Residents of a long-stay geriatric ward at the University Hospital Basel were included in a study to investigate the effects of hypovitaminosis D and immobility. All 91 women (mean age 82.5 years) and 92 men (mean age 78.7 years) were enrolled in the study. Measurements included bone resorption, as measured by urinary deoxypyridinoline (dpd), serum 25-hydroxyvitamin D (25OHD), serum intact parathyroid hormone (iPTH), and their correlations with a four grade mobility score. Mobility score reflected the degree of weight bearing, ranging from walking independently to primarily bed bound. In 86% of all residents, serum 25OHD levels were below the normal limit of 12 ng/ml. Secondary hyperparathyroidism (HPT) was detected in 24% of all patients, using 55 pg/ml as the upper limit for serum iPTH. No significant correlation was found between urinary dpd and serum 25OHD or serum iPTH. Mobility index and both urinary dpd (f: P = 0.001, r = 0.37; m: P < 0.0001, r = 0.47) and serum calcium (female: P = 0.007, r = 0.28; male: P = 0.02, r = 0.24) were positively related. In institutionalized elderly people with a high prevalence of vitamin D deficiency serum intact PTH levels did not correlate with bone resorption as measured by urinary deoxypyridinolin. However, more immobile subjects had significantly higher excretion rates for urinary dpd and higher serum calcium levels. Our results suggest that in elderly people immobility may contribute to bone loss that might preempt the development of secondary HPT through elevation of serum calcium.

BACKGROUND

Lymph nodal involvement in papillary thyroid cancers is very common, but the role of lymph node dissection is still controversial. Surgeons are consequently divided between opposed to and in favor of routine central neck dissection associated with total thyroidectomy.

METHODS

Clinical records of 210 patients undergoing from January 2000 to December 2006 total thyroidectomy without routine lymph node dissection were retrospectively evaluated. One hundred and ninety eight patients (94.2%) underwent radioiodine ablation as well, followed by Thyroid Stimulating Hormone suppression therapy. In patients with loco regional lymph nodal recurrence, central (VI) and ipsilateral (III-IV) lymph node dissection was performed.

RESULTS

Incidence of permanent hypoparathyroidism (iPTH < 10 pg/ml) and permanent vocal fold paralysis were respectively 1.4% and 1.9%. After an 8-year mean follow-up, the rate of loco regional recurrence was 4.2%-9/210 patients. In these cases selective lymph node dissection was carried out without complications.

CONCLUSIONS

The role of neck dissection in papillary thyroid cancer management, is still subject of research and controversial regarding routine or therapeutic indications, surgical extension, its impact on local recurrence and survival.

CONCLUSIONS

A low loco regional recurrence rate may be observed after total thyroidectomy without prophylactic lymph node dissection. Lymph nodal recurrences were more frequent in young male patients, sometime affected by follicular variant, in each case less than 2 cm. There is a general agreement about the extension of therapeutic lymph node dissection, while routine central neck dissection is still controversial and may be indicated in high risk patients.

The somatostatin analogue lanreotide is effective in reducing growth hormone levels in patients with acromegaly. Acromegaly is characterized by calcium homeostasis alterations. The aim of our study was to evaluate the effects of lanreotide on bone turnover markers in a group of acromegalic patients and to verify a possible increase of intact parathormone (iPTH) levels in a transient or persistent way. Serum GH, IGF-I and serum and urinary markers of bone metabolism were measured before treatment and on months 3 and 24. In short-term treatment (3 months), lanreotide significantly decreased GH, IGF-I, serum calcium, osteocalcin and alkaline phosphatase levels, but increased iPTH level (49 +/- 16.7 vs pre-treatment 28.3 +/- 7.6 ng/L, p<0.001). During long-term study (24 months) GH and IGF-I were significantly still low; serum calcium and alkaline phosphatase levels returned to pre-treatment levels. iPTH level was significantly still higher compared with pre-treatment (46.4 +/- 9.2 vs 28.3 +/- 7.6 ng/L, p<0.05). No changes were seen in serum albumin, creatinine and vitamin D during short and long term treatment. The changes of most bone markers during lanreotide treatment can be explained by the decrease of GH and IGF-I. The increase of iPTH concentration suggests that lanreotide has ulterior and long-standing actions on calcium homeostasis: intestinal malabsorption of calcium due to the lanreotide could contribute to this "secondary" hyperparathyroidism. The clinical relevance of these long-standing effects needs to be further investigated.

BACKGROUND

There are few data focusing on the prevalence of vitamin D deficiency in tropical countries.

OBJECTIVE

We determined the vitamin D status in pregnant women and examined the factors associated with vitamin D deficiency.

METHODS

A cross-sectional study of 147 pregnant Thai women aged 18-45 years at Siriraj Hospital (a university hospital in Bangkok, Thailand) was undertaken. Clinical data and plasma levels of 25-hydroxyvitamin D [25(OH)D], intact parathyroid hormone (iPTH), calcium, albumin, phosphate and magnesium were obtained in pregnant women at delivery.

RESULTS

The prevalence of hypovitaminosis D [defined as 25(OH)D <75 nmol/L] in pregnant women at delivery was 75.5% (95% confidence interval (CI), 67.7-82.2%). Of these, vitamin D insufficiency [defined as 25(OH)D 50-74.9 nmol/L] was found in 41.5% (95% CI, 33.4-49.9%) and vitamin D deficiency [25(OH)D <50 nmol/L] was found in 34.0% (95% CI, 26.4-42.3%) of women. The mean 25(OH)D concentration was 61.6 ± 19.3 nmol/L. The correlation between 25(OH)D and iPTH was weak (r = -0.29, P<0.01). Factors associated with vitamin D deficiency by multiple logistic regression were: pre-pregnancy body mass index (BMI in kg/m2, odds ratio (OR), 0.88, 95% CI 0.80-0.97, P = 0.01) and season of blood collection (winter vs. rainy, OR, 2.62, 95% CI 1.18-5.85, P = 0.02).

CONCLUSIONS

Vitamin D deficiency is common among pregnant Thai women. The prevalence of vitamin D deficiency increased in women who had a lower pre-pregnancy BMI and whose blood was collected in the winter. Vitamin D supplementation may need to be implemented as routine antenatal care.

OBJECTIVE

Abnormalities of thyroid function are commonly seen in chronic kidney disease (CKD) patients. They are associated with adverse clinical conditions such as atherosclerosis, endothelial dysfunction, inflammation and abnormal blood pressure variability. We investigated the association between thyroid disorders and endothelial function, assessed by flow-mediated dilatation (FMD) and carotid intima-media thickness (CIMT), and cardiovascular events (CVE) in CKD patients.

METHODS

This observational cohort study included 305 CKD (stages 1-5) patients. Routine biochemistry, including free T3, free T4 and thyroid stimulating hormone, fibroblast growth factor-23 (FGF-23) and FMD, CIMT were measured. We divided patients into four groups according to thyroid hormone status: euthyroidism, subclinical hyperthyroidism, subclinical hypothyroidism, and euthyroid sick syndrome. Fatal and composite CVE were recorded for a median 29 months.

RESULTS

Patients with subclinical hypothyroidism had a higher prevalence of hypertension and diabetes and also were more likely to have higher values of systolic CIMT, phosphorus, intact parathormone (iPTH), FGF-23, homeostasis model assessment-insulin resistance and lower levels of FMD than euthyroid patients. In the unadjusted survival analysis, subclinical hypothyroidism and euthyroid sick syndrome were associated with an increased risk for the outcome as compared with euthyroidism [hazard ratio 30.63 (95 % confidence interval 12.27-76.48) and 12.17 (3.70-39.98), respectively]. The effects of subclinical hypothyroidism and euthyroid sick syndrome were maintained even in fully adjusted models.

CONCLUSIONS

We demonstrated that subclinical hypothyroidism and euthyroid sick syndrome are associated with increased CVE in CKD patients. Further studies are needed to explore these issues.

Atherosclerosis and cardiovascular disease are the main causes of death in hemodialysis patients. Possession of the apolipoprotein E4 (ApoE4) allele has been associated with increased levels of serum lipids and with coronary and carotid artery atherosclerosis. We investigated the possible relationship between ApoE polymorphism and atherosclerosis risk factors in hemodialysis patients. Two hundred sixty-nine hemodialysis patients (115 women, 154 men) were included in our study. The mean patient age and mean hemodialysis duration were 45.8 +/- 15.3 years and 52.6 +/- 40.6 months, respectively. Testing was done on all patients to determine ApoE genotype and serum levels of total cholesterol (T-Cho), low-density lipoprotein (LDL-C), high-density cholesterol (HDL-C), triglyceride (TG), lipoprotein (a) (Lp[a]), intact parathormone (iPTH), and fibrinogen. ApoE genotype was identified with the polymerase chain reaction. Ultrasonographic measurement of carotid artery intima media thickness (IMT) was used to diagnose atherosclerosis. We also analyzed ApoE polymorphism and risk factors such as age, gender, duration of hemodialysis, smoking, and hypertension in relation to the presence of atherosclerosis. Serum T-Cho and LDL-C levels were higher in patients with the ApoE4/3 phenotype than in those with ApoE3/3 and ApoE3/2 phenotypes (P < 0.05). However, there was no statistically significant link between ApoE polymorphism and serum levels of TG, HDL-C, or Lp(a) (P>> 0.05). Apart from a relationship with age and duration of hemodialysis (P < 0.05), we found no significant association between atherosclerosis and ApoE polymorphism or the other risk factors analyzed (P>> 0.05). In conclusion, although ApoE polymorphism significantly affects serum levels of T-Cho and LDL-C in hemodialysis patients, this study indicates that ApoE polymorphism is not associated with the presence of atherosclerosis in these individuals. The high incidence of atherosclerosis in these patients underlines the need for further research on other possible causative factors.

OBJECTIVE

Equivocal parathyroid technetium Tc 99m sestamibi scan results are likely to demonstrate the correct location for parathyroid adenomas.

METHODS

Patients with primary hyperparathyroidism prospectively consented to participate in an institutional review board-approved study. The parathyroid technetium Tc 99m sestamibi scan results were classified as positive, negative, or equivocal.

METHODS

A tertiary private hospital in which university faculty practice.

METHODS

Technetium Tc 99m sestamibi imaging was performed for 464 patients with primary hyperparathyroidism. Eighty-four of these patients had scan results considered equivocal for unilateral adenomas. The algorithm for this group of patients specified that they should receive an injection with technetium Tc 99m sestamibi prior to parathyroidectomy and that an intraoperative parathyroid hormone (iPTH) level decrease of more than 50% be used to define intraoperative success. Seventy-two patients had postoperative calcium levels measured at least 2 weeks after their surgical procedure and defined the study group. The mean follow-up was more than 6 months.

METHODS

Parathyroidectomy.

METHODS

Correlation of equivocal scan interpretation with operative findings and biochemical cure of hyperparathyroidism.

RESULTS

Of the 72 patients, 39 underwent unilateral surgical explorations and 33 underwent bilateral surgical explorations; 67 (93%) of the patients were initially cured and 68 (94%) were ultimately cured. In the unilateral group, 38 (97%) of the patients were cured. The 1 failure was associated with a false-positive iPTH level decrease. In the bilateral group, 29 (88%) of the patients were initially cured and 30 (91%) were ultimately cured. Two failures were associated with a false-positive iPTH level decrease and 2 with failure to find the adenoma. Of the 33 patients in the bilateral group, surgical exploration of the opposite side was purely by surgeon choice in 11 cases. Of the other 22 patients, in addition to the 3 failures, 7 had 4-gland hyperplasia, 4 had double adenomas, and 6 had false-negative iPTH level results with iPTH level decreases of less than 50%.

CONCLUSIONS

Overall, between 48 (67%) and 54 (75%) of the 72 patients would have been cured with unilateral surgical exploration alone.

Although most patients with postmenopausal osteoporosis have normal or low values for serum immunoreactive parathyroid hormone (iPTH), we have reported previously that a small subset (about 10% of the total group) have increased values. We studied three patients representative of this latter group. Serum iPTH was two to three times higher than the age-adjusted normal mean, serum ionized calcium and total calcium were in the lower half of the normal range, and serum 1,25-dihydroxyvitamin D [1,25(OH)2D] was in the low-normal range. Six months of treatment of one patient with 0.5 microgram/day of synthetic 1,25(OH)2D improved calcium absorption and balance; however, serum iPTH remained high. After surgical removal of 1,010 mg of hyperplastic parathyroid tissue, serum iPTH decreased to normal. These and other data suggest that increased serum iPTH in these patients was caused by secondary hyperparathyroidism, possibly because of inadequate conversion of 25-OH-D to 1,25(OH)2D.

BACKGROUND

The availability of intraoperative intact parathyroid hormone monitoring allows the success of minimally invasive parathyroidectomy to be ensured during the operation. However, false-negative results leading to unnecessary explorations and difficulties in interpreting the data raise concern about the effectiveness of the method.

METHODS

Patients with primary hyperparathyroidism (pHPT) and one unequivocally enlarged parathyroid gland on preoperative ultrasound or (99m)Tc-SestaMIBI scintigraphy underwent minimally invasive video-assisted parathyroidectomy according to the technique initially described by Miccoli. Intraoperatively, rapid electrochemiluminescence immunoassay was used to measure intact parathyroid hormone (iPTH) levels before the operation, after complete mobilization of the adenoma (preexcision value), and 5, 10, and 15 min after the excision. The operation was considered successful when more than a 50% decrease in preexcision iPTH levels and subsequent attainment of the normal range within 15 min were observed.

RESULTS

Between November 1999 and November 2009, 235 (43%) of 546 patients with pHPT were eligible for a minimally invasive approach. Intraoperative iPTH monitoring showed 221 true-positive, 1 false-positive, 6 false-negative, and 7 true-negative results. This calculated to a sensitivity of 97% and a specificity of 88%.

CONCLUSIONS

Despite the availability of high-resolution ultrasound and (99m)Tc-SestaMIBI scintigraphy, the presence of multiple glandular disease cannot be ruled out completely. Although the authors observed six false-negative results, they believe that intraoperative iPTH monitoring represents a valuable asset for minimally invasive parathyroidectomy because it identifies sporadic hyperplasia.

OBJECTIVE

To evaluate the value of 99mTc-MIBI double-phase scintigraphy (DPS) and early SPECT/CT in the pre-surgical assessment of patients with primary hyperparathyroidism (PHPT). Also, to calculate the correlation between uptake and some biological parameters.

METHODS

Forty patients with PHPT were included: 37 solitary adenomas, 1 hyperplasia, and 2 double adenomas. Fifteen patients had ectopic glands. DPS and early SPECT/CT were acquired in all patients. Ultrasound was performed in 31/40. All patients underwent surgery, intra-operative iPTH measurements, and histopathological examinations. Qualitative DPS uptake was assessed and correlated to pre-surgical calcium, iPTH levels, gland weight, and maximum diameter.

RESULTS

In the planar study, there were 23 positive cases, 8 doubtful, and 9 negatives. With the SPECT/CT, 8/9 negatives cases were located. All doubtful cases were confirmed as positives. Gland location improved in 16 cases (12 ectopic). DPS+SPECT/CT failed to detect a solitary adenoma and at least one gland in three cases of multiglandular disease (MGD). The sensitivity by patient was: DPS 72.5%, DPS+SPECT/CT 90%, and ultrasound 42%. Ultrasound and scintigraphy (DPS+SPECT/CT) were concordant in 16/31 patients. For the rest of them, scintigraphy proved correct in 14/15, and both techniques failed in one case. There was a significant correlation between level of uptake and iPTH level, gland weight, and maximum diameter.

CONCLUSIONS

Early SPECT/CT improves sensitivity and the locating of parathyroid pathological glands and increases diagnostic confidence. iPTH level, glandular size, and weight are related to the qualitative assessment of 99mTc-MIBI uptake in early DPS.

The objective of this study was to examine the lifestyle factors that influence total body bone mineral content (TB BMC) and total body bone area (TB BA) in Indian preschool children. TB BMC and TB BA were measured by dual-energy X-ray absorptiometry (Lunar DPX PRO) in 71 apparently healthy children aged 2-3 years. A fasting blood sample was analyzed for serum concentrations of ionized calcium (iCa), intact parathyroid hormone (iPTH), phosphorus (iP) and 25-hydroxyvitamin D(3) (25 OHD). Dietary intake of energy, protein, calcium and phosphorus was estimated from a 3-day diet recall. The daily physical activity and sunlight exposure were recorded by a questionnaire. The study children were shorter than their age-gender matched WHO counterparts with a mean height for age Z score of -1.3 ± 1.5. The mean dietary intake of calcium was 46% of the Indian recommended dietary intakes (RDI). Seventy-three percent of children had low iCa concentrations, and 57% were deficient in vitamin D. Generalized linear model analysis revealed that height, lean body mass, weight, activity, sunlight exposure in minutes and dietary intakes of calcium, zinc and iron were the significantly influencing factors (p < 0.05) of TB BMC and TB BA. In conclusion, attaining optimal height for age, achieving the goals of overall nutrition with adequate calcium, iron and zinc intakes as well as adequate physical activity and sunlight exposure play an important role in achieving better TB BMC and TB BA in preschool children.

Osteoporosis is a frequent complication after renal transplantation. Some workers have shown that bisphosphonates may be effective to prevent and treat corticosteroid-induced osteoporosis in these patients. In this study we report our experience with administration of the biphosphonate alendronate to treat renal transplanted patients with established osteoporosis.

METHODS

Twelve to 24 months after transplantation (9 women, 5 men) 14 renal transplant patient were treated with alendronate and 12 patients (7 women, 5 men) were untreated. All patients displayed an iPTH <240 pg/mL and a bone mineral density (BMD) t-score <-2.5. All patients received cyclosporine and prednisone therapy. Biochemical measurements, BMD, and X-rays of the lumbar spine were measured during study. Patients in the treatment group received alendronate 10 mg/d (po) and vitamin D plus calcium (800 UI cholecalciferol and 2.5 g of CaCO(3)) per day while those in the control group only received vitamin D plus calcium, at the same dose.

RESULTS

There was no difference in mean age, weight, time after transplantation, or immunosuppression between the treatment and control groups. There were no significant differences in the biochemical parameters during the study period. Over the 1-year study period, patients receiving alendronate displayed a greater increase in BMD. Lumbar spine BMD increased 4.3 +/- 6.1% in the treatment group versus 0.55 +/- 5.30% in controls. Femoral neck BMD increased 10.3 +/- 11.9% and 2.2 +/- 5.7%, respectively, in the treatment and control groups. Patients receiving alendronate frequently experienced intestinal disconfort.

CONCLUSIONS

The bisphosphonate alendronate is effective to treat renal transplant patients suffering from established osteporosis.

OBJECTIVE

Primary hyperparathyroidism (PHPT) is associated with an increased cardiovascular mortality and morbidity rate. However, the exact role of PTH and/or calcium in the development of cardiovascular disease (CVD) is still controversial. The influence of PHPT on hemostasis is yet unknown. Therefore, the main purpose of this study was to investigate the markers of endogenous coagulation/fibrinolysis and to evaluate the relationships between these hemostatic parameters, serum lipid profile and serum calcium and PTH in patients with PHPT.

METHODS

Twenty-three patients with PHPT and 20 age-matched healthy controls were included in the study. Fibrinogen, factors V, VII, VIII, IX and X activities, von Willebrand factor (vWF), antithrombin III (AT III), protein C, protein S, tissue plasminogen activator (t-PA) and tissue plasminogen activator inhibitor-1 (PAI-1), as well as common lipoprotein variables, were measured. The relationships between biochemical parameters and these hemostatic parameters were examinated.

RESULTS

Compared with the control subjects, platelet count, FVII, FX activities, and D-Dimer levels were significantly increased in patients with PHPT (p<0.001, p<0.05, p<0.001, and p<0.05, respectively). Among the lipids, the levels of TC, TG and LDL-C were significantly increased in patients with PHPT (p<0.01, p<0.001, p<0.001, respectively) than those in controls. In patients with PHPT, we showed a positive correlation between urinary phosphorus excretion and factors VIII, IX, and X (r: 0.572, p<0.01; r: 0.543, p<0.01; r: 0.532, p<0.01, respectively). F IX activity was positively correlated with TC (r: 0.463, p<0.05) and LDL-C (r: 0.549, p<0.01) There was a positive correlation between serum ALP and PAI-1 levels (r: 0.451, p<0.05). ApoB was positively correlated with D-Dimer (r: 0.421, p<0.05). We did not find any significant correlation between iPTH and serum calcium and the hemostatic parameters that we measured.

CONCLUSIONS

In conclusion, we found some important differences in the hemostatic parameters between the patients with PHPT and healthy controls. Increased platelet count, F VII and FX activities and D-Dimer levels in patients with PHPT represent a potential hypercoagulable state, which might augment the risk for atherosclerotic and atherothrombotic complications. This condition may contribute to the excess mortality rate due to CVD in patients with PHPT.

These studies examine the metabolism of highly purified bovine parathyroid hormone [bPTH-(1--84)] by fetal rat calvaria. Enzymatically dispersed bone cells and intact (minced) calvaria were incubated with bPTH-(1--84) and the incubation medium was analyzed for degradation of PTH by polyacrylamide gel electrophoresis. Eluates of gel slices were assayed for immunoreactive PTH (iPTH) in carboxy- and amino-terminal RIAs. Both bone preparations metabolized bPTH-(1--84). The intact hormone progessively decreased with time and carboxy-terminal iPTH fragments were evident by 5 min of incubation. In the isolated cell preparations, intact hormone was completely degraded at submaximal doses of PTH (5 X 10(-9) M), as assessed by cAMP production. Degradation was incomplete in intact calvarial preparations at all doses studied. Intact calvaria were less sensitive to PTH with regard to cAMP production. No amino-terminal fragments were detected in the medium with either cell preparation. Oxidized (biologically inactive) bPTH-(1--84) was not metabolized in these systems. These findings contrast with studies in liver and kidney preparations, where oxidized bPTH has been shown to be degraded. These findings contrast with studies in liver and kidney preparations, where oxidized bPTH has been shown to be degraded. These data suggest that biological activity may be necessary for the metabolism of intact bPTH-(1--84) by bone cells and that skeletal tissue may contribute to the immunoheterogeneity of circulating PTH in the rat.

AMP-activated protein kinase (AMPK) is a key regulator of cellular and body energy homeostasis. We previously demonstrated that AMPK activation in osteoblasts increases in vitro bone formation while deletion of the Ampkα1 (Prkaa1) subunit, the dominant catalytic subunit expressed in bone, leads to decreased bone mass in vivo. To investigate the cause of low bone mass in the Ampkα1(-/-) mice, we analysed bone formation and resorption in the tibia of these mice by dynamic histomorphometry and determined whether bone turnover can be stimulated in the absence of the Ampkα1 subunit. We subjected 12-week-old Ampkα1(+)(/)(+) and Ampkα1(-/-) mice to ovariectomy (OVX), intermittent PTH (iPTH) administration (80 μg/kg per day, 5 days/week) or both OVX and iPTH hormonal challenges. Tibiae were harvested from these mice and bone micro-architecture was determined by micro-computed tomography. We show for the first time that Ampkα1(-/-) mice have a high bone turnover at the basal level in favour of bone resorption. While both Ampkα1(+)(/)(+) and Ampkα1(-/-) mice lost bone mass after OVX, the bone loss in Ampkα1(-/-) mice was lower compared with controls. iPTH increased trabecular and cortical bone indexes in both ovariectomised Ampkα1(+)(/)(+) and Ampkα1(-/-) mice. However, ovariectomised Ampkα1(-/-) mice showed a smaller increase in bone parameters in response to iPTH compared with Ampkα1(+)(/)(+) mice. By contrast, non-ovariectomised Ampkα1(-/-) mice responded better to iPTH treatment than non-ovariectomised Ampkα1(+)(/)(+) mice. Overall, these data demonstrate that Ampkα1(-/-) mice are less affected by changes in bone turnover induced by OVX but respond better to the anabolic challenge induced by iPTH. These results suggest that AMPKα1 activation may play a role in the hormonal regulation of bone remodelling.

BACKGROUND

Deficits of vitamin D are a common finding in the general population, especially among patients with chronic kidney disease. However, there are not much data about its prevalence after renal transplantation. Our aim was to analyze the calcidiol status among a cohort of kidney transplant recipients, in a region of Spain with a high number of annual sunshine hours, as well as the effects of supplementation with oral calcidiol.

METHODS

We included 110 kidney transplant recipients in a retrospective observational study. Measurements of 25-hydroxyvitamin D (25OHD), calcium, phosphate, intact parathyroid hormone (iPTH), serum creatinine and albumin, 24-hour microalbuminuria, and proteinuria were performed at the same time. Patients were classified based on their serum 25OHD levels: normal (>30 ng/mL); insufficiency (16-30 ng/mL); and deficiency (<16 ng/mL). In a second analysis, we included 63 patients with 25OHD<30 ng/mL with adjusted calcium levels below 10.2 mg/dL for treatment with oral calcidiol to approach target levels of 30 to 40 ng/mL. Mineral metabolism parameters were monitored at baseline as well as 6 and 12 months after beginning treatment.

RESULTS

Insufficient or deficient 25OHD levels were present in 106/110 patients (96.3%); they were normal in just four patients (3.6%). Patients with calcidiol deficiency were older. We observed no differences in sex, posttransplant follow up, serum calcium, phosphate, iPTH, glomerular filtration rate, or 24- hour albuminuria or proteinuria. The 63 patients treated with oral calcidiol received a mean dose of 8044±4087 IU/wk at baseline. The 61.3% of them with deficient 25OHD levels at baseline decreased to 2.1% at 6 months and 7.5% at 12 months after treatment. No significant changes in calcium, phosphate or iPTH were observed during the treatment.

CONCLUSIONS

Deficits of 25 OHD was frequent after renal transplantation but improved safely with moderate doses of oral calcidiol without negative secondary effects.

To investigate the relationship between ionized calcium and disease activity, parameters of bone metabolism and bone mineral density (BMD) at the lumbar spine (BMD-LS) and the femoral neck (BMD-FN) measured by dual X-ray absorptiometry in rheumatoid arthritis (RA). In 146 patients with RA, the following parameters were investigated: serum levels of ionized calcium, total calcium, vitamin D metabolites 25-hydroxyvitamin D3 (25D3) and 1,25-dihydroxyvitamin D3 (1,25D3), intact parathyroid hormone (iPTH), interleukin-6, osteocalcin, erythrocyte sedimentation rate (ESR) and c-reactive protein (CRP); renal excretion of pyridinolin (PYD)- and desoxypyridinolin (DPD)-crosslinks. A total of 30.1% of the patients were hypercalcemic (ionized calcium >1.30 mmol/l). In comparison with normocalcemic patients, those with hypercalcemia had significantly higher ESR (P<0.01) and CRP values (P<0.05) and significantly lower serum levels of both iPTH (P<0.01) and 1,25D3 (P<0.05) and a significantly lower BMD-LS (P<0.05). The results indicate that a substantial part of RA patients is hypercalcemic. Hypercalcemia is associated with high disease activity and may contribute to suppression of PTH secretion and vitamin D hormone synthesis. High levels of ionized calcium may be a reflection of disease-activity-related systemic bone loss, and could be a predictor of BMD at the lumbar spine in RA.

We conducted a cross-sectional examination of the role of serum vitamin K levels as they relate to bone metabolism in elderly women with type II diabetes mellitus (DM). Eighty-five elderly women with type II DM were enrolled. Three fractions of vitamin K, phylloquinone (PK), menaquinone 4 (menatetrenone; MK 4), and menaquinone 7 (MK 7), along with undercarboxylated osteocalcin (UcOC), intact osteocalcin (IOC), urinary deoxypyridinoline (udpd), urinary type I collagen N-telopeptide (NTx), and intact parathyroid hormone (IPTH) were measured. Bone mineral density was measured in the lumbar spine (LSBMD) by dual-energy X-ray absorptiometry (DXA), and T scores or Z scores were calculated. The patients were divided into two groups by T score, under -2.5 (osteoporotic group) and over -2.5 (non-osteoporotic group). UcOC levels in osteoporotics patients were significantly higher than those in the non-osteoporotic group (3.09 +/- 3.94 vs 1.82 +/- 1.76 ng/ml, P = 0.02). The correlation between Z score and logarithmic UcOC/IOC levels in type II DM showed a negative trend ( P = 0.07) and a significantly and negatively association with logarithmic NTx ( r = -0.38; P = 0.001). In osteoporotic DM, the UcOC/IOC ratio was significantly correlated with the Z score ( r = -0.61; P (< 0.05). Furthermore, logarithmic UcOC/IOC showed a negative correlation with logarithmic MK 7 ( r = -0.50; P = 0.001). In conclusion, the reduction in LSBMD in elderly women with type II DM may be associated, in part, with a defect in Gamma-glutamylcarboxylation by vitamin K.

BACKGROUND

Fibroblast growth factor (FGF)-23, secreted from osteocytes/osteoblasts, plays major roles in phosphate (Pi)-mediated stimulation of PTH secretion and consequently in regulation of serum Pi. Osteocyte/osteoblast dysfunction develops in patients with type 2 diabetes mellitus (DM).

OBJECTIVE

Our objective was to examine whether increases in serum FGF-23 and PTH after oral Pi stimulation are impaired in type 2 DM.

METHODS

The subjects were 10 DM and 10 non-DM patients without chronic kidney disease stage 3-5. Serum FGF-23, intact PTH (iPTH), and Pi were measured serially after oral Pi administration at a daily dose of 2.0 g.

RESULTS

Pi administration caused significant increases of FGF-23 by 2 h and iPTH by 4 h in non-DM patients. These increases were attenuated in DM patients. After 2 d of Pi stimulation, serum FGF-23 and iPTH remained elevated in non-DM patients but not in DM. In all subjects, initial changes of serum FGF-23 (0-2 h) and iPTH (0-4 h) were positively correlated (r = 0.528) and showed significant negative correlations with later changes in serum Pi (2-4 h) (r = -0.457 and r = -0.673, respectively). Serum Pi (2-4 h) significantly increased in DM patients, consistent with the lack of change in serum FGF-23 and iPTH, whereas serum Pi did not change significantly in non-DM patients.

CONCLUSIONS

These results show that increases of serum FGF-23 and PTH in response to Pi stimulation are impaired in type 2 DM and that serum Pi is significantly increased thereafter. This may be a mechanism underlying advanced atherosclerosis in type 2 DM.

BACKGROUND

Patients with chronic kidney disease (CKD) have a high prevalence of cardiovascular disease (CVD). Arterial stiffness plays an important role in the pathogenesis of CVD; however, to date, there have been no reports of the assessment of arterial stiffness in patients at different stages of non-diabetic CKD.

METHODS

We studied 50 patients with non-diabetic CKD (stages 1-5, 5D) receiving medical treatment at Tokyo Women's Medical University. Pulse wave velocity (PWV) was assessed using an applanation tonometer to determine arterial compliance. All current medications were recorded and biochemical parameters were analyzed.

RESULTS

Non-diabetic CKD stage 5D patients had a higher PWV, and higher serum levels of C-reactive protein (CRP), Ca, P and intact parathyroid hormone (iPTH) than non-diabetic CKD stage 1-5 patients (p=0.03, p=0.009, p=0.006, p=0.00005, and p=0.002, respectably). As compared to non-diabetic CKD stage 1-2 patients, patients with non-diabetic CKD stage 3-5 were older, and had higher serum levels of P and iPTH and a higher PWV (p=0.0002, p=0.009, p=0.03, and p=0.004). Nephrosclerosis was associated with a higher PWV, higher serum levels of CRP, and a higher prevalence of CVD than patients with CKD of other origins.

CONCLUSIONS

We showed a stepwise increase of arterial stiffness with increasing disease severity stage in patients with CKD not associated with diabetes mellitus. CKD caused by nephrosclerosis was found to be associated with increased arterial stiffness and to be a risk factor for CVD.

Calcium infusion in normal men decreases immunoreactive PTH (iPTH). Intact iPTH (I) shows the greatest decline, and there is a greater decrease in carboxyl-terminal iPTH (C) than in midcarboxyl-terminal iPTH (M); thus, C/I, M/I, and M/C ratios are increased. To verify whether this adaptive mechanism to hypercalcemia was present in patients with primary hyperparathyroidism (PHP), we measured total serum calcium (Ca), I, C, and M as well as C/I, M/I, and M/C ratios in 32 normocalcemic normal subjects (NN), in the same normal subjects made hypercalcemic (HN), in 31 patients with PHP, and in 12 patients with nonparathyroid hypercalcemia (NPHN). Eight patients with PHP and the 32 NN were submitted to CaCl2 and Na2 EDTA infusions to evaluate their parathyroid function. Ca was lower (P < 0.005) in NN (2.21 +/- 0.06 mmol/L) than in PHP (2.80 +/- 0.25 mmol/L) or NPHN (2.83 +/- 0.20 mmol/L). The HN Ca value (2.80 +/- 0.18 mmol/L) was similar to those in PHP and NPHN subjects. C, M, and I were increased in PHP compared to the other groups (P < 0.005). PHP had C/I and M/I ratios of 2.03 +/- 0.72 and 9.04 +/- 7.69, values similar to NN (2.29 +/- 0.55 and 8.70 +/- 3.0), but lower than HN (5.36 +/- 2.48 and 25.93 +/- 13.86; P < 0.005) and NPHN (11.91 +/- 13.06 and 18.69 +/- 10.81; P < 0.005). NPHN also had a lower M/C ratio than HN (2.76 +/- 2.02 vs. 4.99 +/- 1.81; P < 0.05). PHP and NN could increase their C/I ratio to the same maximum (4.71 +/- 1.26 vs. 5.70 +/- 2.94), but PHP did so at a much higher set-point (2.67 +/- 0.19 vs. 2.24 +/- 0.10 mmol/L; P < 0.005). PHP also had higher set-points for M/I, and M/C ratios even if they failed to increase the ratios to the high values in NN [M/I 11.6 +/- 6.4 vs. 29.3 +/- 18.3 (P < 0.005); M/C, 2.16 +/- 1.20 vs. 5.0 +/- 1.93 (P < 0.005)]. Thus, carboxyl-terminal fragments are not secreted preferentially in PHP as they are in other hypercalcemic conditions. This relates to a higher set-point for the regulation of C/I and M/I ratios, permitting the secretion of more intact hormone relative to C or M fragments. The lower M/C ratio in NPHN and in PHP made more hypercalcemic compared to HN suggests a lower production or a higher clearance of midcarboxyl-terminal fragments in chronic hypercalcemia.

OBJECTIVE

Permanent hypoparathyroidism is a distressing complication of thyroid surgery. The reported incidence varies between 0.4 and 13.8 % and is directly correlated to the extent of thyroidectomy. The aim of this retrospective study was to analyze whether simultaneous autotransplantation of at least one parathyroid gland during total thyroidectomy for benign thyroid disease could reduce the risk of permanent hypoparathyroidism.

METHODS

Since 01/1999 all thyroid operations are prospectively recorded. Beside daily postoperative measurement of serum calcium level, iPTH is routinely determined on the third post op day. Patients with complications are followed closely. Postoperative hypoparathyroidism persisting for more than 6 months is defined permanent.

RESULTS

Between 01/1999 and 02/2001 146 total thyroidectomies for benign thyroid disease have been performed (81 pat. with Graves disease, 62 with nodular goiter, 3 with thyroiditis de Quervain/Hashimoto). In 37 pat. (25 %) at least one parathyroid gland was simultaneously autotransplanted into the ipsilateral sternocleidomastoid muscle. Group I (no parathyroid autotransplantation, n = 109) and group II (parathyroid autotransplantation, n = 37) were comparable concerning patient age, thyroid disease and lowest post op calcium level (2.07 versus 2.05 mmol/l). The incidence of postoperative symptomatic hypocalcemia (14.7 % versus 21.6 %) and temporary hypoparathyroidism (15.6 % versus 18.9 %) was higher in group II patients (n. s.). Conversely, permanent hypoparathyroidism occurred exclusively in group I patients (2.75 %), patients with parathyroid autotransplantation (group II) did not develop this complication.

CONCLUSIONS

Simultaneous autotransplantation of at least one parathyroid gland during total thyroidectomy for benign thyroid disease seems to minimize the risk of permanent hypoparathyroidism. The potential of routine autotransplantation in this setting has to be evaluated. The incidence of postoperative temporary hypocalcemia may be elevated with this policy.

Congenital rickets in 3 newborns of mothers with advanced nutritional osteomalacia, healed with maternal breast milk feeding when mothers alone were given calcium supplements and 7.5 mg of intravenous D2 and the mother baby pair protected from sunlight. Maternal plasma biochemistry indicated more severe vitamin D deficiency compared to their newborns (intrauterine foetal priority). The first dose of 7.5 mg of vitamin D3 and calcium supplements to mother healed osteomalacia but did not appear to heal the rickets of their breast fed infants (extrauterine maternal priority for vitamin D). A second dose given at 3 months interval healed the rickets in their infants and the biochemistry of the mother and baby returned towards normal. Congenital rickets developed when maternal bone mineral and vitamin D stores had been completely exhausted. Raised IPTH levels in the newborn suggested that foetal parathyroids were responsive to hypocalcaemic stimulus.

BACKGROUND

Lack of sun exposure is one of the primary causes of epidemic vitamin D deficiency worldwide. The aim of this study was to investigate vitamin D status and seasonal changes in summer and winter in office workers.

METHODS

This study was conducted in Ankara located at 39° 52' 30" N, 32° 52' E. The study consisted of 118 premenopausal women and men aged between 21 and 52 years-old. Seasonal changes were evaluated in August and February. Fasting serum was obtained for intact parathyroid hormone (iPTH) and 25-hydroxyvitamin D (25OHD). Additional data were collected by a questionnaire that enquired about age, weight, height, wearing style, dietary calcium intake and sunlight exposure. Serum 25OHD concentration was measured using a precise HPLC assay. Low vitamin D status was defined as a 25OHD concentration less than 30 ng/mL.

RESULTS

Mean serum 25OHD concentration in summer was 28.4±10.4 ng/mL and 13.8±6.6 ng/mL in winter (p<0.001). 35.6% of the subjects were vitamin D insufficient in summer and 12.7% in winter (p<0.001) while 31.5% were vitamin D deficient in summer and 83.9% in winter (p<0.001). A significant increase in iPTH levels (33.1±15.9 pg/mL vs 49.6±24.3 pg/mL, p<0.001) was observed throughout the seasonal change. No significant association was found between 25OHD levels and iPTH, body mass index, age and sun exposure index (p>0.05 for all) in both seasons.

CONCLUSIONS

Vitamin D deficiency is very prevalent in office workers even in summer time and this should be accepted as a public health problem.