25-hydroxyvitamin-d-2 and Parathyroid-Neoplasms

Primary hyperparathyroidism is rare in children. Absence of specific symptoms and limited biochemical evaluation in children has led to lengthy delays in diagnosis with the potential for damage to the kidneys and skeleton.. The setting involved a private practice referral to a large tertiary care center.. Our patient is a 16-yr-old male presenting with gross hematuria, left flank pain, and right foot pain.. A biochemical evaluation revealed hypercalcemia and elevated parathyroid hormone levels. Renal ultrasonography demonstrated bilateral nephrolithiasis. Parathyroid ultrasonography and dual-phase technetium-99m sestamibi scintigraphy revealed a parathyroid adenoma in the left mid/lower anterior thyroid bed. A 4.5-g adenoma was removed at parathyroidectomy.. Bone mineral content and density performed by dual energy X-ray absorptiometry at the time of diagnosis and 1 yr after parathyroidectomy.. The main outcome measurement is a dramatic (24%-whole body and 49.9%-left hip) increase in bone mineral density during the 1-yr interval.. Delay in diagnosis of hyperparathyroidism is common in children, related to vague symptomatology and infrequent use of laboratory evaluations in children. Such delays lead to increased risk of osteoporotic fractures and kidney stones. This case illustrates the emergent need of diagnostic evaluation in children presenting with similar symptoms. We emphasize the importance of bone densitometry in children, which is not often considered as part of the standard evaluation in this age group. The remarkable increase in bone mineral density in the 1 yr after surgery attests to the plasticity of recovery of the growing skeleton.

Topics: 25-Hydroxyvitamin D 2; Absorptiometry, Photon; Adenoma; Adolescent; Bone and Bones; Bone Density; Humans; Hydronephrosis; Hyperparathyroidism, Primary; Kidney; Kidney Calculi; Lithotripsy; Male; Pain; Parathyroid Neoplasms; Parathyroidectomy; Radionuclide Imaging; Radiopharmaceuticals; Spine; Technetium Tc 99m Sestamibi; Trabecular Meshwork; Ultrasonography

Parathyroid adenomas discovered fortuitously grow very slowly and their cell birth rate greatly declines, features explicable by an initial increase in secretory set-point. In the nodules of severe uraemic parathyroid hyperplasia, there is an increased set-point and decreased expression of both the calcium sensing receptor (CaSR) and the vitamin D receptor (VDR). Accordingly, we examined VDR and CaSR expression in parathyroid adenomas.. We studied 24 patients with primary hyperparathyroidism with a wide range of vitamin D nutritional status (plasma 25-hydroxyvitamin D range 10-107 nmol/l). Eighteen patients discovered by biochemical screening were enrolled in a natural history or treatment option study, and six additional US patients matched a group studied concurrently in India with low plasma 25-hydroxyvitamin D level (< 37 nmol/l).. Receptor expression was determined by immunocytochemistry in each tumour and in 11 cases also in adjacent nonadenomatous tissue. VDR expression was reported as the proportion of positive cells (strongly rather than weakly stained) determined by systematic random sampling and CaSR expression as grey scale values of staining intensity in arbitrary units determined by image analysis.. The mean (SD) proportion of cells positive for VDR was 2.93 (2.17)% in the parathyroid adenomas and 95.7 (5.10)% in the nonadenomatous tissue. In about two-thirds of the cases VDR positive cells could have been remnants of a normal gland, but in the remaining one-third they were too numerous to be accounted for by this explanation. The mean (SD) intensity of CaSR expression was 151 (4.71) units in parathyroid adenomas and 218 (5.0) units in nonadenomatous tissue (P<0.001). The frequency of VDR loss and the changes in CaSR immunohistochemistry were unrelated to race, sex, or disease severity, except that the reduction in CaSR was significantly greater in patients with normal vitamin D nutrition (32.1% vs. 29.0%).. (1) There is reduction of vitamin D receptor expression in almost all cells in parathyroid adenomas. This defect was probably present in the founder cell of the tumour clone in the majority of cases. Since mutations in the vitamin D receptor gene have been sought but not found, possible explanations include inhibition of vitamin D receptor gene transcription, decreased amount of the corresponding mRNA, or failure of normal translation. (2) Reduction in calcium sensing receptor could be either the primary defect or (more commonly) secondary to loss of vitamin D receptor and is of sufficient magnitude to account for the increase in secretory set-point and consequent asymptotic growth and stable clinical course.

Topics: 25-Hydroxyvitamin D 2; Adenoma; Adult; Aged; Aged, 80 and over; Analysis of Variance; Cell Nucleus; Chi-Square Distribution; Female; Humans; Immunohistochemistry; Male; Middle Aged; Neoplasm Proteins; Parathyroid Glands; Parathyroid Neoplasms; Receptors, Calcitriol; Receptors, Calcium-Sensing; Receptors, Cell Surface