Low failure rate of fixed administered activity of 400 MBq 131I with pre-treatment with carbimazole for thyrotoxicosis: the Gateshead Protocol.

BACKGROUND: Thyrotoxicosis is associated with significant morbidity, therefore adequate control of the disease is paramount. The outcome of treatment of thyrotoxicosis using radioiodine shows variable failure rates depending, amongst other things, on the administered activity of radioiodine and the use of anti-thyroid drugs. Thus, management should follow an evidence based protocol, which has a low failure rate. METHOD: We prospectively analysed the outcome of treatment using our Gateshead protocol of a fixed administered activity of radioiodine therapy (400 MBq) given to 201 patients (including 140 with Graves' disease, 48 with toxic multinodular goitre (TMNG) and 13 with toxic nodule) followed up for a median period of 12 months (range, 6-77 months). Carbimazole was discontinued in patients rendered euthyroid 16 days prior to radioiodine. No routine anti-thyroid drugs or thyroxine were given following radioiodine unless hypothyroidism or thyrotoxicosis occurred. RESULTS: Following the Gateshead protocol led to a failure rate of 6.5% (eight females with Graves' disease, four females with TMNG and one female with toxic nodule), 29% euthyroidism and 64% hypothyroidism. The rates of hypothyroidism for women and for men were: in Graves' disease 77% and 79%, in TMNG 29% and 75%, in toxic nodule 42% and 0%, respectively. CONCLUSIONS: Our observations show that withholding an antithyroid drug in excess of just over 2 weeks prior to administering a fixed administered activity of radioiodine in patients with thyrotoxicosis leads to the lowest reported failure rate, irrespective of the underlying cause. One possible mechanism for this could be the avoidance of drug induced radio-resistance.

Significance of silent ischemia and microalbuminuria in predicting coronary events in asymptomatic patients with type 2 diabetes.

OBJECTIVES: The aim of this study was to investigate the relationships between future coronary heart disease (CHD) events and baseline silent myocardial ischemia (SMI) and microalbuminuria (MA) in subjects with type 2 diabetes (T2D) free from known CHD. BACKGROUND: Coronary heart disease is often asymptomatic in subjects with diabetes. There is limited information on the prognostic value of SMI and MA in this group. METHODS: Eighty-six patients with T2D and no history of CHD were studied (43 with MA individually matched with 43 normoalbuminuric patients; mean [SD] age 62 [+/-7] years, 62 men). Metabolic assessment, three timed overnight urine collections for albumin excretion rate, a treadmill exercise test and ankle brachial index (ABI) were performed at baseline. Patients were followed for 2.8 years. RESULTS: Forty-five (52%) patients had SMI during treadmill testing. At review, there had been 23 coronary (CHD) events in 15 patients. Univariate Cox regression analysis showed that CHD events were significantly related to baseline ABI (p = 0.014), SMI (p = 0.020), MA (p = 0.046), 10-year Framingham CHD risk >30% (p = 0.035) and fibrinogen (p = 0.026). In multivariate analysis, SMI was the strongest independent predictor of CHD events (p = 0.008); risk ratio (95% confidence interval) for SMI: 21 (2 to 204). In the prediction of CHD events, SMI showed higher sensitivity and positive predictive value than MA or Framingham calculated CHD risk. CONCLUSIONS: The presence of baseline SMI and MA are associated with future CHD events in asymptomatic patients with T2D and may be of practical use in risk stratification.

Partial tachyphylaxis to somatostatin (SST) analogues in a patient with acromegaly: the role of SST receptor desensitisation and circulating antibodies to SST analogues.

OBJECTIVE: Somatostatin (SST) analogues are a key option in the management of a variety of conditions, including acromegaly. Tachyphylaxis to SST analogues is not documented in acromegaly. We describe such a phenomenon. DESIGN AND METHODS: A 74-year-old female with acromegaly previously treated with (90)Y implant, external radiotherapy and thrice daily s.c. octreotide had stable GH levels of 19 mU/l. GH progressively rose following switches to lanreotide and depot octreotide as Sandostatin LAR: from 29 to 126 mU/l. Magnetic resonance imaging and (111)In-pentetreotide scanning revealed no tumour growth or alteration in SST receptor (SSTR) status. Tachyphylaxis to SST analogues was considered. Therapy was discontinued and re-introduced in daily 200 microg/24 h increments by continuous s.c. infusion, to a maximum of 1000 microg/24 h, and maintained over 3 weeks with daily, followed by weekly, GH profiles. Competitive (125)I-octreotide radioligand binding assays measured in vitro bio-activity of anti-SST analogue antibodies. In vitro SSTR binding studies utilised SSTR-expressing rat cortex membrane. RESULTS: Median GH fell by 93% from 504 to 39.5 mU/l and rose reproducibly on continued infusion to 120 mU/l. Octreotide withdrawal for 16 h produced a 64% increase in sensitivity. High-affinity IgG anti-lanreotide (IC(50)=187 pmol/l) and anti-octreotide (IC(50)=82 nmol/l) antibody, with no crossreactivity with natural SST, was demonstrated. In vitro inhibition of (125)I-octreotide SSTR binding by anti-SST analogue crossreacting antibody was observed at 1:1 serum dilution. CONCLUSIONS: This is the first report of tachyphylaxis to SST analogues in acromegaly. We believe that the short time course of resensitisation following acute octreotide withdrawal is suggestive of an effect(s) on receptor function or on the receptor signal transduction cascade at sites further downstream, rather than an immune-mediated phenomenon.