Early Detection of Primary Hyperparathyroidism Essential for Bone Health

By Vikram Krishnamurthy, MD

Primary hyperparathyroidism (PHPT) is a common endocrine condition and the most common cause of hypercalcemia in the outpatient setting. Despite this, PHPT is under-recognized in the general population and likely affects many more patients than are actually diagnosed.1

The symptom profile can range from mild to severe, including the development of kidney stones, difficulty with cognition, and the loss of bone density with resultant fractures. Surgery remains the most durable and is a cost-effective treatment that is extremely safe in experienced hands.2 PHPT can affect individuals at any age, but most often it affects women older than 40. Furthermore, the risk appears to increase with age.

Identifying patients at risk

Given these findings, specialists in our Cleveland Clinic Endocrinology and Metabolism Institute investigated the incidence and recognition of PHPT in patients who were referred for bone mass densitometry. Most of these patients were post-menopausal women; therefore, we expected that they were at high-risk for PHPT. We randomly sampled patients from each month of the calendar year 2012 who underwent bone mass densitometry testing throughout Cleveland Clinic at its main campus, regional hospitals and 18 ambulatory care centers.

In May 2016, we presented our findings at the annual meeting of the American Association of Clinical Endocrinologists.3 Out of 998 patients, 757 had available outpatient calcium levels, of which 90 percent were female and the median age was 65. The incidence of PHPT was 2.2 percent in all patients and 3 percent in those with osteoporosis, which is estimated to be three to fifteen- fold higher than the general population.

Furthermore, outpatient hypercalcemia was found in 28 percent of patients, of which 41 percent had no parathyroid hormone (PTH) level drawn. Medications that could falsely lower calcium or PTH levels were found in 26 percent of patients, potentially interfering with recognition and diagnosis of PHPT. This signified that, despite PHPT being more common in these patients, their evaluation was drastically inadequate.

Why referral is important

A comprehensive evaluation is important for those who undergo bone mass densitometry, because we also found that bone density was worse in patients with PHPT. Mean T-scores of the lumbar spine, hip, and femur were statistically significantly lower in patients with confirmed PHPT when compared to those without the condition.

This encourages the earlier detection of PHPT and prompt referral to surgery to mitigate the deleterious effects on bone health. With three-year follow-up, only 25 percent of patients with PHPT were referred to surgery, despite no obvious contraindication (except one patient with an active malignancy). All patients who underwent surgery did so safely and were cured.

Recognition and Screening

We identified that patients who are referred for bone mass densitometry should be screened for PHPT, and we can work with our providers who order this testing to be vigilant. A careful evaluation should include all available outpatient calcium levels and a comprehensive review for medications that could interfere with the diagnosis. Bone density is worse for patients with PHPT, highlighting the importance of early detection and referral. Surgery continues to be a safe and effective treatment to prevent the long-term effects of untreated parathyroid disease.

Dr. Krishnamurthy is an Endocrine Surgeon in the Department of Endocrine Surgery within the Endocrinology & Metabolism Institute at Cleveland Clinic.

1 Press DM, Siperstein AE, Berber E, Shin JJ, Metzger r, Monteiro R, Mino J, Swagel W, and Mitchell JC. “The prevalence of undiagnosed and unrecognized primary hyperparathyroidism: a population-based analysis from the electronic medical record.” Surgery 2013;154(6):1232-7.

2 Wilhelm SM, Wang TS, Ruan DT, Lee JA, Asa SL, Duh QY, Doherty GM, Herrera MF, Pasieka JL, Perrier ND, Silverberg SJ, Solorzano CC, Sturgeon C, Tublin ME, Udelsman R, and Carty SE. “The American Association of Endocrine Surgeons guidelines for definitive management of primary hyperparathyroidism.” JAMA Surg 2016;[Epub ahead of print].

3 Krishnamurthy VD, Etiwy M, Slotcavage R, Gutnick JG, Jin J, Shin JJ, Berber E, and Siperstein A. “The incidence and recognition of primary hyperparathyroidism in patients referred for bone mass densitometry.” Presented at the Annual Scientific and Clinical Congress of the American Association of Clinical Endocrinologists in May, 2016;[abstract published in Endocr Pract].