Investigation of glucose intolerance in patients with normocalcemic primary hyperparathyroidism: 4-year follow-up

Abstract

Normocalcemic primary hyperparathyroidism (NPHPT) is a clinical phenomenon in which elevated serum PTH levels are observed with normal serum calcium concentrations in lack of secondary causes such as vitamin D deficiency, renal or liver disease or malabsorption [1, 2]. While derangements in glucose and lipid metabolism in primary hyperparathyroid patients are well-defined, only a few reports exist regarding metabolic abnormalities in patients with NPHPT. Recently, we have shown in 18 patients with NPHPT that those patients do not exhibit increased rates of insulin resistance and glucose intolerance [3]. Similarly, Tassone et al. [4] also showed that patients with NPHPT have similar insulin sensitivity and glucose tolerance with age and sexmatched control subjects. Since there is no prospective study in patients with NPHPT, we have evaluated the changes regarding insulin resistance and glucose intolerance in the same patient group after 4 years of follow-up. Sixteen patients (2 males and 14 females) out of 18 with NPHPT were admitted to regular visits during the 4 years after their first diagnosis as NPHPT. Two patients did not come to visits. The whole data of the patients were described previously [3]. All subjects underwent a physical examination and biochemical data including serum calcium, phosphate, alkaline phosphatase (ALP), albumin, creatinine, glucose, serum lipids, 25 (OH) D levels were determined regularly after an overnight fast. Standart oral glucose tolerance test (OGTT) with 75 g glucose were started between 08:00 and 09:00 h. Blood samples were taken just before (0 min) and 30, 60, 90 and 120 min after administration of glucose with 300 ml water orally for the measurement of serum glucose and insulin concentrations. Area under the curves (AUC) of glucose and insulin during OGTT were calculated according to trapezoid rule. Glucose tolerance was evaluated by using the criteria of the American Diabetes Association, and impaired glucose tolerance (IGT) was defined as a 2-h post-load glucose of C140 and \200 mg/dl. Statistical analysis was performed using the SPSS 15.0 program. All data were subjected to a Kolmogorov–Smirnov test for normality and data was presented as mean ± SEM. Paired t test was used to compare differences at the beginning and at the end of the study. P \ 0.05 was accepted as significancy. Four years of data after initial diagnosis for each patient were evaluated. One (6.25 %) patient developed hypercalcemic hyperparathyroidism. The data of this patient was not used in the analysis. Serum PTH level was significantly higher (103.8 ± 12.5 pg/ml) than normal limits (5–65 pg/ml) at the end of the 4 years. None of the patients had vitamin D deficiency [mean serum 25 (OH) D level was 54.6 ± 5.9 ng/ml]. Three out of five patients with IGT had diabetes mellitus and the two others remained as IGT at the end of the 4 years. None of the patients with normal glucose tolerance developed glucose intolerance during follow-up. The patient who developed hypercalcemia and three patients with diabetes mellitus were excluded from the analysis and we found that insulin responses to OGTT were not significantly different before (AUCinsulin 5059 ± 765 mg/dl 9 120 min) and after 4 years (AUCinsulin 4293 ± 537 mg/dl 9 120 min) of follow-up. Serum lipid levels, kidney and liver function tests were also normal during 4 years follow-up. Several previous data demonstrated close relationship between primary hyperparathroidism (PHPT) and impaired H. Diri K. Unluhizarci (&) F. Kelestimur Department of Endocrinology, Erciyes University Medical School, 38039 Kayseri, Turkey e-mail: kursad@erciyes.edu.tr