Jan Calissendorff

Thyroid-Associated Ophthalmopathy after Treatment for Graves’ Hyperthyroidism with Antithyroid Drugs or Iodine-131

CONTEXTnPrevious randomized trials have suggested an association between radioiodine treatment for Graves hyperthyroidism and thyroid-associated ophthalmopathy (TAO).nnnOBJECTIVESnThe aim of the study was to compare the occurrence of worsening or development of TAO in patients who were treated with radioiodine or antithyroid drugs.nnnDESIGNnWe conducted a randomized trial (TT 96) with a follow-up of 4 yr. PATIENTS, SETTING, AND INTERVENTION: Patients with a recent diagnosis of Graves hyperthyroidism were randomized to treatment with iodine-131 (163 patients) or 18 months of medical treatment (150 patients). Early substitution with T(4) was given in both groups.nnnMAIN OUTCOME MEASUREnWorsening or development of TAO was significantly more common in the iodine-131 treatment group (63 patients; 38.7%) compared with the medical treatment group (32 patients; 21.3%) (P < 0.001).nnnRESULTSnThe risk for de novo development of TAO was greater in patients treated with iodine-131 (53 patients) than with medical treatment (23 patients). However, worsening of TAO in the 41 patients who had ophthalmopathy already before the start of treatment was not more common in the radioiodine group (10 patients) than in the medical group (nine patients). Smoking was shown to influence the risk of worsening or development of TAO, and smokers treated with radioiodine had the overall highest risk for TAO. However, in the group of smokers, worsening or development of TAO was not significantly associated with the choice of treatment for hyperthyroidism.nnnCONCLUSIONSnRadioiodine treatment is a significant risk factor for development of TAO in Graves hyperthyroidism. Smokers run the highest risk for worsening or development of TAO irrespective of treatment modality.

Incidence of hyperthyroidism in Sweden

INTRODUCTIONnThe incidence of hyperthyroidism has been reported in various countries to be 23-93/100,000 inhabitants per year. This extended study has evaluated the incidence for ~40% of the Swedish population of 9 million inhabitants. Sweden is considered to be iodine sufficient country.nnnMETHODSnAll patients including children, who were newly diagnosed with overt hyperthyroidism in the years 2003-2005, were prospectively registered in a multicenter study. The inclusion criteria are as follows: clinical symptoms and/or signs of hyperthyroidism with plasma TSH concentration below 0.2 mIE/l and increased plasma levels of free/total triiodothyronine and/or free/total thyroxine. Patients with relapse of hyperthyroidism or thyroiditis were not included. The diagnosis of Graves disease (GD), toxic multinodular goiter (TMNG) and solitary toxic adenoma (STA), smoking, initial treatment, occurrence of thyroid-associated eye symptoms/signs, and demographic data were registered.nnnRESULTSnA total of 2916 patients were diagnosed with de novo hyperthyroidism showing the total incidence of 27.6/100,000 inhabitants per year. The incidence of GD was 21.0/100,000 and toxic nodular goiter (TNG=STA+TMNG) occurred in 692 patients, corresponding to an annual incidence of 6.5/100,000. The incidence was higher in women compared with men (4.2:1). Seventy-five percent of the patients were diagnosed with GD, in whom thyroid-associated eye symptoms/signs occurred during diagnosis in every fifth patient. Geographical differences were observed.nnnCONCLUSIONnThe incidence of hyperthyroidism in Sweden is in a lower range compared with international reports. Seventy-five percent of patients with hyperthyroidism had GD and 20% of them had thyroid-associated eye symptoms/signs during diagnosis. The observed geographical differences require further studies.

Alcohol ingestion decreases both diurnal and nocturnal secretion of leptin in healthy individuals

OBJECTIVE Neuropeptide Y (NPY) stimulates appetite and increases food intake. Leptin inhibits NPY. It is not known whether alcohol influences any of these factors, but it has been suggested that alcohol stimulates appetite in man. The primary objective of this investigation was to determine whether ingestion of ethanol inhibits leptin secretion in normal subjects.

Incidence of hyperthyroidism in Stockholm, Sweden, 2003-2005

OBJECTIVESnTo investigate the incidence of hyperthyroidism in Stockholm County, in those patients who were diagnosed with hyperthyroidism for the first time during the years 2003-2005.nnnDESIGNnAll new cases of hyperthyroidism > or = 18 years of age were prospectively registered to calculate the total incidence of hyperthyroidism, as well as the incidence of the subgroups: Graves disease (GD), toxic multinodular goitre and solitary toxic adenoma (STA). Eight specialized units/hospitals in Stockholm County participated in the registration. The participating physicians were all specialists in medical endocrinology, oncology, nuclear medicine or surgery.nnnRESULTSnDuring a 3-year period, 1431 new patients of hyperthyroidism were diagnosed in a well-defined adult population (> 18 years of age) of in average 1,457,036 inhabitants. This corresponds to a mean annual incidence of hyperthyroidism of 32.7/100,000. The incidence of GD was 24.5/100,000 per year, toxic nodular goitre was 3.3/100,000 per year and STA was 4.9/100,000 per year.nnnCONCLUSIONSnThe total incidence of hyperthyroidism in Stockholm County was found to be 32.7/100,000 per year, of which 75% had GD. There were a higher percentage of smokers among the patients with hyperthyroidism compared with the overall population in Stockholm, but no difference in the frequency of smoking between patients with GD and toxic nodular goitre.

Thyrotoxic periodic paralysis: clinical and molecular aspects.

Thyrotoxic periodic paralysis (TPP) is a rare complication of hyperthyroidism that most often affects young East Asian males but increasingly also in other ethnic groups. The typical presentation is acute attacks varying from mild weakness to total paralysis starting at night or in the early morning a few hours after a heavy meal, alcohol abuse or strenuous exercise with complete recovery within 72xa0h. Signs and symptoms of hyperthyroidism may not be obvious. The hallmark is hypokalemia from increased cellular sodium/potassium-ATPase pump activity with transport of potassium from the extracellular to the intracellular space in combination with reduced potassium output. Recently, KCNJ18 gene mutations which alter the function of an inwardly rectifying potassium channel named Kir2.6 have been detected in 0-33xa0% of cases. Hence, the pathophysiology in TPP includes a genetic predisposition, thyrotoxicosis and environmental influences and the relative impact from each of these factors may vary. The initial treatment, which is potassium supplementation, should be given with caution due to a high risk of hyperkalemia. Propranolol is an alternative first-line therapeutic option based on the assumption that hyperadrenergic activity is involved in the pathogenesis. If thyroid function tests are unobtainable in the acute situation the diagnosis is supported by the findings of hypokalemia, low spot urine potassium excretion, hypophosphatemia with hypophosphaturia, high spot urine calcium/phosphate ratio, and electrocardiographic abnormalities as tachycardia, atrial fibrillation, high QRS voltage, and atrioventricular block. Definitive treatment is cure of the hyperthyroidism. The underlying mechanisms of TPP remain, however, incompletely understood awaiting further studies.

Hunger-satiety signals in patients with Graves’ thyrotoxicosis before, during, and after long-term pharmacological treatment

Patients with Graves’ thyrotoxicosis lose weight despite increased appetite and food intake, thus suggesting a disturbed balance between energy intake and expenditure. Underlying mechanisms are not fully elucidated. The objective of this study was to investigate whether hormonal factors, known to affect hunger/satiety, change significantly over time as pharmacological treatment turns hyperthyroidism into euthyroidism. For that purpose 11 patients with Graves’ thyrotoxicosis were given thiamazole and I-thyroxine for 18–20 mo. They were investigated on three occasions: Test 1: before pharmacological therapy; Test 2: during medication; Test 3: a few months after conclusion of the pharmacological treatment. Sixteen healthy subjects were also investigated for comparison. The participants were fasted overnight. Blood samples for determination of plasma glucose and serum concentrations of free T3 and T4, TSH, albumin, cortisol, insulin, GH, IGF-1, IGFBP-1, leptin, and ghrelin were drawn in the morning from an antecubital vein. Laboratory data obtained in test 1 were statistically compared with those in tests 2 and 3. The study showed that the free T3 level declined from 42.8±4.3 pmol/L in test 1 to 6.0±0.8 pmol/L in test 2 (85±2% decline), and 5.5±0.3 pmol/L in test 3 (86±2% decline). The free T4 level fell concomitantly from 65.2±4.8 to 16.6±1.7 and 14.4±1.2 pmol/L. The glucose level was significantly higher during hyperthyroidism (test 1) than during euthyroidism (tests 2 and 3), whereas cortisol, insulin, GH, IGF-1, and leptin levels were similar. The IGFBP-1 level was initially high (48.8±8.5 µg/L in test 1), but with a relative decline in free T3 of 85±2% (test 2) the IGFBP-1 level declined by 34±13%, and with a free T3 decline of 86±2% (test 3) the binding protein fell by 39±29%. This brought about increased IGF-1 bioavailability as reflected by a rising IGF-1/IGFBP-1 ratio from 5.1±1.1 to 13.8±2.9 (p<0.01). The ghrelin level was low (2454±304 ng/L) in test 1. It increased to 3127±397 ng/L in test 2 (p<0.05), and to 3348±279 ng/L in test 3 (p<0.01). Conclusion: Both ghrelin secretion and IGF-1 bioavailability are low in patients with untreated thyrotoxicosis, but increase markedly as pharmacotherapy makes them euthyroid. These metabolic changes may be caused by the transition of hyperthyroidism into euthyroidism rather than by the pharmacotherapy per se, since the metabolic changes prevailed also in the posttreatment period.

A Prospective Investigation of Graves' Disease and Selenium: Thyroid Hormones, Auto-Antibodies and Self-Rated Symptoms

Background: In Graves thyrotoxicosis tachycardia, weight loss and mental symptoms are common. Recovery takes time and varies between patients. Treatment with methimazole reduces thyroid hormone levels. According to previous research, this reduction has been faster if selenium (Se) is added. Objective: The objective was to investigate whether supplementing the pharmacologic treatment with Se could change the immune mechanisms, hormone levels and/or depression and anxiety. Methods: We prospectively investigated 38 patients with initially untreated thyrotoxicosis by measuring the thyroid-stimulating hormone (TSH), free thyroxine (FT4), free triiodothyronine (FT3), thyroid receptor antibodies and thyroid peroxidase auto-antibodies before medication and at 6, 18 and 36 weeks after commencing treatment with methimazole and levo-thyroxine, with a randomized blinded oral administration of 200 µg Se/day or placebo. The selenoprotein P concentration was determined in plasma at inclusion and after 36 weeks. The patients were also assessed with questionnaires about depression, anxiety and self-rated symptoms before medication was started and after 36 weeks. Results: FT4 decreased more in the Se group at 18 weeks (14 vs. 17 pmol/l compared to the placebo group, p = 0.01) and also at 36 weeks (15 vs. 18 pmol/l, p = 0.01). The TSH increased more in the Se group at 18 weeks (0.05 vs. 0.02 mIU/l, p = 0.04). The depression and anxiety scores were similar in both groups. In the Se group, the depression rates correlated negatively with FT3 and positively with TSH. This was not seen in the placebo group. Conclusions: Se supplementation can enhance biochemical restoration of hyperthyroidism, but whether this could shorten clinical symptoms of thyrotoxicosis and reduce mental symptoms must be investigated further.

Primary aldosteronism: functional histopathology and long-term follow-up after unilateral adrenalectomy.

To investigate the long‐term outcome after unilateral adrenalectomy in patients with primary aldosteronism (PA) and to establish the role of functional pathology for the final diagnosis of aldosterone‐producing adenoma (APA) or hyperplasia.

Thyroid-associated ophthalmopathy; quality of life follow-up of patients randomized to treatment with antithyroid drugs or radioiodine

OBJECTIVEnThe objective of this study was to investigate quality of life (QoL) in patients with Graves disease treated with radioiodine or antithyroid drugs.nnnDESIGN AND METHODSnThe design of the study consists of an open, prospective, randomized multicenter trial between radioiodine and medical treatment. A total of 308 patients were included in the study group: 145 patients in the medical group and 163 patients in the radioiodine group. QoL was measured with a 36-item Short Form Health Status Survey questionnaire (SF-36) at six time points during the 48-month study period.nnnRESULTSnPatient who developed or got worse of thyroid-associated ophthalmopathy (TAO) at any time point during the 4-year study period (TAO group) had lower QoL when no respect was paid to the mode of treatment. TAO occurred in 75 patients who had radioiodine treatment at some time point during the study period as compared with TAO in 40 medically treated patients (P<0.0009). Comparisons between the group of patients who have had TAO versus the group without TAO, in relation to treatments and time, showed significantly decreased QoL scores for the TAO groups at several time points during the study. In patients without TAO, there were no differences in QoL related to mode of treatment.nnnCONCLUSIONSnThe QoL in patients with Graves ophthalmopathy was similar in radioiodine and medically treated patients, but patients who developed or had worsening of TAO had decreased QoL independent of mode of treatment. Furthermore, patients with TAO recovered physically within 1 year but it took twice as long for them to recover mentally.

Alcohol Intake and Its Effect on Some Appetite-Regulating Hormones in Man: Influence of Gastroprotection with Sucralfate

Background. Alcohol stimulates appetite. Ghrelin, obestatin, glucagon-like peptide 1 and leptin are putative mediators. Objective. We studied whether alcohol ingestion affects serum levels of these peripheral hormones, and if gastroprotective sucralfate prevents such an effect. Materials and methods. Ten participants were investigated on four occasions. On one alcohol was ingested; on another alcohol was given after pretreatment with sucralfate; on a third water was ingested; and on a fourth sucralfate was ingested followed by water. Serum hormones and ethanol concentrations were determined. Results. The ghrelin and leptin levels fell after ingestion of alcohol, whereas the obestatin and GLP-1 levels remained unchanged. Sucralfate did not affect any of the basal four hormone levels, nor the ghrelin or leptin responses to alcohol. Conclusions. An appetite-stimulating effect of alcohol is hardly mediated by any of the hormones studied in this investigation, as the GLP-1 and obestatin levels were unaffected by alcohol, the ghelin level decreased, and leptin – although declining after alcohol – has not previously been found to have short-term inhibitory effect on hunger.