Elizabeth L. Chua

TC-1 Is a Novel Tumorigenic and Natively Disordered Protein Associated with Thyroid Cancer

A novel gene, thyroid cancer 1 (TC-1), was found recently to be overexpressed in thyroid cancer. TC-1 shows no homology to any of the known thyroid cancer-associated genes. We have produced stable transformants of normal thyroid cells that express the TC-1 gene, and these cells show increased proliferation rates and anchorage-independent growth in soft agar. Apoptosis rates also are decreased in the transformed cells. We also have expressed recombinant TC-1 protein and have undertaken a structural and functional characterization of the protein. The protein is monomeric and predominantly unstructured under conditions of physiologic salt and pH. This places it in the category of natively disordered proteins, a rapidly expanding group of proteins, many members of which play critical roles in cell regulation processes. We show that the protein can be phosphorylated by cyclic AMP-dependent protein kinase and protein kinase C, and the activity of both of these kinases is up-regulated when cells are stably transfected with TC-1. These results suggest that overexpression of TC-1 may be important in thyroid carcinogenesis.

Prognostic Implications of Lymph Node Yield and Lymph Node Ratio in Papillary Thyroid Carcinoma

BACKGROUND The lymph node yield (LNY) and the lymph node ratio (LNR) have been shown to be important prognostic factors in oral, colon, and gastric cancers. The role of the LNY and LNR in papillary thyroid cancer (PTC) is unclear. The aims of this study were to determine if a high LNR and a low LNY decrease disease-free survival rates. This study further aimed to determine an optimum nodal yield. METHODS A retrospective analysis was conducted of 198 patients with PTC undergoing total thyroidectomy with neck dissection between 1987 and 2011. The LNY and LNR were adjusted by relevant covariates in a multivariate Cox regression analysis with Andersen-Gill extension. RESULTS The LNR was associated with a decrease in disease-free survival (hazard ratio 3.2 [95% confidence interval 1.4-7.3], p=0.005). Patients with an LNR of 0.30 or higher had a 3.4 times higher risk of persistent or recurrent disease compared with patients with an LNR of 0.00 ([95% confidence interval 1.1-10.5], p=0.031). Conversely, patients with an LNR of 0.11 or lower had an 80% chance of remaining disease free during 5 years of follow-up. The LNY showed no significant independent effect and an optimum nodal yield was not determined. CONCLUSIONS The LNR is an important independent prognostic factor in PTC and can be used in conjunction with existing staging systems. A clinical relevant cut-off point of 0.3 (one positive lymph node out of three total) is proposed. No prognostic implications for LNY were identified.

Retinopathy in a Chinese population with type 2 diabetes: factors affecting the presence of this complication at diagnosis of diabetes

This study examined the prevalence of retinopathy in 2131 patients with type 2 diabetes attending a Beijing hospital for the first time. The median age of patients was 58 years (IQR 50-65). The overall prevalence of retinopathy was 27.3% (95% CI: 25.4-29.2) and for proliferative retinopathy 7.8% (95% CI: 6.7-8.9). When all patients were considered together, duration of diabetes (OR=1.8; P=0.001) and albumin excretion rate (OR=1.5; P=0.019) were independent risk factors for retinopathy. Blue-collar occupation (OR=1.5; P=0.047) and blood pressure (OR=1.2; P=0.021) were additional risk factors for non-proliferative and proliferative retinopathy respectively. Amongst the 773 newly diagnosed patients, 21% (95% CI: 17.8-23.6) already had retinopathy. The median age of those patients with retinopathy at diagnosis of diabetes was 3 years higher that those without retinopathy, and blue-collar workers (OR=2.2; P=0.012) as well as female gender were particularly at risk (OR=2.0; P=0.033). There was a strong correlation between duration of diabetes with the presence of retinopathy (r=0.95; P=0.01). By extrapolation, it could be estimated that some degree of hyperglycaemia might have been present for more than 20 years before diabetes was diagnosed. These findings emphasise the importance of earlier diagnosis of diabetes and its complications, especially in socially disadvantaged groups.

Steroid-Induced Diabetes: Is It Just Unmasking of Type 2 Diabetes?

Aims. We compared the demographic profile and clinical characteristics of individuals with new onset steroid-induced diabetes (NOSID) to Type 2 diabetes (T2DM) patients with and without steroid treatment. Methods. The demographic profile and clinical characteristics of 60 individuals who developed NOSID were examined and matched to 60 type 2 diabetes patients receiving steroid therapy (T2DM+S) and 360 diabetic patients not on steroids (T2DM) for age, duration of diabetes, HbA1c, gender, and ethnicity. Results. Patients who developed NOSID had less family history of diabetes (P ≤ 0.05) and were less overweight (P ≤ 0.02). NOSID was more commonly treated with insulin. Despite a matching duration of diabetes and glycaemic control, significantly less retinopathy was found in the group of patients with NOSID (P < 0.03). Conclusions. It appears that steroid treatment primarily precipitated diabetes in a group of individuals otherwise less affected by risk factors of diabetes at that point in time, rather than just opportunistically unmasking preexisting diabetes. Furthermore, the absence of retinopathy suggests that patients with NOSID had not been exposed to long periods of hyperglycaemia. However, the impact of the underlying conditions necessitating steroid treatment and concomitant medications such as immunosuppressants on diabetes development remain to be defined.

The danger of using inappropriate point‐of‐care glucose meters in patients on icodextrin dialysis

Diabet. Med. 28, 1272–1276 (2011)

Ipilimumab-induced hypophysitis in melanoma patients: an Australian case series

Ipilimumab (Yervoy; Bristol‐Myers Squibb) is a novel fully humanised monoclonal antibody that blocks cytotoxic T‐lymphocyte antigen 4, an immune checkpoint molecule, to augment anti‐tumour T‐cell responses. It is associated with significant immune‐related side‐effects including hypophysitis.

Elevated serum thyroglobulin levels at the time of ablative radioactive iodine therapy indicate a worse prognosis in thyroid cancer: an Australian retrospective cohort study.

BACKGROUND Serum thyroglobulin is used as a surrogate marker for well-differentiated thyroid carcinoma recurrence. This study investigates whether thyroglobulin measured at the time of ablative radioactive iodine therapy predicts disease-free survival. METHODS A retrospective review was conducted of patients with well-differentiated thyroid carcinoma presenting from 1989 to 2010 at the Royal Prince Alfred Hospital, New South Wales, Australia. Disease-free survival of patients with a significantly elevated stimulated thyroglobulin level (27.5 µg/l or higher) at the time of ablative radioactive iodine therapy was compared to that of patients without a significantly elevated thyroglobulin level using univariate analysis. RESULTS Patients with a thyroglobulin level of 27.5 µg/l or higher had an increased relative risk of disease recurrence of 4.50 (95 per cent confidence interval = 1.35-15.04). If lateral neck dissection was required at the time of surgery, patients also had an increased relative risk of macroscopic disease recurrence of 4.94 (95 per cent confidence interval = 1.47-16.55). CONCLUSION An elevated thyroglobulin level of 27.5 µg/l or higher at the time of ablative radioactive iodine therapy is a prognostic indicator for macroscopic disease recurrence in well-differentiated thyroid carcinoma.

Acute adrenal insufficiency: an aide-memoire of the critical importance of its recognition and prevention

Adrenal crisis is a life‐threatening emergency that causes significant excess mortality in patients with adrenal insufficiency. Delayed recognition by medical staff of an impending adrenal crisis and failure to give timely hydrocortisone therapy within the emergency department continue to be commonly encountered, even in metropolitan teaching hospitals. Within the authors’ institutions, several cases of poorly handled adrenal crises have occurred over the last 2 years. Anecdotal accounts from members of the Addisons support group suggest that these issues are common in Australia. This manuscript is a timely reminder for clinical staff on the critical importance of the recognition, treatment and prevention of adrenal crisis. The manuscript: (i) outlines a case and the clinical outcome of sub‐optimally managed adrenal crisis, (ii) summarises the clinical features and acute management of adrenal crisis, (iii) provides recommendations on the prevention of adrenal crisis and (iv) provides guidance on the management of ‘sick days’ in patients with adrenal insufficiency.

Management of incidental and non-incidental papillary thyroid microcarcinoma

BACKGROUND The incidence of papillary thyroid cancer is rising, with an increase in the number of microcarcinomas being discovered. There is controversy in the literature regarding the optimal management of these tumours. This study aimed to review our institutions experience with the presentation and management of papillary thyroid microcarcinoma. METHODS Retrospective analysis from the Sydney Head and Neck Cancer Institute, from 1987 to 2009. RESULTS A total of 228 patients were analysed. Papillary thyroid microcarcinomas were discovered incidentally in 116 (50.9 per cent) patients and non-incidentally in the remaining 112 (49.1 per cent) patients. Amongst the non-incidental group, 11.6 per cent of patients presented with lateral cervical lymph node involvement. Non-incidental microcarcinomas were significantly associated with younger age (<45 years) (p = 0.007) and larger tumours (5-10 mm) (p < 0.001). Only four patients in the incidental group suffered recurrent disease (locoregional). No patient developed distant metastatic disease or died during follow up. CONCLUSION Papillary thyroid microcarcinomas present both incidentally and non-incidentally, with equal prevalence. Non-incidental tumours not infrequently present with cervical lymph node disease. The patient outcome is generally excellent.

Focal Bronchiectasis Causing Abnormal Pulmonary Radioiodine Uptake in a Patient with Well-Differentiated Papillary Thyroid Carcinoma

Background. False-positive pulmonary radioactive iodine uptake in the followup of differentiated thyroid carcinoma has been reported in patients with certain respiratory conditions. Patient Findings. We describe a case of well-differentiated papillary thyroid carcinoma treated by total thyroidectomy and radioiodine ablation therapy. Postablation radioiodine whole body scan and subsequent diagnostic radioiodine whole body scans have shown persistent uptake in the left hemithorax despite an undetectable stimulated serum thyroglobulin in the absence of interfering thyroglobulin antibodies. Contrast-enhanced chest computed tomography has confirmed that the abnormal pulmonary radioiodine uptake correlates with focal bronchiectasis. Summary. Bronchiectasis can cause abnormal chest radioactive iodine uptake in the followup of differentiated thyroid carcinoma. Conclusions. Recognition of potential false-positive chest radioactive iodine uptake, simulating pulmonary metastases, is needed to avoid unnecessary exposure to further radiation from repeated therapeutic doses of radioactive iodine.