Preoperative Calcitonin Research Articles

Outcome of Patients with Different MEN2A Germline Mutations

Objectives: Medullary thyroid carcinoma (MTC) behavior in MEN2 present variations, ranging from indolent MTC, in patients harboring intra-cellular “weak mutations, to highly aggressive disease, with RET mutation in codons 634 or 918. We compared the outcomes among patients with different germline mutations. Methods: Retrospective chart review. Between January 2002 and December 2011, 67 MTC patients were operated at our institution: 26 (38.8%) sporadic and 41 (61.2%) carriers of MEN2A germline RET mutations. All patients were tested for RET hot spot mutations (exons 5, 8, 10, 11, 13, 16), pre- and postoperative calcitonin (Ct), carcinoembryonic antigen (CEA), parathyroid hormone, and calcium. They were also submitted to imaging studies (ultrasound, MRI, CT and scintigraphy). Follow-up varied from 1 to 65 months (average 10.9 months). Patients were classified as cured when serum Ct concentration <2pg/mL in the last evaluation (Group A). Patients not cured were divided in two groups: Group B) Ct >2pg/mL and >40pg/mL and Group C) Ct>40pg/mL. Results: Nineteen patients (46.3%) were cured, most of them treated by prophylactic surgery. There was no difference according to the RET mutation. Preoperative calcitonin level ranged from 4.5 to 1367pg/mL (average 124.5) in group A from 9 to 180149 (average 124.5) in group B and from 98 to 8358 (average 2587) in group C. Fifteen patients (36.6%) presented postoperative hypoparathyroidism, not related to cure, although related to extended surgery. Younger patients who underwent prophylactic surgery had better prognosis ( P = 0.02). Conclusions: Genetic test is the most important exam to perform in MTC patients. Outcome was better in younger patients treated by prophylactic surgery.

Hypercalcitoninemia in thyroid conditions other than medullary thyroid carcinoma: a comparative analysis of calcium and pentagastrin stimulation of serum calcitonin

Calcitonin screening aims at uncovering occult medullary thyroid cancer (MTC) in patients with nodular thyroid disease. Elevated basal calcitonin serum levels call for calcitonin stimulation, the level of which may direct the extent of surgery. Because pentagastrin has become restricted, calcium has increasingly been used instead for stimulation. This study identified a new spectrum of patients demonstrating a false-positive hypercalcitoninemia in the absence of C-cell disease, carrying multinodular goiter (MNG), thyroiditis, and non-MTC thyroid malignancy, and endeavored to explore the feasibility of extrapolating pentagastrin-stimulated to calcium-stimulated calcitonin thresholds. Altogether, 43 (9.5 %) of 455 patients with nodular thyroid disease revealed increased basal calcitonin serum levels between 2005 and 2012, for which they underwent intravenous stimulation with pentagastrin (31 patients) or calcium gluconate (12 patients) before and after primary thyroidectomy. Stimulation with calcium gluconate resulted in significantly higher and more variable preoperative calcitonin serum levels after 2 (241.2 vs. 104.9 pg/mL; P = 0.018) and 5 min (240.6 vs. 87.4 pg/mL; P = 0.007) than stimulation with pentagastrin. Stimulation with calcium gluconate produced 10-fold (nodular goiter), 15-fold (thyroiditis), and 21-fold (thyroid neoplasia other than MTC) calcitonin increases over baseline, as opposed to 5-fold, 10-fold, and 8-fold increases after stimulation with pentagastrin. None of the 43 patients, all of whom reverted to undetectable calcitonin serum levels after thyroidectomy, had immunohistochemical evidence of C-cell disease. Subgroup analyses according to gender and thyroid disease, being limited by the low number of patients in each subgroup, did not yield significant differences. Calcium stimulation yields significantly greater calcitonin levels than pentagastrin stimulation, precluding generalization of pentagastrin-stimulated to calcium-stimulated calcitonin thresholds. After calcium stimulation, false-positive findings appear to be more common in patients of female gender and patients with thyroiditis and thyroid neoplasia other than MTC, potentially effecting surgical overtreatment.

Clinical diagnosis and treatment of familial medullary thyroid carcinoma caused by a p.C618Y RET proto-oncogene mutation in a Chinese pedigree

To explore the clinical characteristics, therapeutic and clinical significance for RET proto-oncogene screening in a pedigree with familial medullary thyroid carcinoma. Comprehensive medical history was obtained from 19 members in a 4-generate southern Chinese family. Systemic clinical investigations including biochemical testing, imaging examinations and germline RET screening. RET screening showed heterozygous missense mutations of TGC to TAC at codon 618 on exon 10 in 8 cases (p.C618Y) completely consistent with the clinical manifestations. The clinical data of 7 patients with medullary thyroid carcinoma (MTC) and 2 carriers of asymptomatic RET mutation from were analyzed. Single/bilateral multi-centric MTC with lymph node metastases was confirmed in 6 cases by histopathology and 1 case by clinical examination. There were 1 male and 6 females with an initial mean diagnostic age was 49.6 years (range: 24 - 78). All had palpable neck masses. And the mean maximum diameter of MTC was 2.6 cm (range 1.4 - 4.4). Seven patients underwent thyroidectomy except a 78-year-old female patient: right total and left subtotal thyroidectomy (n = 1), right total thyroidectomy (previous left total thyroidectomy for benign mass) (n = 1) and total thyroidectomy (n = 4) were performed. All procedures were accompanied by at least bilateral level VI lymph node dissection and/or with modified single/bilateral neck dissection. After the first operation, 6 patients still presented a high value of calcitonin: 1 patient died of metastasis 64 months postoperatively; 3 patients underwent reoperation at 6 months after initial operation, the calcitonin levels dropped to normal in 2/3 cases and stayed higher in 1 case; another two cases presented bilateral thyroid gland residua, local lymph node enlargement on imaging examination and elevated levels of calcitonin at 214 and 60 months postoperation respectively. However, 1/2 asymptomatic with elevated pre-operative calcitonin subjects underwent total thyroidectomy and histopathological examination showed bilateral C cell hyperplasia. The other carriers, without surgery, with normal neck images, close monitoring and a 10-month follow-up, still presented undetectable calcitonin. Based on family survey, integrated RET screening and serum levels of calcitonin facilitate an early diagnosis and normalize surgery to improve the prognosis. For asymptomatic RET mutation carriers, their levels of calcitonin shall guide the individualized regimen of prophylactic thyroidectomy or strict monitoring and follow-ups.

La chirurgie prophylactique du cancer médullaire de la thyroïde

Medullary thyroid cancer (MTC) is genetically determined in 30% to 35% of cases, notably through multiple mutations in the RET protooncogene located on chromosome 10, for which a genotype-phenotype relationship determines age of onset. There are three phenotypes: MEN 2 A and B, and isolated familial MTC. The type of mutation determines 3 levels of aggressiveness. Current guidelines recommend thyroidectomy during the first months of life for patients with very-high-risk (level 3) mutations and before 5 years of age for high-risk (level 2) mutations. There are no precise recommendations for lower-risk mutations, for which the surgical decision also depends on the calcitonin level and family history. We describe 18 patients who underwent prophylactic surgery. Regardless of the mutation, all patients with a normal preoperative calcitonin level were cured. However, surgery was performed later than recommended, for various reasons, including late genetic diagnosis and parents' opposition.

Preoperative basal calcitonin and tumor stage correlate with postoperative calcitonin normalization in patients undergoing initial surgical management of medullary thyroid carcinoma

The optimal initial operative management of medullary thyroid cancer (MTC) and the use of biomarkers to guide the extent of operation remain controversial. We hypothesized that preoperative serum levels of calcitonin and carcinoembryonic antigen (CEA) correlate with extent of disease and postoperative levels reflect the extent of operation performed. We assessed retrospectively clinical and pathologic factors among patients with MTC undergoing at least total thyroidectomy; these factors were correlated with biomarkers using regression analyses. Data were obtained from 104 patients, 28% with hereditary MTC. Preoperative calcitonin correlated with tumor size (P < .001) and postoperative serum calcitonin levels (P = .01) after multivariable adjustment for lymph node positivity, extent of operation, and hereditary MTC. No patient with a preoperative calcitonin level of <53 pg/mL (n = 20) had lymph node metastases. TNM stage (P = .001) and preoperative calcitonin levels (P = .04), but not extent of operation, independently correlated with the failure to normalize postoperative calcitonin. Postoperative CEA correlated with positive margins (adjusted P = 04). Neither preoperative nor postoperative CEA was correlated with lymph node positivity or extent of surgery. Preoperative serum calcitonin and TMN stage, but not extent of operation, were independent predictors of postoperative normalization of serum calcitonin levels. Future studies should evaluate preoperative serum calcitonin levels as a determinate of the extent of initial operation.

Medullary and papillary carcinoma of the thyroid gland occurring as a collision tumor with lymph node metastasis: A case report

IntroductionPapillary thyroid carcinoma and medullary thyroid carcinoma are two different thyroid neoplasia. The simultaneous occurrence of medullary thyroid carcinoma and papillary thyroid carcinoma as a collison tumor with metastases from both lesions in the regional lymph nodes is a rare phenomenon.Case presentationA 32-year-old Iranian man presented with a fixed anterior neck mass. Ultrasonography revealed two separate thyroid nodules as well as a suspicious neck mass that appeared to be a metastatic lesion. The results of thyroid function tests were normal, but the preoperative calcitonin serum value was elevated. Our patient underwent a total thyroidectomy with neck exploration. Two separate and ill-defined solid lesions grossly in the right lobe were noticed. Histological and immunohistochemical studies of these lesions suggested the presence of medullary thyroid carcinoma and papillary thyroid carcinoma. The lymph nodes isolated from a neck dissection specimen showed metastases from both lesions.ConclusionsThe concomitant occurrence of papillary thyroid carcinoma and medullary thyroid carcinoma and the exact diagnosis of this uncommon event are important. The treatment strategy should be reconsidered in such cases, and genetic screening to exclude multiple endocrine neoplasia 2 syndromes should be performed. For papillary thyroid carcinoma, radioiodine therapy and thyroid-stimulating hormone suppressive therapy are performed. However, the treatment of medullary thyroid carcinoma is mostly radical surgery with no effective adjuvant therapy.

Factors Predicting Outcome of Total Thyroidectomy in Young Patients with Multiple Endocrine Neoplasia Type 2: A Nationwide Long‐Term Follow‐up Study

BackgroundMultiple endocrine neoplasia type 2 (MEN 2) is caused by a RET mutation in chromosome 10. All MEN 2 patients develop medullary thyroid carcinoma (MTC). The age-related risk of MTC is associated with the type of RET mutation. Our aim was to identify prognostic factors associated with recurrent MTC in MEN 2 patients.MethodsIn a nationwide case–control study, all patients who underwent total thyroidectomy in the Netherlands under the age of 20 years were classified into standard (1), high (2), or very high risk (3) for MTC based on RET-mutation type. Disease-free patients were compared with those with recurrent disease.ResultsA total of 93 patients were included in the study. Sixty-six percent had MTC on histology, the youngest being 1 year old. Codon 634 was most affected. Sixteen (18%) patients had persistent or recurrent disease, one of whom died. Significantly associated determinants of outcome in univariate analysis were higher age at surgery, no age-appropriate prophylactic surgery according to risk level, elevated preoperative calcitonin levels, affected codon, and the presence of lymph node metastases at surgery. On multivariate analysis only age of surgery was the single independent factor associated with persistent disease.ConclusionsProphylactic thyroidectomy beyond the recommended age is associated with persistent/recurrent disease. In addition, codon 634 mutation is associated with a high risk of recurrence requiring early surgery for all these patients.

Detection of medullary thyroid cancer: a focus on serum calcitonin levels

Medullary thyroid cancer (MTC) is a neuroendocrine tumor derived from the C cells of the thyroid. C cells are responsible for the production of calcitonin, a sensitive and specific marker for MTC. Early detection of MTC is essential; overall survival from MTC is related to patient age, stage of disease and extent of surgical resection. Elevated preoperative serum calcitonin levels have been shown to predict the likelihood of biochemical remission postoperatively. The use of routine serum calcitonin measurements as a screening measure for MTC in patients with thyroid nodules has been advocated in Europe. To date, routine calcitonin measurement has not been widely practiced in the USA; a recent cost–effectiveness analysis suggests routine serum calcitonin measurements in patients with thyroid nodules may be comparable to other widely accepted screening programs.

Serum Calcitonin-Negative Medullary Thyroid Carcinoma: Role of CgA and CEA as Complementary Markers

The biochemical activity of medullary thyroid carcinoma (MTC) includes production of calcitonin (CT), chromogranin A (CgA) and carcinoembryonic antigen (CEA). Routine CT measurement has been proposed as part of the initial evaluation of thyroid nodules and its use could ultimately decrease the morbidity and mortality of MTC. We report on a 43-year-old female patient with a large MTC expressing CT, CgA and CEA on immunostains but with negative preoperative CT and CgA results. Serum CEA was slightly increased and its rapid disappearance predicted radical cure by surgery as confirmed by 2-year follow-up. Our report illustrates that a diagnosis of MTC cannot always be excluded by negative preoperative CT. Fine-needle aspiration with cytomorphological analysis and complementary immunocytochemistry remains an essential diagnostic tool. Finally, serum aliquots must be stored before thyroid surgery in order to measure circulating forms of complementary markers found by tissue immunostaining (CEA and CgA).

Medullary Thyroid Cancer Responsiveness to Pentagastrin Stimulation: An Early Surrogate Parameter of Tumor Dissemination?

Because of its outstanding sensitivity, stimulation of calcitonin secretion with iv injection of pentagastrin is widely used for biochemical diagnosis of medullary thyroid cancer. The objective of this study was to explore the relationship between the results of the pentagastrin stimulation test and extent of disease in patients with previously untreated medullary thyroid cancer. This was a retrospective study. The investigation took place at a tertiary referral center. Included were 89 patients with increased basal calcitonin levels who had a pentagastrin test at this institution before initial neck surgery for medullary thyroid cancer. Measurements included basal and stimulated calcitonin levels, carcinoembryonic antigen levels, primary tumor diameter, extrathyroidal extension, lymph node metastases, and distant metastases. There was a strong dose-dependent relationship between a less than 10-fold increase in preoperative calcitonin levels after iv stimulation with pentagastrin and both the frequency (41-54 vs. 4-27%; P = 0.001) and number (means of 3.0-10.8 vs. 0-1.1 positive nodes, P < 0.001) of lymph node metastases. Weaker associations were identified with the respective frequency of extrathyroidal extension (14-27 vs. 0-7%; P = 0.027), distant metastasis (9-23 vs. 0%; P = 0.017), and postoperative normalization of calcitonin (40-55 vs. 53-82%; P = 0.029). On multivariate analysis, only lymph node metastases were associated with a less than 10-fold increase in preoperative calcitonin levels. Based on these clinical data and preclinical literature, reduced responsiveness to stimulation with pentagastrin may reflect early dedifferentiation. Evidence of this condition may enable early risk stratification in patients with medullary thyroid cancer.

Serum calcitonin-negative medullary thyroid carcinoma: role of CgA and CEA as complementary markers

The biochemical activity of medullary thyroid carcinoma (MTC) includes production of calcitonin (CT), chromogranin A (CgA) and carcinoembryonic antigen (CEA). Routine CT measurement has been proposed as part of the initial evaluation of thyroid nodules and its use could ultimately decrease the morbidity and mortality of MTC. We report on a 43-year-old female patient with a large MTC expressing CT, CgA and CEA on immunostains but with negative preoperative CT and CgA results. Serum CEA was slightly increased and its rapid disappearance predicted radical cure by surgery as confirmed by 2-year follow-up. Our report illustrates that a diagnosis of MTC cannot always be excluded by negative preoperative CT. Fine-needle aspiration with cytomorphological analysis and complementary immunocytochemistry remains an essential diagnostic tool. Finally, serum aliquots must be stored before thyroid surgery in order to measure circulating forms of complementary markers found by tissue immunostaining (CEA and CgA).

NEW ERA: PROPHYLACTIC SURGERY FOR PATIENTS WITH MULTIPLE ENDOCRINE NEOPLASIA‐2A

The surgical management of patients with multiple endocrine neoplasia-2A (MEN-2A) continues to evolve with specific genotype-phenotype correlations allowing for a more tailored approach. In this study, we report the surgical management of one of the largest MEN-2A families with a rearranged during transfection (RET) codon 804 mutation. This is a cohort study comprising all at-risk kindred within a single known MEN-2A family. Prophylactic total thyroidectomy with lymph node dissection was recommended to all mutation carriers aged 5 years and older. There were a total of 48 at-risk individuals in the MEN-2A kindred, with 22 patients undergoing thyroidectomy after appropriate preoperative evaluation. A total of 9 patients had medullary thyroid cancer including 5 with a normal preoperative calcitonin level. A total of 11 patients had C-cell hyperplasia and 7 showed histological evidence of parathyroid disease. Only the index case had a phaeochromocytoma. Genetic testing for germline mutations in the RET proto-oncogene has allowed precise identification of affected RET carriers and provided the opportunity for prophylactic or 'preclinical' surgery to treat and in fact to prevent medullary thyroid cancer. This concept of prophylactic surgery based on a genetic test is likely to be applied more widely as the tools of molecular biology advance.

Value of routine measurement of serum calcitonin concentrations in patients with nodular thyroid disease: A multicenter study

The routine measurement of serum calcitonin (CT) has been proposed for patients with nodular thyroid disease (NTD), to detect unsuspected medullary thyroid carcinoma (MTC) before surgery. To assess the prevalence of hypercalcitoninemia and MTC in NTD patients; to compare the ability of CT measurement and fine needle aspiration cytology (FNAC) to predict MTC; to identify age groups of NTD patients who should be better candidates than others to undergo routine measurement of CT. 1425 consecutive patients, referred from April 1, 2003, through March 31, 2004, to four Italian endocrine centers due to NTD, were grouped depending on age, and underwent basal and, in some cases, pentagastrin (Pg)-stimulated CT measurement, FNAC and, when indicated, surgery. Serum CT concentrations were measured by an immunoluminometric assay (ILMA). Hypercalcitoninemia was found in 23 out of 1425 patients. MTC was discovered in 9 patients, all >40 yr old and showing high CT levels. Sensitivity of basal and Pg-stimulated CT to predict MTC before surgery was 100% for both tests, whereas specificity was 95 and 93%, respectively. CT specificity reached 100% when a cutoff value of 20 pg/ml was taken. FNAC showed an overall 86% sensitivity. When >10 mm MTC nodules were considered, FNAC sensitivity approached 100%. On the contrary, a correct cytological diagnosis was obtained in only one out of five patients with <10 mm MTC nodules (microMTC); in one patient with histologically proved microMTC, FNAC even demonstrated a benign lesion. Hypercalcitoninemia or MTC were associated with chronic thyroiditis in 30 or 33% of cases, respectively. C-cell hyperplasia was found in 57% of hypercalcitoninemic patients without MTC. Basal CT measurement detects elevated CT values in 1.6% of NTD patients. Although CT is not a specific marker of MTC, its routine measurement represents a useful tool in the pre-operative evaluation of NTD patients, particularly those >40 yr old presenting with nodules <10 mm, even when FNAC does not show malignant features. To our knowledge, this is the first trial using ILMA to assess the ability of pre-operative CT measurement to predict MTC in a large series of NTD patients.

Prognostic Significance of Disseminated Tumor Cells in the Connective Tissue of Patients with Medullary Thyroid Carcinoma

Disseminated tumor cells in the connective tissue (CT-DTCs) do not have any connection to a primary tumor or the lymph nodes. They are identified quite often in patients with medullary thyroid carcinoma (MTC), but nothing is known regarding their prognostic significance. Among 450 patients with MTC, 69 (15%) were identified as having CT-DTCs. A case-control group of patients without CT-DTCs was selected. The two groups were matched concerning TNM classification, age, heredity, and sex. Because many patients with CT-DTCs had extrathyroidal tumor extension (pT4 category), distant metastases (M1 category), or both, only 35 matched pairs could be identified. The TNM classification in both groups was as follows: pT1, n = 8; pT2, n = 15; pT3, n = 4; pT4, n = 8; pN0, n = 4; pN1, n = 31; M0, n = 30; M1, n = 5. The mean age was 46.8 +/- 17.0 years in the CT-DTC group and 44.4 +/- 15.0 years in the case-control group (NS). In both groups, 23 patients had sporadic MTC, and 12 patients had hereditary MTC. Neither mean basal preoperative nor postoperative calcitonin levels differed significantly between the two groups. In contrast, none of the patients with CT-DTCs was biochemically cured (normal calcitonin level after pentagastrin stimulation) compared to eight patients without CT-DTCs (P < 0.005). The two groups did not differ concerning other parameters (basal calcitonin level > 3000 pg/ml, more than 10 lymph node metastases, more than two involved locoregional lymph node compartments, mediastinal lymph node metastases) that have been reported to correlate with the lack of or almost (< 10%) lack of biochemical cure. In patients with MTC, disseminated tumor cells in the connective tissue correlate with advanced tumor stages and appear to be of prognostic significance.

Investigation of Calcitonin and Calcitonin Gene-related Peptide in 88 Cases of Medullary Thyroid Carcinoma

Objective: To investigate the changes of calcitonin (CT) and calcitonin gene-related peptide (CGRP) in patients with medullary thyroid carcinoma (MTC). Methods: Fifty-eight cases of MTC were selected and the relationship between the CT levels and metastasis was investigated. The immunohistochemical method was used to detect the expression of CT and CGRP in the 58 samples of MTC tissues. The CT and CGRP in 30 newly diagnosed MTC inpatients were measured before operation and in the first few days after operation using a radioimmunoassy. Results: (1) The rate of residual tumor had a significant difference between the normal serum CT group one month after operation and the elevated group at the same period (P<0.01). (2) Immunohistochemical study revealed the positive rate of CT was about 98%, and that of the CGRP was 87.8%. (3) Part of the patients had an elevated CGRP levels while CT levels was normal. (4) The serum CT levels were decreased to a stable range one week after operation. Conclusion: CT is a useful index to evaluate the efficacy of surgical treatment. The measurement of serum CGRP is helpful in the diagnosis of MTC, especially for those whose preoperative CT levels are normal.

Tiroidectomía profiláctica en niños y jóvenes con cáncer medular tiroideo hereditario: Experiencia chilena

With the availability of the RET proto-oncogene genetic testing, it is possible to perform prophylactic total thyroidectomy among carriers of RET mutation. To evaluate the histological findings and the effects of the prophylactic total thyroidectomy in first-degree relatives of Chilean patients with multiple endocrine neoplasia type 2 (MEN 2) based on the Ret proto-oncogene analysis. Nineteen patients belonging to 11 MEN 2 families underwent total thyroidectomy. Of these, 16 either with C cell hyperplasia (CCH) or microscopic medullary thyroid carcinoma (MTC) were selected for the final analysis. The age at the moment of thyroidectomy ranged from 3 to 24 years (median 9.5). The most common mutation was located in codon 634 (69%) followed by codon 620 (25%). Histopathology revealed MTC in 13 patients (81%, youngest 3 years, oldest ones 19 and 24 years) and CCH in 3. A significant correlation was observed between basal preoperative serum calcitonin/tumor size (r = 0.53, P < 0.05) and age/tumor size (r = 0.56, P < 0.03), but not between basal preoperative serum calcitonin and age. Stimulated preoperative calcitonin levels were confounding and not useful for differentiating CCH from MTC. None of patients in whom cervical dissection was done (9/16) presented lymph node metastases, including the oldest ones. All patients but the older ones were biochemically cured after a mean of 5 years of follow-up. Prophylactic total thyroidectomy should be done early in life because there is an age-dependent progression from HCC to MTC. MTC often precedes biochemical detection of the disease.

Lymph node involvement in macroscopic medullary thyroid carcinoma

Medullary thyroid carcinoma (MTC) is a rare disease, with variable tendency to lymphatic spread. The aim of this retrospective study was to identify distinctive features of large MTC with and without nodal metastases. Between 1993 and 2003, 28 consecutive patients underwent total thyroidectomy and neck node dissection for sporadic MTC larger than 10 mm in diameter. All tumours were confirmed to be malignant with a locally invasive pattern of growth. Lymph node metastases were present in 16 patients (N1) and absent in 12 (N0). There were no statistically significant differences between patients with N0 and N1 tumours concerning age (mean 52.1 versus 53.4 years), male:female ratio (0.7 versus 1.0), basal preoperative calcitonin concentration (mean 3238 versus 3076 pg/ml) and tumour size (23.3 versus 23.9 mm). There were differences in the incidence of tumour invasion (P < 0.001), vascular embolism (P = 0.011) and peritumoral thyroiditis (P = 0.039). Measurement of basal and stimulated calcitonin levels after surgery confirmed biochemical cure in all patients with N0 tumours and half of those with N1 disease (P = 0.006). There were no preoperative factors that predicted node status for MTC larger than 1 cm in this series. Total thyroidectomy and nodal dissection remains the optimal treatment.

Results of surgical treatment of sporadic medullary thyroid carcinoma following routine measurement of serum calcitonin

Aim. The aim of this study was to evaluate the results of the surgical management of medullary thyroid carcinoma (MTC), following the introduction of systematic calcitonin measurement in patients referred for thyroid diseases. Method. We included all the patients with elevated calcitonin and MTC from January 1993 to March 2001. Results. Among 8497 patients, MTC was diagnosed in 52 with a mean age of 56.1 years. Thirty-two fine needle biopsies led to diagnose MTC in 19 cases. The median basal pre-operative calcitonin level was 245 pg/ml. Elevated calcitonin serum was the only indicator of MTC in 31 patients. Fifty-one patients underwent total thyroidectomies, with lymphadenectomy in 45. Thirteen patients had lymph node involvement. Post-operatively, 40 (77%) had normal basal and pentagastrin (Pg) stimulated calcitonin serum levels, and remained normal at a mean follow-up of 5.16 years (1.8–8). Conclusion. Routine pre-operative measurement of calcitonin should be performed because it is often the only indicator of MTC at an early stage. This could lead to an improved MTC cure rate.

Postoperative calcitonin study in medullary thyroid carcinoma.

Calcitonin (CT) is a sensitive marker for medullary thyroid carcinoma. Normalization of early postoperative CT level is a favorable prognostic factor. The aim of this study was to establish the prognostic value of CT-level kinetics by preoperative tumor stage and postoperative elimination rate. Blood serum from 22 medullary thyroid carcinoma (MTC) patients without remote metastases was assayed. A commercial RIA DSL-1200 test was used to assay CT levels. Basal CT< or =42 pg/ml and stimulated CT< or =120 pg/ml were considered normal. The patients were divided into three groups according to the intensity of the postoperative CT level reduction in blood serum. Group 1 comprised patients who showed basal CT normalization within the first 2-3 days after surgery. Group 2 included those patients with slow (from 2 to 4 weeks) CT-level normalization. Group 3 included patients with CT levels that reduced within 14 days, but subsequently increased. Preoperative basal CT varies from 216 to 1654 pg/ml and depends on tumor-node-metastasis (TNM) stage. In seven patients, no basal CT decrease to normal values was observed; in five of these patients, disease recurrence was detected 2-6 months after surgery. In the group with slowly decreasing CT levels, no strong correlation between preoperative CT level and the postoperative time to normalization of basal and peak CT could be established; this may be due to the small number of patients. Our study showed that preoperative CT level depended on the disease stage. Postoperative CT elimination rate is independent of preoperative CT level. Postoperative increase in the basal or stimulated CT level is an unfavorable prognostic factor, implying disease recurrence.

When should thyroidectomy be performed in familial medullary thyroid carcinoma gene carriers with non-cysteine RET mutations?

Background Once familial medullary thyroid carcinoma gene carrier status is established, thyroidectomy must be performed in infancy for mutations in exon 10, but in familial medullary thyroid carcinoma with non-cysteine RET mutations, which is characterized by a late onset of C-cell disease, the appropriate timing of thyroidectomy is unclear. Methods We analyzed the cases of 76 patients who underwent thyroidectomy (mean age, 35.2 years); 66 patients underwent concomitant lymphadenectomy. Results Before the operation, 35 patients had abnormal basal calcitonin levels. Nine and 30 patients had negative or positive pentagastrin test results, respectively. We found normal thyroid in 4% of the patients, C-cell hyperplasia in 29% of the patients, medullary thyroid carcinoma in 67% of the patients (microscopic in 82.4%), and nodal metastases in 19.6% of the patients. The aggressiveness of the disease varied significantly between those patients with preoperative positive pentagastrin test results and those patients with high basal calcitonin levels, with a surgical cure rate of 60% and 34.3%, respectively. All patient who did not achieve cure had high basal preoperative calcitonin levels, which were related to macroscopic medullary thyroid carcinoma and nodal metastases in 5 of 9 patients. Conclusion Thyroidectomy should not be delayed until basal calcitonin level becomes abnormal, at which time advanced disease may be present. As soon as the pentagastrin stimulation test becomes abnormal, operation should be undertaken on early staged disease to achieve cure for the patient. When performed while pentagastrin stimulation test is still negative, thyroidectomy may be truly prophylactic and should be recommended at 5 to 6 years.