bluuebunny/crossref_metadata_2025 huggingface dataset:
6847 Poorly Differentiated Thyroid Cancer: A Rare Entity
Authors: Fatima Sanna , Ward Samuel , Champion Amber
Published: October 2024

Disclosure: S. Fatima: None. S. Ward: None. A. Champion: None.

Introduction: Poorly differentiated thyroid carcinoma (PDTC) is a rare thyroid carcinoma originating from follicular epithelial cells. Regarding the degree of differentiation, PDTC ranks between differentiated thyroid cancer and anaplastic thyroid cancer. We hereby present a rare case of PDTC. Case: 29-year-old female with a history of metastatic papillary thyroid cancer (PTC) presented to the emergency department with shortness of breath. She initially noticed a left thyroid mass in 2021. CT neck in 1/2022 showed a 7 cm left thyroid mass with substernal extension, small right thyroid mass with tracheal compression, left bulky cystic nodal masses extending anterior and posterior to carotid and internal jugular vein. PET scan in 3/2022 showed left 7.6 cm thyroid mass SUV 12.1 with tracheal compression, left level II-IV adenopathy with level IV nodal masses 5.1 cm SUV 4.5. Ultrasound-guided FNA in 4/2022 showed PTC in left 8.7cm thyroid nodule; right 2.8 cm nodule showed Atypia of Undetermined Significance; Left 5.5 cm neck level III lymph node (LN) showed PTC metastasis; right 5.1 cm neck level III LN showed PTC metastasis (+ thyroglobulin and TTF-1). CT chest in 11/2022 showed additional involvement of manubrium. Repeat core needle biopsy of left thyroid mass showed left invasive thyroid carcinoma. She was started on neoadjuvant Lenvatinib in 1/2023. Follow-up CT neck in 5/2023 showed a reduction in the size of the left thyroid mass to 5.5cm x 5.8cm x 6.5cm. At this time, she had symptoms of dysphagia, orthopnea, weight loss of about 60 lbs and neck pain. In 11/2023 at time of current presentation she underwent total thyroidectomy, bilateral modified radical neck dissection and manubriectomy. Surgical pathology showed PDTC in left thyroid mass, PTC in right thyroid mass with metastatic PDTC in left proximal sternocleidomastoid, manubrium and LN involvement in neck and mediastinum. OmniSeq Insight testing showed APC and BRCA1 gene mutations, negative BRAF V600E, RET fusion, RET mutation, NTRK1/2/3 fusion and PD L1 immunohistochemistry score is <1%. The patient is planned to receive [1]3[1]I ablation therapy. Conclusion: PDTC accounts for 3–5% of all thyroid carcinomas. The 5, 10-, and 15-year survival rates of patients are 50–85%, 34–50%, and 0%, respectively. RAS gene alterations are found in 25–35%, BRAF mutation in 15–27%, TERT promoter mutation in 40% and mutant TP53 in 16–28% of PDTCs. TERT promoter gene and TP53 mutation usually indicate an aggressive phenotype and a dismal prognosis. Surgery, [1]3[1]I therapy, and external beam radiotherapy constitute the mainstay of traditional treatment for patients with advanced disease; however, treatment is challenging. Tyrosine kinase inhibitors i.e, sorafenib and lenvatinib, have been used in cases of progressive, recurrent, or metastatic disease not responsive to [1]3[1]I therapy. Immunotherapy may be an option in PD-L1-positive tumors.

Presentation: 6/1/2024
7385 Prevalence of Central Hypothyroidism in Cushing Syndrome and Thyroid Function Tests After Cushing Treatment
Authors: Kunavisarut Tada , Sriwijitkamol Apiradee
Published: October 2024

Disclosure: T. Kunavisarut: None. A. Sriwijitkamol: None.

Cushing syndrome can be associated with thyroid dysfunction. We investigated the association between Cushing syndrome and thyroid dysfunction. We conducted a retrospective study at Siriraj Hospital in Thailand and analyzed thyroid function tests in 80 Cushing's patients. The inclusion criteria were patients diagnosed with Cushing syndrome with thyroid function tests recorded at diagnosis of Cushing syndrome. Patients who had an abnormal thyroid function test at diagnosis of Cushing syndrome must have a thyroid function test after treatment of Cushing syndrome. Of the 80 patients, sixty-five patients (81.2%) had normal thyroid function at diagnosis, 12 patients (15%) had central hypothyroidism and three patients (3.8%) had subclinical hyperthyroidism.Interestingly, among 12 patients who had central hypothyroidism, eight patients (66.7%) were diagnosed with Cushing disease. Three patients (25%) were diagnosed with adrenal Cushing syndrome and one patient (8.3%) was diagnosed with ectopic Cushing syndrome. This finding suggested that central hypothyroidism may not be exclusively due to the mass effect of the pituitary tumor on the normal pituitary because adrenal Cushing syndrome and ectopic Cushing syndrome can also cause central hypothyroidism. Among 12 patients with central hypothyroidism at diagnosis of Cushing syndrome, nine patients (75%) normalized their thyroid function after remission of Cushing syndrome without Levothyroxine replacement. Moreover, patients with central hypothyroidism had significantly higher median 24-hour urine-free cortisol levels than euthyroid patients (1030.5 ug/day vs. 404.5 ug/day, p=0.017), indicating a potential correlation between cortisol excess and low FT4 levels. These findings suggest that hypercortisolism in Cushing syndrome can suppress the hypothalamic-pituitary-thyroid axis, but this suppression is often reversible with successful Cushing's treatment. This study highlights the importance of central hypothyroidism, which can occur in all types of Cushing syndrome. If the patients did not have hypothyroid symptoms, Levothyroxine replacement may not be necessary. For patients who already received Levothyroxine and had normal thyroid function tests, Levothyroxine can be carefully tapered and potentially discontinued because successful Cushing syndrome treatment can ultimately normalize thyroid function tests.

Presentation: 6/1/2024
8751 Radiofrequency Thermal Ablation in 32 Patients with Toxic Adenomas with Resolution of Hyperthyroidism in All Cases
Authors: Lima Amato Lorena Guimaraes , Martinho Volpi Erivelto , Moura Volpi Leonardo De , Machado Carani Pedro Henrique , Rahal Antonio
Published: October 2024

Disclosure: L.G. Amato: None. E.M. Volpi: None. L.D. Volpi: None. P.M. Carani: None. A. Rahal: None.

Introduction: In the general population, thyroid nodules are found in 3-7% of individuals on physical examination and in 20-76% on ultrasound. Around 8-10% of benign nodules may present autonomous behavior, being called hot nodules, causing symptoms of hyperthyroidism and being called toxic adenomas (TA). In TAs, autonomous hormone production can be caused by somatic activating mutations of genes regulating thyroid growth and hormone synthesis caused by somatic activating mutations of genes regulating thyroid growth and hormone synthesis. Classically, the proposed treatment for autonomous nodules was surgical resection or radioiodine ablation (RAI). In this context, the prevalence of hypothyroidism after the procedure varies from 2% to 3% following lobectomy, and lower after isthmusectomy in the unique circumstance in which the TA is confined to the thyroid isthmus. A study following 684 patients with TA treated with RAI reported a progressive increase in overt and sub-clinical hypothyroidism. Potential complications following near-total/total thyroidectomy include the risk of permanent hypoparathyroidism (< 2.0%) or recurrent laryngeal nerve injury (RLN) (< 2.0%). A small risk of permanent RLN injury exists with surgery for TA. Following RAI therapy, there have been reports of new-onset Graves Disease (up to 4% prevalence) as well as concern for thyroid malignancy and a very minimal increase in late non thyroid malignancy. Radiofrequency ablation (RFA) has been a precise and effective alternative for the treatment of many benign thyroid nodules over the past ten years, including hot nodules. RFA could preserves normal thyroid function compared to surgery or RAI. Clinical case: We evaluated the effectiveness of a single session of RFA in 32 patients with TA, through hormonal status, achieving normalization of thyroid and volumetric reduction of the nodule. Among the 32 patients included in this study, aged between 25 and 88 years, of these, 31 were women and 1 was a man, all of whom underwent a single RFA procedure (“moving shot” technique associated with hydrodissection). We had a single case of a reversible complication: a patient who had transient vocal cord paralysis, with total reversal. There was a reduction in the volume of all nodules as well as all patients progressed to a state of euthyroidism within 60 days of follow-up. Conclusion: A single session of RFA was effective in treating autonomous nodules, restoring euthyroidism in all patients.

Presentation: 6/3/2024
7009 Resistance to Thyroid Hormone
Authors: Gill Simranpreet , Chavez Luis F
Published: October 2024

Disclosure: S. Gill: None. L.F. Chavez: None.

Resistance to thyroid hormone is a unique phenomenon presenting with a variety of clinical findings due to biochemical elevations in thyroid hormones. We describe a case of a 52 year old male diagnosed with hypertension at age 25 followed by atrial flutter resulting in tachycardia induced cardiomyopathy who presented to the emergency department for lightheadedness and palpitations. He was found to be in atrial flutter and converted to normal sinus rhythm after receiving diltiazem. Labs showed a T4 of 17.4 with a TSH of 2.48. On examination, he was back to baseline and denied heat intolerance, changes in bowel habits, weight loss, hair loss, sweating, recent falls or fragility fractures, and in fact felt cold. Physical exam was remarkable for goiter. Patient was previously referred to endocrinology given an elevated FT4 and total T3 with a non-suppressed TSH level concerning for a TSH producing adenoma. He underwent extensive hormonal workup that revealed normal pituitary functioning apart from elevated FT4, FT3, and FT4 by dialysis. MRI of the brain was performed on two occasions, last done a few months prior to hospitalization which showed no focal lesions in the sella or parasellar regions. Given normal TSH and elevated FT4 levels in the setting of negative imaging, patient thought to likely have resistance to thyroid hormone (RTH). RTH is a rare inherited condition seen in as few as 1 in 40, 000 live births. It stems from an inability of target cells to respond appropriately to thyroid hormones due to dysfunction of thyroid hormone receptors (TRs). The most common variant of RTH is due to a mutation in the THRB gene encoding thyroid hormone receptor beta (RTH beta) located on chromosome 3 followed by defects in the THRA gene encoding thyroid hormone receptor alpha (RTH alpha) located on chromosome 17. Others may not have an identifiable genetic defect and are thought to be due to alterations in TR cofactors. Elevations of all three serum iodothyronines with non-suppressed TSH is seen with RTH beta while borderline high T3 and normal or slightly elevated TSH is seen in RTH alpha. Inadequate response to thyroid hormones can lead to feedback mechanisms attempting to resolve this relative deficiency by promoting synthesis of higher than normal thyroid hormone levels. Treatment is usually not required due to this adaptive mechanism but on occasion levothyroxine is supplemented to normalize the TSH in patients with limited thyroid reserve. Despite elevated circulating thyroid hormones, individuals can be clinically euthyroid or experience symptoms of thyroid hormone excess or deficiency. Conditions mimicking RTH including TSH producing adenomas should be ruled out which present with overt hyperthyroidism as opposed to the more subtle symptoms that can be seen with RTH. Overall, clinicians should be aware of RTH to prevent misdiagnosis and pursue treatment modalities that may otherwise not have been needed.

Presentation: 6/1/2024
6415 Resistance to Thyroid Hormone -A Challenge to Manage
Authors: Altaf Areeba , Iqbal Fizzah , Hamoudeh Eyad , Coyne Christopher , Anne Kiraithe , Buckley Lisa
Published: October 2024

Disclosure: A. Altaf: None. F. Iqbal: None. E. Hamoudeh: None. C. Coyne: None. K. Anne: None. L. Buckley: None.

Background: Resistance to thyroid hormone (RTH) or Refetoff syndrome was first introduced in 1967. It is an autosomal dominant or recessive genetic disease with a mutation in the thyroid hormone receptorβ (THR-β) gene or the thyroid hormone receptorα (THR-α) gene. The distinguishing biochemical feature of RTHβ is an elevated level of circulating free thyroid hormones with normal or high TSH concentration and decreased peripheral tissue response to thyroid hormone. Common signs and symptoms in patients with RTHβ are short stature, attention deficit disorder, and resting tachycardia and many patients might be asymptomatic. Case: We report a case of a 36-year-old patient with past medical history of congenital bilateral hearing loss, atrial fibrillation, CHF, and slow learning/comprehending who presented to the ER with shortness of breath and atrial fibrillation with tachycardia. Admission labs revealed elevated TSH 3.9, elevated fT4 3.28, and elevated TT3 205. He reported that for the past year, he has been on levothyroxine 50mcg for abnormal TSH. Levothyroxine was stopped and the patient was discharged on methimazole 10mg daily. Further workup revealed negative thyroglobulin and thyroid peroxidase antibodies. Thyroid ultrasound with Doppler demonstrated a mildly hypervascular thyroid gland without evidence of nodules. Brain MRI was negative for any pituitary abnormalities. HAMA testing continued to show elevated TSH. Patient was followed by cardiology and due to continued atrial fibrillation, had multiple cardioversions and was managed on a beta blocker. Due to his atrial fibrillation, endocrinology service continued his methimazole till his genetic testing came positive for an autosomal dominant heterozygous pathogenic mutation in THRB c.1373 T>C (p. Val458Ala). His thyroid hormones and TSH continue to be elevated. Currently, he is not on thyroid medication and getting monitored. The need for multiple cardioversions for atrial fibrillation in this patient makes resistance to thyroid hormone management challenging. Discussion: Hyperthyroidism is commonly mistaken for RTH. However, the lack of TSH suppression should be further investigated. Most patients with RTHβ are adequately compensated by the increased endogenous supply of thyroid hormone showing increased serum fT3 and fT4 levels and normal or near normal TSH levels. Beta Blockers like atenolol cannot inhibit the conversion of T4 to T3 and can be used for RTHβ with tachycardia. Triiodothyroaceticacid (TRIAC) or dextrothyroxine (DT4) have also been used to treat thyrotoxicosis. In summary, treatment for RTHβ remains a challenge for clinicians, especially in patients with atrial fibrillation and many patients are misdiagnosed and managed as hyperthyroidism.

Presentation: 6/3/2024
7684 Resistance to Thyroid Hormone Beta Mistaken as Primary Hypothyroidism: Variable Phenotypes and Diagnostic Dilemmas
Authors: Belal H F , Mukhtar A N , Chehade J M
Published: October 2024

Disclosure: H.F. Belal: None. A.N. Mukhtar: None. J.M. Chehade: None.

Background: The differential diagnosis of hyperthyroxinemia and nonsupressed TSH includes assay interference, resistance to thyroid hormone beta (RTHb) and TSHoma. Correlation of laboratory findings with clinical presentation is crucial to avoid misdiagnosis. Clinical Case: A 50 year old female presented with palpitations, tremors, headaches, diarrhea, heat intolerance, chronic attention difficulty, pre-syncope and fatigue over several years. She had regular menses with no birth control use. There was no amiodarone, lithium or biotin use. Exam: vitals stable, no thyromegaly, no hand tremors, no exophthalmos. At 26 years old she was started on Levothyroxine (LEVO) 50 mcg for elevated TSH; FT4 was not measured. Over the past 10 years her labs demonstrated elevated FT4, elevated FT3, elevated FT4 by direct dialysis, normal TBG and inappropriately normal/elevated TSH while on LEVO 75 - 175 mcg. On LEVO 75 mcg: elevated TSH 5.94 uIU/mL (0.27-4.2), elevated FT4 2.2 ng/dL (0.8-1.7), elevated FT3 6.0 pg/mL (2.0-4.4), elevated FT4 direct dialysis 2.9 ng/dL (0.8-1.7), normal pituitary panel (including alpha subunit), low alpha subunit/TSH molar ratio (0.71). During an ED visit for chest pain, EKG revealed poor R wave progression, non-specific T wave abnormality. She was also found to have hepatic steatosis. RTHb was diagnosed and her LEVO was gradually tapered. Conclusion: TSH receptor beta is expressed in hypothalamus, pituitary, cochlea, retina, liver and kidney. TSH receptor alpha is expressed in skeletal muscle, heart, brain and bone. RTHb occurs at a frequency of 1 in 19,000 to 40,000 leading to resistance to thyroid hormone action at the HPA axis and liver. This produces higher FT4 and FT3 that act on normal TSH alpha receptors. Clinical phenotypes vary from euthyroid to hyperthyroid. Mistreating RTHb as hypothyroidism can worsen the thyrotoxic state. Testing for RTHb genetic mutation is available, yet 15% of RTHb patients do not have an identifiable pathogenic variant[1]. Treatment of RTHb ranges from observation, beta blockade, antithyroid drugs or TRIAC, a thyroid hormone analog which act at the HPA axis to inhibit TSH secretion.[1] Life threatening cases may require total thyroidectomy or radioiodine ablation; often avoided due to difficulty managing thyroid hormone replacement afterwards. Cases of goiter and ADHD in RTHb have been successfully treated with supraphysiologic every-other-day liothyronine.2 Management should be patient tailored and symptom specific. References: 1. Moran, Carla. “Syndromes of Resistance to Thyroid Hormone.” 2023 Endocrine Case Management: Meet the Professor, Endocrine Society, Washington, DC, 2023, pp. 311-319. 2. Pappa T, Refetoff S. Resistance to Thyroid Hormone Beta: A Focused Review. Front Endocrinol (Lausanne). 2021 Mar 31;12:656551. doi: 10.3389/fendo.2021.656551. PMID: 33868182; PMCID: PMC8044682.

Presentation: 6/2/2024
7668 Rhabdomyolysis Associated with Severe Hypothyroidism
Authors: Naing Soe Htut , Mikkilineni Pushyami
Published: October 2024

Disclosure: H. Soe: None. P. Mikkilineni: None.

Background: Over 70% of the patients with newly diagnosed hypothyroidism can present with muscle complaints such as weakness, fatigability, cramps, myalgia. However, rhabdomyolysis, which is the rapid breakdown of skeletal muscle cells, is the rare presentation. Clinical Case: A 70-year old male patient with history of rheumatoid arthritis, hyperlipidemia, prior CVA (left hemispheric subcortical stroke) 6 months ago without residual deficit presented to the hospital with poor oral intake and generalized muscle weakness for 3 weeks. He was unable to get out of bed without assistance and also needed adult diapers. Found to have new-onset severe hypothyroidism with TSH 228 uIU/ml (Ref: 0.350-4.940) and FT4 <0.40 ng/dL (Ref: 0.70-1.50), positive TPO antibody 197 IU/ml (Ref: 0-34). No prior thyroid labs were available and no known history of thyroid disorder was recorded. He has never been on Amiodarone or Lithium before. On physical exam, he was alert and oriented. There was no goiter or palpable thyroid nodule. There was no focal neurological deficit and no peripheral edema. There were no other signs and symptoms pertinent to hypothyroidism except mild bradycardia (HR 56-60) and borderline low blood pressure. AM cortisol was 10.1 ug/dL (Ref: 3.7-19.4). EKG showed low-voltage sinus bradycardia. Echocardiogram was normal. Urinalysis was positive for large blood but only 3 RBCs were present which raised the suspicion of rhabdomyolysis. Creatinine kinase (CK) was 15,584 IU/L (Ref: 30-200). Other laboratory studies were significant for acute renal failure with mild hyperkalemia and mild hypocalcemia, also transaminitis; BUN 130 mg/dl (Ref: 8-26), Creatinine 9.51 mg/dl (Ref: 0.72-1.25), eGFR 5 ml/min/1.73 m2 (Ref: >59), AST 435 IU/L (Ref: 5-34), ALT 269 IU/L (Ref: <55), ALP 171 IU/L (Ref: 40-150). On medication review, he was started on Atorvastatin 80 mg daily during prior admission for CVA 6 months ago. He received IV fluids, s/p 1 dose of Hydrocortisone 100 mg IV, Levothyroxine IV 200 mcg, followed by Levothyroxine IV 50 mcg daily x 3 days and switched to Levothyroxine PO 100 mcg daily (weight-based dose). Atorvastatin was on hold. He became anuric during the hospital course and received 2-3 sessions of hemodialysis. 3-4 days later, CK was trending down to 3000 IU/L, FT4 improved to 0.54 ng/dl and there was also significant improvement in kidney and liver functions. The patient was diagnosed with acute renal failure secondary to rhabdomyolysis associated with severe hypothyroidism caused by Hashimoto's thyroiditis, in the setting of high dose statin use. Conclusion: Clinicians should raise the suspicion of rhabdomyolysis in a patient with severe hypothyroidism, especially in patients with recent high dose statin use as rhabdomyolysis can be a rare and fatal complication of severe hypothyroidism, in the presence of precipitating factors.

Presentation: 6/2/2024
12511 Rhabdomyolysis Related Acute Kidney Injury Presenting as First Manifestation of Autoimmune Hypothyroidism: A Case Report
Authors: Tiwari Apoorv , Mantravadi Sushmita , Doshi Nivedita , Dabaja Abed , Saad Chadi
Published: October 2024

Disclosure: A. Tiwari: None. S. Mantravadi: None. N. Doshi: None. A. Dabaja: None. C. Saad: None.

Introduction: Autoimmune thyroiditis is the predominant cause of primary hypothyroidism, with an incidence of estimated 0.3-1.5 cases per 1000 people, with female to male predominance of 7-10[1]. Hypothyroid myopathy affects 79 % of the affected population. Its common presentation is fatigue and cramp but in rare instances rhabdomyolysis can occur with trivial triggers like alcohol, exercise2, Case Presentation: A 32-year-old male with no significant medical history, presented with generalized weakness, myalgia, and facial puffiness for last three months. The patient engaged in regular-intensity workouts and reported consuming 12 beers several times a week for past 5 years. Physical examination revealed facial puffiness and proximal muscle weakness. Initial Laboratory findings showed elevated creatinine (1.68 mg/dL, baseline 1.0 mg/dL in April 2020), CK (8113 U/L), AST (260 U/L), ALT (129 U/L). Urinalysis revealed hematuria and mild proteinuria. Serum electrolytes were unremarkable. Abdominal ultrasound showed diffuse hepatic steatosis with normal kidney appearance. This could not explain the reason for the Acute Kidney Injury and further workup showed TSH (>150 mIU/L) and TPO antibodies (197.9 U/mL). Autoimmune panel was unremarkable. Thyroid ultrasound done subsequently revealed a markedly heterogeneous gland. Treatment included parenteral crystalloids, low-dose prednisone which was empirically added for suspected autoimmune myositis and was later discontinued once the autoimmune panel was negative, and Levothyroxine at the recommended dose. At the time of discharge, his creatinine was reduced to 1.33 mg/dL and CK to 2,298 U/L. Discussion: Severe rhabdomyolysis is a rare but significant complication of autoimmune thyroiditis, potentially leading to acute kidney injury (AKI) if not promptly diagnosed and treated. Resident physicians often attribute symptoms like myalgia and generalized weakness in males to clear evident rhabdomyolysis if they find a cause like alcohol consumption and exercise, potentially overlooking the actual etiology. We recommend thyroid workup in such patients to promptly detect and manage underlying etiology predisposing to muscle damage and subsequent kidney injury. Our patient never had any Physician encounter as his prior medical history was unremarkable, however we suggest thorough family history and thyroid profile should be a part of outpatient workup as well for patients who show other risk factors for rhabdomyolysis like daily alcohol consumption, vigorous workout, consume medications like HMG CoA inhibitors, antipsychotics etc.

Presentation: 6/3/2024
6618 Risks for Cardiovascular Comorbidities Associated with Desiccated Thyroid Extract Administration
Authors: De La Torre Sebastian C , Godar Cassandra , Flynn Kathryn , Anit Patel Arjun , Maxwell Devin , Shakir Mohamed K M , Duc Hoang Thanh
Published: October 2024

Disclosure: S.C. De La Torre: None. C. Godar: None. K. Flynn: None. A.A. Patel: None. D. Maxwell: None. M.K. Shakir: None. T.D. Hoang: None.

Introduction: Levothyroxine (LT4), synthetic thyroid hormone (T4), is considered the standard of care for the management of hypothyroidism based on the current American Thyroid Association (ATA) guidelines. However, there is a small subset of patients demonstrating symptomatic improvement with desiccated thyroid extract (DTE), which is composed of desiccated porcine thyroid containing T4 and triiodothyronine (T3). Limited data or studies are available exploring long-term cardiovascular effects associated with DTE use. In this retrospective review, we aim to identify possible cardiovascular comorbidities associated with DTE use. Methods: The charts of 77 patients at a tertiary hospital center (64 females and 13 males) over the age of 18 who were prescribed DTE were reviewed. Data collected include duration of treatment, dose of treatment, pre-treatment and current weight, blood pressure (BP), TSH, free T4, and total T3 levels. New cardiovascular and other events following initiation of treatment (hypertension, coronary artery disease (CAD), myocardial infarction (MI), stroke, transient ischemic attack (TIA), atrial fibrillation, type 2 diabetes, fractures) were also obtained. Averages, medians, and totals of patient data were used for analysis. Results: Average patient age was 54 years, average duration of therapy was 77.5 months, and median DTE dose was 75 milligrams per day. Review of chart documentation from DTE initiation compared to current values identified a 2.5% increase in weight, 3.6% increase in systolic BP, 0.8% decrease in diastolic BP, 60.9% decrease in TSH, 5.2% decrease in free T4, and 14.4% increase in total T3. 19.5% patients (15 total, 80% of which were female) had recorded new cardiovascular events at any time following initiation of therapy. 15 patients developed HTN, 5 developed CAD, 2 developed atrial fibrillation, 5 developed type 2 diabetes, 5 new fractures, 0 MI, 0 stroke, and 0 TIA. Conclusion: These results demonstrate new cardiovascular events in our study population following the initiation of DTE, but it is unclear whether these events were directly associated with DTE use versus other factors based on our available data. Limitations of our study include small study size, uneven gender distribution, and data significance would be improved with comparison to a control group. Additional studies are needed to further evaluate long-term cardiovascular risk factors associated with DTE use.

Presentation: 6/2/2024
7487 Iatrogenic Cushing’s Syndrome In A Patient On Prezcobix And Fluticasone
Authors: Davis A N , Nicholson M
Published: October 2024

Disclosure: A.N. Davis: None. M. Nicholson: None.

Introduction: The HIV medication Prezcobix contains darunavir, a protease inhibitor which is known to inhibit the hepatic enzyme CYP3A4. This may lead to accumulation of some medications in the blood, including fluticasone. We present a patient with iatrogenic Cushing’s syndrome while on Prezcobix and fluticasone. Case: Patient is a 55-year-old man who presented to clinic 3/13/23 for evaluation for cushingoid appearance at the request of his infectious disease (ID) physician. The patient has history of HIV, asthma, and seasonal allergies and had been taking Prezcobix, inhaled fluticasone, and intranasal fluticasone for over 3 years. Patient noted easy bruising and difficulty with weight loss. Vital signs were remarkable for elevated blood pressure at 165/86 despite taking amlodipine, HCTZ, and carvedilol. He was overweight with BMI 27.2. Physical exam revealed a somewhat rounded face, mild central obesity, no dorsocervical or supraclavicular fat pads, and no purple striae. Labs on 3/8/23 were remarkable for cortisol level <0.40mcg/dL at 4:10PM. Labs on 3/13/23 were remarkable for cortisol <0.40mcg/dL, ACTH level <5.0pg/mL, and urine fluticasone 17-beta carboxylic acid elevated at 540pg/mL (<10pg/mL) at 3:57PM. His ID physician planned to transition the patient off of Prezcobix and onto Tivicay, so patient was started on hydrocortisone 15mg PO daily at 8AM and 5mg daily at 2PM on the day he switched to Tivicay. He was gradually tapered off of hydrocortisone over a 2-3 month period without any symptoms concerning for adrenal insufficiency. His Cortisol level on 7/10/23 off hydrocortisone was 4.98mcg/dL at 7:56AM. Discussion: Prezcobix contains darunavir which is known to inhibit CYP3A4. With most patients, use of inhaled and intranasal fluticasone does not result in physiologically meaningful systemic levels of fluticasone. However, metabolism of fluticasone is dependent on CYP3A4, so systemic levels may increase with use of inhaled fluticasone with Prezcobix resulting in excess of corticosteroids and suppression of the native hypothalamic-pituitary-adrenal (HPA) axis. Fluticasone 17-beta carboxylic acid is a metabolite of fluticasone which is detectable in the urine. Sudden cessation of Prezcobix after prolonged use may result in secondary adrenal insufficiency from prolonged HPA axis suppression. Our case demonstrates how the use of Prezcobix with fluticasone may result in iatrogenic Cushing’s syndrome. Additionally, our case demonstrates that anticipation of secondary adrenal insufficiency after stopping Prezcobix allows for implementation of a safe transition plan.

Presentation: 6/1/2024
7099 Severe Hypothyroidism from Potassium Iodide Supplements: A Case of Failure to Escape from Wolf- Chaikoff Effect
Authors: Gbenga Hamilton Michael , Kulkarni Abhigna , Lekprasert Patamaporn
Published: October 2024

Disclosure: M.G. Hamilton: None. A. Kulkarni: None. P. Lekprasert: None.

Introduction: The Wolf-Chaikoff effect (WCE) is a physiological response of the thyroid gland to supraphysiologic iodide levels. Failure to escape the WCE can lead to thyroid dysfunction, and we present such a case in a patient with Hashimoto’s thyroiditis taking high-dose potassium iodide (KI). Case Description: A 44-year-old female with hypothyroidism secondary to Hashimoto’s thyroiditis presented with 10-pound weight gain, extremity swelling, fatigue, and abnormal menstruation. She was prescribed Levothyroxine several years ago but stopped taking it shortly after as she felt no improvement. On physical exam, she was bradycardic with heart rate of 58 bpm. There is no goiter but dry skin and edematous lower extremities. Labs revealed TSH of 127 pg/mL (0.35-4.94), free T4 0.1ng/dL (0.8-1.8), TPO Ab 645 (<9) IU/mL in comparison to her labs 2 months ago of TSH 11 pg/mL and free T4 0.9 ng/dL. Suspicion for worsening hypothyroidism from Hashimoto’s was low given this dramatic change on labwork and clinically. On further questioning, she had been taking KI 130 mg/day (Iodine 100 mg, daily requirement 150 mcg/day) as advised by her homeopathic doctor. The supplements were stopped, and she was re-started on Levothyroxine. After 8 weeks, she reported improvement of symptoms and weight loss. TSH is normal at 3.54pg/ml and free T4 1.2 ng/dL. Discussion:The WCE serves as a protective mechanism to decrease thyroid hormone production in the setting of high iodide levels to prevent development of hyperthyroidism. WCE is explained by the formation of Iodopeptides inhibits thyroid peroxidase (TPO) mRNA and protein synthesis resulting in an inhibition of thyroglobulin iodination. WCE is temporary and expected to wane over a few days to weeks and is known as the Wolf-Chaikoff escape due to down regulation of the sodium iodine symporter (NIS) thereby decreasing the intrathyroidal inorganic iodine concentration and permitting normal TPO activity. Rarely, failure to escape WCE can lead to hypothyroidism due to continued suppression of thyroid hormone synthesis. Risk factors include underlying thyroid diseases i.e. Hashimoto’s or other causes of thyroiditis, use of Amiodarone, Lithium or Iodine-containing radiocontrast media and KI supplements. In our case, Hashimotos’ thyroiditis predisposed her to thyroid dysfunction and failure to escape from WCE after taking high-dose KI supplements causing severe hypothyroidism. Thus, this report highlights that in clinical practice, especially in patients with pre-existing thyroid dysfunction, a significant TSH increase, a high suspicion index is needed to investigate for other causes like concurrent use of iodine-containing food/drug leading to the failed escape from WCE apart from verifying compliance to thyroid replacement therapy.

Presentation: 6/3/2024
7914 Staged Treatment with Radioiodine Following Lobectomy in a Case of High Risk Papillary Thyroid Carcinoma
Authors: Pathak Leilani , Sharma Arun , Rao Krisha , Jakoby Michael G
Published: October 2024

Disclosure: L. Pathak: None. A. Sharma: None. K. Rao: None. M.G. Jakoby: None.

Introduction: Radioiodine ([1]3[1]I ) is usually reserved for patients with differentiated thyroid carcinoma (DTC) who are at high risk of persistence or recurrence after thyroidectomy. We present a case of papillary thyroid carcinoma (PTC) with extrathyroidal extension managed by lobectomy and staged [1]3[1]I ablation of the contralateral lobe and metastases due to comorbidities that made oncologic resection prohibitive. Case Description: A 58-year-old male had a 2.2 cm focus of PTC in the left thyroid lobe that extended into extrathyroidal soft tissue, adjacent trachea, and completely compromised the left recurrent laryngeal nerve. Due to left vocal cord paralysis and subglottic tracheal stenosis, left lobectomy was performed but oncologic resection (total thyroidectomy and tracheal resection) was deferred. The patient underwent recombinant human TSH (rhTSH) stimulated treatment with 30 mCi (1.1 GBq) of [1]3[1]I for right thyroid lobe ablation followed 60 d later by 180 mCi (6.7 GBq) of [1]3[1]I to treat metastases. Response to treatment was incomplete, with unstimulated thyroglobulin level falling from 293.9 to 18.9 ng/mL 1 y after [1]3[1]I and CT of the neck notable for a 2.7 cm left thyroid bed mass with invasion of adjacent trachea and a 1.0 cm right paratracheal mass, both of which exhibited hypermetabolism on PET imaging and yielded cytology consistent with poorly differentiated thyroid carcinoma (PDTC). A cluster of left supraclavicular lymph nodes showed both hypermetabolism on PET and radioiodine uptake on rhTSH scan. This patient is being prepared for surgical resection of the left thyroid bed and right paratracheal tumors and left lateral lymph node dissection. Discussion: Radioiodine lobar ablation is an alternative to completion thyroidectomy in patients with an unexpected diagnosis of DTC after lobectomy, with a recent meta-analysis finding a success rate of 69%. No difference in thyroid cancer recurrence rates was found in nearly 500 matched pairs of patients undergoing completion thyroidectomy or radioiodine lobar ablation. Unfortunately, staged lobar ablation followed by high dose [1]3[1]I was not successful in treating this high-risk PTC patient. Cases of coexisting PTC and PDTC are reported, and [1]3[1]I treatment was unsuccessful at treating PDTC that was not apparent on postsurgical histopathology. This case indicates that surgery is preferable to staged [1]3[1]I treatment of patients with aggressive PTC, especially if there are no comorbidities that make total thyroidectomy a high-risk procedure.

Presentation: 6/2/2024
12345 Staying Ahead of Cowden’s Syndrome in Differentiated Thyroid Cancer
Authors: Gordon Michael S , Gordon Murray B
Published: October 2024

Disclosure: M.S. Gordon: None. M.B. Gordon: None.

Cowden’s syndrome or multiple hamartoma syndrome, is an uncommon autosomal dominant genodermatosis and is a member of the spectrum of disorders involving mutations in the phosphatase and tensin homolog gene (PTEN). It is associated with differentiated thyroid cancer (DTC), ¾ papillary, including follicular variant (FVPTC), 1/4 follicular (FTC), and other malignancies, including breast (most common), colorectal, renal cell, endometrial and skin cancers. We report a case of Cowden’s syndrome in which the patient presented with FVPTC but had no other apparent indication of a genetic abnormality until she was found to have a melanoma and was noted to have macrocephaly. The patient presented at age 26 with a thyroid nodule of 2.7 cm in maximal dimension. FNA was benign. By age 31 the lesion had grown to 3.3 cm and a repeat FNA showed a follicular neoplasm. She underwent left lobectomy and isthmusectomy revealing a 3.0 cm FVPTC with focal Hurthle cell features. There was capsular irregularity, and subsequently she underwent completion thyroidectomy showing a right sided 8mm FVPTC. She then received 30 mCi I 131. There were no apparent pathologic mucocutaneous lesions, intellectual deficits, and no family history of Cowden’s syndrome. At age 39 she was found to have a Stage IA malignant melanoma of the periumbilical skin which was resected. With two malignancies diagnosed at a relatively young age, she was evaluated for genetic syndromes and it was simultaneously noted that she had macrocephaly with head circumference of 66 cm. (>99 percentile). An analysis of 69 genes by Ambry genetics revealed a pathogenic variant in the PTEN gene (c.388 C>T (p.R130*). PTEN R130* results in a premature truncation of the PTEN protein at amino acid 130 of 403 within the phosphatase tensin-type domain resulting in loss of function. Macrocephaly (2% population frequency) is seen in 80% of patients with PTEN mutations. Twenty percent of patients with thyroid carcinoma and macrocephaly have a PTEN mutation and lifetime risk of melanoma in DTC is 25%. BRAF and RAS mutations may cooperate with PTEN loss and explain the increased co-occurrence of malignancies with BRAF and RAS mutations such as melanoma, FTC, and PTC in Cowden’s syndrome. In conclusion, we suggest that head circumference should be measured in all patients with DTC to screen for PTEN abnormalities. Patients with DTC also should have a thorough skin examination.

Presentation: 6/2/2024
6390 Takotsubo Cardiomyopathy (Case Report)
Authors: Ahmad Ballout Hajar , Malas Ibrahim , Sakor Zahraa , Ismail Mohamad , Najjar Claudette
Published: October 2024

Disclosure: H.A. Ballout: None. I. Malas: None. Z. Sakor: None. M. Ismail: None. C. Najjar: None.

Takotsubo is a reversible stress-induced cardiomyopathyusually associated with emotional or physical stress.Thyroid stormhas been identified as a rare cause of takotsubo. We report a rarecase of 64-year-old female presented with high BP. Blood testsshowed elevated troponin level and high FT4 FT4 Cardiacultrasound revealed normal size of the LV &anteroseptal wallakynisia,low ejection fraction,&diastolic LVD.Cardiac cathshowed normal coronary arteries, ventriculography showed apicalballooning and bulging in the left ventricle, suggesting Takotsubocardiomyopathy as a final diagnosis. patient was treated for thethyroid storm&takotsubo cardiomyopathy.month later she showedsignificant improvement in the cardiac function &thyroid hormone levels. As this case represented a rare stress-induced cardiomyopathy, the early diagnosis &suitable therapy areessential to prevent ongoing myocardial damage and providebetter chance for recovery.

Presentation: 6/2/2024
7445 The Effect of Combination Thyroid Hormone Therapies on Symptoms in Patients with a Suboptimal Response to Levothyroxine: A Post-Hoc Analysis
Authors: Patel A A , Shakir M K , Tuamokumo F , Bianco A C , Hoang T D
Published: October 2024

Disclosure: A.A. Patel: None. M.K. Shakir: None. F. Tuamokumo: None. A.C. Bianco: None. T.D. Hoang: None.

The standard treatment of hypothyroidism is levothyroxine (LT4). Combination therapies such as desiccated thyroid extract (DTE) or LT4 + liothyronine (LT3) are used much less. There is now evidence that combination therapies are effective and safe if serum thyroid stimulating hormone (TSH) is kept within a normal range. We studied whether there is a role for combination therapies specifically in hypothyroid patients who remain symptomatic despite biochemical evidence of adequate treatment with LT4, an issue that remains a challenging clinical conundrum for clinicians and patients alike. We conducted a post-hoc analysis of a prospective, randomized, double-blind, cross-over study of 75 patients with hypothyroidism performed at our institution. Patients were originally allocated to 1 of 3 treatment arms (LT4: Group A, DTE: Group B, or LT4+LT3: Group C) for 22 weeks and then crossed-over to the other two treatment arms sequentially for 22 weeks at a time until they had completed all treatment regimens. The Thyroid Symptom Questionnaire (TSQ) was completed by all patients during the initial study (a set of 12 questions with a total point range of 0-36; a higher score indicates more symptoms). We stratified patients by their TSQ score while on LT4 into three quantiles: Category 1 (TSQ 0-12; n=23), Category 2 (TSQ 13-24; n=42), Category 3 (TSQ 25-36; n=10). Differences were detected with a one-way ANOVA test and the Tukey multiple comparison post-test. No significant difference was found among treatment groups in Category 1 (p=0.063). In Category 2, the DTE group had significantly lower TSQ scores than the LT4 group (mean LTE score 18.9, SD 3.7; mean DTE score 14.3, SD 6.9; p=0.026). In Category 3, the LT4+LT3 group had significantly lower scores than LT4 and DTE groups (mean LTE score 27.7, SD 2.4; mean DTE score 23.1, SD 8.7; mean LT4+LT3 score 15.8, SD 4.7; p<0.001 LT4+LT3 vs LT4; p=0.026 LT4+LT3 vs DTE). This study demonstrates that patients with hypothyroidism who remain symptomatic while on LT4 may benefit from use of combination therapies such as DTE or LT4+LT3. Patients who generally have minimal residual symptoms with LT4 are unlikely to have significant symptomatic improvement on combination therapies. In addition, patients with moderate severity symptoms (TSQ 13-24) on LT4 had significant symptomatic improvement with DTE and patients with the most severe symptoms (TSQ 25-36) on LT4 had significant symptomatic improvement with LT4+LT3. No single TSQ question was more sensitive or prevalent in groups 2 and 3 (the most symptomatic groups). The results suggest a potential clinical role for combination therapies such as DTE and LT4+LT3 in patients who do not have improvement in hypothyroid symptoms on LT4 (TSQ score >13).

Presentation: 6/3/2024
6893 The Interaction Effect Between BMI, Diabetes, and Age at Diabetes Onset on the Risk of Thyroid Cancer: A Population-Based Cohort Study
Authors: Hou T , Li Y , Tian J , Bloomgarden Z , Shi Y
Published: October 2024

Disclosure: T. Hou: None. Y. Li: None. J. Tian: None. Z. Bloomgarden: None. Y. Shi: None.

ObjectiveThe relationship between type 2 diabetes mellitus (T2DM) and thyroid cancer was confounded by some characteristics of diabetes. We aimed to determine the association of the presence of diabetes and, among persons with diabetes, the age at T2DM onset, BMI, and the interactive effect with the subsequent thyroid cancer risk. MethodsWe conducted a population-based longitudinal cohort study including 428,568 persons with new-onset T2DM matched with the general population (100,649,346 person-years). Risk of thyroid cancer by subgroups were calculated based on standardized incidence ratio (SIR), hazard ratio (HR), and Cox proportional hazards models. ResultsIn T2DM patients, 1142 thyroid cancer cases were identified during eight years of follow-up, with an incidence rate of 59.01/100,000 person-years and a higher SIR: 1.21 (95% CI: 1.14-1.28) compared to the general population. New-onset T2DM had an overall 21% higher risk of thyroid cancer. Both the earlier age at T2DM onset and higher BMI were associated with a significant increasing risk of thyroid cancer independently (T2DM onset age <50: SIR 1.46 (1.27-1.69); BMI ≥30.0 Kg/m2 SIR: 1.93 (1.57-2.38)). The highest risk of cancer appeared in the patients with both BMI ≥30.0 Kg/m2 and T2DM onset age <50 years (SIR=3.91, HR=3.04). Among patients with T2DM onset age <60 years, SIR shows an increasing trend of cancer risk with higher BMI levels, while no significant increasing trends with higher BMI in T2DM onset age ≥60 years. For patients with BMI ≥25.0 Kg/m2, SIR of cancer risk decreases with an later T2DM onset age, whereas no significant decreasing trends of cancer risk in BMI <24.9 Kg/m2 group. Obese (BMI ≥30.0 Kg/m2) patients had a significant higher HR of thyroid cancer only when T2DM onset age <60 years. ConclusionsBoth earlier age of T2DM onset (<50 years) and higher BMI (≥30 Kg/m2) contributed to higher risk of thyroid cancer. These results suggest that earlier screening of thyroid cancer might be appropriate in patients diagnosed with T2DM, especially in individuals with young-onset T2DM and obesity.

Presentation: 6/3/2024
6897 The Role of Neutrophil Heterogeneity on T-cell Immunity in Advanced Thyroid Cancer Patients
Authors: Kang Y , Lee S , Yoon J , Kang D , Lee J
Published: October 2024

Disclosure: Y. Kang: None. S. Lee: None. J. Yoon: None. D. Kang: None. J. Lee: None.

Neutrophil heterogeneity is involved in autoimmune diseases, sepsis, and several cancers. However, the link between neutrophil heterogeneity and T-cell immunity in thyroid cancer is incompletely understood. We investigated the circulating neutrophil heterogeneity in 3 undifferentiated thyroid cancer (UTC), 14 differentiated thyroid cancer (DTC) (4 Stage IV, 10 Stage I-II), and healthy controls (n=10) by transcriptomic data and cytometry. Participants with UTC had a significantly higher proportion of immature high-density neutrophils (HDN) and lower proportion of mature HDN in peripheral blood compared to DTC. The proportion of circulating PD-L1+ immature neutrophils were significantly increased in advanced cancer patients. Unsupervised analysis of transcriptomics data from circulating HDN revealed downregulation of innate immune response and T cell receptor signaling pathway in cancer patients. Moreover, UTC patients revealed the upregulation of glycolytic process and glutamate receptor signaling pathway. Comparative analysis across tumor types and stages revealed the downregulation of various T cell related pathways, such as T cell receptor signaling pathway and T cell proliferation in advanced cancer patients. Moreover, the proportions of CD8+ and CD4+ T effector memory CD45RA+ (TEMRA) cells from peripheral blood were significantly decreased in UTC patients compared to DTC patients. Finally, we demonstrated that proportions of tumor infiltrated neutrophils were increased and related with poor prognosis in advanced thyroid cancer using data from our RNA-seq and TCGA (The Cancer Genome Atlas) data. In conclusion, observed prevalence of circulating immature high-density neutrophils and their immunosuppressive features in undifferentiated thyroid cancers underscore the importance of understanding neutrophil dynamics in the context of tumor progression in thyroid cancer.

Presentation: 6/3/2024