Parathyroid mitogenic activity in plasma from patients with familial multiple endocrine neoplasia type 1

Hyperplasia of the parathyroid glands is a central feature of familial multiple endocrine neoplasia type 1. We used cultured bovine parathyroid cells to test for mitogenic activity in plasma from patients with this disorder. Normal plasma stimulated [3H]thymidine incorporation, on the average, to the same extent as it was stimulated in a plasma-free control culture. This contrasted with the results of the tests with plasma from patients with familial multiple endocrine neoplasia type 1, in which parathyroid mitogenic activity increased 2400 percent over the control value (P less than 0.001). Plasma from these patients also stimulated the proliferation of bovine parathyroid cells in culture, whereas plasma from normal subjects inhibited it. Parathyroid mitogenic activity in plasma from the patients with familial multiple endocrine neoplasia type 1 was greater than that in plasma from patients with various other disorders, including sporadic primary hyperparathyroidism (with adenoma, hyperplasia, or cancer of the parathyroid), sporadic primary hypergastrinemia, sporadic pituitary tumor, familial hypocalciuric hypercalcemia, and multiple endocrine neoplasia type 2 (P less than 0.05). Parathyroid mitogenic activity in the plasma of patients with familial multiple endocrine neoplasia type 1 persisted for up to four years after total parathyroidectomy. The plasma also had far more mitogenic activity in cultures of parathyroid cells than did optimal concentrations of known growth factors or of any parathyroid secretagogue. This mitogenic activity had an apparent molecular weight of 50,000 to 55,000. We conclude that primary hyperparathyroidism in familial multiple endocrine neoplasia type 1 may have a humoral cause.     

The parathyroid glands in multiple endocrine neoplasia type 2b.

The histologic features of 21 parathyroid glands obtained from 16 Mayo Clinic patients aged 2 to 52 years who had multiple endocrine neoplasia type 2b (MEN 2b) were evaluated. The findings were correlated with the patients' ages and with the serum concentrations of calcium (15 patients), phosphorus (14 patients), and immunoreactive parathyroid hormone (iPTH) (11 patients), and with the response of serum iPTH to calcium infusion (6 patients). We also studied the histologic features of 13 parathyroid glands obtained from 8 patients not seen at the Mayo Clinic with MEN 2b. The microscopic appearance of the glands was normal in patients under the age of 17; with increased age, the glands did not exhibit normal involution, and an appearance consistent with mild chief-cell hyperplasia was evident. This abnormality was not associated with clinical or laboratory manifestations of hyperparathyroidism. We presently believe that parathyroidectomy for the disorder is not justified.     

Histomorphometric analysis of bone changes in surgically proven primary hyperparathyroidism and nephrolithiasis--the importance of bone biopsy in diagnosis

The morphologic changes in trabecular bone were studied in 60 patients with surgically proven hyperparathyroidism and in 69 patients with nephrolithiasis. The hyperparathyroid bone lesions showed substantial variation in their extent. Four, typical stages were defined. The structure of trabecular bone remained intact in most cases. Bone turnover is significantly higher in the patients with primary hyperparathyroidism. Fifty percent of all patients with nephrolithiasis had bone changes similar to those found in the surgically proven hyperparathyroidism group. In 50% of so-called asymptomatic cases of hyperparathyroidism, the iliac crest biopsy is a useful supplement to clinical and hormonal data in deciding whether to operate on the parathyroid glands. In about 45% of cases, however, no definite diagnoses is possible. The determination of serum parathyroid hormone in primary hyperparathyroidism has a greater importance for diagnostic purposes than morphologic investigation of the bone biopsy.     

西那卡塞对维持性血液透析继发性甲状旁腺功能亢进患者FGF-23的影响

目的 研究西那卡塞对维持性血液透析继发性甲状旁腺功能亢进患者FGF-23的影响。方法 选取2015年1月~2016年10月在天津市第一中心医院血液净化中心行维持性血液透析治疗合并继发性甲状旁腺功能亢进的患者,按入院顺序随机分为观察组及对照组,对照组40例,给予骨化三醇治疗,观察组39例,给予对照组患者相同的骨化三醇治疗的基础上,再加用盐酸西那卡塞片,两组均连续治疗3个月。监测两组治疗前后的尿素氮、血肌酐、KT/V、血清钙、血清磷、碱性磷酸酶、钙磷乘积、全段甲状旁腺激素 (iPTH)及血清FGF-23。结果 治疗后,两组患者的BUN、SCr和Kt/V 较治疗前,差异无统计学意义（P＞0.05）;血清钙观察组治疗后低于对照组（P＜0.05）,对照组治疗前后,差异无统计学意义（P＞0.05）;两组血清磷、ALP、钙磷乘积、iPTH、FGF-23治疗后降低,且治疗后观察组优于对照组,差异有统计学意义 (P<0.05)。结论 西那卡塞对于维持性血液透析合并继发性甲状旁腺功能亢进的患者能够降低甲状旁腺激素及FGF-23水平,缩小甲状旁腺体积。     

Search for the uremic toxin. Decreased motor-nerve conduction velocity and elevated parathyroid hormone in uremia.

In a retrospective analysis to determine whether secondary hyperparathyroidism in uremia has a role in uremic peripheral neuropathy, we simultaneously measured motor-nerve conduction velocity and serum parathormone level in 42 uremic patients. We compared age-matched groups of nondiabetic uremic patients, divided into three groups according to serum parathyroid hormone, for degree of impairment of motor-nerve conduction velocity, and 12 diabetic patients with uremia. The group with highest levels had a significantly (P less than 0.01) lower conduction velocity (25.3 +/- 4.9 m per second) than the group with normal or slightly elevated parathyroid hormone, who had only mild depression of nerve conduction (45.1 +/- 1.3 m per second). Mean serum calcium and creatinine were not significantly different between groups. Nerve conduction velocity was similarly depressed in 17 patients on additional dialysis studied prospectively and divided into groups according to parathyroid hormone levels. These results suggest a relation between high parathormone levels and uremic neuropathy and implicate parathyroid hormone as a uremic toxin.     

Interleukin-6 production and secretion by human parathyroids

Parathyroid hormone (PTH) stimulates osteoblasts to produce the proinflammatory cytokine interleukin-6 (IL-6), causing bone resorption. In patients with primary hyperparathyroidism, elevated serum levels of IL-6 normalize after resection of parathyroid tumours. Because IL-6 is also expressed in normal parathyroids and in other endocrine cells (adrenal and islet), we hypothesized that parathyroid tumours might contribute directly to the elevated serum IL-6 levels in patients with hyperparathyroidism. Immunohistochemistry identified IL-6, PTH, and chromogranin-A (an endocrine and neuroendocrine tumour marker) in normal, adenomatous and hyperplastic parathyroids. Using immunofluorescence and confocal microscopy, IL-6 co-localized with PTH and with chromogranin-A in parathyroid cells. All cultured parathyroid tumours secreted IL-6 at levels markedly higher than optimally stimulated peripheral blood mononuclear cells. Supernates from cultured parathyroids stimulated proliferation of an IL-6-dependent cell line, and anti-IL-6 MoAb abolished this stimulatory effect. IL-6 mRNA was documented in cultured parathyroid tumours, cultured normal parathyroids, fresh operative parathyroid tumours and fresh operative normal specimens. In conclusion, these data show that parathyroid tumours and normal parathyroids contain, produce and secrete IL-6. Our findings present a novel pathway by which human parathyroids may contribute markedly to IL-6 production and elevation of serum IL-6 levels in patients with hyperparathyroidism. The physiological relevance of IL-6 production by human parathyroids remains to be determined, but IL-6 secretion by parathyroid tumours may contribute to bone loss and to other multi-system complaints observed in these patients.     

Use of C-terminal parathyroid assays in a large metropolitan hospital

The use of C-terminal parathyroid (C-PTH) assays, performed at a commercial laboratory, was evaluated for one year at Charity Hospital, New Orleans. Of 72 patients, the most frequent diagnosis was primary hyperparathyroidism (1 degree HPT) (n = 17, 24 percent), followed by malignancy (n = 15, 21 percent), chronic renal disease (n = 10, 14 percent), and thiazide diuretics (n = 5, 7 percent). In the 1 degree HPT group, all were hypercalcemic (mean serum calcium, 11.6 ml per dL) and had elevated C-PTH. Patients with malignancy had higher mean serum calcium levels than patients with 1 degree HPT. Three patients with malignancy had elevated C-PTH; two had suspected coexisting 1 degree HPT and neoplasm; and one had suspected pseudohyperparathyroidism. Patients with chronic renal disease undergoing dialysis treatment had the highest C-PTH recorded (all had elevated C-PTH) but only 50 percent were hypocalcemic. Three of the five patients on thiazide diuretics had increased C-PTH, indicating that the withdrawal of this drug may unmask underlying hyperparathyroidism. Appropriate reasons for ordering C-PTH include evaluation of hypercalcemia (n = 32, 44 percent) or hypocalcemia (n = 12, 17 percent); indicated clinical reasons not included in the hyper- or hypocalcemic groups, including chronic renal disease in patients undergoing dialysis or transplant (n = 5, 7 percent); in suspected 1 degree HPT, (n = 5, 7 percent); and in patients with renal stones (n = 2, 3 percent) or on thiazide diuretics (n = 2, 3 percent). Based on laboratory and clinical criteria, C-PTH assay was appropriately used in 81 percent of the patients surveyed (58/72).     

Value of plasma chloride concentration and acid-base status in the differential diagnosis of hyperpara-thyroidism from other causes of hypercalcaemia

A study is reported of the estimation of plasma chloride concentration and acid-base status in the differentiation of primary hyperparathyroidism from all other causes of hypercalcaemia. In the two groups of patients studied, all of whom had hypercalcaemia, there was complete separation between the two groups on the basis of plasma chloride concentration and acid-base status. In 16 patients with primary hyperparathyroidism the increase in plasma chloride concentration and associated metabolic acidosis could have been accounted for by the known renal tubular effects of parathyroid hormone. In 13 patients with hypercalcaemia due to various other causes the decrease in plasma chloride concentration and associated metabolic alkalosis could be accounted for either by the known effects of an excess of calcium-ion on the renal tubules, or perhaps by suppression of endogenous parathyroid hormone secretion. In patients with hypercalcaemia and hypophosphataemia of ;pseudohyperparathyroidism' associated with non-endocrine tumours it is postulated that the low plasma chloride concentrations and metabolic alkalosis found in these patients were due either to a differing biological activity of the parathyroid-hormone-like polypeptide secreted by the tumour cells, or possibly to simultaneous secretion by these cells of an ACTH-like polypeptide.     

Normocalcemic primary hyperparathyroidism in patients with recurrent kidney stones: pathological analysis of parathyroid glands

The lack of overt elevation of serum calcium concentration in some patients suffering from primary hyperparathyroidism is an intriguing clinical phenomenon. Previous studies have substantiated abnormal parathyroid tissue in these patients, but the extent and mode of derangements remained largely undefined. The parathyroid tissues from patients of normocalcemic primary hyperparathyroidism (NCPHPT) and those having normal parathyroid glands, hypercalcemic primary hyperplasia, secondary hyperplasia, and adenoma were compared by undertaking quantitative immunohistochemistry analysis on tissue microarray. The statistic results suggested that the parathyroid tissue of NCPHPT approximates more to normal gland than to its counterpart in other groups of parathyroid proliferative diseases in terms of the lack of significant alterations of calcium-sensing receptor (CaSR), chromogranin A (CGA), parathyroid hormone (PTH), and proliferation index (Ki67). On the other hand, the depressed vitamin D receptor (VitDR) and elevated cyclin D1 (CyD1) of NCPHPT indicated the inherent functional abnormalities in parathyroid cells. Our results imply that inherent functional disengagement may exist between CaSR and CyD1 or between CaSR and VitDR or both in parathyroid cells of symptomatic NCPHPT. Lack of enhanced release of CGA and PTH and discordance between proliferative activity and CyD1 expression in parathyroid cells may further hinder the development of hypercalcemia.     

Intraoperative monitoring of parathyroid hormone with a rapid automated assay that is commercially available

The Mayo Clinic was one of the first institutions to develop an in-house rapid parathyroid hormone (PTH) assay that used homegrown antibodies to monitor plasma PTH levels during parathyroidectomy. This PTH assay is economical, but it requires highly trained technologists and an experienced laboratory director and it is difficult to perform in the operating suite. We sought a fully automated multipurpose autoanalyzer with bar code reader to identify different patients' names and capacity to manage specimens from several patients who are having simultaneous operations. In addition, after complete tumor removal, the plasma PTH level should decrease to < 25% of the baseline level; otherwise, it may indicate that the antibodies used in the assay have cross-reacted with long half-life fragments other than intact PTH, which has a half-life of only approximately 2 min. An automated multipurpose analyzer, the Immulite 1000 with a Turbo PTH kit (DPC), fits these criteria and has replaced our in-house rapid assay. Of 47 patients who had parathyroidectomy for primary hyperparathyroidism and were tested with the new equipment, 45 (96%) had their plasma PTH levels decrease to < 25% of the baseline levels. In 41 of 47 patients (87%), the PTH value decreased to < 5 pmol/L (provisional reference range) within 20 min after tumor excision. The usefulness of the PTH assay extends from the traditional diagnosis of parathyroid disease to intraoperative monitoring, helping to ensure a higher cure rate.     

Relationship between vitamin D, parathyroid hormone, and bone mineral density in elderly Koreans

There is controversy regarding definition of vitamin D inadequacy. We analyzed threshold 25-hydroxyvitamin D (25[OH]D) below which intact parathyroid hormone (iPTH) increases, and examined age- and sex-specific changes of 25(OH)D and iPTH, and association of 25(OH)D and iPTH with bone mineral density (BMD) in elderly Koreans. Anthropometric parameters, serum 25(OH)D and iPTH, lumbar spine and femur BMD by dual-energy radiography absorptiometry (DXA) were measured in 441 men and 598 postmenopausal women. iPTH increased below serum 25(OH) of 36.7 ng/mL in men, but failed to reach plateau in women. Femur neck BMD above and below threshold differed when threshold 25(OH)D concentrations were set at 15-27.5 ng/mL in men, and 12.5-20 ng/mL in postmenopausal women. Vitamin D-inadequate individuals older than 75 yr had higher iPTH than those aged ≤ 65 yr. In winter, age-associated iPTH increase in women was steeper than in summer. In conclusion, vitamin D inadequacy threshold cannot be estimated based on iPTH alone, and but other factors concerning bone health should also be considered. Older people seemingly need higher 25(OH)D levels to offset age-associated hyperparathyroidism. Elderly vitamin D-inadequate women in the winter are most vulnerable to age-associated hyperparathyroidism.     

An unusual cause of hypercalcemia in polycythemia vera: parathyroid adenoma

In this paper we describe a patient with polycythemia vera (PV), who presented with hypercalcemia due to a parathyroid adenoma. In November 1999, the patient was admitted to our hospital with meteorism and constipation. Her physical examination revealed plethora and hepatosplenomegaly. Laboratory data revealed hyperparathyroidism in addition to PV: Rbc 8 x 10(6)/mm3, Hct 63.7%, serum calcium 13.4 mg/dl, serum phosphorus 1.2 mg/dl, albumin 4.25 mg/dl, and alkaline phophatase activity 433 U/l. Intact Parathyroid Hormone level (iPTH) was 376 pg/ml (n.v.12-72 pg/ml). Twenty-four hour urinary calcium excretion was higher than normal (900 mg). A parathyroid adenoma was detected with Tc-99m sesta-MIBI scanning under the left lobe of the thyroid gland and an ultrasonographic examination of the neck also supported the diagnosis. The patient was recommended for surgery. The histopathological examination confirmed the diagnosis. Postoperatively, iPTH dropped to 53.4 pg/ml at the 15 th minute and to 33.5 pg/ml at the first hour. The calcium level was 7.5 mg/dl one hour after the operation. Five days later, Hct was 40.8%. This case represents a rare association between PV and primary hyperparathyroidism, and may provide evidence for a causal link between PTH and polycythemia vera in our patient. In conclusion, this case indicates that the differential diagnosis of hypercalcemia and polycythemia vera should also include the possibility of a parathyroid tumor in addition to malignancy.     

Rapid intraoperative parathyroid hormone testing with surgical pathology correlations: the "chemical frozen section"

The classic surgical approach to patients undergoing parathyroidectomy for primary or secondary hyperparathyroidism has experienced a dramatic shift owing to preoperative localization of the affected glands and/or the use of rapid intraoperative parathyroid hormone (RI-PTH) assays, allowing for minimally invasive surgical excisions. Institutional experience with 141 patients who underwent parathyroidectomy aided by the use of RI-PTH is reviewed. The orientation provided by the intraoperative assay is essential in guiding the surgeon in these minimally invasive procedures, it helps reveal the cases of primary hyperparathyroidism with involvement of more than 1 gland, and it replaces the need for performing frozen sections, except for cases of secondary hyperparathyroidism.     

Sensitivity of the parathyroid hormone-1,25-dihydroxyvitamin D axis to variations in calcium intake in patients with primary hyperparathyroidism

Previous studies have demonstrated a spectrum of parathyroid responsivity to alterations in the extracellular calcium concentration in patients with primary hyperparathyroidism, but studies employing physiologic amounts of calcium have not, to our knowledge, been reported. We studied 18 unselected patients with primary hyperparathyroidism at the lower (400 mg) and upper (1000 mg) limits of a normal dietary intake of calcium. The diet containing high-normal amounts of calcium induced only a slight increase in 24-hour calcium excretion (from 281 to 337 mg per day) yet was associated with significant reductions in fasting serum levels of immunoreactive parathyroid hormone (from 60 to 50 nleq per milliliter; P less than 0.001), nephrogenous cyclic AMP (from 3.52 to 2.63 nmol per deciliter of glomerular filtrate; P less than 0.001), and plasma levels of 1,25-dihydroxyvitamin D (from 74 to 58 pg per milliliter; P less than 0.001). A wide spectrum of responses was observed, with some patients appearing to have essentially autonomous parathyroid function and others having marked suppressibility (up to 50 per cent) of the parathyroid hormone-vitamin D axis. We conclude that parathyroid function may be suppressed by dietary calcium in some patients with primary hyperparathyroidism.     

Decreased expression of calcium receptor in parathyroid tissue in patients with hyperparathyroidism secondary to chronic renal failure

The response of parathyroid cells to serum calcium is regulated by a calcium-sensing receptor protein (CaR). In patients with chronic renal failure, hypocalcemia contributes to the parathyroid hyperplasia and increased parathyroid hormone secretion characteristic of secondary hyperparathyroidism (sHPT). However, patients with uremia also display reduced sensitivity to extracellular calcium; this seems to be owing to an alteration of the receptor mechanism. This study examined calcium receptor expression in the parathyroid tissue of patients with sHPT, using immunohistochemical technicques and comparison with normal tissue and parathyroid glands of patients with primary hyperparathyroidism. In all the glands studied, immunostaining was more intense in chief cells than in oxyphilic, transitional, and clear cells. The parathyroid glands of patients with sHPT displayed significantly reduced expression of CaR with respect to morphologically normal ones; a very similar reduction is reported in adenomas. Furthermore, in glands displaying multinodular hyperplasia, expression was less marked in nodule-forming cells than in internodular areas. The decreased expression of calcium receptors in the parathyroid tissue of uremic patients was thought to be owing to the different cell populations present; these parathyroid glands contained predominantly transitional, oxyphilic, and clear cells, which normally express fewer receptors than chief cells, which are more abundant in normal glands.     

Substrate-product relation of 1-hydroxylase activity in primary hyperparathyroidism

The synthesis of the active form of vitamin D, 1,25-dihydroxyvitamin D (1,25-(OH)2D), is thought to be relatively insensitive to the serum concentration of its precursor, 25-hydroxyvitamin D (25-OH-D). We compared the effect of oral administration of 25-OH-D3 (50 micrograms per day for one month) on serum concentrations of calcium, phosphate, parathyroid hormone, 25-OH-D, and 1,25-(OH)2D in five healthy adults and in six patients with primary hyperparathyroidism. In normal adults the mean (+/- S.D.) serum level of 25-OH-D rose from 18 +/- 9 to 136 +/- 47 ng per milliliter; no significant changes were observed in the other serum levels. In contrast, comparable increases in the levels of circulating 25-OH-D in patients with primary hyperparathyroidism caused a consistent slight rise in serum calcium and phosphate levels, a partial suppression of parathyroid hormone, and a sharp increase in the level of 1,25-(OH)2D. During this period a significant positive correlation was found between serum concentrations of 25-OH-D and 1,25-(OH)2D (P less than 0.001). These results provide evidence that in patients with primary hyperparathyroidism, levels of circulating 1,25-(OH)2D may be more dependent on the prevailing serum concentrations of 25-OH-D than they are in normal adults.     

Parathyroid hormone immunohistochemistry in dogs with primary and secondary hyperparathyroidism: the question of adenoma and primary hyperplasia

In primary hyperparathyroidism, calcium homeostasis is disrupted by excessive synthesis and secretion of parathyroid hormone (PTH), which is usually caused by a solitary adenoma, or less often by nodular hyperplasia or carcinoma of the parathyroid glands. So far, the distinction between these forms of primary hyperparathyroidism has been made by histological examination. In this report clinical and histological findings, including PTH immunohistochemistry, are described in five dogs with primary hyperparathyroidism, three dogs with secondary hyperparathyroidism due to chronic renal failure, and eight control dogs. In the dogs with primary hyperparathyroidism, nodular adenomatous hyperplasia was found in two animals and parathyroid adenoma in three. The dogs with chronic renal failure had diffuse parathyroid gland hyperplasia. The parathyroid glands of the control dogs and the inactive cells surrounding the hyperplastic nodules showed slight to moderate, localized, paranuclear PTH immunolabelling. In the primary nodular and secondary diffuse hyperplasia, all parathyroid cells had a diffuse cytoplasmic PTH labelling pattern, sometimes in combination with localized paranuclear labelling. In parathyroid adenoma, areas with either paranuclear labelling or diffuse cytoplasmic labelling were observed. As both parathyroid adenoma and primary nodular parathyroid gland hyperplasia have characteristics of intrinsic autonomy (i.e., suppression of the remaining endocrine tissue), there would seem to be no functional difference between the two abnormalities. It is argued that primary (multi)nodular hyperplasia is a multiple form of parathyroid adenoma.     

Rapid Decrease of Intact Parathyroid Hormone Could Be a Predictor of Better Response to Cinacalcet in Hemodialysis Patients

Purpose

Cinacalcet is effective for treating refractory secondary hyperparathyroidism (SHPT), but little is known about the response rates and clinical factors influencing the response.

Materials and Methods

A prospective, single-arm, multi-center study was performed for 24 weeks. Cinacalcet was administered to patients with intact parathyroid hormone (iPTH) level greater than 300 pg/mL. Cinacalcet was started at a dose of 25 mg daily and titrated until 100 mg to achieve a serum iPTH level <300 pg/mL (primary end point). Early response to cinacalcet was defined as a decrease of iPTH more than 50% within one month.

Results

Fifty-seven patients were examined. Based on the magnitude of iPTH decrease, patients were divided into responder (n=47, 82.5%) and non-responder (n=10, 17.5%) groups. Among the responders, 38 achieved the primary end point, whereas 9 patients showed a reduction in serum iPTH of 30% or more, but did not reach the primary end point. Compared to non-responders, responders were significantly older (p=0.026), female (p=0.041), and diabetics (p<0.001). Additionally, early response was observed more frequently in the responders (30/47, 63.8%), of whom the majority (27/30, 90.0%) achieved the primary end point. Multivariate analysis showed that lower baseline iPTH levels [odds ratio (OR) 0.96, 95% confidence interval (CI) 0.93-0.99], the presence of diabetes (OR 46.45, CI 1.92-1125.6) and early response (OR 21.54, CI 2.94-157.7) were significant clinical factors affecting achievement of iPTH target.

Conclusion

Cinacalcet was effective in most hemodialysis patients with refractory SHPT. The presence of an early response was closely associated with the achievement of target levels of iPTH.     

Post-surgical follow-up of primary hyperparathyroidism associated with multiple endocrine neoplasia type 1

The bone mineral density increments in patients with sporadic primary hyperparathyroidism after parathyroidectomy have been studied by several investigators, but few have investigated this topic in primary hyperparathyroidism associated with multiple endocrine neoplasia type 1. Further, as far as we know, only two studies have consistently evaluated bone mineral density values after parathyroidectomy in cases of primary hyperparathyroidism associated with multiple endocrine neoplasia type 1. Here we revised the impact of parathyroidectomy (particularly total parathyroidectomy followed by autologous parathyroid implant into the forearm) on bone mineral density values in patients with primary hyperparathyroidism associated with multiple endocrine neoplasia type 1. Significant increases in bone mineral density in the lumbar spine and femoral neck values were found, although no short-term (15 months) improvement in bone mineral density at the proximal third of the distal radius was observed. Additionally, short-term and medium-term calcium and parathyroid hormone values after parathyroidectomy in patients with primary hyperparathyroidism associated with multiple endocrine neoplasia type 1 are discussed. In most cases, this surgical approach was able to restore normal calcium/parathyroid hormone levels and ultimately lead to discontinuation of calcium and calcitriol supplementation.     

Reduced binding of [3H]1,25-dihydroxyvitamin D3 in the parathyroid glands of patients with renal failure

This study examined the hypothesis that altered binding of 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) to parathyroid receptors might be involved in the pathogenesis of secondary hyperparathyroidism associated with chronic renal failure. The binding of [3H]1,25-(OH)2D3 to hyperplastic parathyroid glands obtained from seven patients with chronic renal failure was measured. These values were compared with those for binding to hyperplastic parathyroid tissue obtained from six patients who had received renal transplants and for binding to parathyroid adenomas removed from five patients who had primary hyperparathyroidism. We found that Nmax (an estimate of the concentration of 1,25-(OH)2D3 receptors) was reduced (42 +/- 15 fmol per milligram of protein) in patients with chronic renal failure as compared with patients with transplanted kidneys (78 +/- 24 fmol per milligram of protein) and patients with primary hyperparathyroidism (114 +/- 30). Nmax correlated inversely with the severity of renal dysfunction, the serum level of phosphorus, and the logarithm of the serum level of immunoreactive parathyroid hormone. These observations suggest that 1,25-(OH)2D3 binding by parathyroid tissue is reduced in chronic renal failure. This may contribute to the pathogenesis of secondary hyperparathyroidism by reducing the inhibition by 1,25-(OH)2D of parathyroid hormone secretion. The low serum levels of 1,25-(OH)2D in chronic renal failure may accentuate this effect.