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- Carling, Tobias, et al.
(author)
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Vitamin D receptor genotypes in primary hyperparathyriodism
- 1995
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In: Nature Medicine. - 1078-8956 .- 1546-170X. ; 1:12, s. 1309-1311
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Journal article (peer-reviewed)abstract
- Vitamin D and parathyroid hormone (PTH) constitute the main regulators of systemic calcium homeostasis. As well as its calcaemic effects, active vitamin D3(1,25(OH)2D3) has a direct regulatory role on parathyroid cells. Active vitamin D3 acts via its receptor (VDR), and binding of the ligand-receptor complex to specific promoter regions of the PTH gene inhibits transcription. Active vitamin D3 constitutes a principal regulator of parathyroid cell growth, and polymorphism in the VDR gene has recently been related to bone mineral density and suggested as predisposing to osteoporosis. Impaired effects of active vitamin D3 may contribute to the relatively enhanced secretion and cell proliferation seen in hyperparathyroidism (HPT). Indeed, VDR dysfunction, of essentially unknown character, has been demonstrated in the pathological parathyroid tissue of primary HPT as well as HPT secondary to uraemia. Consistent with the essential role of active vitamin D3 in parathyroid regulation, the VDR gene polymorphism was studied in 90 postmenopausal women with primary hyperparathyroidism. The VDR genotype bb was found in 60.0% of HPT patients and in 33.3% of the postmenopausal female controls (P < 0.001). As the b allele has been linked to decreased transcriptional activity or messenger RNA stability, reduced VDR expression may impede regulatory actions of vitamin D and may contribute to parathyroid tumorigenesis in these patients.
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- Lundgren, Ewa
(author)
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Primary hyperparathyroidism of postmenopausal women : Prospective population-based case-control analysis on prevalence, clinical findings and treatment
- 1999
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Doctoral thesis (other academic/artistic)abstract
- The need of prospective studies on prevalence, clinical features and treatment of mild primary hyperparathyroidism (HPT) has been emphasised. Population-based screening was performed in 5 202 women attending screening mammography at 55-75 years of age. HPT was diagnosed in 2.1% of the women, and almost one third of them were normocalcemic. The demonstration of parathyroid pathology in 60 of 61 cases treated surgically suggested underestimation of the prevalence of HPT. Examination of the operatively excised parathyroid tissue showed quantitative rather than qualitative discrepancies between normocaldemic and hypercalcemic HPT, and that the hypercalcemic phase of the disorder may be preceded by a period of normocalcemia.Cases and matched controls from the screened population underwent extensive biochemical analyses, bone mass determination, and questionnaires on symptoms, illnesses and medications, and background variables. Despite that the cases were unaware of their biochemically mild HPT and appeared to be asymptomatic, the disorder was coupled to significant psychic complaints, bone loss, and several risk factors for cardiovascular diseases. Case-control analysis on sick leave before the diagnosis of HPT revealed an increased requirement of sickness benefits due mainly to cardiovascular diseases. These findings contradict suggestions on the innocuous nature of mild,asymptomatic HPT, and the generally rare indication for active treatment of the disease in the elderly.Treatment with parathyroid surgery, hormone replacement therapy (HRT), HRT combined with surgery, and conservative surveillance was evaluated prospectively during five years. Surgery was found to be the only treatment that normalised the investigated indices of the calcium homeostasis and made the cases and controls indistinguishable in this respect. Further analysis on the recorded symptoms and signs of HPT will display any clinically relevant benefits from this normalisation.
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