Graves' disease thyroid dermopathy: a case report.

BACKGROUND: Graves' disease is the autoimmune activation of the thyroid gland causing diffuse enlargement and hyperfunction of the gland. Manifestations of Graves' disease are multisystemic and include thyroid orbitopathy; pretibial myxedema, also referred to as thyroid dermopathy; and thyroid acropachy, described as a severe form of thyroid dermopathy. Our paper focuses on an atypical case of thyroid dermopathy. CASE PRESENTATION: An 11-year-old Saudi male presented with a prominent diffuse goiter and exophthalmos. Investigations were consistent with a diagnosis of Graves' disease. The physical exam showed diffuse, non-pitting swelling of the ankle and penis, mimicking a lymphatic malformation. Further, multiple nodules were found on the hands and feet. Treatment of the nodules with cautery resulted in more severe nodules. CONCLUSION: This report describes rare presentations of thyroid dermopathy mimicking lymphatic malformation. The Koebner phenomenon can explain this patient's atypical presentations. Intralesional injections of triamcinolone and total thyroidectomy showed clear improvement.

Clinical Features and Outcomes of Myxedema Coma in Patients Hospitalized for Hypothyroidism: Analysis of the United States National Inpatient Sample.

Background: Hypothyroidism is a common endocrine condition and chronic thyroid hormone deficiency is associated with adverse effects across multiple organ systems. In compensated hypothyroidism, however, patients remain clinically stable due to gradual physiological adaptation. In contrast, the clinical syndrome of decompensated hypothyroidism referred to as myxedema coma (MC) is an endocrine emergency with high risk of mortality. Because of its rarity, there are currently limited data regarding MC. This study analyzes the clinical features and hospital outcomes of MC compared with hypothyroid patients without MC (nonMChypo) in national United States hospital data. Methods: A retrospective analysis of the National Inpatient Sample, a public database of inpatient admissions to nonfederal hospitals in the United States, 2016-2018, including adult patients with primary diagnosis of MC (International Classification of Diseases 10th Revision [ICD-10]: E03.5) or nonMChypo (E03.0-E03.9, E89.0). Patient demographics, relevant clinical features, mortality, length of stay (LOS), and hospital costs were compared. Results: Of 18,635 patients hospitalized for hypothyroidism, 2495 (13.4%) had a diagnosis of MC. Sex distribution and race/ethnicity were similar between patients with MC and nonMChypo, whereas MC was associated with older patient age (p = 0.02), public insurance (p = 0.01), and unhoused status (p = 0.04). More admissions with MC occurred in winter compared with other seasons (p = 0.01). The overall mortality rate for MC was 6.8% versus 0.7% for nonMChypo (p < 0.001), and MC was independently associated with in-hospital mortality after adjusted regression analysis (adjusted odds ratio = 9.92 [CI 5.69-17.28], p < 0.001). Mean LOS ± standard error was 9.64 ± 0.73 days for MC versus 4.62 ± 0.12 days for nonMChypo (p < 0.001), and total hospital cost for MC was $21,768 ± $1759 versus $8941 ± $276 for nonMChypo (p = 0.07). In linear regression analyses, MC was an independent predictor of both increased LOS and total hospital cost. Conclusions: In summary, MC remains a clinically significant diagnosis in the modern era, independently associated with high mortality and health care costs. This continued burden demonstrates a need for further efforts to prevent, identify, and optimize treatment for patients with MC.

Case Report of Graves' Disease in a 45-Year-Old Woman Secondary to Herceptin Treatment for Breast Cancer.

Graves' disease is the most common cause of thyrotoxicosis and is characterized by ophthalmopathy with proptosis, chemosis, or conjunctival injection; pretibial myxedema; and thyroid acropachy. It is an autoimmune disease that can be genetic or influenced by coexisting environmental factors such as exposure to anticancer drugs, including immune checkpoint inhibitors. The incidence rate of breast cancer is increasing due to rising awareness of risk factors and screening for breast cancer, and the mortality rate is decreasing due to recent advances in cancer treatment. However, there are side effects that are attributed to these treatment modalities, manifesting in various forms in breast cancer survivors, which are reflected in the patient in this case study.

Life-Threatening Cardiac Arrhythmias in a Case of Undetected Myxedema Coma: Importance of Early Detection and Medication Adherence.

BACKGROUND Myxedema coma is a rare, life-threatening condition caused by a severe form of hypothyroidism. The dangerously low levels of circulating thyroid hormone can lead to progressive mental status changes and numerous organ dysfunctions, including serious cardiac abnormalities. CASE REPORT We present a case of a 59-year-old woman who presented with altered mental status and fall who was originally thought to have a cerebrovascular accident but was later diagnosed with myxedema coma, after multiple cardiac arrests. It was discovered that the patient had not been taking any of her medications for the last several weeks, after her primary care provider retired from practice. Initial laboratory evaluation was significant for a TSH level of 159.419 mIU/L and an undetectable free T4 level. Complications of the myxedema coma resulted in QTC interval prolongation, causing torsades de pointes and sustained polymorphic ventricular tachycardia, requiring cardioversion. CONCLUSIONS This case demonstrates the importance of early detection and treatment of myxedema coma, as it can cause life-threatening cardiac arrhythmias. It also emphasizes the need to ensure proper medication adherence in patients with chronic medical conditions, as non-compliance can result in dire consequences.

[Pretibial myxedema after Graves' disease: A differential diagnosis of lymphedema]. / Myxœdème prétibial pseudo-tumoral après une maladie de Basedow : un diagnostic différentiel du lymphœdème.

INTRODUCTION: Pretibial myxedema is a rare manifestation of Graves' disease, and pseudotumoral forms may be confused with lower limb lymphedema. OBSERVATIONS: We reported 3 cases of pretibial myxedema in 2 women and 1 man, aged 72, 66, and 49 years, treated for Graves' disease 3, 25 and 32 years previously. Two patients were active smokers. Lymphedema diagnosis of the lower limbs was suspected in the presence of bilateral pseudotumoral lesions of the feet, toes and ankles and the presence of a Stemmer's sign (skin thickening at the base of the 2nd toe, pathognomonic of lymphedema). Lymphoscintigraphy in one case was normal, not confirming lymphedema. CONCLUSION: Pretibial pseudotumoral myxedema is a differential diagnosis of lower limb lymphedema. This diagnosis is confirmed by questioning the patient about preexisting Graves' disease, the underlying etiology, to decide the appropriate treatment and to encourage cessation of smoking, which is a risk factor for pretibial myxedema.

[An integrated approach to the treatment of pretibial myxedema based on pulse therapy with prednisolone and electrical neuromyostimulation (FREMS-therapy) in a patient with Graves' disease and thyroid eye disease].

Graves' disease (GD) is one of the urgent problems of modern endocrinology, characterized by a high frequency, polysystemic damage to the body, a steadily progressive course, diagnostic difficulties, a high degree of disability and often resistance to therapy. The manifestations of the disease include: thyrotoxicosis syndrome with impaired lipid and carbohydrate metabolism, and activation of multiple organ pathology in the form of thyroid eye disease (TED), pretibial myxedema, cardiovascular insufficiency, acropathy, lesions of the nervous, osteoarticular system, and other lesions. The development of multiple organ pathology can have a different sequence, different time intervals and different degrees of severity. Any developments in the direction of clarifying the etiopathogenetic, clinical diagnostic and treatment-rehabilitation measures are of undoubted significance. We present a clinical case of GD, TED and pretibial myxedema, in which an integrated approach was tested in the tactics of treating pretibial myxedema (a combination of pulse therapy with prednisolone and FREMS-therapy), as a result of which positive results were obtained within a short time.

Severe hypoxemia after extubation secondary to myxedema coma: a case report.

Myxedema coma is a rare and life-threatening endocrine emergency characterized by abnormalities in multiple organ systems. A 32-year-old woman with prolonged undiagnosed severe hypothyroidism was referred to our hospital owing to lower abdominal pain and menopause for more than 3 months. She underwent exploratory laparotomy and induced abortion under general anesthesia, and developed severe hypoxemia after extubation. She was diagnosed with myxedema coma, and was subsequently discharged with a good prognosis following treatment. This case suggests that myxedema coma should be considered a potential etiology of peri-operative hypoxemia. The findings in this case emphasize the importance of anesthesiologists' comprehensive understanding of myxedema coma. Prompt diagnosis followed by treatment is essential to reduce the mortality rate associated with this condition.

Large Pericardial Effusion Secondary to Generalized Myxedema from Undiagnosed Hashimoto's Thyroiditis.

BACKGROUND Pericardial effusions are considered to be present when accumulated fluid within the pericardial sac exceeds the small amount that is normally present, causing impairment in the diastolic filling of the right heart. This case demonstrates an uncommon presentation of a large pericardial effusion by showing its relationship to myxedema in a patient with untreated hypothyroidism. CASE REPORT A 42-year-old man with a past medical history of hypertension, diabetes mellitus, and opioid abuse presented to the emergency department due to altered mental status, for which he received Narcan without resolution of symptoms. Computed tomography (CT) of the brain was without any acute intracranial abnormalities to explain the patient's altered mental status. CT chest reported a pericardial effusion, with a subsequent transthoracic echocardiogram (TTE) showing a moderate-to-large circumferential effusion without right atrial/ventricular collapse and no cardiac tamponade physiology. On further investigation, he was found to have severe hypothyroidism with elevated thyroid peroxidase antibodies. Endocrinology was consulted to start IV levothyroxine and liothyronine to treat autoimmune Hashimoto's thyroiditis. Subsequent TTE after starting hypothyroidism treatment showed an ejection fraction (EF) of 45-50% with mildly reduced left ventricular systolic function and moderate-to-large pericardial effusion, with no evidence of tamponade physiology. After treatment of hypothyroidism, the thyroid panel, EF, and pericardial effusion improved significantly. CONCLUSIONS This case illustrates the potential for suffering a large pericardial effusion secondary to generalized myxedema in a patient with severe hypothyroidism from undiagnosed Hashimoto's thyroiditis. It is important to recognize this condition for appropriate therapy and prevention of worsening cardiac conditions.

Localized alopecic myxedema of the scalp.

Myxedema is a rare, cutaneous complication of autoimmune thyroid diseases that most often affects the anterior shins. Herein, we report a patient with a history of Graves disease and Hashimoto thyroiditis who presented with boggy, alopecic patches associated with scalp pruritus. Punch biopsies from these lesions showed increased interstitial mucin in the reticular dermis, consistent with localized myxedema. This report showcases a rare presentation of localized myxedema of the scalp, highlighting the diverse cutaneous manifestations of autoimmune thyroid diseases.

Liquid levothyroxine in the treatment of myxoedema coma.

Not required for Clinical Vignette.

Novel teprotumumab treatment of severe thyroid dermopathy; ototoxicity as an adverse side effect.

Pretibial myxedema, more generally thyroid dermopathy, results from mucopolysaccharide accumulation in the dermis, typically between the knee and dorsal foot. Thyroid dermopathy presents in Graves disease, but can occur in Hashimoto thyroiditis, primary hypothyroidism, and euthyroid patients. Treatment of thyroid eye disease with teprotumumab is established in the literature, with few case reports also showing improvement in pretibial myxedema. Reported is a 76-year-old man with thyroid eye disease and pretibial myxedema treated with teprotumumab; improvement was demonstrated in both conditions. He developed "muffled" hearing as an adverse effect, a complication not widely published in the dermatology literature. At 18 months post-treatment, his symptoms are stable without recurrence, but hypoacusis persists. Given the long-term efficacy and side-effects, dermatologists should recognize the potential benefits and risks of using teprotumumab for thyroid dermopathy. A baseline audiogram may be considered prior to therapy. Additionally, longitudinal data is needed to document the benefits and risks of this novel therapy.

Adult Thyroid Outcomes of Congenital Hypothyroidism.

Background: More than 40 years have passed since the introduction of newborn screening (NBS) for congenital hypothyroidism (CH), and many early diagnosed patients have reached adulthood. Their thyroid morphology and function have been little studied. This cross-sectional, observational study was conducted to characterize the thyroid morphology and function of adult CH patients diagnosed in the framework of NBS for CH. Methods: A total of 103 adult CH patients born after 1979 were enrolled at Ito Hospital, Tokyo, Japan, and were classified into Goiter, Normal gland, and Dysgenesis groups based on ultrasonographic findings. For 60 patients, genetic analysis was performed. Thyroid function test results and the proportion of patients with thyroid nodules were compared among the three groups and between 56 female CH patients and 168 non-CH women matched for thyrotropin levels. Results: A significantly low serum free triiodothyronine/free thyroxine ratio (0.22) was observed in the Dysgenesis group. Thyroid nodules were detected in 14.3% (8/56) of female CH patients, more frequently than in non-CH women. Thyroid nodules were detected most frequently in the Goiter group (71%, 10/14). Genetic defects were identified in 89% (8/9) of patients belonging to the Goiter group, including thyroglobulin defect (33%, 3/9), thyroid peroxidase defect (33%, 3/9), and dual oxidase 2 defect (22%, 2/9). Conclusions: Our results suggest that adults with thyroid dysgenesis on levothyroxine replacement therapy have relative triiodothyronine deficiency. Most adults with goitrous CH have genetic dyshormonogenesis. They are at high risk of developing thyroid nodules. Our findings support the current guideline recommendation that CH patients with dyshormonogenesis should undergo periodic thyroid ultrasonography.

Utility of myxedema score as a predictor of mortality in myxedema coma.

OBJECTIVE: Myxedema crisis (MC) is a rare condition. There is a dearth of data regarding the predictors of mortality in MC. Predictive scores for mortality specific to the clinical and biochemical profile of MC are still lacking. DESIGN AND METHODS: All consecutive patients presenting with MC from September 2006 to December 2020 comprised the new cohort. Patients managed between January 1999 and August 2006 comprised the old cohort. Both cohorts were compared for the determination of secular trends. Combined analysis of both the cohorts was done for clinico-demographic profile and predictors of mortality. Myxedema score (MS) and qSOFA (Quick Sequential Organ Failure Assessment) score were evaluated in all the patients. RESULTS: A total of forty-one patients (new cohort; n = 18 and old cohort; n = 23) were enrolled into the study. There was a female predominance (80.5%). Nearly half (51.2%) of the patients were newly diagnosed with hypothyroidism on admission. Overall mortality was 60.9%. On comparative analysis among survivors and non-survivors, female gender (OR 20.4, p value 0.018), need for mechanical ventilation (OR16.4, p value 0.009), in-hospital hypotension (OR 9.1, p value 0.020), and high qSOFA score (OR 7.1, p value 0.023) predicted mortality. MS of > 90 had significantly higher mortality (OR-11.8, p value - 0.026) while MS of > 110 had 100% mortality. There was no change in secular trends over last 20 years. There was no difference in outcome of patients receiving oral or IV levothyroxine. CONCLUSION: Myxedema crisis is associated with high mortality despite improvement in health care services. The current study is first to elucidate the role of the MS in predicting mortality in patients with MC.

Graves' disease, myxedema, and papillary thyroid carcinoma / Doença de Graves, mixedema e carcinoma papilífero de tireoide

Graves' disease (GD) is the leading cause of hyperthyroidism and diffuse toxic goiter in iodine-sufficient geographi-cal areas. GD is associated with classical manifestations such as ophthalmopathy and thyroid dermopathy, in addi-tion to diffuse goiter, which may be the site of carcinomas, as a complication. Case report: A 52-year-old woman presented with goiter and symptoms compatible with hyperthyroidism, such as heat intolerance, weight loss, fati-gue, increased sweat, tachycardia, fine tremors, increased intestinal transit, anxiety, emotional lability, insomnia, exophthalmos, and pretibial myxedema. A complementary investigation confirmed the diagnosis of hyperthyroidism (high free T4 and total T3 levels and low thyroid-stimulating hormone - TSH levels). Ultrasound images showed dif-fuse enlargement of the thyroid lobes by approximately 10 times and the presence of three thyroid nodules, one of which was larger than 2 cm with heterogeneous echogenicity and vascularization throughout the nodule; ultrasoun-d-guided fine needle aspiration revealed cytology compatible with Bethesda IV; scintigraphy revealed a low uptake area (cold nodule) amid a diffuse high-uptake goiter. A thyroidectomy was performed, and the anatomical specimen diagnosis revealed papillary thyroid carcinoma in the right lobe, with adjacent parenchyma compatible with GD. Histopathological examination of the skin showed the presence of myxedema compatible with Graves' dermopathy. The patient evolved with the normalization of TSH levels and a reduction of cutaneous manifestations. Conclusion:GD abnormalities may not be restricted to the classic clinical manifestations, and a careful investigation may reveal the coexistence of carcinomas. (AU)

A doença de Graves (DG) é a principal causa de hipertireoidismo e bócio difuso tóxico em áreas geográficas com iodo suficiente. DG está associada a manifestações clínicas clássicas como oftalmopatia e dermopatia da tireoide, além do bócio difuso, que pode ser sítio de carcinomas, como uma complicação. Relato de caso: Mulher de 52 anos apresentou bócio e sintomas compatíveis com hipertireoidismo como intolerância ao calor, emagrecimento, fadiga, sudorese aumentada, taquicardia, tremores finos, trânsito intestinal aumentado, ansiedade, labilidade emocional, insônia, exoftalmia e mixedema pré-tibial. A investigação complementar confirmou o diagnóstico de hipertireoidis-mo (níveis elevados de T4 livre e T3 total; níveis baixos de hormônio estimulante da tireoide - TSH). As imagens ultrassonográficas mostraram aumento difuso dos lobos tireoidianos em aproximadamente 10 vezes e a presença de três nódulos tireoidianos, um dos quais, maior que 2 cm, com ecogenicidade e vascularização heterogêneas em todo o nódulo, cuja punção aspirativa por agulha fina guiada por ultrassom revelou citologia compatível com Bethesda IV; e a cintilografia evidenciou uma área de baixa captação (nódulo frio) em meio a um bócio difuso de alta captação. Foi realizada tireoidectomia e o diagnóstico da peça anatômica revelou carcinoma papilífero de tir-eoide em lobo direito, com parênquima adjacente compatível com DG. O exame histopatológico da pele mostrou a presença de mixedema compatível com dermopatia de Graves. A paciente evoluiu com normalização dos níveis de TSH e redução das manifestações cutâneas. Conclusão: As anormalidades da DG podem não estar restritas às manifestações clínicas clássicas, e uma investigação criteriosa pode revelar a coexistência de carcinomas, (AU)

History of the Thyroid.

The history of the thyroid dates from 2697 BCE when the "Yellow Emperor" Hung Ti described the use of seaweed to treat goiter. The English name "thyroid" was coined by Thomas Wharton in 1656 from the Greek word for a shield. Bernard Courtois discovered iodine in 1811 when he noted a residual purplish ash while burning seaweed. Robert Graves is known for his classic 1835 report of "palpitations, goiter, and exophthalmos" in three women, but Caleb Parry observed the same clinical features in 1786. The clinical syndrome we now recognize as hypothyroidism was characterized as "myxoedema" in 1878 by William Ord at St. Thomas Hospital. In 1891, George Murray reported that injection of thyroid extract from sheep led to improvement in symptoms in a woman with myxedema. Thomas Kocher, who reported that patients with goiter who underwent complete thyroidectomy developed cachexia strumipriva, was awarded the Nobel Prize in Physiology and Medicine in 1909. Edward Kendall discovered "thyroxin" on Christmas day in 1914. Studies by David Marine that iodine treatment prevented endemic goiter led to salt iodination, which has largely eradicated endemic cretinism. In 1973, Jean Dussault reported detection of congenital hypothyroidism by screening newborn populations.

Improvement of Pretibial Myxedema Following Administration of Teprotumumab.

Pretibial myxedema (PTM) is a rare complication of Graves' disease. It is characterized by non-pitting edema with hyperpigmented hyperkeratotic papules and plaques on bilateral lower legs. Effective treatments for patients with PTM are lacking. The etiology of PTM is unknown; however, it may be similar to the mechanism of thyroid-associated ophthalmopathy (TAO). Activated fibroblasts produce inflammatory cytokines and synthesize excessive glycosaminoglycans (GAG) that accumulate in the dermis and subcutaneous tissue. A recent, novel pathway implicates IGF-1 receptor as a mediator in this process. We present two patients with refractory PTM that improved following treatment with teprotumumab, an IGF-1 receptor inhibitor approved for use in TAO. J Drugs Dermatol. 2022;21(11):1252-1254. doi:10.36849/JDD.6854.

[A man with a low voice]. / Een man met een zware stem.

A 57-year old man with several non-specific complaints is found to have severe hypothyroidism. Only then he realizes that his voice may have changed. A recording of his voice during and after full recovery illustrates the profound effects that vocal cord myxedema may have of a patient's voice.