Refining calcium test for the diagnosis of medullary thyroid cancer: cutoffs, procedures, and safety.

CONTEXT: Calcitonin (CT) measurement is crucial to the early diagnosis and the follow-up of medullary thyroid cancer (MTC). If the evaluation of stimulated CT levels is required, a provocative test can be performed, being the high-dose Ca test recently reintroduced in clinical practice. OBJECTIVE: Our objective was to identify gender-specific thresholds for MTC diagnosis in a large series of patients who underwent the Ca test. PATIENTS AND METHODS: A total of 91 patients (49 females and 42 males) underwent the Ca test (calcium gluconate, 25 mg/kg) before thyroidectomy and both basal CT (bCT) and stimulated CT (sCT) were compared with histological results by receiver operating characteristic plot analyses. To evaluate possible side effects of Ca administration, cardiac function has been extensively studied. RESULTS: bCT levels were found to harbor the same accuracy as sCT in the preoperative diagnosis of MTC. The best Ca thresholds for the identification of MTC were >26 and >68 for bCT and >79 and >544 pg/mL for sCT in females and males, respectively. The high tolerability and safety of the Ca test was demonstrated and advice offered to be followed before and during the test. CONCLUSIONS: Gender-specific bCT and sCT cutoffs for the identification of C-cell hyperplasia and/or MTC have been defined. The bCT and sCT were found to have a similar accuracy, indicating that serum CT assays with improved functional sensitivity may likely decrease the relevance of the stimulation test in several conditions. Finally, systematic cardiac monitoring confirms the safety of the Ca test.

Comparison of calcium and pentagastrin tests for the diagnosis and follow-up of medullary thyroid cancer.

CONTEXT: The evaluation of basal calcitonin (bCT) and stimulated calcitonin (sCT) can be used for the diagnosis and follow-up of medullary thyroid cancer (MTC). OBJECTIVE: The aim of this study was to evaluate the reliability of high-calcium (Ca) test and to identify gender-specific thresholds for MTC diagnosis. PATIENTS: Patients with MTC in remission (n=24) or in persistence (n=18), RET gene mutations carriers (n=14), patients with nodular goiter (n=69), and healthy volunteers (n=16) were submitted to pentagastrin and Ca (25 mg/kg) tests. RESULTS: In all groups, the levels of calcitonin (CT) stimulated by either pentagastrin or Ca were significantly correlated. The prevalence of both C-cell hyperplasia (CCH) and MTC in women and men paralleled the increasing basal and peak CT levels in a gender-specific manner. Receiver operating characteristic plot analyses showed that the best levels of bCT to separate normal and CCH cases from MTC patients were above 18.7 pg/ml in females and above 68 pg/ml in males. Furthermore, Ca sCT above 184 pg/ml in females and above 1620 pg/ml in males had the highest accuracy to distinguish normal and CCH cases from patients with MTC. At the C-cell immunohistochemical examination, Ca sCT below 50 pg/ml corresponded to a mean number of 30 cells per 10 fields, whereas higher sCT associated with a mean number of 400 cells per 10 fields, often displaying a diffuse and nodular distribution pattern. CONCLUSIONS: High-dose Ca test is a potent and well-tolerated procedure that can be applied worldwide at a low cost. Reference ranges for Ca sCT levels in different groups of patients and CT thresholds to diagnose CCH/MTC have been identified.

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.

Radioactive iodine treatment in medullary thyroid carcinoma.

BACKGROUND: Elevated levels of basal and stimulated calcitonin are commonly seen in hereditary and sporadic medullary thyroid cancer (MTC) following total thyroidectomy. The cause of these high levels can be residual thyroid tissue, possibly with C-cell hyperplasia, and/or residual micro-MTC foci. MTC does not have the ability to concentrate radioactive iodine. However, radioactive iodine trapped by thyroid follicular cells may affect the neighbouring parafollicular cells. AIM: To investigate the effect of radioactive iodine treatment as adjuvant therapy to surgery in seven patients with persistent elevation of basal and stimulated calcitonin levels. METHODS: Pentagastrin testing was performed in each case immediately before surgery and at intervals of 6 months over a maximum period of 5 years (range, 44-60 months) after surgery. RESULTS: A significant decrease in basal and stimulated calcitonin levels was observed in three patients whose disease was localized to the thyroid gland at the final visit. In the remaining four patients, who initially had lymph node involvement at surgery, basal and stimulated calcitonin levels were decreased significantly in only one. At follow-up, of the three patients who showed no decrease in basal and stimulated calcitonin levels, two developed further regional lymph node and distant metastases. CONCLUSIONS: In patients with persistently elevated basal and stimulated calcitonin levels, radioactive iodine treatment may be the therapy of choice for C-cell hyperplasia and/or micro-MTC after optimal thyroid surgery, especially if the disease has not spread beyond the thyroid gland.

[The routine immunohistochemical diagnosis and surgical treatment of medullary carcinoma of the thyroid]. / Rutinna imunokhistokhimichna diagnoza i khirurgichno lechenie na medularniia kartsinom na shtitovidnata zhleza.

Over the period 1977 through 1988, in the Research Institute of Surgery--Medical Academy a total of 372 patients undergo primary operative management for thyroid gland carcinoma. Medullary carcinoma is discovered in 18 patients of the series (4.8 per cent). The preoperative diagnosis is supplemented by thyroscintigraphy with 131iodine or technetium Tc 201. After 1981, calcitonin and carcinoembryonic antigen (CEA), specific medullary thyroid carcinoma (MTC) markers, measurements are routinely done, with substantially elevated levels in the patients under study being found, in those with metastases inclusive. Presumably, the preoperative diagnosis medullary thyroid carcinoma is very difficult, and only a combined approach, including thyroidectomy with ensuing iodine radiotherapy, may account for a good survivorship. Postoperatively, all patients with MTC diagnosis are regularly tested for serum calcitonin and CEA levels. The carefully taken family history and questioning of the patients allows to differentiate familial from cases from sporadic neoplasms.