Repeat Thyroid Function Tests Research Articles

7915 A Case of Severe Hypothyroidism in a Patient with Nephrotic Syndrome presenting with Rhabdomyolysis requiring Levothyroxine and Liothyronine combination therapy

Abstract Disclosure: S.S. Mohammed: None. E.T. Ngo: None. S. Tadisina: None. B.M. Drees: None. Background: Nephrotic syndrome is known to worsen hypothyroidism via urinary loss of thyroid binding globulin, transthyretin, albumin and other proteins, often requiring escalating levothyroxine doses. Severe uncontrolled hypothyroidism can result in rhabdomyolysis, although this presentation is quite rare. Clinical case: We present a case of a 50-year-old male with long-standing Hashimoto’s hypothyroidism, biopsy-proven minimal change disease with nephrotic syndrome, dyslipidemia, and hypertension, who was admitted for generalized myalgia, weakness, and progressive swelling of bilateral hands and feet for one month. He had been off levothyroxine 3 months prior to presentation. He previously required large doses of oral levothyroxine, as high as 350mcg daily, but never achieved a euthyroid state despite reported adherence to therapy with the high levothyroxine doses.Laboratory workup showed severe hypothyroidism (free thyroxine <0.25ng/dL [0.6-1.6ng/dL] with markedly elevated thyroid stimulating hormone 282.03 mIU/mL [0.3-5.6mIU/mL]), along with acute kidney injury and rhabdomyolysis (Creatine kinase 4882 U/L[38-234U/L]). He was hemodynamically stable with intact mentation and was not deemed to be in myxedema coma. Physical examination was consistent with hypothyroidism with periorbital swelling, dry skin, deep hoarse voice, bilateral hand and feet edema, and delayed deep tendon reflexes. Thyroid function tests and clinical symptoms failed to improve after 8 days, despite high doses of levothyroxine IV (200mcg). Creatine kinase remained high at 4994 U/L [38-234U/L] despite adequate fluid hydration. Liothyronine 5mcg orally was started in addition to levothyroxine 200mcg IV. Repeat thyroid function tests after 2 days of combined IV levothyroxine and oral liothyronine therapy showed significant downtrend in TSH to 154.12 uIU/ml [0.3-5.6mIU/mL] and increase in free thyroxine to 0.44ng/dl [0.6-1.6ng/dL]. Creatine kinase also down trended to 3181U/L[38-234U/L] on D4 of IV levothyroxine 200mcg IV with liothyronine 5mcg daily. He was discharged stable and clinically improved on oral levothyroxine and liothyronine. Laboratory evaluation 10 days later showed further improvement in TFTs (TSH 66.0[0.3-5.6mIU/mL]), free thyroxine 0.6 [0.6-1.6ng/dL] Conclusion: This case presents a unique and unusual clinical course in symptomatic primary hypothyroidism with rhabdomyolysis and AKI. Rhabdomyolysis due to hypothyroidism, without an obvious precipitating factor, has been previously reported, but is very rare. There is limited evidence regarding combination treatment with levothyroxine and liothyronine in primary hypothyroidism; however, as demonstrated in this patient, combination therapy resulted in clinical and biochemical improvement of thyroid function. Presentation: 6/2/2024

FRI508 A Case Of Durvalumab Induced Hypothyroidism

Abstract Disclosure: E.D. Cecilio La Riva: None. C. Acosta: None. A.J. Manzano: None. Background: Immune checkpoint inhibitors (ICIs), like Durvalumab, have become a mainstay in cancer treatment as they have significantly improved survival rates, especially for lung cancer. These treatments, however, have been associated with immune-related adverse events (irAEs) including dermatological manifestations, gastrointestinal symptoms, and endocrinopathies. Clinical Case: A 62-year-old male was diagnosed with a poorly differentiated adenocarcinoma with signet ring cell features stage IIIA of the right upper lobe with concurrent prostate cancer who was initially started on chemotherapy with Cisplatin/Pemetrexed for two months (four cycles) and radiation. He was subsequently started on Durvalumab. Thyroid function tests were performed after starting Durvalumab and TSH was 3.46 mlU/L (reference range: 0.40-4.50), Free T4 was 1.2 ng/dL (reference range: 0.8-1.8) and Free T3 was mildly elevated at 4.3 pg/mL (reference range: 2.3-4.2). The patient remained asymptomatic until about 12 weeks later when he began feeling occasional episodes of anxiety and shortness of breath with fatigue that was brought on at random instances. Thyroid function tests at that time showed an undetectable TSH at <0.01, an elevated free T3 at 4.9, and a normal free T4 at 1.6. Immunotherapy was continued and the patient was referred to endocrinology. Repeat thyroid function tests 8 weeks later showed an elevated TSH at 19.55, decreased free T4 at 0.7, and a normal free T3 at 3.1. The patient was started on levothyroxine at that time with improvement of his symptoms. Upon follow-up 4 weeks later, TSH was found at 30.56 and free T4 at 0.9 which improved with levothyroxine dose adjustment. Conclusion: The case of a patient with thyroiditis beginning as transient hyperthyroidism on Durvalumab is described. Hypothyroidism occurs in about 1.82% of patients on ICIs, with more common occurrences on Nivolumab (51.38%) and Pembrolizumab (24.44%). The incidence of hypothyroidism and thyroiditis on Durvalumab is about 3.11% and 2.04% respectively. Thyroid dysfunction with ICIs occurs with PD-1/PD-L1 blockade and an inflammatory, destructive thyroiditis can be seen. Routine monitoring of thyroid function should be performed before and throughout treatment with an ICIs. Preexisting autoimmune thyroid disease may be a risk factor for developing thyroid disease during treatment, but this has not been well studied. Meta-analysis has shown that preexisting autoimmune disease was a risk factor for irAE incidence. This case highlights the importance of proactive monitoring of thyroid function during treatment. Presentation: Friday, June 16, 2023

Abstract 10988: The Dynamic Duo of Electrical and Thyroid Storm Caused by Amiodarone

Case description: A 61 year-old male with a hx of CAD s/p CABG and HFrEF s/p AICD presents with a 4-day history of dizziness and shortness of breath; he was found to be in ventricular tachycardia (VT) storm. ICD interrogation was found to have 13 shocks in 24 hours. His thyroid function tests (TFT) were abnormal: TSH undetectable, elevated FT4 7.7 (0.93-1.7) and T3 246.6 (84-202) ng/dL, respectively. He was diagnosed with severe thyrotoxicosis, likely due to amiodarone-induced thyrotoxicosis (AIT) type 2 and a Burch-Wartofsky score of 50, highly suggestive of thyroid storm (TS). He was started on hydrocortisone, prednisone, propylthiouracil, and metoprolol for the TS. Procainamide drip had been initiated for VT and titrated until VT was controlled. Repeat TFTs in 48 hours showed no changes in TSH or FT4, but T3 had normalized. Procainamide and hydrocortisone were discontinued after VT frequency had decreased. Discussion: An electrical storm (ES) is a state of electrical instability characterized by multiple episodes of VT in 24 hours. In patients with ICD, it is defined as >3 anti-tachycardic pacing therapies or shock. Most patient with ES have severe underlying structural heart disease with various inciting events such as thyrotoxicosis. Amiodarone is the drug of choice in VT; however, complications such as AIT should be recognized. Thyroid hormone has a direct arrhythmogenic effect on the heart through various cellular mechanisms. In our patient, amiodarone was discontinued after the diagnosis of AIT. Procainamide and antithyroid therapy were started, which subsequently controlled the VT. Resistance to therapy can occur, and more elaborate interventions such as plasmapheresis are an option to remove amiodarone, its metabolites, and free thyroid hormones. Conclusion: Amiodarone is the most efficacious medication for VT. However, it is important to recognize possible life-threatening complications of this medication, such as AIT, which itself can exacerbate VT.

Approach to the Patient With a Suppressed TSH.

Subclinical hyperthyroidism (SCH) is a laboratory diagnosis defined by a serum thyrotropin (TSH) concentration below the reference range (< 0.4 mU/L in most assays), and a free thyroxine (FT4) and 3,5,3'-triiodothyronine levels (FT3) in the reference range. Many patients diagnosed with SCH will be clinically euthyroid while others may present with manifestations characteristic of thyroid hormone excess, such as tachycardia, tremor, intolerance to heat, bone density loss, or weight loss. In addition to the laboratory abnormalities, patient factors such as age, symptoms, and underlying heart and bone disease are used to stratify patients for the risk of adverse outcomes and determine the appropriate treatment. Evaluation should include repeat thyroid function tests to document persistent TSH suppression, investigation of the underlying cause, as well as evaluation of the patient's risk of adverse outcomes in the setting of a subnormal TSH. Persistent SCH has been associated with an increased risk of a range of adverse events, including cardiovascular events such as atrial fibrillation and heart failure, bone loss and fracture, and in some studies, cognitive decline. Despite the consistent association of these adverse events with SCH, prospective studies showing improved outcomes with treatment remain limited. Management options include observation without active therapy, radioactive iodine ablation of the thyroid, antithyroid medication, thyroid surgery, or radiofrequency ablation, as appropriate for the patient and clinical setting. The choice of therapy should be guided by the underlying etiology of disease, patient factors, and the risks and benefits of each treatment option.

ODP527 To Treat or Not to Treat Pembrolizumab-Induced Thyroiditis: Using Common Terminology Criteria for Adverse Events as a Decision-Making Aid

Abstract Introduction Programmed cell death-1 (PD-1) checkpoint inhibitors are immunotherapeutic agents that are used to treat advanced malignancies including breast cancer. The adverse effects of these medications include thyroid and pituitary dysfunction and may be treated with glucocorticoids, which may cause steroid-induced effects such as hyperglycemia, osteoporosis, and adrenal suppression. The Common Terminology Criteria for Adverse Events (CTCAE) widely used by oncologists for management can support treatment decisions by endocrinologists in patients undergoing treatment with PD-1 checkpoint inhibitors. Case Description A 42-year-old female with stage IIIc high-grade triple negative left breast invasive ductal carcinoma was started on pembrolizumab immunotherapy (PD-1 inhibitor). Prior to starting treatment, the patient's thyroid function tests were normal: free T4 0.93 ng/dL (normal range [NR] 0.89-1.76 ng/dL) and thyroid-stimulating hormone (TSH) 1.42 uIU/mL (NR 0.55-4.78 uIU/mL). Two weeks later, she developed heat intolerance, diarrhea, weight loss, and dysphagia. At that time, thyroid tests were consistent with thyrotoxicosis with elevated total T3 644.6 ng/dL (NR 60-180 ng/dL) and totalT4 &amp;gt;12. 00 ng/dL with suppressed TSH 0. 01 uIU/mL. Despite negative TSH receptor antibody and thyroid-stimulating immunoglobulin, CT scan of the neck showed diffuse enlargement of the thyroid gland and thickening of the extraocular muscles. On physical examination she had mild exophthalmos. The etiology of thyrotoxicosis was initially thought to be Graves’ disease, but thyroiditis could not be ruled out. Treatment with methimazole and beta blockers was initiated. Three weeks after methimazole was started, her symptoms improved significantly, with repeat thyroid function tests: TSH 3.64 uIU/mL and free T4 1.29 ng/dL. Methimazole was held. Four weeks later, the second dose of pembrolizumab was administered. Later that day, repeat thyroid function tests showed high TSH 53.12 uIU/ml, and low T4 0.55 ng/dL with negative thyroid-stimulating immunoglobulin and thyroid peroxidase antibodies, consistent with thyroiditis. Endocrinology and Oncology teams discussed the CTCAE determining that the severity of thyroiditis was grade 2 (moderate symptoms, able to perform activities of daily living, TSH persistently above 10 uIU/L). Pembrolizumab was continued and hypothyroidism was treated with levothyroxine. Discussion CTCAE is used by oncologists to aid in treatment decisions in patients treated with PD-1 inhibitors. Endocrinologists should consider using the CTCAE grading (severity) scale for each adverse event. Adoption and utilization of the CTACE severity scale by endocrinologists may lead to a more standardized and systematic approach for treatment of thyroid disorders associated with PD-1 inhibitor immunotherapy Presentation: No date and time listed

ODP475 Developing suppurative thyroiditis

Abstract Suppurative thyroiditis is rare and associated with significant mortality. A high level of suspicion and aggressive management is needed to reduce the risk of serious outcomes. A 67-year-old male with a medical history including diabetes type 2, cognitive impairment, and ESRD presented with decreased appetite and lethargy for a few days. He presented with fever, tachycardia, and hypertension. There was a non-tender fullness around the anterior neck region. Initial laboratory tests revealed leukocytosis to 24K/uL, lactic acid of 5. 0 mmol/L, ESR 100 mm/hr, CRP 419 ng/dl, and blood culture was positive for gram-positive cocci in clusters for which he was started on iv vancomycin and piperacillin/tazobactam. CT scan on admission showed a probable inflammatory process in the neck originating from the thyroid bed, concerning acute thyroiditis and developing abscess/abscesses vs. very atypical presentation of thyroid cancer. Thyroid ultrasound showed diffuse thyroid enlargement with heterogeneous echogenicity. Repeat CT obtained due to apparent thyroid enlargement with erythema and tenderness on examination and fever on day 7 showed extensive heterogeneous thyroid enlargement with ill-defined margins to the adjacent soft tissue structures. A modified barium swallow revealed severe oropharyngeal dysphagia leading to thyroid fine-needle aspiration of both thyroid lobes by interventional radiology and subsequent urgent incision and drainage (I&amp;D) of the right neck and thyroid biopsy under general anesthesia by ENT. I&amp;D showed purulent drainage from the thyroid. Cultures were positive for MRSA. Surgical pathology reported a necrotic muscle and abscess and fragment of thyroid tissue. Thyroid function tests (TFTs) on admission revealed a TSH 0.31 mcIU/ml (reference: 0.30 - 5. 0 mcIU/ml) and a free T4 of 2.21 ng/dl (reference: 0.76- 1.46 ng/dl) and repeat TFTs with a TSH of 0.30 mcIU/mL, free T4 of 1.87 ng/dL, free T3 of 2.15 pg/ml (reference: 2.18- 3.98 pg/ml), consistent with sick euthyroid syndrome. TPO and TSI were negative. Subsequently, the patient's fever resolved, and the neck swelling improved. He continued IV vancomycin for a month. TFTs six weeks later showed an elevated TSH of 13.10 mcIU/ml and normal free T4 of 1. 03 ng/dl. Conclusion MRSA suppurative thyroiditis is rare, and its diagnosis may be delayed due to its indolent course, especially in immunocompromised patients. Therefore, a high index of clinical suspicion is needed for this endocrine emergency in a patient presenting with fever and neck swelling. While an early FNA of the thyroid is likely to aid in diagnosing thyroid infection, TFTs may be variable and not helpful. Presentation: No date and time listed

Clinically Symptomatic Resistance to Thyroid Hormone β Syndrome Because of THRB Gene Mosaicism

Resistance to thyroid hormone β syndrome (RTHβ) is caused by pathogenic variants in the THRB gene, but such variants are found in only 85% of cases. We report the case of a patient with RTHβ phenotype but for whom we found a pathogenic variant of the THRB gene in a mosaic state. The patient is a 52-year-old woman with clinical and biological signs of RTHβ. Symptoms included asthenia, cardiac palpitations, and diarrhea. Repeated thyroid function tests showed an elevated serum TSH, elevated serum free T4, and variably normal or slightly elevated serum fT3. Pituitary magnetic resonance imaging was normal, and the thyrotropin-releasing hormone test result was compatible with the diagnosis of RTHβ syndrome. Initial Sanger sequencing on blood samples could not highlight the presence of a mosaic variant because of insufficient sensitivity. When next-generation sequencing became accessible, blood samples were retested and we found a known pathogenic variant: c.949G > A; p.(ala317Thr), with an allelic frequency of 12%. Other samples from tissues of different embryological origin were also tested and found an allelic frequency of 5.7%, 17.9%, 9.9%, 6.4%, and 0% on urine tests, oral swab, nasal mucosa swab, skin biopsy, and conjunctival swab, respectively. Cloning confirmed the allelic frequency observed. We highlight that a pathogenic variant in a mosaic state in the THRB gene may be the cause of an authentic RTHβ syndrome. High-throughput sequencing of multiple tissues eases the detection of pathogenic variant in a mosaic state and allows the correct diagnosis of patients with true RTHβ, thus avoiding patient mismanagement.

Treating hypothyroidism is not always easy: When to treat subclinical hypothyroidism, TSH goals in the elderly, and alternatives to levothyroxine monotherapy.

The majority of patients with hypothyroidism feel better when levothyroxine treatment restores thyroid-stimulating hormone (TSH) concentrations to normal. Increasingly, a significant minority of patients remain symptomatic and are dissatisfied with their treatment. Overzealous treatment of symptomatic patients with subclinical hypothyroidism may contribute to dissatisfaction among hypothyroidism patients, as potential hypothyroid symptoms in patients with minimal hypothyroidism rarely respond to treatment. Thyroid hormone prescriptions have increased by 30% in the United States in the last decade. The diagnosis of subclinical hypothyroidism should be confirmed by repeat thyroid function tests ideally obtained at least 2months later, as 62% of elevated TSH levels may revert to normal spontaneously. Generally, treatment is not necessary unless the TSH exceeds 7.0-10mIU/L. In double-blinded randomized controlled trials, treatment does not improve symptoms or cognitive function if the TSH is less than 10mIU/L. While cardiovascular events may be reduced in patients under age 65 with subclinical hypothyroidism who are treated with levothyroxine, treatment may be harmful in elderly patients with subclinical hypothyroidism. TSH goals are age dependent, with a 97.5percentile (upper limit of normal) of 3.6mIU/L for patients under age 40, and 7.5mIU/L for patients over age 80. In some hypothyroid patients who are dissatisfied with treatment, especially those with a polymorphism in type 2 deiodinase, combined treatment with levothyroxine and liothyronine may be preferred.

Overt Hypothyroidism Induced by Prolonged Therapy With Imatinib

Abstract Background: Imatinib, a tyrosine kinase inhibitor (TKI), is commonly used to treat chronic myelogenous leukemia (CML) and gastrointestinal stromal tumors. TKI-induced thyroid dysfunction is recognized as an adverse class effect with most cases occurring between six to twelve months after treatment initiation. Clinical Case: 76-year-old man with hypertension and CML on Imatinib that had been started twenty months prior was admitted for confusion. The patient also reported constipation, cold intolerance, and weight gain despite no change in diet, appetite, or physical activity. On evaluation, his responses to questioning were noticeably delayed, however he was not lethargic. His vital signs were normal and he was otherwise euthyroid on physical exam. He had no known history of thyroid dysfunction. Labs showed a TSH of 94.7 (0.4 - 4.2 uIU/mL), Free T4 0.4 (0.8 - 1.5 ng/dL), and Total T3 30 (87 - 178 ng/dL). Thyroglobulin antibody was 1016 (0.0 - 4.1 U/mL) and TPO antibody was &amp;gt;2000 (0.0 - 5.6 IU/mL). A TSH checked two months before admission was 1.1. Antibody levels had not been checked previously. Thyroid ultrasound demonstrated a hyperemic and heterogeneous thyroid, consistent with thyroiditis. Levothyroxine at a dose of 50 mcg daily was advised, due to patient’s advanced age as well as history of arrhythmia. The patient’s confusion resolved on hospital day three. Repeat thyroid function tests will be checked four to six weeks after Levothyroxine initiation. Discussion: As a class, tyrosine kinase inhibitors are known to cause thyroid dysfunction with the most common medication being Sunitinib. Data related to the effects of thyroid function during Imatinib treatment are limited. Previous cases of Imatinib-induced thyroid dysfunction report only hypothyroidism in thyroidectomized patients and no clinically significant change in thyroid function among patients who were euthyroid prior to therapy initiation. Our case reports a patient with no prior thyroidectomy who developed overt hypothyroidism while on Imatinib for nearly two years. The mechanism for TKI-induced thyroid dysfunction has not been elucidated. Due to relatively acute onset and markedly positive TPO and thyroglobulin antibodies, we suspect that TKI may alter HLA recognition on thyroid follicular cells, thereby inducing autoimmunity. Our case showcases the need to maintain awareness and continuous surveillance for thyroid dysfunction when patients are on long term TKI as overt hypothyroidism may be induced by prolonged treatment.

Hypothalamic Dysregulation; A Hidden Culprit in Multiple Sclerosis Symptoms

Background: A possible association between multiple sclerosis (MS) and dysregulation of hypothalamic-pituitary axis has been reported and its endocrine manifestations can be confused with many nonspecific symptomatology attributed to MS. We report such a case and present the improvement of symptoms independent of MS therapy. Clinical Case: Case of a 45 years-old female with history of type 2 diabetes mellitus, dyslipidemia, HTN, obesity class I and MS that was evaluated for follow up with complaints of fatigue, weakness, somnolence and memory problems. No menstrual disturbances with regular cycles. Denies weight changes, anorexia, nausea, vomiting or abdominal discomfort. Previous hormonal workup showed normal levels of cortisol, ACTH, prolactin and TSH. Nonetheless, on repeated hormonal profile due to nonspecific complaints, patient was found with normal TSH (2.65 mIU/mL, 0.3-3.0 mIU/mL) and low free T4 (0.65 ng/dL, 0.78-2.19 ng/dL). Repeated thyroid function tests by equilibrium dialysis showed a borderline low FT4 (0.8 ng/dL, 0.78-2.19 ng/dL), despite a persistently normal TSH (2.26 mIU/mL, 0.3-3.0 mIU/mL). Suspecting hypopituitarism, a complete hormonal workup revealed a low normal serum cortisol in early morning of 8.39 mcg/dL and ACTH of 16.7 pg/mL, normal prolactin of 10.5 ng/mL and a first IGF-1 evaluation of 68.9 ng/mL, which was low for female age range (98-261 ng/mL). Due to concerns for possible complications during an insulin tolerance test, a cosyntropin stimulation test was performed with adequate peak cortisol response at 30.5 mcg/dL. Most recent brain MRI without pituitary protocol was remarkable for multiple bilateral demyelinating plaques compatible with MS diagnosis that also involved the left thalamus, although no other area adjacent to the hypothalamus or pituitary gland was described. The patient was subsequently started on levothyroxine replacement to a goal of free T4 at the upper normal range, with overall improvement in symptoms and quality of life. Growth hormone status and gonadal axis to be reevaluated. This case emphasizes the importance of clinical judgement and reminds us that overlapping symptoms can lead to misdiagnosis, particularly in conditions with nonspecific symptomatology as MS. Conclusion: This is an unusual case of a patient with multiple sclerosis presenting with hypopituitarism suggesting the possibility of hypothalamic disturbance as the etiology. It has been proposed that demyelinating MS lesions in fiber bundles in and adjacent to the hypothalamus may compromise hypothalamic function. Mechanisms for fatigue in MS have been mostly associated with hyperactivity of HPA axis, not found in our patient. Hypothalamic dysfunction can be frequently overlooked due to overlapping symptoms with MS, despite being a treatable condition that can greatly improve quality of life in these patients.

A Grave Case of COVID-19: SARS-CoV-2 Induced Autoimmune Hyperthyroidism

Background: Autoimmune hyperthyroidism also known as Graves’ disease is the leading cause of hyperthyroidism. The pathogenesis of Graves’ disease is still an area of active research. We present a case of Graves’ disease, which developed following SARS-CoV2 infection. Clinical Case: A 43-year-old man with no prior history of thyroid disease, presented for evaluation due to fatigue palpitations, tremors, and hair loss in June 2020. Earlier that month, he was diagnosed with SARS-CoV2 infection and his thyroid function tests (TFTs) during a visit to the emergency department revealed thyroid stimulating hormone (TSH) level of <0.010 mIU/L (0.35-4.94) with a free T4 (FT4) 1.4 ng/dL (0.7-1.5); consistent with subclinical hyperthyroidism. He continued to report palpitations and tremors and further workup was done. A thyroid ultrasound showed two sub-centimeter nodules. A thyroid uptake scan followed, which showed heterogeneous activity in the thyroid gland, (12% and 32% uptake at 6 and 24 hours respectively) with focal increased uptake in the medial lobes, without cold nodules or hot nodules. Repeat TFTs one month later showed a suppressed TSH <0.010 mIU/L, and a normal FT4 1.3 ng/dL. Given suspicion for Graves’ disease, further labs were ordered. Thyroid stimulating immunoglobulin (TSI) were found to be elevated at 173 % baseline (<=140). Thyroid peroxidase (TPO) antibodies and thyroglobulin antibodies were also elevated at 362 IU/mL H* (<=9) and 2 IU/mL H* (<=1) respectively. The overall picture was consistent with evolving early Graves’ disease. Conclusion: Multiple factors are frequently cited in the pathogenesis of autoimmune hyperthyroidism including viral and bacterial infections1 and there have been several reported cases of autoimmune disease related to SARS-CoV2 infection2. This case is one of several emerging cases of autoimmune hyperthyroidism possibly linked to COVID-19.

Transdermal Absorption of Methimazole- a Cat’s Tale

Introduction: In modern civilization different kinds of animals live with us as pets. These pets have different diseases and are on medications. Close contact with animals can cause medication adverse reactions or may worsen pre-existing conditions in humans. Here we present an interesting case of hypothyroidism worsened by transdermal absorption of methimazole administered for feline hyperthyroidism. Case History: 66-year-old Caucasian female with past medical history of postoperative hypothyroidism s/p total thyroidectomy secondary to multinodular goiter due to Hashimoto’s thyroiditis with a 0.2 cm papillofollicular microcarcinoma and 0.7 cm follicular adenoma presented for follow up. She complained of weight gain, lethargy and dry skin for the past 4 months. She was on a stable dose of levothyroxine 112 mcg daily for the past year. She took her pill correctly and did not miss any doses. Her other medical problems were impaired fasting glucose, osteopenia and B12 deficiency. Her repeat thyroid function tests showed TSH 11.2 mc IU/ l (0.4 -4) (TSH - 0.538 mc IU/ L 6 months back), T4 - 6.8 mcg/ dl (4.5 - 12) (T4 8.9 6 months back). She had a measurable serum thyroglobulin of 0.4 ng/ml with antithyroglobulin antibody 11 IU/ml (<115) consistent with some residual thyroid tissue despite her history of a “total thyroidectomy”. Due to recent worsening of her symptoms with elevated TSH on background of previous stable levothyroxine requirement, further detailed history was taken. She reported that her cat was suffering from hyperthyroidism, treated with methimazole 10 mg daily. The patient used to cut the pill in half with bare hands and fed it to her pet. She also used to handle wet methimazole that her cat coughed up. Her levothyroxine dose was continued at 112 mcg daily. The patient was advised to use gloves before feeding and wash her hands after feeding her cat. Her symptoms resolved after she took precautions and TSH normalized to 1.170 mc IU/ l with T4 7.6 two months later. Conclusion: Absorption of methimazole by transdermal administration has been shown in cats1. A study by Kasraee et al showed safety of a 5% topical methimazole application for treatment of post inflammatory hyperpigmentation in humans with no change in thyroid function tests2. Our case contradicts this study and indicates that methimazole might be absorbed transdermally in humans. To conclude, more studies are needed to study the effect of transdermal administration of methimazole in humans.

COVID-19 Infection Causing Atypical Thyroiditis

Introduction: Coronavirus disease 2019 (COVID-19) has caused significant health burden across the world. Identification of factors contributing to severe disease is important to enable stratification of risk, optimize the reallocation of hospital resources, and guide public health recommendations and interventions. Subacute thyroiditis is an inflammatory thyroid disease characterized by neck pain and is usually preceded by an upper respiratory tract infection. It may be caused by a viral infection or a post-viral inflammatory reaction, and many viruses have been linked to the disease. We present case of atypical thyroiditis associated with COVID-19 infection. Case Report: 27-year-old female with no significant past medical history apart from recent COVID-19 infection is referred to endocrinology for evaluation of abnormal thyroid function test. Patient states around three months ago she was experiencing the symptoms like unintentional weight loss, nausea, palpitation, insomnia, anxiety, fatigue similar to symptoms she experienced 9 years ago while she was pregnant with her daughter so she thought she is pregnant again and visited her gynecologist. But patient had pregnancy test was done and she was found to be negative but her thyroid function test showed low TSH 0.32mIU/ml (0.47-4.68mIU/ml). Patient states around same time she was diagnosed with COVID-19 infection and she lost 5 pounds during that time but even after recovery from the infection she continued to lose weight and lost a total of 18 pounds in 3 months. Patient states during the time of COVID-19 infection she was having difficulty swallowing and painful swallowing but following infection patient denied any current difficulty swallowing or breathing, headache, vision changes, cold or heat intolerance, diarrhea or constipation, tremors, proximal muscle weakness, bulging of her eyes. Patient continue to have regular monthly menstrual cycles. Three months following infection patients repeat thyroid function tests were done and it showed normal TSH 0.56mIU/ml(0.47-4.68mIU/ml),free T4 1.05ng/dL(0.78-2.19ng/dL) and negative thyroid antibodies like TSI index<1.0, Thyroid peroxidase Antibodies 1.4 IU/mL, Thyrotropin Receptor Ab <1.00 IU/L. Patient also had normal thyroid ultrasound. Patient had complete resolution of hyperthyroid symptoms and did not require any medications. Conclusion: In conclusion, physicians should be engaged in close monitoring of thyroid disease in patients with suspected COVID-19, for timely detecting signs of disease progression. Finally, the presence of thyroid disease shall be regarded as an important factor in future risk stratification models for COVID-19.

Diagnosis and treatment of low T3 syndrome in neurocritical patients.

Low levels of serum triiodothyronine (T3) are a strong predictor of mortality and poor prognosis in critical care patients. Few reports, however, have focused on neurocritical patients. The application of hormone replacement therapy (HRT) in the treatment of neurocritical patients with low T3 syndrome remains controversial. We studied the role of low T3 state as a predictor of outcomes in neurocritical patients and examined the effect of HRT on prognosis. A retrospective analysis was performed on the data of 32 neurocritical patients with low T3 syndrome who were admitted to the neuro-intensive care unit of Peking Union Medical College Hospital between January 2012 and October 2018. While 18/32 (56.25%) patients received HRT (HRT group; n=18), 14/32 (43.75%) patients did not receive HRT (non-HRT group; n=14). Patients were followed up for periods ranging from 3months to 72months. Baseline clinical and laboratory data were compared between the two groups using Mann-Whitney U tests or the t tests. Overall survival was assessed by Kaplan-Meier curve and compared by log-rank tests. Univariate and multivariate regression analyses were performed to identify the factors associated with prognosis and estimate the effect of HRT. We also assessed the influence of HRT on final neurological function, using the Glasgow Coma Scale (GCS) and the Glasgow Outcome Scale (GOS) scores. The neurocritical events in our cohort included post-operative complications (n=18), traumatic brain injury (n=8) and spontaneous intracerebral haemorrhage (n=6). Mean GCS score in the cohort was 6.41 (6.44±3.14 in HRT group vs 6.36±2.06 in non-HRT group). A total of 15/32 (46.87%) deaths were recorded (7 in the HRT group, 8 in the non-HRT group). In the HRT group, 15 patients underwent repeat thyroid function tests after completion of HRT; the low T3 situation was corrected in only 5/15 (33.3%) patients. Overall survival was significantly shorter in the non-HRT group than in the HRT group (16.45months vs 47.47months; P=.034). In univariate regression analysis, the HRT group has the lower mortality risk than the non-HRT group (HR=0.301, 95% Cl: 0.094-0.964; P=.043). However, multivariate regression analysis showed no significant difference in mortality risk between the two groups (HR=0.340 95% CI: 0.099-1.172; P=.087). There was no significant difference in effects of HRT on the short- and long-term neurological function between the groups. Low T3 syndrome may influence the prognosis of neurocritical patients, attention should be paid to the changes in serum T3 levels during treatment. Although it is unclear to what extent HRT can improve the short or long-term outcomes of neurological function, it can significantly improve the survival rates of neurocritical patients.

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

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.

MON-480 Isolated Hyperthyroxinemia - Does Everyone Needs Treatment?

Background: Raised free thyroxine (T4) with normal thyroid stimulating hormone (TSH) levels should be identified and interpreted with caution. Some of these conditions do not need treatment. We present three cases with similar biochemical abnormalities from three different causes. Case 1: A 62-year-old clinically asymptomatic lady was referred to us with Free T4 34.9 pmol/L (10.0 – 24.0 pmol/L), TSH 0.81 mU/L (0.2 – 5.0 mu/L) and negative TSH receptor antibodies (<0.9 IU/L). She was trialled on antithyroid drugs for 6 months. Her Free T4 stayed elevated between 29.0 – 35.0 pmol/L with normal TSH. We worked up for assay interference by running tests on two analysers, Roche Cobas e801 and Siemens ADIVA Centaur CP, both yielded similar results. Alpha1 glycoprotein subunits and SHBG were normal with clinical euthyroid status making TSHoma less likely. Serum protein electrophoresis did not detect any abnormal albumin. We were unable to perform equilibrium dialysis due to non-availability of facility at our centre. Due to strong clinical suspicion and family history of thyroid dysfunction that never needed a treatment, we tested her genetically for familial dysalbumineic hyperthyroxinemia (FDH) using mutation surveyor and fluorescent sequence analysis showed her to be heterozygous for c.725G>A ALB variant confirming diagnosis of FDH. Case 2: A 65-year-old clinically asymptomatic lady, was referred to us with Free T4 28.8 pmol/L (10.0 – 24.0 pmol/L) and TSH 2.50 mU/L (0.2 – 5.0 mu/L). Given inappropriately normal TSH levels, we repeated her TFTs using 3 different analysers, Roche cobas e801, Siemens ADIVA centaur CP and Abbot ARCHITECT i1000SR. Roche and Siemens assays yielded similar results, however Abbot assay showed normal thyroid function tests with TSH 1.01 mu/L (0.4-5.0 mu/L) and free T4 18.7pmol/L (9.0-19.0 pmol/L), confirming assay interference. As Siemens and Roche uses streptavidin-biotin immobilizing system while Abbot uses a magnetic bead-based capture system, the abnormal results could be due to biotin interference. Case 3: A 65-year-old lady, clinically asymptomatic was referred to us with Free T4 29.2 pmol/L (10.0 – 24.0 pmol/L) and TSH 1.59 mU/L (0.2 – 5.0 mu/L), 3 months after stopping amiodarone, which she took for 3 weeks for atrial fibrillation. This was thought to be due to amiodarone, owing to its long half-life of 58 days. We repeated thyroid function tests in 3 months from first clinical encounter i.e. 6 months after stopping amiodarone that showed Free T4 24.2pmol/L and TSH 2.30 mU/L and repeated further 3 months later that were normal, confirming amiodarone induced abnormal biochemical profile requiring no treatment. Conclusion: Hyperthyroxinaemia with normal TSH need to be interpreted with caution as illustrated above. Some of them do not need treatment and inappropriate interpretation can potentially cause anxiety for the patient and harm due to unnecessary treatment.

SAT-683 A Case of Autoimmune Polyglandular Syndrome Type 2 and Guillain-Barré Syndrome

Background: Autoimmune polyglandular syndrome type 2 (APS2) is defined by the occurrence of two or more autoimmune diseases, with Addison’s disease being most prevalent, and autoimmune thyroid disease and type 1 diabetes mellitus also being common. Guillain-Barré syndrome (GBS) is an acute inflammatory demyelinating polyradiculopathy that is also autoimmune in nature, resulting in ascending muscle weakness or paralysis.Clinical Case: A 49 year old female with past medical history of vitiligo, subclinical hyperthyroidism, and Guillain-Barré syndrome (GBS) presented to our institution with fatigue, nausea, vomiting, polyuria, and polydipsia. She had no history of diabetes. Her history was also significant for GBS, diagnosed 5 months prior to her current admission. She was treated with intravenous immunoglobulin (IVIG) and had partial improvement of motor impairment. On exam, she was noted to have dry mucous membranes, epigastric tenderness, and patches of hyopigmented skin. Laboratory studies were consistent with diabetic ketoacidosis, and she was admitted to the ICU for management.Labs from 5 months prior were significant for a HbA1c of 6.4% (4.0-5.6%), TSH <0.002 mIU/L (0.350-4.7 mIU/L), total T3 154.9 ng/dL (79-149 ng/dL), and free T4 1.7 ng/dL (0.7-1.9 ng/dL), and elevated thyroid stimulating immunoglobulin.During the current admission, HbA1c had risen to 13.6%, C-Peptide 0.6 ng/mL (1.1-4.4 ng/mL) and GAD-65 antibody >250 IU/mL (<5 IU/mL), consistent with a diagnosis of late-onset type 1 diabetes. Repeat thyroid function tests (TSH <0.002 mIU/L, total T3 74 ng/dL, and free T4 1.2 ng/dL), were consistent with subclinical hyperthyroidism. A 21-hydoxylase antibody level was 13 U/mL (<1 U/mL), but cortisol rose appropriately in response to cosyntropin. Based on the patient’s constellation of vitiligo, autoimmune thyroid disease, type 1 diabetes, and elevated 21-hydroxylase antibodies, she was diagnosed with APS2.Conclusion: We present an unusual case of a patient with APS2, who was diagnosed with type 1 diabetes 5 months after developing GBS and being treated with IVIG. Prior reports demonstrate an association between GBS and other autoimmune diseases, including one case report of GBS in a patient with APS2. HLA DR3 has been associated with APS2, type 1 diabetes, Addison’s disease and Grave’s disease. Its association with GBS is less clear, although HLA DR3 was increased in one Mexican cohort with GBS. This case report adds to the literature suggesting an association with GBS and other autoimmune diseases, specifically, with APS2.

SAT-501 Thyrotoxicosis with Pre-Ventricular Complexes Resulting in Thyroid Storm and Cardiac Arrest

Background: Ventricular arrythmias are a rare, often lethal complication of thyrotoxicosis. We describe a patient with uncontrolled hyperthyroidism and pre-ventricular complexes (PVCs) who presented with ventricular tachyarrhythmia cardiac arrest and was successfully resuscitated. Clinical Case: A 64 year old woman was diagnosed with thyrotoxicosis secondary to Graves’ disease [TSH < 0.01 (0.40 – 4.5 mcIU/mL) and free T4 of 2.8 (0.8 – 1.8 ng/dL)] 1 year ago in the setting of a 6 month history of weight loss, palpitations, tremors, and a large goiter. She was started on methimazole and metoprolol XL and was intermittently compliant. During follow-up evaluation she complained of light headedness, developed agonal breathing, and became pulseless. Chest compressions were initiated. She regained spontaneous rhythm after receiving 1 shock with an Automated Electronic Defibrillator (AED). She was transferred to the Emergency Room (ER) and intubated for altered mental status.Emergent CT Angiography and bedside echocardiogram showed no pulmonary embolism and normal biventricular function. Troponin T high sensitivity assay was negative and electrolytes were normal. Repeat thyroid function tests showed TSH <0.01, Free T4 of 5.6 and free T3 of 14.5 (2.0 – 4.4 pg/mL). She was started on propylthiouracil, glucocorticoids, potassium iodide and treated for thyroid storm. EKG in the ER showed sinus tachycardia with no ischemic ST changes but PVCs and fusion complexes were noted. These were also present on EKG at the time of her initial diagnosis of hyperthyroidism. EKGs prior to the diagnosis of hyperthyroidism showed normal sinus rhythm.Cardiac arrest was attributed to thyrotoxicosis as there was no infectious nidus and no evidence of structural cardiac disease. The AED rhythm strips could not be obtained but she was presumed to have an appropriately shockable ventricular tachyarrhythmia such as ventricular tachycardia (VT) or ventricular fibrillation (VF).Her thyroid hormone levels declined appropriately over the course of the hospitalization and PVCs were no longer noted on telemetry and daily EKGs. She was discharged on methimazole which she took consistently. She underwent RAI ablation several months after discharge. Conclusion: Failure to achieve rapid euthyroidism in thyrotoxicosis is associated with increased cardiovascular morbidity and mortality (1). Most arrythmias associated with thyrotoxicosis are supraventricular and ventricular arrythmias are a rare sequela (2). This is one of the few cases reported of antecedent PVCs being noted on EKG. The PVCs resolved with anti-thyroid medications.

Durvalumab-induced diabetic ketoacidosis followed by hypothyroidism.

SummaryDurvalumab is a programmed cell death ligand 1 inhibitor, which is now approved in Australia for use in non-small-cell lung and urothelial cancers. Autoimmune diabetes is a rare immune-related adverse effect associated with the use of immune checkpoint inhibitor therapy. It is now being increasingly described reflecting the wider use of immune checkpoint inhibitor therapy. We report the case of a 49-year-old female who presented with polyuria, polydipsia and weight loss, 3 months following the commencement of durvalumab. On admission, she was in severe diabetic ketoacidosis with venous glucose: 20.1 mmol/L, pH: 7.14, bicarbonate 11.2 mmol/L and serum beta hydroxybutyrate: >8.0 mmol/L. She had no personal or family history of diabetes or autoimmune disease. Her HbA1c was 7.8% and her glutamic acid decarboxylase (GAD) antibodies were mildly elevated at 2.2 mU/L (reference range: <2 mU/L) with negative zinc transporter 8 (ZnT8) and islet cell (ICA) antibodies. Her fasting C-peptide was low at 86 pmol/L (reference range: 200–1200) with a corresponding serum glucose of 21.9 mmol/L. She was promptly stabilised with an insulin infusion in intensive care and discharged on basal bolus insulin. Durvalumab was recommenced once her glycaemic control had stabilised. Thyroid function tests at the time of admission were within normal limits with negative thyroid autoantibodies. Four weeks post discharge, repeat thyroid function tests revealed hypothyroidism, with an elevated thyroid-stimulating hormone (TSH) at 6.39 mIU/L (reference range: 0.40–4.80) and low free T4: 5.9 pmol/L (reference range: 8.0–16.0). These findings persisted with repeat testing despite an absence of clinical symptoms. Treatment with levothyroxine was commenced after excluding adrenal insufficiency (early morning cortisol: 339 nmol/L) and hypophysitis (normal pituitary on MRI).Learning points:Durvalumab use is rarely associated with fulminant autoimmune diabetes, presenting with severe DKA.Multiple endocrinopathies can co-exist with the use of a single immune checkpoint inhibitors; thus, patients should be regularly monitored.Regular blood glucose levels should be performed on routine pathology on all patients on immune checkpoint inhibitor.Clinician awareness of immunotherapy-related diabetes needs to increase in an attempt to detect hyperglycaemia early and prevent DKA.

Thyroid autotransplantation following total thyroidectomy in benign thyroid disorders: a new technique to avoid postoperative hypothyroidism

Background: Although total thyroidectomy has become the operation of choice in treatment of BMNG, it leads to permanent hypothyroidism which lead the patient to take a lifelong exogenous hormone replacement therapy, which involves daily administration of levothyroxine at a dose that must be in close follow-up in terms of thyroid hormone levels. In addition, reaching euthyroid status using hormone replacement therapy can be affected in presence of other medical problems that interfere with absorption of the drug as mal-absorption syndrome. When all these are considered, there is a necessity of a novel method to avoid the occurrence of postoperative hypothyroidism.Methods: A case series prospective study carried out over 30 patients with benign thyroid disorders for whom total thyroidectomy is indicated to evaluate the capacity of auto-implanted thyroid tissue in achieving an euthyroid state without any need for life-long hormone replacement therapy. Postoperative Assessment consists of repeated thyroid function tests and thyroid scan with complementary SPECT/CT.Results: significant gradual increase in serum levels of T3 and T4 with corresponding decrease in TSH levels returning to normal levels 6-9 months postoperatively. Thyroid scan with complementary SPECT/CT was done for 15 patients to evaluate the functional capacity of the thyroid implant. Among the 15 patients, 13 patients have functioning thyroid implant (success percent: 6.6%). whereas 2 patients show non functioning thyroid implant (failure percent: 13.3%).Conclusions: Thyroid Auto-transplantation following total thyroidectomy in benign thyroid disorders is an effective method to prevent postoperative hypothyroidism.