Diagnosis, treatment and long-term consequences of hyperthyroidism: use of existing data to generate new knowledge

Hyperthyroidism is a common endocrine disorder with multiple aetiologies, manifestations and potential therapies. This thesis explores the challenges relating to the diagnosis, treatment and long-term consequences of thyrotoxicosis in real-world outpatient and inpatient settings. We performed a number of epidemiological studies analysing data from large, detailed, routinely collected data sources. We confirmed that classical manifestations of hyperthyroidism are significantly less prevalent in older patients and established that newly diagnosed thyroid dysfunction is rare in hospitalised subjects despite high volume thyroid function testing in this setting where we found a high proportion of abnormal thyroid tests in those with pre-existing thyroid dysfunction. We determined that thionamides are effective in a half of subjects treated with a prolonged course and that appropriate patient selection improves success rates. We established that treatment of hyperthyroidism with radioactive iodine results in more weight gain than antithyroid drugs and that hyperthyroidism in hospitalised patients is associated with longer hospital stays, higher frequency of admissions and increased mortality. In conclusion, this thesis provides important new insights into the diagnosis and treatment of hyperthyroidism and highlights that correct evaluation and management of patients may minimise the long-term consequences associated with this common disorder

Predictors of quality of life, functional status, depression and fatigue in early arthritis:Comparison between clinically suspect arthralgia, unclassified arthritis and rheumatoid arthritis

Background: Rheumatoid arthritis (RA) is often preceded by symptomatic phases during which classification criteria are not fulfilled. The health burden of these “at-risk” stages is not well described. This study assessed health-related quality of life (HRQoL), function, fatigue and depression in newly presenting patients with clinically suspect arthralgia (CSA), unclassified arthritis (UA) or RA.Methods: Cross-sectional analysis of baseline Patient-Reported Outcome Measures (PROMs) was conducted in patients from the Birmingham Early Arthritis Cohort. HRQoL, function, depression and fatigue at presentation were assessed using EQ-5D, HAQ-DI, PHQ-9 and FACIT-F. PROMs were compared across CSA, UA and RA and with population averages from the HSE with descriptive statistics. Multivariate linear regression assessed associations between PROMs and clinical and sociodemographic variables.Results: Of 838 patients included in the analysis, 484 had RA, 200 had CSA and 154 had UA. Patients with RA reported worse outcomes for all PROMs than those with CSA or UA. However, “mean EQ-5D utilities were 0.65 (95%CI: 0.61 to 0.69) in CSA, 0.61 (0.56 to 0.66) in UA and 0.47 (0.44 to 0.50) in RA, which was lower than in general and older (≥ 65 years) background populations.” In patients with CSA or UA, HRQoL was comparable to chronic conditions such as heart failure, severe COPD or mild angina. Higher BMI and older age (≥ 60 years) predicted worse depression (PHQ-9: -2.47 (-3.85 to -1.09), P &lt; 0.001) and fatigue (FACIT-F: 5.05 (2.37 to 7.73), P &lt; 0.001). Women were more likely to report worse function (HAQ-DI: 0.13 (0.03 to 0.21), P = 0.01) and fatigue (FACIT-F: -3.64 (-5.59 to -1.70), P &lt; 0.001), and residents of more deprived areas experienced decreased function (HAQ-DI: 0.23 (0.10 to 0.36), P = 0.001), greater depression (PHQ-9: 1.89 (0.59 to 3.18), P = 0.004) and fatigue (FACIT-F: -2.60 (-5.11 to 0.09), P = 0.04). After adjustments for confounding factors, diagnostic category was not associated with PROMs, but disease activity and polypharmacy were associated with poorer performance across all PROMs.Conclusions: Patient-reported outcomes were associated with disease activity and sociodemographic characteristics. Patients presenting with RA reported a higher health burden than those with CSA or UA, however HRQoL in the pre-RA groups was significantly lower than population averages.</div

Patients treated for hyperthyroidism are at increased risk of becoming obese: findings from a large prospective secondary care cohort

YesBackground: The most commonly reported symptom of hyperthyroidism is weight loss; successful treatment increases weight. Weight gain faced by patients with hyperthyroidism is widely considered a simple reaccumulation of premorbid weight, whereas many patients feel there is a significant weight “overshoot” attributable to the treatment. We aimed to establish if weight gain seen following treatment for hyperthyroidism represents replenishment of premorbid weight or “overshoot” beyond expected regain and, if there is excessive weight gain, whether this is associated with the applied treatment modality. Methods: We calculated the risk of becoming obese (body mass index [BMI] >30 kg/m2) following treatment for hyperthyroidism by comparing BMI of 1373 patients with overt hyperthyroidism seen in a secondary care setting with the age- and sex-matched background population (Health Survey for England, 2007–2009). Next, we investigated the effect of treatment with an antithyroid drug (ATD) alone in regard to ATD with radioactive iodine (131I) therapy. We modeled the longitudinal weight data in relation to the treatment pathway to thyroid function and the need for long-term thyroxine replacement. Results: During treatment of hyperthyroidism, men gained 8.0 kg (standard deviation ±7.5) and women 5.5 kg (±6.8). At discharge, there was a significantly increased risk of obesity in male (odds ratio = 1.7 [95% confidence interval 1.3–2.2], p 10 mIU/L; 0.5 kg, 0.3–0.7, p < 0.001) or free thyroxine (fT4) was reduced (fT4 ≤ 10 pmol/L (0.8 ng/dL); 0.3 kg, 0.1–0.4, p < 0.001) during follow-up. Initiation of levothyroxine was associated with further weight gain (0.4 kg, 0.2–0.6, p < 0.001) and the predicted excess weight gain in 131I-induced hypothyroidism was 1.8 kg. Conclusions: Treatment for hyperthyroidism is associated with significant risks of becoming obese. 131I treatment and subsequent development of hypothyroidism were associated with small but significant amounts of excess weight gain compared with ATD alone. We advocate that the discussion over the weight “overshoot” risk forms part of the individualized treatment decision-making process

Financial hardship and health in a refugee population in Australia:A longitudinal study

Refugees and asylum seekers are at a higher risk than the host population to poor health and financial stress. This study uses a unique longitudinal panel from Australia, the Building a New life in Australia (BNLA cohort) to understand the relationship over time between the social determinants of health, health, and financial hardship in refugees and asylum seekers. We employ a longitudinal; dynamic multivariate logistic regression to firstly estimate the relationship between the social determinants of health and poor physical and mental health. Next, we include variables related to financial hardship in our model to determine if there is an association independent of the social determinants of health. Finally, we estimate if there is a relationship between the number of financial hardships and poor physical and mental health. The results show that migrants from North Africa, the Middle East, and Sub-Sahara Africa and women are more likely to suffer from poor health. Financial hardship has an independent association with poor health. We find that going without meals had the highest odds of suffering from poor health. There was evidence of a dose response of financial hardship for those suffering from a limiting long-term health condition and post-traumatic stress syndrome. These findings suggest that refugees in Australia may need additional support past their first year to help them assimilate and contribute to economic productivity