Myxedema Heart Disease: A Rare Disease Entity: Case Report and Brief Review of the Literature.

BACKGROUND: Myxedema heart disease is an extremely rare disease entity and should be suspected in patients with unexplained heart failure refractory to conventional treatment. Myxedema coma with co- existent heart disease is not well known and very few cases have been reported. CONCLUSION: Here, we present an interesting case of myxedema coma with severe valvular cardiomyopathy followed by a concise review of the literature with special emphasis on epidemiology, pathophysiology, diagnosis and therapeutic modalities.

Long-term follow-up and epidemiological trends in patients with pretibial myxedema: an 11-year study from a tertiary care center in northern India.

INTRODUCTION: Pretibial myxedema (PTM) is a rare manifestation of Graves' disease. There is paucity of data regarding long-term follow-up and response to treatment in PTM. MATERIALS AND METHODS: Retrospective study wherein 30 patients of PTM presenting during 2001-2011 attending dermatology and endocrinology outpatient departments were analyzed. RESULTS: Among 30 patients with PTM, 12 were males and 18 females with a ratio of 1 : 1.5 males/females. Four morphological forms were identified: plaques (18 patients), diffuse non-pitting edema of both lower legs (five), nodules (five), and elephantiasis lesions (two). Eighty percent were diagnosed with hyperthyroidism before the development of dermopathy. Twenty-six patients presented with ophthalmopathy. Fourteen patients with plaque had an excellent response to topical clobetasol propionate ointment and attained complete resolution by 3.6 years. Out of 16 patients treated with combination therapy, which included nine treated with topical corticosteroids/intralesional triamcinolone and seven treated with oral, intralesional, and topical corticosteroids, nine attained complete resolution in the lesions by 3.4 years, and none relapsed anytime during four years of post-treatment follow-up. However, the remaining patients (elephantiasis and diffuse forms) failed to achieve complete resolution. CONCLUSIONS: Plaques and nodules are common variants with a favorable clinical response to topical and intralesional corticosteroid; elephantine and diffuse forms responded poorly to therapy. Studies analyzing larger cohorts of patients with PTM and their long-term follow-up are limited, hence more such studies are required.

Extrathyroidal manifestations of Graves' disease: a 2014 update.

INTRODUCTION: Graves' orbitopathy (GO), thyroid dermopathy (also called pretibial myxedema) and acropachy are the extrathyroidal manifestations of Graves' disease. They occur in 25, 1.5, and 0.3 % of Graves' patients, respectively. Thus, GO is the main and most common extrathyroidal manifestation. Dermopathy is usually present if the patient is also affected with GO. The very rare acropachy occurs only in patients who also have dermopathy. GO and dermopathy have an autoimmune origin and are probably triggered by autoimmunity to the TSH receptor and, likely, the IGF-1 receptor. Both GO and dermopathy may be mild to severe. MANAGEMENT: Mild GO usually does not require any treatment except for local measures and preventive actions (especially refraining from smoking). Currently, moderate-to-severe and active GO is best treated by systemic glucocorticoids, but response to treatment is not optimal in many instances, and retreatments and use of other modalities (glucocorticoids, orbital radiotherapy, cyclosporine) and, in the end, rehabilitative surgery are often needed. Dermopathy is usually managed by local glucocorticoid treatment. No specific treatment is available for acropachy. PERSPECTIVES: Novel treatments are presently being investigated for GO, and particular attention is paid to the use of rituximab. It is unknown whether novel treatments for GO might be useful for the other extrathyroidal manifestations. Future novel therapies shown to be beneficial for GO in randomized studies may be empirically used for dermopathy and acropachy.

[Predisposition to autoimmune thyroid diseases within a Tunisian multiplex family]. / Prédisposition aux maladies auto-immunes thyroïdiennes au sein d'une famille tunisienne multiplexe.

The autoimmune thyroid diseases (AITDs) are multifactorial diseases which result from interplays between predisposing genes and triggering environmental factors. In order to study the genetic susceptibility factors to AITDs, we have followed up 115 control members belonging to a large Tunisian family with a high prevalence of AITDs (Akr family) during 15 years between 1990 to 2005. The follow-up of these control members have showed that 13 subjects (11.3%) developed AITDs (G2). The Hashimoto thyroiditis was the most frequently seen in 77% of the cases, whereas the Graves's disease was present in 23% of the cases. One hundred and two members remained controls (G1). High female predominance was noted in the two groups. The mean age of the G1 subjects group was slightly higher than that of G2. The prevalence of positive antithyroglobulin antibody (TgAb) and antithyroperoxydase antibody (TPOAb) was more frequent in G2 group (P=0.27 and P=0.23) respectively. The HLA haplotypes was realized in 42% of control members. The most frequent HLA haplotypes that were found were B37, DRB11 and A1. HLA B37 and DRB11 were significantly more frequent for the patients of G2 (P=0.0001 and P=0.034) respectively. Our study confirms the contribution of the genetic factors in the development of AITDs in 'Akr' family and suggested that the members of this family share the same genetic inheritance.

Pretibial myxedema is associated with polymorphism in exon 1 of CTLA-4 gene in patients with Graves' ophthalmopathy.

Cytotoxic T-lymphocyte associated antigen-4 (CTLA-4) is a well-known molecule that regulates T cell activity, with polymorphisms at different regions of this gene having been associated with autoimmune conditions. Pretibial myxedema (PTM), also called Graves' dermopathy, is an autoimmune extrathyroidal manifestation of Graves' disease. We opted to investigate the relationship between three single nucleotide polymorphisms of the CTLA-4 gene (+49A/G, and -318C/T and -1147C/T) and PTM in Iranian patients with Graves' ophthalmopathy (GO). A total of 105 unrelated Iranian patients with GO from the outpatient endocrine clinic of a large university general hospital as well as 103 healthy controls were studied. The genomic DNA was extracted from venous blood samples by a salting out method, and the polymorphisms at +49, -318 and -1147 positions of the CTLA-4 gene were determined using the polymerase chain reaction-restriction fragment length polymorphism method. The GG genotype (OR = 6.000, 95% CI = 1.805-19.940, P = 0.005) and the G allele (OR = 2.653, 95% CI = 1.314-5.357, P = 0.009) at position +49 were significantly associated with PTM in the patient group. The same genotype and allele were also significantly more common among patients (with or without PTM) than controls. No significant association was found for the other two polymorphisms. In conclusion, the +49G allele is associated with increased risk of PTM in patients with GO. Studies with larger sample sizes are needed to confirm the results of the present study.

Pretibial myxedema: pathophysiology and treatment options.

Pretibial myxedema or localized myxedema or thyroid dermopathy is an autoimmune manifestation of Graves' disease. It also occasionally occurs in Hashimoto's thyroiditis. Lesions of thyroid dermopathy are usually asymptomatic and have only cosmetic importance. Advanced forms of dermopathy are associated with elephantiasis or thyroid acropachy. Almost all cases of thyroid dermopathy are associated with relatively severe ophthalmopathy. Usually ophthalmopathy appears first and dermopathy much later. All patients with localized myxedema have high serum concentrations of thyroid-stimulating hormone receptor antibodies, indicating the severity of the autoimmune condition. Occurrence of thyroid dermopathy in areas other than pretibial skin indicates a systemic process. Similar to Graves' ophthalmopathy, thyroid-stimulating hormone receptors in the connective tissue may be the antigen responsible for the immune process. Both humoral and cellular immune mechanisms are involved in the stimulation of fibroblasts and the production of large amounts of glycosaminoglycans. Localization in the pretibial area relates to mechanical factors and dependent position. Diagnosis of thyroid dermopathy is based on signs and typical pretibial skin lesions in association with a history of Graves' hyperthyroidism and ophthalmopathy. In some cases, skin biopsy is needed for confirmation. The lesions are usually mild and are overshadowed by more symptomatic ophthalmopathy. Most cases of thyroid dermopathy do not require any therapy. In mildly severe symptomatic cases and when there is cosmetic concern, topical corticosteroids applied under occlusive dressing are beneficial. In more severe cases, systemic immunomodulation may be necessary; however, conclusive evidence for long-term efficacy of these modalities is lacking. When significant edema and elephantiasis are present, local compressive therapy may have added benefit. In mild cases that do not require treatment, 50% of patients achieve complete remission after several years. Severe cases that receive topical corticosteroids or other therapies do not have a better outcome than untreated milder cases. Current treatment modalities for thyroid dermopathy and acropachy are at best palliative. Better and safer means of immunomodulation are needed.

Scleromyxedema revisited.

Scleromyxedema is a rare disease characterized by papular mucinous deposits, dermal fibroblast proliferation, and a monoclonal paraproteinemia. Its chronic course tends to be complicated by gastrointestinal, muscular, pulmonary, and neurologic disorders. We review the literature to identify the common systemic manifestations and suggest a clinical approach to this disorder. This should include: identification of the characteristic lesions, a skin biopsy, and serum protein electrophoresis. A thyroid evaluation may help differentiate this condition from others. An early neurologic, gastrointestinal, and cardiovascular evaluation should be considered.

The devastating consequence of iodine deficiency.

Endemic cretinism is the most striking consequence of iodine deficiency. Although cretinism is a serious condition, it usually involves only about 5% of the population even in serious endemic areas. There is a spectrum between cretinism and normality, many are able to perform simple work and look apparently normal, but it is difficult for them to perform skilled labor. Studies in China using the IQ distribution curve revealed that every person in an endemic area lost about 10-15 IQ points, so that the socio-economic development of the community was severely affected.

Myxedema coma in the elderly.

BACKGROUND: Myxedema coma in the elderly, although uncommon, is frequently overlooked and has a high mortality rate. Signs and symptoms are many and are often insidious. Nearly every organ system is involved. Prompt recognition and treatment are mandatory for a successful outcome. METHODS: A case study is presented. Using the key words "myxedema" with the word "aged," MEDLINE files were searched from 1989 to present. Articles dating before 1989 were accessed from the reference lists of the more recent articles. RESULTS AND CONCLUSIONS: This review describes the signs and symptoms of myxedema coma in the elderly. Epidemiology and histopathology of the disorder are discussed. Prompt recognition and emergency medical treatment are essential for a successful outcome. Prevention requires screening of elderly patients at risk for hypothyroidism and assuring thyroid hormone replacement therapy.

Simultaneous assay for three types of thyrotropin receptor antibody activities using FRTL-5 cells in patients with autoimmune thyroid diseases.

The relationships between the different circulating thyrotropin receptor antibodies (TSH-R-abs) in autoimmune thyroid disease (AITD) are complex. In order to investigate them, we have developed an assay for the simultaneous measurement of three types of TSH-R-abs: TSH-binding inhibiting immunoglobulin (TBII): thyroid-stimulating antibody (TS-ab) and TSH-stimulation blocking antibody (TSB-ab). A large number of patients with Graves' disease (GD)--untreated and treated--Hashimoto's thyroiditis (HT), primary myxedema (PM) and non-immune goiter (NIG) were investigated. In untreated Graves' patients the frequency of positive TS-ab and TBII sera was found to be 90 and 69%, respectively, the presence of TS-ab and/or TBII being detected in 98%. After long-term antithyroid treatment administered to GD patients, the frequency of positivity of both TBII and TS-ab was decreased, whether hyperthyroidism was cured or not. The TSB-ab was detected in the serum of 8% of patients with GD, and the frequency of TSB-ab did not increase following treatment and alteration in thyroid function. No significant correlation was found between TSB-ab and thyroid function in Graves' patients. Besides, we found that all the GD patients presenting positive TSB-ab were also TBII positive. A follow-up study of the three TSH-R-abs was performed in 35 patients with GD during a mean of 14.3 +/- 8.5 months (4-34 months) of antithyroid drug treatment. Ten out of 24 patients (42%) with positive TBII and 16 out of 32 (50%) with positive TS-ab turned from positive to negative during the time of follow-up. Regarding relapse in hyperthyroid GD, we found that TS-ab was positive in 80% and TBII was positive in 40% of the patients with Graves' relapse, indicating that the presence of TS-ab is a better index for relapse prediction in Graves' hyperthyroidism than TBII. The TSB-ab was found with higher frequency in HT and PM than in GD, i.e. 21%, 18% and 8%, respectively., The TSB-ab positivity was correlated significantly with TBII in our patients with AITD when TSB-ab was positive. This new simultaneous assay of the three TSH-R-abs should be very helpful for further investigation of the autoimmune aspects of AITD and it should help us to progress in a better understanding of the pathogeny of the different AITDs.

[The tryptophan-associated eosinophilia-myalgia syndrome. A clinical follow-up of 8 patients]. / Tryptophan-assoziiertes Eosinophilie-Myalgie-Syndrom. Klinische Verlaufsbeobachtung bei acht Patienten.

Seven women and one man aged from 51 to 70 years suffered from eosinophilia-myalgia syndrome after taking medicines containing tryptophan for depression or sleep disorders; the total duration of intake ranged from three to 106 months and the average daily dose was 1312 mg. All the patients had muscle pains and skin lesions resembling scleroderma together with impairment of general well being; six of them had high eosinophil counts of up to 2,600 cells/microliters (mean 1,629); other symptoms were weight loss, pruritus, fever, dyspnoea and sensory abnormalities. Discontinuation of tryptophan combined with systemic treatment with prednisone in doses of 32 or 20 mg/d for 4 to 16 weeks soon brought the eosinophil counts down, but the skin lesions, muscle pains and other symptoms showed little improvement over a follow-up period averaging 17.1 months. Treatment with penicillin G (20 mega-units daily for 14 days), azathioprine (100 mg daily for 2 months) or cyclosporin (2.5 mg/kg.day) was tried in some cases but had no significant effect.

Effect of occupational exposure to cobalt blue dyes on the thyroid volume and function of female plate painters.

It has previously been shown that long-term oral exposure to cobalt can cause goiter and myxedema. The effect of industrial cobalt exposure on thyroid volume and function was determined for 61 female plate painters exposed to cobalt blue dyes in two Danish porcelain factories and 48 unexposed referents. Thyroid volume was determined by ultrasonography. The cobalt blue dyes were used in one of two forms, cobalt aluminate (insoluble) and cobalt-zinc silicate (semisoluble). Only the subjects exposed to semisoluble cobalt had a significantly increased urinary cobalt content (1.17 micrograms.mmol-1 versus 0.13 micrograms.mmol-1, P less than 0.0001). These subjects also had increased levels of serum thyroxine (T4) and free thyroxine (FT4I) (P = 0.0001 and 0.0029, respectively), unaltered serum thyroid stimulating hormone (TSH), and marginally reduced 3,5,3'-triiodothyronine (T3), whereas thyroid volume tended to be lower (P = 0.14). The group exposed to insoluble cobalt did not differ significantly in any thyroid-related parameters. No correlation between urinary cobalt and FT4I or thyroid volume was found. The study demonstrates an effect of cobalt on thyroid hormone metabolism.

Endemic cretinism: possible role for thyroid autoimmunity.

Thyroid atrophy, rather than goitre, is a characteristic feature of myxoedematous cretinism but its cause and nature are unknown. In this study, purified IgG fractions of serum from patients with myxoedematous endemic cretinism inhibited thyrotropin-induced DNA synthesis in guineapig thyroid segments in a sensitive cytochemical bioassay. IgG from patients with euthyroid neurological endemic cretinism or from normal subjects did not inhibit thyroid growth. Furthermore, in myxoedematous subjects, the presence of the thyroid-growth-blocking immunoglobulins showed a positive relation with thyroid atrophy found on ultrasound. These findings provide a pathogenic basis for the variable clinical expression of endemic cretinism.

A comparative study of neurological and myxedematous endemic cretinism in western China.

Endemic cretinism occurs in areas of severe iodine deficiency and is manifested by two major clinical patterns, myxedematous and neurological. The relationship between these types and the factors responsible for the clinical variability are not clear. We examined 69 endemic cretins, aged 4-52 yr, categorized clinically at the beginning of the study into the three traditional types of endemic cretins, myxedematous (n = 25), neurological (n = 15), and the mixed form (n = 29), from a previously unreported endemia in Qinghai Province, China. These patients underwent detailed endocrine and neurological examination, including intelligence assessment using the Hiskey-Nebraska Test of Learning Aptitude or the Griffiths Mental Development Scales, audiometry (in a subset of 37 patients); thyroid function testing and thyroid ultrasonography; and radiology of the skull, hand, and hip. We found that categorization of the cretins into the conventional types did not reflect the pathophysiology of the condition, since an identical pattern and intensity of neurological, intellectual, and audiometric deficits were common to and equally present in all three types of endemic cretins regardless of their thyroid function. Gait disorder (in 99%) and pyramidal signs such as patellar hyper-reflexia (in 91%) were the most common neurological abnormalities. There was no difference in mean intelligence test scores among the three groups [overall mean intelligence score (Hiskey or Griffiths tests), 28.8 +/- 12.8 (SD)]. The differing clinical manifestations of cretinism could be explained by the length and severity of thyroid hormone deficiency. Myxedematous cretins were severely thyroid hormone deficient, and as a result sexually immature, dwarfed, and had retarded skeletal maturity. They had clinical and sonographic thyroid atrophy, rather than goiter. Although neurological cretins were euthyroid, linear growth arrest lines (demonstrated radiologically) in the long bones of these cretins suggested previous hypothyroidism. Furthermore, all cretins were growth retarded when compared with peers of similar age and race. Our data therefore suggest that the different clinical types of endemic cretinism are in fact the same disorder phenotypically modified by the length and severity of postnatal hypothyroidism. The neurological manifestations are interpreted as reflecting the effects of maternal and fetal hypothyroxinemia, secondary to severe iodine deficiency, on the developing nervous system.

Endemic goitre in Chinamora, Zimbabwe. The Chinamora Research Team.

In a survey of 3841 rural dwellers in Chinamora, Zimbabwe, goitre was found in 29%. There was associated moderate iodine deficiency, and 8 people out of a subgroup of 229 had biochemical myxoedema; 2 others had biochemical thyrotoxicosis. Thyrotropin levels were not raised in 100 children aged less than one year. There did not seem to be a role for goitrogens in the pathogenesis of the goitres. A nationwide iodinisation programme should be introduced in Zimbabwe.

Epidemiologic features of canine hypothyroidism.

This study investigates the epidemiologic features of 3,206 dogs diagnosed with hypothyroidism (including myxedema) from 1.1 million dogs seen at 15 veterinary teaching hospitals between March, 1964 and June, 1978. Nine breeds found to be at high-risk for hypothyroidism were: golden retrievers, Doberman pinschers, dachshunds, Shetland sheepdogs, Irish setters, Pomeranians, miniature schnauzers, cocker spaniels, and Airedales. Two breed with a significant deficit of risk were German shepherds and mixed breed (mongrel) dogs. Age risk was greatest among younger dogs of high-risk breeds, further suggesting a genetic component to the etiology of this disease. In contrast, low-risk dogs had increasing relative risk through nine years of age. Spayed female dogs displayed a significantly higher risk when compared to intact females. Though not statistically significant, male castrated dogs had 30% more hypothyroidism compared to their intact counterparts. Among the case series were 91 endocrine and hormone-related neoplasms and 198 other endocrine-related disorders. Further studies linking canine hypothyroidism to other conditions, particularly cancer, could provide valuable insight into human disease experience.