Introduction

Primary hyperparathyroidism is a condition characterized by inappropriate excess secretion of parathyroid hormone, leading to hypercalcemia, hypophosphatemia and mild hyperchloremic acidosis. ₁ It occurs in one of every 500 women and one of every 2000 men over 40 years in the U.S.A. Single parathyroid adenoma is the etiology of primary hyperparathyroidism in approximately 85-90% of patients. ₂ Relationship of preoperative biochemical parameters, serum calcium, serum phosphate, serum calcium, serum alkaline phosphatase and serum parathyroid hormone levels with parathyroid adenoma weight and postoperative serum calcium is controversial. To date, results from different studies, which were retrospective, have been variable. We designed this prospective study to see whether the preoperative biochemical markers are valuable in predicting parathyroid adenoma weight, and to evaluate factors that may have influence on postoperative serum calcium level. This correlation could help surgeons to predict which patients will be hypocalcemic postoperatively and to manage them correctly.

Materials and methods

In a prospective study from 2005 to 2007, all patients with primary hyperparathyroidism who underwent parathyroidectomy were enrolled. Exclusion criteria were secondary operation, parathyroid hyperplasia, multiple adenomas and parathyroid carcinoma. Eighty patients with single parathyroid adenoma entered the study. Demographic data (sex, age) and preoperative serum calcium, phosphate, parathyroid hormone and alkaline phosphatase were recorded. All patients had these blood parameters measured within 2 months of surgery. All patients underwent resection of parathyroid adenoma by a single surgeon and confirmed with frozen section. Weight of adenomas was measured in milligrams in the operating room. Postoperative serum calcium was measured 24 hours after adenoma resection.

Data were presented as means with standard deviation or binomial percentages where appropriate. Multiple and binary logistic regression were used to explore relationships between biochemical markers with adenoma weight and postoperative serum calcium. Statistical analysis was carried out using SPSS release 13.0 for Windows (SPSS Inc. Chicago, IL, USA) and a p-value <0.05 was considered statistically significant.

Results

Of 80 patients enrolled, 66 (82.5%) patients were women and 14 (17.5%) were men. The mean age of patients was 48 ± 14 years. Mean preoperative serum calcium was 11.3 ± 1.4 mg/dl, mean parathyroid hormone level 451.6 ± 378.8 ng/l, mean phosphate level 2.47 ± 0.52 mg/dl and mean alkaline phosphatase level 571.75 ± 637 IU/L. Mean adenoma weight was 2.6 ± 2.2 with the range from 0.4 to 10 g and mean 24-hours postoperative serum calcium was 8.5 ± 0.6 mg/dl.

Correlation between adenoma weight and other parameters

There was no correlation between patient age and sex and adenoma weight. But there was a positive correlation between preoperative serum calcium (r = 0.33, p = 0.003), parathyroid hormone (r = 0.61, p = 0.0001), alkaline phosphatase (r = 0.43, p = 0.0005) and adenoma weight. There was no correlation between preoperative serum phosphate and adenoma weight (r = -0.14, p = 0.2). (Fig. 1)

Figure 1

Figure 1: Correlation of adenoma weight with PTH, serum calcium, alkaline phosphatase and serum phosphate (P)

Correlation between postoperative serum calcium and other parameters

There was a weak correlation between postoperative calcium and preoperative serum calcium (r = 0.23, p = 0.03). Also there was non- significant negative correlation between postoperative serum calcium and the preoperative serum alkaline phosphatase level (r = -0.11, p = 0.3), serum parathyroid hormone level (r = -0.11, p = 0.3) and adenoma weight (r = -0.17, p = 0.1). We calculated calcium decline as: preoperative serum calcium – postoperative serum calcium. With regard to calcium decline, there was correlation between serum calcium decline after adenoma resection and preoperative serum calcium (r = 0.92, p = 0.0007), parathyroid hormone level (r = 0.54, p = 0.0005), alkaline phosphatase level (r = 0.3, p = 0.006) and adenoma weight (r = 0.36, p = 0.001). (Fig. 2)

Figure 2

Figure 2: Correlation of postoperative calcium decline with PTH, preoperative serum calcium, alkaline phosphatase and adenoma weight

Discussion

Correlation between serum PTH and adenoma weight has been studied by some authors ₄,₅,₆,₇,₈ as well as serum calcium and adenoma size or mass ₄,₅,₉ ; however, results from different studies have been variable and even sometimes paradoxical. Rutledge et al. ₁₀ found a statistically significant but weak correlation (r = 0.16; Pearson's coefficient) between adenoma weight and preoperative calcium and PTH, while Dubost et al. ₁₁ , Wagner ₁₂ and Randhawa ₇ found no relationship between serum calcium and PTH levels and adenoma weight or volume. A recent study of 63 single adenomas by Bindlish et al. ₄ demonstrated statistically significant correlations between preoperative serum calcium and PTH with adenoma weight (p = 0.001). Likewise, Hedback et al. ₁₃ found a correlation (p<0.001) between preoperative serum calcium and adenoma weight in 713 patients with single parathyroid gland disease operated on between 1956 and 1982.

Further studies examined the relationship between adenoma size and weight and postoperative hypocalcemia with conflicting results. Zamboni et al. ₁₄ reported correlation between hypocalcemia and adenoma weight (p<0.001), but Strickland et al. ₁₅ found no statistically significant correlation between mean preoperative serum calcium, PTH and adenoma weight and postoperative serum calcium level.

We found a positive correlation between serum calcium, PTH and alkaline phosphatase levels with respect to adenoma weight. This means that in patients with higher preoperative serum calcium, parathyroid hormone and alkaline phosphatase level, we can predict heavier and larger adenomas in primary hyperparathyroidism. Our study has shown differences when some of the other studies have not, likely because of the exclusion of patients with double adenoma and hyperplasia. This study also had a large sample size; which has contributed to the positive results.

With regard to postoperative serum calcium, preoperative serum markers and adenoma weight are not reliable to predict postoperative serum calcium, but they can be used to predict calcium decline postoperatively. We suggest a study to evaluate the correlation of calcium decline after adenoma resection with hypocalcemic symptoms in hyperparathyroid patients. This will help to use prophylactic calcium in postoperative patients.

Conclusion

Adenoma weight has a positive impact on preoperative serum calcium, parathyroid hormone and alkaline phosphatase levels, and these parameters can be used to predict adenoma weight and size in primary hyperparathyroid patients. Preoperative serum markers and adenoma weight are unreliable to predict serum calcium level postoperatively, but we can estimate calcium decline postoperatively with preoperative serum calcium, PTH, alkaline phosphatase level and adenoma weight.