Treatment of hyperthyroidism: effects on hepatic lipase, lipoprotein lipase, LCAT and plasma lipoproteins

The activities of hepatic lipase and of lipoprotein lipase, the elimination rate of exogenous triglyceride and the cholesterol esterification rate were determined and related to plasma lipoprotein concentrations in 16 patients before and after treatment for hyperthyroidism. The activity of hepatic lipase was significantly higher (65%) before than after treatment, while the activity of lipoprotein lipase and the elimination rate of exogenous triglyceride remained unchanged. The endogenous cholesterol esterifying ability decreased after treatment, whereas no change occurred in the fractional cholesterol esterification rate measured with normal plasma as substrate. The concentrations of LDL-cholesterol and HDL-cholesterol increased significantly after treatment. The decrease in hepatic lipase activities was correlated to the decrease in S-T3 concentrations (r = 0.77, P less than 0.001) and to the increase in HDL-cholesterol concentrations (r = 0.51, P less than 0.05). The activities of lipoprotein lipase were positively correlated to the concentrations of HDL-cholesterol both before (r = 0.54, P less than 0.05) and after (r = 0.59, P less than 0.05) treatment. These results support the view that hepatic lipase and lipoprotein lipase are both important determinants of plasma HDL concentrations and suggest that an increased hepatic lipase activity contributes to the lower HDL levels in hyperthyroid patients

Comparison of methods for evaluation of the suppressive effects of prednisolone on the HPA axis and bone turnover: changes in s-DHEAS are as sensitive as the ACTH test

Objective: Different hypothalamic-pituitary-adrenal (HPA) axis function tests are used for diagnosing disease and evaluating suppressive effects of corticosteroid treatment. Our objectives were to evaluate sensitivity and precision of different HPA axis tests to be able to select one that combines good performance with good practicability, suitable for investigation of new corticosteroids in clinical trials. Methods: In this descriptive, double-blind, parallel-group study, 60 healthy male volunteers were treated with once-daily morning doses of prednisolone for 2 weeks. The volunteers were randomized to 1 of 5 treatment groups (prednisolone 2.5, 5, 7.5, 10, or 15 mg). We compared the plasma-cortisol (p-cortisol) 24-hour average concentration (C,) with morning (08:00 hours) p-cortisol, daytime p-cortisol C,, and 24-hour urinary cortisol excretion. Adrenocorticotrophic hormone (ACTH) stimulation tests and the metyrapone test were also performed. Furthermore, we analyzed levels of serum dehydroepiandrosterone sulfate (s-DHEAS), insulin, and markers of bone turnover. Results: Dose-related effects were shown, but the magnitude of effects and sensitivities varied greatly between the tests. P-cortisol measurements over the course of 24 hours were used as the reference method. Low- and standard-dose ACTH tests and morning s-DHEAS levels had similar sensitivity. Urinary cortisol excretion and the metyrapone stimulation test had low sensitivity. The effects of prednisolone on markers of bone turnover were, in general, less than those on the HPA axis. Only osteocalcin, procollagen type 1 C-peptide and procollagen type 3 N-peptide were significantly affected. Treatment with prednisolone was well tolerated. Conclusion: Changes in s-DHEAS and the low-dose ACTH test combine good sensitivity and precision for evaluation of the suppressive effect of exogenous corticosteroids on the HPA axis, and they are easy to perform

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

Objective: The objective of this study was to investigate quality of life (QoL) in patients with Graves' disease treated with radioiodine or antithyroid drugs. Design and methods: The 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. Results: Patient 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. Conclusions: The 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

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

Context: Previous randomized trials have suggested an association between radioiodine treatment for Graves' hyperthyroidism and thyroid-associated ophthalmopathy (TAO). Objectives: The 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. Design: We 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 T4 was given in both groups. Main Outcome Measure: Worsening 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). Results: The 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. Conclusions: Radioiodine 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