Calcium-stimulated calcitonin - The "new standard" in the diagnosis of thyroid C-cell disease - clinically relevant gender-specific cut-off levels for an "old test".

INTRODUCTION: Pentagastrin (Pg) stimulated calcitonin (sCT) was used to enhance accuracy in medullary thyroid cancer (MTC) diagnosis. As it is now unavailable, calcium (Ca) has been recommended as an alternative. The aim of this study was to define gender-specific cut-off values to predict MTC in patients with elevated basal CT (bCT) following Pg-sCT and Ca-sCT stimulation and to compare the time courses of CT release during stimulation. MATERIALS AND METHODS: The stimulation tests were applied in 62 consecutive patients with thyroid nodules. Basal calcitonin was measured by chemiluminescent immunometric assay. All patients underwent thyroidectomy and bilateral central neck dissection. C-cell pathology was confirmed by histological and immunohistochemical evaluation. RESULTS: In 39 (0.63) patients MTC was documented while isolated C-cell hyperplasia (CCH) was identified in 23 (0.37) patients. Medullary thyroid cancer was predicted in males with bCT values > 43 pg/mL or sCT concentrations > 470 pg/mL (Pg-sCT) or > 1500 pg/mL (Ca-sCT), and in females with bCT concentrations > 23 pg/mL or sCT concentrations > 200 pg/mL (Pg-sCT) or > 780 pg/mL (Ca-sCT), respectively. Pg-sCT correctly predicted MTC in 16 (0.66) compared to 13 (0.54) after Ca-sCT in males and in 12 (0.80) compared to 11 (0.73) in females; without statistical significance. In patients with CCH or low tumor burden, there was a tendency of faster CT release after Ca stimulation (CT peak after 3min in > 60%) compared to patients with advanced MTC (CT peak after 3min in < 10%). CONCLUSIONS: Using gender-specific cut-off values, Ca could replace Pg to predict MTC with similar diagnostic power.

Correlations and time course of FGF23 and markers of bone metabolism in maintenance hemodialysis patients.

OBJECTIVE: Parathyroid hormone (iPTH) and fibroblast growth factor 23 (FGF23) are elevated in secondary hyperparathyroidism. In hemodialysis, higher dialysate calcium (1.5 mmol/L) induces intradialytic suppression of iPTH, whereas its impact on FGF23 and markers of bone metabolism is unknown. We assessed the time course of FGF23 and markers of bone metabolism in relationship to dialysate calcium. DESIGN AND METHODS: In this prospective cohort study of 19 patients on maintenance hemodialysis, we measured serum calcium (sCa), inorganic phosphate (iP), blood urea nitrogen (BUN), ß2-microglobulin (ßMG), iPTH, FGF23, aminoterminal propeptide type 1 procollagen (P1NP), C-telopeptide of type I collagen for bone degradation (CTX-I), osteocalcin (OC), bone specific alkaline phosphatase (BALP), and tartrate-resistant acid phosphatase (TRAP5b) during a single hemodialysis session at baseline, 1, 2, and 3h of dialysis. The time course of measured parameters was compared according to groups of prescribed dialysate calcium of 1.25 mmol/L and 1.5 mmol/L. RESULTS: iPTH declined in the 1.5 mmol/L dialysis group as serum calcium increased whereas it tended to increase in the 1.25 mmol/L group without significant changes in serum calcium. Patients on long-term dialysate calcium of 1.5 mmol/L had significantly lower CTX-I levels and tended to lower levels of iPTH, FGF23, OC, P1NP and TRAP5b at the start of dialysis compared to those on 1.25 mmol/L. CTX-I, FGF23 and OC but not BALP, P1NP and TRAP5b decreased during dialysis independent of dialysate calcium. CONCLUSIONS: In spite of immediate effects on iPTH, dialysate calcium does not acutely affect other parameters of bone and mineral metabolism. SHORT SUMMARY: Dialysate calcium concentration is known to have both immediate and longer-term impact on parathyroid hormone levels in hemodialysis patients. Little is known about the acute impact of dialysate calcium on bone metabolism. In this cross-sectional study of prevalent hemodialysis patients, we found no evidence of immediate short-term dialysate calcium-induced changes of fibroblast growth factor 23 or anabolic and catabolic markers of bone turnover during hemodialysis. However, differences in CTX-I and to a lesser extent other parameters between groups of higher and lower dialysate calcium suggest a longer-term effect that remains to be validated.

Effects of smoking cessation on ß-cell function, insulin sensitivity, body weight, and appetite.

OBJECTIVE: To stop smoking is commonly associated with significant weight gain, but the mechanisms for this are poorly understood. We assessed the effects of smoking cessation on body weight, insulin sensitivity, ß-cell function, and appetite. SUBJECTS AND METHODS: Twenty-seven long-term smokers (n=27; nine females/18 males, 28±1 years, 22.9±0.6 kg/m(2)) attending an ambulatory smoking cessation program in a community hospital in Vienna, Austria were examined at baseline (Visit A; still smoking) and after a minimum of 3 months of smoking abstinence (Visit B; n=14); relapsed smokers were not followed up. Participants underwent 3-h oral glucose tolerance tests and body composition measurements at each study visit. Fasting (QUICKI) and dynamic (oral glucose insulin sensitivity (OGIS)) insulin sensitivity and ß-cell secretion (insulinogenic index 140 (IGI40)) were calculated. Food intake was quantified with a free choice buffet. Fasting plasma concentrations of neuropeptide-Y (NPY), peptide-YY (PYY), glucagon-like peptide 1 (GLP1), leptin, ghrelin, and visfatin were measured. RESULTS: AFTER 3 MONTHS' SMOKING ABSTINENCE, BODY WEIGHT, AND FAT MASS WERE INCREASED (+4 AND +22% RESPECTIVELY, P0.05) AND FASTING INSULIN SENSITIVITY DETERIORATED (QUICKI: post, 0.37±0.02 vs baseline, 0.41±0.2; P<0.05), while OGIS remained unchanged throughout. IGI40 increased by 31% after >3 months' smoking abstinence (P<0.01). Carbohydrate ingestion increased after stopping smoking (P<0.05). NPY fasting levels were increased after >3 months (P<0.05), PYY, GLP1, leptin, ghrelin, and visfatin were unchanged. CONCLUSION: Smoking cessation is associated with transient metabolic changes including increased ß-cell secretion in response to glucose and fasting insulin resistance. These alterations may be associated with or contribute to the body weight gain after smoking cessation.

Risk factors for "PTH spikes" during surgery for primary hyperparathyroidism.

PURPOSE: Increased intraoperative parathyroid hormone excretion ("PTH spikes") due to unintended manipulation of parathyroid adenoma can be observed frequently during surgery for primary hyperparathyroidism. This may lead to difficulties in interpreting intraoperative PTH curves. The aim of this study was to elucidate possible risk factors for PTH spikes and to evaluate the impact on different interpretation criteria of intraoperative PTH curves. METHODS: Eight hundred forty-seven patients with primary hyperparathyroidism were included. The probability of PTH spikes was analyzed regarding preoperative PTH- and creatinine levels, and size of adenoma and their impact on the Vienna, Miami, and Halle criteria was evaluated. RESULTS: PTH spikes occurred in 102 patients (12 %) and revealed to be independent of PTH- and creatinine levels (p = 0.13) preoperatively. There was a significant negative correlation between "manipulation PTH" and "baseline PTH" values and the gland volume, respectively. Patients presenting with smaller adenomas and those with low-baseline PTH values show significantly higher manipulation values. No risk factor for manipulation was exposed and no significantly higher risk of misclassification as "false positive" in case of PTH spikes was detected for any interpretation criterion. For the "Vienna Criterion," however, a significant increase in the risk of "false negative" misclassification was observed with increasing manipulation values. CONCLUSIONS: In patients with PTH spikes, none of the analyzed criteria show a significant increase in missed adenomas. Nevertheless, the Vienna criterion shows a higher rate of potentially unnecessary explorations with increasing manipulation values. Thus, caution is warranted in detecting PTH spikes and in individual interpretations of specific PTH curves is recommended. The Miami criterion seems to be favorable in this group of patients.

Biomarkers of bone turnover in diagnosis and therapy of osteoporosis: a consensus advice from an Austrian working group.

AIM: Reasonable application of laboratory parameters in prevention, diagnosis, treatment and therapy monitoring of osteoporosis. TARGET GROUPS: Physicians from different specialist disciplines (general medicine, geriatrics, gynaecology, urology, internal medicine-especially endocrinology and metabolism, nephrology, laboratory medicine, rheumatology, nuclear medicine, orthopaedics, paediatrics, rehabilitation and physical medicine, radiology, social medicine, transplantation medicine, accident surgery), moreover social insurances, hospitals and self-help groups. BACKGROUND: Evaluation of aetiology of bone disorders, widening of the therapeutic spectrum for diseases of bone and knowledge on biochemical markers of bone turnover. Improvements in judging the success of therapy and in monitoring the compliance of patients. Research perspectives. BASES: Scientific literature and guidelines, consensus meetings. RÉSUMÉ: Basic and specialized laboratory investigations are important in differentiation between primary and secondary osteoporosis for an adequate therapy. Biochemical markers of bone turnover are an additional aid in evaluation of individual fracture risk. These markers identify responders to bone therapy faster than surveillance of bone mineral density, which helps to improve patient's compliance too. Characteristics, preanalytic precautions and applications are presented for selected markers of bone resorption and formation and for parameters regulating bone metabolism.

Lower serum total testosterone is associated with lymph node metastases in a radical prostatectomy cohort study.

BACKGROUND: Data on testosterone levels of patients with prostate cancer of different grade and stage are inconsistent. We retrospectively investigated serum total testosterone of a radical prostatectomy cohort to further shed light on this problem. PATIENTS AND METHODS: The preoperative level of serum total testosterone of 217 patients (mean age: 65±5.8 years) undergoing radical prostatectomy between 1989 and 2002 was analyzed for possible associations with Gleason score (≤6 vs. <7 vs. 8-10) and tumor stage (pT2 vs. pT3 vs. N+) with adjustment for age, diabetes and obesity. Patients exhibiting prostate-specific antigen (PSA) levels of >10 ng/ml and biopsy Gleason scores of ≥7 were submitted to standard lymphadenectomy. RESULTS: The multivariate model revealed a significant effect of body mass index (BMI) (p=0.0003) and diabetes (p=0.002) on testosterone levels. Significantly lower testosterone levels were recorded in patients with nodal metastases (p<0.0001) compared to patients with non metastatic disease. No significant associations between testosterone, Gleason score and stage were found in patients with non- metastatic disease. CONCLUSION: Testosterone levels prior to radical prostatectomy were lower in patients with nodal involvement.

Anti-Mullerian hormone levels decline under hormonal suppression: a prospective analysis in fertile women after delivery.

BACKGROUND: AMH's reported stability during periods of hormonal change makes it a practical tool in assessing ovarian reserve. However, AMH declines with age and age-specific cut-offs remain to be established in women with proven fertility. This study aims to determine age-specific ranges of AMH in women with proven fertility. METHODS: Two hundred-ten fertile women, aged 18-40 years, were prospectively recruited for AMH measurements within 14 days after delivery and age stratified into 3 groups (18-30, 31-36 and 37-40 years). Eligibility required spontaneous conception within a maximal period of six months. Autoimmune diseases, chemotherapy, radiation, ovarian surgery and polycystic ovary syndrome precluded inclusion. RESULTS: 95% confidence intervals of AMH declined with advancing female age from 0.9-1.1 to 0.6-0.9 and 0.2-0.4 ng/mL (P < 0.001). AMH levels were not statistically associated with day of blood draw after delivery or pregnancy characteristics. Neither were they predictive of resumption of menses. They, however, at all ages were lower than reported in the literature for infertile patients. CONCLUSIONS: Like infertile populations, fertile women demonstrate declining AMH with advancing age. Uniformly lower levels than in infertile women suggest that AMH levels do not appear as stable under all hormonal influences as previously reported.

Testosterone dependent androgen receptor stabilization and activation of cell proliferation in primary human myometrial microvascular endothelial cells.

OBJECTIVE: To clarify, whether uterine endothelial proliferation could be regulated via an autocrine estrogen producing mechanism or direct actions of testosterone. DESIGN: In vitro study. SETTING: Tertiary care facility. PATIENT(S): Human myometrial tissue obtained from 40 women undergoing hysterectomy without further intrauterine pathology. INTERVENTION(S): Cell culture, proliferation assay and CYP19 activity assay on human myometrial endothelial cells treated with testosterone, estradiol, letrozole, flutamide, PD98059, MG-132 alone or in combination. MAIN OUTCOME MEASURE(S): We analyzed whether aromatase is expressed in human myometrial microvascular endothelial cells (HMMECs) and whether it affects proliferation and converts androgens to estrogens. In addition, we aimed to define whether or not T could have a direct capability to affect HMMEC proliferation. RESULT(S): Using quantitative real-time PCR and Western analysis, primary passage four HMMECs were shown to express low levels of aromatase mRNA and protein, respectively. However, HMMECs were unable to convert radioactively labeled 3∗H-1ß-androstenedione to estrogen. Pharmacologic doses of T (10(-6) and 10(-4) M) increased HMMEC proliferation, assessed through a bromodeoxyuridine ELISA. This effect of T on proliferation could not be blocked after pretreatment of cells with the aromatase inhibitor letrozole. In addition, HMMECs were found to express androgen receptors (ARs), and the AR antagonist flutamide abolished T-dependent proliferation. T was shown to increase AR protein levels, which was due to T-dependent receptor stabilization and not activation of gene transcription. CONCLUSION(S): We conclude that myometrial endothelial proliferation is not regulated through myometrial endothelial estrogen production. However, pharmacologic doses of T increase myometrial endothelial proliferation through a receptor-dependent and -stabilizing mechanism.

Vascular function in obese children with non-alcoholic fatty liver disease.

OBJECTIVE: To test whether obese children with non-alcoholic fatty liver disease have impaired vascular function compared with obese children with normal liver fat content. METHODS: Obese children (n = 28, 16 males, mean age 10.9 ± 0.7 years, body mass index [BMI] 31.9 ± 4.5 kg/m(2)) with normal (HCLn) and increased hepatocellular lipid content (HCLi, 2.6 ± 0.8 vs. 12.4 ± 8.2%) were recruited, outcome measures being flow-mediated dilation of the brachial artery [FMD] measured by ultrasound, biochemical markers of inflammation (hs-CRP, hs-IL6) and cell adhesion molecules [CAMs], hepatocellular lipids, visceral and subcutaneous fat quantified by nuclear magnetic resonance spectroscopy and imaging. RESULTS: HCLi and HCLn groups showed no significant differences in terms of age, gender, BMI, waist circumference and subcutaneous fat. Subjects in the HCLi group had significantly higher amounts of visceral fat and higher fasting glucose, insulin and triglyceride, but lower adiponectin levels and were more insulin resistant than their HCLn controls. Hepatic fat fraction (HFF) correlated positively with fasting plasma glucose, HOMA-IR, adiponectin, visceral fat, negatively with WBISI independent of BMI. HFF was not associated with subcutaneous fat, fasting insulin, FFA, HDL-C, TG, hs-CRP, hs-IL6, vCAM, iCAM, and FMD. HCLi patients had significantly higher serum levels of hs-CRP and hs-IL6 than HCLn controls. FMD and serum levels of vCAM and iCAM were comparable between groups. CONCLUSIONS: Obese children with simple steatosis rather than steatohepatitis seem to have intact vascular function. Further studies in obese children with different grades of NAFLD are warranted to elucidate the role of fatty liver as a marker of risk for future cardiovascular events.

Reciprocal role of GATA-1 and vitamin D receptor in human myeloid dendritic cell differentiation.

Two major pathways of human myeloid dendritic cell (DC) subset differentiation have previously been delineated. Langerhans cells (LCs) reside in epithelia in the steady state, whereas monocytes can provide dendritic cells (DCs) on demand in response to inflammatory signals. Both DC subset pathways arise from shared CD14+ monocyte precursors, which in turn develop from myeloid committed progenitor cells. However, the underlying hematopoietic mechanisms still remain poorly defined. Here, we demonstrate that the vitamin D(3) receptor (VDR) is induced by transforming growth factor beta1 during LC lineage commitment and exerts a positive role during LC generation. In contrast, VDR is repressed during interleukin-4 (IL-4)-dependent monocyte-derived DC (moDC) differentiation. We identified GATA-1 as a repressor of VDR. GATA-1 is induced by IL-4 in moDCs. Forced inducible expression of GATA-1 mimics IL-4 in redirecting moDC differentiation and vice versa, GATA-1 knockdown arrests moDC differentiation at the monocyte stage. Moreover, ectopic GATA-1 expression stabilizes the moDC phenotype under monocyte-promoting conditions in the presence of vitamin D3 (VD3). In summary, human myeloid DC subset differentiation is inversely regulated by GATA-1 and VDR. GATA-1 mediates the repression of VDR and enables IL-4-dependent moDC differentiation. Conversely, VDR is induced downstream of transforming growth factor beta1 and is functionally involved in promoting LC differentiation.

Is minimally invasive parathyroidectomy without QPTH monitoring justified?

BACKGROUND: It is matter of discussion if quick parathyroid hormone (QPTH) monitoring is helpful in patients with primary hyperparathyroidism (PHPT) and "localized single-gland disease" (SGD; concordant sestamibi and ultrasound results) to further increase the rate of success (permanent normocalcemia) of performing selective parathyroidectomy by minimally invasive parathyroid exploration (MIP). The aim of this study was to evaluate if a randomized controlled trial was justified in order to clarify this discussion. MATERIALS AND METHODS: The prospective database of patients with sporadic PHPT, SGD, MIP, and QPTH monitoring (1999-2005) was evaluated regarding the "conversion rate" to bilateral exploration and permanent normocalcemia ("QPTH" group). Retrospectively, the patients were analyzed a second time "without" applying QPTH monitoring ("non-QPTH" group). Statistical differences between both groups were calculated (McNemar's test). RESULTS: By definition, 338 patients with "localized SGD" underwent MIP. MIP was finished in 308 (91.1%) patients. Five of 308 patients (1.6%) showed persisting (n = 1) or recurrent disease (n = 4). In 30 of 338 patients (8.9%), a conversion to bilateral exploration was necessary (false preoperative localization 15 patients--one patient not cured; multiple-gland disease correctly indicated by QPTH monitoring 15 patients--one patient not cured). Analyzing the "non-QPTH" group, 14 additional patients showed persisting disease. Thus, without using QPTH monitoring, the rate of persisting PHPT would increase from 0.9% (three patients) to 5.0% (17 patients; p = 0.0005). CONCLUSION: Intraoperative QPTH assay seems necessary even in patients with "localized SGD" by two techniques in an endemic goiter region. Abandoning QPTH monitoring would more than double the rate of persisting disease. A randomized trial seems not to be justified.

PTH secretion of "manipulated" parathyroid adenomas.

PURPOSE: Increased secretion of parathyroid hormone (PTH) and its fragments intraoperatively may influence PTH monitoring. The purpose of this study was to investigate whether "intended intraoperative manipulation" of parathyroid adenomas through mechanical stimulation (through squeezing or manual rubbing) would lead to increased PTH excretion. The different PTH fragments that result from this kind of manipulation were correlated and analyzed. METHODS: The enlarged glands of six consecutive patients who underwent open minimally invasive parathyroid exploration were "manipulated" for 30 s as soon as they had been identified. Blood samples were drawn before skin incision, at the beginning of the manipulation, 30 s, and at 2-, 5-, 10-, and 15-min intervals. Serum levels of (1-84)PTH were measured and (7-84)PTH was calculated. RESULTS: An increased PTH secretion was documented in four of six "manipulated" single adenomas (mean PTH +/- SD 312 +/- 497 pg/ml). The PTH of one patient rose from 343 to 1,747 pg/ml. The ratio of (1-84)PTH to (7-84)PTH was 1.3 +/- 0.6 (median +/- SD):1 at "baseline" and 1.4 +/- 0.2:1 after manipulation. The coefficient of determination (R(2)) for the "baseline values" and for the values after manipulation is R(2) = 0.9816 and R(2) = 0.9985, respectively. CONCLUSIONS: First, secretion of PTH varies widely after manual manipulation of adenomas. Second, PTH fragments circulate in the same ratio before and after "manipulation."

Serum inhibin--not a cause of low testosterone levels in hypogonadal prostate cancer?

OBJECTIVES: High-grade prostate cancer is associated with low serum testosterone levels, which generally recover after radical prostatectomy. The cause of this low testosterone level is unclear, and it has been hypothesized that cancer cells produce a factor that disturbs the pituitary-gonadal axis. Inhibin is a hormone that has a negative feedback effect on this axis. The aim of this study was to investigate the role of serum inhibin in patients with prostate cancer. METHODS: The serum hormone levels of the pituitary-gonadal axis, including inhibin levels, in patients with prostate cancer were compared with those in patients with benign prostatic hyperplasia. Testosterone levels of less than 3 ng/mL were classified as hypogonadal. Prostate cancer was classified according to Gleason score as high grade (Gleason score 7 to 10) or low grade (Gleason score 2 to 6). RESULTS: A total of 196 men (126 with prostate cancer and 70 with benign prostatic hyperplasia) were entered into the study. The serum inhibin levels did not differ significantly between the patients with benign prostatic hyperplasia and those with prostate cancer (150.0 versus 131.75 pg/mL, P = 0.062), between men with hypogonadal and eugonadal disease (143.0 versus 146.5 pg/mL, P = 0.573), or between those with low-grade and high-grade cancer (151.5 versus 146.0 pg/mL, P = 0.830). Men with high-grade cancer had lower levels of serum testosterone than did those with low-grade cancer (3.49 versus 4.09 ng/mL, P = 0.056). CONCLUSIONS: The results of our study have shown that although high-grade prostate cancer is associated with low serum testosterone levels, inhibin does not appear to be the cause of this phenomenon.

Medullary thyroid microcarcinoma recommendations for treatment - a single-center experience.

BACKGROUND: Conflicting recommendations exist regarding lymph node (LN) surgery in microMTC (or=10pg/ml) and pentagastrin-stimulated calcitonin levels (sCT:>100pg/ml) were selected for initial surgery. None of the patient was a member of any known MTC family. Biochemical and morphological data of microMTC were compared with 146 patients with C-cell hyperplasia (CCH). RESULTS: MicroMTC (tumor diameter: 4.2+/-2.6mm; unifocal:68; multifocal:29) was documented in 97 of 159 (61%) MTC patients. In 11 (11%) patients, 1-19 LNs were involved. Correlating bCT and sCT levels neither predicted N-stage, nor differentiated between microMTC and CCH. CONCLUSIONS: The biochemical discrimination cannot be made between patients with CCH and MTC, and patients with MTC with/without LN metastasis. Thus, thyroidectomy and central neck dissection is indicated in patients with "mildly" elevated sCT levels (<560pg/ml) (LN positive: 1 of 37 patients [2.7%]). A lateral neck dissection may be added "on demand" (in the setting of measurable postoperative bCT and/or sCT levels indicating LN metastasis). Patients with "highly" elevated sCT (>or=560pg/ml) must be treated as "palpable" MTC (LN positive: 10 of 54 patients [18.5%]).

Glucocorticoids in the treatment of children with acute lymphoblastic leukemia and hodgkin's disease: a pilot study on the adverse psychological reactions and possible associations with neurobiological, endocrine, and genetic markers.

PURPOSE: We did a controlled study to assess adverse psychological reactions (APR) associated with high-dose glucocorticoid therapy and tried to detect somatic correlates for the observed reactions. PATIENTS AND METHODS: Our study included 37 patients with acute lymphoblastic leukemia (ALL) and 11 patients with Morbus Hodgkin (MH) disease, who were treated with high-dose glucocorticoid therapy, and 26 control patients with other types of malignancies. APRs were assessed with a standardized measure via parent-report. Patients with ALL and MH were further analyzed for signs of neuronal cell death in the cerebrospinal fluid, polymorphisms of the glucocorticoid receptor gene, as well as cortisol, adrenocorticorticotropic hormone, and dehydroepiandrosterone sulfate blood levels. RESULTS: Fifty-four percent of ALL, 36% of MH, and 23% of control patients developed APR in the first few weeks of therapy. Approximately 3.5 months later, the majority of patients with ALL showed no APR, similar to control patients. Patients demonstrating a higher, nonsuppressible secretion of cortisol and/or adrenocorticorticotropic hormone during glucocorticoid therapy were found to be more likely to develop APR. No sign of neuronal cell destruction and no correlation of APR with specific glucocorticoid receptor polymorphisms were found. CONCLUSION: Our results suggest that the development of APR due to glucocorticoid therapy is measurable and correlates with hormonal reaction patterns.

A "defined baseline" in PTH monitoring increases surgical success in patients with multiple gland disease.

BACKGROUND: Parathyroid hormone (PTH) monitoring with a quick intact PTH (QIPTH) assay is used in minimally invasive exploration for primary hyperparathyroidism (PHPT) in order not to miss multiple gland disease (MGD). Controversy exists on which criterion is most reliable to predict cure. METHODS: QIPTH values of 310 consecutive patients (single gland disease [SGD]: n = 289; MGD: n = 21) with sporadic PHPT were analyzed using 3 different criteria: "Vienna Criterion": >/=50% decay from a defined "baseline" level (right after induction of anesthesia before skin incision) 10 min after excision. "Miami Criterion": >/=50% decay from highest (preincision or preexcision) value 10 min after excision; "Halle Criterion": decay of the PTH- level to less than or equal to 35 pg/mL within 15 min after excision. RESULTS: The "Vienna" and "Halle Criteria" correctly detected MGD in 19 (91%) and the "Miami Criterion" in 12 (57%) of 21 patients. Incorrect prediction of incomplete excision occurred in 22 patients (8%) with SGD, using the "Vienna Criterion" ("Miami Criterion": 2%, "Halle Criterion": 29%). All of these were recognized intraoperatively from unintended intraoperative manipulation (n = 18), technical failure (n = 2), or borderline increased PTH values (n = 2), and they did not lead to bilateral exploration. Analyzing patients with SGD and MGD, accuracy and specificity were 92% and 89% for the "Vienna Criterion," 93% and 54% applying the "Miami Criterion," and 72% and 89% using the "Halle Criterion." CONCLUSION: Strict definition of a PTH "baseline level" ("Vienna Criterion") improves intraoperative diagnosis of MGD, thus reducing reoperations and increasing long-term cure.

The value of intraoperative pentagastrin testing in medullary thyroid cancer.

BACKGROUND: The decrease of calcitonin levels after curative operation in patients with medullary thyroid cancer is characterized by individual variation; therefore, intraoperative calcitonin measurements to evaluate the completeness of the resection seem to not be feasible. The aim of this study was to evaluate whether an intraoperative pentagastrin test after thyroidectomy and central neck dissection is useful to predict lymph node involvement of the lateral neck. METHODS: A group of 30 consecutive patients underwent primary surgery. After thyroidectomy and dissection of the central lymph node compartment, an intraoperative pentagastrin test was performed. Biochemical and histologic data were compared retrospectively. RESULTS: Of the group, 20 patients (67%) showed no, or only central neck lymph node, involvement and no increase in calcitonin after intraoperative stimulation. Lymph node involvement was documented histologically in the lateral neck of 10 patients (33%), and 8 patients showed an increase of calcitonin as an indication of lymph node involvement. In two patients, each with 1 single micrometastasis in the lateral neck, the intraoperative pentagastrin test was negative. CONCLUSIONS: Intraoperative calcitonin monitoring after pentagastrin stimulation seems promising in predicting lymph node involvement of the lateral neck to aid selection of patients for lateral lymph node dissection. The development of a highly sensitive, quick calcitonin assay is imperative.

PTH spikes during parathyroid exploration--a possible pitfall during PTH monitoring?

BACKGROUND AND AIMS: Parathyroid hormone (PTH) spikes caused by unintentional manipulation of the hypersecreting glands may lead to interpretation problems in intraoperative PTH monitoring. Their frequency and surgical consequences were evaluated. MATERIALS AND METHODS: Intraoperative PTH values of 401 patients with primary hyperparathyroidism and single gland disease were analysed. Patients were divided into four groups: extensive increase (>150 pg/ml), moderate PTH increase (<150 pg/ml), no increase (+/-50 pg/ml) and decrease before excision as referred to the baseline level before skin incision. PTH was measured before and up to 25 min after removal of the enlarged gland. RESULTS: Twenty-two (5.5%) patients had an extensive and 36 (9%) a moderate intraoperative PTH increase. The PTH decline was prolonged to 15 min in 7 (31.8%) and to 25 min in 12 (54.5%) patients after extensive manipulation and in 9 patients (25%) each after moderate manipulation, respectively. No increase occurred in 162 (40.4%) and a decrease in 181 (45.1%) patients. The surgical approach (bilateral exploration vs open, minimally invasive parathyroidectomy) did not show a difference in the rate of PTH spikes. CONCLUSION: PTH spikes often cause a prolonged PTH decline but, when recognized, do not lead to a change in the surgical strategy.