Spanish consensus for the management of patients with anaplastic cell thyroid carcinoma.

Anaplastic thyroid cancer (ATC) is the most aggressive solid tumor and almost uniformly lethal in humans. The Boards of the Thyroid Cancer Group of the Spanish Society of Endocrinology and Nutrition and the Grupo Español de Enfermedades Huérfanas e Infrecuentes of the Spanish Society of Oncology requested that an independent task force draft a more comprehensive consensus statement regarding ATC. All relevant literature was reviewed, including serial PubMed searches together with additional articles. This is the first, comprehensive Spanish consensus statement for ATC and includes the characteristics, diagnosis, initial evaluation, treatment goals, recommendations and modalities for locoregional and advanced disease, palliative care options, surveillance, and long-term monitoring. Newer systemic therapies are being investigated, but more effective combinations are needed to improve patient outcomes. Though more aggressive radiotherapy has reduced locoregional recurrences, median overall survival has not improved in more than 50 years.

Consensus on the management of advanced radioactive iodine-refractory differentiated thyroid cancer on behalf of the Spanish Society of Endocrinology Thyroid Cancer Working Group (GTSEEN) and Spanish Rare Cancer Working Group (GETHI).

Thyroid cancer is the single most prevalent endocrine malignancy; differentiated thyroid cancer (DTC) accounts for more than 90 % of all malignancies and its incidence has been rising steadily. For more patients, surgical treatment, radioactive iodine (RAI) ablation, and thyroid-stimulating hormone (TSH) suppressive therapy achieve an overall survival (OS) rate of 97.7 % at 5 years. Nevertheless, locoregional recurrence occurs in up to 20 % and distant metastases in approximately 10 % at 10 years. Two-thirds of these patients will never be cured with radioactive iodine therapy and will become RAI-refractory, with a 3-year OS rate of less than 50 %. Over the last decade, substantial progress has been made in the management of RAI-refractory DTC. Given the controversy in some areas, the Spanish Task Force for Thyroid Cancer on behalf of Spanish Society of Endocrinology Thyroid Cancer Working Group (GTSEEN) and the Spanish Rare Cancer Working Group (GETHI) have created a national joint task force to reach a consensus addressing the most challenging aspects of management in these patients. In this way, multidisciplinary management should be mandatory and nuclear medicine targeted therapy, novel molecular targeted agents, and combinations are currently changing the natural history of RAI-refractory DTC.

Consensus on management of advanced medullary thyroid carcinoma on behalf of the Working Group of Thyroid Cancer of the Spanish Society of Endocrinology (SEEN) and the Spanish Task Force Group for Orphan and Infrequent Tumors (GETHI).

BACKGROUND: Of all thyroid cancers, <5 % are medullary (MTC). It is a well-characterized neuroendocrine tumor arising from calcitonin-secreting C cells, and RET gene plays a central role on its pathogeny. METHODS: The electronic search was conducted using MEDLINE (PubMed), EMBASE and Cochrane Central Register of Controlled Trials. Quality assessments of selected current articles, guidelines and reviews of MTC were performed. RESULTS: This consensus updates and summarizes biology, treatment and prognostic considerations of MTC. CONCLUSIONS: Multidisciplinary teams and specialized centers are recommended for the management of MTC patients. In the metastatic setting, those patients with large volume of disease are candidates to start systemic treatment mainly if they are symptomatic and the tumor has progressed in the last 12-14 months. Wait and see strategy should be offered to patients with: disseminated disease with only high levels of calcitonin and no macroscopic structural disease, low burden and absence of progression.

123I-MIBG, 18F-DOPA and 18F-FDG in a patient with MEN2 syndrome and recurrent pheochromocytoma.

Pheochromocytoma is a rare tumor located in the medulla of the adrenal gland that is characterized by high catecholamine synthesis. Surgery is the treatment of choice and is usually curative if appropriately diagnosed and excised. Imaging methods, both morphological and functional, are of great importance in presurgical evaluation. We report the case of a female patient with multiple endocrine neoplasia syndrome type 2, with bilateral adrenalectomy due to two pheochromocytomas and progressive elevation of urinary metanephrine. Magnetic resonance imaging showed a nodular image in the right adrenal fossa. The patient was referred to our unit in order to confirm suspicion of recurrence. Due to the absence of pathological findings in the (123)I-MIBG scintigraphy and high suspicion of recurrence, PET/CT imaging with (18)F-DOPA and (18)F-FDG were performed, and the diagnosis was confirmed.

Value of the negative PET-FDG in the middle term follow-up of differentiated thyroid cancer in patients with negative 131 I-Na scan and elevated thyroglobulin serum levels.

OBJECTIVE: This study has aimed to analyze the evolution of patients diagnosed with differentiated thyroid carcinoma (DTC) with a negative (131)I-Na whole body scan (WBS), high levels of serum thyroglobulin (Tg) and negative (18F)fluorodeoxyglucose positron emission tomography (PET-FDG) study. MATERIAL AND METHODS: Twenty-three patients diagnosed and treated for DTC were studied retrospectively. Patients were aged between 23 and 83 and had shown, between January 2001 and December 2002, negative WBS, Tg values in a range of suspected recurrence or metastasis (Tg>2 ng / mL with thyroid hormone withdrawal) and a negative PET-FDG study. The patients were monitored clinically, radiologically and analytically for a minimum period of 4 years. After this, a new evaluation was made of their state of disease with a control WBS, also observing the evolution of Tg. All WBS were performed with a 185 MBq diagnostic dose of (131)I-Na. RESULTS: In 18/23 patients, Tg decreased and in 5 it increased. Four patients (17%) were free of active disease (negative WBS Tg<2 ng / mL). A total of 16 patients (70%) were free of disease according to the WBS but had elevated Tg. Three patients (13%) had disease and high levels of Tg, two of them with positive WBS and the third with (99m)Tc-MIBI scan and CT positive. CONCLUSIONS: Most patients with a negative WBS, high Tg serum levels and negative FDG PET had good evolution, with descending Tg levels, normal levels even being reached in a significant percentage of them.

[Evaluation of efficacy and clinical impact of 18F-FDG-PET in the diagnosis of recurrent medullary thyroid cancer with increased calcitonin and negative imaging test]. / Evaluación de la eficacia y del impacto clínico de la PET-18F-FDG en el diagnóstico de recurrencia del carcinoma medular de tiroides con calcitonina elevada y pruebas de imagen negativas.

AIM: To evaluate the efficacy and clinical impact of the FDG-PET in the diagnosis of suspicion of recurrence of medullary thyroid cancer (MTC) in patients with elevated serum calcitonin and negative imaging test. MATERIAL AND METHODS: We performed a retrospective study of 31 consecutive cases from february 2001 to october 2007 of 17 women and 14 men, mean age 56.2 years (range: 26-88), with anatomical-pathology diagnosis of medullary thyroid cancer and suspicion of recurrence due to abnormal elevation of calcitonin and negative imaging tests. All of the patients underwent whole body FDG-PET scan with a dedicated PET or PET-CT 60 minutes after intravenous injection of 333-434 MBq of (18)F-FDG. Results were confirmed by pathology study in 45.2% of the patients and by clinical follow-up with a mean of 4 years (range: 16 m-8 years) RESULTS: Sensitivity was 88%, specificity 84.6%, positive predictive value 88%, negative predictive value 84.6% and diagnostic accuracy 87%. The results of the FDG PET modified the therapeutic strategy in 14 cases (45.2%). A comparison was made of the mean values of calcitonin using the Student's "t" test between positive PET studies for the disease and negative ones. No significant differences were found (P=.3). CONCLUSIONS: In patients with MTC and suspected recurrence with elevated calcitonin and negative imaging test, the FDG is the best test for the diagnosis of occult recurrence in MTC with elevated calcitonin and negative imaging techniques with elevated clinical impact. It facilitates the therapeutic management of the patients with MTC recurrence, and should be included in the diagnosis algorithm in these patients.

[Use of 18F FDG-PET in patients with suspicion of recurrent differentiated thyroid cancer by elevated antithyroglobulin antibodies levels and negative ¹³¹I scan]. / Uso de la PET-18F-FDG en pacientes con sospecha de recurrencia de cáncer diferenciado de tiroides por anticuerpos anti-tiroglobulina elevados y rastreo ¹³¹I negativo.

AIM: To evaluate the utility of (18F)FDG-PET for patients diagnosed of differentiated thyroid carcinoma who present risk of disease and invaluable levels of thyroglobulin (Tg) by the presence of antibodies antithyroglobulin (AbTg). MATERIAL AND METHODS: Retrospective study of 7 women of 40 years old and histological diagnosis of differentiated thyroid cancer (7 papillary tumours) that were sent to our department for the accomplishment of(18F)FDG-PET study because of suspicion of disease, due to ¹³¹I negative and high levels of AbTg, between the year 2002 and 2007. 11 PET scans were obtained after the intravenous injection of 370-434 MBq of (18F)FDG in normoglycemia conditions and previous administration of muscle relaxant, hydration and diuretic. The results of (18F)FDG-PET scans were confirmed by pathologic examination or clinical outcome and radiographic examination for more than 24 months. RESULTS: The prevalence of recurrence in our population was 57.14%. All patients presented levels of Tg lower than 3 ng/dl and AbTg superior to 200 UI/ml. Three patients had precedent thyroiditis. Out of 11 scans performed 3 of them were negative and 8 cases were found positive. It ruled out the existence of disease in three patients and localized the presence of recurrence in 4 patients. CONCLUSION: (18F)FDG-PET CONCLUSION: 18F-FDG-PET is a useful diagnostic tool for the detection of recurrence as well as to rule out the existence of disease with a high accuracy, in patients with differentiated thyroid carcinoma with ¹³¹I whole body scan negative but with pathological elevation of antithyroglobulin antibodies.

[Bone metastases from unknown primary. FDG-PET detection of two synchronous tumors]. / Metástasis óseas de tumor primario desconocido. Detección mediante PET-FDG de dos tumores sincrónicos.

A 60-year-old woman presented with noncardiac chest pain over months and negative laboratory findings. Conventional imaging methods and bone scintigraphy detected bone lesions suggesting metastatic disease from an unknown primary tumor. An 18FDG-PET scan performed to orient the search for the primary tumor found focal lesions suggesting lymphoma and identified a focal thyroid lesion and a cervical lymph node accessible for biopsy. The biopsy of this lymph node incidentally detected a papillary differentiated thyroid cancer (DTC), since the existence of a non-Hodgkin's lymphoma was confirmed after a new biopsy. After confirming the presence of a lymphoma, 18FDG-PET enabled the initial staging of the tumor, the evaluation of the response to treatment, and follow-up for detection of recurrence. On the other hand, 18FDG-PET incidentally detected a DTC.

[Patients treated for differentiated thyroid cancer with negative 131I whole-body scans and elevated thyroglobulin levels: a possible course]. / Pacientes tratados por carcinoma diferenciado de tiroides con rastreos de 131I negativos y niveles de tiroglobulina elevada. Una evolución posible.

OBJECTIVE: To verify the existence of patients with treated differentiated thyroid cancer (DTC) with negative 131I whole-body scanning (WBS) and high serum thyroglobulin (Tg) in the follow-up who evolve towards normalization without other therapy interventions. MATERIAL AND METHODS: Retrospective revision of the periodic examinations established in the protocol for patients with DTC, analyzing the levels of Tg found with IRMA annually in those with hormonal treatment and every 1-5 years in absence of previous hormonal treatment to WBS. Minimum surveillance of 2 years. Those who had elevated levels of Tg and WBS and other negative imaging tests in their course were selected. The characteristics of the patients selected were analysed in those whose Tg levels evolved to normalization without specific medical or surgical treatment (Group I) and those who did not reach normalization of Tg (Group II). RESULTS: A total of 130 patients (17.93 %) with high levels of Tg and negative WBS were detected. Group I: 31 patients (4.28 %), 11 men and 20 women; average age at the moment of the diagnosis of 33.4 years (rank: 5-60); average surveillance: 12.4 years (+/- 7.4). HISTOLOGY: 27 papillary and 4 follicular carcinoma. Average ablation dose: 3.260 GBq (88,1 mCi); average total I131 dose: 6.850 GBq (185.13 mCi). Tg normalization average time: 8.2 years. Group II: 99 patients (13.65 %), 27 men and 72 women. Average age of 40.4 years (rank: 7-76). Average surveillance: 9.8 years. HISTOLOGY: 86 papillary and 13 follicular carcinoma. Average ablation dose: 3.266 GBq (88.28 mCi); average total 131I dose: 9.363 GBq (253,06 mCi). Two of the patients in group I had negative PET-FDG. There were 13 patients in whom progressive reduction of the levels of thyroglobulin without reaching normalization with negative PET-FDG was detected. CONCLUSIONS: In patients with radiated DTC, deferred normalization of the levels of the serum thyroglobulin is possible. Empirical treatments cannot be considered the only factor that contributes to this result, which can occur without the administration of high-doses of 131I.

[F-18-fluordeoxyglucose positron emission tomography on patients with differentiated thyroid cancer who present elevated human serum thyroglobulin levels and negative I-131 whole body scan]. / PET con 18FDG en pacientes con cáncer diferenciado de tiroides que presentan niveles elevados de tiroglobulina sérica y rastreos con 131I negativos.

UNLABELLED: This study aimed to evaluate the role of Fluorine-18-fluorodeoxyglucose positron emission tomography (PET-FDG) in patients with elevated serum thyroglobulin (hTg) levels where thyroid cancer tissue does not concentrate radioiodine, rendering false-negative results on I-131 scanning. MATERIAL AND METHODS: Whole-body PET imaging using FDG was performed in 54 patients (37 female, 17 male) aged 17-88 years: 45 with papillary tumors and 9 with follicular tumors who were suspected of having recurrent thyroid carcinoma due to elevated thyroglobulin levels (hTg > 2 ng/ml) under thyroid-stimulating hormone (TSH > or = 30 microIU/ml) in whom the iodine scan was negative. All whole body scans were obtained with diagnostic doses (185 MBq). Whole body PET imaging was performed in fasting patients following i.v. administration of 370 MBq FDG while the patients were receiving full thyroid hormone replacement. Before PET, 99mTc methoxyisobutylisonitrile scintigraphy (99mTc-MIBI) was done in 14 patients and morphologic imaging in 26 by CT scan. RESULTS: Positive PET results confirmed the presence of hypermetabolic foci in 25/54 patients (46.29 %). Positive findings were found for PET-FDG in patients with hTg levels higher than 10 ng/ml receiving full thyroid hormone replacement. 99mTc-MIBI demonstrated lesions in 7/14 patients (50 %). PET-FDG and 99mTc-MIBI had congruent positive results in 4/7 patients. All the lesions found by CT were detected by PET-FDG, while recurrent disease was found in 12/21 patients with previous negative CT. CONCLUSIONS: These results suggest that PET-FDG seems to be a promising tool in the follow-up of thyroid cancer and should be considered in patients suffering from differentiated thyroid cancer with suspected recurrence and/or metastases by elevated thyroglobulin levels, and negative I-131 whole body scans. PET-FDG might be more useful at hTg levels > 10 ng/ml.

Primary hyperparathyroidism in pregnancy.

Gestational primary hyperparathyroidism presents with features which, from a physiological and prognostic viewpoint, entail great difficulty in diagnosis and a high risk of complications. These complications occur at rates of 67% and 80% in the mother and fetus, respectively, and can be reduced by up to four times by means of prompt application of effective therapeutic measures. We report a case involving a pregnant woman in the 16th week of gestation who presented with asymptomatic hypercalcemia secondary to a solitary parathyroid adenoma. When the patient did not improve after conservative therapeutic measures, it was decided to employ surgical treatment in the second trimester of pregnancy. The surgery was successful, and the follow-up period was without complications for the mother and neonate. We therefore agree with the growing evidence that surgery in the second trimester of pregnancy constitutes a safe and effective alternative to conservative treatment.

[Recombinant human thyrotropin in the follow-up of patients with differentiated thyroid carcinoma]. / La TSH humana recombinante en el seguimiento de pacientes con cáncer diferenciado de tiroides.

PURPOSE: To determine the value of the use of radio-iodine scanning diagnostic and radio-iodine therapy during the follow-up of advanced differentiated thyroid cancer without stopping thyroid hormone suppression therapy. MATERIAL AND METHODS: We performed 7 radio-iodine scans and 4 radioiodine therapies in 5 men and 1 woman, aged 39 to 79 years. Five patients had papillary thyroid cancer and one follicular thyroid cancer. Human recombinant thyrotropin was given intramuscularly at a dose of 0.9 mg/ml once a day for two days. Twenty-four hours after the second dose, serum thyrotropin, thyroglobulin (Tg) and thyroglobulin autoantibodies were measured and each patient was given 2 mCi of 131I in postsurgery scans and 5 mCi of 131I in patients previously treated with 131I. Whole-body scans were obtained within 54 hours of injection and in the cases of diagnostic uncertainty a second scan was performed 72 hours after the injection. RESULTS: Four scans were positive and two were negative. One positive scan patient was not treated due to a serious clinical condition. An effective increase of serum TSH was observed in all 6 patients. Four patients had an effective increase of serum Tg; the other 2 cases had a decrease of serum Tg: One case was undifferentiated and in the other case the mass was smaller after surgery. CONCLUSIONS: rhTSH is an effective means of stimulating TSH levels and allowing scan and/or radioiodine treatment. rhTSH has no significant adverse effects. The use of rhTSH avoids all the disadvantages of hypothyroidism and maintains quality of life.

Pheochromocytoma in a pregnant woman with multiple endocrine neoplasia type 2a.

Pheochromocytoma is a rare cause of hypertension. Its coexistence with pregnancy is exceptional and laparoscopic removal has rarely been reported. We describe the case of a 34-year-old woman with multiple endocrine neoplasia type 2a (MEN 2a) with adrenal pheochromocytoma diagnosed in the 6th week of pregnancy. After pretreatment with phenoxybenzamine, a successful transperitoneal laparoscopic adrenalectomy was performed in the twentieth week of gestation. The management of pheochromocytoma in pregnancy and the indications for laparoscopic surgery in pregnant patients are discussed.