Predictive Value of Serum Calcitonin Levels for Preoperative Diagnosis of Medullary Thyroid Carcinoma in a Cohort of 5817 Consecutive Patients with Thyroid Nodules

Costante, Giuseppe; Meringolo, Domenico; Durante, Cosimo; Bianchi, Davide Gianluca; Nocera, Maria; Tumino, Dario; Crocetti, Umberto; Attard, Marco; Maranghi, Marianna; Torlontano, Massimo; Filetti, Sébastiano

doi:10.1210/jc.2006-1590

Cited by 324 publications

(259 citation statements)

References 24 publications

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“…As a corollary, all calcitonin thresholds were consistently higher for men than women. Stimulation with pentagastrin afforded better discrimination between C-cell hyperplasia and medullary thyroid cancer in both women and men, especially when calcitonin levels were lower, as noted previously (Iacobone et al 2002, Karges et al 2004, Vierhapper et al 2005, Costante et al 2007, Scheuba et al 2009). By implication, pentagastrin stimulation should ideally be performed in all patients with increased basal calcitonin levels unless these levels are high.…”

Section: Gender-specific Disparities In Calcitonin Secretionsupporting

confidence: 62%

“…(a) a basal calcitonin level within normal limits of the assay practically excludes medullary thyroid cancer (Elisei et al 2004, Rink et al 2009, Scheuba et al 2009) (b) the likelihood of medullary thyroid cancer is remote when stimulated calcitonin levels are !100 pg/ml (Hahm et al 2001, Karges et al 2004, Vierhapper et al 2005, Rink et al 2009, Scheuba et al 2009) (c) raising calcitonin thresholds lowers the rate of false positives at the cost of missing more subclinical disease (Iacobone et al 2002, Karges et al 2004, Vierhapper et al 2005, Costante et al 2007, Cheung et al 2008, Rink et al 2009). …”

Section: A Machens F Hoffmann Et Al: Calcitonin Thresholds In Mtc Smentioning

confidence: 99%

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Importance of gender-specific calcitonin thresholds in screening for occult sporadic medullary thyroid cancer

Machens¹,

Hoffmann²,

Sekulla³

et al. 2009

Endocrine-Related Cancer

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Men and women differ in thyroidal C-cell mass and calcitonin secretion. This difference may have implications for the definition of calcitonin thresholds to distinguish sporadic C-cell hyperplasia from occult medullary thyroid cancer. This retrospective study examined the hypothesis that gender-specific calcitonin thresholds predict occult medullary thyroid cancer more accurately among patients with increased basal calcitonin levels than unisex thresholds. A total of 100 consecutive patients were evaluated with occult sporadic C-cell disease no larger than 10 mm who were referred for increased basal calcitonin levels and underwent pentagastrin stimulation preoperatively at this institution. Altogether, gender-specific calcitonin thresholds predicted medullary thyroid cancer better than unisex thresholds. At lower (%50 pg/ml basally; %500 pg/ml after stimulation), but not higher, calcitonin serum levels, women revealed medullary thyroid cancer four to eight times more often than men. Most discriminatory between C-cell hyperplasia and medullary thyroid cancer was a basal calcitonin threshold of 15 pg/ml (corrected 20 pg/ml) for women and 80 pg/ml (corrected 100 pg/ml) for men, based on the greatest accuracy at the lowest possible calcitonin level. The respective gender-specific stimulated peak calcitonin thresholds were 80 pg/ml (corrected 100 pg/ml) and 500 pg/ml. Corresponding positive predictive values for medullary thyroid cancer at these calcitonin thresholds were 89 and 90% for women, as opposed to 100% for men. To increase the positive predictive value for women to 100%, the respective calcitonin thresholds would have to be raised to 40 pg/ml (corrected 50 pg/ml) and 250 pg/ml. These findings indicate that gender-specific calcitonin thresholds predict sporadic occult medullary thyroid cancer better than unisex thresholds.

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Section: Gender-specific Disparities In Calcitonin Secretionsupporting

confidence: 62%

Section: A Machens F Hoffmann Et Al: Calcitonin Thresholds In Mtc Smentioning

confidence: 99%

Importance of gender-specific calcitonin thresholds in screening for occult sporadic medullary thyroid cancer

Machens¹,

Hoffmann²,

Sekulla³

et al. 2009

Endocrine-Related Cancer

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“…Despite the ever increasing number of publications recommending routine calcitonin measurements in patients with thyroid nodules to diagnose medullary thyroid cancer in an early and therefore curable stage (Pacini et al 1994, Rieu et al 1995, Niccoli et al 1997, Vierhapper et al 1997, 2005, Ozgen et al 1999, Hahm et al 2001, Elisei et al 2004, Papi et al 2006, Costante et al 2007, 'calcitonin screening' is not recommended in daily practice (Hegedus 2004). 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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“…Routine measurement of calcitonin (CT) in patients with thyroid nodular disease is nowadays strongly advised, at least by the recent European Thyroid Association consensus statement, since it allows accurate, early diagnosis of a rare but frequently fatal tumor, medullary thyroid carcinoma (MTC), and therefore definitive cure in a significant percentage of cases (1). While around 20-25% of MTCs are familial and fall within the multiple endocrine neoplasia (MEN) spectrum, and can be detected by molecular screening for germline RET proto-oncogene mutations, the remaining 75-80% are sporadic (1).…”

Section: Introductionmentioning

confidence: 99%

“…While around 20-25% of MTCs are familial and fall within the multiple endocrine neoplasia (MEN) spectrum, and can be detected by molecular screening for germline RET proto-oncogene mutations, the remaining 75-80% are sporadic (1). The MEN 2A phenotype and biological features of MTC can, to some extent, be predicted by specific RET mutation risk stratification (2,3).…”

Section: Introductionmentioning

confidence: 99%

Uncommon association of germline mutations of RET proto-oncogene and CDKN2A gene

Foppiani

Forzano

Ceccherini

et al. 2008

European Journal of Endocrinology

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Introduction: Calcitonin measurement is advised in the diagnosis of thyroid nodules, as it is an accurate marker of medullary thyroid carcinoma (MTC). C-cell hyperplasia (CCH)-induced hypercalcitoninemia cannot be distinguished from that induced by MTC, unless surgery is performed. Case: We report the clinical and biological features of a patient with a family history of cancer, including melanoma and pancreatic cancer, who had previously undergone surgery for melanoma. He presented the unusual association of papillary thyroid carcinoma (PTC), normocalcemic hyperparathyroidism, and hypercalcitoninemia with a pathological response to pentagastrin, which was histologically deemed secondary to CCH. Multiple endocrine neoplasia (MEN) 2A was diagnosed. RET gene analysis showed a p.V804M missense mutation in exon 14, a low-but variably penetrant defect found in both sporadic and MEN2A-associated MTC/CCH, and a p.G691S polymorphism in exon 11. Furthermore, the germline P48T mutation was found in the CDKN2A gene exon 1, which is known to be associated with melanoma and pancreatic cancer. The patient showed the uncommon coexistence of a germline mutation in two suppressor genes, RET and CDKN2A; this finding, deemed to be a mere coincidence, did not modify the phenotype expected by each single mutation. CCH associated with V804M RET mutation is a precancerous condition and surgery is recommended. In order to exclude MTC, surgery is advised in patients with a pathological calcitonin response to pentagastrin, in the absence of thyroid autoimmunity. CCH-induced hypercalcitoninemia can be associated with thyroid cancers other than MTC (e.g., PTC). Family history is important in scheduling specific genetic screening in high-risk patients and their relatives.

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Predictive Value of Serum Calcitonin Levels for Preoperative Diagnosis of Medullary Thyroid Carcinoma in a Cohort of 5817 Consecutive Patients with Thyroid Nodules

Abstract: CT screening of thyroid nodules is a highly sensitive test for early diagnosis of MTC, but confirmatory stimulation testing is necessary in most cases to identify true positive increases.

Cited by 324 publications

References 24 publications

Importance of gender-specific calcitonin thresholds in screening for occult sporadic medullary thyroid cancer

Importance of gender-specific calcitonin thresholds in screening for occult sporadic medullary thyroid cancer

Sporadic hypercalcitoninemia: clinical and therapeutic consequences

Uncommon association of germline mutations of RET proto-oncogene and CDKN2A gene

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