Change in newly diagnosed Graves' disease phenotype between the twentieth and the twenty-first centuries: meta-analysis and meta-regression.

PURPOSE: According to a few recent studies, the clinical phenotype of Graves' disease (GD) at onset is becoming milder in recent years, in terms of prevalence and severity of hyperthyroidism, goiter and overt eye disease. The aim of this study was to assess the change in GD phenotype across the late twentieth and the early twenty-first centuries. MATERIALS AND METHODS: We carried out a systematic search of studies published between 1/1/1980 and 12/31/2017 describing naïve GD patients at diagnosis. We collected epidemiological, clinical, biochemical and serological data reported in the selected studies, and (1) conducted a single-arm meta-analysis to compare clinical and biochemical characteristics of naïve GD patients before and after year 2000 and (2) performed a meta-regression to identify the trend of the observed clinical presentations. RESULTS: Eighty selected articles were related to the period before the year 2000, 30 to the years 2000-2017. According to demographics, the two defined populations were homogeneous at meta-analysis: overall estimated female prevalence was 81% [95% CI 79-82], mean estimated age of the entire population was 39.8 years [95% CI 38.4-41.1], with no significant differences between pre- and post-2000 groups (p > 0.05). The overall estimated prevalence of smokers was 40% [95% CI 33-46], with no significant difference between the two groups (p > 0.05). Mean estimated free thyroxine (FT4) and free triiodothyronine (FT3) levels at diagnosis were higher in the pre-2000 group: 4.7 ng/dl [95% CI 4.5-4.9] for FT4 and 14.2 pg/ml [95% CI 13.3-15.1] for FT3, as compared to the post-2000 group: 3.9 ng/dl [95% CI 3.6-4.2] for FT4 and 12.1 pg/ml [95% CI 11.0-13.3] for FT3 (all p < 0.01). Goiter estimated prevalence was higher in the pre-2000 group, 87% [95% CI 84-90], than in the post-2000 group, 56% [95% CI 45-67]. Estimated prevalence for Graves' Orbitopathy (GO) was 34% [95% CI 27-41] in the pre-2000 group and 25% [95% CI 19-30] in the post-2000 group (p = 0.03). Accordingly, meta-regression adjusted for covariates showed an average annual reduction of FT4 (- 0.040 ± 0.008 ng/dl, p < 0.0001), FT3 (- 0.316 ± 0.019 pg/ml, p < 0.0001), goiter prevalence (- 0.023 ± 0.008%, p = 0.006), and goiter size (- 0.560 ± 0.031 ml, p < 0.0001). CONCLUSIONS: Our meta-analysis and meta-regression confirmed that GD phenotype at diagnosis is nowadays milder than in the past; we hypothesize that conceivable factors involved in this change are iodoprophylaxis, worldwide decrease in smoking habits, larger use of contraceptive pill and micronutrient supplementation, as well as earlier diagnosis and management.

Autoimmune gastritis.

Autoimmune gastritis (AIG) is an increasingly prevalent, organ-specific, immune-mediated disorder characterized by the destruction of gastric parietal cells, leading to the loss of intrinsic factor and reduced acid output. These alterations result in malabsorption of iron, vitamin B12 (pernicious anaemia) and potentially other micronutrients. For several years, most studies have focused on pernicious anaemia only, generating confusion between the two entities. In AIG, the gastric proton pump, H+/K+ ATPase, is the major autoantigen recognized by autoreactive T cells. The T cell-dependent activation of B cells stimulates the production of anti-parietal cell antibodies, the serological hallmark of AIG. The role of Helicobacter pylori infection in activating or favouring the autoimmune process is still uncertain. Early histopathological alterations allowing a more precise and prompt recognition have recently been described. AIG is burdened by a substantial diagnostic delay as it can present with varied clinical signs including, among others, gastrointestinal symptoms and neuropsychiatric manifestations. In advanced stages, AIG might progress to neuroendocrine tumours and gastric adenocarcinoma. Management includes early detection through a proactive case-finding strategy, micronutrient supplementation and endoscopic surveillance. This Primer comprehensively describes the most important insights regarding the epidemiology, pathophysiology, diagnosis and management of AIG, focusing on the most controversial, outstanding issues and future directions.

Effect of Different 131I Dose Strategies for Treatment of Hyperthyroidism on Graves' Ophthalmopathy.

PURPOSE: The study aims to define the effect of different dose strategies on ophthalmic complications in patients with Graves' disease (GD). METHODS: All the patients with GD and no or inactive ophthalmopathy (clinical activity score; CAS < 3) underwent Snellen chart examination, measurement of proptosis, thyroid volume, and radioactive iodine uptake, and randomized into 1 of 3 groups. In group 1, all the patients received fixed low dose (FLD) of 259 MBq of I, whereas in group 2, all the patients received fixed high dose (FHD) of 555 MBq, and in group 3, calculated dose (CD) was administered to deliver 5.55 MBq/g (thyroid weight) of I. All examinations were repeated 6 months after treatment. The measurement of thyroid function tests and clinical examination were repeated after 12 months. RESULTS: We studied 92 patients (58 female and 34 male) with mean age of 38.2 ± 12.0 years. Overall, 29, 32, and 31 patients were studied in FLD, FHD, and CD groups, respectively. The patients in CD received a mean activity of 240.5 MBq. The 3 groups were not significantly different regarding age, sex ratio, radioactive iodine uptake, smoking, visual acuity, and proptosis. The response rate 12 months after radioactive iodine therapy was 66.7%, 94.4%, and 92.9% in FLD, FHD, and CD groups, respectively (P = 0.05). Overall, CAS was increased significantly after treatment. Delta proptosis and delta CAS were increased significantly in FHD group compared with other groups (P < 0.05). The highest increment in proptosis was seen in FHD group. CONCLUSIONS: The administration of 5.55 MBq/g of I has fewer ophthalmic complications compared with high fixed dose model and is more effective than low fixed dose strategy.

Effects of Supplemental Vitamin D on Muscle Performance and Quality of Life in Graves' Disease: A Randomized Clinical Trial.

Background: Vitamin D deficiency has been proposed to have a role in the development and course of Graves' disease (GD). Muscle weakness and quality of life (QoL) impairments are shared features of GD and vitamin D deficiency. We aimed at investigating whether vitamin D supplementation would improve restoration of muscle performance and thyroid-related QoL in GD and at describing the effect of anti-thyroid medication (ATD) on these outcomes. Methods: In a double-blinded clinical trial, hyperthyroid patients with a first-time diagnosis of GD were randomized to vitamin D 70 µg (2800 IU)/day or matching placebo as add-on to standard ATD. At baseline and after 3 and 9 months of intervention, we assessed isometric muscle strength, muscle function tests, postural stability, body composition, and QoL-impairment by using the ThyPRO questionnaire. Linear mixed modeling was used to analyze between-group differences. (The DAGMAR study clinicaltrials.gov ID NCT02384668). Results: Nine months of vitamin D supplementation caused an attenuation of muscle strength increment in all muscle measures investigated, significant at knee extension 60° where the increase was 24% lower (p = 0.04) in the vitamin D group compared with placebo. Compared with placebo, vitamin D supplementation tended to reduce gain of lean body mass (-24%, p = 0.08). Vitamin D supplementation significantly impeded alleviation of Composite QoL and the same trend was observed for the Overall QoL-Impact and Impaired Daily Life scales. In response to ATD, all measures improved significantly. The increase in muscle strength ranged from 25% to 40% (pall < 0.001), and increment of lean body mass was 10% (p < 0.001). Large changes were observed in all QoL scales. Conclusions: Nine months of vitamin D supplementation caused unfavorable effects on restoration of muscle performance. In contrast, ATD treatment was associated with marked improvement in all measures of muscle performance and thyroid-related QoL. In patients with newly diagnosed GD, high-dose vitamin D supplementation should not be recommended to improve muscle function, but ATD is of major importance to alleviate muscle impairment.

Effect of 9 months of vitamin D supplementation on arterial stiffness and blood pressure in Graves' disease: a randomized clinical trial.

PURPOSE: Risk of cardiovascular disease (CVD) is increased in Graves' disease (GD). CVD is predicted by increased pulse wave velocity (PWV) and blood pressure (BP). GD and these risk factors are all associated with lower levels of vitamin D. We aimed to assess the effect of supplemental vitamin D on PWV and BP in GD. METHODS: In a double-blinded trial, newly diagnosed GD patients were randomized to vitamin D3 70 µg/day (n = 44) or placebo (n = 42) as add-on to anti-thyroid medication. At baseline, 3 and 9 months PWV, BP and wave analysis were performed in office and 24 h setting. Between-group differences in change at 9 months were analyzed using linear mixed modelling. In subanalysis, effect of intervention in regard to baseline vitamin D insufficiency (25(OH)D < 50 nmol/L) was investigated. (The DAGMAR study, clinicaltrials.gov ID NCT02384668). RESULTS: PWV was unaffected by intervention in main analysis. However in the subanalysis, comparing the response to intervention in the vitamin D insufficient (n = 28) and the vitamin D replete patients, supplemental vitamin D induced a significant decrease in office PWV of 1.2 (95% CI: -2.3; -0.1) m/s compared to placebo. Of notice, baseline PWV was non-significantly higher among the vitamin D insufficient as compared to the replete participants. In response to vitamin D, office central systolic BP (-3.9 (95% CI: -7.5; -0.3) and brachial mean BP (-3.3 (95% CI: -6.5; -0.3) declined whereas 24 h measurements were unaffected. CONCLUSIONS: High-dose vitamin D supplementation did not affect PWV. We observed significant reduction in office but not 24 h BP. Subanalysis showed a clinically relevant PWV reduction among vitamin D insufficient participants, although regression towards the mean might contribute to findings. Further studies on supplemental vitamin D in GD should focus on patients with vitamin D insufficiency.

Investigational drugs in early stage clinical trials for thyrotoxicosis with hyperthyroidism.

INTRODUCTION: Thyrotoxicosis with hyperthyroidism is treated with these classical approaches (i) antithyroid drugs to blockade thyroid hormone release and normalize thyroid hormone production and (ii) destruction of the thyroid using radioiodine or surgical removal of the thyroid. The optimal medical therapy, especially for Graves´ disease, remains a subject of debate and there has been little progress in Graves' disease therapeutics over the last decade. AREAS COVERED: Novel treatments of thyrotoxicosis with hyperthyroidism. This includes (i) small molecules such as synthetic thyroid hormone receptor antagonists and environmental molecules and (ii) molecules with interaction between thyroid stimulating hormone (TSH) receptor and TSH receptor antibodies such as M22, ANTAG3, org274179-0, 5C9, and K1-70. Other approaches to Graves´ disease treatment includes immunosuppressive treatment, glucocorticosteroids, rituximab, and intrathyroid injection of dexamethasone. Optimal iodine and selenium supplementation can also be considered. EXPERT OPINION: Clinical trials results suggest that novel thyroid treatments involving small molecule therapy, may predict a good future in Graves' disease treatment; however, a greater understanding of these antagonists is needed. Other treatments comprising immunosuppressives have demonstrated a significant reduction of relapse of the disease, but are not recommended by international guidelines.

Serum Trace Elements Profile in Graves' Disease Patients with or without Orbitopathy in Northeast China.

OBJECTIVE: The purpose of the present study was to investigate serum trace elements in Graves' disease (GD) patients with or without orbitopathy in Northeast China. METHODS: Patients with newly diagnosed Graves' disease (HyGD) (n = 66), GD patients with euthyroid status or subclinical thyroidism after treatment (EUGD) (n = 55), GO patients with euthyroid status or subclinical thyroidism after treatment (GO) (n = 57), and normal controls (NC) (n = 66) were enrolled in this study. Serum trace elements were measured with ICP-MS. RESULTS: Serum selenium (Se) levels in EUGD group (median: 7.53 µg/dL), HyGD group (median: 6.76 µg/dL), and GO group (median: 7.40 µg/dL) were significantly lower than those in NC group (median: 9.20 µg/dL, all P < 0.01). Serum copper (Cu) levels in GO group (median: 95.93 µg/dL) were significantly lower than those in the NC group (median: 113.59 µg/dL, P = 0.015). After being adjusted for multivariables, thyroid-specific antibodies grade was associated with low Se levels. Hyperthyroidism and thyroid-specific antibodies grade were associated with high Cu levels. In addition, orbitopathy was associated with low Cu levels. CONCLUSIONS: Thyroid autoimmunity was associated with low Se levels. Hyperthyroidism and thyroid autoimmunity may be associated with relatively high serum Cu levels. Alternatively, ophthalmopathy may be related to low serum Cu levels.

Effect of Goiter Dispersion Formula on Serum Cytokines in Hyperthyroidism Patients with Neurologic Manifestations of Graves' Disease: A Randomized Trial on 80 Cases.

PURPOSE: This study is aimed to explore the combined use of goiter dispersion formula and antithyroid drugs in the treatment of patients with neurologic manifestations of Graves' disease by examining its modulating effects on patients' cytokines. METHODS: A total of 80 patients with Graves' disease were randomly divided into treatment and control groups. Patients of the treatment group received goiter dispersion formula and antithyroid drugs (methimazole or propylthiouracil), whereas those of the control group received antithyroid drug alone. FT3, FT4, and TSH contents were detected by chemiluminescence immunoassay at pre- and post-treatment; interleukin (IL)-2, IL-8, and IL-17 serum levels before and after the treatment were detected by radioimmunoassay; thyroid B-mode ultrasound and liver and renal function tests were performed in all patients of both groups. An additional cohort of 40 healthy subjects was recruited for baseline measurement. RESULTS: All the enrolled patients completed the trial. The effective treatment rate was higher in the treatment group than in the control group, of which the difference was statistically significant (treatment group, 95%; control group, 75%, p < 0.01). For blood cytokine, before treatment, IL-2 was reduced whereas IL-8 and IL-17 were increased significantly in both groups of patients with Graves' disease comparing with those in healthy subjects (p < 0.01). For patients of the treatment group, after treatment, their IL-2 levels were increased (p < 0.01) with concomitant decreases in IL-8 and IL-17 levels (p < 0.05). There were no significant changes in blood cytokine levels before and after treatment in the control group. CONCLUSIONS: Goiter dispersion formula significantly improved the treatment outcomes of antithyroid drug in hyperthyroidism patients with neurologic manifestations of Graves' disease by modulating IL-2, IL-8, and IL-17. The data supported the rationale for the use of goiter dispersion formula in Graves' disease treatment.

Clinical efficacy of Yingliu mixture combined with metimazole for treating diffuse goitre with hyperthyroidism and its impact on related cytokines.

CONTEXT: Yingliu mixture was developed in 1990s by Affiliated Longhua Hospital of Shanghai University of Traditional Chinese Medicine, for treating diffuse goitre with hyperthyroidism (Graves' disease, GD). Former studies have shown Yingliu mixture combined with methimazole (Y-M) can effectively improve thyroid function and decrease thyrotropin-receptor antibody level. Furthermore, we researched its impact on related cytokines to prove that Y-M improve patients' immunity status. OBJECTIVE: To observe the clinical efficacy of Y-M for treating GD. METHODS: A total of 120 GD patients were randomly divided into two groups, the treatment and the control groups (n = 60). The treatment group's patients were treated with Y-M. The control group's patients were treated with methimazole alone. Yingliu mixture was orally administered, 25 mL three times daily. Methimazole was administered at 5-25 mg/day. After 12 weeks of the treatment, the cytokines, antibodies related to thyroid function, and Chinese medical syndromes were evaluated. RESULTS: After the treatment, the free triiodothyronine and thyroxine levels in both groups decreased. The thyroid-stimulating hormone level increased in the treatment group. The thyrotropin-receptor antibody levels and TNF-α levels decreased in both groups. In the control group, IL-6 and IFN-γ levels were lower than that before the treatment. In the treatment group, CD4+ and CD25+ levels were higher than pretreatment levels, but IL-10 levels were reduced. CLINICAL SYMPTOMS: the total CMS scores for both groups decreased. CONCLUSIONS: The Y-M combination can improve thyroid function, and decrease autoantibodies, cytokines, and clinical symptoms, so its efficacy may surpass that of methimazole alone.

Antenatal management of recurrent fetal goitrous hyperthyroidism associated with fetal cardiac failure in a pregnant woman with persistent high levels of thyroid-stimulating hormone receptor antibody after ablative therapy.

High titer of maternal thyroid-stimulating hormone receptor antibody (TRAb) in patients with Graves' disease could cause fetal hyperthyroidism during pregnancy. Clinical features of fetal hyperthyroidism include tachycardia, goiter, growth restriction, advanced bone maturation, cardiomegaly, and fetal death. The recognition and treatment of fetal hyperthyroidism are believed to be important to optimize growth and intellectual development in affected fetuses. We herein report a case of fetal treatment in two successive siblings showing in utero hyperthyroid status in a woman with a history of ablative treatment for Graves' disease. The fetuses were considered in hyperthyroid status based on high levels of maternal TRAb, a goiter, and persistent tachycardia. In particular, cardiac failure was observed in the second fetus. With intrauterine treatment using potassium iodine and propylthiouracil, fetal cardiac function improved. A high level of TRAb was detected in the both neonates. To the best of our knowledge, this is the first report on the changes of fetal cardiac function in response to fetal treatment in two siblings showing in utero hyperthyroid status. This case report illustrates the impact of prenatal medication via the maternal circulation for fetal hyperthyroidism and cardiac failure.

Euthyroid Graves' orbitopathy and incidental papillary thyroid microcarcinoma.

UNLABELLED: Euthyroid Graves' orbitopathy (GO) combined with incidental papillary thyroid microcarcinoma has rarely been reported. CASE REPORT: A 61-year-old Caucasian woman initially presented with progressive fatigue, exophthalmos, and thyroid function tests within normal limits. She underwent thyroidectomy, was found to have two incidental papillary thyroid microcarcinomas, and received radioactive iodine ablation to eliminate thyroid antigen. In addition to following her eye disease, TSH-receptor antibodies, thyroid stimulating immunoglobulins, and serum thyroglobulin measurements were recorded, demonstrating no evidence of thyroid cancer at four-year follow-up. At first, she had mild GO, developing into moderate-to-severe GO, and at 4 years she had Hertel measurements of 20 mm in both eyes. CONCLUSION: This report underscores the difficulty of managing GO even when thyroid function is normal(ized) and thyroid antigen exposure has been minimized. In addition, it illustrates why antithyroidal antibodies should be considered in cases of concomitant papillary thyroid cancer, as thyroid cells can be stimulated not only by TSH but also by TSH-receptor stimulating antibodies.

Treatment of pretibial myxedema with dexamethazone injected subcutaneously by mesotherapy needles.

Pretibial myxedema (PTM) is a rare extrathyroidal manifestation of Graves' disease that requires treatment when the clinical picture is markedly evident. In addition to topical treatment with steroid ointments, there have been previous reports of subcutaneous injections of steroids. This procedure may cause nodular degeneration of the skin due to fat atrophy when standard needles are used. In the present study, we have tried a novel modality of treatment of PTM by injecting a solution of dexamethasone in the subcutaneous tissue using needles employed for mesotherapy. These needles are ≤4 mm long and deliver the medication within the dermis or the first layer of the subcutaneous fat. We have treated five patients, four with diffuse and one with elephanthiasic PTM. We utilized multiple injections of a solution of dexamethasone, lidocaine, and saline in the PTM plaque and in the pretibial area, both in the PTM plaque and in the area surrounding the lesions, once a week for three consecutive weeks. Two patients with a more severe form of PTM underwent another two cycles four to six weeks after initial treatment. Patients were studied before and after treatment by clinical assessment and ultrasound of the pretibial skin. The treatment was well-tolerated, with only moderate pain upon injection of the solution. One month after treatment, all patients showed improvement of PTM at clinical assessment and a reduction of the thickness of the lesions at ultrasound of ∼15%, involving mostly the dermis. Moreover, all patients reported amelioration of the leg appearance. The present study, although preliminary, shows that intralesion steroid injection with mesotherapy needles in PTM is effective and well tolerated, and does not cause undesired long-term modifications of the skin. More studies are warranted to standardize such treatment in larger groups of patients.

Thyroid function after subtotal thyroidectomy in patients with Graves' hyperthyroidism.

BACKGROUND: Subtotal thyroidectomy is a surgical procedure, in which the surgeon leaves a small thyroid remnant in situ to preserve thyroid function, thereby preventing lifelong thyroid hormone supplementation therapy. AIM: To evaluate thyroid function after subtotal thyroidectomy for Graves' hyperthyroidism. SUBJECTS AND METHODS: We retrospectively reviewed the medical records of all patients (n = 62) who underwent subtotal thyroidectomy for recurrent Graves' hyperthyroidism between 1992 and 2008 in our hospital. Thyroid function was defined according to plasma TSH and free T4 values. RESULTS: Median followup after operation was 54.6 months (range 2.1-204.2 months). Only 6% of patients were euthyroid after surgery. The majority of patients (84%) became hypothyroid, whereas 10% of patients had persistent or recurrent hyperthyroidism. Permanent recurrent laryngeal nerve palsy and permanent hypocalcaemia were noted in 1.6% and 3.2% of patients, respectively. CONCLUSION: In our series, subtotal thyroidectomy for Graves' hyperthyroidism was associated with a high risk of postoperative hypothyroidism and a smaller, but significant, risk of persistent hyperthyroidism. Our data suggest that subtotal thyroidectomy seems to provide very little advantage over total thyroidectomy in terms of postoperative thyroid function.

Evaluation of oxidative status in patients with hyperthyroidism.

Data on the antioxidant levels enzyme in patients with hyperthyroidism are limited and conflicting. Therefore, the objective of this study was to evaluate the oxidative status using an automated method in patients with hyperthyroidism. Thirty-six subjects with hyperthyroidism and 30 healthy controls were enrolled in this study. Serum oxidative status was determined via measurement of total antioxidant capacity (TAC) and total oxidant status (TOS) and calculation of oxidative stress index (OSI). Serum TAC levels were significantly lower in patients with hyperthyroidism than controls (P=0.002), while serum TOS levels and OSI values were significantly higher (P=0.008, 0.004; respectively). Serum TAC levels were correlated with TSH levels (rho=0.223, P=0.032), FT3 levels (rho=-0.434, P=0.002) and FT4 levels (rho=-0.363, P=0.003) in patients. Further, TOS levels and OSI values were correlated with TSH levels (rho=-0.245, P=0.037; rho=-0.312, P=0.011, respectively), FT3 levels (rho=0.293, P=0.017, rho=0.505, P=0.002, respectively), and FT4 levels (rho=0.302, P=0.006, rho=0.321, P=0.008, respectively) in patients. Duration of disease was significantly correlated with OSI values in patients (rho=0.420, P=0.011), while no correlation with serum TAC levels and TOS levels (P>0.05). Oxidants are increased and antioxidants are decreased in patients with hyperthyroidism; as a result, the oxidative-antioxidative balance is shifted to the oxidative side. Increased oxidative stress may play a role in the pathogenesis of hyperthyroidism. It is believed that supplementation of antioxidant vitamins such as vitamins C and E may be helpful for these patients.

[Observation on therapeutic effect of picking therapy on Graves' disease].

OBJECTIVE: To observe therapeutic effect of picking therapy on Graves' disease (GD) and its effects on thyroid function. METHODS: Sixty cases of GD were randomly divided into a treatment group (pricking therapy group) and a control group (medication group). They were treated respectively with pricking thyroid gland high point or oral administration of tapazole. And changes of total triiodothyronine (TT3), total thyroxine (TT4), free T3 (FT3), free T4 (FT4), thyroxine receptor antibody (TRAb), supersensitive thyrotropin (S-TSH) after treatment were investigated. RESULTS: The total effective rate was 93.33% in the treatment group and 76.67% in the control group with a significant difference between the two groups (P < 0.05). After treatment, serum TT3, TT4, FT3, FT4 and S-TSH contents had very significant change in the two groups (P < 0.01), TRAb had very significant change in the treatment group (P < 0.01) and no significant change in the control group (P > 0.05) there were significant differences in decrease of TT3, FT3, TRAb (P < 0.05) and no significant difference in decrease of TT4, FT4 and increase of S-TSH between the two groups (P > 0.05). CONCLUSION: Pricking therapy has a definite therapeutic effect on Graves' disease, which is carried out through regulating thyroid function.

New diagnostic and therapeutic approach to thyroid-associated orbitopathy based on applied kinesiology and homeopathic therapy.

OBJECTIVES: To investigate pathogenetic mechanisms related to the lacrimal and lymphatic glands in patients with thyroid-associated orbitopathy (TAO), and the potential of applied kinesiology diagnosis and homeopathic therapeutic measures. DESIGN: Prospective. SETTINGS/LOCATION: Thyroid outpatient unit and a specialized center for complementary medicine (WOMED, Innsbruck; R.M. and H.M.). SUBJECTS: Thirty-two (32) patients with TAO, 23 with a long-standing disease, and 9 showing discrete initial changes. All patients were euthyroid at the time of the investigation. INTERVENTIONS: Clinical investigation was done, using applied kinesiology methods. Departing from normal reacting muscles, both target organs as well as therapeutic measures were tested. Affected organs will produce a therapy localization (TL) that turns a normal muscle tone weak. Using the same approach, specific counteracting therapies (i.e., tonsillitis nosode and lymph mobilizing agents) were tested. OUTCOME MEASURES: Change of lid swelling, of ocular movement discomfort, ocular lock, tonsil reactivity and Traditional Chinese Medicine criteria including tenderness of San Yin Jiao (SP6) and tongue diagnosis were recorded in a graded fashion. RESULTS: Positive TL reactions were found in the submandibular tonsillar structures, the pharyngeal tonsils, the San Yin Jiao point, the lacrimal gland, and with the functional ocular lock test. Both Lymphdiaral (Pascoe, Giessen, Germany) and the homeopathic preparation chronic tonsillitis nosode at a C3 potency (Spagyra, Grödig, Austria) counteracted these changes. Both agents were used therapeutically over 3-6 months, after which all relevant parameters showed improvement. CONCLUSIONS: Our study demonstrates the involvement of lymphatic structures and flow in the pathogenesis of TAO. The tenderness of the San Yin Jiao point correlates to the above mentioned changes and should be included in the clinical evaluation of these patients.

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.

[Thyrotoxic hypokalaemic periodic paralysis in a Caucasian male]. / Paralysie périodique hypokaliémique thyréotoxique chez un Caucasien.

We report the case of a caucasian patient with a presentation of a periodic paralysis associated with hypokalaemia disclosing Graves' disease. Major pathophysiologics hypothesis are discused in order to explain relationships between hyperthyroidism and paralysis through a disturbance of the excitability of the muscle fibres. A genetic predisposition explain the high incidence of this affection in asiatic population while it is uncommon in caucasian race. Potassium supplementation is not needed in order to correct hypokalaemia except in case of cardiac disturbances. Treatment by beta-blockers is advisable with the specific treatment of hyperthyroidism.

Recession of the inferior rectus muscle under topical anesthesia in thyroid ophthalmopathy.

PURPOSE: To evaluate the results of inferior rectus muscle recession with adjustable loop suture under topical anesthesia for vertical deviations secondary to thyroid ophthalmopathy. PATIENTS AND METHODS: Five patients with a vertical deviation greater than 15 PD and severe limitation of upgaze were enrolled in the study. Before proceeding with corrective strabismus surgery, we waited at least 6 months after stabilization of ocular alignment and normalization of thyroid chemistries. All patients underwent inferior rectus muscle recession with adjustable loop suture under topical anesthesia. The postsurgical follow-up was at least 12 months. RESULTS: Preoperatively, the mean vertical deviation was 24 PD. At 1 year postoperatively, it had decreased to 2.4 PD. Two patients were orthotropic and 3 patients had residual hypotropia ranging from 2 to 6 PD. The limitation of upgaze was relieved significantly in the postoperative period. Two patients had minimal limitation of downgaze, but none complained of diplopia in the primary or reading positions. Surgery did not trigger a flare-up of orbital inflammation in the early postoperative period. CONCLUSION: We advocate that recession of the inferior rectus muscle with adjustable loop suture under topical anesthesia is safe and effective in patients with thyroid ophthalmopathy.

A possible role of immunoglobulin E in patients with hyperthyroid Graves' disease.

To investigate the possible participation of immunoglobulin E (IgE) in the autoimmune process of Graves' disease, incidence of elevation of serum IgE level, TSH receptor antibody (TRAb), and thyroid status were studied in 66 patients with hyperthyroid Graves' disease, 54 patients with Hashimoto's thyroiditis, 19 patients with bronchial asthma, and 15 patients with pollen allergy. In hyperthyroid Graves' patients, elevation of serum IgE levels (> or = 170 U/mL) was found in 19 of 66 patients (29%), 11 of whom had hereditary and/or allergic conditions. Elevations of serum IgE levels were found in 63% of patients with bronchial asthma and in 40% of patients with pollen allergy. Mean values of serum IgE were the same in patients with hyperthyroid Graves' disease and with bronchial asthma. During methimazole treatment TRAb decreased without fluctuation of IgE levels in both groups. The decrease in TRAb was significantly greater in patients with normal IgE than in patients with IgE elevation. After prednisone administration, reduction in TRAb was greater in patients with normal IgE than that in patients with IgE elevation. High incidence of IgE elevation in hyperthyroid Graves' disease and slower reduction in TRAb in association with IgE elevation suggest a difference in the autoimmune processes in Graves' disease with and without elevation of IgE.