Symptomatic Hypercalcemia in Patients with Primary Hyperparathyroidism Is Associated with Severity of Disease, Polypharmacy, and Comorbidity

Abstract

Current primary hyperparathyroidism (PHPT) clinical presentation is asymptomatic in more than 90% of patients, while symptoms concern osteoporosis and rarely kidney stones. Here, we retrospectively investigated the prevalence of PHPT patients presenting with hypercalcemic-related symptoms (HS-PHPT) as cognitive impairment, changes in sensorium, proximal muscle weakness, nausea and vomiting, constipation, and severe dehydration, in a single center equipped with an emergency department and described their clinical features and outcome in comparison with a series of asymptomatic PHPT out-patients (A-PHPT). From 2006 to 2016, 112 PHPT patients were consecutively diagnosed: 16% (n = 18, 3M/15F) presented with hypercalcemic-related symptoms. Gastrointestinal symptoms occurred in 66% of HS-PHPT patients and cognitive impairment in 44%; one woman experienced hypertensive heart failure. Two-thirds of HS-PHPT patients were hospitalized due to the severity of symptoms. Comparing the clinical features of HS-PHPT patients with A-PHPT patients, no gender differences were detected in the two groups, while HS-PHPT patients were older at diagnosis (71 (61-81) vs. 64 (56-74) years, P=0.04; median (IQR)). HS-PHPT patients presented higher albumin-corrected calcium levels (12.3 (11.3-13.7) vs. 10.6 (10.3-11.3) mg/dl, P < 0.001); 4 HS-PHPT presented corrected calcium levels >14 mg/dl. Serum PTH levels and total alkaline phosphatase activity were higher in HS-PHPT. Reduced kidney function (eGFR < 45 ml/min) was prevalent in HS-PHPT patients (42% vs. 5%, P=0.05). No differences in kidney stones and osteoporosis were detected, as well as in the rates of cardiovascular comorbidities and main cardiovascular risk factors. HS-PHPT patients had an age-adjusted Charlson Comorbidity Index higher than that of the A-PHPT patients and were on chronic therapy with a greater number of medications than A-PHPT patients. In conclusion, hypercalcemic-related symptoms occurred in 16% of PHPT patients. Risk factors were severity of the parathyroid tumor function, multimorbidity, and polypharmacy.

Figure 1

Differences in biochemical parameters between HS-PHPT and A-PHPT. Median plasma ionized calcium (a), serum PTH (b), serum total ALP activity (c), eGFR (d), and LDL cholesterol (e) significantly differed between HS-PHPT and A-PHPT patients. Dashed lines indicate normal reference ranges. Data are presented as median and range interquartile by box, and wisker plots represent minimum and maximum values. Statistical significance was determined by the Mann–Whitney test. HS-PHPT, hypercalcemic-related symptomatic PHPT (dark grey boxes); A-PHPT, asymptomatic PHPT (light grey boxes); PTH, parathormone; ALP, alkaline phosphatase; eGFR, estimated glomerular filtration rate; and LDL, low density lipoprotein.

Figure 2

Differences in multimorbidity and polypharmacy between HS-PHPT and A-PHPT. Median values of age-adjusted Charlson index (a) and of the number of medications (b) differed between HS-PHPT and A-PHPT patients. Data are presented as median and range interquartile by box, and wisker plots represent minimum and maximum values. Statistical significance was determined by the Mann–Whitney test. HS-PHPT, hypercalcemic-related symptomatic PHPT (black circles); A-PHPT, asymptomatic PHPT (grey squares).