BACKGROUND

In the treatment of differentiated thyroid cancer (DTC), in absence of enlarged lymph nodes, the role of routine central lymph node dissection (RCLD) remains controversial. The aim of this study is to analyze data resulting from total thyroidectomy (TT) not combined with RCLD in the treatment of DTC.

METHODS

We retrospectively evaluated the clinical records of 80 patients treated between January 1996 and December 2003 with TT without RCLND, in absence of suspected enlarged lymph nodes at preoperative ultrasonography and intraoperatively during neck exploration. In this series, 75 patients (93.7%) underwent radioiodine (RAI) ablation, followed by Thyroid Stimulating Hormone (TSH) suppression therapy. In case of locoregional lymph nodal recurrence, a central (VI) and ipsilateral (III-IV) selective lymph node dissection was performed.

RESULTS

Incidence of permanent hypoparathyroidism (iPTH < 10 pg/ml) and unilateral temporary vocal fold paralysis were respectively 2.55% and 2.55%. Locoregional recurrence, with positive cervical lymph nodes, after a 10.3 ± 4.7 years mean follow-up was observed in 3 patients (3.75%). They were submitted to a central (VI) and ipsilateral (III-IV) selective neck dissection without significant complications.

CONCLUSIONS

In our series, TT not combined with RCLD was associated to a low locoregional recurrence rate, even if the lack of a control group treated with RCLD does not allow any generalized assumption. RCLD may be indicated in high risk patients, in whom lymph nodal recurrence is more frequent. More prospective randomized studies are needed to better define the role of RCLD and postoperative radioiodine ablation.

BACKGROUND

Parathyroid carcinoma (PTCA) is an exceptionally rare malignancy, often with a clinical presentation similar to that of benign atypical parathyroid adenoma. Its low incidence portends unclear guidelines for management. Accordingly, thorough examination of clinical and pathologic variables was undertaken to distinguish between PTCA and atypical adenomas.

METHODS

This was a retrospective analysis of a prospective database at a tertiary academic referral center. Between September 2001 and April 2014, 3,643 patients were referred for surgical treatment of PHPT. Of these, 52 harbored aggressive parathyroid tumors: parathyroid carcinomas (n=18) and atypical adenomas (n=34). We analyzed the surgical and clinicopathologic tumor characteristics, and did a statistical analysis. We measured preoperative and intraoperative variables, and postoperative and pathologic outcomes.

RESULTS

Parathyroid carcinoma patients present with significantly increased tumor size (3.5 cm vs 2.4 cm, respectively; p=0.002), mean serum calcium (13.0 vs 11.8 mg/dL, respectively; p=0.003) and intact parathyroid hormone (iPTH) levels (489 vs 266 pg/mL, respectively; p=0.04), and a higher incidence of hypercalcemic crisis, compared with patients with atypical adenomas (50% vs 19%, respectively; p=0.072). Parathyroid carcinoma more frequently lacks a distinct capsule (47.1% vs 12.9%, respectively; p=0.03) and adheres to adjacent structures (77.8% vs 20.6%, respectively; p=0.017). Of note, there was no significant difference in loss of parafibromin expression between groups.

CONCLUSIONS

Clinical distinction between PTCA and atypical adenomas is of critical importance in determining the appropriate extent of resection and follow-up. Loss of parafibromin has not been shown to distinguish between PTCA and atypical adenoma; clearer definition of clinicopathologic criteria for PTCA is warranted and may lead to improved postoperative management.

Background Renal osteodystrophy is common in advanced CKD, but characterization of bone turnover status can only be achieved by histomorphometric analysis of bone biopsy specimens (gold standard test). We tested whether bone biomarkers and high-resolution peripheral computed tomography (HR-pQCT) parameters can predict bone turnover status determined by histomorphometry.Methods We obtained fasting blood samples from 69 patients with CKD stages 4-5, including patients on dialysis, and 68 controls for biomarker analysis (intact parathyroid hormone [iPTH], procollagen type 1 N-terminal propeptide [PINP], bone alkaline phosphatase [bALP], collagen type 1 crosslinked C-telopeptide [CTX], and tartrate-resistant acid phosphatase 5b [TRAP5b]) and scanned the distal radius and tibia of participants by HR-pQCT. We used histomorphometry to evaluate bone biopsy specimens from 43 patients with CKD.Results Levels of all biomarkers tested were significantly higher in CKD samples than control samples. For discriminating low bone turnover, bALP, intact PINP, and TRAP5b had an areas under the receiver operating characteristic curve (AUCs) of 0.82, 0.79, and 0.80, respectively, each significantly better than the iPTH AUC of 0.61. Furthermore, radius HR-pQCT total volumetric bone mineral density and cortical bone volume had AUCs of 0.81 and 0.80, respectively. For discriminating high bone turnover, iPTH had an AUC of 0.76, similar to that of all other biomarkers tested.Conclusions The biomarkers bALP, intact PINP, and TRAP5b and radius HR-pQCT parameters can discriminate low from nonlow bone turnover. Despite poor diagnostic accuracy for low bone turnover, iPTH can discriminate high bone turnover with accuracy similar to that of the other biomarkers, including CTX.

BACKGROUND

Intraoperative rapid parathyroid hormone (iPTH) assay is changing parathyroid surgery. One surgeon's experience at a tertiary care hospital was followed as minimally invasive parathyroidectomy (MIP) was adopted.

METHODS

In this prospective case study, patients underwent technitium 99m sestamibi scanning, iPTH monitoring, and MIP. A sestamibi-directed incision was made, and iPTH was measured preincision, preexcision of abnormal gland(s), and at 5- and 10-minute intervals. MIP was complete after gland(s) was excised and iPTH fell to less than 50% of preoperative levels. Routine discharge was on the day of surgery with daily calcium and calcitriol to minimize outpatient hypocalcemia. Secondary and tertiary hyperparathyroidism patients were excluded.

RESULTS

From December 1999 to June 2002, 101 patients underwent MIP. Patients were 27% men and 73% women, with two reoperations. Preoperation laboratory results averaged serum calcium 11.08 (normal 8.5 to 10.5 mg/dL) and parathyroid hormone (PTH) 169 pg/mL (normal 10 to 55 pg/mL). Average iPTH values at operative intervals were 152, 151, 68, and 50 pg/mL, respectively. Operation demonstrated 12% of patients had four-gland hyperplasia, 3% had double adenomas, 2% had parathyroid carcinomas, and 83% had single adenomas. Discharge on the day of surgery occurred in 83% of single-adenoma patients. Postoperative laboratory results averaged calcium 9.4 mg/dL (p < 0.001 versus preoperation) and PTH 48 pg/mL (p < 0.001). Fifteen patients (16%) had elevated PTH after operation, but without elevated calcium levels. One patient had persistant hyperparathyroidism.

CONCLUSIONS

MIP with iPTH monitoring is a safe and effective means of treating hyperparathyroidism. This approach allows for limited dissection and early discharge for the majority of patients.

In order to establish whether parathyroidectomy altered the natural history of ectopic calcification in patients with renal failure we undertook a detailed analysis of 62 patients with hyperparathyroidism secondary to chronic renal failure who were submitted to parathyroidectomy. Biochemical data (61 patients) and radiological skeletal surveys (42 patients) were studied before and after parathyroidectomy. Transiliac bone biopsies were obtained at (or some time in the previous six months before) parathyroidectomy in 30 and in 36 patients after surgery. Paired bone biopsies were available from 17 of these patients. In the majority of patients secondary hyperparathyroidism was controlled after parathyroidectomy although in seven patients (11 per cent), who underwent subtotal parathyroidectomy, it relapsed after initial improvement. Non-visceral soft tissue calcification disappeared or decreased in 60 per cent of the patients after parathyroidectomy. However, despite marked improvement in subperiosteal erosions and histological osteitis fibrosa, with significant reductions in iPTH and Ca X P product after parathyroidectomy, small peripheral arterial calcification developed or progressed in 56 per cent of the patients. Histological osteomalacia after parathyroidectomy developed after operation in two patients. Both had positive aluminium stains for excess aluminium in their bone. Numbers of osteoclasts and the amount of marrow fibrosis declined in parallel following parathyroidectomy, but woven bone persisted for months or years.

In 57 patients surgically treated for ulcer, we found low 25OHD concentrations, elevated 1,25(OH)2D concentrations, (P less than 0.001), a normal iPTH level, and a not significantly reduced bone mineral content (BMC) measured by single photon absorptiometry. The 25OHD concentrations were highest in patients regularly taking tablets containing vitamin D (P less than 0.05), whereas the 1,25(OH)2D concentrations and the BMC values were not affected by vitamin D intake. The most severe calcium metabolic disturbances were seen in 15 Billroth I resected patients whose BMC was 89.4 +/- 12.4% of normal. Although the dietary intake of calcium and vitamin D complied with the Scandinavian recommendations and calcium absorption was in the lower part of the normal range, the general state of nutrition appears to influence the bone mass of such patients. In the patients as a group, the 1,25(OH)2D concentrations were significantly related to BMC (r = 0.44, P less than 0.001) and biochemical signs of bone resorption (r = 0.68, P less than 0.001) and formation (r = 0.42, P less than 0.001) Conversely, no relationship could be detected between serum iPTH and bone mass or bone turnover. We suggest that the high 1,25(OH)2D concentrations found after gastric resections express a compensatory process leading to an increase in calcium absorption, and that the initial event in this sequence is a trend toward low serum calcium levels. With increased demands on this regulation or lack of precursor for 1,25(OH)2D synthesis, bone mass declines through the action of 1,25(OH)2D and/or PTH.

BACKGROUND

Minimal invasive surgery for parathyroidectomy has been introduced in the treatment of hyperparathyroidism.

OBJECTIVE

To evaluate the contribution of the sestamibi-SPECT (MIBI) localization, cervical ultrasonography, and intraoperative rapid turbo intact parathormone assay in minimal invasive parathyroidectomy.

METHODS

Between August 1999 and March 2004, 146 consecutive hyperthyroid patients were treated using the MIBI and ultrasound for preoperative localization and iPTH measurements for intraoperative assessment.

RESULTS

Parathyroid adenoma was detected in 106 patients, primary hyperplasia in 16, secondary hyperplasia in 16, tertiary hyperplasia in 5, and parathyroid carcinoma in 1 patient. Minimal invasive exploration of the neck was performed in 84 of the 106 patients (79.2%) with an adenoma, and in 17 of them this procedure was performed under local cervical block anesthesia in awake patients. Adenoma was correctly diagnosed by MIBI scan in 74% of the patients, and by ultrasound in 61%. The addition of ultrasonography to MIBI increased the accuracy of adenoma detection to 83%. In 2 of the 146 patients (1.4%) iPTH could not be significantly reduced during the initial surgical procedure. Minimal invasive surgery with minimal morbidity, and avoiding bilateral neck exploration, was achieved in 79.2% of patients with a primary solitary adenoma.

CONCLUSIONS

Preoperative localizationof the parathyroid gland by MIBI and ultrasound together with intraoperative iPTH measurements resulted in an overall cure rate of 98.6% for the entire series, The addition of ultrasound to the MIBI scan increased the accuracy of adenoma detection.

No differences in either bone mineral density or serum 25OHD levels have been found between 205 women with fibromyalgia (both pre- and postmenopausal) and their controls. However, a lack of the expected 25OHD summer rise was observed in patients.

BACKGROUND

Contradictory data have been published regarding a possible association between fibromyalgia and osteoporosis or hypovitaminosis D. Most studies, however, have been performed in small size samples and have excluded postmenopausal women. We decided to study this association in a larger sample of fibromyalgia patients including both pre- and postmenopausal women.

METHODS

Two hundred five patients were recruited from a clinic specializing in fibromyalgia and 205 healthy controls were enrolled from the census of a Primary Care Center. Controls were matched with patients by age and the time of the year they were included in the study. Bone mineral density (BMD) was measured by DXA. Serum 25OHD, iPTH, P1NP, and CTX were also determined.

RESULTS

BMD was similar in both groups (lumbar spine, 0.971 ± 0.146 g/cm(2) in patients and 0.970 ± 0.132 g/cm(2) in controls; femoral neck, 0.780 ± 0.122 g/cm(2) and 0.785 ± 0.117 g/cm(2), respectively). 25OHD levels were also similar: 23.0 ± 9.5 ng/ml and 24.1 ± 9.6 ng/ml. However, while controls showed the usual summer rise in 25OHD, fibromyalgia patients did not. PTH did not show seasonal changes, but on average was higher in patients (51 pg/ml vs. 48 pg/ml; p = 0.034). P1NP or CTX were similar in both groups.

CONCLUSIONS

No differences in BMD were found between patients and controls. As for 25OHD, a lack of its expected summer rise was observed. It is doubtful whether this has any homeostatic consequence. We consider that the association reported in other studies is merely circumstantial, and not due to the intrinsic characteristics of these disorders.

Secondary hyperparathyroidism (SHPT) is one of the outcomes of vitamin D deficiency that negatively affects bone metabolism. We studied the ethnic differences in vitamin D status in Finland and its effect on serum intact parathyroid hormone (S-iPTH) concentration and bone traits. The study was done in the Helsinki area (60°N) during January-February 2008. A total of 143 healthy women (20-48 years of age) from two groups of immigrant women (Bangladeshi, n 34 and Somali, n 48), and a group of ethnic Finnish women (n 61) were studied in a cross-sectional setting. Serum concentrations of 25-hydroxyvitamin D (S-25OHD) and S-iPTH were measured. Peripheral quantitative computed tomography measurements were taken at 4 and 66 % of the forearm length. In all groups, the distribution of S-25OHD was shifted towards the lower limit of the normal range. A high prevalence of vitamin D insufficiency (S-25OHD < 50 nmol/l) was observed (89·6 %) in the Somali group. The prevalence of SHPT (S-iPTH)65 ng/l) was higher (79·1 %) in Somali women than in Finnish women (16 %). There was a significant association between S-25OHD and S-iPTH (r - 0·49, P < 0·001). Ethnicity and S-25OHD together explained 30 % of the variation in S-iPTH. The total bone mass at all sites of the forearm, fracture load and stress-strain index was higher (P < 0·001) in Bangladeshi and Finnish women than in Somali women. The high prevalence of hypovitaminosis D, SHPT and low bone status in Somali women indicates a higher risk of osteoporosis.

T cells are known to potentiate the bone anabolic activity of intermittent parathyroid hormone (iPTH) treatment. One of the involved mechanisms is increased T cell secretion of Wnt10b, a potent osteogenic Wnt ligand that activates Wnt signaling in stromal cells (SCs). However, additional mechanisms might play a role, including direct interactions between surface receptors expressed by T cells and SCs. Here we show that iPTH failed to promote SC proliferation and differentiation into osteoblasts (OBs) and activate Wnt signaling in SCs of mice with a global or T cell-specific deletion of the T cell costimulatory molecule CD40 ligand (CD40L). Attesting to the relevance of T cell-expressed CD40L, iPTH induced a blunted increase in bone formation and failed to increase trabecular bone volume in CD40L(-/-) mice and mice with a T cell-specific deletion of CD40L. CD40L null mice exhibited a blunted increase in T cell production of Wnt10b and abrogated CD40 signaling in SCs in response to iPTH treatment. Therefore, expression of the T cell surface receptor CD40L enables iPTH to exert its bone anabolic activity by activating CD40 signaling in SCs and maximally stimulating T cell production of Wnt10b.

OBJECTIVE

Both severe, uncontrolled and low parathyroid hormone (iPTH) levels are associated with adverse outcomes in stage 5 chronic kidney disease (CKD) patients; however, the impact of iPTH levels following parathyroidectomy (PTX) is unexplored.

METHODS

A total of 235 stage 5 CKD patients who underwent PTX between 1990 and 2007 were identified, and iPTH levels following surgery were used to divide patients according to the quartile of maximum iPTH recovery during the 5 years following PTX. Survival, biochemistry and pharmacotherapy were analysed.

RESULTS

The maximum iPTH level in each quartile during the follow-up period was <46, 47-139, 140-420 and >420 pg/ml. The overall 5-year survival for the group was 81%. Adjusting for age, time on renal replacement therapy and the presence of diabetes identified an increased hazard for mortality of 2.459 in the quartile of lowest iPTH recovery (p = 0.035). The median 1-alfacalcidol dose during the follow-up period was higher (0.5 μg/day) in the lower iPTH group compared to the 3 quartiles of higher iPTH recovery (0.25 μg/day).

CONCLUSIONS

An association between the lowest quartile of iPTH recovery in the 5 years following PTX and poorer patient survival was found. This finding should be tested in larger datasets.

Because both metabolic (Met Acid) and respiratory acidosis (Resp Acid) have diverse effects on mineral metabolism, it has been difficult to establish whether acidosis directly affects parathyroid hormone (PTH) secretion. Our goal was to determine whether acute Met Acid and Resp Acid directly affected PTH secretion. Three groups of dogs were studied: control, acute Met Acid induced by HCl infusion, and acute Resp Acid induced by hypoventilation. EDTA was infused to prevent acidosis-induced increases in ionized calcium, but more EDTA was needed in Met Acid than in Resp Acid. The PTH response to EDTA-induced hypocalcemia was evaluated also. Magnesium needed to be infused in groups receiving EDTA to prevent hypomagnesemia. The half-life of intact PTH (iPTH) was determined during hypocalcemia when PTH was measured after parathyroidectomy. During normocalcemia, PTH values were greater (p < 0.05) in Met Acid (92 +/- 19 pg/ml) and Resp Acid (77 +/- 22 pg/ml) than in controls (27 +/- 5 pg/ml); the respective pH values were 7.23 +/- 0.01, 7.24 +/- 0.01, and 7.39 +/- 0.02. The maximal PTH response to hypocalcemia was greater (p < 0.05) in Met Acid (443 +/- 54 pg/ml) than in Resp Acid (267 +/- 37 pg/ml) and controls (262 +/- 48 pg/ml). The half-life of PTH was greater (p < 0.05) in Met Acid than in controls, but the PTH secretion rate also was greater (p < 0.05) in Met Acid than in the other two groups. In conclusion, (1) both acute Met Acid and Resp Acid increase PTH secretion when the ionized calcium concentration is normal; (2) acute Met Acid may increase the bone efflux of calcium more than Resp Acid; (3) acute Met Acid acts as a secretogogue for PTH secretion because it enhances the maximal PTH response to hypocalcemia.

Immunoreactive parathyroid hormone (iPTH) levels, nephrogenous cAMP (ncAMP), and tubular maximum phosphate reabsorption (TmP) were measured in 10 young and 12 healthy volunteers. The fasting urinary calcium to creatinine ratio (Ca:Cr) was also quantitated as an index of bone resorption. Aging was attended by increased iPTH levels (6.9 +/- 0.8 vs. 3.4 +/- 0.4 mu leq/ml; P less than 0.01) as well as increased ncAMP levels (2.48 +/- 0.28 vs. 1.12 +/- 0.21 nmol/100 ml glomerular filtrate; P less than 0.005) and decreased TmP (2.9 +/- 0.2 vs. 4.1 +/- 0.2 mg/100 ml glomerular filtrate; P less than 0.005), indicating that the increased iPTH levels reflected the biological effects of the hormone. A significant positive correlation of iPTH and ncAMP and a significant negative correlation of iPTH and TmP were observed. The Ca:Cr was increased in the older volunteers (0.10 +/- 0.02 vs. 0.05 +/- 0.01; P less than 0.05). The elderly subjects had significantly decreased daily calcium ingestion, serum phosphate and albumin, and creatinine clearance. Our findings suggest that the increased biological effects of PTH in the elderly subjects may contribute to the increases in Ca:Cr and bone loss that occur with age.

The aim of this study was to evaluate the effects of a combination of serum 25-hydroxyvitamin D(3) (25(OH)D(3)) levels and exercise on physical fitness in community-dwelling frail elderly in Japan. A longitudinal survey was conducted in a town (latitude 36 degrees north). Eighty women aged 65 years and over attended a 3-month exercise class. A face-to-face interview was conducted based on a questionnaire. The serum levels of 25(OH)D(3), intact parathyroid hormone (iPTH), were measured. Nine physical fitness tests were performed at baseline and at the end of a 3-month follow-up period. Among 80 subjects, 56.3% experienced falls, and 71.3% experienced stumbling more than once during the past year. The prevalence of 25(OH)D(3)<50 nmol/l or 25(OH)D(3)<75 nmol/l was 27.5% and 88.8%, respectively. Significantly greater improvements in alternate step, functional reach (FR), "timed up & go" (TUG), and 5-m walk, and superior functional capacity for the subjects with 25(OH)D(3) levels greater than 67.5 nmol/l (highest quartile) was observed at the end of the class. In contrast, the subjects with 25(OH)D(3) levels <47.5 nmol/l (lowest quartile) did not improve their physical fitness. A serum 25(OH)D(3) level of greater than 47.5 nmol/l may therefore be necessary to maintain walking ability and balance. Greater than 67.5 nmol/l appears to be preferable for lower extremity strength in Japanese frail elderly women.

Interest in quotidian (daily) hemodialysis (HD) is growing. Some advocate short-hours high-efficiency daily HD (SDH) and others long-hours slow-flow nocturnal HD (NH) while the patient is asleep, both being used 5 to 7 d/week. The London Daily/Nocturnal Hemodialysis Study was the first attempt to obtain data of SDH and NH that may be compared with conventional thrice weekly HD (CH). This was a 4-yr observational study designed to enter and follow 40 patients: 10 receiving SDH, 10 receiving NH, and 20 receiving CH. The CH patients were cohort control subjects matched for each SDH and NH patient by age, gender, comorbidity, and original dialysis modality (in-center, home, self-care, or satellite HD). All SDH and NH treatments were at home. Data collection to December 2001 was analyzed. Then enrollment had been completed and all patients had been followed for 15 mo, eight SDH plus six NH for 18 mo, seven SDH plus six NH for 21 mo, and seven SDH and five NH for 24 mo. This report gives data on calcium and phosphorus metabolism in these patients. All patients were initially dialyzed against a 1.25-mmol/L calcium bath. Predialysis serum calcium levels became lower in NH versus SDH patients by the first month and at 9 mo were 2.67 +/- 0.25 mmol/L (M +/- SD) in SDH, 2.40 +/- 0.16 mmol/L in NH, and 2.52 +/- 0.21 mmol/L in CH (SDH versus NH, P = 0.038; SDH versus CH versus NH, NS). Predialysis phosphorus levels were better controlled by NH than by SDH or CH, and with NH, all phosphate binders were discontinued. By 12 mo, a rise in bone alkaline phosphatase was seen in NH patients (but not in SDH or CH patients), which peaked at 15 to 18 mo (NH 191 IU/L +/- 70; SDH 82 +/- 34; CH 80 +/- 36; P < 0.002) and similarly with intact parathyroid hormone (iPTH) levels (NH 159 pmol/L +/- 75; SDH 13.1 +/- 10; CH 18 +/- 18; P < 0.00001). Because of these changes, the dialysate calcium concentration was increased to 1.75 mmol/L for the NH patients. Postdialysis calcium then rose to 2.57 +/- 0.21, and alkaline phosphatase and iPTH normalized completely by 21 mo. These observations prompted mass balance studies that showed that a 1.25-mmol/L calcium dialysate was associated with a mean net calcium loss of 2.1 mmol/h of dialysis time, whereas 1.75-mmol/L calcium dialysate provides a net gain of 3.7 mmol/h. In addition, the mass balance studies showed that phosphate removal by NH (43.5 +/- 20.7 mmol) was significantly (P < 0.05) higher than by SHD (24.2 +/- 13.9 mmol) but not by CH (34.0 +/- 8.7 mmol) on a per-treatment basis. With the increased frequency of treatments provided by quotidian dialysis, the weekly phosphorus removal (261.2 +/- 124.2 mmol) by NH was significantly higher than by SDH (P = 0.014) and CH (P = 0.03). This allowed the discontinuation of P binders in the NH group, which in turn eliminated approximately 8 g elemental Ca/wk oral intake. This, together with a 4 g elemental Ca/wk dialysate loss induced by a 1.25-mmol/L Ca bath, explains the changes in Ca, alkaline phosphatase, and iPTH seen in the NH patients. The SDH patients have weekly dialysis times similar to CH and still require P binders and do not become Ca deficient using 1.25-mmol/L Ca dialysate. With NH but not SDH, an elevated dialysate Ca concentration is required.

BACKGROUND

The ADVANCE (A Randomized Study to Evaluate the Effects of Cinacalcet plus Low-Dose Vitamin D on Vascular Calcification in Subjects with Chronic Kidney Disease Receiving Haemodialysis) Study objective is to assess the effect of cinacalcet plus low-dose active vitamin D versus flexible dosing of active vitamin D on progression of coronary artery calcification (CAC) in haemodialysis patients. We report the ADVANCE Study design and baseline subject characteristics.

METHODS

ADVANCE is a multinational, multicentre, randomized, open-label study. Adult haemodialysis patients with moderate to severe secondary hyperparathyroidism (intact parathyroid hormone [iPTH] >300 pg/mL or bio-intact PTH >160 pg/mL) and baseline CAC score>>or=30 were stratified by CAC score >>or=30-399,>>or=400-999,>>or=1000) and randomized in a 1:1 ratio to cinacalcet (30-180 mg/day) plus low-dose active vitamin D (cinacalcet group) or flexible dosing of active vitamin D alone (control). The study had three phases: screening, 20-week dose titration and 32-week follow-up. CAC scores obtained by cardiac computed tomography were determined at screening and weeks 28 and 52. The primary end point was percentage change in CAC score from baseline to Week 52.

RESULTS

Subjects (n = 360) were randomized to cinacalcet or control. Mean age was 61.5 years, 43% were women, and median dialysis vintage was 36.7 months (range, 2.7-351.5 months). The baseline geometric mean CAC score by the Agatston method was 548.7 (95% confidence interval, 480.5-626.6). Baseline CAC score was independently associated with age, sex, dialysis vintage, diabetes and iPTH. Subjects also had extensive aortic and valvular calcification at baseline.

CONCLUSIONS

Subjects enrolled in ADVANCE have extensive CAC at baseline. The ADVANCE Study should help determine whether cinacalcet attenuates progression of vascular calcification.

Hypocalcaemia is one of the most common major complications after thyroid surgery with the wide range of incidence from 6.9 to 46%. Thyroidectomy is usually first choice treatment for differentiated thyroid carcinoma (DTC). The study comprised 46 adult patients operated at Zagreb University Hospital Centre. Intraoperative and postoperative ionized calcium and intact parathyroid hormone (iPTH) were studied. The object of this study is to investigate risk factors, incidence of hypocalcaemia after surgical treatment of differentiated thyroid carcinoma, and the role of iPTH in comparison to ionized calcium as a predictor for hypocalcaemia.

BACKGROUND

The purpose of this study was to examine the effect of vitamin D intake and production in skin on vitamin D homeostasis in adult Icelanders.

METHODS

Participants were 30-85 years old, randomly selected from the registry of the Reykjavik area (64 degrees N) and answered a thorough questionnaire on diet and vitamin supplements. Concentrations of 25(OH)-vitamin D [25(OH)D] in peripheral blood were examined based on season during the study period February 2001-January 2003, vitamin D intake and age (age groups 30-45, 50-65, and 70-85 years old). We defined vitamin D deficiency as either [25(OH)D] <25 nmol/l or as [25(OH)D] where the inverse relationship between serum iPTH and [25(OH)D] became statistically significant.

RESULTS

Of 2310 invited, 1630 subjects participated (70,6% participation) but 21 individuals were excluded due to primary hyperparathyroidism. Mean [25(OH)D] was 46.5-/+20 nmol/l but varied by season, age and vitamin D intake, highest in June-July, 52.1-/+19.8 and lowest in February-March, 42.0-/+20.5 (p<0.001). [25(OH)D] was highest in the oldest age group, 50.8-/+19.7, but lowest in the youngest, 42.5-/+20 as was the intake 16.6-/+10 microg/day compared to 9.9-/+9 microg/day in the youngest. The correlation between vitamin D intake and [25(OH)D] was highest for the oldest group, r=0.41, p<0.001 but lowest in the youngest, r=0.24, p<0.001. [25(OH)D] was significantly higher among users of vitamin supplements (45.4-/+19.7) or fish oil (53.0-/+18.4) than among non-users (38.0-/+18.9). Vitamin D insufficiency was seen among 14.5% of those participating according to traditional definition, but 50% were below [25(OH)D] of 45 nmol/l where negative correlation between [25(OH)D] and PTH became statistically significant.

CONCLUSIONS

The serum concentration of 25(OH)D at which vitamin D deficiency becomes biochemically significant is higher than traditionally thought. A daily intake of 15-20 microg/day during wintertime would be required to maintain normal homeostasis in Icelandic adults, which is considerably higher than present recommendations of 7-10 microg/day for adults. Further research is needed to define the limit for vitamin-D sufficiency.

OBJECTIVE

Use of intraoperative measurement of intact parathyroid hormone (iPTH) to confirm complete excision of hyperfunctioning parathyroid tissue does not improve overall operative success rates.

METHODS

Case series of patients undergoing parathyroidectomy with or without intraoperative iPTH measurement.

METHODS

University teaching hospital.

METHODS

Fifty patients undergoing parathyroidectomy before our institution of intraoperative iPTH sampling in March 1999 (group 1) were compared with 50 patients undergoing parathyroidectomy after this technique was adopted (group 2). Overall, 100 patients underwent operation between December 1996 and May 2000. Serum calcium and iPTH levels were measured at 1- and 3-month intervals. Intraoperative frozen sections and operative times were also analyzed.

RESULTS

Mean preoperative calcium levels were 2.85 and 2.82 mmol/L (11.4 and 11.3 mg/dL) in groups 1 and 2, respectively. One-month postoperative calcium values were identical in both groups at 2.35 mmol/L (9.4 mg/dL) (group 1 SD = 0.18 [0.74], group 2 SD = 0.20 [0.82]). At 1 month, all but 1 patient in group 1 had normalized calcium values (2% failure rate), while 3 patients in group 2 (6%) remained hypercalcemic. All 3 patients in group 2 had intraoperative iPTH levels that returned to normal. There was a significant difference in the number of intraoperative frozen sections between groups, with a mean (SD) of 3.4 (1.7) in group 1 and 2.0 (1.6) in group 2 (P<.01). There was no significant difference in operative times between groups.

CONCLUSIONS

Use of intraoperative iPTH sampling did not significantly affect the overall success of parathyroidectomy, as determined by postoperative normocalcemia. There was, however, a significant decrease in the number of frozen sections sent at operation.

OBJECTIVE

To assess the effect of bisphosphonates on post-parathyroidectomy hypocalcemia in patients with osteitis fibrosa cystica.

METHODS

Review of the medical records of six patients using bisphosphonates preoperatively.

RESULTS

Mean age was 35.6 ± 10.5 years; serum calcium = 13.51 + 0.87 mg/dL; iPTH = 1,389 + 609 pg/mL. The mean value of urine deoxypyridinoline (UDPD) of three patients was 131 ± 183 nmol/mmol Cr, and of C-telopeptide (CTX), 2,253 ± 1,587 pg/mL. The mean values of bone densitometry (T score) were as follows: 0.673 ± 0.150 g/cm(2) (-4.42 ± 1.23) in lumbar spine (L2-L4); 0.456 ± 0.149 g/cm(2) (-5.58 ± 1.79) in the femoral neck; and 0.316 ± 0.055 g/cm(2) (-5.85 ± 0.53) in radius 33. Patient 1 received oral alendronate, 30 mg/day for four weeks; his calcium decreased from 14 to 11.6 mg/dL, and his UDPD from 342 to 160 nmol/mmol Cr. Patient 2 received oral alendronate, 20 mg/day for six weeks; his calcium decreased from 14 to 11.0 mg/dL and his UDPD from 28.8 to 14 nmol/mmol Cr. Patient 3 received intravenous pamidronate, 90 mg prior to surgery. Patient 4 received oral alendronate, 140 mg/week for six weeks; her calcium decreased from 13.7 to 12.3 mg/dL and her CTX from 2,160 to 1,340 pg/mL. Patient 5 received oral alendronate, 140 mg/ week for six weeks; her calcium levels dropped from 14.3 to 14.1 mg/dL; her CTX did not change. Patient 6 received ibandronate, 150 mg, ten days prior to surgery; his CTX reduced by 62%. No patient developed severe hypocalcemia in the first postoperative week. One year after surgery, the mean gain in bone mineral density was 40% ± 29% in L2-L4, 86 ± 39% in the femoral neck, and 22% ± 11% in radius 33.

CONCLUSIONS

The preoperative use of bisphosphonates seems to attenuate bone hunger without preventing a significant increase in bone mass in the follow-up of parathyroidectomy.

Cinacalcet is a calcimimetic drug for the treatment of secondary hyperparathyroidism (HPT). In a sequential open-label study, ten patients with persistent HPT after renal transplantation received first 30 and then 60 mg oral cinacalcet once daily over 2 weeks each. Cinacalcet steady state oral clearance was 131.1 +/- 20.9 l/h and 92.8 +/- 9.5 l/h (mean +/- SE) after 30 and 60 mg, respectively. Cinacalcet and parathyroid hormone (PTH) concentrations showed an inverse correlation and were fitted to a simple E(max) model (E(max) = 80% reduction vs. baseline, EC(50) = 13 ng/mL). A once daily administration of cinacalcet lowered serum calcium over 24 h without fluctuations. The 8-h fractional urinary excretion of calcium was increased after 60 mg cinacalcet (baseline 0.85 +/- 0.17%, 30 mg 1.53 +/- 0.35%, 60 mg 1.92 +/- 0.37%). Renal function remained stable. Cinacalcet pharmacokinetics and pharmacodynamics showed a pronounced interindividual variability. We conclude that the once daily administration of cinacalcet in patients with secondary HPT after renal transplantation effectively reduced iPTH and serum calcium. The transient calciuria could potentially favor nephrocalcinosis and reduce bone mineral density, suggesting that higher doses of cinacalcet need to be used with caution in renal transplant recipients with severe persistent hyperparathyroidism.

OBJECTIVE

The blood pressure, the most influencing factor in cardiovascular disease in end-stage renal failure patients, follows a seasonal variation during the year. Since vitamin D(3) is known to be related to sun exposure, we wanted to evaluate the putative participation of the vitamin D(3) metabolism in blood pressure modifications.

METHODS

We studied 22 stable hemodialysis patients (11 females and 11 males, mean age +/- SD 56 +/- 1 year) who had been continuously treated in our dialysis unit for more than 1 year between 1994 and 1997 and did not receive pulse vitamin D(3) treatment. Supine systolic and diastolic blood pressures were measured before every dialysis session (>12,000 measurements) and the intact parathormone (iPTH), 25-hydroxyvitamin D(3) [25(OH)D(3)], and 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] levels every 3 months (>300 determinations). The mean values of blood pressure per season and per patient were taken for analysis using a 4-year longitudinal study design.

RESULTS

The blood pressure varied during the years studied following a seasonal trend. It was highest during autumn and tended to decrease during spring and warmer months. Systolic as well as diastolic blood pressures were significantly correlated with the 25(OH)D(3) levels (p = 0.0291 and p = 0.0327, respectively). No correlation was observed between blood pressure and 1,25(OH)(2)D(3) or iPTH levels.

CONCLUSIONS

There is a link between blood pressure and 25(OH)D(3) level. This interrelation is not secondary to a iPTH modulation. Although it cannot be excluded that vitamin D(3) and blood pressure vary following a third factor with seasonal variations, since vitamin D(3) varies during the year, mainly following sun exposure, we suggest that vitamin D(3) is one of the factors participating in the seasonal variation of the blood pressure. Other factors known to control the blood pressure and particularly the extracellular volume overload may also participate.

BACKGROUND

There is no consensus about the usefulness of postoperative intact parathyroid hormone (iPTH) determination to predict permanent hypoparathyroidism (pHPP). We evaluated the value of calcium (Ca2+) and iPTH concentration at 24 hours after total thyroidectomy (TT) for predicting pHPP.

METHODS

Ca2+ and iPTH levels from 70 consecutive patients who underwent TT were measured at 24 hours and 6 months after TT.

RESULTS

Five patients (7.1%) developed pHPP. An iPTH concentration ≤5.8 pg/mL at 24 hours after TT identified patients at risk for pHPP (sensitivity, 100%; specificity, 81.5%), but it was not accurate enough to predict its development (positive predictive value, 30%). Conversely, an iPTH level >5.8 pg/mL predicted normal parathyroid function at 6 months (negative predictive value, 100%). Compared with iPTH, a postoperative Ca2+ level ≤1.95 mmol/L was 60% sensitive and 78.5% specific to predict pHPP.

CONCLUSIONS

An iPTH concentration >5.8 pg/mL on the first postoperative day rules out pHPP with much better diagnostic accuracy than Ca2+. Postoperative iPTH could be helpful in identifying patients at risk for developing pHPP.

Although the kinetics of intraoperative intact parathyroid hormone (iPTH) are well characterised in primary hyperparathyroidism, no data are available for patients with renal hyperparathyroidism and renal insufficiency, partially because of the high costs of intraoperative quick iPTH measurement. Therefore we evaluated an inexpensive laboratory test with a duration of 18 min for intraoperative use and measured iPTH intraoperatively in 34 patients with renal hyperparathyroidism. Samples were taken before and 5 min and 15 min after parathyroid resection. Blood samples were put on ice immediately and sent to the hospital central laboratory via a pneumatic tube system. The first 76 probes were measured in parallel using three assays: the Nichols Quick PTH, the Roche Elecsys and the Biermann Immulite assay. The subsequent samples were only measured using the Elecsys assay. Determination of iPTH from 76 samples showed a correlation coefficient of 0.997 between the Immulite and Elecsys assay and a correlation coefficient of 0.987 for the Nichols Quick PTH and the Elecsys test. In renal hyperparathyroidism the mean iPTH was 26+/-2% of the starting value 5 min after subtotal parathyroidectomy and 18+/-2% after 15 min. Renal function influenced absolute iPTH values in patients with renal hyperparathyroidism but not relative changes. In patients with terminal renal insufficiency iPTH decreased from 615+/-57 pg/m before preparation to 109+/-13 pg/ml 15 min after subtotal resection. In contrast in patients after kidney transplantation iPTH decreased from a lower starting value of 341+/-94 pg/ml to 58+/-9 pg/ml after 15 min. The iPTH kinetics showed a biphasic clearance of iPTH with an initial dominant half-life of 3.2 min and a terminal half-life of 29.2 min. Half-life did not correlate with renal function. All operations were successful as indicated by an adequate drop in PTH (from 709+/-92 pg/ml preoperatively to 22+/-6 pg/ml at discharge) and calcium (from 2.57+/-0.04 mmol/l to 2.32+/-0.04 mmol/l). In conclusion, intraoperative measurement of iPTH is also reliable in patients with renal hyperparathyroidism. Elimination kinetics are similar to that in patients with primary disease. However, the half-life was not influenced by renal function. The availability of a quick, inexpensive, routine iPTH test might expand its use to renal hyperparathyroidism, specifically for surgical decisions in problem cases.