Normocalcaemic, vitamin D-sufficient hyperparathyroidism - high prevalence and low morbidity in the general population: A long-term follow-up study, the WHO MONICA project, Gothenburg, Sweden

Abstract

Objective: There is limited knowledge about the natural history of normocalcaemic, vitamin D-sufficient hyperparathyroidism (nHPT). The aim was to study the prevalence of nHPT and its relation to morbidity.

Design: Cross-sectional and retrospective study at the Sahlgrenska University Hospital, Gothenburg, Sweden.

Subjects: A random population of 608 men and women, age 25-64 years, was studied in 1995 as part of the WHO MONICA study and reinvestigated in 2008 (n = 410, of whom 277 were vitamin D sufficient).

Measurements: A serum intact parathyroid hormone (S-PTH) ≥60 ng/l was considered as HPT, S-calcium 2·15-2·49 mmol/l as normocalcaemia and S-25(OH)D ≥ 50 nmol/l as vitamin D sufficiency. Data on fractures, stroke and myocardial infarction were retrieved until 2013, that is a 17-year follow-up.

Results: The prevalence of nHPT was 2·0% in 1995 (age 25-64) and 11·0% in 2008 (age 38-79). S-PTH was positively correlated with age and BMI. After adjustment for these variables, a high S-PTH level (≥60 ng/l) at follow-up was associated with previously low S-25(OH)D, high osteocalcin, S-PTH and both past and presently treated hypertension. No relation was seen with creatinine, cystatin C, malabsorption markers, thyroid function, glucose, insulin, lipids, calcaneal quantitative ultrasound, fractures, myocardial infarction, stroke or death at follow-up.

Conclusions: This small random population study showed that nHPT was common, 11% at follow-up. Only one individual developed mild hypercalcaemia in 13 years. Previous S-PTH was predictive of nHPT and hypertension was prevalent, but no increase in hard end-points was seen over a 17-year period.

Figure 1

Flow chart for subjects with a serum parathyroid hormone level ≥60 ng/l in 1995 and at follow‐up 13 years later. Left square shows subjects aged 25–64 years with normal S‐calcium (S‐Ca) and elevated serum parathyroid hormone (S‐PTH) levels in 1995 and at the re‐examination 13 years later. Left square, left column shows the flow chart for nHPT. Right square shows subjects with pHPT in 1995 and at follow‐up 13 years later, the WHO MONICA study, Gothenburg, Sweden. Right square, left panel shows the flow chart for subjects with vitamin D‐sufficient pHPT. nHPT, normocalcaemic and vitamin D‐sufficient hyperparathyroidism; pHPT, primary hyperparathyroidism; sHPT, secondary hyperparathyroidism; Vit D insuff., vitamin D insufficiency defined as S‐25(OH)D < 50 nmol/l; Suppl., daily use of calcium/vitamin D supplementation; y, years; Tx, treatment; DM, diabetes mellitus; hypert, hypertension; N = normal

Figure 2

Distribution of subjects, n = 410, regarding S‐Ca in relation to S‐PTH with vitamin D insufficiency (S‐25(OH)D < 50 nmol/l: open circles) and sufficiency (cross in circles). Subjects with normocalcaemic, vitamin D‐sufficient hyperparathyroidism (nHPT) are evenly distributed in the upper middle section. The straight horizontal line indicates the reference level of S‐PTH, 60 ng/l, and the two vertical lines show the reference levels of S‐Ca between 2·15 and 2·49 mmol/l. The equation for the regression line estimate is given below the figure.