The diagnosis and treatment of primary hyperparathyroidism (HPT) present a problem for physicians because patients are often asymptomatic and show few signs of complications resulting from the disease. HPT is typically diagnosed after patients are found to have an elevated serum calcium level on routine biochemical screening. Because of this, conservative treatment is often recommended rather than surgery, despite the fact that parathyroid surgery sometimes corrects many of the consequences of primary HPT. Postmenopausal women comprise a risk group for this condition, with a recent population-based screening study reporting a 2.1 percent prevalence of HPT in this group. Lundgren and colleagues sought to identify some of the less common symptoms associated with primary HPT, including psychiatric complaints, evidence of bone loss and incidence of cardiovascular disease, in post-menopausal women who were diagnosed after initial screening for hypercalcemia.

Women between the ages of 55 and 75 years undergoing routine mammography were eligible for the study. Serum calcium levels were obtained at the time the mammography was performed to screen patients for inclusion in the study group. Of the 5,202 women screened, 109 had a serum calcium level greater than 10.2 mg per dL (2.55 mmol per L) and an elevated parathyroid hormone level. Other requirements for a diagnosis of HPT included a serum creatinine level less than 1.42 mg per dL (130 μmol per L), absence of low urinary calcium clearance and no family history of hypercalcemia. Patients in the control group had normal serum calcium and creatinine levels and were matched by age and time of screening with the HPT patients. All women underwent a physical examination and were questioned about their history of smoking, daily exercise, age of menarche and menopause, medication use and frequency of physician visits. Laboratory studies included a complete blood cell count, urinalysis, determination of uric acid and a complete lipid panel. In addition, all women were asked about a history of kidney stones, muscle weakness or pain, loss of energy during the day, fatigue, depression and memory loss. Patients also completed two survey instruments that evaluated their somatic and psychiatric symptoms. Finally, bone mass density studies of the total body, lumbar spine, cervical spine and greater trochanter were conducted for all patients.

A total of 102 women were in the HPT group, and 95 were in the control group. Mean patient age was 66.5 years, and the groups were similar in incidence of current diseases such as diabetes and hypertension, history of smoking and amount of daily exercise. Age at menarche and menopause was also similar between groups, but women in the HPT group had had more children. In addition, fewer women in the HPT group were taking estrogen replacement therapy for signs and symptoms of menopause. Fewer women in the HPT group reported predefined cardiovascular symptoms of HPT. However, data from the survey instruments indicated that women in the HPT group cited fatigue, daytime sleepiness, muscle weakness and lack of emotional and sexual interest more often than women in the control group. Finally, bone density studies revealed lower values in the HPT group, but no increased history of lumbar, forearm or hip fractures.

Total cholesterol levels were similar between groups, but women in the HPT group had lower high-density lipoprotein levels and higher very-low-density lipoprotein and triglyceride levels than women in the control group. Patients in the HPT group also reported more physician visits and sick leave days than women in the control group, although exact figures were not specified.

The authors conclude that women with mild “asymptomatic” primary HPT have significant psychiatric and somatic symptoms that, in most patients, either are unrecognized or are attributed to other causes. In addition, these women have significant bone loss and an increased risk of cardiovascular disease, based on changes in their lipid profiles, compared with women in the control group. The authors conclude that current treatment strategies for these patients should be reconsidered.

editor's note: The authors of this study are surgeons, which alone would suggest some inherent bias. However, as they point out, a significant number of “asymptomatic” patients are diagnosed with primary HPT based on the results of routine metabolic screening. Perhaps physicians are not asking patients the right questions. It may be an incorrect assumption that because the patients are elderly or have no history of kidney stones they can simply be observed. At the very least, physicians should have a low threshold for choosing to perform bone mineral density studies in all patients with HPT. However, more convincing studies and data on the natural history of this disease are needed before surgical removal of a parathyroid adenoma can be recommended for all patients.—j.t.k.