Myxedema in Both Hyperthyroidism and Hypothyroidism: A Hormetic Response?

Myxedema is a potentially life-threatening condition typically observed in severe hypothyroidism. However, localized or diffuse myxedema is also observed in hyperthyroidism. The exact cause and mechanism of this paradoxical situation is not clear. We report here the analysis of body fluid distribution by bioelectrical impedance analysis (BIA) in 103 thyroid patients, subdivided according to their functional status. All BIA parameters measured in subclinical thyroid dysfunctions did not significantly differ from those observed in euthyroid controls. On the contrary, they were clearly altered in the two extreme, opposite conditions of thyroid dysfunctions, namely overt hyperthyroidism and severe hypothyroidism, indicating the occurrence of a typical hormetic condition. Surprisingly, differences in BIA parameters related to fluid body composition were even more evident in hyperthyroidism than in hypothyroidism. A hormetic response to thyroid hormone (TH)s was previously reported to explain the paradoxical, biphasic, time- and dose-dependent effects on other conditions. Our results indicate that myxedema, observed in both hypothyroid and hyperthyroid conditions, represents another example of a hormetic-type response to THs. BIA offers no additional valuable information in evaluating fluid body composition in subclinical thyroid dysfunctions, but it represents a valuable method to analyze and monitor body fluid composition and distribution in overt and severe thyroid dysfunctions.

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.

A case of fatal myxedema coma with electrocardiogram Osborne J-wave in a patient initially diagnosed with hypothyroidism.

Myxedema coma is a life-threatening endocrine emergency with a high mortality rate resulting from severe insufficiency of thyroid hormones. Intravenous levothyroxine replacement is considered the standard therapy for myxedema coma in many countries. In Japan, however, although there are diagnostic criteria highly suggestive or diagnostic for myxedema coma, no management strategy has been established, despite the availability of levothyroxine. Here we report a 75-year-old man with a history of Alzheimer's disease and schizophrenia who developed somnolence and generalized edema. Except for a pulse rate of 60 bpm, his vital signs and blood oxygen level were stable. Thyroid studies showed an elevated serum thyrotropin level of 219.2 µU/mL and a decreased serum free-thyroxine level of 0.15 ng/dL. On this basis he was diagnosed as having hypothyroidism rather than being highly suggestive for myxedema coma. Daily oral levothyroxine 25 µg was initiated and increased to 50 µg 3 days later. Seven days after being started on levothyroxine, the patient suddenly developed impaired consciousness, hypoxemia, hypotension, hypothermia, and hyponatremia. Electrocardiography revealed junctional bradycardia with Osborne J-wave. Myxedema coma was therefore diagnosed. He went into cardiac arrest in the emergency room but was resuscitated. Despite subsequent intravenous administration of hydrocortisone and levothyroxine, as well as intensive supportive care, he eventually died 12 hours after hospital admission. This case illustrates some of the challenges associated with the management of patients with signs highly suggestive/diagnostic of myxedema coma, including the optimal loading dosage and intervention timing of thyroid hormone replacement.

Local immune microenvironment of skin may play an important role in the development of pretibial myxedema.

Pretibial myxedema (PTM), characterized by the accumulation of glycosaminoglycans in dermis is an autoimmune skin disorder, which is almost always associated with Graves' disease (GD). Although fibroblast stimulated by thyroid-stimulating hormone receptor (TSHR) antibody, cytokines and growth factors have been postulated as target of the autoimmune process in the dermopathy, the pathogenesis of PTM remains unclear. We hypothesize that the local immune microenvironment of the skin including the antigens and antibodies, T cells, B cells, plasma cells and fibroblasts may play an important role in the development of PTM. Results obtained on PTM patients indicate increased thyroid-stimulating hormone receptor antibodies (TRAb) in the blood positively correlate with the dermal thickness of the lesions. Further analysis shows that there were more CD3+ T cells and CD20+ B cells in the skin lesions. These T and B cells are in close contact, indicating that inducible skin-associated lymphoid tissue (iSALT) may be formed in the area. In addition, we found that the infiltrating plasma cells can secrete TRAb, proving that B cells in the skin other than the thyroid are an additional source of TSHR antibodies. Meanwhile, the T and B cells in the skin or skin homogenate of patients can promote the proliferation of pretibial fibroblasts. In conclusion, our results provide evidence that the local immune microenvironment of the skin may play an important role in the development of PTM.

Neurological Complications of Endocrine Emergencies.

PURPOSE OF REVIEW: Endocrine disorders are the result of insufficient or excessive hormonal production. The clinical course is long, and the manifestations are nonspecific due to the systemic effect of hormones across many organs and systems including the nervous system. This is a narrative review of the recent evidence of the diagnosis and treatment approach of these medical and neurological emergencies. RECENT FINDINGS: With the possible exception of diabetic ketoacidosis, hyperosmolar hyperglycemic state, and hypoglycemia, endocrinological emergencies are complex, uncommon yet life-threatening conditions with protean and often nonspecific early clinical signs. They frequently are the first manifestation of the endocrine derangement. The systemic effects of hormones extend to the nervous system and as such, these conditions can present with neurological complications manifested, in most cases, by a diffuse dysfunction of the brain in the form of encephalopathy, delirium, seizures, and coma; or specific and peculiar syndromes such as hemichorea, hemiballism, and epilepsia partialis continua. The severity of these conditions often necessitates management in the intensive care unit requiring substantial supportive care in addition to specific targeted therapy to correct the hormonal metabolic abnormalities while at the same time blocking hormonal activity, in cases of excessive function, or supplementing hormonal deficiencies. Endocrine emergencies and their neurological complications are infrequent. The major challenge for most is early recognition. Their morbidity and mortality are high and their diagnosis requires high index of suspicion. The neurological complication most often improves with the correction of the metabolic derangement and their acuity and severity require admission to the intensive care unit.

Sudden cardiac arrest associated with myxedema coma due to undiagnosed hypothyroidism: a case report.

BACKGROUND: Myxedema coma, which occurs due to hypothyroidism, is a rare and life-threatening condition. Some patients have hemodynamic dysfunction, which consequently leads to cardiac arrest. The rarity of this condition makes it difficult to determine the cause of cardiac arrest. It is important to diagnose myxedema coma based on clinical findings, including physical examination and laboratory parameters. We present a case of undiagnosed and untreated hypothyroidism that initially caused myxedema coma and then led to cardiac arrest. CASE PRESENTATION: A 56-year-old woman who had no medical history was transferred to our hospital for the management of return of spontaneous circulation due to sudden cardiac arrest. Findings of laboratory tests revealed that she had hypothyroidism. On physical examination, she was found to have a puffy face, thin eyebrows, and severe systemic non-pitting edema. Therefore, the patient was clinically diagnosed with myxedema coma, which was the cause of cardiac arrest. She was treated with thyroid hormone and hydrocortisone, resulting in improvement in her general condition, except for the neurological dysfunction. CONCLUSIONS: This case suggests that myxedema coma is caused by undiagnosed and untreated hypothyroidism, leading to sudden cardiac arrest. Our findings are useful in the differential diagnosis of hypothyroidism based on characteristic physical examination findings. Clinicians should be aware of the differential diagnosis of myxedema coma based on findings from physical examination and laboratory testing of thyroid function, and the treatment should be started immediately.

Congenital hypothyroidism presenting as myxedema coma in a teenager.

Congenital hypothyroidism is rare and is screened for in the United States during the newborn period in order to prevent a treatable cognitive delay. Myxedema coma is a complication due to severe hypothyroidism resulting from failure of homeostatic processes, causing altered mental status, generalized edema, and vital sign abnormalities. Treatment of myxedema coma consists of supportive care and hormone replacement. We describe a case of congenital hypothyroidism presenting as myxedema coma in an immigrant teenager.

Decompensated hypothyroidism: A review for the emergency clinician.

BACKGROUND: Decompensated hypothyroidism, formerly known as myxedema coma, is an endocrine emergency that commonly presents with altered mental status, as well as hypothermia and depressed vital signs. The condition is often caused by an inciting event, which may lead to significant delays in the diagnosis and management of this disease. Although the incidence is low, this disease is associated with significant morbidity and mortality. Therefore, it is important for emergency clinicians to be aware of this condition. OBJECTIVE: This narrative review evaluates the emergency medicine diagnosis and management of adult patients with decompensated hypothyroidism. DISCUSSION: Decompensated hypothyroidism is a severe hypothyroid state associated with multiple organ failure. The diagnosis can be challenging due to similarities with more common diseases and lack of consideration of the diagnosis. Many patients may present with altered sensorium or depressed vital signs. Clinicians should obtain a thyroid stimulating hormone and free thyroxine level when considering the diagnosis. Management involves resuscitation, early steroid supplementation, thyroid hormone replacement, and treatment of the inciting event. CONCLUSIONS: Decompensated hypothyroidism should be considered in the evaluation of patients with altered sensorium and depressed vital signs so as to not miss this critical diagnosis.

[A case of elderly myxedema coma patient with end-stage renal failure].

CASE: 84-year-old woman had been diagnosed hypothyroidism before, but she did not take tablets of thyroid hormone prescribed. Anorexia and decreased consciousness level were discovered by workers of the facility. Her family doctor found thyroid function abnormality as a cause, and she was introduced to our hospital to treat because the whole body condition was bad. Her physical examination was observed that JCS was 3-10. Laboratory examination showed that TSH 562.81 µIU/mL, fT4 0.40 ng/mL, pH 7.33, and Na 124 mEq/L. It was not a contradictory finding with the diagnostic criteria of mucus edema coma. Blood and peritoneal dialysis is denied, although her data indicated eGFR 8-10 ml/min/1.73 m2. Her hospitalization was long-term, but exhibited finally good clinical course. After three months of hospitalization, she was discharged from the hospital. The problems were as follows. The clear guideline of myxedema coma with end-stage renal failure state and many complications was not found. She and her family did not hope dialysis under this condition.We treated a case of myxedema coma in a case of an elderly person with terminal renal failure who did not hope dialysis. In addition to myxedema coma as a rare disease, there are many basic diseases in the elderly. Although it was a difficult case, it is important to repeatedly confirm the explanation and the intention of the person and the family with regard to the selection of the treatment policy.

Clinical manifestation and images of a patient having cardiovascular involvement in myxoedema coma.

Myxoedema coma is an endocrine emergency characterised by diminished sensorium associated with features of severe hypothyroidism. The disease carries a high mortality of 30%-60 %. The cardiac manifestation of the disease consists of bradycardia, hypotension, pericardial effusion and certain echocardiographic changes such as heart block and features of hypothermia. Here, we report a case of myxoedema coma with characteristic cardiac manifestations. These manifestations revert promptly on starting treatment, and achieving a eumetabolic status as was demonstrated in this patient.

Parturient with Endocrine Disorders in the Intensive Care Unit.

Almost every endocrine axis is influenced by pregnancy. The diagnosis in acute cases is challenging as the classical symptoms are often masked. Thyroid storm is found in only 1-2% of hyperthyroid parturients (0.1-0.4% of all pregnancies). Burch and Wartofsky scoring system is useful for the identification of thyroid storms. Myxedema coma is an extremely rare complication of overt hypothyroidism with a 20% mortality rate. Diabetic ketoacidosis usually reported in the second and third trimesters carries a risk of fetal loss in 10-25% of cases. The size of the tumor rises in 2.7% of microprolactinomas and 22.9% of macroprolactinomas during pregnancy. Adrenal insufficiency in pregnancy is usually caused by primary adrenal failure, which is mostly autoimmune in origin. Pheochromocytoma may present as preeclampsia during pregnancy. Unrecognized pheochromocytoma is associated with a maternal mortality rate of 50%. Shared decision-making and close coordination between critical care, anesthesiology, obstetrics, and endocrinology can help in assuring good maternal and fetal outcomes. How to cite this article: Singh AK, Sarkar S, Khanna P. Parturient with Endocrine Disorders in the Intensive Care Unit. Indian J Crit Care Med 2021;25(Suppl 3):S255-S260.

Reversible bradycardia secondary to myxedema coma: case-report.

Myxedema coma occurs mostly in patients with long-standing untreated or undertreated hypothyroidism. Bradycardia is a well-known cardiac manifestation for myxedema coma; however, not all bradycardia with hypothyroidism are sinus bradycardia. Sick sinus syndrome is a group of arrhythmias caused by the malfunction of the natural pacemaker of the heart. Tachy-Brady syndrome is considered to be a type of sick sinus syndrome, where the heart alternates between tachycardia and bradycardia, and it is usually treated with pacemaker implantation along with rate slowing medical therapy. Here we report a case of an 83-year-old female who presented with myxedema coma and atrial fibrillation with tachycardia and intermittent slow ventricular response. We attempt to review the relationship between these two diseases and conclude that appropriate diagnosis of myxedema coma, may be beneficial in reducing the need for pacemaker implantation.

Compartment syndrome of the leg after thyroid hormone withdrawal; two cases and a systematic review of the literature.

BACKGROUND: Acute compartment syndrome is a rare complication of severe hypothyroidism. If the symptoms are not recognized promptly and treatment initiated immediately, there is a high risk of permanent damage. Only few other cases of compartment syndrome due to hypothyroidism have been published and the exact pathophysiological mechanism remains unknown. CASE PRESENTATIONS: A 59 year old male developed acute compartment syndrome of his right lower leg after thyroid hormone withdrawal prior to radioiodine remnant ablation after total thyroidectomy for follicular thyroid cancer. He underwent emergency fasciotomy of all four compartments of the lower leg. The muscle tissue in the anterior and lateral compartment was necrotic and was therefore excised. The second patient was a 62 year old female with Hashimoto's thyroiditis, who developed acute compartment syndrome of both lower legs after thyroid hormone withdrawal due to non-compliance. Emergency fasciotomy of all four compartments of both legs was performed. The muscle tissue was viable in all compartments. CONCLUSION: Although compartment syndrome due to hypothyroidism is uncommon, it is a complication physicians should be aware of. The majority of reported cases are caused by an acute withdrawal of thyroid hormones and not by undetected hypothyroidism. No previous case of compartment syndrome caused by an iatrogenic hormone withdrawal in preparation for radioactive iodine has been published. However, as shown in this report, it may be beneficial to inform patients of this rare complication prior to hormone withdrawal in preparation for remnant ablation after thyroidectomy.

Myxedema ascites complicated by ischemic colitis.

Myxedema Ascites is a rare finding of primary hypothyroidism, thereby leading to delayed diagnosis. However, prompt treatment with levothyroxine leads to complete resolution of the condition. We present a rare case of myxedema ascites in an elderly female and highlight the importance of early diagnosis and management. We also present ischemic colitis in the same patient, which has not been reported thus far in literature as a complication of myxedema ascites.

Successful treatment of myxedema coma with a combination of levothyroxine and liothyronine.

Myxedema coma is a rare endocrine emergency resulting from the decompensation of severe hypothyroidism, which is associated with a high mortality rate. It is characterized by the deterioration of mental status, hypothermia, hypotension, hyponatremia, and hypoventilation. Early disease diagnosis and advancements in intensive supportive care have reduced the mortality rate. Besides intensive supportive care, appropriate management of the underlying thyroid hormone deficiency is essential. However, as the disease is rare and unrecognized, evidence-based treatment of myxedema has not yet been established in many countries. An 84-year-old Japanese man with a history of Hashimoto's thyroiditis was referred to our hospital. On arrival, conscious disturbance, hypothermia, hypotension, and hypoventilation were observed. He had discontinued thyroid hormone replacement therapy for a year. He was diagnosed with myxedema coma. Immediately, he received intensive supportive care and a combination therapy of 200 µg levothyroxine and 50 µg liothyronine until the fifth hospital day. Subsequently, monotherapy with levothyroxine was continued at a dose of 150 µg daily. The thyroid hormone level reached the normal range a few days later, and cardiovascular disease did not develop during hospitalization. This case demonstrated the efficacy of the combination of levothyroxine and liothyronine in treating myxedema coma.

[Hoffmann syndrome : about two new cases]. / Le syndrome d'Hoffmann : à propos de deux nouvelles observations.

Hypothyroidism is exceptionnally revealed by hypertrophic myopathy, known as Hoffmann syndrome. We report two new cases of severe hypothyroidism presenting as hypertrophic myopathy, occurring in two men of 49 and 57 years-old.

La myopathie hypertrophique associée à l'hypothyroïdie, connue sous le nom de syndrome de Hoffmann, est une manifestation rare de l'hypothyroïdie et peut à titre exceptionnel en constituer la manifestation initiale. Nous rapportons deux nouveaux cas de myopathie hypertrophique sévère révélant une hypothyroïdie profonde, chez deux adultes âgés respectivement de 49 et 57 ans.

Clinical characteristics and outcomes of myxedema coma: Analysis of a national inpatient database in Japan.

BACKGROUND: Myxedema coma is a life-threatening and emergency presentation of hypothyroidism. However, the clinical features and outcomes of this condition have been poorly defined because of its rarity. METHODS: We conducted a retrospective observational study of patients diagnosed with myxedema coma from July 2010 through March 2013 using a national inpatient database in Japan. We investigated characteristics, comorbidities, treatments, and in-hospital mortality of patients with myxedema coma. RESULTS: We identified 149 patients diagnosed with myxedema coma out of approximately 19 million inpatients in the database. The mean (standard deviation) age was 77 (12) years, and two-thirds of the patients were female. The overall proportion of in-hospital mortality among cases was 29.5%. The number of patients was highest in the winter season. Patients treated with steroids, catecholamines, or mechanical ventilation showed higher in-hospital mortality than those without. Variations in type and dosage of thyroid hormone replacement were not associated with in-hospital mortality. The most common comorbidity was cardiovascular diseases (40.3%). The estimated incidence of myxedema coma was 1.08 per million people per year in Japan. Multivariable logistic regression analysis revealed that higher age and use of catecholamines (with or without steroids) were significantly associated with higher in-hospital mortality. CONCLUSIONS: The present study identified the clinical characteristics and outcomes of patients with myxedema coma using a large-scale database. Myxedema coma mortality was independently associated with age and severe conditions requiring treatment with catecholamines.

[Myxedema coma]. / Coma mixedematoso.

Hypothyroidism is a frequently diagnosed and simply treated disease. If not recognised, however, in time it may develop into the most severe manifestation of hypothyroidism known as myxedema coma. The term "myxedema coma" is generally seen as misleading since most patients do not initially present in a coma. The typical progression is lethargy evolving into stupor and, eventually, into coma with respiratory failure and hypothermia. It mainly affects elderly women, often occurring in winter and is relatively rare. It can be considered a form of decompensated hypothyroidism often triggered by a variety of non-thyroid conditions or diseases provoking an extremely severe condition of multiple system failure with lethal consequences unless an early diagnosis is made and an aggressive treatment is administered.

Hypothyroidism and carpal tunnel syndrome: a meta-analysis.

This study aimed to assess the magnitude of the association between hypothyroidism and carpal tunnel syndrome (CTS). Eighteen studies were included in a random-effects meta-analysis. A meta-analysis of the studies that did not control their estimates for any confounder showed an association between a thyroid disease (hypo- or hyperthyroidism) and CTS (N = 9,573, effect size [ES] = 1.32 (95% confidence interval [CI], 1.04-1.68) and between hypothyroidism and CTS (N = 64,531, ES = 2.15 [95% CI, 1.64-2.83]). When a meta-analysis limited to the studies that controlled their estimates for some potential confounders, the association between a thyroid disease and CTS disappeared (N = 4,799, ES = 1.17 [95% CI, 0.71-1.92], I(2) = 0%), and the effect size for hypothyroidism largely attenuated (N = 71,133, ES = 1.44 [95% CI, 1.27-1.63], I(2) = 0%). Moreover, there was evidence of publication bias. This meta-analysis found only a modest association between hypothyroidism and CTS. Confounding and publication bias may still account for part of the remaining excess risk.