Islet cell and glutamic acid decarboxylase antibodies in hyperthyroid patients : At diagnosis and following treatment

Objectives. To study the frequency of islet cell (ICA) and glutamic acid decarboxylase (GAD-Ab) antibodies in patients with hyperthyroidism of different types at diagnosis before treatment and in the euthyroid state following treatment. Setting. Department of Endocrinology, Malmo University Hospital, Malmo, Sweden. Subjects and design. Blood samples were collected at diagnosis from 129 hyperthyroid patients, and about 6 months later, from 78 of the patients (euthyroid state). Ninety-two patients had Graves' disease (69 females and 23 males, median age 49 years, range 17-85 years), and 37 patients had toxic nodular goitre/solitary toxic adenoma (34 females and three males, median age 69 years, range 24-86 years). Interventions. Most patients were treated by radioactive iodine following the first blood sample. Main outcome measures. ICA and GAD-Ab in serum. Results. At diagnosis of Graves' disease, ICA were detected in two out of 92 (2.2%) patients, two out of 85 (2.4%) without diabetes mellitus and in the euthyroid state in one patient. None of the patients with toxic nodular goitre/solitary toxic adenoma had detectable ICA. At diagnosis of Graves' disease, GAD65-Ab as well as GAD67-Ab were detected in 11 out of 85 (13%) patients without diabetes. As many as six out of 11 GAD67-Ab-positive patients were GAD65-Ab negative. In the euthyroid state, GAD65-Ab were found in six out of 51 (12%) and GAD67-Ab in eight out of 51 (16%) of the non-diabetic Graves' disease patients. The frequencies of GAD65-Ab and GAD67-Ab in toxic nodular goitre/solitary toxic adenoma, diabetes excluded, were 3 and 0%, respectively, in the hyperthyroid state. Conclusion. The frequency of ICA in patients with hyperthyroidism is not increased as compared to the background population. GAD-Ab seems to be associated with Graves' disease and not with hyperthyroidism. The presence of GAD67-Ab in GAD65-Ab negative sera from patients with Graves' disease indicates autoreactivity against a specific GAD67 epitope

80-year-old men have elevated plasma concentrations of catecholamines but decreased plasma renin activity and aldosterone as compared to young men

Plasma concentrations of adrenaline, noradrenaline, aldosterone and plasma renin activity were determined in a selected group of 80-year-old men (N = 41) in good health without clinical signs of cardiovascular disease, and were compared to levels in young healthy males (N = 20, 24-28 years). Plasma adrenaline and noradrenaline concentrations were higher (0.24 median; 25th-75th percentiles 0.16-0.34 nmol/L vs 0.15; 0.11-0.18 nmol/L, p < 0.01 and 2.22; 1.58-3.27 nmol/L vs 1.15; 1.00-1.74 nmol/L, p < 0.001), and plasma renin activity and plasma aldosterone concentration were lower in the old than in the young men (0.65; 0.35-1.04 micrograms/L/1h vs 2.09; 1.23-2.41 micrograms/L/1h, p < 0.001 and 0.12; 0.09-0.19 nmol/L vs 0.38; 0.28-0.54 nmol/L, p < 0.001). In conclusion, increased plasma concentrations of catecholamines and decreased plasma concentration of aldosterone and plasma renin activity in old men, as compared to young men, must be considered when interpreting data of these hormones in elderly men

No increase in fracture incidence in patients treated for thyrotoxicosis in Malmo during 1970-74. A 20-year population-based follow-up

Objectives. To study whether there is an increased fracture incidence following thyrotoxicosis. Design. A case-control study. Setting. Malmo University Hospital, Malmo, Sweden. Subjects: All patients (n = 333) from the population of Malmo who were treated for thyrotoxicosis for the first time during the 5-year period 1970-74. A total of 618 controls were selected from the local municipality registry in Malmo. For each case the aim was to randomly select two age- and gender-specific controls, alive in 1993 and born the same year and month as the case. Main outcome measures. Fracture incidence. Results. Comparing survivors, there were no differences in the percentage of individuals with fractures (all, fragility, non-fragility) between the patients and the controls. Comparing all individuals and including all fractures, the percentage of individuals with fractures in the entire female patient group (24.6%) was lower (P < 0.05) than in female controls (33.1%). There was a similar but non-significant pattern between male patients and controls. The mean number of all fractures was lower in male patients than in controls (P < 0.05), but no significant difference was noted between female patients and controls. For fragility fractures, there were no significant differences in the percentage of individuals with fractures or in the mean number of fractures between female or male patients and controls. Conclusion. In conclusion we found no increased incidence of fragility fractures in patients with previous thyrotoxicosis as compared with controls. Our results do not support the suggestion that screening for osteoporosis should be performed in patients with previous thyrotoxicosis

Maternal Autoimmune Thyroid Disease and the Fetal Immune System.

OBJECTIVE: Several studies indicate that in utero exposure to maternal autoimmune diseases and transplacental passage of autoantibodies affect the risk of autoimmunity in the offspring, e. g., maternally derived GAD65 autoantibody correlates with decreased risk of type 1 diabetes, whereas thyroid peroxidase autoantibody (TPOAb) positivity at birth is associated with increased incidence of autoimmune thyroid disease later in life. The aim of this study was to identify immunological changes in children born to mothers with thyroid autoimmunity that may be related to in utero exposure to autoantibodies. DESIGN AND METHOD: Open label prospective analysis of cord blood lymphocytes and serum cytokines by Flow Cytometry in children born to mothers with autoimmune thyroiditis (AIT) (n=31) and to healthy mothers (n=76) and titers of thyroid autoantibodies were determined in cord blood and in maternal peripheral blood at delivery. RESULTS: We found an increase (almost 30%) in the frequency of cord blood natural killer (NK) cells (p=0.0016) and a minor increase in the subset of T cells expressing NK markers (p=0.028), in children born to AIT mothers. There were no detectable differences in the phenotype or frequency of cord blood memory/activated T cells, including CD4 (+)CD25 (+) T cells, between the 2 groups. The levels of pro-inflammatory cytokines TNF-α, IL-10, IL-12p70, IFN-γ and IL-1β were significantly decreased in offspring of AIT mothers as compared to healthy controls. CONCLUSIONS: Maternal thyroid autoimmunity and transplacental passage of autoantibodies against thyroid antigens may affect the generation or expansion of cells with NK activity and the secretion of inflammatory cytokines