergoing total thyroidectomy for GD (n = 56) or multinodular goiter (MNG; n = 50) were scrutinized for postoperative hypocalcemia and a need for calcium and/or vitamin D substitution. A citrate-calcium (CiCa) clamp was used in 14 patients and 21 controls to quantify the secretion of PTH in relation to the ionized plasma calcium level. The set point, equal to the plasma-ionized calcium concentration at which 50% of the maximal secretion of PTH is inhibited, as well as other CiCa-related parameters were calculated. RESULTS: Hypocalcemia was present in 48% of GD and 41.2% of patients with MNG postoperatively. Patients with GD had lower calcium levels, 18% had serum Ca less than 2.00 mmol/L compared with 4.0% in the MNG group (P = .02). A higher degree of GD patients were given parenteral calcium substitution during the hospital stay (3.6% vs 0 %) and oral calcium substitution at discharge (48% vs 10%), although they had normal vitamin D3 levels. The GD group showed a significantly left-shifted set point compared with the normal group on the CiCa clamp, 1.16 mmol/L vs 1.20 mmol/L (P < .001) as well as an increased PTH release to hypocalcemic stimulus. GD patients also show an association between degree of subclinical toxicosis at time of surgery and risk for developing postoperative hypocalcemia. CONCLUSION: Patients with GD demonstrate dysregulation of the calcium homeostasis by several parameters. GD patients have lower postoperative serum calcium compared with patients with MNG, lower calcium/PTH set point, and a significantly increased release of PTH to hypocalcemic stimulus compared with controls. The CiCa clamp response in GD patients with normal 25-hydroxyvitamin D3 levels mimics that of obese patients in which vitamin D insufficiency has been proposed as an underlying cause.