Is medullary thyroid cancer predictable? A prospective study of 86 patients with abnormal pentagastrin tests

Scheuba, Christian; Kaserer, Klaus; Weinhäusl, Andreas; Pandev, Rumen; Kaider, Alexandra; Passler, Christian; Prager, Gerhard; Vierhapper, H.; Haas, Oskar A.; Niederle, Bruno

doi:10.1067/msy.2099.102268

Cited by 69 publications

(68 citation statements)

References 19 publications

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“…Moreover, present results indicate that the costs can be lower if CCH with neoplastic features is included, leading the overall prevalence of the lesions identified by CT measurement to rise from 0.32 to 1.2%. In this series of patients with nodular thyroid disease, and in accordance to data from the literature (Scheuba et al 1999, Scheuba et al 2000, Kaserer et al 2002, bCT levels O10 pg/ml (range 17-196 pg/ml) and sCT levelsO50 pg/ml (range 61-1783 pg/ml) were always associated with CCH when accurate blocking was done. As demonstrated in the present series and previous reports (Guyetant et al 1997), the partial examination of the thyroid glands may lead to non-representative material, according to the heterogeneity of C-cell distribution.…”

Section: U Verga Et Al: C-cell Hyperplasia In Nodular Goitersupporting

confidence: 68%

“…In the absence of a CT response to Pg, the diagnosis of MTC can be excluded, while the increases in the CT levels after stimulus are often difficult to be interpreted. In general, a CT response !50 pg/ml is considered normal , a response O50 and !100 pg/ml is a borderline result, while a CT rise of O100 pg/ml suggests the diagnosis of MTC and the need for surgical treatment , Scheuba et al 1999, Iacobone et al 2002, Elisei et al 2004). However, no cut-off levels of sCT able to differentiate between reactive and neoplastic CCH or to predict MTC have been identified (Iacobone et al 2002, Gibelin et al 2005.…”

Section: Introductionmentioning

confidence: 99%

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Histopathological and molecular studies in patients with goiter and hypercalcitoninemia: reactive or neoplastic C-cell hyperplasia?

Verga¹,

Ferrero²,

Vicentini³

et al. 2007

Endocr Relat Cancer

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The cut-off values able to differentiate between reactive or neoplastic C-cell hyperplasia (CCH) or to predict sporadic medullary thyroid cancer (MTC) are still debated both for basal and stimulated calcitonin (bCT and sCT). In the present study, the prevalence and the histological patterns of CCH in 15 patients with multinodular goiter (MNG), bCTO10 pg/ml and sCT levels O50 pg/ml were studied. As controls, 16 patients with MNG and bCT levels !10 pg/ml and 4 patients with familial (FMTC) were included. For each case, calcitonin (CT) immunoreactive cells were counted in 60 consecutive high-power fields (400!) and CCH classified as focal, diffuse, nodular, or neoplastic. RET genetic analyses were performed at the germline and tissue levels in MTC and CCH cases. In patients with MNG, sCT levels O50 pg/ml were associated with CCH or MTC, being the total number of C-cells/60 fields significantly higher than that found in MNG with normal bCT (PZ0.0008) and comparable with that detected in FMTCs. In the group with sCTO50 pg/ml, the C-cells displayed a neoplastic phenotype. Neither germline nor somatic RET mutations were found. In conclusion, sCT levels O50 pg/ml were always associated with CCH, without correlation between CT levels and the number of C-cells or the final diagnosis. The C-cells had a morphology and distribution pattern similar to those observed in FMTC. Thus, sCT levels O50 pg/ml indicate the presence of CCH with a possible preneoplastic potential, suggesting the opportunity to perform a prophylactic surgical treatment.

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Section: U Verga Et Al: C-cell Hyperplasia In Nodular Goitersupporting

confidence: 68%

Section: Introductionmentioning

confidence: 99%

Histopathological and molecular studies in patients with goiter and hypercalcitoninemia: reactive or neoplastic C-cell hyperplasia?

Verga¹,

Ferrero²,

Vicentini³

et al. 2007

Endocr Relat Cancer

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“…In accordance with the 'receiver operating characteristic curves' in Scheuba et al (1999), the 260 patients were divided into patients with 'Mildly' elevated stimulated calcitonin levels (Group 1 -CCH or medullary thyroid cancer; Biochemical definition/ 'cut off' calcitonin levels: in normal renal function (Zcreatinine !1.5 mg/ml); basal calcitonin O10 pg/ml %64 pg/ml and stimulated calcitonin O100 pg/ml !560 pg/ml) and into patients with 'Highly' elevated stimulated calcitonin levels (Group 2 -medullary thyroid cancer 100%; Biochemical definition/cut off calcitonin levels: normal renal function; basal C Scheuba et al: Sporadic hypercalcitoninemia consequences www.endocrinology-journals.org calcitonin O64 pg/ml or basal calcitonin O10 pg/ml and (independent renal function) stimulated calcitonin R560 pg/ml; Table 3). …”

Section: Correlation Of Calcitonin Levels C-cell Morphology and Patimentioning

confidence: 99%

“…Differences exist in the literature (Scheuba et al 1999, Iacobone et al 2002, Costante et al 2007) regarding calcitonin cut-off levels, indication, time, and extent of surgery.…”

Section: Introductionmentioning

confidence: 99%

Sporadic hypercalcitoninemia: clinical and therapeutic consequences

Scheuba¹,

Kaserer²,

Moritz³

et al. 2009

Endocrine-Related Cancer

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Abstract'Calcitonin screening' is not accepted as the standard of care in daily practice. The clinical and surgical consequences of 'calcitonin screening' in a series of patients with mildly elevated basal calcitonin and pentagastrin stimulated calcitonin levels are presented. 260 patients with elevated basal (O10 pg/ml) and stimulated calcitonin levels (O100 pg/ml) were enrolled in this prospective study. None of the patients was member of a known medullary thyroid carcinoma family. Thyroidectomy and bilateral central and lateral neck dissections were performed. Testing for the presence of germ-line mutations was performed in all patients. Histological and immunohistochemical findings were compared with basal and stimulated calcitonin levels. All patients were subsequently followed biochemically. C-cell hyperplasia (CCH) was found in 126 (49%) and medullary thyroid cancer was found in 134 (51%) patients. RET proto-oncogen mutations were documented in 22 (8%) patients (medullary thyroid cancer:18, CCH:4). In 56 (46%) of 122 patients, sporadic CCH was classified neoplastic ('carcinoma in situ'). Of 97 (72%; 10 with hereditary medullary thyroid cancer) had pT1 (International Union against Cancer recommendations 2002) and 33 (25%) had pT2 or pT3 and 4 (3%) pT4 tumors. Of 39 (29.1%) had lymph node metastases. 106 (79.1%; 15 (38.5%) with lymph node metastases) patients were cured. Evaluation of basal and stimulated calcitonin levels enables the prediction of medullary thyroid cancer. All patients with basal calcitonin O64 pg/ml and stimulated calcitonin O560 pg/ml have medullary thyroid cancer. Medullary thyroid cancer was documented in 20% of patients with basal calcitonin O10 pg/ml but !64 pg/ml and stimulated calcitonin O100 pg/ml but !560 pg/ml.

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“…Serum C T assays are indicated in nodular thyroid patients if there is a family history of MTC, multiple endocrine neoplasia type 2, or non-defined thyroid cancer (1). In Europe, several researchers have recommended the systematic use of serum C T assays in all nodular thyroid patients, in order to identify sporadic MTC as early as possible (2)(3)(4)(5)(7)(8)(9), optimize surgical treatment (12), and obtain better survival (13).…”

Section: Introductionmentioning

confidence: 99%

Reference range of serum calcitonin levels in humans: influence of calcitonin assays, sex, age, and cigarette smoking

d’Herbomez

Caron²,

Bauters³

et al. 2007

European Journal of Endocrinology

113

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Objective: The objective of this study was to re-evaluate the adult C T reference values determined by five different immunoassays and by introducing criteria for selecting control subjects. Design: A prospective multicenter study. Patients: Three hundred and seventy-five clinically euthyroid subjects. Methods: We used five different C T immunoassays. Sera were assayed for the concentration of TSH, gastrin, procalcitonin, urea, calcium, and anti-thyroperoxidase antibodies. Results: Screening for the various potential causes of hypercalcitoninemia led to the exclusion of 23% of the sera. Our reference value analysis dealt with 287 subjects (142 men and 145 women). The proportion of samples in which no C T was detected varied from 56% (for assay D) to 88% (for assay C). We observed significant correlations (whose magnitude depended on the assay used) between C T levels and age or body mass index (BMI) (primarily in men). The distribution of C T levels showed that 4.7, 9.8, 2.5, 6.5, and 8.0% of the values were over 10 pg/ml respectively. These values corresponded essentially to samples from 11 male subjects (median age: 55 years), most of whom were smokers. The highest C T values were around twice as high in men than women, and were higher in smokers than non-smokers. Conclusion: In clinical practice (and after having excluded the usual causes of raised C T levels), the interpretation of C T assay results must take into account i) the method used; ii) the patient's gender, age, and weight; and iii) the potential influence of cigarette smoking.European Journal of Endocrinology 157 749-755

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Is medullary thyroid cancer predictable? A prospective study of 86 patients with abnormal pentagastrin tests

Cited by 69 publications

References 19 publications

Histopathological and molecular studies in patients with goiter and hypercalcitoninemia: reactive or neoplastic C-cell hyperplasia?

Histopathological and molecular studies in patients with goiter and hypercalcitoninemia: reactive or neoplastic C-cell hyperplasia?

Sporadic hypercalcitoninemia: clinical and therapeutic consequences

Reference range of serum calcitonin levels in humans: influence of calcitonin assays, sex, age, and cigarette smoking

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