Case Presentation: A 50-year-old lady developed recurrent Cushing's disease after being in remission following transsphenoidal surgery (TSS) for a left pituitary microadenoma 16 years ago. The repeat MRI showed a right pituitary microadenoma (1.7 mm × 1.3 mm) for which she underwent a second TSS. However, she continued to have persistent hypercortisolism despite repeated MRIs showing absence of tumour recurrence. She refused bilateral adrenalectomy and external radiotherapy. Ketoconazole was commenced at 200 mg twice daily for disease control but this was hindered by intolerable side effects including pruritus and skin exfoliation. In the meantime, she suffered a right hypertensive basal ganglia hemorrhage. Treatment was subsequently switched to cabergoline and the dose titrated to 0.5 mg daily. Fluconazole 400 mg daily was later added to control the persistent disease. Her clinical and biochemical parameters improved markedly three months after the addition of fluconazole. No adverse event was reported. Her disease has remained stable for the last 15 months up until the time of the recent clinic review.

METHODS AND ANALYSIS: This mixed-method project has two phases. In phase 1, we will identify a list of patient-reported and clinical outcomes through qualitative research and systematic reviews. In phase 2, we will categorise the identified outcomes using the Core Outcome Measures in Effectiveness Trials taxonomy of core domains and the International Classification of Functioning, Disability and Health. We will develop questionnaires from the list of outcomes identified from each domain for the two-round online Delphi exercise, aiming to reach a consensus on the COS. The Delphi process will include patients, carers, researchers and healthcare participants. We will hold an online consensus meeting involving representatives of all key stakeholders to establish the final COS.

ETHICS AND DISSEMINATION: The study has been reviewed and approved by the Ethics Committee for Research Involving Human Subjects, Universiti Putra Malaysia and the Research Ethics Committee, National University of Malaysia. This proposed COS in TD will improve the value of data, facilitate high-quality evidence synthesis and evidence-based decision-making. Furthermore, we will present the results to participants, in peer-reviewed academic journals and conferences.

METHODS: Population-based surveys included 30,721 Malay, 10,865 Indian and 25,296 Chinese adults from The Malaysian Cohort, and 413,737 White adults from UK Biobank. Sex-specific linear regression models estimated associations of anthropometry and body composition (body mass index [BMI], waist circumference [WC], fat mass, appendicular lean mass) with systolic blood pressure (SBP), low-density lipoprotein cholesterol (LDL-C), triglycerides and HbA1c.

RESULTS: Compared to Malay and Indian participants, Chinese adults had lower BMI and fat mass while White participants were taller with more appendicular lean mass. For BMI and fat mass, positive associations with SBP and HbA1c were strongest among the Chinese and Malay and weaker in White participants. Associations with triglycerides were considerably weaker in those of Indian ethnicity (eg 0.09 [0.02] mmol/L per 5 kg/m2 BMI in men, vs 0.38 [0.02] in Chinese). For appendicular lean mass, there were weak associations among men; but stronger positive associations with SBP, triglycerides, and HbA1c, and inverse associations with LDL-C, among Malay and Indian women. Associations between WC and risk factors were generally strongest in Chinese and weakest in Indian ethnicities, although this pattern was reversed for HbA1c.

METHODOLOGY: FPG and HbA1c were taken from 40,667 eligible TMC participants that have no previous history of diabetes, aged between 35-70 years and were recruited from 2006 - 2012. Participants were classified as normal, diabetes and pre-diabetes based on the 2006 World Health Organization (WHO) criteria. Statistical analyses were performed using ANOVA and Chi-square test, while Pearson correlation and Cohen's kappa were used to examine the concordance rate between FPG and HbA1c.

RESULTS: The study samples consisted of 16,224 men and 24,443 women. The prevalence of diabetes among the participants was 5.7% and 7.5% according to the FPG and HbA1c level, respectively. Based on FPG, 10.6% of the participants had pre-diabetes but this increased to 14.2% based on HbA1c (r=0.86; P<0.001). HbA1c had a sensitivity of 58.20 (95% CI: 56.43, 59.96) and a specificity of 98.59 (95% CI: 98.46, 98.70).