bluuebunny/crossref_metadata_2025 huggingface dataset:
Genetic Alterations and Clinical Features in Brazilian Patients With Pheochromocytomas and Paragangliomas
Authors: Lin Wo Julia Mey , Botelho Mariana Coelho , Carvallo Mirna Sánchez , de Sousa Rafaela Marchon , Nascimento João Bosco , Lima Vinicius , Macedo Ana Sofia , Carvalho Denise Pires , Coelho Araujo Paula Bruna Mattos , Lima Jorge , Soares Paula , de Oliveira Naliato Erika Cesar , Violante Alice H D
Published: May 2021

Pheochromocytomas and paragangliomas are tumors derived from chromaffin cells which result from mutations of at least six different genes as autosomal dominant disorders. We evaluated the existence of correlations between genetic alterations and clinical data in 16 patients with pheochromocytomas and/or paragangliomas. From 2007 to 2019, 13 patients with pheochromocytoma [3 men, medium age 39 years (14–61)] and 3 with paraganglioma [1 men, medium age 33 years (22–35)] were evaluated regarding the presence of genetic mutations and possible correlations between the latter and some clinical features. Besides the mutations, tumor size, symptoms and signs present by the time of the diagnosis were studied. Four patients had pathogenic mutations (SDHB deletion encompassing the promoter and exon 1, C98Y in the SDHB gene, N78S in the VHL gene, and C634R in the RET gene) and one subject had a V90M variant in the TMEM127 gene. Two patients did not present mutations and nine had nonpathogenic mutations. Regarding the presence of clinical features before treatment, there was a predominance of arterial hypertension (75.0%), while the prevalence of tachycardia, abdominal pain and headaches was respectively 12.5%, 12.5% and 6.25%. There was no significant difference between the age of patients with pathogenic mutations and that of the other patients (31.2 vs. 38.6 years, p= 0.3952). Moreover, there were no differences regarding the prevalence of pheochromocytoma (p= 0.2143) or clinical features (p: hypertension= 0.6346, tachycardia= 0.4583, abdominal pain= 0.5417, headaches= 0.6875), or tumor dimensions (p= 0.4578) when the two groups were compared. However, the prevalence of paragangliomas was higher in patients with pathogenic mutations (p= 0.0179). In patients with pheochromocytoma and paraganglioma, the absence of correlations between pathogenic mutations and clinical features increases the importance of the genetic studies in the determination of treatment and prognosis of these tumors. Furthermore, subjects with germline mutations associated with pheochromocytoma and paraganglioma should undergo lifelong clinical, biochemical and imaging surveillance and their families should receive genetic counseling.
Interfering Medications in Older Adults on Thyroid Hormone Replacement: Who Is at Risk?
Authors: Beeson Rachel , Coe Antoinette B , Reyes-Gastelum David , Haymart Megan R , Papaleontiou Maria
Published: May 2021

Background: Thyroid hormone prescriptions have steadily increased in the past few years with levothyroxine being one of the most frequently prescribed medications in the United States. Population-based studies have shown that older age is a significant predictor for thyroid hormone initiation, with use continuing long-term. Thyroid hormone management in older adults is complicated by the presence of comorbidities and polypharmacy, particularly due to medications that can interfere with thyroid function tests. However, the prevalence of concurrent use of thyroid hormone and interfering medications in older adults and patient characteristics associated with this practice remain unknown. Methods: We conducted a population-based, retrospective cohort study of 538,137 thyroid hormone users aged ≥65 years from the Corporate Data Warehouse of the Veterans Health Administration (2004-2017). First, we described the prevalence of concurrent use of thyroid hormone and medications that commonly interfere with thyroid function tests (i.e., prednisone, prednisolone, carbamazepine, phenytoin, phenobarbital, amiodarone, lithium, interferon-alpha, tamoxifen). Then, we performed a multivariable logistic regression analysis to determine patient characteristics associated with concurrent use of thyroid hormone and at least one interfering medication during the study period. Covariates included in the model were patient age, sex, race, ethnicity and number of comorbidities. Results: Overall, 170,261 (31.6%) of patients were on at least one interfering medication while on thyroid hormone during the study period (median follow up 56 months). Non-white race [odds ratio (OR) 1.18, 95% confidence interval (CI) 1.15-1.21], compared to white race), Hispanic ethnicity (OR 1.11, 95% CI 1.08-1.14, compared to non-Hispanic), female sex (OR 1.12, 95% CI 1.08-1.15, compared to male sex), and presence of comorbidities (e.g. Charlson-Deyo Comorbidity Score ≥2, OR 2.47, 95% CI 2.43-2.52, compared to zero) were more likely to be associated with concurrent use of thyroid hormone and interfering medications. Older age (e.g., ≥85 years, OR 0.47, 95% CI 0.46 - 0.48, compared to age 65-74 years) was less likely to be associated with concurrent use of thyroid hormone and interfering medications. Conclusions: Almost one-third of older adults on thyroid hormone were taking medications that have been known to interfere with thyroid function tests. Our study highlights the complexity of managing thyroid hormone replacement in older patients, many of whom are at risk for adverse effects in the context of polypharmacy and comorbidities.
Does Primary BCG Vaccination Prevent Autoimmune Hypothyroid Disease?
Authors: Agrawal Kanhaiya , Basak Preetam , Dutta Pinaki , Walia Rama , Bhansali Anil , Sachdeva Naresh
Published: May 2021

Autoimmune thyroid disease (AITD) involves autoimmune destruction of thyrocytes marked by the presence of anti-TPO and/or anti-TG antibodies. In autoimmune diseases, an immunomodulatory role of BCG vaccination has been reported with decreased autoantibody production and induction of regulatory T cells (Tregs). We hypothesize that the loss of efficacy of BCG vaccine in adulthood might be associated with the appearance of AITD. To evaluate the protective efficacy of primary BCG vaccination, we assessed the anti-mycobacterial responses, thyroid function, and anti-thyroid autoimmune responses in autoimmune subclinical hypothyroid (SCH) (n=39) and non-autoimmune SCH (n=25) subjects. The anti-mycobacterial responses were determined by the Mantoux test and by BCG induced in-vitro proliferation of peripheral blood mononuclear cells in terms of proliferation index (PI). The immunophenotyping of autoreactive CD8+ T cells recognizing TPO derived epitopes was performed by flow cytometry using APC labelled dextramers by flow cytometry in patients with HLA-A*02 and HLA-A*24 alleles. We observed that the autoimmune SCH group had more subjects with a negative Mantoux reaction (less than 5mm) (61.5% vs 33.3%, p= 0.01). The PI with BCG stimulation was similar in both groups (2.55±0.31 vs 2.51±0.41, p = 0.667). The correlations (r) between Mantoux test and PI in autoimmune SCH and non-autoimmune SCH were, insignificant. The autoimmune SCH group had more subjects with diffused thyroiditis (43% vs 13%, p= 0.02). The SCH subjects with the presence of a BCG scar (n=11) had lower TSH (µIU/ml) (7.94±1.67 vs 6.75±1.56, p= 0.026) levels and lower frequencies of TPO-reactive CD8+ T cells (3.35±0.72% vs 1.77±0.98%, p= 0.061), as compared to subjects with the absence of a BCG scar (n = 53). The SCH subjects with positive Mantoux test (more than 10mm) demonstrated similar titres of anti-TG antibody (IU/ml) [(230 (56.71-508.90) vs 85.5 (15-345.9), p= 0.055] and anti-TPO antibody (IU/ml) [29.9 (5-135) vs 12 (5-83), p= 0.665)] as compared to those with a negative Mantoux test. The TPO-reactive CD8+ T cells and anti-TG antibody titres had a negative correlation in autoimmune SCH (r= -0.695, p=0.038) and non-autoimmune SCH (r= -0.642, p=0.024) subjects. Next, we observed a similar frequency of TPO-reactive CD8+ T cells in non-autoimmune and autoimmune SCH subjects (8.40±3.74% vs 9.02±4.17% p= 0.937). The absence of anti-TPO or anti-TG antibody did not rule out the presence of any underlying autoimmunity. The persistence of the protective effects of either BCG vaccination or exposure to Mycobacterium species might be involved in modulating autoimmune responses towards the thyroid gland. Our study warrants further research on the immunomodulatory role of BCG in adult subjects with a family history of autoimmune diseases including AITD.
Management of Thyrotoxicosis Induced by PD1 or PD-L1 Blockade
Authors: Brancatella Alessandro , Lupi Isabella , Montanelli Lucia , Ricci Debora , Viola Nicola , Sgrò Daniele , Antonangeli Lucia , Sardella Chiara , Brogioni Sandra , Piaggi Paolo , Molinaro Eleonora , Bianchi Francesca , Aragona Michele , Antonuzzo Andrea , Sbrana Andrea , Lucchesi Maurizio , Chella Antonio , Alfredo Falcone , Del Prato Stefano , Elisei Rossella , Marcocci Claudio , Caturegli Patrizio , Santini Ferruccio , Latrofa Francesco
Published: May 2021

Context: Thyrotoxicosis is a common immune-related adverse event in patients treated with PD1 or PD-L1 checkpoint inhibitors. A detailed endocrinological assessment, including thyroid ultrasound and scintigraphy is missing, as are data on response to treatment and follow-up. Objectives: To better characterize the thyrotoxicosis secondary to immune checkpoint inhibitors, gaining insights into pathogenesis and informing management. Methods: We conducted a prospective cohort study of 20 consecutive patients who had normal thyroid function before starting immunotherapy and then experienced thyrotoxicosis upon PD1 or PD-L1 blockade. Clinical assessment was combined with thyroid ultrasound, scintigraphy, and longitudinal thyroid function tests. Results: Five patients had normal scintigraphic uptake (Sci+), no serum antibodies against the TSH receptor, and remained hyperthyroid throughout follow-up. The other 15 patients had no scintigraphic uptake (Sci-) and experienced destructive thyrotoxicosis followed by hypothyroidism (N= 9) or euthyroidism (N= 6). Hypothyroidism was more readily seen in those with normal thyroid volume than in those with goiter (P= 0.04). Among Sci- subjects, a larger thyroid volume was associated to a longer time to remission (P<0.05). Methimazole (MMI) was effective only in Sci+ subjects (P<0.05). Conclusions: Administration of PD1 or PD-L1 blocking antibodies may induce two different forms of thyrotoxicosis that appear similar in clinical severity at onset: a type 1 characterized by persistent hyperthyroidism that requires treatment with MMI, and a type 2 characterized by destructive and transient thyrotoxicosis that evolves to hypo- or eu-thyroidism. Thyroid scintigraphy and ultrasound help differentiating and managing these two forms of iatrogenic thyrotoxicosis
The Potential Impact of the COVID-19 Pandemic on Clinical Management of Thyroid Disorders in Japan
Authors: Inoue Kosuke , Noh Jaeduk Yoshimura , Yoshihara Ai , Watanabe Natsuko , Watanabe Masako , Fukushita Miho , Suzuki Nami , Hoshiyama Ayako , Mitsumatsu Takako , Suzuki Ai , Kinoshita Aya , Mikura Kentaro , Yoshimura Ran , Sugino Kiminori , Ito Koichi
Published: May 2021

Background: The indirect influence of the coronavirus disease 2019 (COVID-19) pandemic on clinical practice has received great attention. However, the evidence about how the pandemic has affected clinical management of hypothyroidism and hyperthyroidism, two common diseases worldwide, is lacking. We therefore aimed to examine the trends in the number of outpatients with thyroid disorders and their thyrotropin (TSH) levels before and during the pandemic in Japan. Methods: This cohort study included all patients aged ≥20 years who visited Ito Hospital, one of the largest hospitals that specialize in thyroid disorders in Japan, during 2019/1-2020/6. Our outcomes of interest were 1) trends in the aggregated number of visits at the clinic and 2) trends in average TSH levels from January 2019 to June 2020. The trends in TSH according to the clinic visit in early 2020 were assessed utilizing difference-in-difference models controlling for age, sex, and city of residence, stratified by each medication use (i.e., levothyroxine [LT4], antithyroid drug [ATD], potassium iodine [KI], or no medication). Results: During 2019/1-2020/6, we observed 517,412 visits at Ito Hospital for thyroid disorders, and the average number of visits per month was significantly decreased for both the first visits (1,995 in 2019 vs. 1,268 in 2020; reduction rate, 36%; p<0.001) and the follow-up visits (29,509 in 2019 vs. 21,959 in 2020; reduction rate, 26%; p<0.001). Among 15,455 patients who had been followed in 2019, we found a higher TSH at the follow-up visits during 2020/4-2020/6 among patients with LT4 who did not visit the clinic during 2020/1-2020/3 than those who did (difference-in-difference [95%CI]=+1.77 [1.25-2.29], p<0.001). We also found decreased trends in TSH among patients with ATD or KI who visited the clinic during 2020/1-2020/3 (p<0.001 for both categories), but not among patients with no medications (p=0.29). Conclusions: In this large cohort in Japan, we found the decreased number of outpatients with thyroid disorders since 2020/1 with a nadir in 2020/4. Using individual-level data, we also found the association between visiting the clinic in early 2020 and TSH control at the following visit among patients with medications. These findings highlight the importance of careful monitoring of patients with medications for thyroid disorders during the COVID-19 pandemic.
Thyroid Function Before, During and After COVID-19
Authors: Eu Khoo Bernard Chong , Tan Tricia , Mills Edouard , Clarke Sophie A , Patel Bijal , Modi Manish , Phylactou Maria , Eng Pei Chia , Thurston Layla , Alexander Emma C , Meeran Karim , Comninos Alexander N , Abbara Ali , Dhillo Waljit Singh
Published: May 2021

Context: The effects of COVID-19 on the thyroid axis remain uncertain. Recent evidence has been conflicting, with both thyrotoxicosis and suppression of thyroid function reported. Objective: We aimed to detail the acute effects of COVID-19 on thyroid function and determine if these effects persisted upon recovery from COVID-19. Design: Cohort observational study. Participants and Setting: Adult patients admitted to Imperial College Healthcare National Health Service Trust, London, UK with suspected COVID-19 between March 9 to April 22, 2020 were included, excluding those with pre-existing thyroid disease and those missing either free thyroxine (FT4) or TSH measurements. Of 456 patients, 334 had COVID-19 and 122 did not. Main Outcome Measures: TSH and FT4 measurements at admission, and where available, those taken in 2019 and at COVID-19 follow-up. Results: Most patients (86·6%) presenting with COVID-19 were euthyroid, with none presenting with overt thyrotoxicosis. Patients with COVID-19 had a lower admission TSH and FT4 compared to those without COVID-19. In the COVID-19 patients with matching baseline thyroid function tests from 2019 (n=185 for TSH and 104 for FT4), both TSH and FT4 were reduced at admission compared to baseline. In a complete cases analysis of COVID-19 patients with TSH measurements at follow-up, admission and baseline (n=55), TSH was seen to recover to baseline at follow-up. Conclusions: Most patients with COVID-19 present with euthyroidism. We observed mild reductions in TSH and FT4 in keeping with a non-thyroidal illness syndrome. Furthermore, in survivors of COVID-19, thyroid function tests at follow-up returned to baseline.
“High Risk” Features of Differentiated Thyroid Cancer Are Commonly Found in Autopsy Studies: Implications for the ATA Guidelines
Authors: Robenshtok Eyal , Neeman Bar , Reches Liran , Ritter Amit , Bachar Gideon , Shimon Ilan , Mizrachi Aviram
Published: May 2021

Background: While the popularity of lobectomy for differentiated thyroid cancer (DTC) has increased since the 2015 American Thyroid Association guidelines, several recent studies reported that “high risk” histological features may be found in up to half of lobectomy specimens, questioning the validity of this approach. In turn, the actual risk associated with some “high risk” features (multifocality, minimal extra-thyroidal extension (ETE), and small lymph node (LN) metastases) has been questioned in recent years. Aim: To assess the prevalence of “high risk” pathological features in occult DTC detected in autopsy studies. Methods: Meta-analysis of autopsy studies of the thyroid gland in subjects without history of thyroid cancer. Studies with DTC lesions and details on histological features were included. Results: Twenty nine studies including 8,750 subjects fulfilled the inclusion criteria, with incidentally discovered DTC in 740 autopsies (prevalence of 8.5%). Age was reported in 17 studies, with a median age of 61 years (range 41-68 years). Multifocality was reported in 27 studies with a calculated event rate of 28.2% (95%CI 23.1% to 33.8%, random effect), with bilateral involvement in 18% (95%CI 12.6%-25/1%). Minimal ETE was reported in five studies, with an event rate of 24.5% (95%CI 9.3% to 50.7%, random effect), and the presence of LN metastases was reported in 13 studies with an event rate of 11% (95%CI 6.1% to 19.1%, random effect). Vascular invasion was reported in seven studies with an event rate of 16% (95%CI 4% to 47%, random effect). Conclusions: “High risk” histological features are common in occult DTC found in autopsy studies, and do not seem to be markers of aggressive disease. These data support a less aggressive therapeutic approach in patients with microscopic “high risk” features which were not detected on pre-operative ultrasound.
BRAF-Like and RAS-Like Thyroid Cancer is Characterized by Distinct Metabolic Phenotypes
Authors: Kumari Sonam , Adewale Ruth , Thakur Shilpa , Cardenas Stephanie , Klubo-Gwiezdzinska Joanna
Published: May 2021

Background: Next generation sequencing has led to the categorization of thyroid cancer (TC) based on the molecular and transcriptomic profile into the BRAF-like and RAS-like tumors. The BRAF-RAS score (BRS) has been developed to quantify the extent to which the gene expression profile resembles either the BRAFV600E- or RAS-mutant profiles and is utilized as a continuous measure from -1 to +1, respectively. Oncogene-driven signaling pathways have an impact on the intracellular metabolism– glycolysis and oxidative phosphorylation (OXPHOS). There are limited data on the genotype-metabolic phenotype correlation in TC cells. Therefore, the goal of this study was to perform a comprehensive analysis of the association between the BRS and TC cell metabolism. Methods: We analyzed the mRNA expression of key enzymes involved in glycolysis (lactate dehydrogenase LDHA) and OXPHOS (ATP synthase) in 496 BRAF-like and RAS-like human TC tissue samples based on The Cancer Genome Atlas. We performed an in vitro study using 8 TC cell lines– 4 BRAF-like with BRS between -1 and 0, and 4 RAS-like with BRS between 0 and +1. OXPHOS was determined by measuring oxygen consumption rate (OCR) of each cell line using Seahorse XF Cell Mito Stress Test Kit, while Seahorse XF Glycolysis Stress Test Kit was used to measure the extracellular acidification rate (ECAR) due to anaerobic glycolysis The association between the OCR, ECAR and BRS was tested using the Pearson correlation coefficient (r). Student T-test was used to compare the continuous variables between the groups with a p-value of ≤ 0.05 as statistically significant. Results:RAS-like tumors were associated with higher mRNA expression of the OXPHOS marker ATP synthase than BRAF-like lesions, as evidenced by a moderate positive correlation (r = 0.5) between ATP synthase expression and BRS. BRAF-like tumors were characterized by a relatively higher mRNA expression of a glycolytic enzyme LDHA, as documented by a moderate negative correlation (r = -0.6) between LDHA expression and BRS. Consistently, functional in vitro studies revealed that RAS-like cell lines had a higher OXPHOS compared with BRAF-like cell lines (maximum OCR: 2538.4±1601.3 vs 548.5±276.5, p=0.049, respectively). The glycolysis rate was comparable between RAS-like and BRAF-like cell lines (maximum ECAR: 1290.4±520.5 vs 2399.9±1413.1, p=0.19, respectively). There was a strong positive correlation between the BRS and OCR (r=0.78) and a low to negligible negative correlation between BRS and ECAR (r=-0.26) in examined TC cell lines. Conclusions:BRAF-like and RAS-like tumors are characterized by distinct metabolic phenotypes with RAS-like TC more likely to utilize OXPHOS to meet metabolic demands. Therapeutic strategies targeting oncogene-driven signaling pathways and cancer metabolism based on distinct metabolic phenotypes may provide an individualized approach to TC therapy.
Quality of Life in Patients With Low and Very Low Risk Differentiated Thyroid Cancer Who Underwent Thyroidectomy in Quito-Ecuador 2020
Authors: Baquero Stefany A , Hill Dana M
Published: May 2021

Low-risk papillary thyroid cancer (less than one centimeter and entrusting the thyroid) is a common pathology, over-diagnosed and therefore mainly over-treated in young women. Considered a public health problem mainly by two premises: 1) psycho-emotional involvement in people who suffer from it and undergo treatments; 2) and because unnecessary interventions are sometimes carried out that represent a futile cost to the health budget, especially for emerging economies such as the Ecuadorian. Objective: Demonstrate the affectation of the quality of life (QoL) after total thyroidectomy in patients with differentiated thyroid cancer of low and very low risk, who underwent surgery with or without adjuvant radioactive iodine treatment. In addition, to identify if variables such as gender, age, and sequelae of surgery such as hypoparathyroidism and scar influence QoL. M&M: A mixed study (qualitative-quantitative) was carried out, where information was collected electronically (via the whats app) and video call from 25 patients who have been affected by low and very low-risk thyroid cancer, in follow-up in the General Hospital San Francisco de Quito. After approval of the study by the teaching department and the ethics committee, we contacted the patients and asked for demographic data (age, gender); clinical data (use of levothyroxine, calcium); and they were also asked to fill out a self-applicable survey of the quality of life of the University of Washington (UW-Qol v.4). Subsequently, an interview with semi-structured questions was carried out and the participants were asked to make a graph of their neck. Results: In the UW-QoL v.4, it was shown that the physical aspects of quality of life, (chewing, swallowing, shoulder, speech, taste, and saliva) scored 90 points on average, did not present as much impact as the emotional aspects (pain, mood, activity, appearance, recreation, and anxiety) with an average of 83 points. In the interview and in the drawing it is corroborated that the emotional aspect where the appearance with the scar and the decrease in activity is included determine a worse quality of life. Neither gender nor age, nor the appearance of hypoparathyroidism determines a worse QoL. Discussion: The QoL for the WHO has elements that influence the physical and emotional health of a subject, their state of independence, and their social and environmental relationship. The study showed that QoL is affected with low and very low risk thyroid cancer on an emotional level, but not physically. This leads us to raise the possibility that differentiated thyroid cancer due to its low risk of mortality and recurrence in patients could be kept on follow-up and benefit from surgery only in the case that in active follow-up, it increased and became intermediate risk (ATA). Studies with a larger patient population are required to determine if support networks are an important parameter that affects QoL.
A Case of Diffuse Sclerosing Variant of Papillary Thyroid Cancer: An Aggressive Variant Presenting With Recurrent Locoregional Nodal Disease
Authors: Cruz Yaniris García , Báez Negrón Laisha M , Mangual García Michelle Marie , González Alex N
Published: May 2021

Diffuse sclerosing variant (DSV), a subtype of papillary thyroid carcinoma (PTC), has been considered more aggressive than classical PTC given that it usually presents with extrathyroidal invasion and lymph node metastasis at the time of diagnosis. Data about the risk of recurrence and prognosis is still debatable. Hence, we report a 29-year old woman with recurrent DSV-PTC that presented with pulmonary metastasis after multiple surgical interventions, radioactive iodine (RAI) therapy and a negative whole-body scan (WBS) ten months prior to this finding.

A 29-year old woman without history of systemic illness, family history of thyroid cancer or neck radiation exposure, developed diffuse goiter at age 23. A thyroid and neck ultrasound revealed an enlarged heterogeneous thyroid gland with innumerable small bright echogenicities scattered throughout and bilateral neck adenopathy. No thyroid nodules were seen. Anti-thyroglobulin antibodies (anti-Tg Ab) were positive. A fine needle aspiration biopsy (FNAB) was positive for PTC with cytologic features suggestive of DSV. Subsequently, total thyroidectomy was performed, and 15 lymph nodes were positive for PTC. Thyroid suppression therapy was started maintaining goal of TSH <0.1ng/dL. Patient had a second neck dissection one month later, where 7 lymph nodes were positive for PTC. Pathology revealed chronic lymphocytic thyroiditis with bilateral multifocal PTC and staging pT3N1b. Two months after thyroidectomy, RAI therapy was provided with 153.6mCi of I-131. Post RAI therapy WBS and SPECT/CT demonstrated persistent metastasis to lymph nodes. After this finding, a third left neck dissection was done with additional lymph nodes resection positive for PTC. A second RAI therapy with 138mCi of I-131 was administered the following year. Continued surveillance suggested recurrence of PTC due to new suspicious nodules on neck along with increased anti-Tg Ab level from 44.64 to 95 IU/mL. FNAB confirmed PTC of five different locations of the thyroid bed. She had two additional neck dissections. Metastasis of lymph nodes was confirmed at multiple levels in the right neck and central compartment. Ten months after being without evidence of PTC recurrence in previous WBS and FDG-PET/CT, she started to develop hemoptysis. A neck and chest CT scan demonstrated innumerable bilateral hyperdensities consistent with pulmonary metastasis. At this time, TSH continued suppressed in 0.06 mIU/mL but, anti-Tg Ab had increased to 160 IU/mL.

DSV-PTC has been shown to be at an advanced stage upon diagnosis. Furthermore, it has been documented that distant metastasis could also be present at this time with pulmonary metastasis being the most common. Nonetheless, some authors suggest that the advanced presentation could be due to delayed diagnosis rather than DSV intrinsic behavior. Besides its aggressive nature, DSV-PTC risk of recurrence remains controversial.
Anaplastic Thyroid Cancer Presenting With Brain Metastasis: 17-year Progression Free Survival
Authors: Howard Kathryn Kay , Lapkus Morta , Luehmann Natalie , Nagar Sapna , Czako Peter
Published: May 2021

Anaplastic Thyroid Cancer is the most aggressive thyroid cancer with a median survival of just five months. Long term survival has been reported in locally aggressive cases but has yet to be reported in metastatic disease. This is a report of a 34-year-old male who presented with symptoms of dizziness, confusion, intermittent headaches, and erratic behavior for two weeks found to have metastatic anaplastic thyroid cancer. CT of the head revealed a 1 cm ring enhancing lesion and he was taken to the operating room for a left parietal craniotomy with mass removal. Initial pathology suggested papillary thyroid origin. His neck exam revealed a palpable 3 cm mass in the right thyroid lobe and he subsequently underwent total thyroidectomy. Final pathology revealed anaplastic carcinoma identical to the brain lesion. Post-operatively, he underwent 15 cycles of whole brain radiation therapy. Two additional brain lesions were identified after thyroidectomy and a third was identified after whole brain radiation. He underwent stereotactic radiosurgery of these three lesions less than two months after thyroidectomy. The patient went on to receive modified mantle field irradiation to the neck, thyroid bed, and the upper mediastinum and chemotherapy with doxorubicin for 6-8 weeks and temozolomide for 2 years. Radioactive iodine treatment was not administered. The patient has currently survived 17 years and his persistent, but stable, brain lesions are being followed with serial imaging. He remains clinically and neurologically asymptomatic. This is the first case presenting with long-term survival in a patient with metastatic anaplastic thyroid carcinoma.
Coincidence? - Graves’ Disease & Thyroid Cancer
Authors: Correia Sara , Almeida Lucia Santos , Silva José Diogo , Tavares Patricia , Rocha Gustavo Melo , Oliveira Maria Joao
Published: May 2021

Background: DG coincidently with thyroid carcinoma has been reported as a rare phenomenon. It was thought that DG would be a protective condition in the development of cancer. However, published studies indicate the opposite, reporting an increased prevalence of differentiated thyroid cancer in DG compared to the general population. Some authors even report greater aggressiveness of this type of cancer in the presence of DG, with higher rates of, multifocality, metastatic disease and with a higher risk of recurrence. Clinical Case: Female, 46 years old, smoker 10 U.M.A., sent to the Endocrinology consultation due to symptomatic hyperthyroidism. No history of exposure to cervical radiotherapy, contact with iodinated products or cervical pain. Analytically, TSH <0.008 uUI / mL (0.27-4.2), free T4 4.09 ng/dL(0.93-1.70), free T3>20 pg/mL(2.57-4, 43), high levels of anti-thyroid and anti-TSH receptors 11.4IU/L (N <1.75), diagnosing with Graves’ disease. The thyroid ultrasound revealed a globose and hypervascularized thyroid. In the right hemithyroid, an echogenic nodular area of ​​ill-defined limits of about 12mm was identified, associated with some hyperechogenic elements. Bilateral cervical and submandibular lymph nodes were visualized with a short 8 mm axis, highlighting a ganglion in the right jugular chain, questioning the presence of millimeter echogenic foci. She started metibasol, with improved thyroid function and opted for ultrasound surveillance. Four months later, she repeated the ultrasound of the thyroid, maintaining a hypercogenic area, with ill-defined limits in the right lobe, with a 13mm longest axis. She also maintained adenopathies in the right jugulo-carotid chain, rounded, without hilum, the largest one with 13x9x17mm, and it was performed a fine needle aspiration of the ganglion. There was no measurement of thyroglobulin in the wash. The morphological changes were compatible with ganglion metastasis due to papillary thyroid carcinoma with a predominantly follicular pattern. She started 5% lugol solute, 7 drops every 8 hours for 8 days before surgery and underwent total thyroidectomy and central and lateral lymphadenectomy, with the identification of a mixed, multifocal papillary carcinoma. in the right lobe and isthmus, the microscopic size of the largest focus was 40mm, without invasion of the capsule or vascular invasion, with ganglion metastases in the lateral (9/46) and central district (6/6) (pT2N1b). She underwent treatment with I131 at a dose of 120mCi. Conclusion: This clinical case stands out for its uniqueness, given the simultaneity of Graves’ disease and thyroid cancer. The presence of cervical adenomegaly, which is rare in DG, increased clinical suspicion. Due to the increase of the adenopathy in a short period of time, we decided to perform a biopsy, which in this case was essential for the diagnosis and subsequent treatment.
Not Your Typical “Lipoma”; An Unusual Case of Thyroid Cancer Presenting With a Skull Lesion
Authors: Abdulhadi Basma , Bahl Deepti
Published: May 2021

Background: Bone metastases from thyroid cancers tends to more commonly afflict the long bones, pelvis, ribs, vertebrae and sternum. Skull metastases are exceedingly rare being found in only ~2.5% of patients with thyroid cancer, more commonly in patients with Follicular thyroid carcinomas. We present an unusual case of thyroid cancer presenting with skull metastasis. Clinical Case: A 55 year- old male with a slowly growing skull lesion was referred to our center after an attempt to remove this scalp lesion was aborted as the lesion extended through a calvarial defect. This lesion was noted by the patient 1 year prior to presentation and was slowly growing in size. He opted for watchful monitoring as this was presumed to be a lipoma at the time. Imaging revealed a 6.4 x 4.6 x 6.3 cm lesion in the left parietal region with a large extra-axial and soft tissue components with intervening bone destruction as well as adjacent dural thickening. Differential for the lesion given the radiological appearance included meningioma, hemangiopericytoma, or an osseous/dural metastasis with an unclear primary malignancy. Excision of the extra-axial parietal lesion was consistent with metastatic thyroid carcinoma (follicular variant of papillary carcinoma). Further imaging revealed a multi nodular goiter with a prominent 6 cm left thyroid nodule. Patient had no obstructive symptoms. He underwent a total thyroidectomy with findings of a 6.8 cm minimally invasive follicular carcinoma with multifocal capsular invasion and a focus of vascular invasion. The right lobe revealed 1.5 cm classic PTC. Notably, margins were free of disease and cervical lymph nodes were negative for disease. Imaging revealed no other metastatic lesions. Patient received RAI after his total thyroidectomy and was started on suppressive doses of levothyroxine. He has been followed with annual MRI Brain, USG thyroid and Thyroglobulin levels and remains free of recurrence for the past 36 months. Conclusion: Thyroid cancer can present with skull metastasis without causing significant morbidity. This is a rare manifestation of disease and can be easily misdiagnosed. This case highlights the importance of keeping a broad differential when evaluating skull lesions.
Sarcoidosis-Lymphoma Syndrome Associated With Primary Thyroid Lymphoma: A Case Report
Authors: Yamashita Saori , Matsuda Yayoi , Muta Hiroki , Nagao Toshihiko , Nakao Hiroshi , Haji Shojiro , Nakashima Yasuhiro , Sakamoto Ryuichi , Ogawa Yoshihiro
Published: May 2021

Background: Sarcoidosis is occasionally accompanied by hematologic malignancies, including lymphoma, called sarcoidosis-lymphoma syndrome. Although the mechanism underlying the induction of lymphomas is still unknown, understanding the immunological background of sarcoidosis could help explain the possible mechanisms of the induction of lymphomas. Case Presentation: A 52-year-old woman was diagnosed chronic thyroiditis with normal thyroid function. One year later, she underwent a screening chest radiograph and identified bilateral hilar adenopathy and mediastinum lymphadenopathy. Subsequent mediastinoscopy demonstrated sarcoidosis. Because of the lack of clinical symptoms, steroid treatment was not initiated and regular follow-up was performed. One and a half years after the diagnosis of chronic thyroiditis, she presented with rapid swelling of the thyroid gland. FDG-PET/CT showed intense uptake of FDG in the thyroid gland and multiple lymphadenopathy. Fine-needle aspiration (FNA) cytology of the thyroid gland was only suggestive of a lymphoproliferative disorder and did not provide a definitive diagnosis. Partial thyroidectomy was performed, and the pathology indicated diffuse large B-cell lymphoma (DLBCL) such as high-grade transformation of extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) lymphoma. The results of an examination of a paraffin block histopathology specimen by fluorescence in-situ hybridization (FISH) detected BCL6 rearrangement (3q27), which is the most common chromosomal abnormality in DLBCL. After the treatment with R-EPOCH (rituximab, etoposide, vincristine, doxorubicin, cyclophosphamide, and prednisone) chemotherapy, the thyroid gland enlargement has improved markedly, while the lymph nodes remained swelling, that suggested lymph node involvements were due to sarcoidosis. Conclusions: Rapid swelling of the thyroid gland in the setting of chronic thyroiditis should raise suspicion for thyroid lymphoma. Furthermore, our present case might suggest that sarcoidosis accelerate the development and high-grade transformation of thyroid lymphoma. To our knowledge, this is the first reported case of sarcoidosis and primary thyroid lymphoma in the same patient.
The Importance of Lymph Node Dissection in Medullary Thyroid Carcinoma Management
Authors: Villavicencio Camila Alejandra , Franco-Akel Alberto , Belokovskaya Regina
Published: May 2021

Medullary thyroid carcinoma (MTC) is a rare endocrine malignancy that arises from calcitonin (Ct) parafollicular C-cells. Most cases are sporadic with frequent presentation being a solitary thyroid nodule. Total thyroidectomy with central neck dissection of lymph nodes (LN) is the standard treatment for MTC. The need for lateral neck dissection is controversial, with poor efficacy of non-surgical treatments presenting a problem. We present a case of MTC with preoperative Ct >500 pg/mL and negative imaging for metastases who underwent total thyroidectomy without LN exploration with an excellent postoperative biochemical response.

This is a case of a 52-year-old female with a three-year history of anterior neck growth. The repeat fine needle aspiration (FNA) of a, previously negative for malignancy, growing nodule was consistent with MTC. Preoperative Ct and CEA levels were significantly elevated, 834.0 pg/mL and 11.2 ng/dL, respectively; a preoperative pan- CT scan did not reveal any suspicious LN or metastatic lesions and a negative RET oncogene mutation with normal plasma normetanephrines and metanephrines suggested a spontaneous rather than familial MTC. Patient underwent total thyroidectomy without LN exploration. Pathology confirmed MTC stage T1b. The one and three months postoperative follow up showed a significant downtrend with no normalization of Ct and CEA levels, 9.1 – 9.2 and 11.1 – 1.2, respectively. Reoperation for central and lateral neck dissection was considered; however, given the excellent biochemical response as well as the lack of radiographic evidence of disease, it was decided to continue monitoring of Ct and CEA levels for now.

MTC response is monitored by the postoperative serum Ct and CEA levels when compared to the preoperative values. Serum Ct serves as a sensitive tumor marker, which is thought to have correlation with malignancy mass size and its cellular differentiation. The term biochemically cured, refers to the postoperative normalization of CEA and undetectable levels of Ct which carries a 5-year recurrence of 5%. It is believed that the higher the levels and the faster doubling time of these tumor markers the worse is the prognosis. In addition, it is suggested that patient’s age and extent of disease at the time of surgery are proportionally correlated with disease recurrence. However, there are reports of large MTC metastatic deposits with low serum Ct and CEA, rising up the hypothesis that levels reflect cell production potential for tumor markers rather than the number of cells. Reoperation rarely results in biochemical cure, but it may slow disease progression. Normal postoperative Ct levels predict cure; however, the clinical course of those with upper normal limit levels postoperatively is markedly variable. Careful regular biochemical and imaging follow-up will be of the utmost importance for the patient presented in this case.
What Lies Beneath? - Medullary Thyroid Cancer in Nodular Graves’ Disease
Authors: Wang Rongzhi , Vallepu Shirisha R , Chen Herbert , Nambron Rajasree
Published: May 2021

Background: Medullary thyroid carcinoma (MTC) accounts for 1%-2% of thyroid cancers in the United States (US). MTC originates from thyroid parafollicular C-cells, occurring either sporadically or hereditarily as part of type 2 multiple endocrine neoplasia (MEN) or familial MTC (FMTC). Hyperthyroidism is prevalent in approximately 1.2%, and Graves’ Disease (GD) is the most common cause of hyperthyroidism in the US. GD is an autoimmune disorder that results in increased thyroid hormone production due to the stimulation of TSH receptor by thyrotropin receptor antibodies (TRAb). Thyroid carcinoma in general is uncommon in GD patients, while MTC is extraordinarily rare. We report a case of sporadic MTC in GD, which is extremely rare. A recent publication stated that there were only 15 reported cases of MTC coexisting in GD until 2019. Clinical Case: A 62-year-old male with hypertension, diabetes and obesity presented to the endocrine surgery clinic with symptoms of diaphoresis, chest pain and fullness, shortness of breath, and palpitations. The patient had a brother with a pancreatic mass of unknown pathology and multiple family members with thyroid disease. On physical exam, there was a palpable non-tender left-sided nodule with no lymphadenopathy. His FT4 was 8.5 (0.76-1.46 ng/dL), TSH was <0.006 (0.36-3.74 μIU/dL) and thyroid-stimulating antibody was 1.25 (<0.10 IU/L). Ultrasound showed a multinodular goitre with a dominant nodule in the left lower pole measuring 2.3x1.9x1.5 cm. He was diagnosed with GD, treated with methimazole, and his symptoms improved. Subsequent nuclear medicine uptake scan showed diffusely increased uptake and a cold nodule in the left thyroid lobe. Repeat labs showed low TSH (<0.01μIU/dL) and elevated FT4, CEA, calcitonin, PTH, metanephrine, and normetanephrine (1.04 ng/dl, 5.2 (3-5 ng/ml), 796 (<18 pg/ml), 58.10 (18.40-88.00 pg/mL), 90 (< OR = 57 pg/ml) and 222 (< OR = 148 pg/ml), respectively). A thyroid fine-needle aspiration (FNA) was suggestive of MTC (Bethesda Category VI). Total thyroidectomy with left central lymph node dissection revealed a 2.5cm MTC confined in the left lobe with focal lymphovascular invasion. His postoperative course was uneventful, and CEA and calcitonin levels trended down (1.1 ng/ml and <2 pg/mL, respectively). Conclusion: The coexistence of medullary thyroid carcinoma and Graves’ Disease is rare, incidental, with five-year survival rates lower than other thyroid cancers. A delayed diagnosis of MTC would be detrimental. Patients with thyroid nodules and GD are five times more likely to be diagnosed with thyroid carcinoma. Radiation, chemotherapy and thyroidectomy are standard treatment options for MTC, with total thyroidectomy being the preferred option. It is necessary to evaluate patients with GD for possible thyroid cancers, especially in the presence of nodules.
A Case for Lithium Pretreatment Prior to Radioactive Iodine Ablation in Grave’s Disease
Authors: Thakkar Aditi , Chen Constance Lee
Published: May 2021

Radioactive iodine ablation (RAIA) therapy with Iodine-131 (I-131) is an established treatment for grave’s thyrotoxicosis. However, there is 10 to 20% chance of treatment failure. Lithium, a drug used to treat bipolar disorder, has significant effects on thyroid function. The most clinically relevant is the inhibition of thyroid hormone release. It is also known to inhibit colloid formation, and is involved in blocking organic iodine as well as thyroid hormone release from the thyroid gland without an effect on radioiodine uptake. This leads to increased radioiodine retention in the thyroid gland. Here, we present a case which exemplifies this action of lithium. A 46 year old male with a history of atrial fibrillation and grave’s disease presented to the endocrine clinic. TSH was <0.01 and FT4 was 36. RAI uptake (RAIU) scan showed diffusely increased uptakes with 4 and 24 hour values of 61.2 and 54.6 %. He subsequently underwent RAI ablation with 18 mCi of I 131. He then presented three years later with persistent hyperthyroid symptoms. TSH <0.01 and FT4 4.3. RAIU showed 24-h thyroid uptake of 41%. Patient opted for a second treatment with RAIA and was treated with 30 millicuries of I 131. He however continued to have clinical and biochemical evidence of thyrotoxicosis and was started on methimazole (MMI). Although he was biochemically euthyroid on MMI, he continued to complain of hyperthyroid symptoms such as palpitations, tremors and weight loss. When methimazole was briefly held six months after initiation, TSH was undetectable and FT4 had increased from 0.83 to 1.42. He subsequently underwent a third RAIU off MMI which showed normal 4 and 24 hour uptake, measuring 15.7% and 28% respectively. Patient subsequently opted for third trial of RAI ablation with lithium pretreatment. He declined surgery. He was started on lithium 900mg/day for 6 days, starting on the day of RAI ablation. He underwent RAI ablation with 45 mCi I-131. Patient tolerated the procedure well with subsequent tests indicating hypothyroidism requiring levothyroxine supplementation. Patient’s hyperthyroid symptoms resolved. Several factors affect the efficacy of radioiodide therapy for hyperthyroidism including the short persistence of radioiodide in the thyroid gland. In hyperthyroid Graves’ patients, radioactive iodide uptake is enhanced due to presence of TSH receptor antibody, however, radioiodide is also rapidly discharged because of its increased turnover. Lithium can significantly reduce the release of iodine from the thyroid gland and thus increase iodine retention. There is evidence to suggest that adjuvant lithium can increase thyroidal radioiodine uptake in patients with a low baseline RAIU (< 30%). This case demonstrate that lithium can be used safely prior to RAI therapy in cases of RAI ablation failure even with low baseline RAIU.