Quantitative assessment of extraocular muscles in Graves' ophthalmopathy using T1 mapping.

OBJECTIVE: To evaluate the performance of T1 mapping in the characterization of extraocular muscles (EOMs) of Graves' ophthalmopathy (GO) patients and investigate its feasibility in assessing the response to glucocorticoid therapy in active GO patients. METHODS: A total of 133 participants (78 active GO, 23 inactive GO, 18 Graves' disease (GD) patients, and 14 healthy volunteers) were consecutively enrolled from July 2018 to December 2020. Native T1 (nT1) and postcontrast T1 (cT1) values of EOMs were measured and compared. The variations in T1 mapping metrics of EOMs were compared pre/post glucocorticoid treatment in 23 follow-up active GO patients. Logistic regression analysis and receiver operating characteristic (ROC) curve analysis were performed. RESULTS: The nT1 of EOMs in GO patients was higher than that in GD patients and healthy volunteers. The nT1 of superior rectus (SR) in active GO was higher than that in inactive GO patients, and it could be used as a potential marker of GO activity (OR: 1.003; 95% CI: 1.001, 1.004), with a diagnostic sensitivity of 86.3% and specificity of 43.7%. Meanwhile, the cT1 of SR, inferior rectus (IR), and medial rectus (MR) in inactive GO patients were higher than those in active GO patients. The nT1 of EOMs achieved sufficient diagnostic performance in evaluating the response to glucocorticoid therapy for follow-up active GO patients (AUC, 0.797; sensitivity, 71.9%; specificity, 85.7%). CONCLUSIONS: T1 mapping could quantitatively assess the activity of GO and the response to glucocorticoid therapy in active GO patients and may even potentially reflect the fibrosis of EOMs. CLINICAL RELEVANCE STATEMENT: T1 values can reflect the pathological status of the extraocular muscle. T1 mapping could help to quantitatively assess the clinical activity of GO and the response to glucocorticoid therapy in active GO patients. KEY POINTS: • Graves' ophthalmopathy patients had greater nT1 of extraocular muscles than Graves' disease patients and healthy volunteers, and nT1 of the superior rectus could be a potential marker of Graves' ophthalmopathy activity. • The cT1 of extraocular muscles in inactive Graves' ophthalmopathy patients was higher than that in active Graves' ophthalmopathy patients, and it might be associated with muscle fibrosis. • nT1 of extraocular muscles could offer sufficient diagnostic performance in evaluating the response to glucocorticoid therapy for follow-up active Graves' ophthalmopathy patients.

Risk of Permanent Hypoparathyroidism Requiring Calcitriol Therapy in a Population-Based Cohort of Adults Older Than 65 Undergoing Total Thyroidectomy for Graves' Disease.

Objective: Total thyroidectomy for Graves' disease (GD) is associated with rapid treatment of hyperthyroidism and low recurrence rates. However, it carries the risk of surgical complications including permanent hypoparathyroidism, which contributes to long-term impaired quality of life. The objective of this study was to determine the incidence of permanent hypoparathyroidism requiring calcitriol therapy among a population-based cohort of older adults undergoing total thyroidectomy for GD in the United States. Methods: We performed a population-based cohort study using 100% Medicare claims from beneficiaries older than 65 years with GD who underwent total thyroidectomy from 2007 to 2017. We required continuous enrollment in Medicare Parts A, B, and D for 12 months before and after surgery to ensure access to comprehensive claims data. Patients were excluded if they had a preoperative diagnosis of thyroid cancer or were on long-term preoperative calcitriol. Our primary outcome was permanent hypoparathyroidism, which was identified based on persistent use of calcitriol between 6 and 12 months following thyroidectomy. We used multivariable logistic regression to identify characteristics associated with permanent hypoparathyroidism, including patient age, sex, race/ethnicity, neighborhood disadvantage, Charlson-Deyo Comorbidity Index, urban or rural residence, and frailty. Results: We identified 4650 patients who underwent total thyroidectomy for GD during the study period and met the inclusion criteria (mean age = 72.8 years [standard deviation = 5.5], 86% female, and 79% white). Among this surgical cohort, 104 (2.2% [95% confidence interval, CI = 1.8-2.7%]) patients developed permanent hypoparathyroidism requiring calcitriol therapy. Patients who developed permanent hypoparathyroidism were on average older (mean age 74.1 vs. 72.8 years) than those who did not develop permanent hypoparathyroidism (p = 0.04). On multivariable regression, older age was the only patient characteristic associated with permanent hypoparathyroidism (odds ratio age ≥76 years = 1.68 [CI = 1.13-2.51] compared with age 66-75 years). Conclusions: The risk of permanent hypoparathyroidism requiring calcitriol therapy among this national, U.S. population-based cohort of older adults with GD treated with total thyroidectomy was low, even when considering operations performed by a heterogeneous group of surgeons. These findings suggest that the risk of hypoparathyroidism should not be a deterrent to operative management for GD in older adults who are appropriate surgical candidates.

Does Age or Sex Relate to Severity or Treatment Prognosis in Graves' Disease?

Background: The prognosis of Graves' disease (GD) is reportedly related to sex, age, and genetic factors, although there is no consensus. The objective of this study was to investigate the relationship between severity and prognosis of GD and sex or age. Methods: Subjects were patients newly diagnosed with GD between January 2005 and June 2019, and medical records were retrospectively reviewed. Patients diagnosed between January 2009 and December 2010 and followed up for at least 12 months were enrolled. Patients were divided into nine age-stratified groups. Remission was defined as maintenance of a euthyroid state for more than one year after withdrawal of antithyroid drugs (ATDs). Results: Participants comprised 21,633 patients (3954 males, 17,679 females). Initial free triiodothyronine (fT3) and free thyroxine (fT4) levels significantly decreased with increasing age, including after sex stratification. fT4 was significantly higher in males than females aged 20-39 years. In 2191 patients treated with ATDs alone, median durations until remission were 37.7 and 30.6 months in males and females, respectively. Remission and recurrence were observed in 1391 patients (204 males, 1187 females) and 262 patients (37 males, 225 females), respectively. By Kaplan-Meier analyses, males required a significantly longer time to achieve remission than females (p < 0.0001), although there were no significant age-related differences (p = 0.08). Cox proportional hazard modeling showed a 41% higher hazard ratio (HR) for remission in females than males (adjusted HRs [aHR] confidence interval [CI] = 1.41 [1.21-1.64]), and each additional 10 years of age had a 14% lower rate of recurrence (age [per 10-year increase], aHR [CI] = 0.86 [0.78-0.94]); no significant relationship between recurrence rate and sex was identified. Conclusions: Severity of hyperthyroidism in GD was significantly higher in males in their 20s and 30s, declining with advancing age in both sexes. Females were more likely to achieve remission than males, and younger patients had a higher risk of recurrence, although recurrence was unrelated to sex.

Short-term Change in Resting Energy Expenditure and Body Compositions in Therapeutic Process for Graves' Disease.

Objective In the medical treatment of Graves' disease, we sometimes encounter patients who gain weight after the onset of the disease. To estimate the energy required during the course of treatment when hyperthyroidism ameliorates, we measured the resting energy expenditure (REE) and body composition in patients with Graves' disease before and during treatment in the short-term. Methods Twenty patients with newly diagnosed Graves' disease were enrolled, and our REE data of 19 healthy volunteers were used. The REE was measured by a metabolic analyzer, and the basal energy expenditure (BEE) was estimated by the Harris-Benedict formula. The body composition, including body weight, fat mass (FM), muscle mass (MM) and lean body mass (LBM), were measured by a multi-frequency body composition analyzer. We tailored the nutritional guidance based on the measured REE. Results Serum thyrotropin levels were significantly increased at three and six months. Serum free thyroxine, free triiodothyronine and REE values were significantly decreased at one, three and six months. The REE/BEE ratio was 1.58±0.28 at the onset and significantly declined to 1.34±0.34, 1.06±0.19 and 1.01±0.16 at 1, 3 and 6 months, respectively. Body weight, MM and LBM significantly increased at three and six months. Conclusion The REE significantly decreased during treatment of Graves' disease. The decline was evident as early as one month after treatment. The REE after treatment was lower than in healthy volunteers, which may lead to weight gain. These data suggest that appropriate nutritional guidance is necessary with short-term treatment before the body weight normalizes in order to prevent an overweight condition and the emergence of metabolic disorders.

Glucose variability before and after treatment of a patient with Graves' disease complicated by diabetes mellitus: assessment by continuous glucose monitoring.

A 48-year-old woman was diagnosed and treated for Graves' disease (GD) in 1999 but she discontinued treatment at her own discretion. In 2011, she was admitted to a local hospital for management of thyrotoxic crisis. Treatment with propylthiouracil, iodide potassium (KI), and prednisolone (PSL) was started, which resulted in improvement of the general condition. PSL and KI were discontinued before she was transferred to our hospital. At the local hospital, fasting plasma glucose (FPG) was 212 mg/dL and hemoglobin A1c concentration was 11.2%; intensive insulin therapy had been instituted. Upon admission to our hospital, FPG level was 122 mg/dL, but insulin secretion was compromised, suggesting aggravation of thyroid function and deterioration of glycemic control. The FPG level increased to 173 mg/dL; continuous glucose monitoring (CGM) identified dawn phenomenon at approximately 0400 h. Resumption of KI resulted in improvement of FPG and disappearance of the dawn phenomenon, as assessed by CGM. These results indicate that in patients with compromised insulin secretion, hyperthyroidism can induce elevation of not only postprandial blood glucose, but also FPG level due to the dawn phenomenon and that the dawn phenomenon can be alleviated with improvement in thyroid function. To our knowledge, no studies have assessed glucose variability by CGM before and after treatment of Graves' disease. The observations made in this case shed light on the understanding of abnormal glucose metabolism associated with Graves' disease.

An assessment of psychiatric disturbances in Graves disease in a medical college in eastern India.

BACKGROUND: Graves' disease is a unique conglomeration of cardiovascular, neurological, ophthalmological, and other systemic manifestations. In this study we have tried to explore the psychiatric dimensions of this disease. AIMS: This study attempted to explore clinical features, types, and treatment outcome of psychiatric disturbances in Graves disease. STUDY DESIGN: This is a purposive study following the criteria of DSM IV. MATERIALS AND METHODS: A total of 36 adult patients of newly diagnosed Graves disease and 30 age- and sex-matched controls were included. Data enumerated were age, sex, date of admission, analysis of psychiatric signs, and symptoms by one independent observer, diagnostic categorization, effect of treatment, and outcome. Follow-up evaluation was done after 1 year. Statistical Analysis : Statistical analysis was done by the standard error of difference, the chi-square test, and paired Student's T-test. RESULTS: Among 36 patients 32 were female and 4 were male. Fifteen patients (41.67%) were diagnosed with generalized anxiety disorders (GAD), 6 (16.67%) with mood disorder, 6 (16.67%) with obsessive compulsive disorder (OCD), and 2 each with personality disorder and schizophreniform disorder. The common symptoms were insomnia, irritability, and anxiety. The frequency of GAD was statistically more significant in the Graves disease group in comparison to control. Fourteen patients agreed to take both antithyroid and antipsychotropic medications (group 1). The rest were treated with only antithyroid drug (group 2). There was significant improvement in both groups and no difference between the groups. CONCLUSION: The prevalence of certain psychiatric manifestations in Graves' disease was significantly higher than in the control group. There was no significant difference between therapy with antithyroid drugs and combination of antithyroid with psychotropic medications.

[Cost-effectiveness of the clinical treatment of Grave's disease in a public University Hospital: a retrospective analysis and prospective projection for a therapeutic approach]. / Impacto médico-social do tratamento medicamentoso da moléstia de Graves-Basedow em Hospital Público Universitário: avaliação retrospectiva e projeção prospectiva de conduta terapêutica.

The aim of the present study was to evaluate a new proposal for increasing compliance to the clinical management of patients with Graves' disease (GD) in a large and public University Hospital. The patients were carefully selected (no previous GD treatment, goiter volume less than 6 mL must be living in the metro area of São Paulo), received medication at no cost, were contacted frequently by the social worker and alerted for the date of consultation and only referred to a single endocrinologist during all phases of treatment. We recruited 229 patients with GD that were initially treated with methimazole (MMI--60 mg q.d) in a single daily dose followed by a combination of MMI (20 mg) plus L-T4 (100 microg) daily for 24 months. Only 83 patients (36.2%) completed the protocol and were subdivided in: Group 1 (n= 34) that were in remission for 3 years after discontinuation of the MMI and Group 2 (n= 49) that presented recurrence of GD between 2 and 36 months without MMI. Predictive factors associated with remission were: decrease of the glandular volume, serum TG< 40 ng/mL and normal TRAb values. We concluded that in spite of a careful protocol planned to increase compliance, more than 60% of patients with GD did not complete the therapeutic trial and were referred for radioiodine treatment. The solution for this low therapeutic success for GD should be the possible identification of factors that would indicate patients that are not inclined to follow a long period of clinical therapy.

Impacto médico-social do tratamento medicamentoso da moléstia de Graves-Basedow em Hospital Público Universitário: avaliação retrospectiva e projeção prospectiva de conduta terapêutica / Cost-effectiveness of the clinical treatment of GraveÆs disease in a public University Hospital: a retrospective analysis and prospective projection for a therapeutic approach

O objetivo do presente estudo foi avaliar esquema terapêutico medicamentoso para aumentar a aderência ao tratamento da moléstia de Graves-Basedow (MGB) em Hospital Público Universitário. Os pacientes foram selecionados segundo critérios rigorosos, que incluíam volume glandular inferior a 60cm³, origem da área urbana de São Paulo e não submetidos a terapia prévia da MGB. Receberam gratuitamente a medicação, eram avisados antecipadamente da data da consulta e acompanhados por um único médico durante todo o tratamento. Foram incluídos 229 pacientes, tratados inicialmente com metimazol (MMI - 60mg/dia) em dose única diária, seguindo-se com combinação de MMI (20mg) com LT4 (100æg) em dose única diária por 24 meses. Apenas 83 pacientes (36,2 por cento) completaram o protocolo quando foram subdivididos em 2 grupos, após a suspensão do MMI+LT4: Grupo 1 (n= 34), que permaneceram em remissão por 3 anos, e Grupo 2 (n= 49), que apresentaram recidiva da doença entre 2 e 36 meses. Os fatores preditivos associados à remissão foram: decréscimo do volume glandular, tireoglobulina sérica < 40ng/ml e valores séricos normais de anticorpos anti-receptor de TSH. Constatamos que apesar do planejamento cuidadoso, mais de 60 por cento dos portadores de MGB não completaram o protocolo e foram encaminhados a tratamento com radioiodo. Admitimos que esse baixo êxito terapêutico poderia ser melhorado mediante identificação dos fatores capazes de indicar quais pacientes estariam propensos a seguir um tratamento de longa duração.

[Cost-utility analysis of antithyroid drug therapy versus 131I therapy for Graves' disease].

There is no comparative cost-utility study between 131I therapy and antithyroid drugs (ATD) therapy for Graves' disease, though 131I therapy has higher remission rate and less side effects. The objective of the study was to analyze the cost-utility of ATD therapy versus 131I therapy by calculating life-long medical costs and utility, based on the responses of Graves' disease patients to questionnaires. To determine the expected cost and expected utility, a decision tree analysis was designed on the basis of the 2 competing strategies of ATD therapy versus 131I therapy. A simulation of 1000 female patients weighing > or =50 kg who assumed to experience the onset of Graves' disease at the age of 30, to first complain of thyrotoxic symptoms and moderate goiter 2-3 mo. previously, and to undergo a 40-years-long cohort study, was created for each strategy using a decision tree and baselines of other relevant variables. The variables and costs were based on the literature and hospital bills. The maximum and minimum values of utility were defined as 1.0 and 0.0, respectively. Future costs and utilities were discounted 5%. The medical costs and utilities were 85,739-88,650 yen/patient/40 years and 16.47-16.56/patient/40 years, respectively, for the ATD therapy strategy, and 81,842 yen/patient/40 years and 17.41/patient/40 years, respectively, for the 131I therapy strategy. These results quantitatively demonstrated that the 131I therapy strategy was superior to the ATD therapy strategy in terms of both cost and utility. 131I therapy should be used more widely in Japan because of its greater utility and lower cost.

[The assessment of usefulness of humoral markers estimation in patients with autoimmune thyroid diseases]. / Ocena przydatnosci oznaczania wskazników odpowiedzi humoralnej u chorych z autoimmunologicznymi chorobami tarczycy.

UNLABELLED: Autoimmune thyroid diseases (AITD) constitute a group of the most common disorders caused by autoaggression of the immune system, comprising up to 1.5% of the human population. That is why optimalisation of diagnostics of Hashimoto thyroiditis (ChH) and Graves' disease (ChG) is an important issue. Aim of the study was to assess usefulness of humoral markers estimation: antithyroperoxidase antibodies (anty-TPO), antithyreoglobulin antibodies (anty-TG) and antithyroropin receptor antibodies (anty-TSHR). MATERIAL AND METHODS: The study was carried out in 5 groups of subjects: 1/14 patients with GD in euthyreosis on methimazol (Geu) 2/20 patients with hyperthyroid GD (Ghiper) 3/15 patients with ChH in euthyreosis on levothyroxine (Heu) 4/16 patients with hypothyroid ChH (Hhipo) 5/12 healthy volunteers age and sex-matched to group 1-4. The serum levels of anty-TPO and anty-TG were determined by the ELISA kit. Anty-TSHR were measured by the RIA method. RESULTS: The highest level of anty-TPO were observed in Hhipo group: 2.81 IU/I (1.79-3.22) (p<0.001 vs controls, p<0.05 vs ChH in euthyreosis). Among ChG patients higher values of anty-TPO were found in Ghiper group: 1.87 IU/I (0.68-2.88) (p<0.01 vs controls, p<0.05 vs ChG in euthyreosis). In ChH patients a positive correlation was observed between serum TSH and anty-TPO (R=0.47, p<0.01). In studied groups it was found a positive correlation between anty-TPO and anty-TG. Levels of anty-TG were increased in all studied patients as compared to controls, however there were no significant differences in anty-TG values between the groups. The highest concentration of anty-TSHR were found in Ghiper group: 6.71 (3.92-11.32) (p<0.001 vs controls, p<0.001 vs ChG in euthyreosis). There was a significant difference in anty-TSHR concentration between ChH groups: Hhipo i Heu (p<0.05). There was a negative correlation between serum TSH and anty-TSHR level in ChG patients (R=-0.05, p<0.001). CONCLUSIONS: In diagnostics of humoral markers in patients with AITD the most valuable in clinical practice is estimation of antithyroperoxidase antibodies serum level in Hashimoto thyroiditis and antithyroropin receptor antibodies serum concentration in Graves' disease.

Pentoxifylline (PTX)--an alternative treatment in Graves' ophthalmopathy (inactive phase): assessment by a disease specific quality of life questionnaire and by exophthalmometry in a prospective randomized trial.

PURPOSE: To investigate the effect of pentoxifylline (PTX) in subjects with inactive Graves' ophthalmopathy (GO) through a specific quality of life (QOL) questionnaire and exophthalmometry readings. METHODS: Eighteen females were randomly divided in two groups. Group A (n=9) was treated with PTX 1200 mg orally/day for 6 months. Group B (n=9) received placebo during the initial 6 months and then PTX for another 6 months. Proptosis measurements were carried out every 3 months and a questionnaire graded from 0 to 10 according to the severity of the symptoms was performed at baseline and after placebo and PTX administration. RESULTS: At baseline, Group A questionnaire score values were 5.5 (median; range 3.5 to 8.0), and 5.0 after 6 months (3.0 to 6.0; p=0.01). In Group B, baseline values were not significantly different after 6 months of placebo: 6.0 (4.5 to 7.0) and 5.5 (4.5 to 7.0), respectively. However, a significant change was observed 6 months after PTX: 4.0 (2.0 to 5.0; p<0.001). Patients in Group A had a progressive improvement of proptosis during PTX: at baseline, 23 mm (median; range 20 to 32); after 3 months, 23 mm (18 to 30; p=0.02); and after 6 months, 23 mm (18 to 30; p=0.005). In Group B, proptosis remained stable during placebo: at baseline, 23 mm (21 to 25); after 3 months, 23 mm (20 to 25); and after 6 months, 23.5 mm (20 to 25). A significant change was observed after 3 and 6 months of PTX: 22 mm (19 to 24; p=0.0006) and 20.8 mm (17 to 25; p=0.0003), respectively. CONCLUSIONS: Pentoxifylline seems to improve the QOL of patients in the inactive phase of GO. The objective findings of the proptosis readings corroborate to suggest that PTX may be an effective and promising drug in the inactive phase of GO.

[Assessment of early immunosuppressive therapy in the prevention of complications of Graves' disease]. / Ocena wczesnego zastosowania leczenia immunosupresyjnego w zapobieganiu powiklaniom choroby Graves-Basedowa.

UNLABELLED: Regardless the autoimmune origin of Graves' disease, the preferred method of its treatment remains antithyroid drug administration. Use of immunosuppressive agents (mostly steroids) is still limited to the therapy of disease complications, such as proliferative ophthalmopathy. The aim of the study was to assess the influence of early immunosuppressive treatment of autoimmune thyrotoxicosis with azathioprine on the course of the disease and the incidence of its complications. The study comprised 64 patients (47 females and 17 males aged 20-43 years) for the first time diagnosed with Graves' disease. The subjects were randomised into two groups. Group I consisted of 28 patients treated only with antithyroid drugs, the remaining 36 subjects additionally receiving azathioprine were included into group II. The dose of both drugs was adjusted during the treatment according to metabolic status of each patients. The treatment was continued for 8-14 months, the follow-up duration after therapy withdrawal was 5 years. Euthyreosis was achieved in all patients 2-8 weeks after treatment initiation. No drug intolerance symptoms were observed in group I. In four patients additionally treated with azathioprine, gastrointestinal side effects or leucopenia were present. The disease relapse was observed during the follow-up period in 15 (53.5%) patients of group I and in 3 (8.3%) of group II, the difference was statistically significant (p<0.01). Only one patient receiving additionally azathioprine presented ophthalmic symptoms compared with seven subjects (25%) treated only with antithyroid drugs (p<0.001). The patients of group I were also more frequently referred to surgical treatment due to rapid goitre growth (accordingly 5 (17.8%) and 1 (2.7%) patients, p=0.07), the difference between both groups not being statistically significant. CONCLUSIONS: Additional early immunosuppressive treatment significantly decreased frequency of Graves' disease complications and thyrotoxicosis recurrence. The use of azathioprine may be advised in patients with contraindications to the radical Graves' disease treatment and in prophylaxis of its complications.

The cost of immunosuppressive therapies currently used in patients with thyroid eye disease.

Thyroid eye disease (TED) is an inflammatory condition of the orbit occurring in patients with autoimmune disease. In patients with mild TED, the most important therapeutic measure is reassurance. In severe cases, immunosuppressive therapy is the mainstay of treatment and around 10 immunosuppressive regimens have been suggested and used in such patients so far. The efficacy of these regimens varies according to the number of studies that have addressed these issues. "Response" to the treatment is also variably defined. However, to the best of our knowledge, no study has reported on the cost of immunosuppressive therapy in such patients. The aim of this study was mainly to provide information concerning the cost of different immunosuppressive regimens that patients with active thyroid ophthalmopathy undergo in different European countries. We have shown that the cheapest treatment is oral glucocorticoids (GC) and the most expensive is iv immunoglobulins. Cyclosporine is the second cheapest treatment. Radiotherapy plus oral GC have a cost between 850-3200 Euro; while SS analogues (SS-a) are expensive with a cost between 5000-10000 Euro. However, it is worth noting that the patients studied so far in this group were only few and most of them selected on a basis of a positive octreoscan, the cost of which has to be considered when choosing this type of treatment. Germany is by far the most expensive country as regards the costs of the main remedies, whereas Greece is the cheapest. Denmark is the most expensive country concerning radiotherapy, while Germany is the cheapest.

Avaliaçäo do intervalo de tempo e custo médio para a obtençäo do eutiroidismo na doença de Graves tratada com drogas antitiroidianas em um hospital geral / Evaluation of time interval middle cost for obtention of euthyroidism in Grave's disease treated with antithyroid drugs in a geral hospital

Os pacientes com doença de Graves tornam-se eutiróideos usualmente 6 a 12 semanas após iniciar os antitiroidíanos. Aderência à medicaçäo é vital para o sucesso da terapêutica. Com os objetivos de avaliar retrospectivamente o tempo necessário para a obtençäo do eutiroidismo clínico e laboratorial e o custo da terapêutica clínica, analisamos 82 pacientes com doença de Graves atendidos entre fevereiro/96 e novembro/97 e acompanhados até julho/99. Destes, 49 (59,8 por cento) foram acompanhados até o eutiroidismo, ocorrido em 24,8 semanas. Apenas 11 alcançaram o eutiroidismo em 12 semanas. Dezesseis pacientes näo aderentes despenderam tempo significantemente maior até o eutiroidísmo que os aderentes (37,3 vs. 18,7 semanas). O abandono do tratamento ocorreu em 36,6 por cento dos pacientes. O custo do tratamento em 24,8 semanas somou R$248,72, contra R$151,68 em 12 semanas. Assim, nossos pacientes demoram mais tempo para alcançar o eutiroidísmo que o usualmente descrito, implicando em um custo 64 por cento maior. A falta de aderência é a justificativa mais importante para este atraso na compensaçäo da tirotoxicose.

[The assessment of urinary glycosaminoglycans (GAG) excretion during therapy of patients with progressive Graves' ophthalmopathy]. / Ocena wydalania z moczem glikozaminoglikanów (GAG) w trakcie leczenia postepujacej oftalmopatii obrzekowo-naciekowej w przebiegu choroby Gravesa i Basedowa.

Excessive accumulation of hydrophilic glycosaminoglycans (GAG) in the retrobulbar tissue leads to many of the clinical manifestations of Graves' ophthalmopathy (GO). We examined the quantitative urinary GAG excretion in 35 patients with GO. GAG were isolated from 24-h urine collections by precipitation with cetylpyridinum chloride and ethanol according to Bitter. Patients with progressive ophthalmopathy showed on the average a twofold increase in urinary GAG excretion in comparison to patients with stable ophthalmopathy. The elevated values of GAG decreased significantly under treatment and correlated with the clinical picture of GO, however no correlation was found between the urinary GAG values and actual severity of ophthalmopathy classified according to Werner and Donaldson. There was no significant difference in GAG excretion between group 1, treated with methylprednisolon and irradiation of retrobulbar tissue and group 2, under therapy with methylprednisolon. In conclusion, elevated urinary GAG excretion is characteristic for the clinical picture of the progressive GO. The remarkable decrease in GAG values during treatment correlated to the positive response to immunosuppressive therapy.

Color Doppler measurement of blood flow in the inferior thyroid artery in patients with autoimmune thyroid diseases.

PURPOSE: The aim of the study is to find out whether the measurement of peak systolic velocity in the inferior thyroid artery (ITA) is a valuable parameter to differentiate autoimmune thyroid diseases (hyper-, normo- or hypofunctional) and to evaluate the efficacy of medical treatment. MATERIAL AND METHODS: The ITA of 31 patients (eight with Graves' disease, 23 with subclinical hypothyroidism) was examined with color Doppler and pulsed Doppler. The final diagnosis was obtained by cytology and by hormonal and antibodies assays. The patients were monitorized by ultrasound for a period of 8 months. RESULTS: In all the patients with Graves' disease the peak systolic velocity was always over 150 cm/s, while in other autoimmune thyroiditis the peak systolic velocity was within the normal range, and never exceeding 65 cm/s. In the first group, the measurement taken in the ITA showed also the efficacy of the pharmacological treatment earlier and more reliably than the color Doppler pattern obtained in the parenchyma. CONCLUSIONS: The color Doppler measurement of the ITA seems to be a promising technique with low-cost and easy approach. In our experience, the color Doppler of the ITA could have a clinical role in the differential diagnosis of diffuse thyroid diseases and in the follow-up of the Graves' disease during medical treatment.

Optimizing the diagnostic criteria for standard (250-microg) and low dose (1-microg) adrenocorticotropin tests in the assessment of adrenal function.

ACTH stimulation is the standard test for assessment of adrenal function. It was suggested that the low dose (1 microg) would be more sensitive for detecting mild secondary adrenal insufficiency than the usual dose of 250 microg. The aim of this study was to find the optimal diagnostic criteria and to compare standard dose test (SDT) with the low dose test (LDT). A group of patients treated with corticosteroids for the 6 months was considered to have hypothalamo-pituitary-adrenal impairment. Studies were performed in 14 corticosteroid-treated and 28 control subjects in random order on 2 consecutive days. Tests were analyzed using the receiver operating characteristic curve method. The best test was cortisol increment at 15 min of the LDT. It was significantly better than the cortisol concentration at 15 min of the SDT, the best test during the SDT (receiver operating characteristic curve area and 95% confidence interval: LDT, 0.997 and 0.956-0.999; SDT, 0.827 and 0.662-0.929; P = 0.0113). For the cortisol increment at 15 min of the LDT at 100% sensitivity, the diagnostic value was 100 mmol/L, and the specificity was 96%. Therefore, the LDT is superior to the standard dose test in the assessment of secondary adrenal insufficiency.