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.

Physical Activity-Dependent Regulation of Parathyroid Hormone and Calcium-Phosphorous Metabolism

“…Patients with mild PHPT usually complain of depression, anxiety, fatigue, reduced memory, and concentration, but whether and how symptoms improve following PTX has not been determined [ 103 ]. Gastrointestinal symptoms in patients with PHPT may arouse suspicion of pancreatitis and peptic ulcer disease [ 153 , 154 ].…”

"Primary Hyperparathyroidism and Psychosis: A Case Report and Review of the Literature"

“…However, psychiatric symptomatology does not bear a direct relationship to the serum calcium level. However, studies show that symptoms that are related to hypercalcemia are associated with severity of parathyroid dysfunction, pre-existing comorbidities and polypharmacy [11]. Research suggests that elderly patients have a lower tolerance to changes in serum calcium levels [10].…”

The effect of evocalcet on vagus nerve activity of the gastrointestinal tract in miniature pigs

“…Although it is difficult to elucidate the mechanism of nausea and vomiting induced by calcimimetics, GI symptoms associated with hypercalcemia has been reported in various reports [ 19 – 21 ], which is an important knowledge for understanding. For example, it was reported the GI symptoms (anorexia, nausea, vomiting, abdominal pain, and constipation) occurred in 66% of primary hyperparathyroidism patients with hypercalcemia [ 22 ]. Details concerning how cinacalcet stimulates the GI tract remain unclear; however, it is likely that the GI side effects induced by cinacalcet are caused by the direct stimulation of CaR expressed in the GI tract.…”