Peter O'Leary

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.

Australian Study on Public Knowledge of Human Genetics and Health

Aims: This study was designed to obtain data on public understanding of genetic concepts in the adult population of Western Australia. It explored knowledge of genetic risk of disease, inheritance, biology, determinism, and factors that predict relatively higher genetic knowledge within the general population. Method: A cross-sectional telephone survey of 1,009 respondents. Results: Most members of the Western Australian community are aware of basic genetic concepts and the link between genes, inheritance, and risk of disease. Significantly fewer understand the biological mechanisms underlying these concepts and there was some misconception around the meaning of ‘increased genetic risk’. The odds of higher genetic knowledge (>19 out of 24 questions correct) were greater among those with 12 years or more education (OR = 3.0), those aged 18–44 years (OR = 2.3), women (OR = 2.0), those with annual household income of AUD 80,000 or more (OR = 1.8), and those who had talked with someone (OR = 1.7) or searched the internet (OR = 1.6) for information on genes and health. Conclusions: This study provides evidence of an association between social location and public knowledge of human genetic concepts related to health and disease. This is consistent with previous findings and raises questions about the acquisition of textbook genetics knowledge within socio-cultural contexts. The impact of misconceptions about genetic concepts on the uptake of preventive health behaviors requires further investigation, as does the level of genetics knowledge that is required to empower informed participation in individual and societal decisions about genetics and health.

Evaluating genetic counseling: client expectations, psychological adjustment and satisfaction with service.

Periodic evaluations of genetic counseling services are useful for determining the effectiveness of counseling in meetings its psycho-educational aims, as well as identifying where improvements to the service may be made. This study aimed to evaluate the genetic counseling services provided by Genetic Services of Western Australia (GSWA) to determine the impact of counseling on client expectations, satisfaction with the service, and psychological adjustment, defined as wellbeing and perceived personal control (PPC). A total of 122 clients participated in a self-administered survey conducted pre- and post-counseling. Client expectations of the service as a means of providing information were met, and opportunities for counselors to meet client’s expectations of psychological support were identified. Furthermore, counseling was found to maintain and enhance psychological wellbeing of clients. The role of counseling in facilitating the development of PPC was a key contributor to a high sense of satisfaction in clients.

Early Loss of the Glucagon Response to Hypoglycemia in Adolescents With Type 1 Diabetes

OBJECTIVE To assess the glucagon response to hypoglycemia and identify influencing factors in patients with type 1 diabetes compared with nondiabetic control subjects. RESEARCH DESIGN AND METHODS Hyperinsulinemic hypoglycemic clamp studies were performed in all participants. The glucagon response to both hypoglycemia and arginine was measured, as well as epinephrine, cortisol, and growth hormone responses to hypoglycemia. Residual β-cell function was assessed using fasting and stimulated C-peptide. RESULTS Twenty-eight nonobese adolescents with type 1 diabetes (14 female, mean age 14.9 years [range 11.2–19.8]) and 12 healthy control subjects (6 female, 15.3 years [12.8–18.7]) participated in the study. Median duration of type 1 diabetes was 0.66 years (range 0.01–9.9). The glucagon peak to arginine stimulation was similar between groups (P = 0.27). In contrast, the glucagon peak to hypoglycemia was reduced in the group with diabetes (95% CI): 68 (62–74) vs. 96 (87–115) pg/mL (P < 0.001). This response was greater than 3 SDs from baseline for only 7% of subjects with type 1 diabetes in comparison with 83% of control subjects and was lost at a median duration of diabetes of 8 months and as early as 1 month after diagnosis (R = −0.41, P < 0.01). There was no correlation in response with height, weight, BMI, and HbA1c. Epinephrine, cortisol, and growth hormone responses to hypoglycemia were present in both groups. CONCLUSIONS The glucagon response to hypoglycemia in adolescents with type 1 diabetes is influenced by the duration of diabetes and can be lost early in the course of the disease.

First-trimester combined screening for Down syndrome and other fetal anomalies.

OBJECTIVE: This study assessed fetal outcomes for pregnancies identified at increased risk for Down syndrome by first-trimester combined ultrasound examination and maternal serum biochemistry screening. METHODS: First-trimester combined screening data were obtained from ultrasound clinics across Western Australia between August 2001 and October 2003. Prenatal screening data were linked with pregnancy outcome information held in state health database registers using probabilistic record-linkage techniques. RESULTS: In 50 of the 60 pregnancies affected by Down syndrome, the adjusted risk was greater than 1 in 300, providing a detection rate of 83% (95% confidence interval [CI] 74–93%). Among all women screened (n = 22,280), 827 had increased risk results but did not have a Down syndrome pregnancy, representing a false-positive rate of 3.7% (95% CI 3.5–3.9%). Ten cases of Down syndrome were detected among women considered not at increased risk, consistent with a false-negative rate of 1 in 2,227. First-trimester combined screening reduced the number of Down syndrome births by 50 in 22,280 (2.24 cases per 1,000 births), which represents the detection of one case of fetal Down syndrome for every 446 women screened. Furthermore, 25% of pregnancies with other birth defects occurred among those identified at increased risk of Down syndrome, and 1 in 8 pregnancies at increased risk were found to have a significant chromosomal or structural defect. CONCLUSION: First-trimester combined screening in Western Australia detected 83% (95% CI 74–93%) of Down syndrome pregnancies at a 3.7% (95% CI 3.5–3.9%) false-positive rate. LEVEL OF EVIDENCE: II-2

Prenatal screening for Down syndrome in Australia: Costs and benefits of current and novel screening strategies

To analyse the cost‐effectiveness and performance of noninvasive prenatal testing (NIPT) for high‐risk pregnancies following first‐trimester screening compared with current practice.