P. M. Bell

Effects of low-dose oral hydrocortisone replacement versus short-term reproduction of physiological serum cortisol concentrations on insulin action in adult-onset hypopituitarism.

objective Hypercortisolism is associated with impaired glucose tolerance and insulin resistance. For many years hydrocortisone 30 mg was the standard total daily replacement dose in adult hypopituitarism. The use of this conventional dose has now been shown to result in mild biochemical hypercortisolism and might contribute to the increased cardiovascular risk reported in hypopituitarism. The use of lower doses of hydrocortisone replacement therapy might prevent some of the adverse metabolic effects seen with conventional doses.

Insulin action and hepatic glucose cycling in Cushing's syndrome

Although it is well established that hypercortisolism causes insulin resistance, the mechanisms responsible for impaired insulin action in Cushings syndrome are unclear. This study investigated the contribution of the glucose/glucose‐6‐phosphate substrate cycle (G/G6P).

Prevalence of diabetes and impaired glucose tolerance in adult hypopituitarism on low dose oral hydrocortisone replacement therapy.

OBJECTIVE The conventional dosage of hydrocortisone, used for many years in the management of hypopituitarism (30u2003mg per day), has now been shown to be more than is physiologically necessary. On this conventional corticosteroid therapy studies have demonstrated an increased prevalence of diabetes and impaired glucose tolerance, which may contribute to the increased vascular morbidity and mortality reported in the condition. In these studies no information is available on oral glucose tolerance test (OGTT) timing in relation to administration of oral steroid and variable hydrocortisone doses were employed.

Factors affecting the adhesion of Candida albicans to epithelial cells of insulin-using diabetes mellitus patients

This study investigated the influence of the carbon source of the growth medium, strains of Candida albicans and source of epithelial cells, and the influence of smoking and gender, on the adhesion of C. albicans to epithelial cells from insulin-using diabetic patients. Adhesion was determined by an autologous adhesion assay with exfoliated buccal or palatal epithelial cells and one strain of C. albicans isolated from each patient. The type strain CBS 562 was also used. Glucose or sucrose were used as the predominant carbon sources of the growth medium. The autologous strain of C. albicans adhered selectively to the oral mucosa of diabetic patients. Palatal epithelial cells retained significantly more C. albicans in vivo and adhesion was influenced by the availability of sugars in the growth medium and the strain of C. albicans.

Serum 25-hydroxyvitamin D and insulin resistance in people at high risk of cardiovascular disease: a euglycaemic hyperinsulinaemic clamp study

In observational studies, low serum 25‐hydroxyvitamin D (25‐OHD) concentration is associated with an increased risk of type 2 diabetes mellitus (DM). Increasing serum 25‐OHD may have beneficial effects on insulin resistance or beta‐cell function. Cross‐sectional studies utilizing suboptimal methods for assessment of insulin sensitivity and serum 25‐OHD concentration provide conflicting results.

Conventional withdrawal of thyroid hormone before radioiodine therapy in differentiated thyroid carcinoma: how frequently are adequately raised TSH levels attained?

Adequate surgical treatment, long-term suppression of TSH and the use of RAI therapy have been shown to produce reduced recurrence rates and lower disease specific mortality in patients with differentiated thyroid carcinoma. Recent recommendations are that serum TSH levels of > 30 mU/l should be achieved to ensure maximal uptake and effectiveness of RAI therapy in the treatment of thyroid carcinoma. 1,2 Different strategies may be employed to ensure that TSH levels are increased. The most common method is to substitute tertroxin for T4 for a period of 4 weeks and then to discontinue it also for 2 weeks prior to therapy. 2 Alternatively, T4 therapy may simply be withdrawn for 4 weeks without a need for thyroid hormone replacement, 1 but this often leads to very symptomatic hypothyroidism. Another newer but expensive option is the use of recombinant TSH which provides a means of elevating the TSH level without the need for withdrawal of thyroid hormone therapy. A study by Liel 3 suggested that attaining target TSH levels before radioactive iodine therapy requires a considerably shorter time than currently recommended. The mean interval required to reach TSH > 30 mU/l (after withdrawal of T4 without tertroxin substitution) was 17 days. However, 95% confidence intervals (15–19) and range (11–28) days were wide. A further study by Serhal et al . 4 looked at the rise in TSH concentrations after total thyroidectomy or withdrawal of suppressive T4 therapy in preparation for RAI. The time required for TSH levels to reach > 30 mU/l was 8–26 days (mean ± SD, 14·2 ± 4·8) after thyroidectomy without replacement therapy and 9–29 days (18·1 ± 4·1) after T4 withdrawal without tertroxin substitution. However, the wide inter-individual variations raise concerns about the appropriateness of these strategies for the individual patient. We report in this letter an audit of the effectiveness of a conventional, widely used regimen of substitution of tertroxin for T4, 6 weeks prior to radioiodine therapy and then its subsequent discontinuation 2 weeks prior to therapy, in achieving adequate levels of TSH. We studied 52 consecutive ablative RAI therapy sessions for thyroid carcinoma (29 papillary, 20 follicular and 3 mixed). Twenty-five patients were on tertroxin immediately postsurgery, while the 27 who had been on T4 were switched to tertroxin 6 weeks prior to RAI and then all discontinued it 2 weeks before measurement of TSH. Thyroid hormone withdrawal was associated with a serum TSH level of > 30 mU/l in 46 out of 52 (88·5%) of patients. However, 6 out of 52 (11·5%) did not achieve a TSH level of 30 mU/l with TSH between 20 and 30 mU/l in three, and between 15 and 20 mU/l in the remaining three. These six patients would be considered as having sub optimal TSH levels which may have compromised the effectiveness of treatment. In five of these six patients, there was uptake on late scanning and in one patient there was not (TSH 16·9 mU/l). A study by Menzel et al . 5 showed a slight trend towards less extensive TSH stimulation after thyroid hormone withdrawal in elderly patients. In our audit the mean age of those achieving TSH > 30 mU/l was 53·5 ± 2·47 years and 56·7 ± 4·28 years in those who did not with no significant difference between the two groups. The British Thyroid Association 1 has produced guidelines for the management of differentiated thyroid cancer. The aims of these is to improve long-term overall and disease free survival, enhance patients’ health-related quality of life, and improve referral pattern and management of patients with thyroid cancer. In order to use 131 I either for imaging or as ablative therapy in patients with differentiated thyroid cancer, high levels of TSH must be present. The minimal length of time needed to achieve maximal 131 I uptake has not been fully determined. Extending the time-off thyroid hormone may lead to prolonged and unpleasant symptoms of hypothyroidism. The logistics of ordering high dose radioiodine therapy and arranging planned admission make organization based on a late TSH measurement very difficult without prolonging the symptomatic hypothyroid phase for the patient. Our audit demonstrates that the 6-week protocol outlined above is effective. If TSH is shown to have been < 20 mU/l at the time of therapy then (i) radioiodine may be given again under recombinant TSH stimulation, if no uptake was seen in the late scan after initial therapy and subsequent thyroglobulin levels suggest that abnormal tissue remains (2% of cases); and (ii) if future therapy is required, either recombinant TSH or longer withdrawal should be considered in those whose serum TSH was < 30 mU/l and yet in whom uptake was seen with the initial treatment. A more radical solution, to avoid the 11·5% of patients who do not achieve TSH > 30 mU/l, would be to use recombinant TSH in all cases, but to date that remains expensive and is unnecessary in 88·5% cases. This audit therefore demonstrates that our routine procedure of thyroid hormone withdrawal for therapeutic radioiodine therapy is extremely effective in achieving adequate levels of TSH (> 30 mU/l in 88·5%). We conclude that a standard practice of switching T4 to tertroxin 6 weeks before RAI and then discontinuing tertroxin 2 weeks before RAI is preferable to a straight withdrawal of T4 with the latter methods’ wide variability in achieving TSH > 30 mU/l.

Change in frequency and severity of limited joint mobility in type 1 diabetes. 1982-2002

ConclusionThe prevalence of LJM has decreased most likely as a result of improved blood glucose control during the past 20 years. LJM remains a useful clinical risk indicator of microvascular disease.

Rosiglitazone does not improve endothelial function in patients with essential hypertension

ConclusionRosiglitazone improves insulin sensitivity in patients with essential hypertension. However, despite this there was no change in endothelial function.