Thyroid crisis caused by metastatic thyroid cancer: an autopsy case report.

BACKGROUND: Thyroid crisis is a life-threatening condition in thyrotoxic patients. Although differentiated thyroid cancer is one of the causes of hyperthyroidism, reports on thyroid crisis caused by thyroid cancer are quite limited. Here, we describe a case of thyroid crisis caused by metastatic thyroid cancer. CASE PRESENTATION: A 91-year-old woman was admitted to our hospital because of loss of appetite. Two years prior to this hospitalization, she presented with subclinical thyrotoxicosis and was diagnosed with histologically unidentified thyroid cancer with multiple metastases, and she refused aggressive medical interventions. On admission, she exhibited extreme thyrotoxicosis, and the presence of fever, severe tachycardia, impaired consciousness, and heart failure revealed the presence of thyroid crisis. All thyroid autoantibodies were negative. Multidisciplinary conservative treatment was initiated; however, she died on the fifth day after admission. Autopsy revealed the presence of primary anaplastic thyroid carcinoma and multiple metastatic foci arising from follicular thyroid carcinoma. Both primary and metastatic follicular thyroid carcinoma likely induced thyrotoxicosis, which could have been exacerbated by anaplastic thyroid carcinoma. CONCLUSIONS: Even though the trigger of thyroid crisis in this patient is not clear, the aggravated progression of her clinical course suggests that careful monitoring of thyroid hormones and appropriate intervention are essential for patients with thyroid cancer.

Acromegaly caused by a somatotroph adenoma in patient with neurofibromatosis type 1.

Although acromegaly has been reported in patients with Neurofibromatosis type 1 (NF1), these cases have not been associated with growth hormone (GH)-producing somatotroph adenoma, but with optic pathway glioma. A 68 year-old Japanese woman, who had been clinically diagnosed with NF1, was referred to our hospital due to a thyroid tumor and hypercalcemia. Acromegaly was suspected due to her facial features, and subsequent examinations revealed the presence of GH excess with a pituitary tumor, leading to the diagnosis of acromegaly. Histological and immunohistochemical analysis demonstrated an eosinophilic pituitary adenoma with diffuse positivity for GH, indicating typical somatotroph adenoma. In addition, her thyroid tumor was diagnosed histologically as follicular thyroid carcinoma (FTC) with primary hyperparathyroidism (PHPT). To investigate the pathogenesis of this untypical multiple endocrine tumor case of NF1, genetic analysis was performed using peripheral leukocytes and tissue of resected tumors. A heterozygous novel germline nonsense mutation (p.Arg1534*) in exon 35 of the NF1 gene was detected from peripheral leukocytes, which results in a truncated protein lacking the critical domain for GTPase activity, strongly suggesting its causal role in NF1. The loss of heterozygosity (LOH) in exon 35 of the NF1 gene was not detected in the somatotroph adenoma, parathyroid adenoma, and FTC. Although any mutations of the following genes; MEN1, CDKN1B, and PAX8-PPARγ were not detected, a heterozygous GNAS R201C mutation was detected in the somatotroph adenoma. To our knowledge, this is the first rare MEN1-like case of genetically diagnosed NF1 complicated with acromegaly caused by a somatotroph adenoma.

A case of metastatic follicular thyroid carcinoma complicated with Graves' disease after total thyroidectomy.

Thyroid cancer and Graves' disease may present simultaneously in one patient. The incidence of the development of hyperthyroidism from metastatic differentiated thyroid carcinoma is rare. We herein report a case of metastatic follicular carcinoma complicated with Graves' disease after total thyroidectomy. A 57-year-old woman underwent right hemithyroidectomy for follicular carcinoma. Metastatic lesions appeared in the lungs and skull two years after the first surgery, and remnant thyroidectomy was performed for radioactive iodine-131 (RAI) therapy, during which the TSH receptor antibody (TRAb) was found to be negative. The patient was treated with RAI therapy four times for four years and was receiving levothyroxine suppressive therapy. Although radioiodine uptake was observed in the lesions after the fourth course of RAI therapy, metastatic lesions had progressed. Four years after the second surgery, she had heart palpitations and tremors. Laboratory data revealed hyperthyroidism and positive TRAb. She was diagnosed with Graves' disease and received a fifth course of RAI therapy. 131I scintigraphy after RAI therapy showed strong radioiodine uptake in the metastatic lesions. As a result, the sizes and numbers of metastatic lesions decreased, and thyroid function improved. Metastatic lesions produced thyroid hormone and caused hyperthyroidism. RAI therapy was effective for Graves' disease and thyroid carcinoma.

Association between p53-binding protein 1 expression and genomic instability in oncocytic follicular adenoma of the thyroid.

Oncocytic follicular adenomas (FAs) of the thyroid are neoplasms of follicular cell origin that are predominantly composed of large polygonal cells with eosinophilic and granular cytoplasm. However, the pathological characteristics of these tumors are largely unexplored. Both the initiation and progression of cancer can be caused by an accumulation of genetic mutations that can induce genomic instability. Thus, the aim of this study was to evaluate the extent of genomic instability in oncocytic FA. As the presence of p53-binding protein 1 (53BP1) in nuclear foci has been found to reflect DNA double-strand breaks that are triggered by various stresses, the immunofluorescence expression pattern of 53BP-1 was assessed in oncocytic and conventional FA. The association with the degree of DNA copy number aberration (CNA) was also evaluated using array-based comparative genomic hybridization. Data from this study demonstrated increased 53BP1 expression (i.e., "unstable" expression) in nuclear foci of oncocytic FA and a higher incidence of CNAs compared with conventional FA. There was also a particular focus on the amplification of chromosome 1p36 in oncocytic FA, which includes the locus for Tumor protein 73, a member of the p53 family implicated as a factor in the development of malignancies. Further evaluations revealed that unstable 53BP1 expression had a significant positive correlation with the levels of expression of Tumor protein 73. These data suggest a higher level of genomic instability in oncocytic FA compared with conventional FA, and a possible relationship between oncocytic FA and abnormal amplification of Tumor protein 73.

Oncologic outcomes after completion thyroidectomy for patients with well-differentiated thyroid carcinoma.

BACKGROUND: At our institution, thyroid lobectomy is employed as a definitive operation for unifocal intrathyroidal low risk cancers and thus completion thyroidectomy is rarely performed. The purpose of this study was to identify the indications for selective completion thyroidectomy and to report oncologic outcomes. METHODS: A retrospective review was performed to identify patients who underwent planned completion thyroidectomy for well-differentiated thyroid carcinoma (WDTC) from 2001 to 2010 based on initial lobectomy pathology. Assessment for risk of recurrence was based on the American Thyroid Association Initial Risk Stratification. RESULTS: During the 10-year study period, 79 patients underwent completion thyroidectomy for WDTC. Forty-four (56 %) patients were low risk and 35 (44 %) were intermediate risk. Completion thyroidectomy was recommended for 64 patients, whereas 15 patients were given an option of surveillance but ultimately decided to have surgery. Patients in the "recommended group" had more T3 tumors and fewer T1a tumors (p = 0.005 and 0.006, respectively). These patients also were more likely to be intermediate risk (p = 0.008) and to present with aggressive histology (p = 0.002). The rate of contralateral tumors (n = 27) was similar between both groups (35 and 33 %, respectively). Contralateral cancers were micropapillary in 24 of 27 (89 %) patients, 10 (40 %) of whom had multifocal disease. There were two pulmonary recurrences and no local-regional recurrences (median follow-up of 42.3 months). CONCLUSIONS: Completion thyroidectomy is infrequent and performed for a select group of intermediate and low risk WDTCs at our institution with low recurrence rates. Incidental multifocal and unifocal contralateral cancers are common after completion thyroidectomy.

Effects of short-term metformin therapy associated with levothyroxine dose decrement on TSH and thyroid hormone levels in patients with thyroid cancer.

AIM: Suppressive therapy with levothyroxine is the main step in treatment of differentiated thyroid cancer (DTC). However, subclinical hyperthyroidism is associated with deleterious effects on cardiovascular and skeletal systems. Metformin may have a suppressive effect on TSH level. METHODS: We performed a single blind randomized controlled trial on the effect of short term Metformin therapy on 50 non-diabetic patients with DTC (mean age of 39.68 ±8.7 years) under suppressive therapy with levothyroxine. Metformin (500 mg) or placebo was added to the drug regimen of the patients and levothyroxine dose decreased by 33%. TSH and thyroid hormone values were measured at the beginning of the study and 3 months after treatment. RESULTS: Forty-six patients had papillary and 4 had follicular carcinoma. The mean dose of levothyroxine was 2.2±0.48 µg/kg. The mean TSH level at the beginning of the study was 0.05±.04 mIU/L. The mean age, weight and baseline TSH level was not significantly different between metformin and placebo groups (P>0.2). In the metformin group, the mean (±SD) TSH level was significantly increased from 0.03±0.04 to 3.1±5.7 mIU/L after 3 months of intervention (P=0.01) and the mean thyroid hormone levels were significantly decreased (P<0.001). In the placebo group, the mean TSH level increased from 0.04±0.04 to 3.1±4.7 mIU/L after 3 months (P=0.003). Delta TSH was 3.0±5.6 mIU/L and 3.1±4.7 mIU/L in metformin and placebo groups, respectively (P=0.9). CONCLUSION: Adding 500 mg of metformin to drug regimen was not useful to compensate for 33% of levothyroxine dose reduction in patients with DTC.

UNCOMMON PRESENTATION OF FOLLICULAR THYROID CARCINOMA: WHEN CHRONIC BACK PAIN SHOULD RAISE A FLAG.

Follicular thyroid carcinoma is the second most common type of thyroid cancer, and its incidence has increased dramatically in recent years. Although it typically presents as a thyroid nodule, it can spread to distant sites via hematogenous dissemination. Spinal cord compression complicating thyroid carcinoma is rare with only few cases reported in the literature. This case illustrates a minimally invasive follicular carcinoma that showed such an aggressive behavior, and thus the importance of considering metastatic thyroid carcinoma in the differential diagnosis of chronic back pain, which may possibly progress to spinal cord compression carrying severe morbidity.

Community-acquired pneumonia associated with immunosuppression due to follicular thyroid cancer: a case report.

BACKGROUND: We present the case of a woman with cancer, which weakened the immune system and increased the risk of infection. Thus, infections are a frequent complication of cancer. The development of community-acquired pneumonia, an acute respiratory infectious disease that damages the lung parenchyma, caused by the invasion of pathogenic microorganisms, can lead to respiratory failure with multiorgan failure due to respiratory sepsis. CASE PRESENTATION: Case report of a 38-year-old mixed-race woman with diabetes mellitus and irregular treatment, who was admitted with community-acquired pneumonia complicated by type I respiratory failure requiring mechanical ventilation. During her hospital stay, she developed ventilator-associated pneumonia, recurrent empyema, bronchopleural fistula, refractory septic shock and multiorgan dysfunction despite multiple interventions. The patient required prolonged mechanical ventilation, vasopressor support and antibiotic therapy. After 62 days, metastatic papillary thyroid carcinoma was diagnosed. She presented with hypoparathyroidism and permanent hypocalcemia. She died after multiple complications and a refractory critical condition. CONCLUSION: The case exemplifies the potential severity of community-acquired pneumonia in a patient with risk factors such as diabetes and immunosuppression. It highlights the complexity of treating multiple comorbidities and the importance of multidisciplinary management with close surveillance for timely interventions for complications.

Follicular carcinoma of thyroid following successful liver transplantation--a report.

Follicular carcinoma of the thyroid is a relatively rare malignancy in childhood even in paediatric solid organ transplant recipients. The risk of developing de novo malignancies after liver transplantation is higher compared to the general population. We report an 18-yr-old girl who had successfully undergone liver transplantation five yr earlier for neonatal sclerosing cholangitis complicated by the development of dysplastic nodules. Baseline immunosuppression was with tacrolimus and prednisolone. Mycophenolate mofetil was later added in view of steroid-resistant episodes of graft rejection. She subsequently suffered from marked obesity and essential hypertension needing antihypertensive medication. Five yr after liver transplantation, she presented with a right-sided thyroid swelling that was rapidly progressive with no associated lymphadenopathy and normal systemic examination. Ultrasound of her neck revealed a solid lesion in the right lobe of the thyroid gland with ill-defined margins, and a diagnostic right thyroid lobectomy confirmed the diagnosis of follicular carcinoma with focal capsular and vascular invasion. She underwent total thyroidectomy and currently remains well on thyroxine supplements. Our report highlights the need for high level of suspicion and prompt investigation into any abnormal lesion in the long-term follow-up of solid organ transplant recipients.

Surgical management of primary thyroid carcinoma arising in thyroglossal duct cyst: an experience of a single institution in Serbia.

Thyroglossal duct cyst (TDC) carcinoma is a comparable rare entity and treatment strategies have not been standardized. Here, we report a favorable outcome of TDC carcinoma patients based on our therapeutic strategy. Twelve patients with TDC carcinoma treated in our department from 1986 to 2012 were enrolled. Ten patients underwent Sistrunk's procedure in other institutions and referred to our institution for re-operation after the diagnosis of TDC carcinoma and the remaining two underwent initial surgery in our institution. Eleven patients were diagnosed as papillary and one as follicular carcinoma originating from TDC. We performed total thyroidectomy for 11, and limited thyroidectomy for one patient. Three patients (25%) had carcinoma lesions in the thyroid. We routinely dissected level I bilaterally and 6 of 11 patients (55%) with papillary carcinoma-type TDC carcinoma had metastasis. Level II/III nodes were biopsied and if positive, we performed level II-IV dissection. Of the 5 patients positive for level II/III, 2 were also positive for level IV. For the 3 patients with synchronous carcinoma in the thyroid, we performed level VI dissection and two had metastasis in this level. To date, 1 patient showed a recurrence to the lung, but none of the patients in our series died of carcinoma. For surgery of TDC carcinoma, Sistrunk's procedure, total thyroidectomy with level I dissection is mandatory. Whether level II-IV dissection is performed depends on pathology of biopsied level II/III nodes. Level VI dissection is also recommended especially when carcinoma lesions are pre/intra operatively detected in the thyroid.

Central compartment reoperation for recurrent/persistent differentiated thyroid cancer: patterns of recurrence, morbidity, and prediction of postoperative hypocalcemia.

BACKGROUND: Incidence rates of hypoparathyroidism and vocal cord paralysis are high following central compartment reoperation, but few prospective studies have assessed morbidities and factors predictive of hypocalcemia after reoperation. We investigated recurrence patterns, morbidity, and factors predictive of postoperative hypocalcemia in patients undergoing central compartment reoperation for recurrent/persistent differentiated thyroid cancer (DTC). METHODS: We prospectively evaluated 45 consecutive patients with recurrent/persistent DTC. Thyroid remnants or recurrent cancers were removed in 16 patients, the unilateral or bilateral central compartment was cleared in all patients, and the lateral compartment on the diseased side was comprehensively removed from 24 patients. Recurrence patterns were assessed histopathologically, morbidities were monitored, and serum concentrations of calcium and intact parathyroid hormone (iPTH) were measured in all patients. RESULTS: Eleven patients (24.4%) had tumor invasion into the recurrent laryngeal nerve and/or the tracheoesophagus. Central nodal involvement occurred frequently (86.7%), and the ipsilateral jugular nodes of the lateral compartment were frequently involved. Temporary and permanent vocal cord paralysis developed in 10 (22.2%) and 8 (17.8%) patients, respectively, due primarily to intentional nerve resection following tumor invasion. Of 41 patients without preoperative hypoparathyroidism, 21 (46.3%) had temporary and 2 (4.9%) had permanent hypocalcemia. Multivariate analysis showed that bilateral central compartment dissection and low iPTH levels (<12.0 pg/ml) were independent predictors of postoperative hypocalcemia. CONCLUSIONS: Most patients with recurrent/persistent DTC harbor lesions in the central compartment. Central compartment reoperation may lead to high rates of morbidity, including hypoparathyroidism, which can be predicted by surgical extent and low serum iPTH levels.

Risk factors for nonsynchronous second primary malignancy and related death in patients with differentiated thyroid carcinoma.

BACKGROUND: Differentiated thyroid cancer (DTC) survivors are at increased risk of developing nonsynchronous second primary malignancy (NSPM). This study aims to examine possible risk factors leading to occurrence of NSPM as well as risk factors leading to NSPM-related death in patients with DTC. METHODS: Of the 1,106 patients with DTC managed at our institution, 92 (8.3%) patients developed NSPM and 40 (3.6%) patients died of NSPM. All causes of death were confirmed by medical record, autopsy report or death certificate. Clinicopathological variables were compared between those without NSPM and with NSPM as well as between those who died of NSPM and did not die of NSPM. Significant variables on univariate analysis were entered into a Cox proportional hazards model. RESULTS: The median latency period from diagnosis of DTC to NSPM was 142.7 (range 16.8-511.0) months. For occurrence of NSPM, age at DTC diagnosis ≥50 years old [relative risk (RR) = 2.35], cumulative radioactive iodine (RAI) activity 3.0-8.9 GBq (RR = 2.38), and external local radiotherapy (ERT) (RR = 1.95) were significant risk factors. For NSPM-related death, age at DTC diagnosis ≥50 years old (RR = 3.32) and nonbreast cancer (RR = 5.76) were significant risk factors. CONCLUSIONS: NSPM accounted for 18.7% of all deaths in DTC, but mortality was high (43.5%). Age at DTC diagnosis ≥50 years old, cumulative RAI activity 3.0-8.9 GBq, and ERT were significant risk factors for occurrence of NSPM, whereas age at DTC diagnosis ≥50 years old and the diagnosis of nonbreast cancer were significant risk factors for NSPM-related death.

Larger tumor size predicts nodal involvement in patients with follicular thyroid carcinoma.

AIMS AND BACKGROUND: Lymph node metastases are rare in patients with follicular thyroid carcinoma, with an average incidence of 5.5% of all cases reported in the literature. In the present study we focused on the search for risk factors predictive of lymph node involvement in patients with follicular thyroid carcinoma to plan the most appropriate management and follow-up. METHODS AND STUDY DESIGN: We carried out a cross-sectional study among patients with follicular thyroid carcinoma and lymph node metastasis at diagnosis and patients without lymph node involvement. From January 1998 to April 2008, 930 patients underwent thyroidectomy in our surgical department for a variety of thyroid disorders, 420 (45.2%) of them for a differentiated thyroid carcinoma. The medical records of 55 patients with histological diagnosis of follicular thyroid carcinoma were analyzed. RESULTS: Four patients (7.3%) had lymph node metastasis from follicular thyroid carcinoma at presentation in both the lateral and central neck compartments. Mean tumor size was significantly greater for follicular thyroid carcinomas with nodal metastasis (5.1 ± 1.4 cm) than for those without nodal involvement (3.0 ± 1.2 cm, P <0.010). Among factors supposed to influence the presence of nodal metastasis at diagnosis (age, gender, tumor size, multifocality, tumor poorly differentiated, tumor widely invasive, vascular invasion, thyroid capsular invasion, and extra thyroid invasion), tumor size larger than 4.0 cm was the only factor retained in the multivariate statistical model. CONCLUSIONS: Lymph node dissection must be planned only in the case of large follicular thyroid carcinomas. Since follicular carcinoma is usually diagnosed postoperatively, more attention should be paid to nodal involvement in the tumor re-staging during follow-up of those patients with tumors larger than 4.0 cm in diameter.

Follicular thyroid cancer in a patient with Pendred syndrome.

We present the clinical and molecular studies of a family with Pendred syndrome, in which one affected individual developed follicular thyroid cancer. Two siblings with classic Pendred syndrome triad were operated on because of enormous multinodular goiter. Histopathology showed a follicular thyroid cancer in the male and a multinodular goiter in the female. PDS gene analysis revealed G-to-A transition in the splice donor site of intron 8 (IVS8+1G>A/c.1001+1G>A). Careful surveillance is needed in all cases of thyroid nodules in patients with Pendred syndrome, due to the high risk of malignancy.

Blocking the Thyrotropin Receptor with K1-70 in a Patient with Follicular Thyroid Cancer, Graves' Disease, and Graves' Ophthalmopathy.

Background: We report the therapeutic use of K1-70™, a thyrotropin receptor (TSHR) antagonist monoclonal antibody, in a patient with follicular thyroid cancer (FTC), Graves' disease (GD), and Graves' ophthalmopathy (GO). Methods: A 51-year-old female patient, who smoked, presented in October 2014 with FTC complicated by GD, high levels of TSHR autoantibodies with high thyroid stimulating antibody (TSAb) activity, and severe GO. K1-70 was administered at 3 weekly intervals with the dose adjusted to block TSAb activity. Her cancer was managed with lenvatinib and radioiodine therapy. Results: Following initiation of K1-70 therapy, TSAb activity measured in serum decreased and GO (proptosis and inflammation) improved. On K1-70 monotherapy during the pause in lenvatinib, several metastatic lesions stabilized while others showed progression attenuation compared with that before lenvatinib therapy. Conclusions: These observations suggest that blocking TSHR stimulation with K1-70 can be an effective treatment for GO and may also benefit select patients with FTC and GD.

Thyroid cancers amongst goiter population in a Nigerian tertiary hospital: surgical and radiographic perspective.

BACKGROUND: Goiters are commonly benign, but cases of malignancy can develop. Thyroid cancer is known to be commoner in whites than in blacks and in females than in males. Bone metastasis is a common occurrence and may be the initial manifestation in a small subset. We hope to determine the incidence and the cervical radiographic patterns of thyroid cancer amongst goiter population in Nigeria. METHOD: Surgical, histological and radiographic findings in patients with goiter who had thyroidectomy in our hospital from 1999 to 2006 were reviewed. Those with proven cancer were analyzed for sex, age and radiographic changes using SPSS 11.0 for windows. RESULTS: Thirteen (8.2%) cases out of the 160 goiters were malignant and distant metastases were present in 1.3% at presentation. The histological sub-types of malignant goiters were follicular (5.0%), papillary (1.9%) and poorly differentiated or anaplastic thyroid carcinoma (1.3%). As much as 30% of thyroid cancers demonstrated calcification on plain neck radiograph, which were commonly scattered or diffused. CONCLUSIONS: Carcinomatous goiters occurred in 9.3% of the goiter population studied with predominance of follicular variant. Surgery remains the main stay but was inappropriate in about 1.2% of population with goitre. Aside evidence of bony destruction, TC should be suspected in goiters with mixed (diffused or scattered) calcifications.