Therapeutic Implications of Diffuse Hepatic Uptake Following I-131 Therapy for Differentiated Thyroid Cancer

ObjectiveTo determine if diffuse hepatic uptake (DHU) of radioactive iodine (I-131) following radioactive iodine treatment has prognostic implications in otherwise scan-negative patients.MethodsThis is a retrospective review of patients treated for differentiated thyroid cancer (DTC) at Beth Israel Deaconess Medical Center between January 1990 and June 2006. This group included patients receiving therapy to ablate presumed remnant tissue, as well as treatment for persistent disease as measured by thyroglobulin or imaging. All patients included in the study had no remnant uptake and otherwise negative posttherapy scans. A total of 57 patients with 63 scans met these criteria. The scans were then scored for DHU on a scale of 0 to 5, with 0 being no uptake and 5 being intense uptake relative to background.ResultsSixteen of 63 treatments were remnant ablations. Ten of 57 patients had positive thyroglobulin antibodies. Average DHU was similar in the ablation and therapeutic groups (1.9 vs. 2.3, P = .3). There was no correlation with either I-131 dose or the presence of thyroglobulin antibodies. There was a difference for DHU in the rate of disease-free survival, (undetectable thyroglobulin and no clinical or radiographic evidence of metastasis); 50% of patients with hepatic uptake scores of 0-2 were disease-free compared to 15% with scores of 3-5 (P<.01). The average length of follow-up for disease-free patients was 4.6 years.ConclusionIn patients with DHU with otherwise negative whole-body scans following I-131 treatment, more intense hepatic uptake is associated with lower likelihood of complete response to I-131 treatment. (Endocr Pract. 2013;19:263-267)     

Increased Risk of Radioiodine Treatment Failure Associated with Graves Disease Refractory to Methimazole

Objective: Iodine 131 (I-131) radioactive iodine (RAI) therapy has been the preferred treatment for Graves disease in the United States; however, trends show a shift toward antithyroid drug (ATD) therapy as first-line therapy. Consequently, this would favor RAI as second-line therapy, presumably for ATD refractory disease. Outcomes of RAI treatment after first-line ATD therapy are unclear. The purpose of this study was to investigate treatment failure rates and potential risk factors for treatment failure, including ATD use prior to RAI treatment.Methods: A retrospective case control study of Graves disease patients (n = 200) after I-131 RAI therapy was conducted. Treatment failure was defined as recurrence or persistence of hyperthyroidism in the follow-up time after therapy (mean 2.3 years). Multivariable regression models were used to evaluate potential risk factors associated with treatment failure.Results: RAI treatment failure rate was 16.5%. A majority of patients (70.5%) used ATD prior to RAI therapy, predominantly methimazole (MMI) (91.9%), and approximately two-thirds of patients used MMI for >3 months prior to RAI therapy. Use of ATD prior to RAI therapy (P = .003) and higher 6-hour I-123 thyroid uptake prior to I-131 RAI therapy (P<.001) were associated with treatment failure. MMI use >3 months was also associated with treatment failure (P = .002).Conclusion: More patients may be presenting for RAI therapy after failing first-line ATD therapy. MMI use >3 months was associated with RAI treatment failure. Further studies are needed to investigate the association between long-term first-line ATD use and RAI treatment failure.     

Graves Ophthalmopathy After Radiation Treatment of Thyroid Cancer

ObjectiveTo describe a patient with metastatic thyroid cancer who developed Graves ophthalmopathy after treatment with radioiodine (I 131) and external beam radiation.MethodsWe present a case report that includes clinical, laboratory, and radiologic findings and a brief review of the literature.ResultsA 49-year-old woman who had had a total thyroidectomy and neck dissection followed by I 131 treatment 5 years earlier for papillary thyroid cancer presented for follow-up management after recent neck dissection for recurrent disease. Because she had thyroglobulin antibodies, she was again treated with I 131 after preparation with recombinant human thyroid-stimulating hormone. A post-treatment scan revealed uptake in the right iliac crest. A fludeoxyglucose F 18 positron emission tomography/computed tomography fusion scan revealed osseous metastases in the right pelvis, and external beam radiotherapy was delivered to this area. Approximately 5 months later, she developed periocular swelling and excessive tearing. Magnetic resonance imaging of the orbits revealed enlargement of the extraocular muscles. Serum thyroid-stimulating immunoglobulins were greatly elevated.ConclusionThis case corroborates an earlier report to suggest that radiation-associated thyroid injury in a patient with thyroid cancer may be followed by Graves ophthalmopathy and appearance of thyroid-stimulating immune-globulins in the serum. (Endocr Pract. 2008;14:419-421)     

Prognosis of High-Risk Papillary Thyroid Cancer Patients with Pre-Ablation Stimulated TG <1 NG/ML

Objective: The prevalence of undetectable pre-ablation stimulated thyroglobulin (s-Tg) and its clinical implications in high-risk papillary thyroid cancer (PTC) patients remain poorly described. We investigated the rate of tumor recurrence in PTC patients initially classified as high risk but with pre-ablation s-Tg <1 ng/mL and negative anti-Tg antibody (TgAb).Methods: In order to have a follow-up period of at least 5 years for each patient, PTC patients consecutively seen at our department from May 2008 to June 2013 with the following characteristics were selected: (i) classified as American Thyroid Association high risk on the basis of tumor histopathologic features; (ii) submitted to adjuvant ¹³¹I therapy after total thyroidectomy; (iii) a postoperative pre-ablation s-Tg <1 ng/mL and negative TgAb.Results: Among 767 high-risk PTC patients submitted to adjuvant ¹³¹I therapy, 69 patients met the inclusion criteria. Sixty-seven patients (97.1%) were diagnosed as classical PTC, and the remaining 2 patients (2.9%) were diagnosed as follicular variant PTC. When evaluated 9 to 12 months after ¹³¹I therapy, 67 patients (97.1%) were classified as excellent response. Two (2.9%) patients had an s-Tg >1 ng/mL (<3 ng/mL) in the absence of apparent disease, as detected by imaging methods (indeterminate response). During a median follow-up duration of 5.6 years, recurrence was observed in only 2 (2.9%) patients. The 67 (97.1%) patients without tumor recurrence were not submitted to any additional therapy, and all had a suppressed Tg <1 ng/mL in the last assessment.Conclusion: High-risk PTC patients with pre-ablation s-Tg <1 ng/mL and negative TgAb had a favorable prognosis.Abbreviations: CT = computed tomography; L-T4 = levothyroxine; PTC = papillary thyroid cancer; SPECT/CT = single photon emission computed tomography/computed tomography; s-Tg = stimulated thyroglobulin; T4 = thyroxine; TgAb = anti-thyroglobulin antibody; US = ultrasound     

Ultrasonographic Differentiation of Cervical Lymph Nodes in Patients with Papillary Thyroid Carcinoma After Thyroidectomy and Radioiodine Ablation: A Prospective Study

ObjectiveThe objective of the present study was to validate an ultrasound (US) classification of cervical lymph nodes (LNs) in patients with papillary thyroid cancer (PTC) after thyroidectomy and radioactive iodine (¹³¹I) ablation.MethodsWe performed a prospective study in which the patients were submitted to thyroidectomy and ¹³¹I ablation and then followed until neck US revealed LN(s) ≥ 5 mm. A total of 288 LNs from 112 patients with PTC were evaluated. Patient management was based on LN characteristics grouped according to the classification system studied here.ResultsThe presence of microcalcifications and/or cystic degeneration of cervical LNs were highly suggestive of a metastatic etiology (specificity of 99.4%). In contrast, the most sensitive finding for LNs affected by PTC was the absence of an echogenic hilum (sensitivity of 100%). In the absence of these findings (microcalcifications, cystic degeneration, echogenic hilum), a metastatic etiology was the most likely in the case of a round LN (specificity of 89%). The differentiation of a spindle-shaped LN without a visible hilum by Doppler analysis permitted us to dichotomize an initial probability of metastases of 13% in 25% (with peripheral vascularization) versus 3.3% (without peripheral vascularization).ConclusionsOur results confirm that the classification proposed for cervical LNs in patients with PTC is valid for determining patient management following initial therapy. (Endocr Pract. 2014;20:293-298)     

Hyperthyroidism due to Coexistence of Graves’ Disease and Struma Ovarii

ObjectiveTo report an unusual case of persistent thyrotoxicosis after treatment of Graves’ disease, because of coexistence of struma ovarii.MethodsWe report the clinical history, imaging studies, laboratory and pathologic data, and treatment in a patient with persistent hyperthyroidism after surgical treatment of Graves’ disease. In addition, we discuss some aspects of the pathogenesis of hyperthyroidism due to functioning struma ovarii.ResultsA 42-year-old woman underwent near-total thyroidectomy for treatment of Graves’ disease. Post-operatively, hyperthyroidism was still present. Methimazole was administered again, and performance of a ¹³¹I whole-body scan demonstrated a focus of intense uptake in the pelvis. Pelvic ultrasonography revealed a mass (11 by 8 by 7.1 cm) arising from the right ovary, with both solid and cystic components. Abdominal surgical exploration was performed, and the final histologic diagnosis was struma ovarii. The symptoms of hyperthyroidism diminished, and 3 weeks postoperatively, the thyroid hormone levels were in the hypothyroid range.ConclusionIn patients with refractory hyperthyroidism after thyroid surgical treatment, radioiodine scanning should be performed to diagnose or exclude the functioning profile of ovarian masses. (Endocr Pract. 2007;13:274-276)     

A Case of Hypercalcemia Associated with Castleman Disease

ObjectiveTo present a case of hypercalcemia associated with Castleman disease.MethodsThe details of case presentation, evaluation, diagnosis, and treatment are reviewed in a 25-year-old woman with severe hypercalcemia, joint pain, conjunctival injection, and lymphadenopathy.ResultsEndocrinopathies such as primary hyperparathyroidism were ruled out. Infectious and rheumatologic laboratory evaluations revealed normal results. On a whole-body scan, the patient was noted to have diffusely increased osseous uptake in conjunction with increased periarticular uptake, consistent with a metabolic superscan. After extensive evaluation, the patient underwent a right axillary lymph node biopsy and was found to have multicentric Castleman disease. She was treated with high-dose corticosteroids and eventually immunomodulators to help control her disease.ConclusionTo the best of our knowledge, this is the first published case report demonstrating hypercalcemia in association with Castleman disease. The pathologic mechanism is likely bone turnover mediated by cytokines such as interleukin-6. (Endocr Pract. 2010;16:1007-1011)     

Papillary Hyperplastic Nodule: Pitfall in the Cytopathologic Diagnosis of Papillary Thyroid Carcinoma

ObjectiveTo identify the pitfalls of overdiagnosing papillary formation as papillary thyroid carcinoma (PTC) in thyroid cytology specimens.MethodsPatients with papillary hyperplastic nodules who had preoperative fine-needle aspiration biopsy (FNAB) were selected for this study. All patients had been diagnosed as having either PTC or lesions suggestive of PTC on preoperative FNAB. Pathology reports, surgical reports, and cytopathology slides were reviewed and analyzed for demographic data, nature of surgery, and pathologic features.ResultsSix women and 2 men with a mean age of 49 years (range, 16-79 years) were included. The lesion size ranged from 1.0 to 3.5 cm. Four patients were diagnosed as having PTC and 4 as having lesions suspicious for PTC. FNAB specimens were available for review in 6 cases. Surgical pathology slides were reviewed in all cases. When cytologic material was evaluated for the morphologic features that led to the misdiagnosis of PTC by comparing it with FNAB specimens of classic variant of PTC, the specimens from these patients showed follicular cells arranged in short, nonbranching papillae in a background of watery colloid and macrophages. The follicular cells were round and demonstrated oncocytic change with nuclear enlargement, prominent central nucleoli, nuclear chromatin clearing, and intranuclear grooves.ConclusionsCaution should be exercised rendering the diagnosis of PTC on FNAB samples when a thyroid lesion shows papillary configurations and oncocytic cells and if convincing nuclear features of PTC are not present. Furthermore, some morphologic features on thyroid aspiration can help differentiate these cases from true PTC. (Endocr Pract. 2008;14:863-868)     

Factors Associated With Radioactive Iodine Therapy–Acquired Nasolacrimal Duct Obstruction

ObjectiveTo identify factors associated with radioactive iodine (RAI)-acquired nasolacrimal duct obstruction (NLDO).MethodsRetrospective chart review and telephone surveys of patients who received RAI therapy for thyroid carcinoma at an academic institution were conducted. Telephone surveys were used to screen for post-RAI NLDO diagnoses. Databases were reviewed for documented NLDO, demographics, RAI dose, total number of RAI treatments, and sialadenitis. Routine post-RAI whole-body scintigraphy (WBS) images were analyzed for the presence or absence of ¹³¹I sodium iodide (I-131) in the nasolacrimal duct. Intranasal I-131 activity was graded as none, low, moderate, and high; those with moderate or high activity were considered to have “increased” activity. Logistic and ordinal logistic regression models were used to evaluate the associations with NLDO while adjusting for I-131 dose.ResultsOf the 209 patients who completed the survey, 15 (7%) had NLDO diagnoses. Increased intranasal I-131 activity on WBS, presence of nasolacrimal I-131 WBS activity, presence of documented post-RAI sialadenitis, and history of >1 RAI treatment were associated with the development of NLDO from univariate analyses (P ≤ .013). After adjusting for the administered dose of I-131, the presence of sialadenitis and nasolacrimal I-131 activity on WBS were the remaining 2 factors significantly associated with NLDO development (P < .001 and P = .01, respectively).ConclusionsThe presence of sialadenitis and nasolacrimal I-131 activity on WBS are I-131 dose-independent correlative factors for RAI-associated NLDO. Patients with these characteristics should be counseled on their increased risk of NLDO after RAI therapy for thyroid carcinoma.     

Insular Variant of Poorly Differentiated Thyroid Carcinoma

ObjectiveTo present a case of an insular variant of poorly differentiated thyroid carcinoma (PDTC) and to review the literature related to diagnosis, natural history, and treatment of this unusual form of thyroid cancer.MethodsWe present the clinical, laboratory, and pathologic findings of the study patient and review Englishlanguage literature related to PDTC published between 1970 and the present.ResultsPDTC is a controversial and rare epithelial thyroid cancer, intermediate between differentiated thyroid carcinoma and anaplastic thyroid carcinoma that exhibits increased aggressiveness, propensity to local recurrence, distant metastases, and increased mortality. PDTC warrants aggressive management with total thyroidectomy followed by radioactive iodine ablation and potentially additional therapy for residual or recurrent disease. Some carcinomas do not take up radioactive iodine, and dedifferentiated clones of distant metastases may evolve. It is unclear whether chemotherapy is beneficial. Use of additional imaging modalities, including positron emission tomography, 18-fludeoxyglucose positron emission tomography/computed tomography, 18-fludeoxyglucose positron emission tomography/computed tomography/magnetic resonance imaging, ¹²⁴I positron emission tomography/computed tomography, positron emission tomography/magnetic resonance imaging fusion studies, and recombinant human thyrotropin-stimulated radioactive iodine uptake for cancer surveillance are discussed.ConclusionsPDTC is an unusual and aggressive form of thyroid cancer. Fine-needle aspiration cytology may not yield sufficient information to specifically diagnose PDTC. Aggressive management with total thyroidectomy and neck dissection followed by high-dose radioactive iodine remnant ablation is standard. Iodine I 131 whole body scanning is often the initial test for tumor surveillance, with other imaging modalities applied as needed. (Endocr Pract. 2011;17:115-121)     

Intrathyroidal Ectopic Thymic Tissue Mimicking Thyroid Cancer in Children

ObjectiveTo increase awareness of the important differential diagnosis between thyroid cancer and intrathyroidal ectopic thymic tissue when performing neck ultrasound (US) in pediatric patients.MethodsWe report 2 cases of intrathyrodal thymic tissue that were initially referred as possible papillary thyroid cancer (PTC). US and cytologic features of these lesions are described, and the distinguishing US characteristics of intrathyroidal thymic tissue versus PTC are discussed.ResultsTwo pediatric patients who underwent thyroid US were diagnosed with thyroid nodules suggestive of PTC. The suspected lesions in both patients exhibited an echo texture identical to the normal thymus gland. Fine-needle aspirate (FNA) biopsy of the nodule in the first case revealed numerous lymphocytes with positive immunocytochemical staining for CD3, confirming a T cell phenotype. The second patient underwent follow-up US imaging 8 months later that showed stability of the intrathyroidal nodule.ConclusionIntrathyroidal ectopic thymic tissue can be mistaken for PTC as both conditions have similar US features. Increased awareness of this unique mimicry may help to avoid unnecessary invasive investigations and surgery in these young patients. (Endocr Pract. 2014;20: e241-e245)     

Papillary Carcinoma of a Thyroglossal Duct Cyst in a Patient with Thyroid Hemiagenesis: Effectiveness of Conservative Surgical Treatment

ObjectiveTo describe a case of thyroglossal duct cyst carcinoma that arose in a patient with right thyroid lobe hemiagenesis.MethodsWe present the imaging, physical examination findings, treatment, and clinical course of the study patient.ResultsA 35-year-old woman was evaluated for a neck mass that had been present for 6 months and was slowly growing. She reported a previous diagnosis of right hemithyroid agenesis. The patient’s preoperative workup included ultrasonography of the neck and head and neck T1- and T2-weighted magnetic resonance imaging, which showed right hemithyroid agenesis and a cystic lesion in the median region of the neck below the hyoid bone. Findings from chest x-rays and thyroid function tests were normal. The patient underwent a modified Sistrunk procedure that included removal of the median portion of the hyoid bone. Histologic findings showed a 2.5-cm thyroglossal duct cyst with a 0.6-cm focus of follicular variant of papillary carcinoma with invasion of the cyst wall. Total thyroidectomy was not performed because of the absence of tumoral invasion of the parenchyma around the thyroglossal duct cyst and because the patient was at low risk for aggressive disease. Cervical ultrasonography examinations were performed 6, 12, and 24 months after treatment, and all findings were normal. Presently, the patient is symptom-free after 4 years of follow-up and has no evidence of disease.ConclusionIncidentally discovered, well-differentiated thyroid cancer that is confined to a thyroglossal duct cyst in a patient at low risk for aggressive disease can be adequately treated by a modified Sistrunk procedure that includes the median portion of the hyoid bone. (Endocr Pract. 2008;14:465-469)     

An Interesting Case of Peripheral Vascular Disease,Vascular Reperfusion,and Subsequent Development of Pain Due to Paget's Disease of Bone

ObjectiveTo present a case of Paget’s disease of bone that was unmasked after vascular reperfusion.MethodsIn this case study, we review the presentation, evaluation, diagnosis, and management of a patient with Paget’s disease and peripheral vascular disease.ResultsA 79-year-old-woman with a history of coronary artery heart disease and recent finding of a T5 compression fracture was hospitalized for evaluation of right lower extremity claudication. Angiography demonstrated a focal complete occlusion of the distal right femoral and popliteal arteries. A self-expanding stent was placed in the distal femoral and popliteal arteries. Approximately 48 hours after the procedure, the patient developed severe, right lower leg pain. On endocrine evaluation, the patient was found to have clinical signs suggesting Paget’s disease of bone, which was subsequently confirmed by imaging.ConclusionThis patient’s development of severe pain following reperfusion of distal femoral and popliteal arteries is in keeping with the known and aforementioned hypervascularity of pagetic bone. The finding of increased warmth over an area of skeletal deformation should always raise the possibility of Paget’s disease of bone.(Endocr Pract. 2013;19:e61-e63)     

Timing of Radioactive Iodine Therapy does not Impact Overall Survival in High-Risk Papillary Thyroid Carcinoma

Objective: Postthyroidectomy radioiodine (RAI) therapy is indicated for papillary thyroid carcinoma (PTC) with high-risk features. There is variability in the timing of RAI therapy with no consensus. We analyzed the impact of the timing of initial RAI therapy on overall survival (OS) in PTC.Methods: The National Cancer Data Base (NCDB) was queried from 2003 to 2006 for patients with PTC undergoing near/subtotal or total thyroidectomy and RAI therapy. High-risk patients had tumors >4 cm in size, lymph node involvement, or grossly positive margins. Early RAI was ≤3 months, whereas delayed was between 3 and 12 months after thyroidectomy. Kaplan-Meier (KM) and Cox survival analyses were performed after adjusting for patient and tumor-related variables. A propensity-matched set of high-risk patients after eliminating bias in RAI timing was also analyzed.Results: There were 9,706 patients in the high-risk group. The median survival was 74.7 months. KM analysis showed a survival benefit for early RAI in high-risk patients (P = .025). However, this difference disappeared (hazard ratio [HR] 1.26, 95% confidence interval [CI] 0.98–1.62, P = .07) on adjusted Cox multivariable analysis. Timing of RAI therapy failed to affect OS in propensity-matched high-risk patients (HR 1.09, 95% CI 0.75–1.58, P = .662).Conclusion: The timing of postthyroidectomy initial RAI therapy does not affect OS in patients with high-risk PTC.Abbreviations:CI = confidence intervalCLNM = cervical lymph node metastasisFVPTC = follicular variant papillary thyroid carcinomaHR = hazard ratioKM = Kaplan-MeierNCDB = National Cancer Data BaseOS = overall survivalPTC = papillary thyroid carcinomaRAI = radioactive iodine     

Serial Neck Ultrasound is More Likely to Identify False-Positive Abnormalities than Clinically Significant Disease in Low-Risk Papillary Thyroid Cancer Patients

Objective: American Thyroid Association (ATA) low-risk papillary thyroid cancer (PTC) patients without structural evidence of disease on initial posttreatment evaluation have a low risk of recurrence. Despite this, most patients undergo frequent surveillance neck ultrasound (US). The objective of the study was to evaluate the clinical utility of routine neck US in ATA low-risk PTC patients with no structural evidence of disease after their initial thyroid surgery.Methods: We performed a retrospective review of 171 ATA low-risk PTC patients after total thyroidectomy, with or without radioactive iodine (RAI) ablation, who had a neck US without suspicious findings after therapy. The main outcome measure was a comparison of the frequency of finding false-positive US abnormalities and the frequency of identifying structural disease recurrence.Results: Over a median follow-up of 8 years, 171 patients underwent a median of 5 neck US (range 2–17). Structural recurrence with low-volume disease (≤1 cm) was identified in 1.2% (2/171) of patients at a median of 2.8 years (range 1.6–4.1 years) after their initial diagnosis. Recurrence was associated with rising serum thyroglobulin (Tg) level in 1 of the 2 patients and was detected without signs of biochemical recurrence in the other patient. Conversely, false-positive US abnormalities were identified in 67% (114/171) of patients after therapy, leading to additional testing without identifying clinically significant disease.Conclusion: In ATA low-risk patients without structural evidence of disease on initial surveillance evaluation, routine screening US is substantially more likely to identify false-positive results than clinically significant structural disease recurrence.Abbreviations:18FDG-PET = 18-fluorodeoxyglucose-positron emission testingAJCC = American Joint Committee on CancerATA = American Thyroid AssociationCT = computed tomographyETA = European Thyroid AssociationMRI = magnetic resonance imagingPTC = papillary thyroid cancerRAI = radioactive iodineTg = thyroglobulinTgAb = antithyroglobulin antibodiesTSH = thyroid-stimulating hormoneUS = ultrasound     

Adjuvant I-131 therapy for T0–3 N1b M0 differentiated thyroid cancer with many (≥ 5) positive nodes

BackgroundIn patients with well-differentiated thyroid cancer, there is controversy about the prognostic importance of a large number of positive neck nodes and the potential value of radioiodine therapy. The purpose of this study was to evaluate this issue in the group of patients for whom it is most clinically important — those with classic histology and favorable T and M stage.Materials and methodsTwenty-five patients met the following inclusion criteria: classic histology of papillary or follicular thyroid carcinoma treated with total thyroidectomy and neck dissection followed by adjuvant I-131 treatment in our department between January 1, 2003, and December 31, 2013; adult age of > 21 years; and American Joint Committee on Cancer (AJCC ) stage (8^th edition) of T0–3, N1b with ≥ 5 positive nodes, and M0.ResultsThe median positive node number was 10 (range, 5–31). The median adjuvant I-131 dose was 158 mCi (range, 150–219 mCi). The median follow-up in patients without recurrence after treatment was 7.3 years. The 10-year actuarial rates were favorable: overall survival, 100%; freedom from visible recurrence, 82%; and visible or biochemical recurrence, 72%.ConclusionRecurrence was infrequent in our study population with ≥ 5 positive nodes following moderate-dose adjuvant I-131 treatment. These results are valuable in directing initial adjuvant therapy and follow-up intensity. Our results do not inform the question of the use of postoperative thyroglobulin (Tg) level to select N1b patients for low-dose I-131 treatment.     

Use of Methotrexate to Treat Isolated Graves Ophthalmopathy Developing Years After Thyroidectomy and Iodine 131 Treatment of Papillary Thyroid Cancer

ObjectiveTo describe a case of Graves ophthalmopathy developing years after subtotal thyroidectomy and radioactive iodine treatment of papillary thyroid cancer.MethodsWe present a case report including clinical and laboratory data. Current relevant literature is reviewed and summarized with regard to Graves ophthalmopathy.ResultsIn 2001, a 51-year-old woman presented with an asymptomatic thyroid nodule. Fine-needle aspiration biopsy results showed Hürthle cells, and the patient had a subtotal thyroidectomy in 2002. Stage 2 follicular variant of papillary thyroid carcinoma was diagnosed. She received radioactive iodine (I 131) therapy (94.8 mCi and 147.2 mCi) in 2003. Thyrotropin was suppressed with levothyroxine. The patient remained asymptomatic and had undetectable thyroglobulin antibodies. In 2007, her eyes became irritated (ie, erythematous, pruritic, watery). Thyroperoxidase and thyroglobulin antibodies were undetectable, but thyrotropin receptor antibody was elevated to 44% (reference range, < 16%). On physical examination, moderate periorbital edema and conjunctival injection were present; orbital magnetic resonance imaging was normal. Computed tomography of her orbits showed symmetric bilateral exophthalmos and prominence of orbital fat. Other ophthalmologic etiologies were ruled out by 2 independent ophthalmologists. She had minimal improvement with oral and intravenous steroids. Subsequent treatment with methotrexate resulted in marked symptomatic improvement and lowered the thyrotropin receptor antibody level to 24%.ConclusionsIsolated Graves ophthalmopathy in a patient after treatment of thyroid cancer and radioactive iodine ablation has not been previously reported. Methotrexate therapy may be a useful therapeutic approach in this setting. (Endocr Pract. 2008;14:422-425)     

Vitamin D–Mediated Hypercalcemia and Cushing Syndrome as Manifestations of Malignant Pleural Mesothelioma

ObjectiveTo report a case of coincident hypercalcemia and Cushing syndrome arising from mesothelioma.MethodsWe describe the clinical, laboratory, imaging, and pathologic findings of a patient with malignant pleural mesothelioma and elucidate the underlying biologic mechanisms resulting in concurrent overexpression of steroid and polypeptide hormones.ResultsA 62-year-old woman presented with chest discomfort and cough. Radiologic imaging revealed a diffuse pleural-based mass encasing the right lung. There was no invasion into the chest wall, diaphragm, or mediastinum, and there was no distant disease. Laboratory analyses documented hypercalcemia and Cushing syndrome, which were due to ectopic overproduction of 1,25-dihydroxyvitamin D (1,25[OH]₂D) and corticotropin. Surgical resection resulted in normocalcemia with normalization of serum 1,25(OH)₂D and reduction in hypercortisolemia. The extrapleural pneumonectomy specimen revealed overexpression of the 1,25(OH)₂D synthetic enzyme 25- hydroxyvitamin-D-1α-hydroxylase (1α-hydroxylase) and underexpression of the 1,25(OH)₂D catabolic enzyme 24- hydroxylase. Immunohistochemistry and electron microscopy demonstrated corticotropin and secretory granules in the tumor tissue.ConclusionThese findings support the evidence for a paracrine role of vitamin D in the resistance of the human host to antigen. (Endocr Pract. 2008;14:1011-1016)     

Role of Prophylactic Central Compartment Lymph Node Dissection on the Outcome Of Patients With Papillary Thyroid Carcinoma and Synchronous Ipsilateral Cervical Lymph Node Metastases

Objective: Prophylactic central compartment lymph node dissection (pCCND) results in a higher percentage of surgical-related complications. To date, no evidence of the impact of pCCND on the clinical outcome of papillary thyroid carcinoma (PTC) patients with synchronous ipsilateral cervical lymph node metastases has been reported.Methods: We evaluated all consecutive patients affected by PTC and synchronous ipsilateral cervical, but without evidence of central compartment, lymph node metastases. We selected 54 consecutive patients (group A) treated by total thyroidectomy, ipsilateral cervical lymph node dissection, and pCCND and 115 patients (group B) matched for sex, age at diagnosis, number and dimension of the metastatic lateral cervical lymph nodes, without pCCND. Clinical outcome after a median of 5 years and surgical-related complications were assessed.Results: The two groups were completely similar in terms of clinical features. Clinical outcomes showed a higher percentage of biochemical and indeterminate but not structural response in group B. Group B required significantly more radioiodine treatments, but no difference was shown in the need to repeat surgery for recurrences. Conversely, the prevalence of permanent hypoparathyroidism was significantly higher in group A (14.8%) than in group B (4.3%).Conclusion: In PTC patients with synchronous ipsilateral cervical lymph node metastases, in absence of clinically evident lymph node metastases of the central compartment, performing pCCND does not improve the 5-year outcome in terms of structural disease, despite a greater number of ¹³¹I treatments. However, pCCND is severely affected by a higher percentage of permanent hypoparathyroidism, even in the hands of expert surgeons.Abbreviations: IQR = interquartile range; pCCND = prophylactic central compartment lymph node dissection; PTC = papillary thyroid carcinoma; Tg = thyroglobulin; US = ultrasound     

Long-Term Follow-Up of a Patient With Papillary Thyroid Carcinoma,Elevated Thyroglobulin Levels,and Negative Imaging Studies

ObjectiveTo describe a patient with papillary thyroid carcinoma who had measurable thyroglobulin (Tg) levels for 20 years without clinical or imaging evidence of a malignant lesion.MethodsWe reviewed the clinical course, pathologic findings, Tg measurements, and results of various imaging studies in our patient and reviewed the literature regarding Tg-positive, diagnostic total-body radioiodine scan-negative patients with thyroid cancer.ResultsFour months after a 3.5- by 3.5-cm follicular thyroid cancer was removed from the anterior neck area of a 5-year-old girl, a bilateral subtotal thyroidectomy was performed. At age 12 years, she presented with a 2-cm mass on the right side of the neck. After a completion thyroidectomy, recurrent mixed papillary-follicular thyroid cancer was found scattered throughout the remaining thyroid parenchyma. Although a postoperative diagnostic total-body radioiodine scan did not reveal uptake of ¹³¹I, the Tg level was 58 ng/mL. Despite Tg levels as high as 2,528 ng/mL, the patient had no clinical evidence of thyroid cancer during a 20-year period of follow-up. Moreover, numerous imaging studies, including total-body scanning after the administration of 150 mCi of ¹³¹I and [¹⁸F]fluorodeoxyglucose positron emission tomography, were negative. Review of pathologic specimens from both operations with use of updated diagnostic criteria indicated that the tumor was a papillary thyroid carcinoma.ConclusionOur observations and the observations of other investigators indicate that some thyroid cancers produce Tg so efficiently that high levels of Tg may be associated with tumors that remain too small to be detected by imaging studies. The Tg levels may remain stable, decline, or even disappear over time without treatment. (Endocr Pract. 2005;11:43-48)