bluuebunny/crossref_metadata_2025 huggingface dataset:
Real-World Evidence of Clinical Outcomes in Patients With Assumed Classic Congenital Adrenal Hyperplasia in the United States
Authors: Farrar Mallory , Farber Robert , Sen Ginny P , Yonan Charles , Chan Jean Lin
Published: May 2021

Background: Classic congenital adrenal hyperplasia (CAH) is an autosomal recessive disorder, usually due to a deficiency in the 21-hydroxylase enzyme, that results in impaired cortisol synthesis and excess androgen production. Patients with classic CAH experience both disease-related features from excess androgens and treatment-related complications from the chronic, supraphysiologic use of glucocorticoids (GCs) often required for androgen control. This study was conducted to evaluate the demographics and clinical characteristics of adult and pediatric patients in the United States (US) with assumed classic CAH based on International Classification of Diseases (ICD) codes, GC prescriptions, and medical claims. Methods: Analyses were based on longitudinal patient-level data from the Decision Resources Group Real World Evidence repository, which links medical claims, prescription claims, and electronic health records from >300 million US patients. Data were analyzed for patients aged ≥18 years (adult) and <18 years (pediatric) with assumed classic CAH based on ICD 9/10 codes associated with “adrenogenital disorders” and whose proportion of days covered with a GC in 2018–2019 was >75%. These patients were matched 1:3 with a control cohort based on age, gender, geographic region, and insurance type. Both assumed CAH and control cohorts had continuous coverage with at least 1 medical claim and 1 pharmacy claim in each year, 2018–2019. Results: Of 1,111 patients with assumed classic CAH, 778 were ≥18 years old (65% female; mean age [±SD], 43±17 years) and 333 were <18 years old (51% female; mean age [±SD], 11±4.7 years). Both adult and pediatric patients with assumed classic CAH were more likely than matched controls (adult N=2334; pediatric N=999) to experience events that could be related to chronic GC use, including infection (adult: 49.9% vs 37.3% [control]; pediatric: 49.5% vs 40.0%), weight gain (adult: 5.9% vs 2.5%; pediatric: 9.0% vs 2.6%), and moon face (adult: 44.0% vs 0.1%; pediatric: 37.8% vs 0.1%); all P<0.01 vs control. Adult patients were more likely than matched controls to experience acne (6.0% vs 3.6%), hirsutism (8.1% [47/508] vs 5.5% [84/1524]), and infertility (1.7% vs 0.4%); all P<0.01. Pediatric patients were more likely to experience pubertal development issues (10.5% vs 1.8%), acne (8.4% vs 5.1%), and advanced bone age (1.2% vs 0.1%); all P<0.05. Conclusions: Compared to matched controls, both adult and pediatric patients with assumed classic CAH had significantly more disease-related comorbidities and potential GC treatment-related conditions, indicating the challenges with current GC treatments. This study was limited by the assumed nature of classic CAH due to lack of a specific ICD code, but the combination of chronic GC use (>75% days) with the diagnosis code most likely used in these patients (adrenogenital disorder) supports the validity of this analysis.
Adenomatous, Unilateral, Retrosternal Extension of the Thyroid Gland presenting as a Mediastinal Mass
Authors: Glass Aisling , Griffin Margaret Elizabeth , Moran Carla M
Published: May 2021

Background: Thyroid-related causes of mediastinal masses include retrosternal goiters and thymic enlargement associated with Graves’ disease. Here, we present a case of significant unilateral retrosternal growth of the thyroid gland, presenting as an incidental mediastinal mass, without any evidence of contralateral disease. Associated subclinical hyperthyroidism presents a therapeutic challenge. Clinical Case: A 68-year old gentleman presented to the emergency department with a non-infective exacerbation of known Chronic Obstructive Pulmonary Disease. CT Pulmonary Angiogram revealed a right sided 5.6cm paratracheal mass, which seemed to originate from the posterior aspect of the right lobe of the thyroid and extended to the subcarinal region. The mass displaced the oesophagus and was close to, but did not compress, the trachea. The left thyroid lobe was normal. Thyroid ultrasound was reported as normal, but was later acknowledged to be suboptimal at visualization of the posterior aspect of the gland. Thyroid scintigraphy confirmed increased radionuclide uptake within the mass. Thyroid function tests showed subclinical thyrotoxicosis [TSH 0.04 (0.4-4.0mIU/mL), FT4 17.4 (10-22pmol/L) and FT3 3.36 (2.89-4.88 pmol/L)]. TSH receptor antibody was negative [< 1.1 (<1.75 IU/L)]. On review of prior imaging from other hospitals, the mass had been present since 1999 and was stable in size for at least the past 7 years. The patient was discharged on carbimazole with a plan to perform interval scanning to monitor size. Discussion: Although technetium uptake can be seen in thymus tissue, the identification on imaging that the mass is contiguous with the thyroid gland leads us to believe this is an adenomatous extension of the thyroid gland. Ectopic thyroid tissue is possible, but the size of the mass suggests some prior period of growth. Thyroid carcinoma seems unlikely given the current stability in size, and there are no compressive symptoms, so there is no clear indication for surgery at present. However, given the subnormal TSH level, there is evidence of autonomy, so treatment is indicated. Radio-iodine treatment may be associated with thyroiditis, with attendant swelling of the gland and risk of compression of vital structures, so treatment with ATDs and regular imaging surveillance was deemed most appropriate in his case.
Challenging Thyroid Storm in Pregnancy, Case Report
Authors: Alamer Zaina Abdelhalim , Alkhatib Mohammed , Naem Emad , Suleiman Noor Nabeel M , Mokhtar Marwa Gomaa , Al-Mohanadi Dabia Hamad
Published: May 2021

Background: Thyroid storm is a rare complication of hyperthyroidism. It can lead to life-threatening complications such as Arrhythmias, multiorgan failure and disseminated intravascular coagulation (DIC) (1). In pregnant patients can cause spontaneous abortions, fetal demise (2). Aggressive treatment under critical care settings is needed.

Clinical Case: We report a case of 24-year-old Indian female twelve weeks pregnant; background of Graves’ disease for five years, was on carbimazole but she discontinued since she became pregnant. Presented to Hamad general hospital with nausea, vomiting and altered mental status for one day. She was afebrile, normotensive, tachypneic, tachycardiac with heart rate of 150bpm, and confused. Investigations showed supraventricular tachycardia aborted by adenosine and amiodarone, TSH was < 0.01mIU/l(0.3-4.2) and FT4> 100 pmol/L(11.6-21.9),normal baseline liver function and complete blood counts. In the emergency department, she was managed for thyroid storm with hydrocortisone, propranolol, propylthiouracil (PTU), iodine solution and cholestyramine. Then suddenly she deteriorated requiring intubation and vasopressor support under care of Medical Intensive Care Unit (MICU) progressed to multiorgan failure; acute liver injury, acute kidney injury and DIC. So, PTU was stopped and started on plasma exchange followed by total thyroidectomy and tracheostomy. US pelvis showed nonviable fetus, so dilation and curettage were done by obstetric team. Afterwards, she markedly improved except her conscious level and kidney function which required Hemodialysis. MRI brain showed small subdural hematoma treated conservatively and Wernicke encephalopathy treated with thiamine with substantial response and spontaneously breathing. Post thyroidectomy she required calcium supplementation and levothyroxine, liver function and coagulation parameters back to baseline.

Conclusion: Thyroid storm in pregnancy is a medical emergency with high mortality rate, it needs high index of suspicion and early aggressive management by a multidisciplinary team. Plasmapheresis may be considered for challenging cases as a bridge for definitive therapy. Thyroidectomy may be the only option in selected cases like our case.

References: 1. Karger S, Führer D. Thyreotoxische Krise--ein Update [Thyroid storm--thyrotoxic crisis: an update]. Dtsch Med Wochenschr. 2008 Mar;133(10):479-84. German. doi: 10.1055/s-2008-1046737. PMID: 18302101. 2. Ma Y, Li H, Liu J, Lin X, Liu H. Impending thyroid storm in a pregnant woman with undiagnosed hyperthyroidism: A case report and literature review. Medicine (Baltimore). 2018;97(3):e9606. doi:10.1097/MD.0000000000009606
Graves’ Disease and Evans’ Syndrome as First Manifestation of Systemic Lupus Erithematosus
Authors: Gómez-Noronha Andrés Alberto , López-Huamanrayme Eddy , Quiroa-Alfaro Carmen Cecilia
Published: May 2021

Background: Graves’ disease is the most common cause of hyperthyroidism triggered by antibodies called thyroid-stimulating immunoglobulin (TSI) which stimulates an overproduction of thyroid hormones. Evans’ syndrome is a rare condition characterized by autoimmune hemolytic anemia and immune thrombocytopenic purpura. Systemic lupus erythematosus (SLE) is also an autoimmune disease with extreme heterogeneity and potentially involvement of any organ or system. It is well known when a patient is diagnosed with an autoimmune disease, it is about time to show up other manifestations of another one, just as it happened in this case report. Clinical Case: A 31-year-old pregnant woman (22 weeks) was admitted to the obstetric emergency room due to headaches, weakness and tinnitus. During anamnesis, she said she was diagnosed with hypertension several weeks before she was pregnant. At physical examination, a 160/100 mm/Hg blood pressure and a heart rate over 100 bpm were found. Initial tests were solicited congruent with severe thrombocytopenia (20 000/mm3) and severe anemia (6 gr/dl), there was also a modest increase in transaminases levels. Transfusion support was needed and a “HELLP syndrome” was diagnosed. Gynecologists decided to perform an emergency hysterotomy and the end of pregnancy. During the post-operative care and the following days, the patient persisted with an average of 100 bpm heart rate and hypertension despite of the use of antihypertensive medication. Physicians also noticed the presence of malar rash and goiter. Thyroid hormones levels where requested and the results were consistent with primary hyperthyroidism (TSH: <0.005 Mu/L, FT4: >100 pmol/L). Further tests were required such as TSI (positive), a thyroid scintigraphy (high thyroid uptake), antinuclear antibodies (ANA: + 1/160 speckled pattern, anti- Smith: +) and extractable nuclear antigen antibodies (ENA) panel. Grave’s disease and SLE were diagnosed. Rheumatologists suggested that the diagnosis of HELLP Syndrome was unclear and they strongly believed that thrombocytopenia and anemia during pregnancy were part of Evans’s syndrome and at the same time of SLE. Antithyroid drugs (thiamazol), beta blockers (propranolol) hydroxychloroquine and corticoids (prednisone) were given to the patient with an excellent clinical and biochemical response. Conclusion: A 25% of patients with SLE can be diagnosed with an autoimmune thyroid disease, such as Graves’ disease (1). Frequent evaluation of thyroid hormones and antithyroid antibodies should be performed in patients with SLE, especially when there are related symptoms of a thyroid disorder. References: 1.Chan AT, Al-Saffar Z, Bucknall RC. Thyroid disease in systemic lupus erythematosus and rheumatoid arthritis. Rheumatology (Oxford). 2001;40:353---4.
Hashimoto’s Thyroiditis Presenting With Hoffman’s Syndrome in a Patient With the Coronavirus Disease 2019 (COVID 19): Hormone Replacement in the Time of the Pandemic
Authors: Larrazabal Ramon Bagaporo , Chiu Harold Henrison Chang , Magnaye Franz Michael Millar , Acampado Laura T
Published: May 2021

Introduction: Hoffmann’s syndrome is a very rare and reversible manifestation of hypothyroidism presenting as classic features of hypothyroidism with muscle stiffness, weakness, and pseudohypertrophy.

Clinical Case: A 62-year-old man was admitted to our institution due to dyspnea. He also had progressive muscular weakness and recurrent cramps four months prior. On admission, he was seen in respiratory distress and was eventually intubated and hooked to mechanical ventilation for acute respiratory failure brought about by COVID-19 pneumonia (confirmed by a reverse transcriptase-polymerase chain reaction of a nasopharyngeal swab on admission). He had an unremarkable head and neck examination; both of his calf muscles were hypertrophied. On neurological examination, he had mild proximal lower limb muscle weakness (power 4/5) and deep tendon reflexes were sluggish (+1). The patient was subsequently admitted into the intensive care unit. Laboratory data showed inflammatory markers associated with COVID-19 were elevated: Lactate Dehydrogenase (857 u/L; NV: 120-246 u/L) and Interleukin-6 (137 pg/mL; NV: 0-50 pg/mL). He was given tocilizumab, convalescent plasma therapy, and underwent hemoperfusion. His serum chemistry was unremarkable. Thyroid function tests were consistent with primary hypothyroidism from Hashimoto’s thyroiditis: TSH (22.6712 UIU/mL; NV: 0.35-4.94 UIU/mL), fT3 (<2.30 PMOL/L; NV: 2.89-4.88 PMOL/L), fT4 (<5.15 PMOL/L; NV: 9.01-19.05 PMOL/L), anti-Tg Ab (1810.3 IU/mL; NV: <50 IU/mL) and Anti-TPO Ab (2610.4 IU/mL; NV: <100 IU/mL). There was a consideration of Hoffman’s syndrome; muscle enzymes were noted to be elevated also: CK-Total (2589 U/L; NV: 55-170 U/L) and CK-MB (85.7 U/L; NV: 0-16 U/L). This is consistent with Hoffman’s syndrome. He was supposed to start hormone replacement therapy. However, he developed ileus (attributed to sepsis and hypothyroidism) which precluded the use of oral levothyroxine. To circumvent this roadblock, levothyroxine was given as an enema via the rectal route at 300 mcg once daily (approximately twice the oral dose). Upon initiation of hormone replacement, his sensorium, hemodynamic parameters, and bowel movement improved. Thus, we were able to shift to oral levothyroxine eventually. Unfortunately, he went into sudden cardiac arrest and expired after the 11th hospital day.

Conclusion: COVID 19 infection could lead to exacerbations of pre-existing conditions such as Hashimoto’s Thyroiditis (in this case, manifesting with Hoffman’s syndrome). Hormone replacement is still the treatment of choice. Concomitant COVID 19 infection and treatment is not a contraindication to delay hormone replacement.

Reference: (1) Senanayake, Hemal Ms et al. “Hoffmann syndrome: a case report.” International archives of medicine vol. 7,1 2. 6 Jan. 2014, doi:10.1186/1755-7682-7-2.
Hyperthyroidism Times 2: Dual Cause of Thyroid Hormone Excess
Authors: Ortiz Yineli , Cruz Alegyari Figueroa , Marin Luis Norberto Madera , Mora Gabriel , Torres Angela , Garcia-Mateo Jose M
Published: May 2021

The most common etiology of Hyperthyroidism is due to circulating antibodies that are directed against the thyroid-stimulating hormone (TSH) receptor, known as Grave’s Disease (GD). Another cause is an autonomously functioning thyroid nodule over-producing hormones or Toxic Adenoma. The mechanism of these two pathologies are very distinct, but the question that arises is, can they coexist?

This is a case of 44-year-old female who comes to the clinic referred by her ophthalmologist after been diagnosed with severe thyroid-associated orbitopathy currently on steroid therapy. Thyroid ultrasound has done previously showed enlarged homogenous thyroid gland with a single isoechoic nodule of 2.2x1.6x1.9cm with faint peripheral calcifications and vascularity. The patient was presenting with palpitations, heat intolerance, sweating, and discriminatory features such as double vision and left eye exophthalmos. On physical examination, there was no goiter or palpable thyroid nodules, but it was remarkable for left eyelid lag retraction and mild proptosis. Evaluation showed clinical and biochemical hyperthyroidism with TSH: 0.068 mU/ml (n:0.5-5.0mU/ml), FT4: 1.39ng/dl (n:0.87-1.85ng/dl), TSH receptor antibody: <1.10IU/L and thyroid-stimulating immunoglobulin: 0.54IU/L (borderline high). The patient was placed in antithyroid drugs and B-blockers for disease control. Afterward, the patient underwent a thyroid uptake scan reporting toxic adenoma on the left lobe, however even when the biochemical workup of GD is inconclusive, patient clinical findings are highly suggestive of it. Due to the risk of worsening orbitopathy with radioactive iodine therapy, patient was referred for surgical excision of toxic adenoma and total thyroidectomy was decided since residual thyroid tissue may expose the patient to circulating thyroid-stimulating immunoglobulin leading to hyperthyroidism recurrence and put her at risk of associated thyroid excess detrimental complications. Surgical specimen gross pathology biopsy reported the thyroid gland with hyperplastic changes of Grave’s Disease. Severe thyroid-associated orbitopathy was managed with decompression surgery but did not improve, for which an alternative therapeutic approach is decided with novel immunomodulatory agent and recent approved therapy, Teprotumumab. A monoclonal antibody that works on TSHR/IGF-1R signaling complex involved in Thyroid Eye Disease.

Is unusual to see two different superimposing thyroid pathologies, but disease presentations can be atypical and can be present concomitantly. In this scenario, several factors must be taken into consideration when choosing an adequate therapy approach. Our case is an example that we need to individualize management options based on guidelines recommendations, patient’s clinical settings and decreased risks of future complications.
Iatrogenic Hyperthyroidism With Recurrent Functioning Thyroid Tissue 40 Years After Thyroidectomy for Graves’ Disease
Authors: Penquite Sara Ashlyn , Galvez Juan Pablo
Published: May 2021

Background: Graves’ disease is an immune-mediated cause of thyrotoxicosis treated with anti-thyroid drugs (ADTs), radioactive iodine (RAI) or thyroidectomy. Thyroidectomy has been documented to have the lowest rate of recurrence amongst treatment options1. Data regarding long-term recurrence rates is limited beyond 54 months.

Clinical Case: An asymptomatic 59 year old female was found to have recurrent thyrotoxicosis on routine laboratory testing. The patient underwent thyroidectomy at age 19 years for Graves’ disease. Prior records unavailable to clarify initial surgical intervention. The patient had post-surgical hypothyroidism which was managed with levothyroxine 100mcg once daily for over 20 years. A biochemically euthyroid state was clearly documented on prior laboratory testing. Initial laboratory testing with TSH <0.01mIU/L (0.45-4.50), FT3 2.8ng/dL (0.8-1.7). Levothyroxine was discontinued with persistent thyrotoxicosis after 8 weeks: TSH <0.01, FT3 5.7, FT4 1.74. Radioactive Iodine Uptake and scan was obtained after administration of 6uCi of iodine-131 which demonstrated 50.8% uptake of radioactive iodine at 24 hours (Normal 10-30%). The left thyroid gland was noted to be in normal position and enlarged with diffuse increase intensity of radiotracer uptake. The right thyroid gland was surgically absent. The patient subsequently underwent completion thyroidectomy with endocrine surgery with resolution of hyperthyroid state. Surgical pathology was benign and consistent with Graves’ disease and multinodular goiter. The patient did become hypothyroid post-operatively and required levothyroxine replacement. She is clinically and biochemically euthyroid on levothyroxine 100mcg once daily 14 months post-operatively.

Conclusion: This is a case of recurrent hyperthyroidism approximately 40 years after definitive treatment with thyroidectomy. Although it is unclear whether patient underwent total thyroidectomy or subtotal thyroidectomy for initial intervention, the recurrence of thyrotoxicosis after such a long period of time has not previously been reported in the literature to the knowledge of this writer. This has important implications regarding the underlying pathophysiology of Graves’ disease and the ability of remnant thyroid tissue to regenerate over time. This also has important implications for long-term monitoring in patients with history of thyroidectomy for Graves’ disease.

Reference: 1. Sundaresh, V., Brito, J. P., Wang, Z., Prokop, L. J., Stan, M. N., Murad, M. H., & Bahn, R. S. (2013). Comparative effectiveness of therapies for Graves’ hyperthyroidism: a systematic review and network meta-analysis. The Journal of clinical endocrinology and metabolism, 98(9), 3671–3677.
Low-Dose Prednisone Therapy is Efficacious in Treating Painful Subacute Thyroiditis
Authors: Shakir Mohamed K M , Leimbach Robert D , Sherin Rinsha P V , Orestes Michael I , Mai Vinh Q , Hoang Thanh Duc
Published: May 2021

Subacute thyroiditis (SAT) usually presents with neck pain, radiating to ears and is often associated with hyperthyroidism. Currently the available treatment involves administration of NSAID or in more symptomatic patients prednisone 40mg daily tapered over 6 weeks or longer. We report successful treatment of 3 patients (Pts) with SAT with low-dose prednisone therapy (20mg/day) (LDP20) initially and tapered over 4 weeks. Patient 1: A 32-year-old female presented with severe neck pain radiating to both ears and low- grade fever of 2-weeks duration. Two weeks prior, patient had cold-like symptoms lasting for 3 days. Physical examination: HR 110bpm, tremors of fingers noted, tenderness of the anterior neck present, thyroid 30-gms in size. Labs: ESR 92 mm/hr, CRP 3.2 mg/dL, TSH <0.005 uIU/mL, free T4 2.71 ng/dL, total T3 168 ng/mL. Thyroid scan and uptake showed a 24-hrs uptake <1%, thyroid gland not visualized, consistent with SAT. Patient was treated with atenolol and LDP20 tapered over 4 weeks. Pain significantly improved after 2 days of treatment. Six weeks later TSH was 0.9 uIU/mL with a free T4 1.4 ng/dL and ESR 8 mm/hr. Patient 2: A 19-year-old female presented with left-ear pain, anterior neck pain, fever, and extreme fatigue. PE: HR 111bpm, heat shield present, tender-to-palpation thyroid, brisk DTR. Lab: CBC normal, ESR 98 mm/hr, CRP 9.9 mg/dL, TSH <0.01 uIU/mL, free T4 3.8 ng/dL, total T3 210 ng/mL. Thyroid scan and uptake: uptake <1%, no thyroid gland visualized and SAT was diagnosed. Patient was started on LDP20 and atenolol. Four days following prednisone therapy her symptoms completely resolved and prednisone was tapered off over 4 weeks. Thyroid functions were normal by the seventh week. Patient 3: A 38-year-old male presented with fever, fatigue, severe neck pain, palpitation and a weight loss of 8 pounds. PE: HR 120 bpm, thyroid severely tender on palpation, brisk DTR. Lab: normal CBC, ESR 128 mm/hr, CRP 11.9 mg/dL, TSH <0.001 uIU/mL, free T4 4.2 ng/dL, total T3 201 ng/mL. Thyroid scan: thyroid gland not visualized and uptake was < 1%. SAT was diagnosed and patient was treated with propranolol and LDP20. After 5 days the dose of prednisone was reduced to 15mg/day and the prednisone was tapered over five weeks. Patient had resolution of symptoms in 70 hours and remained asymptomatic for the next 12 months of follow-up. Thyroid function normalized by the eighth week. Conclusion: SAT is a painful disabling thyroid disorder apparently caused by a viral infection; and NSAID or high-dose steroid treatment remains the standard of care. We have treated 3 Pts with relatively lower doses of prednisone than previously recommended and attained remission successfully. Thus side effects can be avoided with lower prednisone dose.
Lyme Disease: An Autoimmunity-Based “Destructive Thyroiditis” or Just Another “Non-Thyroidal Illness”?
Authors: Dhliwayo Nyembezi , Wajahat Rana , Havrylyan Andriy , Moid Alvia , Khayr Walid , Barsano Charles P
Published: May 2021

There is considerable evidence that some Borrelial (Lyme spirochetal) proteins share significant antigenic properties with several thyroid-related proteins (e.g. TSH receptor, thyroglobulin, thyroid peroxidase) and can induce thyroid autoimmunity, sometimes associated with Hashimoto’s thyroiditis and perhaps also a “destructive thyroiditis” such as “silent” thyroiditis or “Hashitoxicosis.” As an acute illness, Lyme disease may also constitute a “non-thyroidal illness” capable of perturbing thyroid function tests without causing thyroid dysfunction. We report a 22-year old woman admitted with an acute paranoid schizophrenia, thyroid function tests consistent with autoimmunity, transient thyrotoxicosis (tachycardia, lid-lag, brisk DTR’s) and a greatly reduced radioiodine uptake. The thyroid was not palpably enlarged, nodular or tender. On screening assay, reactivity was demonstrated to 4 of 13 Borrelial proteins. Anti-Lyme IgM but not IgG, antibodies, were positive. This was consistent with recent Lyme disease infection. Serum TSH (NL: 0.358-3.74 mcU/ml), Free T4 (NL: 0.76-1.46 ng/dl), and Free T3 (NL: 2.18-3.98 pg/ml) were, respectively: Day1: 0.087 mcU/ml (suppressed), 1.52 ng/dl (slightly elevated), 2.07 pg/ml (slightly reduced); Day2: 0.148 (suppressed), 1.18 (normal), no FT3; Day4: 0.827 (normal), no FT4 or FT3; Day5: 1.66 (normal), 0.89 (normal), 1.77 (low). Anti-Tg and Anti-Peroxidase antibodies were both moderately elevated. Thyroid Stimulating Immunoglobulins were not elevated. The radioactive iodine uptake on Day4 was 2.8% (NL: 15-30% at 24 hr). Thyroid ultrasonogram was normal. An attractive explanation is that Lyme disease triggered a “destructive thyroiditis,” perhaps but not necessarily mediated by thyroid autoimmunity. This would account for the brief interval of thyrotoxicosis accompanied by a very low radioiodine uptake. Alternatively, Lyme disease, as an acute process, would expectedly be capable of eliciting the thyroid function abnormalities of “non-thyroidal illnesses” in general, as would acute psychosis, well-known to often resemble Graves’ disease at admission.
Mitral Valve Disease in Thyroid Storm
Authors: Menjura Sandra Rocio Rivera , Moyano Rivas Lia G , Gamboa Camila Parraguez , Balmaceda Cristobal , Peralta Juan P , Rocha Luis
Published: May 2021

Introduction: The cardiovascular effects that thyroid gland causes are widely studied. In fact, there is a known correlation between Graves’ Disease and mitral valve damage. We present the case of a patient admitted with thyroid storm and heart failure associated with severe structural damage of the mitral valve papillary muscle.

Case Report: 24 year old woman with hyperthyroidism diagnosed 12 years ago, treated irregularly with thiamazole and propranolol, leaving treatment a year ago, presents dyspnea, class III functional capacity, diarrhea and logic dysphagia of a month of evolution. Heart rate over 170 bpm, respiratory rate 48 rpm and blood pressure 143/84 mmHg. Physical exam positive for exophthalmos, grade III goiter, crackles in both lung bases, pretibial myxedema and fulfilling criteria for a thyroid storm (65 points in Burch-Wartofsky Point Scale).

First Lab Results: TSH<0.005µU/mL, free T4>7.7ng/dl and TRAB 37.8UI/L. Chest ray: Global cardiomegaly and pulmonary edema. EKG: Narrow complex supraventricular tachycardia. Thyroid ultrasound: Intrathoracic goiter. Transesophageal echocardiogram: Severe mitral insufficiency (Carpentier Type I and IIIB), right cavities and left ventricular enlargement, preserved right ventricular function and severe pulmonary hypertension (PSAP 71-76 mmHg).

First treated with thiamazole, hydrocortisone IV, cholestyramine and sedation, falling time after into ventilatory failure and developing delirium, requiring invasive mechanical ventilation. Tested positive for COVID- 19. Starts preparation with Lugol and undergoes Total Thyroidectomy. After surgery develops severe hypocalcemia secondary to transitory hypoparathyroidism.

During hospitalization presents multiple infections including pneumonia (Pseudomonas Aeruginosa), lung aspergillosis, bacteriuria (Enteroccocus Faecium) and candiduria (Candida Albicans and Glabrata), each one treated with multiple antibiotics and vasoactive drugs. Once stable, mitral valve replacement is realized, after which, the patient progresses favorably being discharged with programmed ambulatory controls.

Conclusion: We report a case of a patient who was presented with positive thyroid storm criteria associated with heart failure and severe mitral valve insufficiency. The case gets complicated as multiple infections take place, including COVID-19. Fortunately, because of the early and aggressive multidisciplinary management, the patient evolved favorably, overcoming the life-threatening conditions she went through.

Key Words: Thyroid storm, mitral valve insufficiency, heart failure.

Bibliography: Klein I, Danzi S. Thyroid disease and the heart. Circulation. 2007 Oct 9;116(15):1725-35. doi: 10.1161/CIRCULATIONAHA.106.678326. Erratum in: Circulation. 2008 Jan 22;117(3):e18. PMID: 17923583.
Myxedema Coma Disguised as Alcohol Withdrawal
Authors: Pahwa Dhivya , Belkin Alexander , Katriyar Neeraj
Published: May 2021

Introduction: Myxedema coma is a medical emergency whose symptoms may sometimes mimic other diseases such as alcohol withdrawal.

Case: A 64-year-old male with a history of alcohol abuse and bipolar disorder (on no medications) presented to the emergency department after being found on the floor surrounded by multiple open alcohol bottles. He was a poor historian but reported a previous fall. Vitals on presentation were BP 109/70, HR 110, RR 22, SpO2 of 90% on room air, and rectal temperature of 97.6 F. The remainder of the exam revealed he was alert and oriented to self and place but not time; his neck was supple and no thyroid masses were palpated; he had tremors, head swelling and abdominal tenderness. Labs demonstrated CPK 1300 U/L, Creatinine 1.0 mg/dl, glucose 120 mg/dl, and sodium 142 mmol; urine toxicology was negative and alcohol level was not elevated. He was admitted and treated for suspected alcohol withdrawal and rhabdomyolysis with intravenous fluids and benzodiazepines. However, his mental status continued to decline; he became obtunded and was hypothermic and bradycardic. Thyroid function tests (TFT) revealed TSH 98.9 uIU/mL with free T4 0.27 ng/dl. He was subsequently managed for myxedema coma and given IV levothyroxine and hydrocortisone. He improved clinically after initiation of therapy and was transitioned to oral thyroid replacement. The patient was pending discharge to sub-acute rehab however his hospital course was later complicated by aspiration pneumonia.

Discussion: Myxedema coma is a medical emergency as severe hypothyroidism leads to slowed functioning of multiple organs. Risk factors include female gender and age above 60 years; it is seen more commonly in colder months. Symptoms include decreased mental status, feelings of cold and tongue swelling while physical exam may reveal hypothermia, hypoventilation, bradycardia, an enlarged goiter, thinning hair and non-pitting edema. Lab studies usually reveal an elevated TSH with low T4; there may also be hyponatremia and hypoglycemia. Myxedema coma is a clinical and laboratory diagnosis; if there is clinical suspicion for myxedema coma, IV thyroid replacement should be administered promptly without waiting for lab results. Stress-dose steroids should also be administered and TFTs should be monitored every 48 hours. Clinical symptoms usually improve over one week of treatment. Mortality of myxedema coma is reported to be up to 40% in hospitalized patients. Our patient’s presentation of suspected alcohol withdrawal masked his diagnosis of myxedema coma.

Conclusion: Physicians should keep myxedema coma in the differential for patients who present with suspected alcohol withdrawal and develop worsening mental status and hypothermia.

Reference: DynaMed. (2020, October 22). Myxedema Coma. Retrieved October 23, 2020, from https://www-dynamed-com.arktos.nyit.edu/topics/dmp~AN~T1584563697784.
Myxedema Coma: Improving Outcomes With Prompt Recognition and Therapy
Authors: Parihar Aisha
Published: May 2021

Background: Myxedema coma, a misnomer for severe hypothyroidism, is a rare endocrine emergency with an incidence of 1.08 cases per million people per year and a high mortality rate ranging from 30-50%. A delay in diagnosis and treatment worsens the prognosis and increases morbidity and mortality. Delayed management often leads to decompensation, presenting as uncontrolled persistent hypothermia, severe electrolyte derangements, and a potential for ventilator requirement needing ICU care. We present a patient in hypothyroid crisis who was promptly managed in a non-ICU setting who demonstrated a relatively early improvement in vital signs, thyroid lab values, and return to baseline mental status.

Clinical Case: A 75 year old female with past medical history of hypothyroidism, atrial fibrillation, hypertension, coronary artery disease, depression, tardive dyskinesia, and dementia presented to the hospital in the month of December due to confusion after a mechanical fall that resulted in a head laceration requiring multiple stitches. Trauma work up included a CT scan of the head that was negative. On presentation, patient was also hypothermic, bradycardic, hypotensive, and lethargic with an altered mental status. Sepsis work up was negative. TSH was checked on day of admission and found to be significantly elevated to > 100 mcIU/mL, consistent with severe hypothyroidism. Free T4 and total T3 levels were low. Patient was immediately given intravenous levothyroxine 300 mcg followed by oral levothyroxine 125 mcg daily. In addition, intravenous hydrocortisone 100 mg every 8 hours was started until adrenal insufficiency was ruled out with a normal cortisol level. Upon discussion with family, it was learned that patient had not been taking her home medications indicating non-compliance to thyroid replacement therapy as the etiology for her hypothyroid crisis. Within a day of initiating therapy, TSH levels drastically improved with a reduction by 50%. Bradycardia, hypotension, and hypothermia resolved as well. In three days, patient’s mentation improved back to baseline and TSH, free T4, and total T3 continued to normalize.

Conclusion: This case demonstrates how prompt recognition of hypothyroid crisis and immediate therapy can lead to early improvement in outcomes such as reversibility of mental status, normalization of vital signs and lab values, prevention of escalation of care to an ICU setting, and overall morbidity and mortality.
New Onset Recurrent Acute Infectious Thyroiditis in an Adult Patient
Authors: Al Hommos Nisreen Abu , James Deirdre
Published: May 2021

Introduction: Acute infectious thyroiditis can be seen in patients with congenital abnormalities of the piriform sinus, underlying autoimmune disease, or the immunocompromised. In most patients, an upper respiratory tract infection precedes the development of the neck abscess. Case description: The patient is a 39-year-old Caucasian woman with history of Hidradenitis suppurativa (HS) and thrombocytopenia who presented to the hospital with sore throat, dysphagia and left-sided neck swelling. She was recently started on Humira for HS. Review of systems was significant for heat intolerance, weight loss, palpitations and panic attacks. Family history was positive for Hashimoto’s thyroiditis. Initial lab evaluation was significant for elevated erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), mildly elevated free T4 (FT4) with suppressed thyroid stimulating hormone (TSH). She was found to have a nearly 6 cm left-sided thyroid abscess, which was eventually drained. Contrasted CT imaging showed multiple left laryngeal space abscesses with extension to the left thyroid gland. TSH gradually increased over two months to nearly 4 times upper limit of normal accompanied by low normal FT4. TSI and TPO antibodies were negative. Clinical course was complicated by recurrent abscesses which required percutaneous drainage and intravenous antibiotics. Discussion: Acute infectious thyroiditis is extremely rare disorder of the thyroid gland in adults. Most patients present with recurrent abscesses early during childhood. Imaging studies such as CT scan, preferred over MRI, and barium swallow can show a fistula connecting the piriform sinus and left lobe of the thyroid gland. Treatment includes needle aspiration, followed by drainage and IV antibiotic therapy. Surgical excision of the entire sinus tract and the involved area of the thyroid gland is the best method to achieve definitive cure.

Conclusion: Lower left-sided thyroid abscess extending from the pyriform fossa to the thyroid bed should raise the suspicion for underlying third or fourth branchial fistula. Most cases present during childhood, but one third of cases occur in adults. Surgical excision after confirming the presence of a fistulous tract with imaging is the treatment of choice.
Oscillating Hypo-Hyperthyroidism; a Rare Type of Autoimmune Thyroiditis in Adolescence
Authors: Akinseye Leah I
Published: May 2021

Background: Spontaneous conversion of hypothyroidism to hyperthyroidism and vice versa is a unique autoimmune entity characterized by the oscillating activity of thyrotropin blocking inhibiting immunoglobulin (TBII) and thyroid-stimulating immunoglobulin (TSI). The simultaneous presence of both antibodies is a rare phenomenon in children. Clinical Case: At 11 years of age a female with Trisomy 21 and mild developmental delay had elevated TSH 5.4uIU/mL (0.4-4.5), normal thyroxine (T4), negative thyroglobulin peroxide antibody (anti-TPO), and thyroglobulin antibody (Anti-Tg). Levothyroxine (LT4) 1.2mcg/kg/day was started. At 12 years of age, she relocated, and the same treatment was continued. About 7 months later, she was referred for weight loss of 8lbs, tachycardia, high BP, suppressed TSH <0.015uIU/mL, high total T4 15.9ng/dL (4.5-12.0), and anti-TPO 38 IU/mL (<9). She was diagnosed with hyperthyroidism and LT4 was discontinued. Repeat lab showed persistently undetectable TSH, high T4, TBII 70 (normal <16%), and TSI 698 (<140 %). Methimazole (MMI) 0.38mg/kg/day and Atenolol 25mg daily was started for Grave’s disease.

At 15 years of age, she presented with symptoms of hypothyroidism; 10lb weight gain in 2months, high TSH >150mIU/L, low FreeT4 0.12ng/dl (0.8-2), anti-TPO 95 IU/mL, and TSI 2.1 IU/L (0.0 - 0.55). MMI was discontinued and she was started on LT4 0.9mcg/kg/day. Repeat TFT’s 5weeks later showed a normal TSH and Free T4. Thyroid ultrasound showed a diffusely enlarged gland; right lobe - 3.9 x 2.0 x 2.0 cm (volume of: 7.6 mL) and left lobe 4.5 x 1.6 x 2.4 cm (volume: 8.6 mL) with increased vascularity on color Doppler consistent with diffuse thyroiditis. A year later, she developed hyperthyroid symptoms for the second time with 6lb weight loss, tachycardia, suppressed TSH <0.015uIU/mL, elevated free T4 >6.9ng/dl, TBII 8.6 U/L (<1.0), and TSI 12 IU/L. However, this time her TSI level was significantly higher than when she was hypothyroid. She was treated with MMI 0.15mg/kg/day which was increased to 0.3mg/kg/day, and 3months later she reverted to hypothyroidism; TSH 17.5uIU/mL, Low free T4 0.54ng/dl, normal total T3, with 15lb weight gain. Her MMI dose was lowered to 0.15mg/kg/day, however more definitive treatment options including thyroidectomy and radioactive iodine ablation was discussed with the family. Conclusion: The spectrum of autoimmune thyroid disorders span between extremes of Hashimoto’s thyroiditis and Graves’ disease, but rarely in adolescents, these conditions can co-exist, and management can be challenging and tedious to the patient, family, and physician. Since autoantibody status/titer may not always predict the clinical course, it is important for clinicians to keep a high index of suspicion of this process when the clinical course is atypical. Definitive therapy with thyroidectomy or radioactive iodine ablation may be a suitable option in these cases.
Outcome of Teprotumumab Treatment for Graves Orbitopathy After Multiple Attempts at Orbital Decompression Surgery
Authors: Kabir Purnima , Lewis Chantal , Hendrix Joshua
Published: May 2021

Background: Graves’ Orbitopathy, also known as Thyroid Eye Disease (TED) is a severe ocular manifestation of Graves’ Disease. It manifests as an autoantibody mediated reaction to the thyroid hormone stimulating receptor (TSH-R), these receptors are closely linked with the insulin-like growth factor-1 receptors (IGF-1R). The TSH-R antibodies play a major role in the pathogenesis of TED. The activation of the TSH-R and IGF-1R on orbital fibroblasts and adipocytes lead to IGF-1 expression. This initiates inflammation, fibroblast proliferation and accumulation of glycosaminoglycans in the orbital tissue. Treatment modalities include glucocorticoids, orbital radiation and orbital decompressions. Recent understanding of the molecular basis of TED has resulted in targeted therapy with Teprotumumab, an inhibitory monoclonal antibody against IGF-1R. There is limited literature on the outcomes of Teprotumumab use after orbital decompression surgery.

Clinical Case: 43-year-old female presented with symptoms of diplopia, periorbital pain, dry eyes and tremor. Ocular exam: Vision was correctable to 20/20 in each eye, restricted motility, bilateral lid edema, lid retraction with superior scleral show and conjunctival injection. Clinical Activity Score > 4. Diagnostic tests: TSH 0.00 undetectable (N:0.5-5.0mIU/L) FT4 3.19 (N:0.7-1.9ng/dL) TSI thyroid stimulating immunoglobulin 490% of baseline (N: 130% of baseline). Diagnosis of Graves’ disease with associated orbitopathy was made. In addition to medical management for Graves’ thyroid disease she was referred to ophthalmology. She was treated with high dose steroids for 4 weeks with no resolution of symptoms. She was then referred to an oculoplastic surgeon for bilateral orbital decompressions which resulted in mild improvement in diplopia but a residual proptosis. The decision was made to treat with teprotumumab, which had recently been FDA approved. Patient reported improved symptoms without complicating enophthalmos. Review confirmed improved proptosis on Hertel Exophthalmometry. The right eye improved from 22 mm to 16 mm and the left eye from 21 mm to 17 mm (N <20.1 mm Caucasian females) with preserved visual acuity, improved lid retraction, resolved conjunctival chemosis and decreased periorbital pain after 6 doses of Teprotumumab therapy.

Conclusion: Graves’ orbitopathy can result in debilitating symptoms affecting quality of life. Targeted molecular therapy such as teprotumumab is an effective treatment even after orbital decompression.

Reference: Ting, M., Ezra, D.G. Teprotumumab: a disease modifying treatment for graves’ orbitopathy. Thyroid Res13, 12 (2020). https://doi.org/10.1186/s13044-020-00086-7
Preeclampsia and Thyrotoxicosis: A Case of Impending Storm
Authors: Wilson Marianne K , Hermayer Kathie L
Published: May 2021

Introduction: Preeclampsia is a complication of pregnancy defined by new onset hypertension after 20 weeks with proteinuria or new onset thrombocytopenia, renal or liver dysfunction, pulmonary edema or cerebral/visual symptoms. Hyperthyroidism in pregnancy is usually due to Graves’ disease, and if poorly controlled can increase the risk of preeclampsia and thyroid storm. In this case report we present a case of preeclampsia with impending thyroid storm treated successfully with medical therapy, delivery, and plasmapheresis. Case Description: A 40-year-old female who is 31 6/7 weeks pregnant presents with cough and dyspnea. She has no known thyroid disease. Her systolic blood pressure at presentation is >160 mmHg. She is diagnosed with preeclampsia based on elevated spot protein/creatinine ratio (1.4 g/g) and persistent hypertension. A brain natriuretic peptide is elevated to 847 (reference range <= 100 pg/ml). Complete blood count and comprehensive metabolic panel are normal, with exception of mild alkaline phosphatase elevation. A CT pulmonary angiogram is negative for pulmonary embolism but shows bilateral pleural effusions. She is started on intravenous antihypertensive medications and furosemide. Due to persistent tachycardia, thyroid function is checked and is notable for a thyroid stimulating hormone level of 0.05 (non-pregnant reference range 0.35 – 4.94 mIU/L), an elevated free T3 of 13.7 (non-pregnancy reference range 1.7 – 3.7 pg/ml), and an elevated free T4 > 4 (non-pregnancy reference range 0.70-1.48 ng/dL). She is started on therapy for impending thyroid storm, including maximum doses of propranolol, propylthiouracil, hydrocortisone and saturated solution of potassium iodide. Her thyroid stimulating immunoglobulin is > 500 (reference range <= 122%) and TSH receptor antibody is > 40 (reference range <= 1.75 iU/L) leading to a new diagnosis of Graves’ disease. On hospital day three, she develops altered mental status and fetal bradycardia, warranting emergency cesarean section. On hospital day five she develops worsening confusion, abnormal liver function tests and increasing levels of free T4 and free T3. At this time, she is started on plasmapheresis therapy. Free T4 and free T3 values normalize after two rounds. Her medications are slowly weaned, and she is discharged from the hospital on methimazole 20 mg daily. Her baby is discharged after a brief hospital stay for sequela of prematurity. Discussion: While far less common than preeclampsia, thyrotoxicosis may present with similar symptomatology and can pose significant morbidity and mortality risk for pregnant patients. However, with prompt diagnosis and appropriate therapies, the disorder can be treated successfully and without lasting harm to the mother or fetus. For these reasons, it should remain on the differential for patients with symptoms of preeclampsia, and thyroid studies should be considered.
Rare Case of Thyroid Storm Masked by Diabetic Ketoacidosis
Authors: Nachawi Noura , Repp Anita Lopes
Published: May 2021

Introduction: Diabetic ketoacidosis can be triggered many other clinical conditions. In this case we describe uncommon presentation of diabetic ketoacidosis in the setting of thyroid storm. Clinical Case: An 82-year-old woman with history of type 2 diabetes treated with Insulin and Metformin presented with multiple falls preceded by fatigued and decreased oral intake for two weeks. On initial presentation, she was noted to have hyperglycemia and labs consistent high anion gap metabolic acidosis and positive serum and urine ketones suggesting diabetic ketoacidosis. Investigations were negative for any triggering infections. Diabetic ketoacidosis resolved with intravenous fluids and Insulin. However, patient remained consistently tachycardic. Repeated thyroid workup showed declining TSH (from 0.66 to 0.12 mIU/mL) (n: 0.270 - 4.200 mIU/mL), free T4 of 4.3 ng/dL (n: 0.9 - 1.7 ng/dL) and free T3 of 9.7 ng/dL (n: 79 - 165 ng/dL), thyroid peroxidase antibodies and thyroid stimulating immunoglobulin were both elevated of 293 IU/mL (n: <5.6 IU/mL) and 7.2 IU/L (n: <0.55 IU/L) respectively. Thyroid ultrasound showed several nodules in the isthmus and left lobe with multiple nodules with largest one measuring 1 X 2.3 cm. Treatment with Methimazole and Prednisone was initiated with good response. On follow up with endocrinology, repeated TSH was 28 mIU/mL and her Methimazole dose was reduced. Due to patient wishes of being conservative in management, no thyroid radioiodine uptake scan to evaluate the nodules.

Conclusion: Literature review shows several similar case reports of newly diagnosed thyrotoxicosis manifested by DKA in known type 1 and type 2 diabetic and obscured by other confounding conditions including pericarditis, flu syndrome, psychosis and cellulitis ultimately delaying diagnosis and treatment of thyroid storm. Fortunately, none of these cases were associated with adverse outcome. By presenting this case we emphasis on including thyroid function test as part of initial work up of diabetic ketoacidosis to avoid any potential adverse outcomes.