Screening is expected to diagnose and treat early stage disease in the hope of deriving survival benefits with decreased iatrogenic morbidity. This model is little argued for malignant disease but triggers intense debate for primary hyperparathyroidism (PHPT).
Despite an estimated incidence of 20/100 000 persons-years, relatively small numbers of patients undergo parathyroidectomy yearly. In the USA, over 75% of subjects are observed without parathyroid surgery, with minimal impact on this rate after the 1990 NIH consensus conference on asymptomatic PHPT. Equivalent figures for the UK are not available.
The threshold of hypercalcaemia that defines mild PHPT varies between studies (<2.8 mmol/l, <3 mmol/l). Long-term follow-up is initially considered appropriate for the majority of such patients and lacking the classical symptoms of PHPT. Only a minority of patients progress to more severe biochemical disease but within 1015 years surveillance a third of patients develop complications/indications for surgery or refuse to continue regular medical assessments.
Even in the presence of mild PHPT, there is a reduction in the average mineralization density that correlate with the high bone turnover rate and explains the reduced stiffness of bone tissue and the increased fracture risk. Left ventricular hypertrophy, an increased risk of arrhythmia and/or myocardial infarction, changes in the atherogenic lipid profile and impaired glucose tolerance are observed in cohorts of patients with moderate hypercalcemia. The severity of symptoms and altered quality of life/neuropsychiatric symptoms do not correlate with the degree of hypercalcaemia and hence patients mild PHPT are likely to benefit just as much from parathyroidectomy.
Multicentre cohort studies of patients with mild PHPT randomised to immediate or delayed surgical treatment could address some of these debated issues. Until such studies are set up, most surgeons would consider that parathyroidectomy represents the treatment of choice for all patients and many physicians would favour long-term follow-up.