bluuebunny/crossref_metadata_2025 huggingface dataset:
The Dexamethasone-CRH Stimulation Test: A Single-Center Experience
Authors: Wehbeh Leen , Alwahab Ula Abed , Mikhael Alexandra , Dobri Georgiana , Kennedy Laurence , Hamrahian Amir Hekmat
Published: May 2021

Background: The diagnostic value of adding a Corticotropin Releasing Hormone (CRH) Stimulation Test to the 2-day Low Dose Dexamethasone Suppression Test (Dex-CRH Test) has been debated in the literature. We hypothesized that adding CRH to LDDST would provide additional case detection in patients suspected of having Cushing’s disease (CD).

Methods: We identified 118 patients who underwent the Dex-CRH test to evaluate ACTH-dependent CS from a prospectively maintained pituitary database over 12 years. Seven patients were excluded (2 lost to follow up, 2 were on Dilantin with no available Dexamethasone (Dex) level, 2 had cyclic CD, and 1 suspected noncompliance with Dex intake). Three patients with ectopic ACTH Syndrome had very high cortisol levels after both LDDST and Dex-CRH tests. The remaining 108 patients are the subjects of this analysis. Patients were instructed to take 8 doses of Dex 0.5 mg PO every 6 hours starting at noon with the last dose of Dex taken at 6 AM. Ovine CRH injection (1 µg/kg, max 100 mcg) was given IV 2 hours afterwards. Cortisol was measured 2 hours after the last Dex dose prior to and 15 minutes after CRH administration. CD diagnosis was made based on positive ACTH staining on pituitary pathology and/or development of hypocortisolism postoperatively. Patients with no Cushing disease (NCD) are the group of patients in whom CD diagnosis could not be confirmed after a minimum follow up of 30 months.

Results: Among 108 patients who underwent Dex-CRH test, 66 had CD and 42 had NCD. The female sex ratio, and median (range) for each of age, BMI, and follow-up duration in months were as follows with no statistically significant difference between the two groups: CD: 83%, 40 (15–82), 34 (30–42) and 63 (24–102). NCD: 88%, 40 (20–71), 37 (31–43) and 52 (30–67). Among 66 patients with CD, 5 patients (7.6%) had a cortisol level ≤ 1.4 µg/dl after LDDST but were appropriately classified as CD with a cortisol level >1.4 µg/dL at 15-min post CRH stimulation. In contrast, 3/42 patients (7.1%) in NCD had an abnormal Dex-CRH test. In only one of these three patients the LDDST was normal (cortisol post-Dex was 1.4 µg/dL and increased to 3.1 µg/dL 15-min post CRH). A cortisol cut-off value of > 1.4 µg/dL at 15 min during Dex-CRH test provided a sensitivity of 100%, specificity of 93%, and diagnostic accuracy of 97% to diagnose CD. When patients without a Dex level were excluded from the analysis (n=74), the sensitivity did not change but specificity and accuracy of Dex-CRH test further increased to 97% and 99%, respectively.

Conclusion: The CRH test addition to the 2-day LDDST provided additional case detection in 5/66 (7.6%) of patients with CD. It resulted in one additional false-positive case compared to LDDST. Measurement of Dex level provided improved diagnostic accuracy of DEX-CRH test.
Regrowth of Thyroid Gland: Is This Possible????
Authors: Techathaveewat Pawarid , Alhakim Manal , Correa Ricardo Rafael , Vinales Karyne Lima
Published: May 2021

Introduction: Adult Thyroid gland which derived from primitive pharynx and neural crest is considered a non-regenerative organ. In this nature, partial or total thyroidectomy is considered a curative treatment for compressive non-malignant goiter. While there is a potential regrowth from stimulating by pituitary thyroid stimulating hormone (TSH), such growth is rarely significant and suppressive TSH therapy is currently indicated only for thyroid malignancy. We present an unusual case of rapid regrowth of normal thyroid tissue that expanded both of the lobes from a single unilateral remnant.

Case: 58-year-old male with prior history of multinodular goiter status post subtotal thyroidectomy due to compressive symptoms in 2006 present to our clinic for follow up. Post-operatively, case was complicated with Iatrogenic Hypoparathyroidism thus on replacement of calcium and calcitriol. Follow up neck ultrasound (US), showed no thyroid gland with minimal residual tissue in the right fossa and pathology was benign. In 2011, patient complained of new onset globus sensation, and voice changes which initially concern for gastroenterology issue as the etiology. A neck US unexpectedly revealed normal right thyroid lobe of 5.7 cm without any tissue on the left and no nodule. FNA subsequently performed which was benign tissue. Due to high risk of complication for repeat surgery, annual US was planned for monitoring. In 2013 there was a significant new growth of left thyroid of 1.7 cm in size, no nodules. A repeat US six months later revealed an increase in size in the right from 5.7 to 6.1 cm as well as 1.7 to 2.1cm on the left. Patient denied any compressive symptoms, so we continue with neck US surveillance. By 2020, the right lobe was 6.4 cm and left lobe at 2.4 cm. Within both lobes, now multiple nodules start appearing. FNA were performed on several of those nodules with a benign cytopathology in all of them. Of note, other than regrowth of his thyroid, it is also physiologically functional as patient is euthyroid without levothyroxine replacement since 2013.

Discussion: When patient underwent thyroidectomy for benign multinodular goiter, thyroid function test is the only routine test for follow up without additional further images. While it is considered a curative treatment, some regeneration or recurrence is still a possibility which is shown in our case. This is one of the few cases in the literature that we could found about normal thyroid tissue regrowth. It is still unclear how the mechanism for this phenomenon occurs. Further studies may need to be pursued with regards to suppressive TSH therapy or even radioactive iodine ablation for benign goiter that have regrowth potential. It is crucial that physicians become aware of such occurrence may happen since new thyroid nodules can also develop in the new thyroid tissue and fine needle aspiration should be performed accordingly.
Reverse T3 in Patients With Hypothyroidism, Helpful or a Waste of Time?
Authors: Wilson Julian Bryant , Friedman Theodore C
Published: May 2021

Background: Reverse T3 (rT3) is a biologically inactive form of T3 that is created by peripheral 5 deiodination of T4 by type 1 and type 3 deiodinases and may block T3 binding to the thyroid hormone receptor. As about 15% of patients on L-T4 replacement with a normalized TSH report continued fatigue and other hypothyroid symptoms, efforts are needed to understand why this occurs and how it can be corrected. Decades ago, endocrinologists realized that in severe illnesses, rT3 is often high and T3 is often low and termed this “sick euthyroid syndrome”. However, more recently, alternative doctors, including functional medicine doctors, have argued that high rT3 is detrimental and can block T3 from binding to the thyroid hormone receptor. Without peer-reviewed publications, these functional medicine doctors rely heavily on rT3 levels to treat patients that may have no other laboratory findings of hypothyroidism and often prescribe them L-T3-only preparations to try to lower the rT3. Also poorly characterized in the literature are the effects of hypercortisolism and hypopituitarism, both of which should modulate the expression of deiodinases to increase rT3. Hypotheses: 1) Patient rT3 levels will vary significantly with the type of thyroid medication taken. 2) Patient rT3 levels will be clinically significant in the management of patients on thyroid medications. 3) Hypercortisolism and hypopituitarism will increase rT3 levels. Methods: The most recent rT3 measurements were analyzed from 621 patients currently being managed by TCF. The upper limit of normal for rT3 at either Quest or LabCorp, which is usually 24.1 ng/dL was used as a cut-off for a high result and below 9.2 ng/dL as the low cut-off. Results: Elevate rT3 levels was seen in 3% of patients of patients not on thyroid replacement (5/143), seen in 8% of patients (17/203) taking desiccated thyroid. It was more prevalent in patients taking desiccated thyroid with synthetic T3 (27%, 7/26) or T4 (15%, 16/104) and was seen in 15% of patients (9/58) taking synthetic T4 alone. Changes were made to the amount or type of medications in 199 patients. Levels of rT3 levels were outside the normal range in 27% of these patients (54/199), being above normal range in 16% of these patients (32/199). Hypercortisolism was seen in 37 patients, 36 from Cushing’s disease, however above normal rT3 was seen in only 2 patients. Hypopituitarism was diagnosed in 22 patients, only one had above normal rT3 levels because they couldn’t afford their growth hormone replacement. Conclusion: Measuring rT3 may be helpful in patients who are already on thyroid treatments, and is of greater importance in patients taking synthetic preparations. It is not recommended in patients who are not taking thyroid medicine (even if experiencing hypercortisolism) or in patients with hypopituitarism that are taking adequate hormone replacement.
Subacute Thyroiditis After mRNA Vaccine for Covid-19
Authors: Franquemont Stephanie , Galvez Juan
Published: May 2021

Introduction: Subacute thyroiditis is a well-documented clinical condition which typically presents 1-2 weeks after an acute viral illness. Presenting symptoms are classically those of thyrotoxicosis but with associated tenderness in the thyroid. Treatment of acute symptoms is possible and the thyroid function will generally normalize with time. Subacute thyroiditis has rarely been reported after administration of viral vaccinations such as the seasonal flu vaccine. We present a case of subacute thyroiditis which presented after administration of the mRNA COVID-19 vaccine.

Case: Patient is a 42yo female with no past medical history. She received the first dose of the Pfizer/BioNTech mRNA vaccine for COVID-19 on 12/22/20. Five days later, the patient complained of sore throat and palpitations. These symptoms progressed and she was evaluated in an urgent care on 12/31/20 where she was found to have tachycardia. Infectious work-up, including PCR for COVID-19, was negative and she was sent home. She took ibuprofen with some improvement of her symptoms. The following day she went to the ED; she was found to have a heart rate in the 130s with sinus tachycardia on EKG. Thyroid function testing was done which revealed TSH <0.01, fT4 4.58, fT3 11.8. Her TPO antibody was <28 and inflammatory markers were elevated including sed rate of 62. The patient was prescribed prednisone 40mg daily and propranolol 20mg as needed for symptoms. She reports rapid improvement of symptoms with prednisone. On 1/21/20, thyroid function showed TSH <0.01, fT4 down to 3.2, tT3 normal at 135. Thyroglobulin was elevated at 140.8 with negative thyroglobulin antibody, TRAb and TSI. Her inflammatory markers had decreased with sed rate of 26 and normal C-reactive protein. She had improved symptoms.

Discussion: Cases of subacute thyroiditis are most commonly associated with upper respiratory viruses but cases have been reported with traditional inactivated viral vaccines or live-attenuated vaccines such as those for annual influenza. We present the case of a 42-year-old female who has presented with a classic case of subacute thyroiditis which occurred in the time frame after receiving the Pfizer mRNA vaccine for COVID-19. Research has been ongoing for decades regarding development of mRNA vaccines but the mRNA vaccines for the SARS-CoV-2 virus have been the first to be widely distributed to the general population. Thyroiditis has not been reported as a common side effect but the cross recognition between the coronavirus spike protein targeted with the mRNA vaccine and healthy thyroid cell antigens exists as evidenced by this case.

Sources: 1. Prummel M, Strieder T, Wiersinga WM. The environment and autoimmune thyroid diseases. Eur J Endocrinol. 2004;150:605-618. Altay FA, Guz G, Altay M. 2. Subacute thyroiditis following seasonal influenza vaccination. Hum Vaccin Immunother. 2016;12(4):1033-1034.
Subacute Thyroiditis Associated With Liraglutide
Authors: Erturk Banu , Dagdelen Selcuk
Published: May 2021

Objective: Incretins are expressed in thyroid tissue but without clearly-known clinical significance in human. The long-term effect of GLP-1 receptor activation on the thyroid is unknown. In the literature, liragludite-related thyroiditis has not been reported yet and here we wanted to draw attention to this association. Case Summary: A 52-year-old woman with type 2 diabetes mellitus presented with thyroid tenderness, tremor and fever. Her lab results were as follows: undetectable TSH, free T4 (FT4) = 2,4 ng/dl (0.93-1.7), free T3 (FT3) = 4.4 pg/mL (2-4.4). Erythrocyte sedimentation rate (ESR) was 60 mm/hour, C-reactive protein (CRP) was 80 mg/L. Thyroid autoantibodies were negative. USG revealed that thyroid gland was in normal localization and the right lobe was 24x22x46 mm and the left lobe was 20x21x45 mm, isthmus thickness was 5 mm. The parenchyma was heterogeneous, coarsely granular, with bilateral patchy hypoechoic areas. All these findings suggested that the patient had subacute thyroiditis. When we examine the etiological factors of subacute thyroiditis in the patient, there was no history of trauma, no previous viral or bacterial illness, contrast agent exposure. But, she had only been using liraglutide for a week. Firstly liraglutide therapy was ceased and than 20 mg prednisolone and 40 mg beta-blocker therapy was initiated. At the 8 weeks’ of cessation, patient had no symptoms. Also thyroid function tests and other laboratory values were all in normal limits. Conclusions: It has been proven by previous studies that liraglutide has several effects on the thyroid gland. Liraglutide therapy might be related to subacute thyroiditis, as well.
Superior Sagittal Vein Thrombosis in the Setting of Thyroid Storm
Authors: Moran Heberth , Sosa-Pagan Max
Published: May 2021

A 25-year-old female with a two-month history of left lower quadrant pain, found to have an ovarian cyst and recently started on OCPs, presented to an outside medical center after a witnessed seizure with fever, tachycardia, and altered mental status. Her husband reported that she had been lethargic, complained of headaches, and had brief intermittent episodes of staring into space or stopping mid-task four days prior to the current event.

On physical exam, she was hypertensive to 170/90s, tachycardic to 120s, febrile to 101, with hyperreflexia and altered mental status without focal deficits. Burch Wartofsky scale was calculated to be 50, suggestive of thyroid storm. Initial labs showed a suppressed TSH (<0.01 uIU/mL) and an elevated free T4 (7.27 ng/dL). Blood cultures and a lumbar puncture demonstrated no evidence of infection. A non-contrast brain CT showed no acute intracranial findings. She was started on propylthiouracil (PTU), propranolol, hydrocortisone, and Lugol’s solution. Thyrotropin Receptor Antibody and Thyroid Stimulating Immunoglobulin levels were elevated, confirming the diagnosis of Grave’s disease.

After the initial management, her vital signs normalized and free T4 decreased to 4.2 (ng/dL), but she had no mental status improvement. Although she had no further seizure activity, she continued to have waxing and waning levels of consciousness. She then developed left sided focal deficits and was transferred to our hospital for the management of a possible cerebrovascular event. MRI and MRV of the brain were performed and demonstrated a thrombus within the superior sagittal sinus. She was started on heparin and bridged on warfarin prior to discharge. Her anti-thyroid regimen was down titrated, steroids tapered and discontinued, PTU changed to methimazole, and propranolol changed to metoprolol. Her mental status and focal deficits improved prior to discharge.

Patients who present with hyperthyroidism and new-onset neurological symptoms, especially in the setting of OCP use or other risk factors for a hypercoagulable state, should be evaluated for possible cerebral venous thrombosis. The association between overt hyperthyroidism and acute venous thrombosis, especially at cerebral sites, has been documented in numerous case reports.
The Improvement in Hepatic Steatosis After Cushing’s Syndrome Treatment Is an Early Sign of Metabolic Recovery
Authors: Hamimi Ahmed , Sater Zahraa Abdul , McGlotten Raven , Matta Jatin , Pierce Annie , Abd-elmoniem Khaled , Ouwerkerk Ronald , Nieman Lynnette K , Gharib Ahmed M
Published: May 2021

Context: Cushing Syndrome (CS) is characterized by cortisol excess, impaired glucose tolerance, and obesity. As assessed by CT imaging, 20% of CS patients develop steatohepatitis (NASH). The gold standard test, liver biopsy, is associated with CS complications and cannot be used to confirm the diagnosis. This study evaluated the ability of magnetic resonance spectroscopy (MRS).

Objective: To identify the prevalence of NASH and its temporal changes in relation to other metabolic parameters in CS before and after successful treatment. Primary Outcome Measure: PDFF measured by MRS at 3T before, 6 and 12 months after Cushing’s syndrome treatment DESIGN: In this prospective IRB-approved study, 41 consecutive CS patients (44±1.8 y; 34(85%) females, 32.6±1.5 kg/m²; urine cortisol excretion 2242.7±1806.3 [3.5–45.0 mcg/24h]) underwent MRS before, 6 and 12months after successful treatment. PDFF was measured by MRS at 3T; NASH was defined as >5% PDFF. Metabolic markers – glycohemoglobin (A1C) and body mass index (BMI) – were measured; Wilcoxon matched-pairs signed-rank test evaluated changes over time, and spearman rank test evaluated the correlation between variables. Results: At baseline, mean PDFF was 10.4±1.7 and correlated positively with BMI (r=0.5710, p<0.0001). NASH was present in 32% of patients. After treatment, PDFF decreases were similar at 6 and 12 months (-52%, p=0.001 and -50%, p=0.02, respectively); rates of NASH declined to 13% and 11%. BMI decreased (-9%; p=0.0018 and -12%, p=0.0003) but without a statistically significant change overweight/obese status. A significant decrease in A1C followed at 12 months (-12%, p=0.0005).

Conclusions: MRS-PDFF is valuable for diagnosing NASH in Cushing Syndrome, which can affect a third of this patient population. Liver fat decreases by 6 months after normalization of cortisol and precedes the improvement of A1C. Indicating that liver insulin resistance due to fat accumulation has an essential role in diabetes pathophysiology in CS.
The Grave Hematologic and Hepatic Effects of Hyperthyroidism
Authors: Ahmad Sara Miriam , Jiang Bryan
Published: May 2021

Background: Hyperthyroidism can present with a myriad of symptoms including some rare, but morbid systemic manifestations. Here we present the case of a patient who presented with thyrotoxicosis, pancytopenia and cholestatic liver disease.

Clinical Case: A 37 year-old Hispanic female with no significant past medical history presented with weight loss, fatigue, jaundice and irregular menstrual cycles ongoing for 10 months. Upon presentation, vitals were notable for mild tachycardia. She had significant jaundice and a visibly enlarged thyroid gland, while no thyroid eye disease was noted. The patient was found to have a hemoglobin level of 6.5 g/dL (12.0 - 16.0 g/dL), white blood cell level of 2.3 K/uL (4.5 - 11.0 K/uL) and platelet count of 82 K/uL (150 - 400 K/uL). Alkaline phosphatase was elevated to 214 U/L (34.0 - 104.0 U/L) and total bilirubin was 8.7 mg/dl (0.2 - 1.2 mg/dL) with direct bilirubin of 5.4 mg/dL (0.0 - 0.2 mg/dL). Thyroid panel revealed an undetectable TSH and a free T4 of 5.58 ng/dL (0.61 - 1.18 ng/dL). Hematological work-up was negative for malignancy but did note severe iron deficiency. Hepatitis B and C virus, parvovirus B19 serology, magnetic resonance cholangiopancreatography, and autoimmune disease work-up all returned normal. Thyroid uptake scan showed diffuse uptake without nodular disease and a 24-hour uptake of 57% (normal 7-32%). Thyroid stimulating antibodies were positive at 115 IU/L (0.00-0.55 IU/L). Since all other work up was negative, it was concluded that her pancytopenia and cholestatic pattern of liver injury were likely due to hyperthyroidism with plan to do a bone marrow biopsy if she does not have improvement in blood cell counts. Patient was treated with radioactive iodine (RAI) ablation. A week after treatment she had further elevation in total bilirubin, whereas her blood counts had improved. It was decided to initiate methimazole with close monitoring of her liver function tests. Two months after treatment, her thyroid function improved and she was eventually transitioned to levothyroxine for post-ablative hypothyroidism. Bilirubin improved to normal range and her pancytopenia resolved without additional intervention. She had complete resolution of jaundice and started having regular menses 2 months after her RAI treatment.

Conclusion: The etiology of pancytopenia has been thought to be multifactorial with consumption of nutrients (including iron, manifesting as iron deficiency anemia), stimulation of erythropoiesis and sequestration of blood cells due to splenomegaly. Thyroid associated hepatic dysfunction has been proposed to be secondary to relative hypoxia in the perivenular regions and the direct toxic effect of thyroid hormone on hepatic tissue. In patients with concurrent hepatic disease and thyrotoxicosis, it is reasonable to consider treatment with thionamides with close monitoring, if other etiologies for hepatic disease are ruled out.
Thyroid Paraganglioma- An Unusual Head and Neck Tumour
Authors: Sim Sing Yang , Al-Mrayat Ma’en
Published: May 2021

Paragangliomas are neuroendocrine tumour originating from the neural crest-derived paraganglia with majority arising from the head and neck. (1)Thyroid paraganglioma are exceedingly rare neuroendocrine tumours accounting for <0.1% of thyroid malignancy (1)

We present a 57 years old gentleman who was referred to ENT surgeon following discovery of a two month history of lump on his left neckIt has not changed in size and not caused any symptoms such as anxiety, sweats, palpitations, dizziness or unexplained headaches. He has a Past medical history of epilepsy following a Road traffic accident 28 years ago leaving him seizure prone. He has no family history of neuroendocrine tumours His ultrasound scan of his thyroid gland showed a 25 x 23 x 15mm lesion lying anteriorly within the left thyroid lobe. There are two highly reflective foci which could represent microcalcification. It was classified as U5 lesion He proceeded with fine needle aspiration which confirmed carcinoma of the left thyroid gland with no clear differentiation between follicular or papillary carcinoma. He undergone a total thyroidectomy and left central level VI lymph node dissection His histology confirmed a thyroid paraganglioma staining strongly positive for neuroendocrine markers (Synaptophysin and chromogranin) while S-100 shows positivity in the sustentacular cells. He was referred for genetic testing which demonstrate no evidence of mutation in FH, SDHAF2, SDHB/C/D, RET, MAX, TMEM127 and VHL gene. He was commenced on levothyroxine replacement at a dose of 150micrograms OD. His urine metanephrines is 178.1pmol/L (0-510), urine normetanephrines 192.9pmol/L (0-1180) and 3-methoxytyramine <75pmol/ L (0-180) (all normal). His MRI neck revealed no synchronous tumour. He continues to be followed up under our endocrine clinic.

Conclusion: Due to the rarity of these tumours, their natural history is mostly unknown. Nevertheless, postoperative surveillance should include plasma or urinary metanephrines and ultrasonography.

References: 1 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3824793/
Thyroid Storm: A Diagnostic Conundrum
Authors: Maharaul Mashrutee S , Raghuwanshi Maya P , Umar Rehan , Pishdad Reza
Published: May 2021

Thyroid storm is a life threatening complication of hyperthyroidism which comes with multi-system involvement and is associated with a mortality of 8-25% despite modern advancements in treatment and supportive measures.

A 47 year old woman with past medical history of hypertension and morbid obesity presented to the emergency room with 3 week history of shortness of breath and chest pain associated with productive cough, bilateral leg swelling, orthopnea and palpitations. Upon evaluation, she was in moderate respiratory distress, restless, tachypneic and tachycardic. She had bilateral proptosis and visible jugular venous pulsation along-with bibasilar crackles and pitting edema bilaterally. Lab tests revealed BNP 539 pg/ml and D-Dimer 6401 ng/ml. ECG showed atrial flutter, Chest X-Ray showed bilateral pleural effusions, and CT Chest was negative for pulmonary embolism but revealed anterior mediastinal mass, differential of which included thymoma or teratoma. She was admitted to CCU for aggressive diuresis, control of heart rate and was started on anticoagulation. A review of medical records from outside hospital revealed patient was hyperthyroid 8 months ago, however, was not on any medications. Given a Burch-Wartofsky score >70, she was started on IV hydrocortisone and cholestyramine for severe thyrotoxicosis. Endocrinology was consulted and added PTU to management. TFTs revealed a TSH 0.006 IU/ml, FT4 4 ng/dL and T3 2.5 ng/ml. Bedside ECHO showed LVEF of 14% with global hypokinesis and thyroid ultrasound revealed an enlarged, heterogenous thyroid with a solid, isoechoic, calcified left lobe nodule measuring 0.8 x 0.4 x 0.5 cm. Her serum TSI and thyrotropin receptor antibodies were elevated at 17.20 IU/L and 20.20 IU/L, respectively. She responded to treatment and was discharged on metoprolol, losartan, spironolactone, and furosemide for new-onset heart failure, apixaban for atrial flutter, and PTU and cholestyramine for hyperthyroidism, with Cardiology and Endocrinology follow-ups.

Thyroid disease is a common illness affecting 9 to 15 percent of the adults. Thyrotoxicosis refers to the clinical syndrome of hyper-metabolism due to excessive amount of circulating thyroid hormones. The incidence of thyroid storm is 0.57 to 0.76 per 100,000 people per year in the US. It most commonly occurs in women and is more common in patients with underlying Grave’s Disease. The exact underlying mechanism that leads to thyroid storm is not well understood but adrenergic activation seems to have a major role. Our patient had long standing untreated hyperthyroidism with a solid nodule which led to the crisis. The most common cause of death is cardiopulmonary failure and hence treatment should be initiated as soon as diagnosis is suspected owing to high mortality.

Awareness of thyroid pathology affecting the heart is important to remember in evaluating the etiology of heart failure in patients.
Thyroid Storm: A Dreaded Complication of Percutaneous Tracheostomy
Authors: Pradeep Pallavi , Kazi Mohammed Hussain
Published: May 2021

Background: Thyroid gland may be manipulated during tracheostomy. Although uncommon, this may result in potentially life-threatening thyroid storm especially in patients with underlying thyroidal illness. Plasmapheresis maybe used as a treatment modality for these patients.

Clinical Case: A 65-year-old Hispanic male was admitted to the hospital for acute exacerbation of heart failure and pneumonia. Medical history was significant for atrial fibrillation. He had been on amiodarone for 2 years, which was discontinued 2 months ago when he was diagnosed with amiodarone indued thyrotoxicosis (AIT). He was never started on any treatment for AIT. Lab work on admission was significant for undetectable TSH, fT4 of 4.4 ng/ml (RR: 0.8-1.5 ng/ml) and fT3 of 4pg/ml (RR: 2.2- 4.0 pg/ml). TSH receptor antibody was negative. Thyroid ultrasound showed mildly atrophic gland with no nodules. Methimazole, cholestyramine and hydrocortisone were initiated, and TFTs were trending down. Hospital course was complicated by cardio-respiratory failure requiring mechanical ventilation. After a short-term improvement in his clinical status, patient underwent percutaneous tracheotomy due to failure to wean from mechanical ventilation. On POD1, he was found to be tachycardic and febrile with Burch-Wartofsky score of 55, which was highly suggestive of thyroid storm. fT4 was >8ng/ml and fT3 was 11.4pg/ml. He did not respond to maximal doses of thionamides, steroids and b-blocker. Thyroidectomy was considered, but patient was deemed to be high risk for any surgical intervention. Plasmapheresis was initiated for 5 days. TFT started trending down and patient improved clinically. On POD 14, fT4 was 2.1ng/ml, fT3 was 3.8 pg/ml.

Conclusion: This case highlights a rare complication of tracheostomy in a patient with known history of AIT. Studies have shown that there can be a significant increase in serum thyroid hormone levels after tracheostomy, even in euthyroid patients. There may even be a role of performing tracheostomy with thyroidectomy in non-euthyroidal patients. Use of plasmapheresis for thyroid storm is recommended by American Society of Apheresis when first line medical therapy fails. It maybe particularly effective in AIT as amiodarone and its active metabolite are highly bound to plasma proteins. To our knowledge, this is the first case of thyroid storm with a history of AIT, which was precipitated by tracheostomy, and successfully treated with plasmapheresis.

References: 1. Esen E, Karaman M, Deveci I, Tatlıpınar A, Tuncel A, Sheidaei S, Esen S. Analysis and comparison of changing in thyroid hormones after percutaneous and surgical tracheotomy. Auris Nasus Larynx. 2012 Dec;39(6):601-5.2. Muller C, Perrin P, Faller B, Richter S, Chantrel F. Role of plasma exchange in the thyroid storm. Ther Apher Dial. 2011 Dec;15(6):522-31.
Thyrotoxic Periodic Paralysis in Young Caucasian Male
Authors: Panthi Sujata , Bhattacharya Rajib Kumar
Published: May 2021

Background: Thyrotoxic periodic paralysis (TPP) can be a medical emergency as delay in diagnosis can lead to life-threatening arrhythmia. Periodic paralysis is more prevalent in the Asian population. We report a case of thyrotoxic periodic paralysis in a young Caucasian male.

Case: A 24-year-old male with a past history of Graves’ disease, hypertension, and asthma was brought to the hospital due to leg weakness and fall. He was initially diagnosed with Graves’ disease 2 years ago. The patient could not take methimazole or metoprolol due to the affordability issue for the last 18 months. On presentation, he fell on the floor while attempting to stand up from the couch. He could not stand up or pick his cell phone. He remained on the floor for 2-3 hrs. A review of the system was positive for palpitation and fatigue and negative for diarrhea, weight loss, anxiety, sleep problem, and dry eyes. On arrival, he had a pulse of 100/min, BP of 157/85 mmHg with rest of vitals signs normal. Motor strength on bilateral lower extremities were 2/5. Upper extremity strength was normal. No thyromegaly or thyroid bruit was noted in the exam. The rest of the physical exam was normal. Labs showed Potassium 1.9 with a normal reference range (RR) of 3.5 - 5.1 mmol/l. His TSH was < 0.01 (RR 0.35 - 5.00 MCU/ML), Free T4 was 5.0 (RR 0.6- 1.6 NG/DL), Total T3 was 425 (RR 87 - 180 NG/DL) and CK was 70 (RR 35- 232 U/L). EKG showed sinus rhythm at 90 bpm with no PR, T/ST, or QT abnormalities. He was given IV potassium and was also started on methimazole 10mg TID and metoprolol. His weakness and tachycardia were improved the next day. We discussed with him the options of medical management vs. surgery. He underwent a total thyroidectomy. Biopsy showed nodular hyperplasia consistent with graves’ disease.

Discussion: Thyrotoxic periodic paralysis (TPP) is characterized by hypokalemia and episode of acute muscle weakness in lower extremities in the setting of hyperthyroidism. The pathophysiology of TPP remains uncertain. Hyperthyroidism is a hyperadrenergic state in which beta-2-adrenergic stimulation in muscle cells directly induces cellular K+ uptake by increasing cAMP, leading to activation of Na/K ATPase. The increase in the influx of intracellular K+ leads to hypokalemia and skeletal muscle weakness. Some studies show pathophysiology can be different in Caucasians compared to the Asian population that there could be abnormalities in Na and K channels other than Na/K ATPase. Potassium replacement should be done with caution as hypokalemia is due to intracellular shift and rebound hyperkalemia is common during the management. Beta-blocker may reverse adrenergic overstimulation of Na/K ATPase. It can help rapidly improve paralytic symptoms.
The Prevalence of Adrenal Insufficiency in Kidney Transplant Recipients
Authors: Martin-Grace* Julie , Tomkins* Maria , Kennedy Carmel , Enroe Olive Mc , Heverin Karen , Srinivasan Shari , Little Dilly , Conlon Peter , De Freitas Declan , Denton Mark , Magee Colm , O’Seaghdha Conall , O’Reilly Michael William , Thompson Chris John , Sherlock Mark
Published: May 2021

Long term glucocorticoid therapy is a key component of immunosuppression for kidney transplant recipients (KTR), leading to a significant cumulative glucocorticoid exposure in this cohort. However, assessment of adrenal function and steroid education do not feature in clinical practice guidelines for KTR. This study aims to investigate the prevalence of adrenal insufficiency (AI) in KTR on maintenance prednisolone and develop a simple screening algorithm to identify patients at highest risk of AI. 67 KTR receiving prednisolone were recruited, with a median age of 52 yrs (IQR 39–64) and median time since transplantation of 79 months (IQR 46–146). Patients with known hypothalamic-pituitary-adrenal axis pathology, exposure to oral oestrogens or impaired graft function (creatinine >170 umol/l) were excluded. Participants underwent a short synacthen test [SST, Roche Elecsys II immunoassay, pass cortisol > 430 nmol/l, CV assay 1.8-2,1%)], assessment of lifetime glucocorticoid exposure and an assessment of metabolic health.72% (n=48) of participants failed the SST(30 min cortisol < 430nmol/l). Participants with AI had a higher daily prednisolone dose (4.9 vs 4.2mg/day, p=0.002), a greater cumulative glucocorticoid exposure (289 vs 111 mg/kg, p=0.03) and lower estimated glomerular filtration rate (63 vs 81 ml/min/1.73m2, p=0.03) than those with intact adrenal function. There was no difference in duration of glucocorticoids post transplantation, previous transplant history, pre-transplant glucocorticoid exposure, immunosuppression regime, exposure to other glucocorticoid preparations, BMI and cortisol binding globulin concentration between those who passed or failed a SST. Participants with AI had a lower baseline cortisol (143 vs 303 nmol/l, p<0.001), lower baseline serum ACTH (14 vs 20 pg/ml), a lower peak stimulated cortisol (325 vs 490 nmol/l, p< 0.001) and lower cortisol response (139 vs 189 nmol/l, p=0.013) to synacthen testing than those with normal adrenal function. A morning cortisol of <294 nmol/l predicted AI result with 100% sensitivity (95% CI 92–100%, p< 0.001) and 63% specificity, therefore AI could be excluded if morning cortisol >300nmol/l, reducing the need for stimulatory testing. Our results suggest KTR are at higher risk for AI than previously reported, highlighting a need for greater patient and physician awareness regarding AI. We suggest that KTR with a morning cortisol < 300nmol/l are at high risk of AI, and dynamic testing should be considered for these patients.
Transdermal Absorption of Methimazole- a Cat’s Tale
Authors: Mittal Ashima , Gordon Murray B
Published: May 2021

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.

References: 1. Hill KE, Mills PC, Jones BR et.al. Percutaneous absorption of methimazole: an in vitro study of the absorption pharmacokinetics for two different vehicles. J Vet Pharmacol Ther. 2015;38(6):581-589. PMID: 25683868 2. Kasraee B et al. Safety of topical methimazole for the treatment of melasma. Transdermal absorption, the effect on thyroid function and cutaneous adverse effects. Skin Pharmacol Physiol. 2008;21(6):300-305. PMID: 18667842
Unusual Presentation of Myxedema Coma in Type 1 Diabetes Mellitus With Hyperglycemia and Polysubstance Abuse
Authors: Hamid Yumna , Douedi Steven , Nold Johnathan , Ong Raquel Kristin , Cheng Jennifer , Zin Khin
Published: May 2021

Background: Myxedema coma is a severe manifestation of hypothyroidism that typicallypresents with altered mental status and requires close monitoring in the intensive care unit dueto 30-60% mortality rate. Clinical Case: A 56 year old white male with type 1 diabetes with recurrent DKA, polysubstanceabuse, Bipolar disorder on lithium and post surgical hypothyroidism presented due to change inmental status after being brought in by sister. Patient was found to be lethargic with confusionthat worsened over the last week. The patient was admitted several times in the past monthsecondary to pneumonia, sepsis, and recurrent DKA. On physical examination, he found to have lethargy, macroglossia, hyporeflexia, and periorbitaledema. Patient had acute respiratory failure with metabolic encephalopathy, bradycardia,tachypnea, severe hyperglycemia, hypotension of 77/51, tachypnea of 31 breaths per minuteand hyponatremia. Laboratory findings showed T4 levels 2.87(n=5.28-9.87ug/dL) withundetectable FT4 and elevated TSH (>50, n=0.300-4.500uIU/mL). Electrolyte panel showedhyponatremia (133, n=136-145mmol/L), hyperglycemia up to 532mg/dL and lithium levels werewithin normal limits (n=0.5-1.5 mmol/L). Urine drug screen was positive for cocaine. A CT scanof the head was negative. His myxedema score was diagnostic (>60). The patient wasdiagnosed with myxedema coma and admitted to the ICU. Patient was treated with IV LT4 400mcg, LT3 10mcg and hydrocortisone 100mg and started onIV LT4 100mcg daily, LT3 2.5mcg daily and hydrocortisone 100mg Q8 hours. There was wideglycemic variation from 46-532 mg/dL on POCT. The patient improved clinically, with resolutionof lethargy, confusion, fatigue, improved appetite, and improved lab work of FT3 2.30 (n=2.28-3.96pg/mL), FT4 at 0.76 (n=0.50-1.26ng/dL) and was downgraded from the ICU. On hospitalday four, he was transitioned to oral levothyroxine and discharged home. Conclusion: It is important to diagnose early and promptly manage decompensatedhypothyroidism in the setting of other comorbidities such as hyperglycemia in diabetes andpolysubstance abuse. The cocaine in the system may cause tachypnea and tachycardia. Manyconditions may have altered mental status, but with a history of hypothyroidism, Myxedemacoma should be on the differential due to its high mortality rate.
Atrial Fibrillation Does Not Negatively Impact the Outcomes of Patients Admitted for Hyperthyroidism: Analysis of the National Inpatient Sample
Authors: Akuna Emmanuel , Asemota Iriagbonse , Shaka Hafeez , Edigin Ehizogie , Velazquez Genaro , Nwachukwu Praise , Asotibe Jennifer Chiagoziem
Published: May 2021

Introduction: Hyperthyroidism is a well-known risk factor for the development of atrial fibrillation(AF), but the outcomes hyperthyroidism in patients with atrial fibrillation is unclear. This study aims to compare the outcomes of patients primarily admitted for hyperthyroidism with and without a secondary diagnosis of AF.

Methods: Data were abstracted from the National Inpatient Sample (NIS) 2016 and 2017 Database. NIS is the largest inpatient hospitalization database in the United States. The NIS was searched for hospitalizations with a principal diagnosis of hyperthyroidism with and without AF as secondary diagnosis using ICD-10 codes. Hospitalizations for adult patients (age≥ 18 years) from the above groups were identified. The primary outcome was inpatient mortality. Hospital length of stay (LOS), total hospital charges, cerebrovascular accident and acute respiratory failure were secondary outcomes of interest. Multivariate logistic and linear regression analysis was used accordingly to adjust for confounders.

Results: There were over 71 million discharges included in the combined 2016 and 2017 NIS database. 17,705 hospitalizations were for adult patients who had a principal ICD-10 code for hyperthyroidism. 4,165 (23%) of these hospitalizations had co-existing AF. AF group were older (57 vs 44 years, P < 0.0001) and had less females (65% vs 78%, P < 0.0001). Hospitalizations for Hyperthyroidism with AF had similar inpatient mortality (0.96% vs 0.33%, AOR: 1.7, 95% CI 0.58-5.14, P=0.324) with longer LOS (5.1 vs 3.2 days, P=0.000), increased total hospital charges ($51,904 vs $34,471, P=0.002), increased odds of cerebrovascular accident (0.8% vs 0.1%, AOR: 5.01, 95% CI 1.1-22.2, P<0.034) and increased odds of acute respiratory failure(4.4% vs 1.3%, AOR: 3.01, 95% CI 1.8-5.0, P<0.000) compared to those without AF.

Conclusions: Patients admitted primarily for hyperthyroidism with co-existing AF had similar inpatient mortality but with longer LOS, increased total hospital charges, increased likelihood of having cerebrovascular accident and acute respiratory failure when compared to those without AF.
Chronic Stress During Adolescence Blunts the Exercise-Induced Expression of Thyroid Hormone-Target Genes in Metabolically Active Tissues of Male and Female Rats
Authors: de Oca Marco Antonio Parra-Montes , Garduño-Morales Karen Lissette , Joseph-Bravo Patricia
Published: May 2021

Voluntary exercise activates HPT axis1, that contributes to energy mobilization and energy expenditure. Chronic stress in adulthood inhibits HPT response to voluntary wheel running in a sex dependent manner, inhibiting lipolysis of WAT2. We evaluated the effect of chronic stress during adolescence on HPT axis response to voluntary exercise in adulthood3, with emphasis on metabolic response in skeletal muscle and WAT. Wistar male and female rats (N=36 per sex) were divided in an undisturbed group (Control, C; n=18) and one chronic variable stress during adolescence group (CVS; n=18) (males: PND 30-70; females: PND 30-60). As adults (males: PND 84; females: PND: 74) rats were divided in: 1) exercise group: rats placed individually in a cage with a running wheel per 14 nights, 2) sedentary group with ad libitum feeding, 3) sedentary pair-fed group offered the same amount of food consumed by the exercised group, and kept in individual cages during 14 nights (6 rats/group). WAT weight was determined at sacrifice, hormones quantified by RIA and ELISA, gene expression by RT-PCR. Exercise-induced loss of fat mass was not detected in CVS rats. Exercise decreased corticosterone levels in C males and females of both treatments, supporting sex difference on HPA axis reprogramming by CVS. HPT axis response to voluntary exercise is attenuated by CVS also in a sex dimorphic manner: CVS decreased Trh expression in hypothalamic paraventricular nucleus and no changes in thyroid hormones concentration in males, whereas in females, slightly increased TSH, T4 and T3 levels. Sex also influenced the response of skeletal muscle and WAT to CVS. Dio2 and Pgc1a slightly increased expression in skeletal muscle of males, not of females. Adrb3 expression in WAT increased in females, but not in males; exercise-induced stimulation of Hsl expression was not observed in either sex after CVS. These results suggest that CVS imposed during rat adolescence inhibits the responses to voluntary exercise of HPT axis activity of thyroid hormone-targets in WAT and skeletal muscle in sex dependent manner. These changes could lead to reduced mobilization and the utilization of energy fuels coincident with the fatigue observed after exercise in patients with subclinical or clinical hypothyroidism. (Funded: CONACYT 284883, DGAPA IN213419)1Uribe, Endocrinology 155:2020-2030, 2014.2Parra, Front Endocrinol 10(418):1-13, 2019.3Parra, J Endocr Soc 4(Abstract Supp) Abstract SAT-451, 2020.