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.

Unusual malignant tumors of the thyroid gland.

BACKGROUND: Although situated on the last places among the statistical hierarchy of human malignancies, thyroid cancers (TC) are the most common tumors of the endocrine system. Follicular epithelium neoplasms account for more than 90% of these lesions with a favourable prognosis, while resting tumors (medullary, anaplastic, lymphoma, sarcoma etc) generally present a rapid unfavorable evolution with a low rate of survival. PATIENTS AND METHODS: In a series of 464 thyropathies personally treated, 72 cases of TC (15.5%) were identified. Fifty-seven patients presented epithelial TC a 34 papillary variant, 20 follicular variant and 8 mixed forms. Alongside these there were two medullary TC, 9 anaplastic TC and insular TC, and primary lymphoma and metastasis to the thyroid of a lung carcinoma each single case. Four cases have been described in patients who were aged 2-6 years at the time of the Chernobyl disaster. Out of the common types, based on our own taxonomic criteria, we selected a group of 36 TC with unusual clinical, histological and behavioural characteristics or particular pathological associations. RESULTS: Seven cases of occult TC, 7 cases with precessive adenopathy TC and 11 patients with TC associated with hyperthyroidism were registered. All of them underwent adapted thyroidectomies in which the presence of cancer was decisive for the extent of surgery. Medullary, insular and anaplastic TC were the most aggressive lesions and even extended surgery and complementary therapy failed to improve the prognosis of these patients. In the same category we included the cases presenting the coexistence of two TC types, pathologic dedifferentiation in recurrences and concurrent presence of another endocrine or nonendocrine cervical lesion. The a surgical dogma of total thyroidectomy cannot always be respected, so complementary therapeutic solutions must be applied. RESULTS were complex, registering steady recoveries in occult, hyperfunctioning and even in coexisting pathological lesions, but many recurrences and reinterventions with poor survival rates (a few weeks up to 2 years) in cases with reduced or absent histologic differentiation were also noted. Some lesions were inoperable. DISCUSSIONS AND CONCLUSIONS: Increasing clinician, surgeon and pathologist awareness of these distinct, but not rare anatomoclinical contingencies could contribute to their adequate diagnosis and treatment. Recent progress in knowledge of molecular carcinogenesis and promising successes of targeted chemotherapy trials with new drugs offer promising perspectives in the management of advanced or metastatic TC. Surgery still remains the cornerstone treatment for thyroid cancers.

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.

[Differentiated thyroid cancer -- 2009]. / Differenciált pajzsmirigyrák -- 2009.

Three years ago continental guidelines were published referring management and follow-up of low risk thyroid cancer patients. The aim of this paper is to summarize the changes and new directions in this field. High risk patients require another protocol. Neck ultrasound plays important role in differential diagnosis and in detecting recurrences. Some new ultrasound techniques are discussed, too. FDG-PET can help to solve the problem of patients having negative scan and increased thyroglobulin level. In recent years there was an expansion of our knowledge about the pathomechanism of thyroid cancer. It appears that genetic alterations frequently play a key role in carcinogenesis. There are molecular methods that allow the detection of these genetic events in thyroid fine needle aspirations samples providing important information for diagnosis, management and prognosis. Instead of diagnostic whole body scanning the posttherapeutic scan became preferable but in high risk cases the diagnostic whole body scintigrams serve useful data. Primary therapy of thyroid cancer is an adequate surgery: total thyreoidectomy and, if necessary, lymph node dissection or limited surgery in selected cases. Nowadays radioguided surgery can help to improve the results. Radioiodine therapy (e.g. rest ablation) proved to be a safe and effective method to complete surgery. It can prevent relapses and results in longer survival. Thyroid hormone withdrawal or recombinant human thyrotropin stimulation can increase thyrotropin level before radioiodine treatment. These two methods have similar success rate of rest ablation but irradiation burden of blood is lower in the case of exogenous stimulation which avoids hypothyroid state and preserves quality of life. Since tumor cells fail to maintain the ability to perform physiological functions they undergo dedifferentiation. Therefore, an important aim is to reactivate some function of differentiated cells, e.g. iodine uptake, production of thyroperoxydase and thyroglobulin. Opportunities for this therapeutic effort are also mentioned. Restoration of iodine uptake enables radioisotope treatment. Until now there has been little interest in the development of new drugs for the treatment of thyroid cancer. However, advances in our understanding of tumor cell biology will lead to a paradigm shift in the therapy that is likely to benefit patients who have high risk disease and who do not almost have any therapeutic option. There are new drugs in clinical trials that appear to be more effective than earlier cytotoxic agents. Probably modern chemotherapy of advanced thyroid cancer will have significant results in the near future.

Cáncer medular de tiroides esporádico de curso agresivo, en un adolescente varón / Madullary thyroid cancer in a 14 years old male: case report

Medullary thyroid cancer can appear sporadically or as part of a multiple endocrine neoplasia type 2A or 2B. In both conditions, it is associated with mutations of proto oncogene RET (rearranged during transfection). We report a 14 years old male presenting with a bone lesion in the skull followed by a hard cevical mass. A CAT scan showed an invasive thyroid nodule with involvement of regional lymph nodes , osteolytic lesions in skull, spine and ribs and liver metastases. Serum calcitonin was markedly elevated (9752 pg/ml, normal below 14 pg/ml). Fine needle biopsy showed a medullary thyroid carcinoma and the patient was subjected to a total thyroidectomy and radical cervical dissection. In the postoperative period the patient required calcium and vitamin D supplementation. Serum calcitonin 15 days after surgery was 11.692 pg/ml. Palliative radiotherapy was indicated for spine pain. A percutaneous gastrostomy was indication for nutritional support. The molecular study did not detect mutations of RET gene between exons 10 and 16.

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.

A prospective study of thyroid nodular disease in children and adolescents in western Poland from 1996 to 2000 and the incidence of thyroid carcinoma relative to iodine deficiency and the Chernobyl disaster.

BACKGROUND: In Poland, where soil is deficient in iodine, supplementation of iodine was introduced in 1935, discontinued in 1980, and then re-introduced in 1997. One of the effects of inadequate iodine intake, prior to 1997, was an increase in the prevalence of thyroid nodular disease (TND) in children. Chernobyl, located in the neighbouring country of Ukraine, suffered a catastrophic nuclear explosion in April 1986. PROCEDURE: A total of 411 children with TND (an incidence of 7.53/100,000) were diagnosed and registered in western Poland between 1996 and 2000 and further evaluated as a population-based study. RESULTS: Based on the patient's clinical status, ultrasound examination, scintiscan, laboratory tests, cytology and the family history, many of the patients qualified for surgery and, as a result, histopathologic data were obtained from 155 of the 411 patients operated on to date (37.7% of all TND). Thyroid carcinoma was detected in 37 of the operated children, i.e. 23.9% or 9.0% of all children with TND with a median incidence of 0.68/100,000. Papillary carcinoma was the predominant histologic type (26-70.3%) compared to follicular carcinoma (10-27.0%) and medullary carcinoma (1-2.7%). Retrospective analysis of the figures for the 23 years (1972-1995) showed that in that period a total of 23 thyroid carcinomas were registered. However, only 12 of these were detected in the 20-year period between 1972 and 1991, none in the years 1992-1993 and, significantly, 11 from 1994 to 1995. CONCLUSIONS: Thyroid carcinoma appears to be an ongoing and increasing problem in the children and adolescents of our region, and it is developing more intensively when compared, both to other parts of Poland and to previous statistics (2000 vs. 1985; P<0.002). Iodine deficiency and radiation resulting from the Chernobyl disaster might be important risk factors in the development of thyroid carcinoma in the young population analysed in our region in the period since 1994. The high percentage of follicular carcinoma and follicular adenoma with an undetermined prognosis (19 out of 46) indicates that the long-term iodine deficiency in our region may be more significant in the pathogenesis of malignant transformation than has previously been postulated.

Two cases of medullary thyroid carcinoma.

INTRODUCTION: Medullary thyroid carcinoma (MTC) is a rare thyroid malignancy but accounts for a significant mortality. We present 2 cases of MTC and review the literature regarding its management and genetic screening. CLINICAL PICTURE: Patient 1 presented after a routine health screening and subsequently was found to have a germline mutation for MEN 2A. Patient 2 presented with sweating irritability and a thyroid mass which illustrates the progressive relentless nature of the disease and highlights current imaging practice. TREATMENT: Both patients underwent extensive surgery and received postoperatively ablative dose of radioactive iodine. Patient 2 also had a large dose I-131 MIBG therapy and further surgery. OUTCOME: In Patient 1, postoperative calcitonins remained elevated indicating residual disease. Patient 2 underwent further radioguided surgery; however, his postoperative calcitonins remained elevated. CONCLUSION: MTC can be relentless. Routine genetic screening of all patients with MTC, Tc-99m pentavalent (V) DMSA imaging, near total thyroidectomy with routine central neck dissections and removal of all lymph nodes in the central neck compartment should be performed.

Thyroid carcinoma in children and adolescents.

UNLABELLED: A clinical and pathological study was undertaken to define the prevalence, clinical presentation and outcome of thyroid carcinoma in children and adolescents. Clinical records from 48 patients under 20 years of age at diagnosis, out of 372 patients with thyroid cancer examined between 1980 and 1994, were retrospectively reviewed. Female/male ratio was 3.8/1. None had a previous positive history of head and neck irradiation. Patients underwent near-total (44 patients) or partial (4 patients) thyroidectomy followed by 131I ablation of residual thyroid tissue. The mean follow up period was 58.4 months, ranging between 2 and 190 months. Clinically a thyroid mass was present in 41 patients, 28 of whom also showed neck lymph node involvement. Node metastases were present in 50% of the patients and lung metastases in 4.2%. Histological type was papillary in 41, follicular in 6, and medullary in 1 case. Surgical complications were observed in 19 patients (40%). In 3 patients papillary thyroid cancer was associated with chronic lymphocytic thyroiditis. All patients were treated with 1-thyroxine suppressive therapy. Recurrences of cancer after surgical and radio-iodine treatment was observed only in one patient 8 months after surgery. CONCLUSION: Our experience demonstrates that thyroid carcinoma in childhood cannot be considered a rare occurrence, since it represents about 13% of all thyroid cancers, and is frequently associated with lymph node but rarely with distant metastases. Nevertheless, the prognosis of thyroid carcinoma in childhood is fairly good.

[Surgical treatment of multinodular goiter at the Instituto Nacional de la Nutrición Salvador Zubirán]. / Tratamiento quirúrgico de bocio multinodular en el Instituto Nacional de la Nutrición Salvador Zubirán.

BACKGROUND: Surgical treatment is the first option for patients with obstructive multinodular goiter. The extent of the resection and the use of postoperative hormonal therapy are, on the other hand, still under debate. OBJECTIVE: To analyze the results of surgical treatment in 101 patient with multinodular goiter seen from 1980 to 1995. MATERIALS AND METHODS: The clinical/pathologic charts of all patients were reviewed with emphasis to the clinical diagnosis, extent of resection, final histology, type and number of complications, and long-term follow-up. The mean follow-up was three years (range 0.5-12). RESULTS: Ten males and 91 females with a mean age of 46 years were included. Surgery was recommended for a nodule suspicious of malignancy in 60 patients, for airway compression in 33, and for cosmetic reasons in eight. Unilateral lobectomy was performed in 30, bilateral subtotal thyroidectomy in 55 and total thyroidectomy in 16. Postoperative hormone therapy was administrated to 83 patients. Surgical complications occurred in six patients. Four developed permanent hypoparathyroidism and two vocal cord paralysis. There was no operative mortality. A final diagnosis of multinodular goiter was established in 89 whereas 12 had cancer. There were three asymptomatic recurrences in the group with benign lesions (they had undergone unilateral lobectomy followed by hormonal therapy). CONCLUSION: Bilateral subtotal thyroidectomy was the best treatment for multinodular goiter in our series. This procedure had few complications and there was no recurrence of the disease.

[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.