Psychiatric symptoms, bone density and non-specific symptoms in patients with mild hypercalcemia due to primary hyperparathyroidism: A systematic overview of the literature

To determine (1) the relationship between primary hyperparathyroidism with mild hypercalcemia and psychiatric disturbances, bone density, or non-specific symptoms, and (2) the effect of parathyroidectomy on these outcomes, a systematic and critical review of the literature was conducted. Relevant citations were identified using MEDLINE (1966 to August, 1995) and PsycINFO (1967 to August, 1995). Studies were included for the overview if they described patients with mild hypercalcemia (< 12 mg/dl), and if they dealt with at least one of the following outcomes: psychiatric disturbances, bone density, joint pain, constipation, polyuria/nocturia or weight loss. Either a calculated effect size or Z score was used to estimate the effect of the disease or parathyroidectomy on these outcomes. Seven studies met the inclusion criteria for this overview. Two out of three case-control studies on psychiatric symptoms found a significant association between primary hyperparathyroidism with mild hypercalcemia and psychiatric disturbances (effect sizes; 0.17, 1.2 and 1.6). One of the three studies also examined the effect of parathyroidectomy on psychiatric symptoms, and found an effect size of 1.5. All four cross-sectional studies that measured bone mass showed significantly reduced bone density in the forearm and the lumbar spine. The bone loss ranged from 0.9 to 1.4 standard deviation below the age- and sex-adjusted mean value in the forearm, and was 0.5 in the spine. There was no relevant study regarding non-specific symptoms. Among the seven studies, five did not explicitly indicate whether the patients had classical symptoms of either osteitis fibrosa cystica or renal stones. Primary hyperparathyroidism with mild hypercalcemia is associated with psychiatric disturbances and reduced bone density. Nevertheless, further research is needed to determine the symptoms, particularly for a group of patients without either classical bone disease or renal stones. The effects of parathyroidectomy on these outcomes also remain to be determined.