Diagnostic delay in patients with primary hyperparathyroidism and its impact on disease outcomes

Currently, the diagnosis of primary hyperparathyroidism (PHPT) is often based on detected asymptomatic hypercalcemia incidentally during routine biochemical testing. Despite this, in clinical practice there are patients who have documented hypercalcemia but are not evaluated for PHPT in a timely manner, resulting in a delayed diagnosis. The aim of this study was to determine the proportion of PHPT patients who had a delay in diagnosis and to evaluate whether there was a difference between the clinical and laboratory data of patients with and without a delay in diagnosis. The data of patients diagnosed with primary hyperparathyroidism (PHPT) were evaluated retrospectively. The time when the patients' hypercalcemia was first detected, the time when PHPT was diagnosed, the time between the detection of hypercalcemia and the diagnosis of PHPT, demographic characteristics, clinical features, concomitant diseases, biochemical and hormonal results, radiological findings, data regarding the operation process, and pathology results were examined. Patients who received a PHPT diagnosis within one year after the first documented hypercalcemia were classified as having no diagnostic delay, whereas those who were diagnosed more than one year after the initial hypercalcemia were classified as having a diagnostic delay. Clinical and laboratory variables of patients with and without diagnostic delay were compared. A total of 306 patients diagnosed with PHPT were included in the study, of whom 20.3% (n=62) were male and 79.7% (n=244) were female. The median time from the first documented hypercalcemia to the diagnosis of PHPT was 571 days (range: 5–3290 days). We found that only 42.2% of PHPT patients were diagnosed within one year of initial hypercalcemia. The rest of the PHPT patients (57.8%) were diagnosed more than one year after initial hypercalcemia and there was a delay in diagnosis in those patients. From the time of initial hypercalcemia to the time of diagnosis, 43.5% of patients had more than two years, 27.5% had more than three years, 21.9% had more than four years, and 14.4% had more than five years. The time from initial hypercalcemia to diagnosis was significantly longer in the delayed-diagnosis group compared with the non-delayed group, respectively (1043 days (range: 366–3290) versus (vs) 99 days (range: 5–363)). There was no significant difference between the groups regarding comorbidities at the time of the first hypercalcemia. However, the presence of comorbidities at the time of PHPT diagnosis was significantly higher in the delayed-diagnosis group (80.2% vs. 65.9%). Although the prevalence of osteoporosis was similar between the groups at the time of first hypercalcemia, it was significantly frequent at the time of PHPT diagnosis in the delayed-diagnosis group (37.9% vs. 24%). The frequency of nephrolithiasis during PTHP diagnosis was significantly higher in patients with the delayed PHPT diagnosis of more than 5 years compared with patients with in the non-delayed group, respectively (43.2% vs 21.7%). Additionally, we found that 50 patients developed new chronic conditions such as osteoporosis and hypertension from initial hypercalcemia to diagnosis. When the time from the first hypercalcemia to the time of diagnosis was compared between the 50 patients who developed a new comorbidity and the other patients, we found that the time from the first hypercalcemia to the time of diagnosis was significantly longer in the 50 patients who developed a new comorbidity (1049 days vs. 475 days). In conclusion, our study demonstrated that the diagnosis of PHPT is frequently delayed in patients with hypercalcemia, and this delay is associated with increased morbidity.