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[Primary hyperparathyroidism: parathyroid scintigraphy and ultrasound in problem patients].

AIM: In a retrospective study, the sensitivity of parathyroid scintigraphy and ultrasound was investigated in patients with primary hyperparathyroidism (HPT) with prior histories of surgery of the thyroid or parathyroid (unsuccessful or recidive). METHODS: Preoperative ultrasound and parathyroid scintigraphy were performed on 65 patients who had had successful surgery and on 12 who had had unsuccessful surgery. The scintigraphy was carried out using a combined double phase/double nuclide technique with 300-600 MBq 99mTc-sestamibi for parathyroid imaging and 80-100 MBq 99mTc-pertechnetate for thyroid imaging. RESULTS: The sensitivity of parathyroid scintigraphy was 86% in patients with normal thyroid glands, 77% in those with recurrent goiter, and 62% in those with recurrent or persistent HPT. The ultrasound sensitivity was 86%, 50%, and 57% respectively. CONCLUSION: The sensitivity of parathyroid scintigraphy and ultrasound decreases considerably after surgery. That of parathyroid scintigraphy lay significantly below results published to date. However, parathyroid scintigraphy should be performed precisely in these cases, because the number of alternative parathyroid imaging methods aside from ultrasound are limited.

Adult↗

Long-term effect of intravenous calcitriol on the treatment of severe hyperparathyroidism, parathyroid gland mass and bone mineral density in haemodialysis patients.

We conducted this study on 15 chronic haemodialysis patients to evaluate the efficacy of i.v. calcitriol over a 1-year period in the treatment of severe secondary hyperparathyroidism (HPT), in particular its effect on bone mineral density (BMD) and parathyroid gland mass. Mean age was 39 +/- 11.9 (20-65) years and dialysis duration was 58 +/- 3 (19-130) months. i.v. calcitriol was given at a dose of 1 microg post-dialysis 3 times/week for 3 weeks; the dose was then adjusted to maintain the total serum calcium at less than 2.88 mmol/l. The maximum dose was 3 microg 3 times/week. Serum calcium (Ca) and phosphorus (P) were determined prior to treatment, then weekly for 6 weeks and every 2 weeks thereafter. Skeletal survey, dual photon densitometry and parathyroid ultrasound (US) were done prior to treatment and after 1 year. Bone biopsy was done in 10 patients at the beginning of treatment. There was a significant reduction (p < 0.01) in pre-treatment mid-region serum parathyroid hormone (PTH) from 1,476 +/- 895 to 489 +/- 485 P mol/l, as well as alkaline phosphatase (p < 0.04) from 236.5 +/- 221 to 116.3 +/- 49 U/l. This was without a significant increase in serum Ca (2.15 +/- 0.25 to 2.44 +/- 0.26 mmol/l, p = 0.08). Three patients had recurrent hypercalcaemia which responded to reduction of Ca in dialysate. There was a significant increase in BMD over the spine from 1.071 +/- 0.25 to 1.159 +/- 0.22 g/cm2 (p < 0.003) with a percent increase of 9.3 +/- 8.9% as well as over the femoral neck from 0.834 +/- 0.002 to 0.89 +/- 0.09 g/cm2 (p < 0.001) with a percent increase of 7.45 +/- 6.81%. Five patients had enlarged parathyroid glands by US and in 3 of these, there was a significant reduction to normal with treatment. Bone biopsy was done in 10 patients. Six patients had predominant hyperparathyroid bone disease and 4 had mixed uraemic osteodystrophy. In conclusion, long-term i.v. treatment with calcitriol is effective in the treatment of severe secondary HPT. PTH decreased without a significant increase in serum Ca. BMD also increases during this therapy.

Absorptiometry, Photon↗

[Tertiary hyperparathyroidism: parathyroid cancer with liver metastases in a hemodialyzed patient].

Parathyroid cancer is very rare in chronic renal failure. Only twelve cases have been described, but the actual incidence might be under estimated. Monoclonal proliferation have been demonstrated in hyperplasic parathyroid glands of uremic patients and the diagnosis between benign or malignant tumor may be difficult. Evidence for a deletion of the "Retinoblastoma Tumor Suppressor gene" (RB gene) is helpful for the diagnosis of parathyroid cancer, especially in the absence of dissemination. A 46-years old male patient on dialysis since 1989 for polycystic kidney disease developed a refractory and persistent hyperparathyroidism after parathyroidectomy with vascular and osteoarticular complications. Liver nodules were localised by sestaultrasonography. MIBI radionucleid scan and were confirmed by CT-scan, and ultrasonography. Diagnosis of parathyroid cancer was confirmed by the immuno-histochemical study of the biopsied liver nodules and the histopathological review of the removed parathyroid glands.

Adenocarcinoma↗

Mast cells in parathyroid glands of hyperparathyroidism.

Parathyroid glands from cases of hyperparathyroidism have been examined with particular attention to mast cells. In ;normal' glands accompanying an adenoma they were common, although there was a wide range in their frequency, whereas in pathological tissue, both adenoma and hyperplasia, mast cells were scarce. This difference between glands was examined with respect to alterations in gland size, to variations in the amount of interstitial tissue, to degrees of overactivity, and to anatomical development of the glands. No conclusions can be drawn with regard to the significance of mast cells in parathyroid tissue.

Adenoma↗

Relationship between external and cytoplasmic calcium concentrations, parathyroid hormone release and weight of parathyroid glands in human hyperparathyroidism.

Parathyroid hormone (PTH) release and cytoplasmic calcium concentrations were investigated at ambient calcium concentrations of 0.5-3.0 mmol/l in dispersed parathyroid cells from 44 hypercalcaemic patients with primary or uraemic hyperparathyroidism (HPT). In comparison with parathyroid cells from adult cattle, release of PTH by human preparations was reduced and values of the ambient calcium concentration causing half-maximal inhibition of PTH release (median effective dose, ED50) were significantly increased. Half-maximal inhibition of PTH release was obtained with concentrations of cytoplasmic calcium almost identical to the concentrations of ionized calcium in the plasma of the individual patients. Cytoplasmic concentrations of calcium in the parathyroid cells were inversely related to release of PTH. Concentrations of cytoplasmic calcium were significantly lower in human than in bovine cells and the ED50 for ambient calcium increase on cytoplasmic calcium was raised to the same extent as the ED50 for ambient calcium inhibition of PTH release in human compared with bovine cells. The magnitude of the increased ED50 for ambient calcium inhibition of PTH release and increase of cytoplasmic calcium concentration was similar in adenomas and sporadic as well as hereditary primary hyperplasias, but the secretion was the least aberrant in uraemic hyperplasias, although they had by far the largest glandular mass. Serum concentrations of total calcium before surgery correlated with the ED50 for ambient calcium effects of PTH release and cytoplasmic calcium, but not with glandular weight. These findings demonstrate a universally abnormal regulation of cytoplasmic calcium in HPT and its importance for PTH release, and that disturbance of cytoplasmic calcium rather than the increased glandular mass contributes to the hypercalcaemia in adenomatous and hyperplastic HPT.

Calcium↗

Trial to predict malignancy of affected parathyroid glands in primary hyperparathyroidism.

Parathyroid cancer is rare but relatively frequent in Japan compared to Western countries. Surgical parathyroidectomy is the primary choice for radical treatment of primary hyperparathyroidism (pHPT), hence it is important to distinguish malignant from benign tumor in the determination of surgical indication as well as method of operation. However, it is not easy to diagnose parathyroid cancer prior to operation. In the present study, we analyzed the background data, biochemical data and bone mineral density (BMD) of 131 patients with pHPT (111 benign and 20 malignant). BMD of the lumbar spine and mid-radius was measured by dual-energy X-ray absorptiometry. Serum levels of calcium, alkaline phosphatase (ALP), and parathyroid hormone (PTH) were significantly higher in malignant group compared to benign one. The extent of elevation of mid PTH seemed to be higher than that of intact PTH in malignant group. Age-, gender-, and race-adjusted BMD of distal one-third of radius was significantly decreased in malignant group compared to benign one, although that of lumbar spine was not significantly different between the two groups, indicating that osteopenia was marked in the region which was rich in cortical bone in malignant group. On the other hand, serum levels of calcium, ALP, and mid PTH as well as age were selected as predictors of malignancy in univariate logistic regression analysis, while serum level of intact PTH was not selected. In conclusion, radial BMD was lower in malignant group compared to benign one in pHPT. Serum levels of calcium, ALP and mid PTH were useful to predict malignancy of affected parathyroid glands in pHPT patients.

Alkaline Phosphatase↗

Influence of 1,25-dihydroxycholecalciferol on parathyroid activity in patients with primary hyperparathyroidism.

Parathyroid morphology and blood chemistry were studied in five patients with primary hyperparathyroidism treated with 1,25-dihydroxycholecalciferol (1,25-DHCC) for 2 to 11 days before planned operation. Before the institution of treatment all patients were hypercalcemic, whereas the serum immunoreactive parathyroid hormone (iPTH) concentration either was elevated or normal. During the treatment the urinary phosphate excretion was significantly increased, whereas the calcium excretion and the serum concentrations of calcium and phosphate were unaffected or only slightly changed. Serum iPTH decreased during the first days of treatment, but returned then to increased levels close to the pretreatment ones. The treatment was tolerated well by the patients. Light and electron microscopy of the removed parathyroid glands disclosed one adenoma in each of the five patients, the other glands exhibiting either a slight hyperplasia or a normal appearance. Both the adenomatous and the non-adenomatous parathyroid tissue showed a predominance of dark chief cells and three of the adenomas exhibited a varying number of atrophic and oxyphil cells. The non-adenomatous glands were composed of atrophic and dark chief cells. Signs of low functional activity were ultrastructurally observed in the parathyroid parenchymal cells. It is suggested that 1,25-DHCC treatment of patients with primary hyperparathyroidism inhibits parathyroid hormone secretion.

Adult↗

Localization of parathyroid tumors using endoscopic ultrasonography in primary hyperparathyroidism.

Parathyroid adenomas responsible for primary hyperparathyroidism may be difficult to detect preoperatively. Furthermore parathyroid adenomas may arise behind the (nodular) thyroid gland, in a deep cervical location, and plans should be plane. The purpose of the present prospective study was to evaluate echoendoscopy, and to compare its accuracy to that of non invasive tests. Fourteen consecutive patients with primary hyperparathyroidism were prospectively studied. All patients underwent echoendoscopy, ultrasonography (US), CT scanning or magnetic resonance imaging (MRI) and Tc 99m sestamibi scanning before undergoing initial neck exploration. The parathyroid pathology was a solitary adenoma in 13 patients and a 4 glands hyperplasia in one. All tests were corroborating in 5 cases. Four adenomas were localized to the correc tside (33%), and no test accurately localized all hyperplastic glands. EUS, sestamibi and CT scanning or MRI correctly identified 10 parathyroid tumors in 14 cases (71%). US correctly localized only 5 adenomas (sensitivity 36%). The sensitivity of EUS to detect parathyroid adenomas is superior to US (p<0.05) and comparable to that of other non invasive tests. We conclude that EUS may be an useful tool to localize parathyroid lesions. This method may replace US prior to initial neck exploration with further miniaturization of probes, or find an intermediate place among invasive and noninvasive preoperative localization procedures in patients with persistent or recurrent PHPT.

Adenoma↗

The parathyroid calcium receptor: a novel therapeutic target for treating hyperparathyroidism.

Parathyroid cells, C-cells, and certain cells in the kidney express a cell surface calcium (Ca2+) receptor which enables these cells to detect and respond to changes in the concentration of extracellular Ca2+. This receptor protein is a member of the G protein-coupled receptor superfamily and shares limited sequence homology only with metabotropic glutamate receptors. The Ca2+ receptor is the primary physiological mechanism regulating the secretion of parathyroid hormone (PTH) and plays a pivotal role in maintaining systemic Ca2+ homeostasis. Compounds that act as Ca2+ receptor agonists are called calcimimetics because they mimic or potentiate the effects of extracellular Ca2+ on parathyroid cell function. NPS R-568 is a small organic calcimimetic compound that acts as a positive allosteric modulator to increase the sensitivity of the Ca2+ receptor to activation by extracellular Ca2+. In normal rats, orally administered NPS R-568 decreases plasma levels of PTH and Ca2+ and, at higher doses, increases plasma levels of calcitonin. The changes in the circulating levels of these two hormones explain the hypocalcemia caused by this compound. NPS R-568 also effectively lowers plasma PTH levels in normal humans and in rat models of secondary hyperparathyroidism. Calcimimetic compounds that target the Ca2+ receptor provide a novel therapeutic approach for treating primary and secondary hyperparathyroidism.

Animals↗