Peter Feddema

Age-Related Changes in Thyroid Function: A Longitudinal Study of a Community-Based Cohort

CONTEXT In cross-sectional studies, serum TSH concentrations increase with age. This has not been examined longitudinally, and it is uncertain whether the TSH increase reflects healthy aging or occult thyroid failure. METHODS We measured serum TSH, free T(4), thyroid peroxidase, and thyroglobulin antibodies in 1100 participants in the 1981 and 1994 Busselton Health Surveys and derived a reference group of 908 individuals without thyroid disease or thyroid antibodies. We examined changes in thyroid function longitudinally and, in 781 participants, explored associations with the CAPZB polymorphism rs10917469. RESULTS At 13 yr follow-up, mean serum TSH increased from 1.49 to 1.81 mU/liter, a change in mean TSH (ΔTSH) of 0.32 mU/liter [95% confidence interval (CI) 0.27, 0.38, P < 0.001], whereas mean free T(4) concentration was unchanged (16.6 vs. 16.6 pmol/liter, P = 0.7). The TSH increase was most marked in the elderly, such that gender-adjusted ΔTSH increased by 0.08 mU/liter (95% CI 0.04, 0.11) for each decade of baseline age. People with higher baseline TSH values had proportionally smaller increases in TSH, with each additional 1.0 mU/liter of baseline TSH associated with a 0.13 mU/liter decrease (age and gender adjusted) in ΔTSH (95% CI 0.09, 0.16). The ΔTSH did not differ significantly by CAPZB genotype. CONCLUSIONS Aging is associated with increased serum TSH concentrations, with no change in free T(4) concentrations. The largest TSH increase is in people with the lowest TSH at baseline. This suggests that the TSH increase arises from age-related alteration in the TSH set point or reduced TSH bioactivity rather than occult thyroid disease.

Thyrotropin and thyroid antibodies as predictors of hypothyroidism: a 13-year, longitudinal study of a community-based cohort using current immunoassay techniques.

CONTEXT Longitudinal studies of risk factors for hypothyroidism are required to inform debate regarding the TSH reference range. There are limited longitudinal data on the predictive value of thyroid antibodies measured by automated immunoassay (as opposed to semiquantitative methods). METHODS We measured TSH, free T(4), thyroid peroxidase antibodies (TPOAbs), and thyroglobulin antibodies (TgAbs) using the Immulite platform on sera from 1184 participants in the 1981 and 1994 Busselton Health Surveys. Outcome measures at follow-up were hypothyroidism, defined as TSH greater than 4.0 mU/liter or on thyroxine treatment; and overt hypothyroidism, defined as TSH above 10.0 mU/liter or on thyroxine treatment. Receiver-operator characteristic analysis was used to determine optimal cutoffs for baseline TSH, TPOAbs, and TgAbs as predictors of hypothyroidism. RESULTS At 13 yr follow-up, 110 subjects (84 women) had hypothyroidism, of whom 42 (38 women) had overt hypothyroidism. Optimal cutoffs for predicting hypothyroidism were baseline TSH above 2.5 mU/liter, TPOAbs above 29 kIU/liter, and TgAbs above 22 kIU/liter, compared with reference range upper limits of 4.0 mU/liter, 35 kIU/liter, and 55 kIU/liter, respectively. In women with positive thyroid antibodies (TPOAbs or TgAbs), the prevalence of hypothyroidism at follow-up (with 95% confidence intervals) was 12.0% (3.0-21.0%) when baseline TSH was 2.5 mU/liter or less, 55.2% (37.1-73.3%) for TSH between 2.5 and 4.0 mU/liter, and 85.7% (74.1-97.3%) for TSH above 4.0 mU/liter. CONCLUSIONS The use of TSH cutoffs of 2.5 and 4.0 mU/liter, combined with thyroid antibodies, provides a clinically useful estimate of the long-term risk of hypothyroidism.

Investigations of thyroid hormones and antibodies based on a community health survey: the Busselton thyroid study

Objective  Overt or subclinical thyroid dysfunction is common within the community, yet the significance of subtle anomalies in thyroid function tests remains contentious. The aims of this study were to: (a) establish reference intervals for serum‐free thyroxine (FT4), thyroid‐stimulating hormone (TSH) and thyroid antibodies (antithyroperoxidase, TPOAb and antithyroglobulin, TgAb) in the Busselton community of south‐western Western Australia; and (b) determine the prevalence of thyroid hormone anomalies in this community.

Thyroid dysfunction and serum lipids: a community‐based study

Objective  It is uncertain whether subclinical hypothyroidism (SCH) is associated with hypercholesterolaemia, particularly in subjects with SCH and serum TSH ≤ 10 mU/l.

Subclinical thyroid dysfunction and blood pressure : a community-based study

Objective  Overt hypothyroidism and hyperthyroidism are associated with hypertension, but it is uncertain whether the same is true of subclinical hypothyroidism and hyperthyroidism.

Significant association between thyroid hormones and erythrocyte indices in euthyroid subjects

Objective  Hypothyroidism and hyperthyroidism are each associated with anaemia, but relationships between thyroid function and erythrocyte indices in euthyroid subjects have not been examined. The aim of this study was to examine these relationships in a community‐based cohort.

The log TSH–free T4 relationship in a community-based cohort is nonlinear and is influenced by age, smoking and thyroid peroxidase antibody status

The TSH–T4 relationship was thought to be inverse log‐linear, but recent cross‐sectional studies of selected populations report a complex, nonlinear relationship. The TSH–T4 relationship has not been evaluated in an unselected, community‐based cohort, and there are limited data regarding clinical factors which affect it.

Effect of asthma treatment on urinary growth hormone excretion in children

We measured growth hormone (GH) concentrations in first morning urine samples in 110 prepubertal children to determine whether asthma therapies affected GH secretion. The children with asthma were assigned to two groups depending on their asthma treatments: 1) 16 children with a history of asthma, currently not on any treatment; and 2) asthmatics taking inhaled corticosteroids (n = 37), short‐term oral corticosteroids (n = 15), or long‐term non‐corticosteroidal therapies (n = 19). Results obtained from these children were compared with a control group of healthy prepubertal children (n = 23) without previous or current symptoms of asthma. Five consecutive urine samples were collected from each child, and GH concentrations (corrected for urine creatinine) were determined by an enzyme immunoassay. The mean (±SD) urine GH concentration determined in the control group (23 healthy prepubertal children) was 15.6 ± 8.7 ng/L (1.88 ± 1.29 ng GH/mmol creatinine). The mean (±SD) urine GH concentrations in overnight samples were similar in untreated asthmatics (14.1 ± 6.1 ng/L) and in the treatment groups (14.1 ± 7.7 ng/L, inhaled corticosteroids; 16.5 ± 11.7 ng/L, oral corticosteroids; 15.9 ± 9.8 ng/L, long‐term non‐corticosteroidal therapies). Irrespective of the manner of expression of urine GH (ng/L) or after correction for urine creatinine concentration (ng GH/mmol), no significant differences were found in the GH excretion among any of the groups. In this study, the intra‐individual coefficient of variation for urine GH, expressed as ng/L, ranged between 11 and 87% (median, 32%). When the urine GH was expressed as ng GH/mmol creatinine, the coefficient of variation ranged between 12 and 92% (median, 35%), accounting for approximately 60% of the inter‐individual coefficient of variation (mean CV, 56%) and 47% when the urine GH is expressed as ng GH/mmol creatinine. We were unable to determine any short‐term differences in urine GH excretion between non‐asthmatic children and asthmatics treated with inhaled corticosteroids, oral corticosteroids, or bronchodilators. Our results suggest that there is not an adverse effect of current corticosteroid therapies for childhood asthma on GH secretion. Pediatr Pulmonol. 1996; 21:361–366.