bluuebunny/crossref_metadata_2025 huggingface dataset:
A Case of Rhabdomyolysis in a Patient With Hashimoto’s Thyroiditis
Authors: Ataallah Basma , Abdulrahman Mustafa , Kulina Georgia
Published: May 2021

Introduction: Hashimoto’s thyroiditis (HT) is an autoimmune disease that presents with musculoskeletal symptoms like proximal muscle weakness, stiffness, pain or cramps in the majority of patients. Rhabdomyolysis which is a breakdown of the skeletal muscles, is a rare but serious manifestation of hypothyroidism and if occurs, it is usually related to trauma, strenuous exercise or use of statins. We report a patient with unrecognized Hashimoto’s thyroiditis who presented with severe rhabdomyolysis without reported history of strenuous exercise, seizures or statin use and surprisingly, He did not have any complications from rhabdomyolysis like electrolytes abnormalities or acute kidney injury. Case Report: A 56-year-old man with no reported past medical history who presented with severe generalized weakness, bilateral leg pain, and recurrent falls for three months. He also reported constipation, fatigue and dry skin. Denied any prior personal or family history of thyroid disease, seizure disorder, statin use, trauma or tick bite. He was afebrile with a heart rate of 80 beats/minute, a blood pressure of 126/71mmHg. Initial laboratory testing showed normal metabolic panel, elevated thyroid stimulating hormone 30.6 uIU/mL (Range 0.27-4.2 uIU/mL), FT4 0.1 ng/dL (Range 0.93-1.7ng/dL), TPO Ab 300IU/mL (N<43IU/mL), Creatine Kinase (CK) level 10,000U/L (N<200U/L), ESR 27 mm/Hr (N<20mm/Hr) and Lactate Dehydrogenase 621U/L (N <225U/L). A muscle biopsy was done to rule out polymyositis as a cause of his severe muscle pain, weakness and tenderness and it was negative. Patient was diagnosed with HT with associated rhabdomyolysis after excluding other causes of rhabdomyolysis. Supportive treatment with intravenous fluids and Levothyroxine were initiated and resulted in dramatic clinical improvement. Conclusion: Rhabdomyolysis is a rare but potentially a serious complication of hypothyroidism. Screening for hypothyroidism in patients with elevated muscle enzymes should be considered, as early diagnosis and prompt treatment of hypothyroidism is essential to prevent rhabdomyolysis and its consequences like acute kidney disease and electrolytes abnormalities. Appropriate fluid resuscitation is the mainstay therapy for AKI prevention and should be initiated in a timely manner. Key Words: HT: Hashimoto’s Thyroiditis, ESR: Erythrocyte Sedimentation Rate, TPO Ab: Thyroid Peroxidase Antibody, TSH: Thyroid Stimulating Hormone, FT4: Free Thyroxine level, AKI: Acute Kidney Injury.
A Grave Case of COVID-19: SARS-CoV-2 Induced Autoimmune Hyperthyroidism
Authors: Matos Moises , Merino-Chavez Hilda Maria , Martinez Suzanne
Published: May 2021

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. References: 1. Smith, T. J . Graves’ Disease. New England Journal of Medicine. 2016 October 20; 375:1552-1565 2. Mateu-Salat, M., Urgell, E., Chico, A. SARS-COV-2 as a trigger for autoimmune disease: report of two cases of Graves’ disease after COVID-19. Journal of Endocrinological Investigation. 2020 July 19
A Grave Turn on Hashimoto’s Thyroiditis - A Case Series on Four Patients With Autoimmune Hypothyroidism that Converted to Grave’s Disease
Authors: Lee Michelle N , Colburn Jeffrey A
Published: May 2021

Disclaimer: The view(s) expressed herein are those of the author(s) and do not reflect the official policy or position of Brooke Army Medical Center, the U.S. Army Medical Department, the U.S. Army Office of the Surgeon General, the Department of the Army, the Department of the Air Force, or the Department of Defense or the U.S. Government.

Introduction: The most common cause of hypothyroidism is Hashimoto’s thyroiditis, a destructive autoimmune injury to the thyroid gland. Rarely, autoimmune hypothyroidism can be caused by thyroid-stimulating hormone (TSH) receptor blocking antibodies (TSHRab), and can be difficult to differentiate clinically from Hashimoto’s. Grave’s disease is the most common etiology of hyperthyroidism, and is typically caused by activation from TSHRab acting as an agonist for the TSH receptor. Patients with autoimmune thyroiditis, whether from TSHRab or Hashimoto’s, have been infrequently reported to convert to Grave’s disease1–3. Presentation: We present four cases whom initially presented with typical symptoms of hypothyroidism, were diagnosed with autoimmune hypothyroidism and started on levothyroxine. All four cases were later found to be hyperthyroid and ultimately diagnosed and treated for Grave’s disease.

Conclusion: Primary hypothyroidism can rarely transition to a hyperthyroid state, although these cases may be underreported. The mechanism isn’t well understood, but is hypothesized to be from a switch of a predominance of TSH receptor blocking antibodies (TBAb) to that of thyroid stimulating antibodies (TSAb)1. Assays using competitive binding for TSH receptor antibodies will not differentiate between blocking and stimulating antibodies4. A high index of suspicion is needed to diagnose these individuals.

References: 1. McLachlan SM, Rapoport B. Thyrotropin-blocking autoantibodies and thyroid-stimulating autoantibodies: Potential mechanisms involved in the pendulum swinging from hypothyroidism to hyperthyroidism or vice versa. Thyroid. 2013;23(1). doi:10.1089/thy.2012.03742. Takasu N, Matsushita M. Changes of TSH-stimulation blocking antibody (TSBAb) and thyroid stimulating antibody (TSAb) over 10 years in 34 TSBAb-positive patients with hypothyroidism and in 98 TSAb-positive graves’ patients with hyperthyroidism: Reevaluation of TSBAb and TSAb in TSH-receptor-antibody (TRAb)-positive patients. J Thyroid Res. 2012;2012. doi:10.1155/2012/1821763. Gonzalez-Aguilera B, Betea D, Lutteri L, et al. Conversion to graves disease from hashimoto thyroiditis: A study of 24 patients. Arch Endocrinol Metab. 2018;62(6). doi:10.20945/2359-39970000000864. Li Y, Kim J, Diana T, Klasen R, Olivo PD, Kahaly GJ. A novel bioassay for anti-thyrotrophin receptor autoantibodies detects both thyroid-blocking and stimulating activity. Clin Exp Immunol. 2013;173(3). doi:10.1111/cei.12129
A Rare Case of a Toxic Thyroid Nodule Found in a Hypothyroid Patient on Levothyroxine Therapy
Authors: Purewal Tiffany , Lesniak Christopher , Ravin Andrew , Cheng Jennifer
Published: May 2021

Introduction: A hyperfunctional thyroid nodule can lead to symptoms of overt or subclinical hyperthyroidism but the association between a hyperfunctional thyroid nodule and hypothyroidism has not been well reported. We present a patient with a prior history of hypothyroidism previously controlled on Levothyroxine who later presented with an enlarging hot nodule. Case Presentation: A 62-year-old female with a history of factor V Leiden, hypothyroidism on levothyroxine therapy, and a meningioma presented to an outpatient clinic with complaints of fatigue, constipation, and 37-pound weight loss in one year. She was diagnosed with hypothyroidism 7 years ago after delivering her third child, but the underlying cause of her disease was unknown. She began taking levothyroxine 50mcg every morning after her diagnosis. She reported compliance and proper pill taking technique. Physical examination revealed a palpable thyroid nodule. The patient had a previous work up for thyroid nodules with a thyroid uptake and scan a few years prior, which showed a 1.42 x 0.96 x 1.87 cm hot nodule at the right middle lobe with a 24-hour uptake of 15.3%. The patient was asymptomatic at that time and thyroid function tests were within normal limits. She was instructed to continue taking levothyroxine. Repeat RAI Uptake scan at the time of her presentation to our office again showed the right middle lobe hot thyroid nodule with an increased 24-hour uptake of 27.5%. Ultrasound showed bilateral thyroid nodules and a hypervascular solid nodule measuring 2.28 x 1.27 x 1.9 cm that has increased in size. Lab work at this visit revealed a TSH of 0.329 uIu/mL, and free T4 of 1.25 ng/dL. Due to her low TSH and clinical presentation, the levothyroxine was discontinued. Anti-thyroid peroxidase antibodies were obtained to assess for Hashimoto’s Thyroiditis but were found to be normal. The patient was later referred to an endocrine surgeon for a total thyroidectomy. Conclusion: Although uncommon, hyperfunctional nodules in hypothyroid patients can create a confusing clinical picture with overlapping symptoms of underactive and overactive thyroid disease. It has been reported that patients with Hashimoto’s Thyroiditis can have hot nodules and coexisting hypothyroidism but the prevalence of hyperfunctional nodules in hypothyroid patients without Hashimoto’s Thyroiditis, as in this case, is not well-documented. Patients with hypothyroidism are treated with Levothyroxine but if coexisting hyperfunctional nodules are not detected, the patient may develop thyrotoxicosis. Clinicians should be aware of this rare but potentially life-threatening clinical condition.
A Severe Case of Hypothyroidism: Immunotherapy Induced
Authors: Chunchulu Srivani
Published: May 2021

Background: Immune check point inhibitors are playing a crucial role in the treatment of many cancers. Their primary role is to reactivate anti tumor cytotoxic T cells. Programmed cell death 1(PD 1) is a transmembrane protein expressed on T cells, B cells and Natural killer cells. PD 1 ligand is expressed in many tumor cells along with hematopoietic cells and their interaction directly inhibits apoptosis of the tumor cell. Pembrolizumab binds PD1. FDA approved pembrolizumab initially for nonsquamous cell lung cancer and metastatic melanoma that express PD1 ligand which showed improved survival compared to standard therapy. Additionally it has been used in several others tumors with more than 50% PD L1 expression. Although well tolerated, these agents can cause immune related adverse events. Thyroid dysfunction is reported to range between 3.2-10.1% patients receiving pembrolizumab. Clinical Case: 86 year old Caucasian female with past medical history of hypertension and osteoarthritis was diagnosed with stage III metastatic colon cancer in the hepatic flexure and underwent hemicolectomy. Pathology showed 6.5cm mass and 2/30 lymph nodes positive. Due to fear of side effects from chemotherapy, patient refused further treatment. Her follow up labs showed elevation of carcinoembyronic antigen (CEA). Her oncologist suggested Pembrolizumab, immunotherapy. She was started on 5 cycles every 3 weeks. She had fatigue and fell twice after first cycle, but her CEA levels were improving, so it was decided to continue treatment. Soon after fifth cycle she became extremely weak, lethargic, and unable to do any ADLS and was exhausted all the time. Her labs showed TSH 137, free T4 0.4. At that point decision was made to stop pembrolizumab. She was started on levothyroxine 25mcg by her oncologist and referred to me few months later. She complained of tiredness, low energy. On exam Pulse 78, Blood pressure 152/77. Her labs showed TSH 106 and Free T4 0.45. Her levothyroxine dose was increased to 75mcg and followed her 6 weeks later. Her energy levels improved significantly and she is back to her normal self. Her thyroid function was normal. At this point patient has decided not to undergo any treatments for colon cancer. Conclusion: Immune related thyroid events are increasingly noticed with wide use of pembrolizumab. There is insufficient evidence to suggest the cause of these events. Reversible destructive thyroiditis and overt hypothyroidism are the common clinical presentations. It is important to recognize patients at high risk for these adverse events so these highly efficacious agents can be safely used in patients. Thyroid has been a frequent target for anti PD 1 treatments, further research can be of benefit to use against thyroid cancers.
Call for Emergency Room Guidelines to Identify Hyperthyroid Patients Prior to Contrast Imaging
Authors: Bassin Sandhya , Amorosa Louis F
Published: May 2021

Background: Thyrotoxicosis can be mistaken for conditions such as atrial fibrillation and pulmonary embolism (PE) given the nonspecific symptoms of fatigue, palpitations, and dyspnea. Patients often undergo further imaging on presentation to the emergency room (ER), many of which use iodine for contrast. This can put patients at increased risk for iodine induced hyperthyroidism and delay definitive treatment in patients with Graves’ disease, the most common cause of hyperthyroidism.

Clinical Case: A 53-year-old male with history of hyperthyroidism, atrial fibrillation, and prior PE presented with palpitations to the ER. He developed worsening dyspnea on exertion and palpitations over the last three days. He was unable to afford his medications, including methimazole, for the last nine months. In the ER he was in atrial fibrillation with rapid ventricular response. Due to concern for PE, he underwent a CTA with contrast, which was negative. His physical exam was notable for a diffusely enlarged goiter. His labs showed low TSH <0.01 (norm 0.35-5.50mIU/L) and high free T4 >7.77 (norm 0.9-1.8ng/dL). TSH stimulating antibodies were elevated at 1.9 (norm <1.3 TSI index), consistent with Graves’ hyperthyroidism. Endocrinology was then consulted for severe thyrotoxicosis, initially treating the patient with PTU and propranolol. The patient was transitioned to methimazole and continued propranolol on discharge. Since he was given contrast, plan was for repeat thyroid uptake scan and iodine ablation in 3 months. However, patient was not compliant with medications, resulting in readmission for thyrotoxicosis 3 months later.

Conclusion: This case highlights the impact of increased use of contrast in imaging in hyperthyroid patients. Hyperthyroid patients are at an increased risk for emboli. However, iodine can cause contrast-induced hyperthyroidism and delay definitive treatment of Graves’ disease. As almost half of thyrotoxic patients receive iodinated contrast prior to an endocrine consultation, endocrinologists should work with emergency physicians to develop a set of guidelines to identify at risk populations for hyperthyroidism (1). We advocate for urgent thyroid testing in patients with new onset atrial fibrillation, a history of Graves’ disease, specific symptoms of Graves’, or those taking thyrotoxic-inducing medications. This will assist in determining if patients should receive a prophylactic dose of anti-thyroid medication prior to iodinated contrast imaging. These guidelines can help prevent contrast induced hyperthyroidism and disruptions in treatment of Graves’ while still imaging patients for other diagnoses on the differential.

Reference: (1) Giacomini A, et al. Urgent thyroid-stimulating hormone testing in emergency medicine: A useful tool? J Emerg Med. 2015;49(4):481-487.
Case Report of Postpartum Thyroid Nodule Size Reduction
Authors: Havranova Jana , Gallagher Thomas , Arastu Mohammad Ishaq
Published: May 2021

Introduction: Thyroid nodules are very common. They occur more commonly in women with an increased prevalence of thyroid nodules reported in pregnancy. Most thyroid nodules diagnosed during pregnancy are benign. Pregnancy causes major physiological changes including changes in the levels of thyroid hormones and the elevation of thyroid binding globulin. Thyroid nodules may also occur in people with abnormal thyroid function tests manifesting as hyperthyroidism or hypothyroidism. We present a unique case of a new diagnosis of a large thyroid nodule that has significantly decreased in size after 20 months postpartum. Case description: Patient is a 31 year old female with past medical history of anxiety and white coat hypertension who was diagnosed with a 3.3 x 2.3 x 2.1 cm thyroid nodule a month following delivery. Patient did not have any abnormalities in her thyroid function tests before, during, or after pregnancy. She remained euthyroid throughout the pregnancy and in the postpartum period. Fine needle aspiration biopsy of the nodule showed atypia of undetermined significance (Bethesda Category III). The specimen was further analyzed by afirma testing that confirmed benign pathology. Twenty months postpartum, the thyroid nodule significantly decreased in size to 1.9 x 1.4 x 1.2 cm. Conclusion: Thyroid hormone levels physiologically change during pregnancy and this may affect the growth of thyroid nodules. We just presented a patient who exhibited a significant decrease in the size of her thyroid nodule. Sahin et al. showed that while the size of the thyroid nodule increases during pregnancy the number of nodules remains unaffected. Kung et al. showed that pregnancy is associated with an increase in the size of preexisting thyroid nodules as well as the number of newly developed thyroid nodules. Vanucchi et al. showed that although the thyroid gland becomes larger, particularly in late pregnancy, the sizes of any preexisting thyroid nodules remained unchanged and patients’ thyroid gland size returned to normal after delivery. The current literature provides conflicting data on this topic. The true association between pregnancy and thyroid nodules is unknown. Contemporary literature is ambiguous on this topic and more scientific studies are required to find the true association between pregnancy, the formation of thyroid nodules, and increase in the size or number of thyroid nodules.
Choriocarcinoma Induced Thyrotoxicosis in a Male Adult
Authors: Radovanovic Natasa , De Castro Alicia , Cao Yenong , Ammana Hima Reddy , Kwak Leigh
Published: May 2021

Introduction: Germ cell tumors normally occur in the gonads but may be found in extragonadal sites (due to abnormal migration of germ cells during embryogenesis). Metastatic choriocarcionomas are non-seminomatous germ cell tumors which overproduce beta Human Chorionic Gonadotropin (hCG). Rarely, thyrotoxicosis can be driven by germ cell tumor-mediated hCG excess. This hormone binds to the TSH receptor with reduced potency compared to intact TSH. Paraneoplastic thyrotoxicosis, driven by extremely high levels of hCG, is a rare condition which can be associated with choriocarcinomas. Case Presentation: We present a case of 29-year-old man with metastatic extragonadal choriocarcinoma under active treatment with oxaliplatin, paclitaxel, gemcitabine (2 cycles completed), right upper lobe resection and whole brain radiation. He was admitted for small bowel obstruction and persistent tachycardia which prompted evaluation of thyroid function. His initial labs were remarkable for TSH <0.01 mclU/mL (0.27-4.20 mclU/mL), FT4 of 6.38 ng/dL (0.93-1.70 ng/dL), total T3 261 ng/dL (75-170 ng/dL), and beta hCG 578,259 mlU/ML (0-2 mlU/ML). His most recent round of chemotherapy was 7 days prior to admission. He was started on atenolol and methimazole but his FT4 rapidly declined, hence methimazole was stopped after one dose of 40 mg. Sevenfold decrease in FT4 to 0.93 ng/dL correlated with fivefold decrease in beta hCG levels to 98,921 mlU/ML. A week later his FT4 increased to 2.42 ng/dL along with increase of beta hCG to 448,116 mlU/ML. At this point he developed multiple complications due to progressive metastatic disease including acute urinary retention, shortness of breath, abdominal pain, tachycardia, acute anemia and thrombocytopenia, anxiety and was started on methimazole as part of palliative treatment for symptom relief. Unfortunately, he passed away three weeks after initial presentation of thyrotoxicosis due to widespread disease. Discussion: Choriocarcinoma is very rare and aggressive germ cell tumor especially in males. Unfortunately, the widespread nature of choriocarcinomas at the time of diagnosis is a major main reason for poor prognosis. Clinical manifestations of thyrotoxicosis associated with choriocarcinoma such as tachycardia, anxiety, tachypnea are variable and often can overlap with constitutive symptoms in widespread malignancy. Even if a definitive cure of choriocarcinoma is not attainable, recognizing an associated paraneoplastic thyrotoxicosis can provide an important pathway to provide palliative symptom relief.
Risk of Mental and Sleep Disorders After the Diagnosis of Adrenal Adenomas: A Population-Based Cohort Study
Authors: Singh Sumitabh , Zhang Catherine , Atkinson Elizabeth , Achenbach Sara , Ebbehoj Andreas , Li Dingfeng , Kaur Ravinder Jeet , Stricker Nikki H , Mielke Michelle , Bostwick J Michael , Rocca Walter A , Bancos Irina
Published: May 2021

Background: Adrenal adenomas are incidentally diagnosed in 7% of adults undergoing abdominal imaging. Mild autonomous cortisol secretion is present in 50% of adrenal adenomas, and even “nonfunctioning” adrenal adenomas demonstrate abnormal steroid profile. We aimed to 1) investigate the prevalence of mental and sleep disorders in patients with adrenal adenomas and to 2) determine the risk of mental and sleep disorders after the diagnosis of adrenal adenoma in patients compared to the referent subjects from the same population Methods: Using a medical records linkage system, we identified adult patients living in the Olmsted County, MN diagnosed with an adrenal adenoma during 1995–2017. Patients with overt hormone excess were excluded. Every patient with adenoma was matched by sex and age to a referent subject from the same population. Subjects were followed until death or end of the study. Mental health related comorbidities and sleep disorders were assessed at baseline and during follow up. Results: Our cohort included 1004 patients with adrenal adenomas and 1004 referent subjects (58% women, median age of 63 years). Patients were more likely to smoke (70% vs 54%, p <0.001) and had a higher BMI (30 kg/m2 vs 28 kg/m2, p < 0.001). Within 5 years prior to the index date (diagnosis of adenoma), and after adjusting for BMI and smoking, patients demonstrated a higher prevalence of depression (Odds ratio, OR of 1.3 (CI95% 1.1–1.6), p=0.02), anxiety (OR of 1.4 (CI95% 1.1–1.8, p=0.003), substance abuse disorders (OR of 2.4 (CI 95% 1.7–3.4), p<0.001), but not insomnia (OR of 1.2 (CI95% 0.9–1.7) and sleep related breathing disorders (OR of 1.3 (CI 95% 0.9–1.7). During follow-up, starting 1 year after the diagnosis, patients demonstrated a higher risk of new onset depression (HR of 1.9, CI95%1.5–2.4), anxiety (HR of 1.5,CI95% 1.2–1.9), schizophrenia (HR of 1.7, CI95% 1.2–2.4), and substance abuse disorders (HR of 1.6, CI95% 1.2–2.0). Risk of sleep disorders 1 year after diagnosis was also high for insomnia (HR of 1.4, CI95% 1.1–1.9), sleep-related breathing disorders (HR of 1.8, CI95% 1.4–2.3), hypersomnias of central origin (HR of 2.0, CI95%1.04–3.96), parasomnias (HR of 2.4, CI95%1.2–4.7), and sleep-related movement disorders(HR of 1.9, CI95%1.3–2.6). Conclusion: Patients with adenomas are at increased risk for mental and sleep disorders, possibly explained by the underlying subtle cortisol secretion. Further prospective studies with an in-depth characterization of both hormonal secretion and mental/sleep disorders are needed. Reversibility or improvement of mental health and sleep disorders with adrenalectomy should be investigated.
Graves’ Disease After Hematopoietic Allogeneic Bone Marrow Transplant in a Patient With Sickle Cell Disease
Authors: Alameri Majid
Published: May 2021

Endocrinopathies are among the most recognized late complications post hematopoietic stem cell transplant (HSCT). Dysfunctions of hormonal axes including the hypothalamus, pituitary, gonads, thyroid and adrenals reported. Moreover, thyroid dysfunctions including thyroiditis, hypothyroidism and hyperthyroidism has been reported to develop 8-32 months after HSCT.

We report a 27-year-old male with sickle cell disease diagnosed at age of 5. He had multiple painful vasoocclusive sickle crises treated with blood transfusions, folic acid and rituximab. At age of 21, he presented with sudden right sided weakness and slurred speech. Further investigations, including magnetic resonance imaging of brain revealed occlusion of the left middle cerebral artery resulting in ischemic infarction. Subsequently, he had multiple red blood cell exchange transfusions on regular basis. He remained with residual weakness and slurred speech after rehabilitation. Bone marrow transplant was recommended as a curative treatment for his sickle cell disease by haematology team. A year later, he underwent a geno-identical allogeneic bone marrow transplantation harvested from his brother. He remained well for 22 months post-transplant without any evidence of graft versus host disease. 23 months post-transplant, he presented with loose motions, 2 kg wight loss and fine tremors. He was referred to endocrine department for further workup. Physical examination revealed a small smooth goitre. He had discrete exophthalmos of his left eye without any signs of active inflammation. Thyroid function tests confirmed diagnosis of Graves’ disease with TSH<0.01 milli IU/L, Free T4=23.9 pmol/L, and TSH receptor antibodies of 3.79 IU/ml. Ophthalmological consultation suggested 6 months of selenium supplementation (200 mcg/day) with regular follow up. There has been no family history of autoimmune diseases or thyroid disorders. He started carbimazole (CMZ) 30 mg daily. His symptoms improved within 8 weeks, with normalization of Free T4 and Free T3 (TSH remained suppressed). 18 months later, he remained asymptomatic on carbimazole. He had recurrence of hyperthyroidism symptoms after 4 weeks trail of stopping carbimazole with elevation of Free T4 and Free T3. Carbimazole was restarted and he has been offered other treatment modalities of Graves’ disease. He elected to undergo total thyroidectomy. His sickle cell and blood counts remained stable during follow up period. Conclusion: Transplanted patients carries a life-long risk for developing endocrinopathies post initial transplant therapy. Acknowledging the wide spectrum of post-transplant endocrinopathies, an individualized case based periodic screening can be helpful to improve health outcomes of such patients. Because of the usual late presentation of such endocrine complications, transplanted patients might need life-long endocrine follow-up.
Hashimoto’s Thyroiditis Associated Thyroid Eye Disease:A Success Story of Teprotumumab
Authors: Jamal Issra
Published: May 2021

Background: Thyroid-associated eye disease is more common in patients with Graves’ disease. However, patients with Hashimoto’s may also be affected by thyroid-associated eye disease in up to 6% of patients. Clinical Case: 44 year old female patient with history of Hashimoto’s thyroiditis presented to the clinic for her hypothyroidism and evaluation of thyroid eye disease. The patient was experiencing episodes of bilateral and unilateral inflammation of her eyes described as redness, dryness, bulging of the eyes. She was evaluated by ophthalmology and was diagnosed with thyroid eye disease and was prescribed a course of steroids with partial improvement of the symptoms. Orbital MRI was ordered and it showed symmetrical enlargement of the inferior rectus muscles bellies bilaterally with the left being slightly more enlarged than the right, retro orbital fat pad was grossly inflamed. TPO was elevated,TSI and TRAb were negative. Patient continued to have frequent flare ups with suboptimal response to steroid therapy. A discussion about starting Teprotumumab was made due to lack of optimal response to steroids and worsening of her symptoms and therapy was started. Patient did develop significant hyperglycemia, but she did not have recurrent flare ups. Studies have found that Thyroid-associated eye disease was present in up to (6%) of Hashimoto’s thyroiditis patients, those with thyroid-associated eye disease tended to be older, have a longer duration of Hashimoto’s thyroiditis, heavy smokers, and were less likely to present with another associated autoimmune disease. TSAb was positive in 5.5% in the patients with Hashimoto’s and thyroid-associated eye disease. Teprotumumab ([IGF-1] receptor inhibitor) was approved for the treatment of Graves’ orbitopathy by the (FDA) in 2020. Conclusion: Hashimoto’s thyroiditis associated thyroid eye disease is a rare clinical presentation. Teprotumumab is a new FDA approved treatment for thyroid eye disease that was successful in treating the symptoms and prevented flare ups in this patient. Careful monitoring of side effects is recommended.

References: Kahaly GJ et al Thyroid stimulating antibodies are highly prevalent in Hashimoto’s thyroiditis and associated orbitopathy. J Clin Endocrinol Metab. March 10, 2016\Krassas GE, Wiersinga WM. - Thyroid eye disease: current concepts and the EUGOGO perspective. Thyroid International. 2005;4:3–4. Teprotumumab for Thyroid-Associated Ophthalmopathy. Smith TJ, Kahaly GJ, Ezra DG, Fleming JC, Dailey RA, Tang RA, Harris GJ, Antonelli A, Salvi M, Goldberg RA, Gigantelli JW, Couch SM, Shriver EM, Hayek BR, Hink EM, Woodward RM, Gabriel K, Magni G, Douglas RS SO N Engl J Med. 2017;376(18):1748.
Hyperthyroid Manifestation in Beta HCG Secreting Tumor
Authors: Oktavia Nani , Pratiwi Chici , Mokoagow Muhammad Ikhsan , Epriliawati Marina , Nasaruddin Jerry , Kshanti Ida Ayu
Published: May 2021

Background: Serum β-Human Chorionic Gonadotropin (HCG) levels can be increased not only in pregnancy but also in various malignancies such as germ cell malignancy, lung cancer, ovarian cancer, and breast cancer. The alpha subunit of HCG and TSH are homologous, so β-HCG can cross-react with the TSH receptors and induce hyperthyroidism. High level of β-HCG serum can lead to hyperthyroidism, which can aggravate the patient’s malignant manifestations.

Case Presentation: A 33-year old woman admitted to our hospital with chief complaint general weakness one week before admission. The patient was 8 week-pregnant and the transabdominal ultrasound showed a gestational sac and she had also a positive urine β-HCG test. The patient had slight vaginal bleeding 1 month ago. The physical examination revealed tachycardia, pale conjunctiva, and multiple nodules in both breasts. On laboratory examination, we found low level of Hb 6.7 (n 11.7 - 15.5 g/dl), serum iron 18 (n 65 - 175 mg/dL), TIBC 164 (n 253 - 435 mg/dL), and ferritin 1971(n 4.63-204 mg/dL), positive urine β-HCG, potassium 2.5 (n 3.1 - 5.1 mmol/L). On transvaginal and transabdominal ultrasound examination, there was no gestational sac in the uterine cavity and there are no abnormalities in other gynecology organs. The chest X-ray showed a nodule in the upper right lung suggestive of metastasis with thickening of the soft tissue of the left mammary region suggestive of a left breast mass. We also found a consistent positive result of urine β-HCG, though it had passed four weeks after the occurrence of vaginal bleeding. Finally, the serum β-HCG examination was carried out and showed an increased result, 290,398 (n <5 mIU/ml). The chest CT showed a heterogeny mass (mixed iso-dense and hypodense) that enhanced contrast on the inferior lobe of left lung (4.1 cm x 12.1 cm x 14.1 cm), a mass on apical segment of right lung, subpleural nodule, a mass on the right kidney, spleen, and mediastinal lymphadenopathy. The patient had packed red cell transfusion and after the Hb level reached 11 mg/dl, she still had tachycardia, so we examined the TSHs level. TSHs was found to be low at 0.014 (n 0.48-4.17 mg/dL), and FT4 increased to 2.82 (n 0.89-1.76 mg/dL). Thyroid ultrasound showed small simple cysts in both inferior thyroid pools, no solid mass and no increased vascular flow to the thyroid parenchyma. The patient was then thought to have hyperthyroid manifestation due to β-HCG secreting tumor. She was had methimazole and propranolol therapy, and a lung biopsy was planned.

Conclusion: Trophoblastic and non-trophoblastic tumors that secrete high level of β-HCG can induce hyperthyroid manifestations, particularly if the level was more than 20,000 mIU/mL
Hyperthyroidism and Immune Thrombocytopenia (ITP) Overlap Presenting as Hypoxic Ischemic Encephalopathy in a 38-Year-Old Filipino Female: A Case Report
Authors: Sarigumba Marion Bagaloyos , Cating-Cabral Monica Therese B
Published: May 2021

Background: The coexistence of these two conditions can mimic severe sepsis in critically ill patients which may leave severe thyrotoxicosis unrecognized. Its higher incidence in Asian population suggests a possible genetic propensity.

Clinical Case: A 38-year-old Filipino female sought consult due to changes in behavior. Two months prior, patient had persistent heavy menstrual bleeding but refused work-up. There was progressive weakness and pallor in the interim but no consult was done until she had an aggressive behavior hitting everyone she sees. Patient has Graves disease, maintained on methimazole 15 mg/day and propranolol 30 mg/day. Patient was advised to undergo radioactive iodine therapy but was lost to follow-up for 2 years. Likewise, no medication adjustment nor monitoring of biochemical parameters was done during the same period. On admission, patient was disoriented, tachycardic and febrile. She was generally pale with petechiae on the extremities and blood clots on her lips. Internal examination of the introitus revealed fresh blood with clots. Pregnancy test was negative. Initial laboratory evaluation revealed severe anemia (3.3 g/dl) and thrombocytopenia (3000/uL). Peripheral smear showed mild anisocytosis of red blood cells with no blasts nor atypical lymphocytes and platelet clumps seen. Patient received 1 unit platelet apherese and 2 units packed red blood cells (PRBC) and was started on broad spectrum antibiotic. Neurologic evaluation was negative for craniopathies. Baseline cranial CT scan was not done due to absence of lateralizing signs and was managed as a case of hypoxic ischemic encephalopathy from severe blood loss. Patient was biochemically hyperthyroid with TSH 0.065 uIU/ml, FT4 2.67 ng/dl and 10-fold elevated anti-TPO. Methimazole was then resumed at 20 mg/day and propranolol at 30 mg/day. Neck ultrasound showed an enlarged thyroid with diffuse parenchymal disease. Furthermore, patient had negative Coombs test, normal fibrinogen and procalcitonin. Patient was weakly positive for ANA at 1:160 dilution but negative for other markers in the lupus panel. Consistent with ITP, patient was started on IV hydrocortisone. In the interim, patient had less vaginal bleeding but with persistent bicytopenia which required multiple platelet and PRBC transfusions. A bone marrow biopsy was contemplated. However, on the 7th hospital day, patient had sudden onset of right sided paresthesia with dysarthria and hematomas on extremities. MRI of the brain revealed a large intraparenchymal hemorrhage and patient eventually succumbed to it.

Conclusion: Bone marrow dysfunction secondary to the hyperthyroid state may explain the lack of response to standard therapy of ITP. There is short platelet lifespan, which is rather metabolic in nature, from increased reticuloendothelial phagocytic activity by upregulation of Fc receptor activity in patients with hyperthyroidism.
Hyperthyroidism: A Rare Cause of Cerebral Venous Thrombosis
Authors: Arguinchona Joseph , Pinjala Anusha , George Andrea
Published: May 2021

Background: Cerebral venous thrombosis (CVT) accounts for <1% of strokes. In most cases, there is a predisposition to hypercoagulability; however, in about 30% of cases there is no identifiable etiology. Risk factors include pregnancy, puerperium, oral contraceptives, and coagulopathies and rarely hyperthyroidism. To the best of our knowledge there is no reported cases of CVT in uncontrolled hyperthyroidism with no underlying hypercoagulable disorder. We present a case where a woman developed CVT in the setting of uncontrolled hyperthyroidism. Clinical Case: A 24 year-old Caucasian woman was diagnosed with hyperthyroidism during 1st trimester of pregnancy based labs and was treated with propylthiouracil (PTU) 150 mg bid. At 34 weeks of pregnancy her FT4 normalized and PTU was discontinued. Three and half months post-partum she presented with left frontal headache, photophobia, phonophobia and transient visual loss on the right. Physical exam revealed right homonymous hemianopia without meningismus and an enlarged thyroid. Vitals showed BP 108/57 mm of Hg, HR 162 beats/min, RR of 23/min. CT head without contrast showed 8 mm focal hyperdensity along the left tentorium projecting at the left occipital lobe. She developed seizures after admission. MRI brain with and without contrast showed diffusely small left transverse and sigmoid sinus with a focal area of dural sinus thrombosis. MRI venogram of head confirmed CVT. She was started on levetiracetam and low dose heparin drip. Further workup showed: TSH <0.005 UIU/ml with FT4>8 ng/dl, TSH receptor antibodies 11.10 (normal range 0.00 - 1.75 IU/L), thyroid peroxidase antibody >1300 (normal range <=59 u/ml), and thyroid stimulating antibodies 6.85 (0.00 - 0.55 IU/L) suggestive of Graves disease. She was initiated on PTU 200 mg Q8hrs, propranolol 80 mg Q8hrs and lugol’s iodine 5 drops Q8hrs. Hypercoagulable workup except for protein C and S returned unremarkable. Over the next several days, thyroid levels improved significantly. She was discharged home on warfarin and methimazole. Conclusion: The exact pathophysiology of CVT in hyperthyroidism remains unclear. Some proposed mechanisms include increased activity of pro coagulative plasma constituents including Von Willebrands Factor, Factor IX, X, antithrombin, and fibrinogen as well as an increased aPTT and a decrease in thrombolytic factors like t-PA. These changes result in an increased risk of thrombosis. This case demonstrates the potential development of CVT as a result of untreated overt hyperthyroidism. It highlights the importance of treatment and close follow up of Graves’ disease to prevent severe complications. Further studies need to be done to understand the process of coagulation in hyperthyroidism and this could allow clinicians to better identify hyperthyroid patients at risk for clotting.
Intrathyroidal Branchial Cleft Cysts Presenting as Bilateral Thyroid Nodules
Authors: Faisal Sobia , Rosenblatt Joseph
Published: May 2021

Introduction: Intrathyroidal brachial cleft cysts are a rare entity and are usually associated with Hashimoto’s thyroiditis. Etiology is not very clear at this point, but they are thought to arise from the ultimobranchial body remnant during embryogenesis of the gland versus originating secondary to chronic inflammation as a form of squamous metaplasia. They are a common finding in the lateral neck but not with the thyroid. We present a case of a suspicious appearing bilateral thyroid nodules which were found to branchial cleft cysts on biopsy.

Clinical Case: A 56-year-old woman presented to us for evaluation of thyroid nodules. Her past medical history was pertinent for endometrial cancer status post surgery and radiation, obesity, sleep apnea, hyperlipidemia and hypothyroidism. She was diagnosed with hypothyroidism around 30 years ago and had been on Levothyroxine since then. She was recently noted to have a low TSH level on routine labs done by her primary care provider and therefore her Levothyroxine dose was adjusted. She also underwent a thyroid ultrasound due to exam findings of a palpable thyroid nodule. The ultrasound revealed a suspicious 2.2 cm hypoechoic solid nodule with irregular margins and micro-calcifications in the left mid thyroid lobe. Additionally, she was also noted to have a 0.8 cm hypoechoic nodule with irregular margins in the right mid thyroid lobe. No concerning cervical lymphadenopathy was identified. She was hence referred to us for further evaluation. She denied having compressive symptoms and did not have history of head/neck radiation or family history of thyroid cancer. Both nodules were biopsied but were interpreted as non-diagnostic with insufficient follicular cells and colloid. She underwent repeat biopsy of both nodules which again was interpreted as non-diagnostic. After discussion with patient, given her suspicious ultrasound findings and inconclusive biopsy results she was referred to endocrine surgery for surgical evaluation. Shortly after she underwent total thyroidectomy with pathology consistent with bilateral benign branchial cleft like cysts associated with adjacent thyroid follicles undergoing squamous metaplasia admixed with chronic inflammation.

Conclusion: Pathogenesis of these intrathyroidal branchial cleft cysts is still unclear and not many similar cases have been reported in the literature so far. These commonly present as a painless mass but sometimes can also be an incidental finding. There are not a lot of specific details in the literature regarding imaging or pathology characteristics of these lesions therefore resulting in surgical intervention to reach a definitive diagnosis.
Pancytopenia in a Patient With Severe Hypothyroidism: A Case Report
Authors: Bulut Aysegul , AlSibai Khaled , Norman Catalina
Published: May 2021

Introduction: Hypothyroidism usually affects red blood cell line most commonly seen as normochromic normocytic anemia. We present a unique case of a patient with pancytopenia in the setting of severe hypothyroidism, which improved following IV thyroid hormone replacement.

Case: An 85-year-old female with history of type II diabetes mellitus and hypothyroidism who was admitted for open reduction and internal fixation (ORIF) of a displaced left femur fracture following a mechanical fall. Patient has a long-standing history of hypothyroidism on replacement with levothyroxine 75 mcg, which was inadvertently discontinued at the nursing home 2 weeks prior to presentation. CBC on admission was notable for pancytopenia with macrocytic anemia with hemoglobin of 6.2 g/dl (baseline of 11), leukopenia with WBC of 4.2 x103/ul and thrombocytopenia with platelet of 77 X 103 /ul. TSH was 83 uIU/mL (reference range: 0.34 - 5.6) and Free T4 was < 0.11 ng/dl (reference range: 0.93 - 1.7). Patient was on the verge of developing myxedema coma as she presented with hypotension with blood pressure of 103/55 mmHg, hyponatremia 133 mmol/L and mild change in mental status. There was no evidence for hypothermia or bradycardia. Presence of a small thigh hematoma on examination partially explained the acute drop in hemoglobin. Iron panel, folic acid and vitamin B12 levels were found to be within normal range. Patient had no active of infection to suggest sepsis and she did not receive any myelosuppressive medication. Rapid replacement with IV levothyroxine was started before proceeding with surgery to prevent development of myxedema coma. Free T4 normalized at 1.05 ng/dl after receiving a total of 700 mcg of IV levothyroxine on day 5 of hospitalization. ORIF was done with no complications. Pancytopenia resolved upon thyroid replacement therapy and she was discharged on her regular dose of levothyroxine 75 mcg daily.

Discussion: Most common hematologic abnormality associated with hypothyroidism is normochromic normocytic anemia. Currently, there are less than 10 reported cases of pancytopenia associated with hypothyroidism. The exact mechanism is unclear but proposed hypothesis is transient bone marrow hypoplasia. The most common clinical presentation, as seen in our patient, is profound hypothyroidism with ultimate outcome of myxedema coma. Most of these patients had resolution of pancytopenia following adequate thyroid hormone replacement. Interestingly, all cases have been reported in female patient population. Further research is needed to understand pathophysiology, risk factors, prognosis and the risk of pancytopenia recurrence in patients with severe hypothyroidism. More importantly, hypothyroidism must certainly be entertained as a differential diagnosis of pancytopenia.
Postpartum Thyroid Abnormalities and Systemic Lupus Erythematosus: Is There a Link?
Authors: Albrecht Jordan , Ahmed Moeed , Nandala Sudha , Farooqi Saad , Anderson Robert J
Published: May 2021

Introduction: Postpartum Thyroiditis (PPT) is an autoimmune disorder characterized by destruction of the thyroid gland within the first year after delivery. Systemic Lupus Erythematosus (SLE), another autoimmune disease, has been associated with a spectrum of thyroid disorders. While the prevalence of thyroid diseases in patients with SLE is increased, the association between SLE and PPT is not well known. The infrequency of encountering SLE and PPT makes abnormal thyroid tests in the postpartum period a diagnostic challenge.

Clinical Case: A 27-year-old G1P1001 who was five months postpartum and not breast feeding was referred to Endocrinology clinic for evaluation of abnormal thyroid function tests. Past medical history was significant for SLE with renal and pericardial involvement. SLE was well controlled, treated with hydroxychloroquine. Family history was significant for hypothyroidism in her mother.

She was asymptomatic and appeared clinically euthyroid. Vitals were stable and physical exam was negative for goiter, nodule or orbitopathy. Lab results at two months postpartum showed an elevated TSH of 3.87 UIU/mL (Normal 0.40-3.8 UIU/mL) and at four months postpartum TSH was low at 0.012 UIU/mL. Repeat labs at five months postpartum continued to show a low TSH at 0.007 UIU/mL with mildly elevated Free T4 at 1.7 ng/dL (Normal 0.6-1.6 ng/dL) and elevated Free T3 of 6.0 pg/mL (Normal 2.1-3.8 pg/mL). Anti-thyroid peroxidase antibodies (TPO), thyroid stimulating antibodies (TSI) and TSH receptor antibodies (TRAb) were negative. Thyroid Ultrasound with Doppler was within normal limits. Radioactive Iodine Uptake and Scan, obtained at 6 months postpartum, showed high normal uptake (17% and 32% at 4 hours and 24 hours respectively), suggestive of recovery phase of PPT. The most recent TSH was elevated at 8.5 UIU/mL and Free T4 was low at 0.7 ng/dL. Disease course was consistent with PPT.

Conclusion: The Th1 (T-helper) lymphocyte immune predominance in autoimmune thyroid disease and SLE is the immune-pathogenetic base of the association between both diseases. Postpartum thyroiditis is a variant of chronic autoimmune thyroiditis. Serum anti-TPO antibodies vary during pregnancy and tend to increase early and may decline later. Immunologic tolerance increases during pregnancy, fades in the postpartum period and makes interpretation of thyroid function tests and disease process challenging.

Pregnant and postpartum patients who have SLE have increased prevalence of thyroid disease. Causes are multifactorial with a higher prevalence of hypothyroidism and thyroid autoantibodies. Hyperthyroidism is much less likely. One comparable study found 6 of 43 (14%) women with SLE developed PPT and only one of these patients had positive thyroid antibodies. These reports and our patient illustrate the variability of thyroid function tests in patients with SLE.