Double-phase parathyroid MIBI ((99m)Tc-sestamibi) was performed in 27 patients with secondary hyperparathyroidism (SPT). Focal areas of increased uptake were scored for intensity on a three-point scale. All patients underwent subtotal parathyroidectomy (SPTx), and a total of 78 glands were removed at operation. Blood was obtained from the jugular vein before and after SPTx to measure the parathyroid hormone (PTH) levels. The volume and weight of the glands were calculated. The tissue was divided, with one aliquot being used for cell cycle analysis. The nuclei were acquired by flow cytometry and analyzed using CELLEIT software. Cell viability was assessed by flow cytometry and analyzed with LYSIS II software. Positive MIBI uptake was observed in 88.8% of patients. Focal MIBI uptake of one, two, or three glands was observed in 6, 11, and 8 patients, respectively. All patients experienced an 86% decrease in PTH blood level after SPTx compared to that before excision. A correlation was found between the volume of glands and the blood levels of intact PTH (iPTH) (r = 0.5, p < 0.05). A positive correlation was observed between MIBI uptake and the iPTH levels before SPTx (p < 0.01) and between the uptake of MIBI in the parathyroid glands and the cell cycle phases; low-grade uptake correlated with the G(0) phase and higher uptake with G(2)+S phase (r = 7, p < 0.01). No correlation was observed between MIBI uptake and the weight of the glands. MIBI scintigraphy accurately reflects the functional status of the hyperplastic parathyroid glands: Higher uptake grades correlated with the active growth phase. MIBI uptake does not reveal parathyroid enlargement; rather, it identifies the presence of hyperfunctioning autonomous glands. SPTx and total parathyroidectomy with autografting (TPTx+A) are the most widely accepted surgical approaches for patients with SPT. Reoperation for recurrence is necessary in 6% to 15% of cases. MIBI is now considered to be the radionuclide of reference for parathyroid gland scanning, although it is widely accepted that it produces poor results when trying to detect hyperplastic glands.

OBJECTIVE

Primary hyperparathyroidism (HP1) in childhood is thought to be extremely rare. Its exact incidence remains unknown, as do the characteristics of HP1. A retrospective study collection was conducted on cases supplied by members of the Working Group on Calcium Metabolism throughout France over a 20-year period (1984-2004), since the availability of the intact parathormone (iPTH) radioimmunoassay.

RESULTS

55 cases were collected of which 11 were neonates. Among the 44 children and adolescents, there were 18 male and 26 female patients, ranging in age from 6 to 18 (mean 13) years. 83% were symptomatic and 43% had nephrolithiasis. Symptoms were associated with high serum calcium and inappropriate iPTH levels. Ultrasonography and technetium-labelled methoxyisobutylisonitrile scintigraphy are useful tools for the preoperative localization of adenomas, particularly in adolescents. Intraoperative iPTH assays are effective in minimizing invasive parathyroidectomy. All patients, except neonates, underwent surgery: 29 adenomas and 11 hyperplasias were found. Two multiple endocrine neoplasias (MENs) were subsequently discovered. Since the calcium-sensing receptor (CaSR) mutation was reported, the form of management in neonates has become more medical (intravenous diphosphonates) than surgical. On follow-up no recurrence was observed except for MEN.

CONCLUSIONS

These national results reflect HP1 epidemiology. HP1 is a rare entity and appears to be a severe disease in terms of symptoms with regard to management. The use of molecular biology tests could be useful not only in neonatal cases (CaSR mutation) but also prior to surgery in children (MEN mutation).

OBJECTIVE

To conduct a retrospective study of 15 patients with persistent (n = 4) and recurrent (n = 11) hyperparathyroidism.

BACKGROUND

Secondary hyperparathyroidism may persist or recur because of hyperfunction of the parathyroid remnant or transplanted parathyroid tissue. It is a great challenge to localize the parathyroid tissue either in the neck or at the arm before surgery.

METHODS

From June 1994 to June 2000, 15 patients with recurrent and persistent secondary hyperparathyroidism were selected for surgery for the removal of parathyroid tissue. The indications for surgery included bone pain, hypercalcemia, general weakness, and skin itching. Their ages ranged from 23 to 66 years. The average period of persistent hyperparathyroidism after total parathyroidectomy with autotransplantation was 3.8 months; that of recurrent hyperparathyroidism was 53 months. Serum levels of calcium, phosphorus, parathyroid hormone (iPTH), and alkaline phosphatase were measured before surgery and 1 week after surgery. Before surgery, the parathyroid gradient in the blood draining the graft-bearing arm versus the contralateral arm was measured. A 99mTc-sestamibi (MIBI) scan was performed including the neck and the arm area, and a computed tomography (CT) scan of the neck was performed to confirm the localization. The neck and mediastinal exploration was done directly at the side of localization under general anesthesia to remove the parathyroid tissue that had been located with the MIBI scan or CT scan. An arm exploration was done under local anesthesia to remove all parathyroid tissues detected in the MIBI scan or palpable masses during surgery. If all glands were removed, 0.5 x 0.5 x 0.5 cm of tissue (60-100 mg) was maintained in situ or the same amount of tissue was reimplanted.

RESULTS

The average ratio of iPTH in the graft-bearing arm to the contralateral arm in the 5 patients with parathyroid tissue in the neck was 1.17 +/- 0.16, and that in the 10 patients with parathyroid at the arm was 14.15 +/- 16.62. A significant difference was found between the two groups. MIBI scans showed parathyroid tissues in the neck in four of five patients and in seven of eight patients at the arm. Computed tomography showed the parathyroid tissues in the neck and mediastinum in five of five patients (100%). Five glands were removed from these five patients, three in the neck, one in the mediastinum, and one in the carotid sheath. In total, 20 glands and 2 half-glands were removed from 10 patients; among these, 14 glands were shown in the MIBI scan. All patients had improvements of symptoms and signs after surgery. Serum levels of calcium, phosphorus, and iPTH decreased rapidly after surgery, but alkaline phosphatase did not.

CONCLUSIONS

With the results obtained from the ratio of iPTH of the graft-bearing arm to the contralateral arm, clinical palpation of the arm, MIBI scan, CT scan, careful surgical exploration, and adequate resection, recurrent and persistent secondary hyperparathyroidism can be successfully treated with surgery in the neck or at the arm.

BACKGROUND

Intraoperative parathyroid hormone assay (IOPTH) has been suggested to have value in predicting the development of postoperative hypoparathyroidism after thyroid surgery. IOPTH has been validated in identification of patients at risk of postoperative hypocalcemia requiring early onset of calcium supplementation therapy and in improving selection of patients eligible for a safe early discharge. However, the value of IOPTH has not been assessed in a randomized study as a guide for the surgeon to parathyroid tissue autotransplantation (PA). The objective of this study was to evaluate the applicability of IOPTH in guiding the surgeon to selective parathyroid tissue autotransplantation during total thyroidectomy (TT).

METHODS

Between January 2005 and December 2005, 340 patients qualified for total thyroidectomy (TT) who met the inclusion criteria were randomized to two equal-sized groups (n=170): group A, in which elective PA of at least one parathyroid gland was performed in all cases without IOPTH as a guide; and group B, in which selective IOPTH-guided PA was performed, if only the iPTH plasma level was <10 ng/L at 10-20 min after TT (before skin closure). The standard technique of PA consisting of implanting the parathyroid tissue into 10-20 sternocleidomastoid muscle pockets was used in both groups. IOPTH measurements were performed by the STAT-Intraoperative-iPTH-Assay. Serum calcium was routinely monitored at 4, 12, 24, 48, and 72 hr postoperatively. The incidence and severity of hypocalcemia and related symptoms were matched with the IOPTH results. On follow-up, serum calcium and plasma iPTH values were measured at 1, 3, and 6 months postoperatively. The primary end point was the success rate in preventing permanent postoperative hypoparathyroidism. The secondary end point was the use of postoperative medication for transient hypocalcemic symptoms.

RESULTS

Twenty-one group B patients (12.3%) had plasma iPTH levels<10 ng/L at 10-20 min after TT (before skin closure) and they underwent selective IOPTH-guided PA. None of the patients from both groups experienced permanent postoperative hypoparathyroidism. Transient postoperative hypocalcemia occurred in 22.3% vs. 11.2% of patients (group A vs. B, respectively; p<0.05). The mean cumulated serum calcium values were significantly lower for group A vs. group B patients within the entire 3-month period after TT (2.12+/-0.09 mmol/L vs. 2.27+/-0.05 mmol/L, respectively; p<0.001). The mean oral calcium supplementation was significantly higher for group A vs. group B patients during the 3 months after TT (2.7+/-0.9 g/day vs. 0.9+/-0.4 g/day, respectively; p<0.001).

CONCLUSIONS

IOPTH offers valuable information during TT, correctly identifying patients at risk of postoperative hypocalcemia. Selective IOPTH-guided PA in patients with plasma iPTH levels<10 ng/L at 10-20 min after TT reduces the risk of permanent postoperative hypoparathyroidism to zero, and this approach seems to be as effective as elective PA of at least one parathyroid gland without IOPTH guidance. Moreover, selective IOPTH-guided PA significantly decreases the incidence of transient postoperative hypoparathyroidism and the need for calcium supplementation therapy compared with elective PA without IOPTH.

BACKGROUND

Parathyroid hormone (PTH) is a cardinal factor in the pathogenesis of bone disease in the dialysis population. The spectrum of renal osteodystrophy has been reported to have changed during the past years, and adynamic bone disease has emerged as the most common bone disorder in these patients. Continuous ambulatory peritoneal dialysis (CAPD) is considered a risk factor for the development of this condition, and furthermore, the adynamic bone lesion is associated with a state of relative hypoparathyroidism (hypo-PTH). Calcium, vitamin D, and phosphorus play a key role in the control of parathyroid gland function in uremic patients. However, magnesium may also be able to modulate PTH secretion in a way similar to calcium.

OBJECTIVE

The aims of this study were (1) to analyze the serum Mg concentration in a large group of CAPD patients, (2) to study the relationship between serum Mg and PTH levels, and (3) to investigate whether this relationship is independent of other factors, such as calcium, phosphorus, and calcitriol, that regulate parathyroid function.

METHODS

We studied 51 stable patients, aged 23-77 years, under maintenance CAPD for more than 6 months (range 8-48 months). Calcium carbonate was used as a phosphate binder in all patients, and 9 subjects also received aluminum hydroxide. No patient had been previously treated with vitamin D. Biochemical parameters were prospectively evaluated over 6 months, and the mean values were computed.

RESULTS

The mean serum Mg was 1.08 +/- 0.19 mmol/L, and hypermagnesemia, defined as a Mg level higher than 1.01 mmol/L, was found in 30 patients (59%). Thirty-one subjects (60%) had an intact PTH (iPTH) level lower than 120 pg/mL and were diagnosed as having relative hypo-PTH. Except for the values of iPTH and alkaline phosphatase, the only difference between the two groups was the serum Mg concentration, which was significantly higher in patients with hypo-PTH (1.16 +/- 0.15 mmol/L vs 0.91 +/- 0.14 mmol/L; p< 0.001). Furthermore, iPTH levels were lower in patients with hypermagnesemia than in subjects with normal serum Mg (69 +/- 49 pg/mL vs 190 +/- 89 pg/mL, p < 0.001). There was a significant correlation between serum Mg and PTH levels (r= -0.70, p< 0.01). After controlling for the effect of other variables by partial correlation analysis, a significant positive association between P and PTH (r= 0.25, p < 0.05), and a negative relationship between Mg and PTH (r= -0.57, p < 0.001) were evident. A forward stepwise multiple regression analysis showed that only P and Mg predicted PTH values (multiple r = 0.59, p < 0.001).

CONCLUSIONS

Hypermagnesemia and hypoparathyroidism are frequent in CAPD patients. There is a significant inverse relationship between serum Mg concentration and iPTH levels. Furthermore, this association is independent of the most important factors regulating parathyroid gland function (calcium, phosphorus, and calcitriol). These results suggest that hypermagnesemia may have a suppressive effect on PTH synthesis and/or secretion. Therefore, elevated serum Mg levels may play a role in the pathogenesis of adynamic bone disease.

OBJECTIVE

With the advent of serum chemistry autoanalyzer and routine estimation of serum calcium as a part of annual physical examination, there has been a dramatic change in the presentation of primary hyperparathyroidism (PHPT) from symptomatic to asymptomatic disease in the United States. However, such trend has not been documented from India. We carried out this retrospective study to analyse the changes in clinical presentations of PHPT patients over a period of two decades in a tertiary care centre in north India.

METHODS

This retrospective study included patients with PHPT treated at a single centre of north India between March 1990 and October 2010. Two decades were divided into four different time periods, i.e. 1990 to 1994, 1995 to 1999, 2000 to 2004 and 2005 to 2010. Clinical presentations, biochemical parameters and surgical outcomes were compared between different time periods using appropriate statistical methods.

RESULTS

Data of 202 patients with PHPT with male: female ratio of 3:7 were analyzed. There was a rise in the number of cases of PHPT diagnosed in the last decade compared to the previous decade (28 cases vs 174 cases, P<0.001). Change in the mean age, male: female ratio, lag time for the diagnosis of PHPT and clinical presentations of PHPT (predominance of bone and stone symptoms) did not differ across different time periods. Non-significant decrease in serum calcium levels at the time of diagnosis of PHPT and a significant, decline in the serum alkaline phosphatase levels (P<0.01) were found in the last decade, however, iPTH levels were higher in the last decade ( P <0.05). There was no change in the site and size of parathyroid adenoma in the two decades, however, postoperative symptomatic hypocalcemia was less frequent in the last decade.

CONCLUSIONS

The findings of this retrospective analysis show that the PHPT still remains symptomatic disease with increasing awareness over the last two decades in our center. There was not much change in the clinical presentation, in the past two decades.

BACKGROUND

Vitamin D-binding protein (DBP) and catabolism have not been examined in the clinical setting of childhood chronic kidney disease (CKD).

METHODS

The concentrations of serum vitamin D {25-hydroxyvitamin D [25(OH)D], 1,25-dihydroxyvitamin D [1,25(OH)(2)D], 24,25-dihydroxyvitamin D [24,25(OH)(2)D]}, DBP, intact parathyroid hormone (iPTH), and fibroblast growth factor-23 (FGF23) were measured in 148 participants with CKD stages 2-5D secondary to congenital anomalies of the kidney/urinary tract (CAKUT), glomerulonephritis (GN), or focal segmental glomerulosclerosis (FSGS). Free and bioavailable 25(OH)D concentrations were calculated using total 25(OH)D, albumin, and DBP concentrations.

RESULTS

The concentrations of all vitamin D metabolites were lower with more advanced CKD (p < 0.001) and glomerular diagnoses (p ≤ 0.002). Among non-dialysis participants, DBP was lower in FSGS versus other diagnoses (FSGS-dialysis interaction p = 0.02). Winter season, older age, FSGS and GN, and higher FGF23 concentrations were independently associated with lower concentrations of free and bioavailable 25(OH)D. Black race was associated with lower total 25(OH)D and DBP, but not free or bioavailable 25(OH)D. 24,25(OH)(2)D was the vitamin D metabolite most strongly associated with iPTH. Lower 25(OH)D and higher iPTH concentrations, black race, and greater CKD severity were independently associated with lower levels of 24,25(OH)(2)D, while higher FGF23 concentrations and GN were associated with higher levels of 24,25(OH)(2)D.

CONCLUSIONS

Children with CKD exhibit altered catabolism and concentrations of DBP and free and bioavailable 25(OH)D, and there is an important impact of their underlying disease.

OBJECTIVE

To determine the frequency of subclinical vitamin D deficiency in an ambulatory care setting.

METHODS

This was an observational study which measured 25 vitamin D levels in medical clinic patients. Patients with chronic renal failure, known osteomalacia and rickets were excluded. A total of 119 patients were evaluated. They were divided in three diagnostic categories based on their serum 25 vitamin D levels. Those with levels below 8 ng/ml were categorized to have severe deficiency, levels between 8 - 20 ng/ml as moderate deficiency and levels of 21-35 mg/ml as mild deficiency.

RESULTS

Of 119 patients, 92% had vitamin D deficiency. Their mean age was 44.3 +/- 18.3 years, with female to male ratio of 5:1. Sixty two percent (62%) had severe, 24% moderate and 8% had mild deficiency. Nearly half of all these patients (including those with severe deficiency) were asymptomatic. Whereas a low serum calcium, elevated phosphate and elevated alkaline phosphatase were reflective of severe deficiency. It was only an elevated iPTH that correlated with mild to moderate deficiency.

CONCLUSIONS

Subclinical vitamin D deficiency is extensive in the adult ambulatory care patients. Serum calcium, phosphate and alkaline phosphatase are poor markers of moderate to mild deficiency. A serum 25 vitamin D level and an iPTH are better biofunctional markers of this deficiency.

OBJECTIVE

To investigate via the vitamin D status whether patients with peripheral arterial disease (PAD) tend to develop vitamin D deficiency that in turn influences their clinical symptoms.

METHODS

Cross-sectional.

METHODS

University hospital.

METHODS

Three hundred twenty-seven patients were evaluated; subjects with secondary causes of bone disease or bone active medication were excluded. One hundred sixty-one patients with either PAD stage II (n = 84) or stage IV (n = 77) were enrolled and compared to 45 age- and sex-matched healthy controls.

RESULTS

All patients underwent determinations of serum chemistry, 25-hydroxyvitamin D (vitamin D3) intact parathyroid hormone (iPTH), alkaline phosphatase (ALP), and osteocalcin and were further stratified according to an individual restriction score into 3 groups: mildly, moderately, or severely restricted in daily life due to the underlying disease. Patients with PAD IV showed significantly lower vitamin D3 (P =.0001), and calcium (P =.0001) values and significantly higher iPTH (P =.0001), osteocalcin (P =.0001) and ALP (P =.02) levels as compared to patients with PAD II. Patients considering themselves as severely restricted due to the underlying disease showed lower vitamin D3 and higher iPTH levels than those who described only a moderate (vitamin D3: P <.001; iPTH: P <.01) or mild (vitamin D3: P <.001; iPTH: P <.001) restriction in daily life.

CONCLUSIONS

Patients with PAD IV, especially those who feel severely restricted due to the disease, are at high risk of developing vitamin D deficiency, secondary hyperparathyroidism, and ultimately osteomalacia due to immobilization and subsequent lack of exposure to sunlight, all of which in turn lead to further deterioration. Monitoring of vitamin D metabolism and vitamin D replacement therapy could be a simple, inexpensive approach to mitigating clinical symptoms and improving quality of life in patients with advanced PAD.

The manufacture of garments is the main industry in Bangladesh and employs 1.6 million female workers. Due to the indoor lifestyle and low dietary intake of calcium, we hypothesised that they are at risk of low vitamin D and bone mineral status. Two hundred female garment workers (aged 18-36 years) were randomly selected. Serum 25-hydroxyvitamin D (S-25OHD), serum intact parathyroid hormone (S-iPTH), serum calcium (S-Ca), serum phosphate (S-P) concentration and serum alkaline phosphatase activity (S-ALP) were measured from fasting samples. Bone indexes of hip and spine were measured by dual-energy X-ray absorptiometry. The mean S-25OHD (36.7 nmol/l) was low compared to that recommended for vitamin D sufficiency. About 16% of the subjects were found to be vitamin D-deficient (S-25OHD 21 ng/l) was associated with progressive reduction in bone mineral density at the femoral neck and lumbar spine. According to the WHO criteria, the mean T-score of the femoral neck and lumbar spine of the subjects were within osteopenic range. We observed that subjects with a bone mineral density T-score < -2.5 had a trend of lower values of BMI, waist-hip circumference, mid-upper-arm circumference, S-25OHD and higher S-iPTH and S-ALP. The high prevalence of hypovitaminosis D and low bone mineral density among these subjects are indicative of higher risk for osteomalacia or osteoporosis and fracture.

OBJECTIVE

Coronary artery calcification (CAC) is associated with future cardiovascular events and/or death of patients on hemodialysis (HD). We investigated whether progression of CAC in patients on HD could be delayed by switching from a calcium (Ca)-based phosphate (Pi) binder to lanthanum carbonate.

METHODS

The CAC scores were evaluated at study enrollment and after 6 months in 52 patients on HD using calcium carbonate (CC) as a Pi binder. Patients were randomly divided into 2 groups assigned to receive either CC or lanthanum carbonate (LC), and the CAC scores were evaluated after a 6-month treatment period. Progression of CAC was assessed, as were serum levels of Ca, Pi, and intact parathyroid hormone (iPTH).

RESULTS

Forty-two patients completed the study (23 receiving CC and 19 receiving LC). In the 6 months prior to randomization, all patients were treated with CC. During this 6-month period, the CAC scores increased significantly in all 42 patients. Once randomized, there was significantly less progression in the group treated with LC than with CC. Changes in CAC scores from 6 to 12 months were significantly smaller in the LC group than the CC group (-288.9 ± 1176.4 vs 107.1 ± 559.6, P = .036), and percentage changes were also significantly different (-6.4% vs 41.2%, P = .024). Serum Ca, Pi, and iPTH levels were similar in both groups during the study period.

CONCLUSIONS

This pilot study suggested that LC delayed progression of CAC in patients on HD compared with CC.

Hypovitaminosis D is common in Asian Indians. Physicians often prescribe 1500 mug (60 000 IU) cholecalciferol per week for 8 weeks for vitamin D deficiency in India. Its efficacy to increase serum 25-hydroxy vitamin D (25(OH)D) over short (2 months) and long (1 year) term is not known. We supplemented a group of twenty-eight apparently healthy Asian Indians detected to have low serum 25(OH)D (mean 13.5 (sd 3.0) nmol/l) on screening during January-March 2005. Serum parathyroid hormone (PTH) level was supranormal in 30 % of them. Oral supplementation included 1500 mug cholecalciferol per week and 1g elemental Ca daily for 8 weeks. Serum 25(OH)D, total Ca, inorganic P and intact (i) PTH were reassessed in twenty-three subjects (twelve females and eleven males) who had follow up at both 8 weeks and 1 year. At 8 weeks the mean 25(OH)D levels increased to 82.4 (sd 20.7) nmol/l and serum PTH normalized in all. Twenty-two of the twenty-three subjects had 25(OH)D levels>49.9 nmol/l. At 1 year, though the mean 25(OH)D level of 24.7 (sd 10.9) nmol/l was significantly higher than the baseline, all subjects were 25(OH)D deficient. Five subjects with supranormal iPTH at baseline showed recurrence of biochemical hyperparathyroidism. Thus, with 8 weeks of cholecalciferol supplementation in Asian Indians with chronic hypovitaminosis D, mean serum 25(OH)D levels would be normalized and serum PTH value would be reduced to half. However, such quick supplementation would not maintain their 25(OH)D levels in the sufficient range for 1 year. For sustained improvement in 25(OH)D levels vitamin D supplementation has to be ongoing after the initial cholecalciferol loading.

Zinc (Zn) deficiency has been reported in 40-78% of hemodialysis (HD) patients and may be associated with anemia and pruritus and probably limiting the expression of renal osteodystrophy. This study was designed to explore possible correlation between serum zinc concentration and anemia, intact parathyroid hormone (iPTH) concentration and pruritus severity in HD patients. During a case-control study, the serum Zn concentration of patients on maintenance HD was compared with those of the healthy controls and with the cut-off point of 70 mcg/dL as the risk of Zn deficiency. The mean serum Zn concentration in patients on maintenance HD was significantly lower than that of the control group; however, it was not different with the cut-off point of 70 microg/dL. No correlation between serum Zn concentration and hematologic indices was detected. A significant positive correlation between serum Zn concentration and erythropoietn dose was noted. No correlation was found between serum Zn concentration and PTH level or pruritus severity. In conclusion, the results of this study showed that zinc concentrations were lower in HD patients compared to controls, however, the effects of routine supplementation of zinc to control anemia, serum PTH level or pruritus severity are yet doubtful.

This investigation of 68 hemodialysis patients (ages 33 to 91) analyzed the association of biochemical indicators of vitamin K nutriture and bone metabolism, and related both to past bone fracture history and prospective bone fracture risk. Phylloquinone concentrations were significantly lower in the 23 patients with previous fractures compared to those without (0.93 vs. 1.50 nmol/liter, P < 0.003) and a smaller percentage of their serum osteocalcin was carboxylated (48.8 vs. 53.6%, P < 0.03). The 41 patients who never had fractures had nearly three times higher phylloquinone concentrations than the nine patients with fractures during a four-year follow-up period (1.59 vs. 0.55 nmol/liter, P < 0.002) and more carboxylated serum osteocalcin (55.2 vs. 42.0%, P < 0.01). None of the patients with phylloquinone concentrations over 2.2 nmol/liter had elevated intact parathyroid hormone (iPTH) concentrations, and only patients with less than 1 nmol/liter phylloquinone had severe hyperparathyroidism (iPTH>> 300 ng/liter). Our data thus indicate that suboptimal vitamin K nutriture in hemodialysis patients is associated both with increased bone fracture risk and with a high prevalence of hyperparathyroidism.

The aim of this study was to compare the clinical, biochemical, and pathologic findings of normocalcemic patients with macroscopically enlarged parathyroid tissue identified at thyroid surgery with those of patients treated surgically for preoperatively proved primary hyperparathyroidism (PHPT). The records of 28 patients with incidental parathyroid enlargement and 533 patients with PHPT were reviewed to compare age, sex, serum calcium and phosphate, intact parathyroid hormone (iPTH), parathyroid weight, number of diseased glands, cell and histologic types, PTH content, and cure rate. Incidentally found lesions were lighter and developed in younger patients. Biochemistry and pathology found them to be less hyperfunctioning. Sex, number of diseased glands per patient, and cell type were not different. PTH content was low in the incidental lesions. Incidentally discovered enlarged parathyroid glands are mildly hyperfunctioning at the time of discovery. They may represent an early stage of lesion responsible for overt PHPT. In the absence of knowledge concerning their significance and evolution, we recommend that enlarged parathyroids found during the course of a thyroid operation be removed.

OBJECTIVE

Abnormalities in mineral metabolism [calcium, phosphate, and immunoreactive parathyroid hormone (PTH)] and vitamin D have been linked to increases in central arterial stiffness. Central arterial stiffness can be measured using noninvasive technologies, including augmentation index (AIx), a composite measure of arterial stiffness.

METHODS

In 131 outpatients identified from individual cardiac or kidney disease clinics, we examined conventional demographic and laboratory risk factors, vitamin D levels (1,25-OH2D3 and 25-OHD3), and markers of inflammation or endothelial function [C-reactive peptide (hsCRP), matrix metalloproteinase 2 (MMP-2), matrix metalloproteinase 9 (MMP-9), and IL-6] in relationship to AIx.

RESULTS

The median eGFR was significantly different between clinics (range 25-81 ml/min). Subjects with higher phosphate or MMP-9 levels were found to have a higher AIx (P = 0.02 and 0.07, respectively). Lower 1,25-OH2D3 levels or reduced eGFR were associated with higher AIx (P = 0.002 and 0.005, respectively). The associations between 1,25-OH2D3 and phosphate levels and AIx were observed for values within the normal range. No association was noted for calcium, iPTH, 25-OHD3, or hsCRP and AIx. Adjusting for potential confounders [eGFR, calcium, phosphate, and (log) iPTH] the association of lower 1,25-OH2D3 with AIx remained statistically significant.

CONCLUSIONS

This exploratory study demonstrates a significant association between AIx and 1,25-OH2D3 in a diverse group with cardiac, kidney disease, or both. These increasing understanding of the role of vitamin D in vascular health lends a context to these findings and raises questions as to additional modifiable risk factors in complex patients. Further studies are required.

An underrecognized side effect of long-term lithium carbonate therapy is hyperparathyroidism with associated hypercalcemia and hypocalciuria. Because cessation of lithium carbonate therapy usually does not correct the hyperparathyroidism and associated hypercalcemia, parathyroidectomy frequently is necessary. This is the initial report of 2 patients with lithium carbonate-induced hyperparathyroidism treated with cinacalcet hydrochloride (HCl), which normalized serum calcium levels and reduced intact parathyroid hormone (iPTH) secretion. The patients, both with bipolar disease and a 15- to 30-year history of lithium carbonate therapy, were evaluated for stage 3 chronic kidney disease, persistent hypercalcemia, and hyperparathyroidism. A 67-year-old woman was administered cinacalcet HCl, 30 mg/d, for 11 months. Mean serum calcium level decreased from 10.8 +/- 0.4 mg/dL (2.69 +/- 0.10 mmol/L) to 9.9 +/- 0.4 mg/dL (2.47 +/- 0.10 mmol/L; P < 0.001), and iPTH level decreased from 139 +/- 31 pg/mL (139 +/- 31 ng/L) to 114 +/- 39 pg/mL (114 +/- 39 ng/L; P = not significant). A 63-year-old man was administered 30 mg/d of cinacalcet HCl for 8 months, then 60 mg/d for another 2 months. Mean serum calcium and iPTH levels decreased from 11.0 +/- 0.5 mg/dL (2.74 +/- 0.12 mmol/L) to 10.3 +/- 0.4 mg/dL (2.57 +/- 0.10 mmol/L; P < 0.001) and 138 +/- 10 pg/mL (138 +/- 10 ng/L) to 73 +/- 7 pg/mL (73 +/- 7 ng/L; P = 0.03), respectively. Urinary fractional excretion of calcium was low for both patients before (<0.026 and <0.015) and after (0.026 and 0.008) treatment with cinacalcet HCl. These findings suggest that cinacalcet HCl can provide an alternative nonsurgical means to control this disorder in patients with hypercalcemia of variable severity for whom surgical treatment is not a consideration because of perceived mildness of disease or unsuitability of the patient for surgical intervention.

OBJECTIVE

The use of intraoperative intact parathyroid hormone (iPTH) assay in secondary renal hyperparathyroidism (SHP) has been limited by the relatively low cost effectiveness of the assay in improving the success rate for primary bilateral neck exploration. The study aimed at determining, in a prospective, randomised trial, the cost effectiveness and impact of the routine employment of a "six-sample" versus "two-sample" algorithm of the intraoperative iPTH assay during surgery for SHP on intraoperative decision making and surgical success rate.

METHODS

One hundred and two consecutive patients with severe SHP and qualified for subtotal parathyroidectomy were randomly allocated to two equal-sized groups: group A, in which the intraoperative iPTH serum level was determined in six consecutive samples: preoperative, pre-excision, 5, 10, 20 and 60 min, and group B, in which the intraoperative iPTH serum level was determined twice only: preoperatively and 10 min. The STAT intraoperative intact-PTH immunoassay was employed. In group B, in patients with serum iPTH decrease lower than 60% of the baseline at 10 min, an additional measurement was performed at 20-min post-excision. If a decrease of 80% or more of the baseline was not obtained, the exploration was extended in search of remaining hyperfunctioning parathyroid tissue.

RESULTS

The surgical success rate was 96.1% and 98.0% (in group A and B, respectively). The impact of the intraoperative iPTH assay on surgical decision making was demonstrated in 13.7% and 15.7% (in group A and B, respectively). The assay was helpful in identifying patients with supranumerary hyperfunctioning parathyroid tissue (5.9% vs 7.8% in group A and B, respectively), patients with fewer than four parathyroid glands (3.9% vs 5.9% in group A and B, respectively) and patients with remaining hyperfunctioning parathyroid tissue suspected to be located within the mediastinum in cases of negative bilateral neck exploration who benefit from transcervical thymectomy. The diagnostic accuracy of the intraoperative iPTH assay was 100% in both groups. The accuracy of two-sample algorithm increased from 96% to 100% if an additional serum iPTH determination was performed in borderline cases with an iPTH drop lower than 60% of the baseline at 10 min. The cost-effectiveness analysis showed significant savings in group B, equal to Euro 87.6 per patient, with the unchanged diagnostic accuracy of the two-sample algorithm.

CONCLUSIONS

The intraoperative iPTH assay in patients operated on for secondary hyperparathyroidism offers support in surgical decision making in the majority of patients, allowing for correct identification of patients with supranumerary ectopic hyperfunctioning parathyroid glands, and in patients with fewer than four parathyroid glands. It also correctly identifies patients who do not benefit from blind thymectomy. The two-sample algorithm, extended to include three determinations in selected cases, has the same 100% diagnostic accuracy as the six-sample algorithm, the former being a much more cost-effective procedure.

BACKGROUND

Hyperparathyroid condition might influence endothelial cells. The aim of this study was to assess flow mediated dilatation (FMD) in patients with primary hyperparathyroidism (PHPT).

METHODS

We prospectively evaluated 21 patients with PHPT (9 women, 12 men; aged 50 +/- 11 years, serum calcium 11.6 +/- 0.7 mg/dl, intact parathyroid hormone (iPTH) 489 +/- 495 pg/ml) and 27 healthy control subjects (13 women, 14 men; aged 49 +/- 10 years, serum calcium 9.4 +/- 0.5 mg/dl, iPTH 28 +/- 8.5 pg/ml). Endothelial function, measured as FMD of the brachial artery using ultrasound, was calculated in two groups. To avoid confounding factors, conditions known to affect endothelial function like diabetes mellitus, hypertension, dyslipidemia, smoking, coronary and peripheral artery disease were excluded from both groups.

RESULTS

FMD was lower in patients with PHPT than that in those without (10.2 +/- 5.8 vs. 19.8 +/- 5.8, P = 0.0001). FMD negatively correlated with serum calcium (r = -0.55, P = 0.002).

CONCLUSIONS

Endothelium-dependent FMD may impair in patients with PHPT compared to controls. Endothelial dysfunction can contribute to the deleterious cardiovascular effects of PTH excess. Therapy to reduce or retard endothelial dysfunction in patients with PHPT may lead to decreased cardiovascular morbidity and mortality.

Chronic lithium (Li) therapy, used extensively in the treatment of bipolar affective disorders, is one of psychiatry's most effective treatments. The data on the effects of Li on baseline PTH and calcium (Ca) levels are conflicting. A clear resetting of the PTH set-point to the right was documented in vitro; however, the effect of Li on the Ca-PTH axis has not been rigorously studied in vivo. In this study, we used a Ca and citrate infusion protocol to fully characterize PTH dynamics in seven female patients, 40 +/- 11 yr old, on chronic Li therapy for 5.23 +/- 4.0 yr, compared with seven controls, 41 +/- 16 yr old (mean +/- SD). Baseline ionized Ca (Cai) and intact PTH levels were 5.2 +/- 0.06 mg/dL and 38.4 +/- 5.7 pg/mL in the Li group and 4.9 +/- 0.06 mg/dL and 21.2 +/- 5.0 pg/mL in the controls, (mean +/- SEM) P = 0.008 and 0.042, respectively. We defined an inverse sigmoidal curve between Cai and the intact biologically active PTH molecule (iPTH) for the two study groups and demonstrated a significant shift in the iPTH set-point to the right in the Li-treated patients, compared with controls. The set-point was 5.08 +/- 0.04 for the former group and 4.88 +/- 0.04 mg/dL for the latter, P = 0.004. Patients on Li had significantly higher Cai levels during citrate and Ca infusions, P = 0.0008 and 0.012, respectively; however, iPTH levels were not significantly different between the two study groups during either infusion. The shift in the iPTH set-point to the right in the Li-treated patients and the similar iPTH levels, despite higher serum Cai levels during both infusions, establish the presence of a clear alteration in PTH dynamics in patients on chronic Li therapy.

The cytochrome P450 enzyme 24-hydroxylase (CYP24) plays a critical role in regulating levels of vitamin D hormone. Aberrant expression of CYP24 has been implicated in vitamin D insufficiency and resistance to vitamin D therapy. We have demonstrated amplified CYP24 expression in uremic rats, suggesting that CYP24 has an etiological role in vitamin D insufficiency commonly associated with chronic kidney disease (CKD). We have designed two new analogues of 1alpha,25-dihydroxyvitamin D3 (1alpha,25(OH)2D3), namely CTA091 and CTA018/MT2832, which are potent inhibitors of CYP24. In vitro studies with CTA091 show that it enhances the potency of 1alpha,25(OH)2D3. In vivo studies demonstrate that CTA091 decreases serum intact parathyroid hormone (iPTH) levels and increases circulating 1alpha,25(OH)2D3. CTA091 increases both Cmax and AUC of co-administered 1alpha,25(OH)2D3. These studies indicate that CYP24 inhibition can increase cellular responsiveness to vitamin D hormone and potentiate vitamin D therapy. CTA018/MT2832 differs from CTA091 in that it also has the ability to activate vitamin D receptor-mediated transcription. CTA018/MT2832 effectively suppresses elevated iPTH secretion at doses which do not affect serum calcium or phosphorus levels in a rodent model of CKD. Studies with both new analogues underscore the potential utility of CYP24 inhibition in the treatment of secondary hyperparathyroidism in CKD.

Hypocalcemia is the main factor responsible for the genesis of secondary hyperparathyroidism in chronic renal disease. Studies with parathyroid cells obtained from uremic patients indicate that there is a shift in the set point for calcium-regulated hormone (parathyroid hormone [PTH] secretion. Studies were performed in dogs to further clarify this new potential mechanism. Hypocalcemia was prevented in uremic dogs by the administration of a high calcium diet. Initially, ionized calcium was 4.79 +/- 0.09 mg/dl and gradually increased up to 5.30 +/- 0.05 mg/dl. Despite a moderate increase in ionized calcium, immunoreactive PTH (iPTH) increased from 64 +/- 7.7 to 118 +/- 21 pg/ml. Serum 1,25(OH)2D3 decreased from 25.4 +/- 3.8 to 12.2 +/- 3.6 pg/ml. Further studies were performed in two other groups of dogs. One group received 150-200 ng and the second group 75-100 ng of 1,25(OH)2D3 twice daily. The levels of 1,25(OH)2D3 increased from 32.8 +/- 3.5 to a maximum of 69.6 +/- 4.4 pg/ml. In the second group the levels of serum 1,25(OH)2D3 after nephrectomy remained normal during the study. Amino-terminal iPTH did not increase in either of the two groups treated with 1,25(OH)2D3. In summary, the dogs at no time developed hypocalcemia; however, there was an 84% increase in iPTH levels, suggesting that hypocalcemia, per se, may not be the only factor responsible for the genesis of secondary hyperparathyroidism.

Circulating levels of immunoreactive (i) PGE, calcium and parathyroid hormone (iPTH) were examined in 21 patients with neoplasia and 3 patients with primary hyperparathyroidism. Plasma iPGE was elevated in 4 of 11 hypercalcemic cancer patients; all extracts of liver metastases obtained from 3 of these 4 patients had elevated iPGE levels (metastases = 19.43 +/- 3.43, n = 11; normal liver = 2.04 +/- 0.23; ng/g tissue, x +/- SE, P less than .001). In contrast, only one of 10 normocalcemic cancer patients and none of 3 hyperparathyroid patients had elevated plasma iPGE. There were no apparent relationships between the presence of metastases and either hypercalcemia or elevations of plasma iPGE. Serum iPTH levels were undetectable or below the mean of the normal range in 19 of 21 cancer patients; only the three hyperparathyroid patients had elevated levels. Seven hypercalcemic patients were treated with indomethacin; plasma iPGE decreased in 6 (-34 +/- 10% decrement, n = 6, P less than .01). Decreases in serum calcium occurred only in those patients (2 of 6) who had abnormally elevated plasma iPGE prior to the therapy. It is concluded that plasma iPGE elevations are found in some cancer patients, especially those with hypercalcemia, and that this marker may identify those patients who will respond to indomethacin treatment.