Usefulness of preoperative serum calcitonin in patients with nodular thyroid disease without suspicious history or cytology for medullary thyroid carcinoma / Utilidade da calcitonina sérica pré-operatória em pacientes com doença nodular tireoidiana sem história ou citologia suspeitas para carcinoma medular de tireoide

OBJECTIVE: To evaluate the usefulness of preoperative serum calcitonin (sCT) in patients with nodular disease without suspicion of medullary thyroid carcinoma (MTC) in history or cytology. PATIENTS AND METHODS: sCT was measured before thyroidectomy in 494 patients with nodular disease who had no family history of MTC or multiple endocrine neoplasia type 2, and no cytological suspicion of MTC. RESULTS: Basal sCT was < 10 ng/mL in 482 patients and none of them had MTC. One patient with basal sCT > 100 pg/mL had MTC. Among the 11 patients with basal sCT between 10 and 100 pg/mL, MTC was diagnosed in only one. The two patients with MTC were submitted to total thyroidectomy, combined with elective lymph node dissection indicated exclusively based on hypercalcitoninemia, and sCT was undetectable after six months. CONCLUSIONS: Preoperative sCT is useful for the detection of sporadic MTC in patients with nodular disease, even in the absence of suspicious history or cytology.

OBJETIVO: Avaliar a utilidade da calcitonina sérica (sCT) pré-operatória em pacientes com doença nodular sem suspeita de carcinoma medular de tireoide (CMT) pela história e citologia. PACIENTES E MÉTODOS: Antes da tireoidectomia, sCT foi dosada em 494 pacientes com doença nodular, sem história familiar de CMT ou neoplasia endócrina múltipla tipo 2 e sem citologia suspeita para CMT. RESULTADOS: sCT basal foi < 10 ng/ml em 482 pacientes e nenhum possuía CMT. Um paciente com sCT basal > 100 pg/ml realmente possuía CMT. Dos 11 pacientes com sCT basal entre 10 e 100 pg/ml, CMT foi diagnosticado em apenas um. Os dois pacientes com CMT foram submetidos à tireoidectomia total com dissecção eletiva de linfonodos, indicada exclusivamente pela hipercalcitoninemia, e após seis meses apresentaram sCT indetectável. CONCLUSÕES: Em pacientes com doença nodular, mesmo sem história ou citologia suspeitas, a sCT pré-operatória é útil para detecção do CMT esporádico.

Carcinoma medular de tiroides: experiencia de 20 años / Medullary thyroid carcinoma: 20 years experience

Background: Medullary thyroid carcinoma (MTC) is a rare malignant tumor that arise from C cells. Surgical treatment and its results are controversial, so we decided to study it. Aim: To describe clinically MTC, treatment and outcomes in the long term. Material and Method: We retrospectively reviewed medical records of patients with MTC operated in our hospital between the years 1987 and 2007. We analyzed the cli-nical characteristics, treatment, morbidity and long-term follow up. Results: There were 24 patients operated with a mean age of 46.1 +/- 16.6 years. The main form of presentation was painless increased cervical volume (56.2 percent). In 15 percent this pathology was part of a MEN 2b. All of them have had a total thyroidectomy, which was extended in 50 percent of cases. The 35.2 percent were multifocal, 29.4 percent bilateral and 62.5 percent had metastatic lymph node involvement. Five patients remained higher calcitonin levéis in the postoperative period and 9 patients recurred clinically on average 4.5 years after surgery. The presence of persistent disease was significantly associated with hereditary MTC (p = 0.0088) and the clinical recurrence was significantly determined by the presence of not expanded total thyroidectomy (p = 0.0196). The probability of surviving more than 19 years was 66.6 percent (95 percent CI = 0.24 to 0.89). Conclusions: The MTC is a rare tumour and treatment of choice is surgery. The persistent disease is associated with hereditary MTC form, and the clinical recurrence is associated with not expanded total thyroidectomy. We recommend total thyroidectomy with central voiding and radical modified jugular dissection.

Antecedentes: El carcinoma medular de tiroides (CMT) es un tumor maligno poco frecuente, originado a partir de las células C. Su tratamiento quirúrgico y resultados son controvertidos, por lo que hemos decidido estudiarlo. Objetivo: Describir clínicamente el CMT, tratamiento y resultados a largo plazo. Material y método: Se revisaron retrospectivamente las fichas clínicas de pacientes con CMT operados en nuestro hospital entre 1987 y el 2007. Se analizaron las características clínicas, tratamiento, morbilidad y seguimiento a largo plazo. Resultados: Se operaron 24 pacientes, cuya edad media fue 46,1 +/- 16,6 años. La principal forma de presentación fue aumento de volumen cervical (56,2 por ciento). Un 15 por ciento formaba parte de una NEM 2b. A todos se les realizó una tiroidectomía total, ampliada en el 50 por ciento de los casos. El 35,2 por ciento eran multifocales, el 29,4 por ciento bilaterales y el 62,5 por ciento tenía metástasis ganglionar. Cinco pacientes mantuvieron niveles de calcitonina elevados en el postoperatorio y nueve pacientes recurrieron clínicamente, en promedio, a los 4,5 años. La enfermedad persistente se asoció significativamente con CMT hereditario (p = 0,0088) y la recurrencia clínica a tiroidectomía total no ampliada (p = 0,0196). La probabilidad de sobrevivir más de 19 años fue 66,6 por ciento (IC 95 por ciento = 0,24 a 0,89). Conclusiones: EL CMT es un tumor raro cuyo tratamiento de elección es la cirugía. La persistencia de enfermedad se asocia con la forma hereditaria, y la recurrencia clínica con la tiroidectomía total no ampliada, lo que nos hace recomendar una tiroidectomía total asociada a vaciamiento central y disección yugular radical modificada.

Identification of occult metastases of medullary thyroid carcinoma by calcitonin measurement in washout fluid from fine needle aspiration of cervical lymph node / Identificação de metástase oculta do carcinoma medular de tireoide através da dosagem de calcitonina no lavado da agulha de punção aspirativa de linfonodo cervical

Medullary thyroid carcinoma (MTC) may occur sporadically or as a manifestation of an autosomal-dominant inherited syndrome, the multiple endocrine neoplasia type 2. DNA-based RET genotype analysis gained worldwide acceptance in the identification of asymptomatic gene carrier. MTC synthesize and secrete calcitonin, a well established tumor marker and postoperative level of serum calcitonin, indicates whether residual disease was left behind and whether reintervention is necessary. However, management is difficult when routine imaging studies for MTC are negative. This paper brings a report of an illustrative case of a patient with MTC diagnosed by molecular screening, who persisted with detectable levels of serum calcitonin after surgical procedure. After 48 months, an increase in serum calcitonin impelled us to investigate the disease focus. Cervical-US and calcitonin measurement in washout fluid from fine needle aspiration was successfully used to identify MCT metastasis in a lymph node, allowing appropriated reintervention and illustrating the potential clinical applicability of this method.

O carcinoma medular de tireoide (CMT) pode ocorrer na forma esporádica ou como manifestação da síndrome genética neoplasia endócrina múltipla tipo 2. Mutações de linhagem germinativa do proto-oncogene RET causam a forma hereditária, e o diagnóstico molecular é a base para o manejo adequado. O CMT sintetiza e secreta a calcitonina e os níveis séricos da calcitonina pós-tireoidectomia indicam se o paciente está curado ou se há necessidade de reintervenção. No entanto, o manejo é difícil quando exames de imagem são negativos. Neste estudo mostramos um caso ilustrativo de uma paciente com CMT hereditário diagnosticado por meio de rastreamento genético que persistiu com calcitonina sérica detectável pós-tireoidectomia. Após 48 meses, observou-se aumento da calcitonina sérica, determinando investigação para localizar o foco da doença. A utilização do US-cervical e a dosagem da calcitonina no lavado da agulha da punção aspirativa de linfonodo possibilitaram o diagnóstico e a reintervenção terapêutica, ilustrando a potencial aplicabilidade clínica desse método.

Sporadic medullary thyroid carcinoma: clinical data from a university hospital

INTRODUCTION: Medullary thyroid carcinoma may occur in a sporadic (s-medullary thyroid carcinoma, 75 percent) or in a multiple endocrine neoplasia type 2 form (MEN2, 25 percent). These clinical forms differ in many ways, as s-medullary thyroid carcinoma cases are RET-negative in the germline and are typically diagnosed later than medullary thyroid carcinoma in MEN2 patients. In this study, a set of cases with s-medullary thyroid carcinoma are documented and explored. PURPOSE: To document the phenotypes observed in s-medullary thyroid carcinoma cases from a university group and to attempt to improve earlier diagnosis of s-medullary thyroid carcinoma. Some procedures for diagnostics are also recommended. METHOD: Patients (n=26) with apparent s-medullary thyroid carcinoma were studied. Their clinical data were reviewed and peripheral blood was collected and screened for RET germline mutations. RESULTS: The average age at diagnosis was 43.9 years (± 10.82 SD) and did not differ between males and females. Calcitonin levels were increased in all cases. Three patients presented values that were 100-fold greater than the normal upper limit. Most (61.54 percent) had values that were 20-fold below this limit. Carcinoembryonic antigen levels were high in 70.6 percent of cases. There was no significant association between age at diagnosis, basal calcitonin levels or time of disease onset with thyroid tumor size (0.6-15 cm). Routine thyroid cytology yielded disappointing diagnostic accuracy (46.7 percent) in this set of cases. After total thyroidectomy associated with extensive cervical lymph node resection, calcitonin values remained lower than 5 pg/mL for at least 12 months in eight of the cases (30.8 percent). Immunocyto- and histochemistry for calcitonin were positive in all analyzed cases. None of the 26 cases presented germline mutations in the classical hotspots of the RET proto-oncogene. CONCLUSION: Our cases were identified late. The basal ...

Hypercalcitoninemia is not pathognomonic of medullary thyroid carcinoma: [revision]

Hypercalcitoninemia has frequently been reported as a marker for medullary thyroid carcinoma. Currently, calcitonin measurements are mostly useful in the evaluation of tumor size and progression, and as an index of biochemical improvement of medullary thyroid carcinomas. Although measurement of calcitonin is a highly sensitive method for the detection of medullary thyroid carcinoma, it presents a low specificity for this tumor. Several physiologic and pathologic conditions other than medullary thyroid carcinoma have been associated with increased levels of calcitonin. Several cases of thyroid nodules associated with increased values of calcitonin are not medullary thyroid carcinomas, but rather are related to other conditions, such as hypercalcemias, hypergastrinemias, neuroendocrine tumors, renal insufficiency, papillary and follicular thyroid carcinomas, and goiter. Furthermore, prolonged treatment with omeprazole (> 2-4 months), beta-blockers, glucocorticoids and potential secretagogues, have been associated with hypercalcitoninemia. An association between calcitonin levels and chronic auto-immune thyroiditis remains controversial. Patients with calcitonin levels >100 pg/mL have a high risk for medullary thyroid carcinoma (~90%-100%), whereas patients with values from 10 to 100 pg/mL (normal values: <8.5 pg/mL for men, < 5.0 pg/mL for women; immunochemiluminometric assay) have a <25% risk for medullary thyroid carcinoma. In multiple endocrine neoplasia type 2 (MEN2), RET mutation analysis is the gold-standard for the recommendation of total preventivethyroidectomy to relatives at risk of harboring a germline RET mutation (50%). False-positive calcitonin results within MEN2 families have led to incorrect indications of preventive total thyroidectomy to RET mutation negative relatives. In this review, we focus on the differential diagnosis of hypercalcitoninemia, underlining its importance for the avoidance of misdiagnosis...

Treatment evaluation, follow-up and familial screening of medullary thyroid carcinoma by highly specific calcitonin measurements.

BACKGROUND: Calcitonin is the most sensitive and specific marker for medullary thyroid carcinoma (MTC). AIMS: The aim of this study was to emphasize the role and the limits of plasma basal calcitonin (bCT) measurement in the management of Moroccan MTC patients and their relatives. SETTINGS AND DESIGN: This is a retrospective study on 6 MTC patients referred to our institute from January 1996 to December 2004. MATERIALS AND METHODS: Serum bCT levels were measured in 36 individuals comprising six known MTC cases, 18 relatives and 12 healthy volunteers, using two-sites immunoradiometric assay method. Five of MTC patients have been followed from 12 to 96 months after surgery. STATISTICAL ANALYSIS USED: Calculations were performed using SPSS 10.0 program. Data comparison was done by Student's t -test. RESULTS: The circulating preoperative bCT concentrations were elevated for all MTC patients (range, 44,8 -2055 pg/ml, normal <10). Recent postoperative bCT determinations varied from 24.4 to 1972 pg/ml in four patients. In one patient, the bCT value decreased to an undetectable level during a follow-up of 12 months. The mean bCT level of relatives was 4.90 +/- 3.54 pg/ml; two patients had slightly elevated bCT. Five (42%) healthy volunteers had undetectable bCT levels and all had less than 10 pg/ml; the mean bCT value was 3.06 +/- 2.51 pg/ml. CONCLUSIONS: Routine plasma bCT measurement still has an important place in the preoperative diagnosis and follow-up treatment of MTC.

Review analysis of medullary carcinoma thyroid--15-year Indian experience.

To emphasize the importance of adequate primary surgery in cases of medullary carcinoma of the thyroid, 44 cases of treated medullary carcinoma of thyroid were retrospectively reviewed in Government General Hospital, Chennai between 1987 and 2002. Patients who underwent total thyroidectomy with only central compartment dissection were compared with those who had undergone total thyroidectomy with meticulous triple compartment (bilateral lateral and central groups) nodal dissection. The group of total thyroidectomy with only central compartment dissection had high rate of lymph nodal recurrence and persistent hypercalcitoninaemia when compared with the group of total thyroidectomy with meticulous triple compartment nodal dissection. (Chi square value 4.503 with p<0.05).