Association of symptomatic gallstones and primary hyperparathyroidism: a propensity score-matched analysis

If the prevalence of primary hyperparathyroidism (PHPT) in patients with symptomatic gallstones is higher than that in the general population, PHPT screening could reveal important clinical implications. We observed that the prevalence of PHPT in these patients was higher compared to that of healthy matched controls.


Dear Editor
Gallstones may be a complication related to primary hyperparathyroidism (PHPT) 1,2 but the prevalence is not known. Screening could reveal important clinical implications if the prevalence of PHPT is higher than that of the general population. This retrospective propensity score-matched study evaluated the association between symptomatic gallstones and PHPT .
Data were collected from April 2012 to May 2020 at International Goodwill Hospital, Kanagawa, Japan (approved by the ethics committee). Patients who underwent a cholecystectomy for symptomatic gallstones were compared with healthy matched controls who underwent a general health screening at the hospital during the same period. The exclusion criterion was renal insufficiency (a serum creatinine level greater than 1.47 mg/dl). Patients who underwent a cholecystectomy at the time of another operation (for example, gastric surgery) and those with gallbladder tumours, adenomyosis, asymptomatic gallstones or acalculous cholecystitis were excluded.
The primary outcome measure was the rate of hypercalcaemia. Because screening rates of PHPT in hypercalcaemic patients typically remain surprisingly low 3,4 , a predicted rate of PHPT was used. Table 1 Comparison of characteristics and outcomes between the control and symptomatic gallstone groups before and after propensity score matching Before propensity score-matching After propensity score-matching During the 8-year period, 930 patients underwent a cholecystectomy, and 2219 individuals underwent the general health screening. After exclusions, 709 and 2211 patients were included in the symptomatic gallstone and control groups, respectively. After matching, 702 patients were extracted from each group. The two groups were well matched for key confounders, that is age, sex, BMI and serum creatinine level ( Table 1). Compared with the controls, the symptomatic gallstone group's rate of hypercalcaemia (0.4 versus 2.3 per cent; P ¼ 0.003), rate of diagnosed PHPT (0 versus 0.7 per cent; P ¼ 0.025) and predicted rate of PHPT (0.4 versus 2.1 per cent; P ¼ 0.004) were significantly higher. Among the patients with hypercalcaemia, 43.8 per cent underwent a PHPT screening test. It is interesting to note that 80 per cent of the PHPT patients with symptomatic gallstones needed to undergo a parathyroidectomy for other surgical indications.
The prevalence of hypercalcaemia and the predicted prevalence of PHPT in the patients with symptomatic gallstones were both over five-fold higher than those for the healthy matched individuals. Although it is unclear whether a parathyroidectomy is indicated in PHPT patients simply because they have symptomatic gallstones, most of the PHPT patients with symptomatic gallstones had other surgical indications.
The pathogenesis of gallstones in PHPT remains unclear. Possible mechanisms may involve gallbladder stasis and a modification of bile composition. Because hypercalcaemia is known to decrease the body's bile flow and increase the biliary ionized calcium concentration, gallbladder stasis may lead to an increase in bile concentration, precipitation of cholesterol and calcium salts, retention of biliary precipitates and maturation of gallstones 2 . Some study limitations should be noted: normocalcaemic PHPT was not investigated, and the prevalence of both PHPT and gallstones varies globally. Conducting the proper checks on serum albumin and calcium in routine preoperative blood tests in patients with symptomatic gallstones could reduce the risks of PHPT-related diseases that are associated with overlooked or untreated PHPT.
Disclosures. The authors declare no conflict of interest.