Graciela Cross

Outcomes of patients with differentiated thyroid cancer risk-stratified according to the American thyroid association and Latin American thyroid society risk of recurrence classification systems.

OBJECTIVES The aims of this study were to validate the proposed Latin American Thyroid Society (LATS) risk of recurrence stratification system and to compare the findings with those of the American Thyroid Association (ATA) risk of recurrence stratification system. SUBJECTS AND METHODS This study is a retrospective review of papillary thyroid cancer patients treated with total thyroidectomy and radioactive iodine at a single experienced thyroid cancer center and followed according to the LATS management guidelines. Each patient was risk-stratified using both the LATS and ATA staging systems. The primary endpoints were (i) the best response to initial therapy defined as either remission (stimulated thyroglobulin [Tg] <1 ng/mL, negative ultrasonography) or persistent disease (biochemical and/or structural), and (ii) clinical status at final follow-up defined as no evidence of disease (suppressed Tg <1 ng/mL, negative ultrasonography), biochemical persistent disease (suppressed Tg >1 ng/mL in the absence of structural disease), structural persistent disease (locoregional or distant metastases), or recurrence (biochemical or structural disease identified after a period of no evidence of disease). RESULTS One hundred seventy-one papillary thyroid cancer patients were included (mean age 45 ± 16 years, followed for a median of 4 years after initial treatment). Both the ATA and LATS risk stratification systems provided clinically meaningful graded estimates with regard to (i) the likelihood of achieving remission in response to initial therapy, (ii) the likelihood of having persistent structural disease in response to initial therapy and at final follow-up, (iii) the likely locations of the persistent structural disease (locoregional vs. distant metastases), (iv) the likelihood of recurrence, and (v) the likelihood of being no evidence of disease at final follow-up. The likelihood of having persistent biochemical evidence of disease was not significantly different across the staging categories. CONCLUSIONS Both the ATA and LATS risk of recurrence systems effectively risk-stratify patients with regard to multiple important clinical outcomes. When used in conjunction with a staging system that predicts disease-specific mortality, either of these systems can be used to guide risk-adapted individualized initial management recommendations.

Androgen-secreting adrenal adenomas.

BACKGROUND The androgen source in women with hirsutism and signs of virilism may be the ovary or adrenal gland. CASES Three patients with androgen excess are reported. Two had hyperandrogenemia and Cushing syndrome with an adrenal mass greater than 5.5 cm; the third had a small adrenal adenoma secreting only testosterone and responsive to human chorionic gonadotropin. In all cases, the pathologic report from surgery and the long-term resolution of symptoms confirmed the benign nature of the tumors. CONCLUSION Basal and dynamic hormonal tests cannot precisely differentiate ovarian from adrenal tumors. Adrenal adenomas must be considered as a cause of hyperandrogenic syndrome.

Rapid response of hypercortisolism to vandetanib treatment in a patient with advanced medullary thyroid cancer and ectopic Cushing syndrome

Medullary thyroid carcinoma (MTC) may rarely present with paraneoplastic syndromes. Among the most frequent ones are the appearance of diarrhea and ectopic Cushing syndrome (ECS). The ECS in the context of MTC is usually present in patients with distant metastatic disease. The use of drugs such as ketoconazole, metyrapone, somatostatin analogs and etomidate have been ineffective alternatives to control hypercortisolism in these patients. Bilateral adrenalectomy is often required to manage this situation. Recently, the use of tyrosine kinase inhibitors has been shown to be a useful tool to achieve eucortisolism in patients with metastatic MTC and ECS. We present a patient with sporadic advanced persistent and progressive MTC with lymph node and liver metastases, which after 16 years of follow-up developed an ECS. After one month of 300 mg/day vandetanib treatment, a biochemical and clinical response of the ECS was achieved but it did not result in significant reduction of tumor burden. However the patient reached criteria for stable disease according to response evaluation criteria in solid tumors (RECIST 1.1) after 8 months of follow-up.

Patients with familial non-medullary thyroid cancer have an outcome similar to that of patients with sporadic papillary thyroid tumors

OBJECTIVE The purpose of this study was to determine whether familial non-medullary thyroid cancer (FNMTC) is more aggressive than sporadic thyroid cancer. SUBJECTS AND METHODS We compared the clinical behavior and outcome of 16 subjects with FNMTC from 7 unrelated kindred with those observed in 160 subjects with sporadic PTC (SPTC) from our database. RESULTS The only different baseline characteristics observed between both groups were: bilateral malignancy, 38% vs. 24%, respectively (p = 0.03), and lymph node metastasis, 56.2% vs. 39%, respectively (p = 0.01). Considering the outcome, in the FNMTC, 9 (56.2%) patients were rendered free of disease, one patient died from thyroid cancer (6%), and 6/16 (37.5%) had persistent disease. In the SPTC Group, 87 (54%) patients were considered free of disease, 11 (7%) died due to PTC, and 62 (38%) had persistent disease (p = ns). CONCLUSIONS Despite the higher incidence of lymph node metastasis in FNMTC patients this situation seemed not to alter the compared outcome.

Long-term survival and low effective cumulative radioiodine doses to achieve remission in patients with 131Iodine-avid lung metastasis from differentiated thyroid cancer.

Objective To evaluate long-term survival and response to RAI treatment in patients with differentiated thyroid cancer (DTC) and 131Iodine-avid metastatic lung disease. Patients and Methods A retrospective review of 639 DTC patients followed-up at the Hospital de Clínicas, Buenos Aires, Argentina, showed that 42 (6%) patients had lung metastasis, and 24 patients were included for analysis. Results Seventeen were women, and 7 were men (F:M = 2.4:1). Eighteen patients (75%) had PTC, and 6 (25%) had FTC. The median age at diagnosis was older than 45 years in 50%, and the median follow-up was 13 years. Good response to treatment (GRT: no evidence of disease or biochemical persistence without structural correlate) was observed in 46% of patients (all with diffuse postdose radioiodine uptake and no structural images higher than 1 cm in diameter); and 21% patients died from disseminated lung metastasis. Overall survival at 5 and 10 years was 100% and 88.4%, respectively. The Cox proportional hazard ratio showed that extrathyroidal invasion, positive uptake of 18-FDG, and metachronous diagnosis of the lung metastasis were variables that significantly predicted death. Those patients who had a GRT did with a mean effective cumulative RAI dose of 457.3 ± 29.7 mCi 131I (range, 300–600 mCi 131I). Conclusions Lung metastasis showed a slow progression with a high long-term overall survival. The presence of synchronous lung metastasis, the absence of nodules larger than 1 cm, and the lack of uptake of 18FDG were predictive factors for an early response to treatment with RAI cumulative doses lower than 600 mCi 131I.

Thyroglobulin levels measured at the time of remnant ablation to predict response to treatment in differentiated thyroid cancer after thyroid hormone withdrawal or recombinant human TSH.

The objective of our study was to evaluate the prognostic value of stimulated thyroglobulin levels at the moment of remnant ablation for predicting an initial excellent or a structural incomplete response to treatment according to the risk of recurrence in patients with differentiated thyroid cancer. Patients were divided into two groups according to the preparation mode for remnant ablation (thyroid hormone withdrawal or recombinant human TSH). We included 219 patients followed-up for at least for 24 months after remnant ablation. The primary endpoint was the best response to initial therapy assessed in the first 9–18 months of follow-up. An excellent response was observed in 45.1 % of patients prepared after recombinant human TSH compared to 44.6 % of patients prepared after thyroid hormone withdrawal (P = NS). The cutoff value of thyroglobulin level after recombinant human TSH for predicting an excellent response was 8 ng/ml (n = 51), with a sensitivity of 73.9 %, and a positive predictive value of 61 %. It was similar for patients with low vs. intermediate to high risk of recurrence. This cutoff value for thyroglobulin level after thyroid hormone withdrawal was 22 ng/ml (n = 168), with a sensitivity of 94.7 % and a positive predictive value of 61.7 %. In the thyroid hormone withdrawal group the thyroglobulin cutoff level was 12 ng/ml for low-risk patients compared to 16 ng/ml for those with intermediate to high risk of recurrence (P = 0.003). The cutoff value of the thyroglobulin level for predicting a structural incomplete response to initial treatment was 20 ng/ml after rhTSH, with a negative predictive value of 91.4 %. This level was higher in thyroid hormone withdrawal group, and it was established at 25 ng/ml, with a negative predictive value of 97.7 %. The stimulated Tg level seems to be different depending on the preparation mode (rhTSH or THW) for RA. It has a high NPV to predict the absence of a structural incomplete response and it is also a good predictor of the initial excellent response and the NED status at the end of follow-up.

Partial response to sorafenib treatment associated with transient grade 3 thrombocytopenia in a patient with locally advanced thyroid cancer

Advanced radioactive refractory and progressive or symptomatic differentiated thyroid carcinoma (DTC) is a rare condition. Sorafenib was recently approved for the treatment of these patients. We present the case of a 67 year old woman diagnosed with DTC who underwent a total thyroidectomy with central, lateral-compartment neck dissection and shaving of the trachea and esophagus due to tumor infiltration. A local recurrence was detected 14 months later requiring, additionally, two tracheal rings resection. The patient received a cumulative 131I dose of 650 mCi and developed dysphagia and dyspnea 63 months after initial surgery. A 18FGD-PET/CT showed progression of the local mass associated to hypermetabolic pulmonary nodules. Sorafenib 800 mg/day was then prescribed. A dose reduction to 400 mg/day was necessary due to grade 3 thrombocytopenia that appeared four months after drug prescription. Platelet count went to normal after this dose reduction. Five months after initiation of sorafenib, a partial response of the local mass with significant intra-tumoral necrosis was observed. We conclude that sorafenib is a valid option for locally advanced DTC and that the platelet count should be evaluated regularly because it seems that thrombocytopenia might be more frequently observed in DTC than in other types of tumors.

Should Age at Diagnosis Be Included as an Additional Variable in the Risk of Recurrence Classification System in Patients with Differentiated Thyroid Cancer

Objective: To evaluate the influence of age at diagnosis on the frequency of structural incomplete response (SIR) according to the modified risk of recurrence (RR) staging system from the American Thyroid Association guidelines. Patients and Methods: We performed a retrospective analysis of 268 patients with differentiated thyroid cancer (DTC) followed up for at least 3 years after initial treatment (total thyroidectomy and remnant ablation). The median follow-up in the whole cohort was 74.3 months (range: 36.1-317.9) and the median age at diagnosis was 45.9 years (range: 18-87). The association between age at diagnosis and the initial and final response to treatment was assessed with analysis of variance (ANOVA). Patients were also divided into several groups considering age younger and older than 40, 50, and 60 years. Results: Age at diagnosis was not associated with either an initial or final statistically significant different SIR to treatment (p = 0.14 and p = 0.58, respectively). Additionally, we did not find any statistically significant differences when the percentages of SIR considering the classification of RR were compared between different groups of patients by using several age cutoffs. Conclusions: When patients are correctly risk stratified, it seems that age at diagnosis is not involved in the frequency of having a SIR at the initial evaluation or at the final follow-up, so it should not be included as an additional variable to be considered in the RR classifications.

Recombinant Human Thyroid-Stimulating Hormone-Aided Remnant Ablation Achieves a Response to Treatment Comparable to That with Thyroid Hormone Withdrawal in Patients with Clinically Relevant Lymph Node Metastases

It has already been shown that remnant ablation in patients with thyroid cancer and lymph node (LN) metastases has similar results when patients are prepared after recombinant human thyroid-stimulating hormone (rhTSH) therapy or thyroid hormone withdrawal (THW). Due to the current changes in the risk-of-recurrence classifications, we decided to evaluate the initial response to treatment and the outcome at medium-term follow-up in 40 consecutive patients with clinically relevant lymph nodes who received radioiodine remnant ablation after rhTSH therapy (n = 20) or THW (n = 20). Each patient received either 100 or 150 mCi 131-I for ablation based on TNM status, and the mean amounts of 131-I used in the 2 groups were not significantly different. An excellent response to treatment was observed in 45% of the patients prepared after rhTSH therapy compared to 20% of those prepared after THW (p = 0.08). Three patients (2 in the THW group and 1 in the rhTSH group) who had N1a in the initial surgery presented with structural persistence as an initial response to treatment. One patient in the THW group had a follow-up of the persistent disease with no surgical treatment, and 2 others received a lateral LN dissection. When the status at final follow-up was considered (median follow-up 3.3 years, range 3-4.2), 60% of the patients ablated after rhTSH therapy were considered with no evidence of disease, compared to 30% of those who underwent THW. The frequency of structural persistence (metastatic LN) was similar in the 2 groups (15 vs. 25%), and the distribution of the responses at final follow-up was not statistically significantly different (p = 0.12). We conclude that preparation after rhTSH therapy seems to be as effective as after THW for patients with clinically relevant LN metastases.

Contents Vol. 3, 2014

Maria Alevizaki, Athens Ana Aranda, Madrid Rebecca Bahn, Rochester, Minn. Paul Banga, London Luigi Bartalena, Varese Bernadette Biondi, Naples Anita Boelen, Amsterdam Georg Brabant, Lübeck Henning Dralle, Halle Creswell J. Eastman, Westmead, N.S.W. Murat Erdogan, Ankara Valentin Fadeyev, Moscow Ulla Feldt-Rasmussen, Copenhagen Laszlo Hegedus, Odense George J. Kahaly, Mainz Rui Maciel, São Paolo Ana Luiza Maia, Porto Alegre Jens Mittag, Stockholm Ralf Paschke, Leipzig Simon Pearce, Newcastle-upon-Tyne Robin Peeters, Rotterdam Kris Poppe, Bruxelles Samuel Refetoff , Chicago, Ill. Jacques Samarut, Lyon Pilar Santisteban, Madrid YoungKee Shong, Seoul Jan Smit, Leiden Weiping Teng, Shenyang Mark Vanderpump, London Th eo Visser, Rotterdam Paolo Vitti, Pisa Graham Williams, London Shunichi Yamashita, Nagasaki Mariastella Zannini, Naples Luca Persani, Milan (Translational Th yroidology)