Management of Hyperosmolar Hyperglycaemic State (HHS) in Adults: An updated guideline from the Joint British Diabetes Societies (JBDS) for Inpatient Care Group.

Hyperosmolar Hyperglycaemic State (HHS) is a medical emergency associated with high mortality. It occurs less frequently than diabetic ketoacidosis (DKA), affects those with pre-existing/new type 2 diabetes mellitus and increasingly affecting children/younger adults. Mixed DKA/HHS may occur. The JBDS HHS care pathway consists of 3 themes (clinical assessment and monitoring, interventions, assessments and prevention of harm) and 5 phases of therapy (0-60 min, 1-6, 6-12, 12-24 and 24-72 h). Clinical features of HHS include marked hypovolaemia, osmolality ≥320 mOsm/kg using [(2×Na+ ) + glucose+urea], marked hyperglycaemia ≥30 mmol/L, without significant ketonaemia (≤3.0 mmol/L), without significant acidosis (pH >7.3) and bicarbonate ≥15 mmol/L. Aims of the therapy are to improve clinical status/replace fluid losses by 24 h, gradual decline in osmolality (3.0-8.0 mOsm/kg/h to minimise the risk of neurological complications), blood glucose 10-15 mmol/L in the first 24 h, prevent hypoglycaemia/hypokalaemia and prevent harm (VTE, osmotic demyelination, fluid overload, foot ulceration). Underlying precipitants must be identified and treated. Interventions include: (1) intravenous (IV) 0.9% sodium chloride to restore circulating volume (fluid losses 100-220 ml/kg, caution in elderly), (2) fixed rate intravenous insulin infusion (FRIII) should be commenced once osmolality stops falling with fluid replacement unless there is ketonaemia (FRIII should be commenced at the same time as IV fluids). (3) glucose infusion (5% or 10%) should be started once glucose <14 mmol/L and (4) potassium replacement according to potassium levels. HHS resolution criteria are: osmolality <300 mOsm/kg, hypovolaemia corrected (urine output ≥0.5 ml/kg/h), cognitive status returned to pre-morbid state and blood glucose <15 mmol/L.

A dose-effect correlation for radioiodine ablation in differentiated thyroid cancer.

PURPOSE: The aim of this study was to determine the range of absorbed doses delivered to thyroid remnants, blood, and red marrow from fixed administrations of radioiodine and to ascertain whether the success of ablation is more dependent on these absorbed doses than on the administered activity. METHODS: Twenty-three patients received 3,000 MBq radioiodine following near-total thyroidectomy. The maximum absorbed dose to remnants was calculated from subsequent single photon emission tomography scans. Absorbed doses delivered to blood and red marrow were calculated from blood samples and from whole-body retention measurements. The protein bound iodine (PBI) was also calculated. RESULTS: Maximum absorbed doses to thyroid remnants ranged from 7 to 570 Gy. Eighteen of the 23 patients had a successful ablation. A significant difference was seen between the absorbed doses delivered to thyroid remnants, blood, and red marrow for those patients that had a successful ablation compared to those with a failed ablation (p = 0.030, p = 0.043 and p = 0.048, respectively). The difference between the PBI values acquired at day 1 and day 6 were also indicative of response (p = 0.074). CONCLUSIONS: A successful ablation is strongly dependent on the absorbed dose to the thyroid remnant. Dosimetry-based personalized treatment can prevent both sub-optimal administrations, which entails further radioiodine therapy, and excessive administration of radioactivity, which increases the potential for radiation toxicity.

Thyroid cancer causing obstruction of the great veins in the neck.

BACKGROUND AND AIMS: To report our experience and review the literature of thyroid cancer obstructing the great veins in the neck, highlighting clinical aspects and response to treatment. METHODS: Clinical data were collected from the thyroid cancer register and from follow-up clinic visits of patients referred to the Thyroid Unit at the Royal Marsden Hospital. A Medline literature search was conducted between 1980 and 2007. RESULTS: Of 1448 patients with thyroid cancer on our cancer register and treated in our unit over the last 60 years, we identified five patients, four women and one man, aged 43 - 81 years with a median follow up of 28 (24-78) months in whom tumour had occluded the great veins in the neck. All patients underwent total thyroidectomy and all subsequently received ablative 131I with the exception of patient 3 whose post-operative isotope scan shown no significant 131I uptake. External beam radiotherapy to the neck and upper mediastinum was used for residual disease control in the 5 patients. The median survival was 28 months and the disease-free survival was 24 months. One patient remains asymptomatic but with disease 53 months after initial presentation. Survival in this small series is significantly better than that previously reported for this condition. CONCLUSION: A multimodality therapeutic approach comprising surgery, radioiodine and external beam radiotherapy may give the best results for patients in whom thyroid cancer is occluding the great veins.

131I activity for remnant ablation in patients with differentiated thyroid cancer: A systematic review.

CONTEXT: Radioiodine ablation of the thyroid remnant after thyroidectomy is commonly performed in the management of patients with differentiated thyroid cancer. Although many centers administer an activity of 100 mCi, there is uncertainty over using a lower activity. OBJECTIVE: A systematic review of the published literature was used to compare the success rates of remnant ablation using approximately 30 mCi with approximately 100 mCi (1.1 vs. 3.7 GBq). DATA SOURCES: Data were obtained from MEDLINE and EMBASE for the years 1966 to March 2006. STUDY SELECTION: All studies that reported rates of successful ablation associated with approximately 30 or approximately 100 mCi of radioiodine were reviewed. DATA EXTRACTION: Studies were based on reviews of patient case notes (n = 41), prospective cohorts (n = 12), and randomized trials (n = 6). We obtained the success of thyroid remnant ablation according to different administered activities of radioiodine. Where a study reported on two or more activities, the risk ratio of having a successful ablation (approximately 30 vs. approximately 100 mCi) was calculated and combined in a meta-analysis. DATA SYNTHESIS: Observational studies confirmed the high ablation success rate ( approximately 80%) using approximately 100 mCi, although 22% of studies reported a rate of 90% or greater. The pooled ablation success rate in these studies was 10% lower using 30 mCi compared with 100 mCi (95% confidence interval, 3-17%; P = 0.01). The meta-analysis of the randomized trials produced equivocal results. For example, the rate of successful ablation in patients given 30 mCi was 8% lower compared with 100 mCi (95% confidence interval, 29% lower or up to 20% greater, P = 0.58), consistent with there being no difference or that 30 mCi is much less effective. CONCLUSIONS: From the published data, it is not possible to reliably determine whether ablation success rates using 30 mCi are similar to using 100 mCi. Large randomized trials are needed to resolve the issue and guide clinical practice.

Metastatic thyroid carcinoma causing superior vena caval obstruction diagnosed on I-131 scan.

An 80-year-old woman was referred for a painless mass arising in right side of her neck of 4 months' duration. Ultrasound revealed a multinodular goiter, but cytology confirmed a follicular carcinoma. Thyroid function was normal. Total thyroidectomy was performed with evidence of tumor infiltration into the strap muscles extending up to the right submandibular gland and right internal jugular vein, which was completely occluded. Radioiodine was considered as the treatment of choice postoperatively. This is an unusual case of SVC obstruction caused by tumor embolus diagnosed on I-131 scan.

Treatment of advanced differentiated thyroid carcinoma with high activity radioiodine therapy.

OBJECTIVES: This was a retrospective study to assess the efficacy and morbidity of high activity I therapy in patients with advanced differentiated thyroid carcinoma. METHODS: From 1975 to 2003, 38 patients with locally advanced or metastatic differentiated thyroid cancer (16 follicular, 20 papillary, one Hurthle cell, one insular) were treated with high activity radioiodine therapy (9 GBq) as the cancers had previously not responded to standard activities (5.5 GBq). RESULTS: Cumulative total activities received ranged from 11.8 to 84.5 GBq (mean 29.4 GBq per patient). Staging at presentation showed pT4 and/or M1 disease in 27/38 of patients (71.1%). Moderate (grade 2) and poorly differentiated (grade 3) tumours were present in a total of 9/38 patients (23.7%). Outcomes were evaluated according to the results of I whole-body scans, serum thyroglobulin, radiological assessments and physical examination. Neither [18F]flurodeoxyglucose positron emission tomography (F-FDG PET) nor 99mTc sestamibi were available during this study. The mean duration of follow-up was 83 months. A complete response was observed in 7/38 patients (18.4%), progressive disease in 27/38 (71.1%) and stable disease in 4/38 (10.5%). The mean survival from initiation of high activity treatment was 36.6 months. For patients with lung disease the mean survival was 45 months, neck disease 38.9 months, bone disease 35 months and multiple sites was 30.9 months. Twelve patients died during follow-up (10 due to thyroid carcinoma). After high activity treatment, 9.7% of patients suffered grade 3 and 3.2% suffered grade 4 WHO haematological toxicity. Significant salivary gland morbidity was observed (30% dry mouth, 27% salivary swelling). CONCLUSIONS: Repeated treatment with high activity (9 GBq) I in patients with advanced differentiated thyroid carcinoma appears to be of no apparent benefit and may lead to late morbidity.