Missed, delayed diagnoses of primary hyperparathyroidism linked to worse symptoms

Missed or delayed primary hyperparathyroidism diagnosis is associated with significantly increased rates of associated symptoms and diagnoses, a recent study found.

Researchers conducted a retrospective cohort study of patients ages 40 years and older with two instances of hypercalcemia (serum calcium level ≥10.5 mg/dL) during 2010 to 2020, with three years of follow-up. They used data from the TriNetX Research Network, which provided access to electronic medical records from about 58 million patients ages 40 years and older from 63 U.S. health care organizations. The researchers compared existing symptoms and diagnoses associated with primary hyperparathyroidism (osteoporosis, fractures, urolithiasis, major depressive disorder, anxiety disorders, hypertension, gastroesophageal reflux disease, malaise or fatigue, joint pain or myalgias, constipation, insomnia, polyuria, weakness, abdominal pain, headache, nausea, amnesia, and gallstones) in those deemed high risk for but not diagnosed with primary hyperparathyroidism versus matched controls. They also compared outcomes by whether the time from documented hypercalcemia to diagnosis and from diagnosis to treatment was more or less than a year. Results were published Dec. 27, 2022, by JAMA Network Open.

Of 135,034 patients with hypercalcemia (72% women; mean age, 63 years), 54,946 (40.7%) underwent measurement of parathyroid hormone (PTH) levels. Of those whose PTH levels were obtained, 13,136 (23.9%) had a diagnosis of primary hyperparathyroidism, 17,816 (32.4%) had PTH levels less than 50 pg/mL and no diagnosis, and the remaining 23,994 (43.7%) had PTH levels of 50 pg/mL or more yet did not receive a diagnosis. After excluding patients with elevated albumin or normal ionized calcium levels in the latter group, the researchers identified 20,176 patients (14.9%) as the first high-risk cohort. Of the 80,088 patients (59.3%) who did not have PTH levels obtained, they placed 24,905 (18.4%) with no diagnosis of primary hyperparathyroidism and no recorded explanation for hypercalcemia in the second high-risk group. Compared with matched controls, high-risk patients had significantly increased rates of all associated symptoms and diagnoses. Compared with those diagnosed with primary hyperparathyroidism within one year of hypercalcemia, those whose workup exceeded one year had significantly increased rates of major depressive disorder, anxiety disorders, hypertension, gastroesophageal reflux disease, malaise or fatigue, joint pain or myalgias, polyuria, weakness, abdominal pain, and headache at three years. In the group with delayed diagnosis, rates of osteoporosis increased from 17.1% (628 patients) to 25.4% (935 patients) over the study period. A total of 5,280 diagnosed patients (40.2%) underwent parathyroidectomy; surgery beyond one year of diagnosis was associated with significantly increased rates of osteoporosis and hypertension compared to surgery within one year.

The study may have incorrectly categorized a patient as having had an insufficient workup if they received some of their workup outside an included health care organization, the authors noted. They added that some patients who were excluded as having another explanation for hypercalcemia may have had concomitant undiagnosed primary hyperparathyroidism, among other limitations.

A feature story in the April 2022 ACP Internist explained how internal medicine physicians can better diagnose primary hyperparathyroidism and refer patients for timely treatment.