bluuebunny/crossref_metadata_2025 huggingface dataset:
Utility of Stimulated Thyroglobulin in the Differentiate Thyroid Cancer
Authors: Romero Fabiola , Galeano Sandra , Cabrera Francisco , Vigo Liliana , Laterza Carlos , Thompson Oscar Codas , Valinotti Elizabeth
Published: May 2021

Introduction: The treatment of differentiated thyroid cancer has changed considerably, total thyroidectomy and radioactive iodine ablation represented the initial treatment for these patients, currently with a great debate around the choice of which patient should undergo ablation with radioactive iodine in the post-surgical period. Objective: To determine the values of stimulated thyroglobulin (in hypothyroidism) in patients with differentiated thyroid carcinoma who have had surgery and its relationship with the ATA 2015 recurrence risk stratification and the presence of distant or locoregional metastasis in post ablative total body scan with I131 Methodology: Retrospective study, which included patients with differentiated thyroid carcinoma, patients who have had total thyroidectomy surgery and subsequent ablation with I131 in 45 days at the Central Hospital of Instituto de Prevision Social, from 2011 to 2018. There were evaluated: post-surgical thyroglobulin dosage in hypothyroidism, antithyroglobulin antibody measurement, and total body scan results at 72 hours post ablation with I131. There were excluded: Patients with positive antithyroglobulin antibodies, eu /hyperthyroidism, or incomplete data. Results: 100 patients conformed by women (88.0%), whose average age was 44.7 (± 16.1), intermediate risk 60%, high risk 31% and low risk 9%. According to the stimulated thyroglobulin values, 3 groups were classified: Group A thyroglobulin less than 1 ng/dl 32%, Group B 1 to 10 ng/dl 39%, Group C greater than 10 ng/dl 29%. Of the patients at intermediate risk n: 60, 23 (38%) belonged to group A, 27 (45%) to group B and 10 (17%) to group C. Of high-risk patients n: 31, 7 (22%) belonged to group A, 8 (26%) to group B, and 16 (52%) to group C. Of low risk patients n: 9, 2 (22%) belonged to group A, 4 (44%), group B, and 3 (33%) to group C. Post-ablative body scan detected locoregional or distant metastases in 23 (23%) patients, of which 2 (8.6%) belonged to group A, 6 (26%) to group B, 15 (65%) to group C. They were intermediate risk 10 (43%) and high risk 13 (57%) of them. No low-risk patient presented a positive RCT. There was found a relationship between thyroglobulin and high ATA risk (p <0.05) with positive RCT. Association between thyroglobulin> 10ng / dL and the presence of metastasis (p = 0.0001), Exp (B) 15.1 with R2 25 and 35%. Conclusion: A stimulated postoperative thyroglobulin dosage greater than 10 ng/ dL increases the chances of recurrence 15 times, with 25 to 37% chance of it. So, it would be important to consider ablation with iodine 131 in this type of patients.
Morning Serum Cortisol May Be Less Accurate for Diagnosing Adrenal Insufficiency in Hospitalized Patients, Particularly Those on Opioids
Authors: Colling Caitlin Ann , Nachtigall Lisa B , Biller Beverly M K , Miller Karen Klahr
Published: May 2021

Introduction: The positive predictive value of a low morning serum cortisol to diagnose adrenal insufficiency (AI) is reported to be >90%, which is the basis for guidelines recommending morning cortisol as the first-line test for central AI. A level <3 µg/dL is considered diagnostic. However, studies that established this cut-off were conducted primarily in outpatients, not hospitalized patients in whom diurnal variation may be disrupted. Studies suggest that opioids suppress cortisol levels acutely, may disrupt diurnal cortisol rhythm, and cause adrenal insufficiency in 8–50% of chronically-exposed patients. The impact of hospitalization, particularly in the setting of opioid use, on the accuracy of diagnostics for AI is unknown. We hypothesized that low morning cortisol values in hospitalized patients, especially those prescribed opioids, do not accurately diagnose adrenal insufficiency, as determined by corticotropin stimulation test (CST) peak cortisol <18 µg/dL. Methods: We performed a retrospective analysis of CSTs in hospitalized patients in the Mass General Brigham health system from 5/2015 to 9/2020. Opioid-exposed adults who underwent CST were included if they had a morning cortisol (5–9 AM) result. Control patients were matched by age, gender and race and had no opioid prescriptions within 30 days of testing. Patients were excluded if tested in the outpatient or ICU setting, had a history of cirrhosis or pituitary disease, had an elevated ACTH, were prescribed oral estrogen, or received oral, IV or intraarticular glucocorticoids within 30 days. Results: The analysis included 124 opioid-exposed and 322 control patients, mean (±SD) age 60.8±14.4 and 63.8±15.3y, and 55.6% and 45.0% female, respectively. Twenty-two (17.7%) opioid-exposed and 33 (10.2%) control patients were diagnosed with AI by CST (p=0.031). Nineteen opioid-exposed (15.3%) and 22 control (6.8%) patients had morning cortisol of <3 µg/dL (p=0.005). A morning cortisol <3 µg/dL had a positive predictive value of 36.8% (CI 19.1–59.0%) for AI in opioid-exposed and 50.0% (CI 30.7–69.3%) in control patients. In opioid-exposed patients with low morning cortisol levels, mean daily morphine milligram equivalent and duration of opioid exposure did not differ between those with AI confirmed by CST and those with normal CST (p=0.13 and 0.38, respectively). Conclusion: Among hospitalized patients with suspected AI, those prescribed opioids have a higher prevalence of central AI than controls. Serum morning cortisol <3 µg/dL is not an accurate test for AI in hospitalized patients, including those prescribed opioids in whom low morning cortisol is more prevalent than in controls. Given the risks associated with misdiagnosis of AI, caution should be exercised in relying on morning cortisol values for the diagnosis of AI in hospitalized patients.
An Unusual Case of Coexistence:De-Differentiation of a Papillary Thyroid Carcinoma into SquamousCell Carcinoma
Authors: Enverga Mariel C , Crisostomo Thelma D
Published: May 2021

Background: Squamous cell carcinoma (SCC) of the thyroid is a rare condition comprising less than 1% of thyroid cancer. SCC of the thyroid may arise from de-differentiation of aggressive thyroid carcinomas secondary to chronic thyroid gland inflammation1. Thyroid SCC is a variant of undifferentiated thyroid carcinoma and is also associated with tall-cell variant of Papillary thyroid carcinoma (PTC). Given its aggressive clinical course, early recognition of the disease is essential to management.

Clinical Case: A 67-year-old, Filipino male, presented with anterior neck mass over a period of 11-months. He was clinically euthyroid. Neck ultrasound showed enlarged thyroid gland with hypoechoic left thyroid nodule (1.9cm x 1.2cm) where fine needle aspiration biopsy showed a colloid nodule. Patient then manifested with compressive symptoms, undocumented weight loss and easy fatigability. He had total thyroidectomy with histopathology consistent with Diffuse Sclerosing Variant of PTC with Squamous Differentiation, arising from chronic lymphocytic thyroiditis with extra-thyroidal extension. Immunohistochemical markers showed (+) TTF-1, (+) HBME-1 and (+) PAX – 8. Two months after thyroidectomy, he noticed palpable cervical nodes and hoarseness of voice. PET-CT scan showed hypermetabolism in the thyroid bed and tumor recurrence with 2 FDG-avid lymph nodes, on Level III with SUVS up to 8.5. RAI imaging showed functioning thyroid tissues. Patient had completion thyroidectomy with selective neck dissection within 3 months after initial surgery. Histopathology revealed Keratinizing Squamous Cell Carcinoma metastatic to lymph nodes. Molecular studies were not pursued by patient. Repeat PET/CT Scan showed rapid tumor recurrence in the left thyroid bed with strap muscle and thyroid cartilage infiltration, as well as cervical lymph node invasion. PEG insertion and prophylactic tracheostomy addressed nutritional status and airway protection, respectively. He was treated with course of external beam radiation (60 Gy in 33 fractions). He had concurrent chemotherapy with Carboplatin-Paclitaxel regimen for only 2 cycles. After 13 months of initial presentation, patient eventually succumbed to cardiac arrest.

Conclusion: This transformation of the thyroid is a malignancy with high mortality, with average survival length of only less than a year. Combined modality with surgery, radiotherapy and chemotherapy to prevent disease progression and local recurrence is needed. Multidisciplinary approach is significant in the management due to its poor survival rate.

References: (1)Hararah KM, Gertz JR, Sippel SR, et. Al. (2015) De-differentiation of Conventional Papillary Thyroid Carcinoma into Squamous Cell Carcinoma. Thyroid Disorders Ther 4: 192. doi:10.4172/2167-7948.1000192
An Unusual Riddle of Thyroid Swelling; Hodgkin’s Lymphoma Masquerading as Riedel’s Thyroiditis
Authors: Gunda Rohini , Tyler Xenia , Rehman Shoib Ur
Published: May 2021

Introduction: Thyroid swellings are one of the most common encountered endocrinological presentations however the prevalence of malignancy is about 4-6.5%. Hodgkin lymphomas usually present as neck swelling in form lymphadenopathy and Hodgkin disease affecting the thyroid gland is extremely rare (1-2.5% of all lymphomas). It usually occurs in middle age and has predilection for female gender. It can pose a diagnostic challenge with the histology of sclerosing fibrosis mimicking Riedel’s thyroiditis; another rare cause of stony hard goitre. Case History: A 39yr old female presented with rapidly enlarging painful thyroid mass. She complained of mild dysphagia but denied to have dyspnoea, dysphonia wheeze or stridor. There was no history of weight loss, B symptoms or any significant past illness. Clinically and biochemically she was euthyroid with normal TSH 0.73mU/l(0.35-3.50), Free thyroxine 13pmol/L (8-21), Free T3 3.9pmol/L (3.8-6.0). Blood count showed mild neutrophilia 8.21 (2-7x109/L). IGG subclasses 1-4 were all with normal limits. Initial Ultrasonography demonstrated 4.6 X 3.6cm U3 thyroid nodule extending retrosternally. FNA x2 was THY. Core biopsy demonstrated dense core of fibrous tissue with crushed aggregates of mature lymphoid cells and mixed neutrophils and histiocytes in keeping with fibro inflammatory process suggestive of Riedel’s thyroiditis. Patient was initiated on Prednisolone 100mg OD by the ENT surgeons after MDT discussion and patient had some symptomatic improvement in pain but no discernible reduction in size. Due to side effects from steroids she was referred to endocrinology department. Tamoxifen 20mg BD was started for symptom management. CTNCAP was organised to rule out lymphoproliferative disorder which was negative barring the known thyroid mass. She had no response to Tamoxifen either hence she underwent surgical resection. Surgical resection deemed very difficult due to mass infiltrating the strap muscles and neck vasculature hence wedge resection of the isthmus was done. Histology now revealed bands of dense fibrous tissue with admixed large lymphoid cells showing enlarged, red nucleoli. Immunohistochemistry of the large atypical lymphoid cells expressed CD30, CD15, MUM1, PAX5, CD20, CD79a and BCL6 and diagnosis was revised to Classic Hodgkin lymphoma, nodular sclerosis subtype. She was then referred to haematologist who initiated ABVD chemotherapy and her latest FDG PET scan shows complete metabolic response with significant reduction in the thyroid mass to 17mm X16 mm. Conclusion: Primary thyroid lymphoma can mimic Riedel’s and other forms of fibrosing thyroiditis. Most lymphomas arise from Hashimoto’s thyroiditis. Stony hard neck swellings are difficult to FNA and even core biopsy may not reveal the diagnosis, hence surgical resection and histological diagnosis should be sought earlier as most lymphomas respond well to chemotherapy.
Concurrent Papillary Carcinoma of Thyroglossal Duct Cyst and Thyroid Isthmus, Beyond the Sistrunk Procedure
Authors: Riaz Aiman , Khan Aysha , Jabiev Azad , Osakwe Ibitoro Nnenna
Published: May 2021

Introduction/Background: Papillary carcinoma (PC) originating from the thyroglossal cyst is a rare entity. It is even more uncommon to have concurrent thyroglossal duct cyst PC and papillary thyroid carcinomas (PTC). The surgical approach for such patients would involve a combination of a Sistrunk’s procedure and total thyroidectomy. We describe management of a patient found to have multi focal PC originating from a thyroglossal duct cyst and thyroid isthmus with extensive cervical lymph node metastasis. Clinical Case: 30-year-old male presented to PCP with palpable bilateral cervical adenopathy most prominent in the right supraclavicular region. Neck ultrasound confirmed multiple metastatic appearing nodes (largest 4cm) in the central, right and left lateral cervical compartments as well as a hypoechoic, TI-RADS category 5 right thyroid isthmus nodule. FNA of the cervical nodes confirmed metastatic PTC. Neck CT in addition to extensive cervical adenopathy revealed a 2 cm solid mass inferior to the central hyoid bone with infiltrative borders and calcifications suspicious for a primary tumor. Patient underwent total thyroidectomy with central compartment lymph node dissection, excision of thyroglossal cyst and bilateral modified radical neck dissections. Histopathology report revealed a 2.4 cm thyroglossal duct tumor and a 1.1 cm tumor in the thyroid isthmus, confirming two separate tumors both being classical variants of papillary thyroid carcinoma, with no lympho-vascular invasion and 8/53 positive lymph nodes. BRAF V600E mutation was positive. On follow up, the patient is doing well and has deferred adjuvant radioactive iodine treatment for 6 months for personal reasons. Clinical Lesson/ Conclusion: PC of the thyroglossal cyst with synchronous isthmic PTC merits total thyroidectomy and central compartment dissection in addition to the Sistrunk’s procedure, as the likelihood of local metastasis is high. Presence of BRAF V600E mutation has been identified as a predictor of more aggressive behavior in isolated PC of the thyroglossal duct cyst, suggesting a need for more than a Sistrunk’s procedure in such patients. Our patient, who presented with local lymph node metastasis supports this conclusion. Determining BRAF mutation status preoperatively may be a helpful strategy in planning the extent of surgery. Keywords Thyroglossal duct cyst, Papillary thyroid carcinoma, BRAF mutation
Differentiated Thyroid Carcinoma With Metastatic Presentation: 2 Clinical Cases
Authors: Almeida Lucia Santos , Castro Sofia Fontão , Duarte Hugo
Published: May 2021

Introduction: Papillary thyroid carcinoma is the most common endocrine malignancy. Distant metastasis from differentiated thyroid carcinoma is infrequent, usually seen in lungs and bone. The incidence of bone metastasis is 1%-7% in papillary thyroid carcinoma. Hurtlhe cell carcinoma is a rare malignancy of the thyroid gland that can present with local or distant metastases. Main treatment for metastatic well-differentiated thyroid carcinoma includes radioactive iodine (131I) and surgical resection.

Clinical case 1: In 2019, a 57 year-old woman, without significant prior medical history, with diffuse upper back and thoracic (10th -12th rib location) pain complaints, for over a year, is submitted to full body bone scintigraphy which reveals a lytic lesion located in the 10th left rib: histology is compatible with metastatic disease, from thyroid follicular carcinoma. Thoracic-abdominal-pelvic computed tomography (CT) has no sign of disease, but thyroid ultrasound shows a left located 24 mm nodule. The patient is submitted to total thyroidectomy and after histology revealed a papillary thyroid carcinoma (follicular variant), 131I treatment takes place (5550 MBq /150 mCi). Post–treatment131I scintigraphy presents with neck foci, in relation with thyroid residual tissue along with intense uptake in a massive lesion around the 10th left rib. Excision of this lesion is decided. The patient remains under clinical and imaging surveillance, being treated with levothyroxine 125 µg and without further complications, until today. Clinical case 2: In 2018, a 78 year-old woman, with prior medical history of hypertension and dyslipidemia, is sent to Neurology practice in the set of diplopia of recent onset. During the evaluation, a thoracic CT reveals a single 4 mm pulmonary lesion and a calcified infracentimetric thyroid nodule. The patient is submitted to bronchofibroscopy and immunohistochemistry of the collected tissue was compatible with metastasis of oncocytic thyroid carcinoma. Thyroid nodule citology is suggestive of Hurthle cell thyroid carcinoma. Total thyroidectomy with central neck lymphadenectomy takes place and histology confirms the diagnosis. After 131I treatment (5550 MBq/150 mCi), 131I scintigraphy reveals 131I uptake foci on the neck, in relation with thyroid residual tissue and a pulmonary uptake focus (known lesion). A second 131I treatment is performed and posterior scintigraphy shows improvement of metastatic disease. The patient remains under clinical and imaging surveillance, being treated with levothyroxine 100 µg and without further complications, until today.

Conclusion: These cases reflect the importance of patient complaints in the differential diagnosis, especially osteoarticular complaints, showing that thyroid cancer can present itself already in the metastatic phase and the need to better treat our patients.
Incidental Poorly Differentiated Thyroid Cancer in Trauma Patient
Authors: Grana Santini Alberto Javier , Alvarado Milliette , Gonzalez-Rodriguez Loida Alejandra , Ramirez Margarita , Ortega Nydia Ivette Burgos , Canales Nicolle
Published: May 2021

Poorly differentiated carcinomas tend to arise de novo or transform from differentiated thyroid carcinomas. Females, middle-aged and elderly adults are most commonly affected. Patients present with an enlarging thyroid mass which is often locally advanced at presentation. This is a case of 30-year-old male patient admitted after burn injury who presented with neck enlarging mass. He had no family history of thyroid CA, no radiation exposure and normal thyroid function tests. Neck CT imaging found with heterogeneous enhancing mass arising from the left thyroid lobe. Thyroid ultrasound consistent with a large left thyroid lobe lesion described as a complex solid component measures at least 5.2 cm long x 4.0 cm AP by 5.0 cm transverse with coarse scattered echogenic foci, and smaller bright echoes with comet-tail artifacts. Fine needle biopsy was non-diagnostic or unsatisfactory. Second FNA with Atypia of undetermined significance. Left hemithyroidectomy performed consistent with a 5cm Poorly differentiated thyroid carcinoma arising in a preexisting papillary thyroid carcinoma with extensive necrosis, pT3aNx, TTF1 +, PAX 8 +, CK7 +. Right thyroid was negative for malignancy. A Therapeutic dose of 135.7 mCi of 131-iodine was given. Subsequent whole body scan with focal findings in the thyroid bed region is consistent with residual functional thyroid tissue. Follow up with normal thyroglobulin levels and negative thyroglobulin antibodies. Neck ultrasound without abnormal tissue or nodules seen at either thyroid bed. Follow up with 18-F-FDG PET/CT scan abnormal study with avid lymph node in the right side of the neck, Level 3. FNA lymph node, cervical right level 3, 1.1cm, ultrasound guided biopsy negative for metastatic carcinoma. Poorly differentiated thyroid carcinomas present as large thyroid masses. The tumor spreads by local invasion into perithyroidal tissues and by distant metastases. Poorly differentiated carcinoma is supported by immunohistochemical staining for Tg, TTF1, and paired box protein Pax 8 (PAX8). There is no standardized treatment for PDTC to date. If possible, a total thyroidectomy including lymph node dissection should be performed to improve survival rates. Due to the higher rate of ETE, positive margins, neck disease, and distant metastases, adjuvant treatment should be considered. Some experts recommended considering adjuvant RAI in all PDTC patients, giving the potential benefit and lack of morbidity. However, despite the capability of RAI uptake in a high percentage of PDTC, no significant impact on survival has been reported. It is important to recognize prognosis of PDTC is distinctly less favorable than that of PTC or FTC. Several factors have been identified to affect patient prognosis such as extensive tumor necrosis, >45 year of age, tumor size (>5 cm), extrathyroidal extension and distant metastases are unfavorable prognostic factors.
Noninvasive Encapsulated Papillary RAS-Like Thyroid Tumor (NEPRAS)
Authors: Rosario Pedro Weslley , Mourão Gabriela Franco
Published: May 2021

Introduction: The diagnosis of thyroid tumors arising from follicular cells that are encapsulated/well delimited and noninvasive is a challenge. When unequivocal nuclear alterations are present, the final diagnosis can range from noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) and classical/encapsulated papillary thyroid cancer (PTC), including aggressive subtypes, to poorly differentiated carcinoma. As proposed recently, the presence of papillae in the absence of exuberant nuclear alterations (nuclear score 2), given that the other criteria for NIFTP are met, may not be sufficient for the diagnosis of PTC. This condition is called “noninvasive encapsulated papillary RAS-like thyroid tumor” (NEPRAS), whose nature would be borderline and not malignant. Revising our cases of tumors > 1 cm that were diagnosed previously as PTC and that were encapsulated/well delimited and noninvasive, we found three cases of NEPRAS. We now revised our cases of tumors > 1 cm diagnosed previously as well-differentiated tumor of uncertain malignant potential (WDT-UMP) because the nuclear alterations were not considered to be sufficient for the diagnosis of PTC on that occasion. Case: In a 29-year-old euthyroid male patient with a single thyroid nodule whose fine-needle aspiration had revealed indeterminate cytology, a single tumor measuring 3.2 cm was reclassified from WDT-UMP to NEPRAS. For this diagnosis, the tumor met the following criteria: encapsulation or clear demarcation, no vascular or capsular invasion, presence of papillae, < 30% solid/trabecular/insular growth pattern, no tumor necrosis or high mitotic activity, and nuclear score 2. The BRAFV600E mutation was absent. The patient continues to show no signs of recurrence 7 years after lobectomy. Conclusion: Despite the presence of papillae, some tumors may be reclassified from malignant (encapsulated PTC) to borderline (NEPRAS). This proposal would result in a change of management, with the same implications as those seen for the change from noninvasive encapsulated follicular variant of PTC to NIFTP. References: Ohba K et al. Encapsulated Papillary Thyroid Tumor with Delicate Nuclear Changes and a KRAS Mutation as a Possible Novel Subtype of Borderline Tumor. J Pathol Transl Med. 2019;53:136-41 AND Rosario PW. Noninvasive encapsulated papillary RAS-like thyroid tumor (NEPRAS) or encapsulated papillary thyroid carcinoma (PTC). J Pathol Transl Med. 2020;54:263-4.
Papillary Thyroid Carcinoma With Axillary Lymph Node Metastasis
Authors: Khan Mehvish , Sperling Scott Brian
Published: May 2021

Papillary thyroid carcinoma (PTC) is typically known to be a non-aggressive form of thyroid follicular epithelial-derived cancer. It is characterized histologically by classic and variant forms. Metastases are uncommon and spread mainly via lymphatic channels to cervical lymph nodes and less commonly via hematogenous spread to lungs and bone. Axillary lymph node (ALN) metastasis is a rare sequela of disease presentation. A 59-year-old female presented for evaluation of shortness of breath and chest pain for one week. She had a longstanding history of hypothyroidism due to chronic lymphocytic thyroiditis which was stable on levothyroxine. Her physical exam revealed a firm mass on the inferior aspect of the left neck. Computed tomography (CT) angiogram ruled out pulmonary embolism but noted a superior mediastinal mass and significant left axillary and subpectoral adenopathy. Mammogram was negative for breast malignancy. Left axillary ultrasound showed a 1.1 x 1.8 x 1.9 cm enlarged lymph node. Thyroid ultrasound showed a 3 mm nodule on the left lower pole and a 3.7 x 2.9 x 2.1 cm heterogeneous and irregular mass in the left neck. Positron emission tomography/CT showed increased uptake in left lower paratracheal, left supraclavicular and axillary lymph nodes. Fine needle aspiration of the left neck mass and left ALN confirmed metastatic papillary carcinoma. She underwent total thyroidectomy, left modified neck, central neck, and left ALN dissection along with partial esophageal wall excision. Intraoperatively, she was found to have a multifocal tumor in the left thyroid lobe with the largest dimension of 1 cm. Surgical pathology noted that the primary tumor in the left thyroid was classic type of papillary carcinoma, and the metastatic tumor in the lymph nodes was of tall cell variant. I-123 thyroid uptake and scan after surgery showed low residual thyroid uptake of 0.6%. She underwent adjuvant ablation with 155 millicuries (mCi) of radioiodine (RAI or I-131) following levothyroxine withdrawal protocol. Post ablation therapy thyroid uptake and scan showed no radiotracer uptake within the thyroidectomy bed. According to the American thyroid association (ATA) risk stratification system, she was categorized as high risk. This case illustrates that PTC may exceptionally spread to axillary lymph nodes. Physiologic flow is centripetal to the jugulosubclavian junction and there is no communication between cervical and axillary lymphatics. However malignant tumors can alter and partially block lymphatic pathways, resulting in ALN metastasis in a retrograde direction. This case also demonstrates that PTC can be transformed into aggressive forms associated with worse prognosis such as tall cell variant. Further comprehensive monitoring and management approaches are needed to plan treatment and gauge prognosis of patients with PTC who present with ALN metastasis.
Primary Thyroid Lymphoma: Maintaining Diagnostic Scrutiny
Authors: Chang Diana Juhee , Mosaferi Tina , Kim Sarah Sangnim Rhee
Published: May 2021

Background: Primary thyroid lymphoma (PTL) is a rare condition representing <5% of thyroid malignancies with diffuse large B-cell lymphoma (DLBCL) as the most common subtype (1). Although not commonly managed in the endocrine sphere, identification is paramount to prognosis and treatment. We present a case of PTL to highlight the importance of diagnostic scrutiny and clinical follow up.

Clinical Case: A 69-year-old man with a history of Hashimoto’s thyroiditis presented with an enlarging neck mass. The patient noted development of a left-sided anterior neck mass 3 days prior to seeking care. He denied compressive symptoms and B symptoms (weight loss, fevers, and night sweats). Physical exam revealed a large, firm left-sided thyroid nodule. Serum studies were notable for TSH 39.1 mcIU/mL (0.30-4.7 mcIU/mL), FT4 0.9 ng/dL (0.80-1.70 ng/dL), and TPO Ab 127 IU/mL (<=20 IU/mL). Levothyroxine 100 mcg daily was started. Neck ultrasonography showed a 54 mm hypoechoic, solid left thyroid nodule without calcifications. No abnormal cervical lymph nodes were present. FNA revealed a mixed population of small lymphocytes with no monoclonal B cell population or T cell aberrancies on flow cytometry. In the setting of ongoing nodular growth, the patient underwent core needle biopsy which revealed DLBCL (Ki67 proliferation index >80%, EBV-EBER negative). For diagnostic confirmation and staging, a whole-body FDG-PET scan was performed with an intensely FDG-avid left thyroid mass and no metabolic evidence of additional lymphoproliferative disease. Bone marrow biopsy did not show lymphomatous involvement. The patient was diagnosed with primary thyroid lymphoma and started on chemotherapy with R-CHOP.

Conclusion: PTL commonly presents as a rapidly enlarging, painless neck mass that may be accompanied by B symptoms. Hashimoto’s thyroiditis is a known risk factor. Our case in particular required more diligence in the setting of an FNA with mixed lymphoid cells and negative flow cytometry. Initial differential diagnosis included intrathyroidal lymph node, Hashimoto’s thyroiditis, thyroid adenoma/malignancy with a false FNA, and lymphoma. Notably, FNA biopsy is only associated with 71% sensitivity in diagnosing PTL, whereas core biopsy has a 93% sensitivity rate (2). Upon histopathologic disease diagnosis, collaboration with oncology is needed for further staging and initiation of chemotherapy +/- radiation.

References: (1) Pavlidis ET, Pavlidis TE. A Review of Primary Thyroid Lymphoma: Molecular Factors, Diagnosis and Management. J Invest Surg. 2019;32(2):137-142. (2) Diaconescu MR, Costea I, Glod M, Diaconescu S. An Unwonted Clinicopathological Subtype of Thyroid Primary Lymphoma. Chirurgia. 2016;111(5):428-431.
Radioactive Iodine Resistant Papillary Thyroid Cancer “Redifferentiated” With Dabrafenib
Authors: Zayouna Christine , Sonnabend Hajerah , Amblee Ambika
Published: May 2021

Background: Differentiated thyroid cancers (DTC) make up 95% of all thyroid cancers. Radioactive iodine therapy (RAI Rx) is an integral part of DTC management. However, 5-15% of DTC and 50% of metastatic DTC become resistant to RAI Rx and carries a 10-year survival of only 10%. One of the newer therapeutic options target “redifferentiation” of the tumor using RAI sensitizers, notably with short-term use of tyrosine kinase inhibitors (TKI). Clinical Case: A 62-year-old women with a 3-year history of Papillary TC s/p surgery (Sx) and 175 mCi RAI presented to establish care and was found to have bulky palpable disease in her left lateral neck. Imaging showed bilateral enlarged lymph nodes in the neck and multiple bilateral pulmonary nodules. Her stimulated thyroglobulin (TG) level was 5341 (1.59 - 50.03 ng/dL) with negative TG antibodies. Bone scan showed no evidence of bone mets. She underwent repeat neck dissection (49 positive lymph nodes) and was BRAF V600E positive. Post-Sx her non-stimulated (NS) TG was 340 ng/dL (0.00 - 41.00 ng/mL) and she received 200mCi RAI Rx with post-Rx whole body scan (WBS) showed uptake only in the thyroid bed. Imaging 6 months later showed stable lung nodules but increase in lymphadenopathy in the neck and her NS-TG was 181 ng/dL. She received 250 mCi of RAI Rx, 10 months after the first dose. Post Rx WBS again showed uptake only in the neck. Her non-stim TG, 9 months later was still high at 130 ng/dL. Given the discordant imaging and TG findings, functional imaging was done which showed multiple avid lesions in bone and lymph nodes confirming the diagnosis of radioiodine-refractory (RAI-R) DTC. Given BRAF V600E positive status, she received Dabrafenib 150 mg PO BID for 6 weeks followed by RAI 300 mCi. Post-RAI WBS showed extensive uptake in base of skull, sternum, cervical spine and right supraclavicular area. Six months post Dabrafenib and RAI, her NS-TG had come down from 130 to 25.7 ng/dL and imaging showed stable structural disease. Her TG levels and imaging have remained stable over the last 18 months indicating both biochemical and structural response to Dabrafenib. Conclusion: The goal of TKIs in redifferentiation of RAI-R DTC is to target specific molecular mechanisms to render the tissue sensitive to RAI. There are several published trials using TKIs for redifferentiation based on the mutation present. Dabrafenib alone and in combination with other TKI’s (Vemurafenib, Trametinib) followed by RAI has shown some response in 60-70% of treated patients with RAI-R tumors. In a study with 10 RAI-R patients with BRAF V600E mutations, dabrafenib used as a radiosensitizer showed RAI uptake in 60%. Three months post Rx, 2 of 6 had a reduction in disease burden while the other 4 had stable disease. Redifferentiation Rx can be successful in slowing disease progression and could be an option in the treatment of RAI-R DTC before initiation of long term TKI Rx.
Thyroid Lymphoma: A Rare Cause of Thyroid Malignancy
Authors: Cartwright Carmen , Lekprasert Patamaporn
Published: May 2021

Background: Primary Thyroid Lymphoma is rare accounting for 2-5% of all thyroid malignancies and less than 2% of extranodal lymphomas. Data has suggested annual incidence to be 2 per 1 million. (1)

Clinical Case: A 72-year-old female with coronary artery disease, hyperlipidemia and hypothyroidism was diagnosed with extranodal follicular cell lymphoma of the breast. FDG-PET showed evidence of diffuse avidity within her thyroid gland, with SUV of 13.8. She denied any drastic change in the size of her neck or any compressive symptoms. Thyroid ultrasound performed months before her diagnosis of lymphoma, showed a two-fold increase, most notable to the right lobe compared to prior imaging; her gland remained otherwise unchanged with heterogenous echotexture.

Fine needle aspiration and flow cytometry were obtained on thyroid tissue that showed follicular cell lymphoma. She was started on single-therapy Rituxan regimen with oncology. Several months later appearance and examination of her neck had improved with decrease in size of thyroid gland.

Repeat FDG-PET scans, with the most recent being 11 months after starting Rituxan therapy, showed reduction in the avidity within the thyroid gland and decreasing size; with SUV of 7.8.

Repeat thyroid ultrasound continued to show heterogeneous echotexture with overall decrease in volume in gland size by nearly 50% within the right lobe and approximately 30% within the left lobe.

Conclusion: Thyroid lymphoma should be suspected in a rapidly enlarging thyroid gland with or without pain or compressive symptoms. However, we propose that it should also be considered in the setting of FDG-PET avidity in thyroid tissue in setting of clinical suspicion.

Diffuse FDG-PET scan avidity in the thyroid gland does not automatically equate to malignancy as prospective and retrospective information has shown that diffuse uptake can be seen incidentally, in cases of diffuse goiter, Graves disease or chronic lymphocytic thyroiditis and that the uptake has been seen to range between 5.6-16.8 SUV. (2) The American Thyroid Association 2015 thyroid cancer guidelines propose that if diffuse uptake is seen within the thyroid gland on PET imaging that thyroid ultrasound imaging and functional testing be undertaken. If imaging shows findings suggestive of only chronic lymphocytic thyroiditis (diffuse heterogeneous gland) that no further action is required. In this patient a different approach was taken with investigations pursued in the setting of enlarging thyroid gland on imaging and known extranodal lymphoma allowing for ultimate diagnosis.

References: 1. Stein, S., et al. “Primary Thyroid Lymphoma: A Clinical Review.” The Journal of Clinical Endocrinology & Metabolism, vol. 98, no. 8, 2013, pp. 3131-3138

2. Karantanis, D., et al. “Clinical Significance of Diffusely Increased 18F-FDG Uptake in the Thyroid Gland.” Journal of Nuclear Medicine, vol. 48, no. 6, 2007, pp. 896-901
Graves’ Disease, a Late Complication of Chronic Graft vs Host Disease
Authors: Kreit Helen , Rehman Aziz Ur , Bright Tamis Marie
Published: May 2021

Introduction: Graft-versus-host disease (GVHD), a complication of bone marrow transplant (BMT), occurs when the donor white blood cells attack the recipient’s host cells and can occur acutely or chronically several years post-transplant. It is very rare for chronic GVHD to cause hyperthyroidism due to Grave’s disease and thyrotoxicosis years after BMT. Hyperthyroidism after BMT is thought to occur by GVHD or by donor’s auto-reactive lymphocytes transferred to recipient, with majority of cases occurring with donors that have an underlying autoimmune thyroid condition.

Case Report: We report a 62 year old male who presented with palpitations, tremors, sweating, weight loss, and anxiety for 3 weeks. Past medical history was significant for allogenic BMT due to AML 14 years ago, which was further complicated by GVHD of eye, liver and skin. Physical exam was negative for thyromegaly or thyroid tenderness. Initial work up showed TSH 0.03 (normal 0.4-5.0 MUI/l), free T4 3.32 (normal 0.6-1.2 ng/dl), TSI 194 % (normal <140 %). Ultrasound revealed a diffuse hypervascular thyroid gland with numerous avascular cystic areas in both lobes and increased homogenous, symmetrical uptake consistent with Graves’ disease was noted on radioactive iodine uptake scan. With clinical suspicion of GVHD leading to Graves’ disease with subsequent thyrotoxicosis, he was started on methimazole. However, due to persistent increase in transaminases, concern for agranulocytosis with methimazole, and risk of developing worsening GVHD of the skin or eye with radioactive iodine therapy, he underwent total thyroidectomy. His pathology showed bilateral lymphoepithelial lesions with florid follicular hyperplasia, marked monocytoid hyperplasia, and Germinal B cells positive for CD10 and negative for BCL2. Lymphoepithelial lesions can be seen in chronic lymphocytic thyroiditis due to persistent inflammation.

Conclusion: This case raises the question on the etiology of thyroid nodules and Graves’ disease occurring after BMT. We believe that his pathology findings may be due to chronic GVHD. Hyperthyroidism after BMT is extremely rare, with only a few case reports documenting this phenomenon. We believe that our patient developed hyperthyroidism 14 years after BMT most likely as a sequela of chronic GVHD with underlying immune dysregulation leading to formation of TSI and thyroiditis due to cellular invasion. This suggest a multifactorial etiology of hyperthyroidism in patients with GVHD. However, more prospective studies are required to the explain etiology of hyperthyroidism in GVHD. Moreover, such patients should be closely monitored for development of thyroid dysfunction or thyroid nodules.
A Case of Atypical Thyroid Storm Presentation With Subsequent DIC, Hypoglycemia, Kidney Failure and Shock Liver
Authors: Xue Liang , Singh Samar
Published: May 2021

Background: Thyroid storm is a rare and life-threatening emergency requiring prompt intervention that is diagnosed based on a combination of clinical, physical and biochemical findings. Presented here is a case of thyroid storm which proved a diagnostic challenge due to its atypical presentation and whose management was further complicated by uncommon sequelae including DIC, hypoglycemia, kidney failure and shock liver. Clinical Case: A 37-year-old female with Graves’ disease presented to the Emergency Department with a chief complaint of facial swelling with concern for recent food allergy. Initial labs revealed elevated fT4 of 5.17 ng/dL (n 0.6-1.12 ng/dL) and suppressed TSH <0.01 uIU/mL (n 0.45-4.12 uIU/mL), but otherwise normal range BMP and CBC. While awaiting admission in the ED, she had normal cognition, stable vitals and scored 25 per Burch-Wartofsky scale. Given significant thyrotoxicosis and history of non-compliance with Graves’ treatment, patient was nevertheless empirically started on treatment for suspected thyroid storm in addition to treatment for possible allergic reaction. In the ED patient suddenly went into cardiac arrest with ROSC achieved after 2 rounds of CPR. Following ROSC, labs showed BG of 24 mg/dL (n<115 mg/dL), WBC to 24 thousand/mcL (n 4.0-10.5 thousand/mcL), lactate >10 mmol/L (n< 2mmol/L), D-dimer >20,000 ng/mL (n<500 ng/mL), AST 1869 U/L (n<52 U/L). Patient underwent a prolonged hospital course requiring treatment for hypoglycemia, shock liver, acute kidney injury, heart failure, atrial fibrillation, DIC and embolic CVA. Her initial shock liver improved and transitioned into a cholestatic picture, prompting a change in her thionamides from PTU to Methimazole, then back to PTU later on. Her multi-organ failure improved gradually over 3 weeks with mechanical ventilation, CRRT, blood transfusion, stress dose steroids and comprehensive critical care treatment. Patient was eventually discharged with close endocrine, ENT, cardiology, and neurology follow up. Conclusion: In diagnosing and treating this rare but life-threatening endocrine emergency, a strong clinical suspicion should not be detracted by an atypical presentation and prompt action is needed. It is vital to remember that this is first and foremost a clinical diagnosis that can be further supported with laboratory and physical findings. Furthermore, this case is an example of the extent of multi-organ failure that can result from thyroid storm.
A Case of Parathyroid Adenoma Three Decades Post Radioactive Iodine Therapy: Is It Just a Coincidence or Real Risk?
Authors: Panjawatanan Panadeekarn , Sekar Vijaykumar , Hughes Joseph
Published: May 2021

Background: External radiation to the head and neck is a known risk factor for the development of parathyroid adenoma. But the incidence is very rare in internal radiation recipients. Here we describe a case of parathyroid adenoma after 30 years of radioactive iodine therapy for Graves’ disease.

Clinical Case: A 50-year-old female presented during an annual visit with progressive fatigue, polyuria, polydipsia, nocturia, muscle weakness, and some memory impairment. She had a past medical history of Graves’ disease treated with radioactive iodine therapy 30 years ago with subsequent hypothyroidism, controlled essential hypertension, asthma, and obesity BMI 32.5 kg/m2. There was no history of nephrolithiasis, fractures, pituitary tumor, or acid reflux. Family history was noted for thyroid diseases, no calcium issues or hyperparathyroidism. Neck examination did not reveal any thyromegaly or palpable nodule. Laboratory tests showed calcium 11.4 mg/dL (8.6-10.3), ionized calcium 6.1 mg/dL (4.2-5.4), parathyroid hormone 213.9 pg/mL (12-88), total vitamin D 22 ng/mL (31-100), TSH 0.47 uIU/mL (0.34-3.00), Free T4 1.1 ng/dL (0.6-1.6), creatinine 0.7 mg/dL (0.6-1.2), eGFR >60 ml/min/1.73 m2, 24-hr urine calcium 405 mg (40-350). Bone density revealed T-score -4.9 at the lumbar spine, -2.8 at the total hip, -3.1 at the femoral neck, and -2.9 at distal 1/3 radius. Neck ultrasound showed atrophy of the thyroid gland with a lobulated hypoechoic area measuring up to 1.3 x 0.9 x 0.9 cm without internal blood flow at posterior inferior to the right lobe of the thyroid gland. Parathyroid SPECT/CT scan revealed no evidence of parathyroid adenoma. The hypoechoic lesion was suspected to be a lymph node according to imaging studies. However, according to laboratory and bone density results, we suspected primary hyperparathyroidism in which the patient required surgery due to current symptoms. The patient underwent surgery with an intraoperative finding of a nodule at the superior of the right parathyroid gland. A frozen section of the nodule was sent which confirmed parathyroid adenoma. The gland, weighted 483 mg, was removed with subsequent improvement of intraoperative parathyroid hormone level from 238.5 pg/mL to 26.5 pg/mL. Follow up calcium was at 9.5 mg/dL. The patient was supplemented with calcium and vitamin D afterward. Her symptoms improved significantly.

Conclusion: Hypercalcemia in a patient with prior history of radioactive iodine therapy should raise concern for parathyroid adenoma. Imaging of the parathyroid gland should be cautiously interpreted with laboratory tests as it could be a false negative. Due to patient met criteria for surgery, the surgical approach should be pursued for both diagnostic confirmation and definite treatment. Intraoperative parathyroid hormone monitoring is beneficial in equivocal imaging and in reflecting successful resection of uniglandular disease.
A Case of Recurrent Paralysis and Low Potassium: Is It the Thyroid?
Authors: Do Justin , Mufti Hoveda
Published: May 2021

Introduction: Thyrotoxic periodic paralysis (TPP) is a rare complication of hyperthyroidism that is characterized by episodes of hypokalemia and acute weakness. Although hyperthyroidism is more common in females, over 95% of cases of TPP have been observed in males, especially in Asian males with an incidence of 2% among hyperthyroid patients. In non-Asian populations, the incidence in hyperthyroid patients is estimated to be around 0.1 to 0.2% [1]. We describe a case of TPP seen in a Hispanic male.

Case Report: A 36-year-old Hispanic male with no past medical history presents with weakness in all extremities and difficulty breathing after consuming a carbohydrate heavy meal the night prior. He reports a recent, similar episode evaluated in another ER, which resolved after given potassium supplementation. He denied any vomiting, diarrhea, polyuria, diaphoresis, use of insulin or other medications, or any family history of paralysis.

His labs were significant for hypokalemia of 1.9, TSH of <0.005 (0.358-3.740), free T4 of 2.22 (0.76-1.46), and total T3 of 2.7 (0.60-1.81). Thyroid stimulating immunoglobulin was 0.12 (0.0-0.55). His symptoms improved and potassium levels normalized following the administration of potassium chloride. He was discharged on propranolol and advised to follow up for further workup of his hyperthyroidism with radioactive iodine uptake scan.

Discussion: Thyrotoxic periodic paralysis is a potentially life-threatening condition associated with cardiac arrhythmias and respiratory failure. Hyperthyroidism increases response to β-adrenergic stimulation, which increases activity of the sodium-potassium ATPase and causes hyperpolarization of skeletal muscle [2]. Hyperthyroid patients are prone to episodes of paralysis due to their increased susceptibility to the hypokalemic action of insulin, which activates the sodium-potassium ATPase pump, and epinephrine, which stimulates β-adrenoreceptors. Management of an acute attack of TPP includes potassium administration. In cases where paralysis and hypokalemia are not reversed, intravenous propranolol has been shown to resolve the attack by blocking the β-adrenergic receptors. Definitive treatment of TPP includes managing the hyperthyroid state with medical therapy, radioactive iodine therapy, or surgery. Until the euthyroid state is reached, a β-blocker can prevent episodes of acute paralysis. Avoidance of carbohydrate heavy meals, exercise, and stress are recommended as these factors can potentially exacerbate hypokalemia. In patient with acute paralysis, it is important to consider the diagnosis of TPP as this condition can be prevented once euthyroidism is achieved. Diagnosis and management will lead to prevention of morbidity and mortality associated with the hypokalemia.

References: 1.Vijayakumar A, et al. J Thyroid Res. 2014;2014:649502. 2.Layzer RB. Annals of Neurology. 1982;11(6):547–552.