Weight homeostasis & its modulators in hyperthyroidism before & after treatment with carbimazole.

Background & objectives: Hyperthyroidism is associated with increased food intake, energy expenditure and altered body composition. This study was aimed to evaluate the role of adipocytokines in weight homeostasis in patients with hyperthyroidism. Methods: Patients (n=27, 11men) with hyperthyroidism (20 Graves’ disease, 7 toxic multinodular goiter) with mean age of 31.3±4.2 yr and 28 healthy age and body mass index (BMI) matched controls were studied. They underwent assessment of lean body mass (LBM) and total body fat (TBF) by dual energy X-ray absorptiometer (DXA) and blood sample was taken in the fasting state for measurement of leptin, adiponectin, ghrelin, insulin, glucose and lipids. Patients were re-evaluated after 3 months of treatment as by that time all of them achieved euthyroid state with carbimazole therapy. Results: The LBM was higher (P<0.001) in healthy controls as compared to hyperthyroid patients even after adjustment for body weight (BW), whereas total body fat was comparable between the two groups. Serum leptin levels were higher in patients with hyperthyroidism than controls (22.3±3.7 and 4.1±0.34 ng/ml, P<0.001), whereas adiponectin levels were comparable. Plasma acylated ghrelin was higher in patients than in controls (209.8±13.3 vs 106.2±8.2 pg/ml, P<0.05). Achievement of euthyroidism was associated with significant weight gain (P<0.001) and significant increase in lean body mass (P<0.001). The total body fat also increased but insignificantly from 18.4±1.8 to 19.9±1.8 kg. There was significant decrease (P<0.05) in serum leptin and acylated ghrelin but adiponectin levels remained unaltered after treatment. Serum leptin positively correlated with TBF and this correlation persisted even after adjustment for BW, BMI, gender and age (r=0.62, P=0.001). However, serum leptin and acylated ghrelin did not correlate with the presence or absence of hyperphagia. Interpretation & conclusion: Patients with hyperthyroidism predominantly had decreased lean body mass which increased after achievement of euthyroidism with carbimazole. The hyperphagia and the alterations in weight homeostasis associated with hyperthyroidism were independent of circulating leptin and ghrelin levels.

Early treatment with low fixed dose (5 mCi) radioiodine therapy is effective in Indian subjects with Graves' disease.

There is little consensus regarding the most appropriate dosage regimen for radioiodine treatment in Graves' disease. The authors evaluated the efficacy of low fixed dose (5mCi) of radioiodine therapy, in terms of its cure rate and promptness of control, as well possible factors influencing the outcome. One hundred and twenty five consecutive patients with Graves' disease with persistent disease activity despite receiving carbimazole were treated with 5 mCi fixed dose of I131. Patients, who remained hyperthyroid at 1 year, received a second dose of 7.5 mCi of I113. After first dose 73.6% were cured (36.8% hypothyroid and 36.8% euthyroid), while 26.4% patients did not respond. Those who achieved cure had significantly lesser goiter size (84.6% with grade I goiter and 70.7% with grade II) and had received significantly shorter duration of prior carbimazole therapy (22 +/- 10 months versus 63 +/- 27 months) (p < 0.01). Age, sex, baseline T3, T4, 24 hour I131 uptake did not affect the cure rate. Mean time to response was 7 +/- 4 months. One hundred and three (82.4%) patients were cured after 2 doses while only 22 (17.6%) were nonresponsive. Hence, low fixed dose (5mCi) radio active iodine (RAI) therapy seems to be effective in Graves' disease particularly in patients with small sized goiter and short duration of pretherapy with thionamides.

Myelodysplastic syndrome and pancytopenia responding to treatment of hyperthyroidism: peripheral blood and bone marrow analysis before and after antihormonal treatment.

Hematological disorders, especially single lineage abnormalities, have been described in hyperthyroidism. Pancytopenia has been reported, without myelodysplastic syndrome or megaloblastic anemia. We studied the peripheral blood smear and the bone marrow aspiration and biopsy of a 65-year-old lady, who presented with pancytopenia and thyrotoxicosis due to multinodular goiter. She denied ingesting any toxic medication. At diagnosis: WBC: 2500/ul, platelets count: 58,000/ul, hemoglobin level: 6.5 g/dl. The bone marrow was moderately hyper cellular with moderate myelofibrosis and arrested hematopoiesis. The TSH level was: 0.02 mIU/l (N: 0.25-4), the fT3: 18 pmol/l (N: 4-10), the routine serum immunologic tests were negative. After treatment with single agent neomercazole (carbimazole), complete recovery of the blood cell counts was obtained within one month. The bone marrow aspiration, performed three months after starting therapy, showed normal hematopoiesis. The thyroid function tests returned to normal and no autoimmune reaction was detected on routine serum testing. Persistent response was observed six months later under medical treatment. The patient has refused surgical treatment. Reversible myelodysplastic syndrome may also be part of the changes in blood picture of patients with hyperthyroidism, probably due to direct toxic mechanism.

Juvenile hyperthyroidism: an experience.

OBJECTIVE: To analyze the clinical profile of juvenile hyperthyroidism at presentation, their treatment outcome; predictors of remission and relapse. METHODS: Retrospective analysis of medical records of 56 patients with juvenile hyperthyroidism seen over a period of 16 years. A cohort of 38 females and 18 males with mean (+/-SD) age of 14.9 +/- 3.4 years (range 3 to 18 years) was analyzed. RESULTS: Majority of patients was in the age group of 12-16 years. Common symptoms observed at presentation were weight loss (82.1%), excessive sweating (78.6%), heat intolerance (76.8%), increased appetite (73.2%) and diarrhea in 48.2%. In addition, accelerated linear growth was observed in 7.1% of patients. Goiter was present in 98.2% of children; 94.5% of which was diffuse and 4.8% was multinodular. The mean ((+/-SD) T3 was 4.8 +/- 3.4 ng/mL (N, 0.6-1.6), T4 was 218 +/- 98 ng/mL (N, 60-155) and TSH was 0.44 +/- 0.36 (N, 0.5-5.5 microIU/mL). TMA positivity seen in 36.9% of patients. All patients were treated with carbimazole; subsequently 4 patients required thyroidectomy and one required radioactive iodine ablation. Mean (+/-SD) duration of follow-up in our patients was 4.9 +/- 3 years, ranging between 1.6 to 16 years and mean (+/-SD) duration of treatment was 34.4 +/- 22.6 months (range 12 to 120 months). Mean (+/-SD) duration to achieve euthyroidism was 5.2 +/- 4.7 months, ranging between 1-33 months. On intention to treat analysis, remission with carbimazole was achieved in 47.6%, remaining patients failed to achieve remission with drug treatment. CONCLUSION: Graves disease is the commonest cause of juvenile hyperthyroidism. Carbimazole is safe, effective, cheap, and easily available form of therapy. It is occasionally associated with serious side effects but requires prolonged follow up.

Paroxysmal kinesigenic dyskinesia manifestation of hyperthyroidism.

Sporadic paroxysmal kinesigenic dyskinesia (PKD) secondary to thyrotoxicosis is an extremely rare entity. A 36-year-old female presented with the features of PKD. Her investigations revealed thyrotoxicosis. Her dyskinesia did not respond to carbamazepine but remitted with the anti-thyroid drug, neomercazole. Perhaps hyperthyroidism-related PKD is a result of a metabolic disturbance of the basal ganglia circuits rather than a permanent and irreversible change.

Thyrotoxic hypokalaemic paralysis in a pregnant Afro-Caribbean woman. A case report and review of the literature

This paper reports the case of a 21-year-old Afro-Caribbean pregnant woman with hyperthyroidism and hypokalaemic quadriparesis and reviews the literature on the topic. Thyrotoxic periodic paralysis is a very rare condition in the Caribbean. This case reminds West Indian physicians to consider this rare condition in any patient that presents with paralysis

Hyperthyroidism in children.

This study was done to characterize the clinical features, laboratory parameters and response to therapy and outcome of childhood hyperthyroidism. The evaluation included history, examination, laboratory investigations: serum T3, T4, TSH, free T3, free T4 by RIA or immunochemiluminescence (IC), antithyroid antibodies by standard techniques, bone age (BA) by Greulich and Pyle's method, clinical and laboratory response to treatment, and follow-up of 15 children with hyperthyroidism seen in past eight years. Age of onset, presentation, nature and duration of symptoms, family history, anthropometry and signs of hyperthyroidism were recorded. There were 10 girls and 5 boys (2:1). Three families had a history of thyroid disorders. Mean ages of onset and presentation were 8.25 +/- 3.4 and 9.27 +/- 3.2 years respectively. Clinical features included weight loss, heat intolerance and sweating, diarrhoea, behavioral problems, ophthalmopathy and tachycardia. BA was advanced. Serum T3 (mean = 4.29 +/- 1.77 ng/mL), T4 (18.75 +/- 5.64 micrograms/dL), FT3 (7.11 +/- 4.58 pg/mL) and FT4 (2.93 +/- 0.29 ng/mL) were markedly elevated. TSH was suppressed. Anti-microsomal antibodies (AMA) and anti-thyroglobulin antibodies (ATG) were positive in five. They were started on standard treatment with carbimazole 0.5-0.7 mg kg-1. Clinical and biochemical euthyroidism was achieved within 2.5 to 6 months in all, after which the drug was tapered, however, they required treatment for 2 years to 7.5 years. Four children were retreated for relapse and are now euthyroid and off treatment. Childhood hyperthyroidism requires long term treatment and careful monitoring. This study shows a remission rate of 67%.

Modalidades terapêuticas na doença de Basedow-Graves / Therapeutical approaches in Basedow-Graves disease

Neste artigo säo analisadas as três grandes modalidades terapêuticas do hipertireoidismo - o tratamento clínico, o radioiodo e a cirurgia -, discutindo-se detalhadamente cada uma delas, enfocando seus mecanismos de açäo, vantagens e desvantagens, principais indicaçöes e contra indicaçöes. A abordagem terapêutica também será analisada em grupos especiais como neonatos, crianças e adolescentes, gestantes e idosos

Dyspnoea, lung function & respiratory muscle pressures in patients with Graves' disease.

To understand the pathophysiology of dyspnoea in patients with hyperthyroidism, lung function, maximum inspiratory, expiratory respiratory muscle pressures (MIP and MEP) and intensity of dyspnoea (after six minutes walking test) were recorded in 12 consecutive patients with active Graves' disease. Reassessment was done after achieving euthyroidism with 8-12 wk of carbimazole therapy. Patients covered similar distance during 6 min walking before and after carbimazole therapy. However, there was a significant reduction in dyspnoea following euthyroidism. This was accompanied by significant decrease in respiratory rate, minute ventilation, forced expiratory volume in one second (FEV1%) and improvement in the forced vital capacity (FVC). No significant changes in tidal volume (TV) and maximum-midexpiratory flow rates (MMEFR), MIP and MEP were observed. Lung function parameters, MIP and MEP did not correlate with the severity of dyspnoea. Serum T4 levels correlated inversely with the distance covered during 6 min walking test, MIP and MEP. To conclude, increased breathing effort in presence of reduced FVC may lead to dyspnoea during hyperthyroid phase in patients with active Graves' disease. Lack of correlation between the severity of dyspnoea and abnormalities in lung function suggests that other mechanisms of dyspnoea may also operate in these patients.

Remission with carbimazole therapy & assessment of T4 suppression test as an index of relapse in patients with Graves' disease in India.

This study determined the relapse rate following the use of antithyroid drugs (ATD) in patients with Graves' disease and assessed T4 suppression test as a follow up index for predicting relapse after carbimazole treatment in 21 patients who had taken 9-12 months of ATD treatment continuously with good compliance. T4 suppression test was done before stopping ATD treatment. During one year of follow up after stopping ATD therapy, 12 (57%) patients relapsed and 9 (43%) remained in remission. Six of the 12 relapses occurred in the first 3 months of stopping ATD therapy. The response following the use of carbimazole therapy was comparable to that reported from iodine sufficient western countries and may be because of the salt iodination programme in our country. T4 suppression test was normal in 14 (66%) and abnormal in 7 (34%) patients. All the patients with abnormal T4 suppression test relapsed after stopping ATD. The overall accuracy of the T4 suppression test (76%) also favourably compared with reported values of other useful but less readily available markers such as thyrotropin releasing hormone (TRH) stimulation test and thyroid receptor antibodies. Thus, in our experience antithyroid drugs were able to induce long term remission in 43 per cent patients with Graves' disease and abnormal T4 suppression test can be used as a reliable parameter for predicting relapse.

Thyrotoxicosis--treatment by I131 therapy and early prediction of hypothyroidism following this therapy.

This study was undertaken in 68 thyrotoxic patients to assess the predictive value of various post treatment biochemical and immunological tests for early hypothyroidism after I131 therapy and to determine whether pretreatment with carbimazole protects against post I131 therapy hypothyroidism. Early changes observed in serum T3, T4, TSH, thyroid microsomal and thyroglobulin antibody levels were found to be of no predictive value. A sharp increase in TRAb levels around 3 months following I131 therapy indicated that hypothyroidism was likely to occur as this rise reflected a greater degree of thyroid damage. Lower levels of thyroglobulin in patients who became hypothyroid by 12 months after treatment would support this view. Carbimazole pretreatment for eight weeks did not appear to protect against hypothyroidism, in our study.

Hyperkalemic periodic paralysis associated with thyrotoxicosis.

A 32 year old male presented with episodic pure motor weakness for 1 1/2 months. On evaluation he was found to be thyrotoxic. Hyperkalemic challenge test provoked similar weakness with raised serum potassium (6 meq/L). He responded to treatment with neomercazole. Till he became euthyroid, he responded to the addition of acetazolamide to his medication. He is symptom free on antithyroid drug alone over 8 months of follow up.

Lithium carbonate therapy for induction of euthyroid state in thyrotoxicosis. A preliminary study.

Lithium carbonate was tried in 27 patients with Graves' disease to induce euthyroid state. Each patient received 1200 mg of lithium carbonate in three divided doses. The study protocol included monthly monitoring of serum lithium, total serum T3, T4 and T3/T4 ratio, and a repeat radioactive iodine uptake (RAIU) at the end of three months. Twenty three patients completed the study. Of these, only 9 (39.1%) achieved euthyroid state, with a significant reduction in serum T3 and T4 but not in T3/T4 ratio and RAIU, suggesting a major effect of lithium on thyroid hormone release. No significant correlation was observed between serum lithium and circulating T3 and T4.

Thyroid stimulating hormone receptor antibody in thyroid diseases.

Thyroid stimulating hormone receptor antibody (TRA) was estimated as a measure of TSH binding inhibitory immunoglobulin (TBII) in 48 persons. These included (i) 14 controls; (ii) 23 patients with Graves' disease who were tested for TRA within 3 months of commencing treatment with carbimazole of which 13 were studied serially; (iii) 5 patients with toxic nodular goitre; (iv) 4 with euthyroid exophthalmos; and (v) 2 neonates of thyrotoxic mothers. TRA was measured with an RIA system, while total thyroxine (T4), free thyroxine concentration (FTC) and TSH were also estimated along with TRA. All controls showed undetectable TRA levels; 87 per cent of patients with Graves' disease were TRA positive within 3 months of starting carbimazole therapy. In the serial study, 5 patients with Graves' disease who had undetectable TRA initially remained so while on treatment. Seven out of the remaining 8 patients showed a decline of TRA levels to normal over 3 to 18 months. This decline coincided with clinical and biochemical recovery.