scholarly journals SAT-LB55 A Case of Central Hyperthyroidism From a TSH Secreting Pituitary Adenoma

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Maria Guia Estrella dela Cruz Almeda
Keyword(s):  
Pituitary Adenoma ◽  
Vision Loss ◽  
Csf Leak ◽  
Thyroid Function Tests ◽  
Free T4 ◽  
Initial Work ◽  
History Of ◽  
Urine Cortisol ◽  
Central Hyperthyroidism ◽  
Work Up

Abstract This is a case of a 41 year old Filipino female, with one month history of palpitations, unintentional weight loss and increased frequency of bowel movement. Patient was tachycardic and had a slightly enlarged thyroid on physical exam. There were no cushingoid or acromegalic features. Initial work-up revealed elevated TSH 7.10 U/mL prompting referral to an endocrinologist who had an initial consideration of central hyperthyroidism, MRI was done revealing a pituitary adenoma with dimensions of 7.4 x 11 x 5.8 mm. Prolactin level was at 118.9 ng/mL, gonadotropins (FSH 5 mIU/mL, LH 4.3 IU/L) were within normal range for pre-menopausal non pregnant women and early 24h urine cortisol was within normal at 63.79 nmol/ day. Patient was started on propranolol 40 mg thrice daily and methimazole 20 mg twice a day which prompted slight relief. She was also referred to neurosurgery service for further management. Patient underwent transsphenoidal surgery which was tolerated well. Subsequent clinical course revealed improvement of hyperthyroid symptoms with no evidence of post-operative complications such as hematomas, CSF leak, vision loss, diabetes insipidus or central adrenal insufficiency. Immunohistochemical staining was positive for TSH. On outpatient follow-up, repeat thyroid function tests were within normal with TSH 1.260 and free T4 15.07 pmol/L. Patient is currently symptom free and off methimazole or propranolol. Future plans include a repeat MRI after 6 months of surgery and hormonal testing to confirm cure.

scholarly journals A Rare Case of a Plurihormonal Pituitary Adenoma

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A565-A565
Author(s):  
Alisha Hossain ◽  
Emily Skutnik ◽  
Arjan Ahluwalia ◽  
Lindor Gelin ◽  
Sonum Singh ◽  
...  
Keyword(s):  
Pituitary Adenoma ◽  
Thyroid Function ◽  
Pituitary Adenomas ◽  
Alpha Subunit ◽  
Histological Evaluation ◽  
Benign Tumors ◽  
Thyroid Function Tests ◽  
Free T4 ◽  
Function Tests ◽  
Suppression Test

Abstract Background: Pituitary adenomas are usually benign tumors that arise from adenophypophyseal cells and produce one or two types of hormones. Plurihormonal adenomas are a rare subtype that produce two or more hormones and represent less than 1% of all pituitary adenomas. Clinical Presentation: A 76-year-old female presented for evaluation of abnormal thyroid function test results. She was found to have an elevated free T4 of 1.92 ng/dL and total T4 of 14.4 ug/dL with an inappropriately normal TSH of 2.11 uIU/mL. Physical examination was significant for tachycardia, tremors, diaphoresis, coarse facial features, and enlarged hands. Further biochemical evaluation of her pituitary hormone levels demonstrated an elevated prolactin (PRL) of 237.2 ng/mL, elevated insulin-like growth factor 1 (IGF-1) of 787 ng/mL, normal morning ACTH of 47 pg/mL, normal morning cortisol of 17.0 ug/dL, an inappropriately suppressed FSH of <5.0 mIU/mL, an elevated alpha subunit of pituitary glycoprotein hormones (PGH) of 6.9 ng/mL, and an elevated free T4 of 3.5 ng/dL by equilibrium dialysis. She underwent an MRI of the pituitary and brain which demonstrated a pituitary adenoma measuring 1.2 x 1.3 x 1.8 cm with a portion herniating into the sella turcica with no mass effect of the optic chiasm. A formal visual field examination was normal. The patient underwent workup for Cushing’s Disease with a low dose overnight dexamethasone suppression test, resulting in an appropriate response with an 8 AM cortisol of <1.0 ug/dL. Glucose suppression test confirmed the diagnosis of acromegaly with growth hormone at 120 minutes of 19.90 ng/mL. Neurosurgery performed a trans-sphenoidal pituitary adenoma resection. Thyroid function tests on post-operative day 4 demonstrated a suppressed TSH of 0.01 uIU/mL and an elevated free T4 of 2.30 ng/dL. Histological evaluation revealed dual expression of transcription factors pituitary-specific positive transcription factor 1 (PIT1) and steroidogenic factor 1 (SF1) as well as PRL, GH, TSH and FSH expression. Immunostaining for LH and ACTH were negative. Post-operative IGF-1 and GH levels were 106 ng/mL and 0.51 ng/mL at 17 weeks, respectively. Post-operative TSH normalized to 0.82 uIU/mL, free T4 normalized to 1.04 ng/dL, and PRL normalized to 8.1 ng/mL at 12 weeks. The patient remained symptom free after successful surgical resection. Discussion: Our case demonstrates the clinical course of a unique patient with clinical and biochemical manifestations of thyroid dysfunction and acromegaly with a pituitary adenoma immunoreactive for GH, TSH, FSH, and PRL. The co-secretion of GH, TSH, PRL, and FSH as well as positivity for the alpha-subunit is extremely unusual. This case emphasizes the importance of considering pituitary abnormalities as a cause for abnormal thyroid function tests.

scholarly journals MON-478 Impaired Sensitivity to Thyroid Hormone - A Diagnostic and Therapeutic Challenge

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Jorge Pedro ◽  
Vanessa Gorito ◽  
Cristina Ferreras ◽  
Ferreira João Silva Maria ◽  
Sofia Ferreira ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Thyroid Function ◽  
Thyroid Function Tests ◽  
Pediatric Endocrinology ◽  
Free T4 ◽  
Peripheral Tissues ◽  
Free T3 ◽  
Function Tests ◽  
Trh Stimulation ◽  
History Of

Abstract Background: Impaired sensitivity to thyroid hormone refers to any process that negatively affects its action, including defects in its transport, metabolism and action on the receptor. Resistance to thyroid hormone due to beta-receptor mutations (RTH-beta) is the most common form of this entity and is characterized by reduced response of peripheral tissues to the action of thyroid hormone. The genetic variability of cofactors involved in the action of thyroid hormone explains the heterogeneity of resistance among affected individuals. Generally, patients with this disorder, have increased levels of free T4 and free T3 in association with normal or high TSH. Clinical case: 11-year-old boy, with personal history of Attention-deficit/hyperactivity disorder (ADHD). A pediatric endocrinology consultation was requested to evaluate abnormalities in his thyroid function tests. A few months earlier, his father was referred to endocrinology consultation because of thyroid function tests abnormalities: TSH - 3.01 μIU / mL (N: 0.35 - 4.94); Free T4 1.7 ng / dL (N: 0.7-1.48); Free T3 4.77 pg / mL (N: 1.71-3.71). Initially, two diagnostic hypotheses were considered: central hyperthyroidism or impaired sensitivity to thyroid hormone. The adult underwent pituitary magnetic resonance, which raised the hypothesis of a pituitary microadenoma, and TRH stimulation test, whose result was strongly suggestive of the second diagnostic possibility. A genetic study was requested and the presence of the c700 G> A variant (p. Ala 324 trh) in the THRB gene was identified, which confirmed the most likely hypothesis. At the time of the pediatric endocrinology consultation, the 11-year-old boy had the results of his lab tests: TSH - 6.67 μIU / mL (N: 0.35 - 5); T4L 2.27 ng / dL (N: 0.88-1.58); T3L 7.79 pg / mL (N: 2-4.20). Given his perfect height and weight evolution and the absence of symptoms suggestive of hypo or hyperthyroidism, it was decided not to start any medication, keeping only periodic surveillance. Conclusion: This case exemplifies unusual thyroid function tests. This discordance between serum thyroid hormone and TSH concentrations should raise the possibility of impaired sensitivity to thyroid hormone. In this condition, patients may present with symptoms of hypo or hyperthyroidism and the etiology of thyroid function tests abnormalities are not easily recognized. This can lead to misdiagnosis and consequently unnecessary treatment.

scholarly journals A173 RECOGNIZING RARE PRESENTATIONS OF POLYPOSIS SYNDROMES AND THEIR ASSOCIATED MALIGNANCIES IN PEDIATRIC PATIENTS

2020 ◽  
Vol 3 (Supplement_1) ◽  
pp. 38-39
Author(s):  
N E Reitzel ◽  
M Sherlock ◽  
M Zachos ◽  
J Arredondo ◽  
E Ratcliffe
Keyword(s):  
Abdominal Pain ◽  
Ileoanal Anastomosis ◽  
Bilateral Mastectomy ◽  
Total Proctocolectomy ◽  
Case Review ◽  
Screening Endoscopy ◽  
Initial Work ◽  
History Of ◽  
Polyposis Syndromes ◽  
Work Up

Abstract Background There is a range of polyposis syndromes and presentations in pediatrics. There are also associated extra-colonic malignancies of which to be cognizant when orchestrating the initial work-up of the various polyposis syndromes. Aims To use case review to highlight the importance of recognizing the breadth of presentations of polyposis syndromes in pediatrics. Methods Two recent pediatric presentations of polyposis with extra-intestinal manifestations were identified, chart review completed, and compared with newly published ESPGHAN guidelines. Results Two patients with intestinal polyposis are presented, in which extra-colonic malignancies and genetic mutations were identified. The first patient presented at age 16 with a history of fatigue and abdominal pain, and was found to have pancytopenia and splenomegaly. Initial work up included a bone marrow biopsy that was normal. The patient then underwent upper and lower endoscopic evaluation for increasing abdominal pain and persistent anemia and was found to have polymorphic polyps in the duodenum, sigmoid and rectum. On pathology, polyps were mostly inflammatory, but one was found to be hamartomatous. Additional screening revealed a thyroid nodule, found to be follicular carcinoma, requiring hemithyroidectomy. The patient was confirmed to have a PTEN mutation and was diagnosed with Cowden syndrome; following this diagnosis proceeded with a prophylactic bilateral mastectomy. The second patient was referred at age 15 with a strong family history of APC-associated FAP. At the time of consultation she was asymptomatic and she remained so throughout her work-up. Screening endoscopy revealed 70–90 recto-sigmoid adenomatous polyps as well as scattered gastric and duodenal polyps. Her initial work-up also uncovered an early papillary thyroid carcinoma. Her treatment included a total thyroidectomy and total proctocolectomy with J-pouch and ileoanal anastomosis. Follow-up endoscopy continues for surveillance of numerous gastric adenomas which to this point have not progressed to high-grade dysplasia or malignancy. Conclusions These 2 cases highlight the importance of recognizing that neoplastic conditions typically diagnosed in adulthood can also present in the pediatric age group. Ideally, further guidelines in pediatrics would be beneficial to ensure a consistent approach to investigating polyposis and associated malignancies. Pertaining to our specific patients, each had identification of a thyroid malignancy before the recommended screening age of 18 as per the currently accepted guideline, and neither were symptomatic. More cases are needed to establish if this earlier recognition of disease is meaningful in postulating potential mortality associated with a later diagnosis. Funding Agencies None

scholarly journals SUN-504 A Case of T3 Thyrotoxicosis

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Isabelle Daneault Peloquin ◽  
Matthieu St-Jean
Keyword(s):  
Thyroid Function ◽  
Thyroid Function Test ◽  
Nutritional Supplement ◽  
Thyroid Function Tests ◽  
Free T4 ◽  
Endocrine Society ◽  
Product Consumption ◽  
Function Tests ◽  
History Of ◽  
Receptor Antibodies

Abstract Clinical vignette ENDOCRINE SOCIETY 2020 Title: A case of T3 thyrotoxicosis induced by a dietary supplement. A 24 yo man consulted for a 2 weeks history of diaphoresis, fatigue, insomnia, palpitations and headache associated with a 20 pounds lost. The patient didn’t have a goiter or any signs of orbitopathy. The results revealed a free T3 level of 45.8 pmol/L upon arrival (normal (N) 3.4- 6.8 pmol/L), free T4 level of 6.4 pmol/L (N 11.0–22.0 pmol/L) and TSH level less than 0.005 mUI/L (N: 0.35 to 3.50 mUI/L). Facing those results, a complete review of the patient medication and natural product consumption was done. The patient revealed that he was using, since a month, a vegetable extracts nutritional supplement that didn’t included iodine. He was asked to stop the nutritional supplement and propranolol 10 mg twice daily was prescribed. Thyroid function tests were done 3 days after. The results demonstrate a fT3 level of 4.6 pmol/L, a fT4 level of 5.6 pmol/L and a TSH that still suppressed. A thyroid scintigraphy was performed 7 days later and showed a homogeneous uptake of 18.5% (N 7.0% – 35.0%). We saw the patient 2 weeks later and we ordered another thyroid function test with TSH receptor antibodies, TPO antibodies and thyroglobulin. The results were the following: fT3 of 5.1 pmol/L, fT4 of 12.1 pmol/L, TSH of 2.31 mUI/L, thyroglobulin of 19.8 ug/L (N: 1.4 – 78) and normal levels of antibodies against TPO and TSH receptors. To confirm the contamination of the nutritional supplement by fT3 we used a plasma pool of normal patients in which we measured thyroid function tests at baseline and after we have added the nutritional supplement powder to reflect the dose suggested by the manufacturer. The results showed that fT3 level increased by 36.5%, fT4 by 11.2% and TSH didn’t changed. The powder was then analyzed by an external laboratory that wasn’t able to demonstrate the presence of fT3 nor fT4. The two diagnostic possibility facing those results were that the powder induced an interference with immunoassay used to measure fT3 and fT4 but not TSH or thyrotoxicosis induced by the nutritional supplement with limitation in the technique that tried to identify fT3 in the powder. Given the presentation of the patient, we are convinced that this case represents a thyrotoxicosis induced by a nutritional supplement. In conclusion, Graves’ disease is responsible for 60–80% of the cases of hyperthyroidism. However, there are few cases reports of thyrotoxicosis induced by nutritional supplement1,2, but some studies demonstrate the presence of thyroid hormone in significant amounts in some commercially available health supplements3. This case highlights the importance of verifying exposition to medications and natural products when confronted to cases of thyrotoxicosis. 1.Regina A et al. MMWR Morb Mortal Wkly Rep. 2016 2. Panikkath R et al. Am J Ther. 2014 3. Kang GY et al. Thyroid. 2013

Amiodarone-induced type 2 thyrotoxicosis

2021 ◽  
Vol 14 (1) ◽  
pp. e238145
Author(s):  
Darryl Portelli ◽  
Simon Mifsud ◽  
Alexia Abela ◽  
Stephen Fava
Keyword(s):  
Atrial Fibrillation ◽  
Weight Loss ◽  
Thyroid Gland ◽  
Thyroid Stimulating Hormone ◽  
Thyroid Function Tests ◽  
Exertional Dyspnoea ◽  
Free T4 ◽  
Tsh Receptor Antibody ◽  
History Of

The authors present a case of a 55-year-old gentleman with a medical history of atrial fibrillation on amiodarone who presented with weight loss, palpitations and exertional dyspnoea. Thyroid function tests revealed thyrotoxicosis with a free thyroxine (T4) of 117 pmol/L and a thyroid-stimulating hormone (TSH) of <0.008 mIU/L. Interleukin-6 level was low. The negative TSH-receptor antibody status, the presence of a small thyroid gland with heterogeneous echotexture and decreased internal vascularity on ultrasound together with the relatively quick drop in free T4 and free tri-iodothyronine (T3) levels once prednisolone therapy was added to carbimazole suggested that this was typical of amiodarone-induced thyrotoxicosis (AIT) type 2. Subsequently, carbimazole was discontinued and treatment with prednisolone was continued. This case highlights that AIT management may be challenging and it is of paramount importance to establish the type of AIT present as this will guide management and is key to improving prognosis.

scholarly journals Presentation of spinal cord and column tumors

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. i18-i24
Author(s):  
Jared S Fridley ◽  
Sohail Syed ◽  
Tianyi Niu ◽  
Owen P Leary ◽  
Ziya L Gokaslan
Keyword(s):  
Back Pain ◽  
Systemic Treatment ◽  
Early Recognition ◽  
Spinal Metastases ◽  
Appropriate Treatment ◽  
Initial Work ◽  
History Of ◽  
Patient Prognosis ◽  
Work Up ◽  
Spine Disease

Abstract Metastatic spine disease occurs in more than 10% of all cancer patients. Advances in systemic treatment for cancer has led to improved overall survival for many types of cancer, which has increased the overall incidence of spinal metastases. The most common presenting complaint of patients with spinal metastases is pain. Pain originating from spinal metastases can be oncological, mechanical, and/or neurological in nature. Early recognition of these symptoms is helpful to guide treatment and accurately gauge patient prognosis. Unfortunately, the prevalence of degenerative back pain in the general population can complicate early clinical recognition of patients with metastatic spine disease. Therefore, back pain in any patient with a history of malignancy should prompt clinicians to perform an expedited workup for metastatic disease of the spine. Diagnostic imaging and laboratory studies are part of the initial work up. Obtaining pathology via biopsy to establish tumor histology is essential to determine the appropriate treatment.

THYROTOXICOSIS SECONDARY TO ALEMTUZUMAB TREATMENT FOR MULTIPLE SCLEROSIS PRESENTING AS PULMONARY HYPERTENSION

2015 ◽  
Vol 86 (11) ◽  
pp. e4.12-e4
Author(s):  
S Healy ◽  
MD Willis ◽  
TP Pickersgill ◽  
M Page ◽  
NP Robertson
Keyword(s):  
Multiple Sclerosis ◽  
Pulmonary Hypertension ◽  
Early Stage ◽  
Significant Risk ◽  
Thyroid Function Tests ◽  
Free T4 ◽  
Pulmonary Angiogram ◽  
History Of ◽  
Ct Pulmonary Angiogram ◽  
Relapsing Multiple Sclerosis

Alemtuzumab has been approved for use in the treatment of relapsing multiple sclerosis. Despite its proven clinical efficacy acquired autoimmune disease remains a significant risk. In particular thyroid disease is common and robust surveillance mechanisms are required to identify disease at an early stage. We present the case of a 31-year-old female patient who presented with signs consistent with pulmonary hypertension as the presenting feature of thyrotoxicosis. 12-months after the first alemtuzumab treatment course the patient presented to clinic with a 2-week history of exertional dyspnoea, palpitations and headaches. On examination, she had a new pansystolic murmur loudest in the pulmonary area and bilateral pitting oedema to the knees. An echocardiogram demonstrated elevated right ventricular pressure (40 mm Hg) and tricuspid regurgitation consistent with pulmonary hypertension. A CT pulmonary angiogram did not demonstrate evidence of a pulmonary embolus. Thyroid function tests revealed profound thyrotoxicosis (free T4 37.3 pmol/l and TSH <0.02 mU/l), which was thought to be the likely cause. Carbimazole was started but discontinued due to a rash with euthyroidism eventually achieved with radio-iodine. Her symptoms have subsequently resolved. This case highlights the need for neurologists using Alemtuzumab to be vigilant of the varied and sometimes acute presentations of thyroid dysfunction; and the growing repertoire of induced autoimmunity.

scholarly journals Sporadic Creutzfeldt-Jakob Disease with Worsening Depression and Cognition

2007 ◽  
Vol 34 (4) ◽  
pp. 464-466 ◽  
Author(s):  
Mark Hudon ◽  
Richard Farb ◽  
Taim Muayqil ◽  
Zaeem A. Siddiqi
Keyword(s):  
Cerebral Atrophy ◽  
Early Morning ◽  
Thyroid Function Tests ◽  
Cell Counts ◽  
Mini Mental Status Examination ◽  
History Of ◽  
Brain Magnetic Resonance Image ◽  
Jakob Disease ◽  
One Year ◽  
Work Up

A 58-year-old male presented with a one-year history of low mood, early morning awakening from sleep, apathy, difficulty with memory, concentration and organization. This had been associated with intrusive concerns of a recent social stressor. He was no longer able to work and was on medical disability. Except for a 20kg weight loss there were no other constitutional or neurological symptoms. He had hypertension and hypercholesterolemia and was on atorvastatin and aspirin. He scored 28/30 on mini-mental status examination (MMSE) with errors on object recall; however he could recall forgotten items after cueing. He had difficulty with concentration, was apathic andhad a negative outlook to the future. His neurological examination and a detailed hematological work up including chemistry, cell counts, vitamin B12, folate, and renal, hepatic and thyroid function tests were normal. A brain magnetic resonance image (MRI) showed mild cerebral atrophy. Based on a formal neuropsychological assessment he was diagnosed with depression and started on Venlafaxine.

scholarly journals MON-481 Remarkable Euthyroid Hyperthyroxinemia Mistaken for Thyrotoxicosis

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Annavi Baghel ◽  
Joshua D Maier
Keyword(s):  
Thyroid Hormone ◽  
Thyroid Function ◽  
Clinical Status ◽  
Thyroid Function Tests ◽  
Thyroid Disorder ◽  
Diagnostic Challenge ◽  
Free T4 ◽  
Free T3 ◽  
History Of ◽  
Euthyroid Hyperthyroxinemia

Abstract CLINICAL CASE A 46 year old caucasian female with past medical history of menorrhagia was referred from primary care for evaluation of thyrotoxicosis. Thyroid function was assessed in the context of menometrorrhagia. She did not have any history of thyroid disorder or abnormal thyroid function tests. Per outside records, recent labs demonstrated TSH 0.88 uIU/mL (0.36-3.74), Free T4 &gt; 8.00 ng/dL (0.76-1.46), Free T3 2.9 pg/mL (2.18-3.98). All other labs were within normal limits. Thyroid ultrasound revealed normal parenchyma and volume. She did not take any medications or supplements including biotin. She denied heat intolerance, anxiety, palpitations, dyspnea, tremors, hyperdefecation, or change in hair, skin, or mood. No epiphora, diplopia, or eye irritation was reported. Her father had been diagnosed with hyperthyroidism, mother with hypothyroidism. Repeat labs at our visit revealed normal TSH of 1.05 uIU/mL (0.358- 3.74), normal Free T3 2.58 pg/mL (2.18- 3.98), normal Total T3 136 ng/dL (80-200), elevated Free T4 &gt;8.00 ng/dL (0.76-1.46) and elevated Total T4 11.6 ug/dL (4.5-10.5). These lab values were not consistent with patient’s euthyroid clinical status, prompting assessment of Free T4 by dialysis, normal at 1.5 ng/dL (0.9-2.2) and T3 uptake, high at 40% (24-39%). This picture was consistent with Familial Dysalbuminemic Hyperthyroxenemia (FDH). The decision was made not to treat the patient with anti-thyroid medications and to perform a confirmatory genetic testing to test for mutations in the ALB (albumin) gene. DISCUSSION The free T4 assay used by our institution is performed on the Siemens Dimension Vista platform using a two-step chemiluminescent immunoassay. While in theory two-step assays should not yield abnormal results in FDH, several two-step assays are known to yield falsely high results in patients with FDH (1, 2, 3). Other potential etiologies for discordant Free T4 levels include thyroid hormone autoantibodies, heterophile antibodies, biotin use, and anti-streptavidin antibodies (3). CONCLUSION Recognition of laboratory error in the workup of thyroid disease is essential. Clinicians must ensure thyroid function labs are consistent with each other and with the patient’s presentation. In such cases misdiagnosis of hyperthyroidism or thyroid hormone resistance may lead to unnecessary testing and inappropriate treatment (3). References 1. Cartwright D et al. Familial dysalbuminemic hyperthyroxinemia: a persistent diagnostic challenge. Clin Chem. 2009 May;55(5):1044-6 2. Ross HA et al. Spuriously high free thyroxine values in familial dysalbuminemic hyperthyroxinemia. Clin Chem. 2011 Mar;57(3):524-5 3. Favresse J et al. Interferences With Thyroid Function Immunoassays: Clinical Implications and Detection Algorithm. Endocr Rev. 2018 Oct 1;39(5):830-850.

scholarly journals SAT-477 Melanoma Treated with Pembrolizumab Leading to Thyroiditis and Subsequent Hypothyroidism

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Heather Fishel
Keyword(s):  
Thyroid Function ◽  
T Cell Activation ◽  
Thyroid Dysfunction ◽  
Subsequent Development ◽  
Thyroid Function Tests ◽  
Free T4 ◽  
Specific Patient ◽  
Normal Thyroid ◽  
Free T3 ◽  
History Of

Abstract Background: Pembrolizumab (PD-1) is an immune checkpoint inhibitor used for treating melanoma and has been associated endocrine immune-related adverse events. Case Presentation: 76-year-old Caucasian male presented for evaluation of abnormal thyroid labs. Significant co-morbidities included recurrent melanoma, heart failure, atrial fibrillation, coronary artery disease, type 2 diabetes, hypertension. Patient’s melanoma was being treated with Pembrolizumab. Further history revealed no family/personal history of thyroid disease but a history of mouth cancer treated with radiation over 30 years ago. He denied any recent glucocorticoid or biotin use. Symptoms included worsening fatigue, weight loss, and diarrhea. He was afebrile and vitally stable. Physical exam was unremarkable. Prior to this year, patient had normal thyroid labs. Recent thyroid labs showed TSH of 0.01 uIU/mL (normal 0.34-4.94 uIU/mL), confirmed with repeat labs a week later (TSH: &lt; 0.01, Free T4: 2.23 ng/dL, normal Free T4: 0.7-1.48 ng/dL). There was a high suspicion that these labs were related to Pembrolizumab, but other etiologies were evaluated. Completed thyroid uptake and scan showed no evidence of increased activity (4-hour uptake: 1.6%, 24-hour update: 1.2%). Repeat thyroid labs indicated recovering thyroid function with a TSH: 0.14 uIU/mL, Free T4: 0.49 ng/dL, Free T3: 1.5 pg/mL (normal Free T3 2.3-4.2 pg/mL), TSI: 96% (normal &lt; 140%), TPO Ab: 111 IU/mL (normal TPO Ab &lt; 9 IU/mL). One month later thyroid tests resulted as TSH: 72.81 uIU/mL, Free T4: &lt; 0.40. He was started on levothyroxine, which was titrated over several weeks. Discussion: Pembrolizumab (PD-1) is an IgG4 programmed cell death 1-directed monoclonal antibody, whose mechanism of action is to inhibit cancer cells ability impede T-cell activation. However, because of this mechanism, some T-cells, will remain activated, leading to autoimmune diseases. PD-1 has been associated with thyroid dysfunction, with an incidence rate as high as 14-20%. The clinical presentation varies from isolated thyrotoxicosis to overt hypothyroidism. In our patient, he developed thyrotoxicosis with subsequent development of hypothyroidism. Generally, the timing of thyroid dysfunction after the initiation of PD-1 ranges from 3 to 40 weeks, with the median onset at week 6. Baseline TSH and free T4 should be obtained with rechecking of these labs monthly for the first 6 months. For patients who present with thyrotoxicosis, Grave’s disease should be ruled out, and initial treatment should include beta-blockers. Hypothyroidism should be treated with levothyroxine with titration to normal thyroid function tests. What remains to be determined is the mechanism in which PD-1 causes thyroid dysfunction and if specific patient characteristics, such as thyroid antibodies, can be used to risk stratify the likelihood of a patient developing thyroid dysfunction.

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