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H Gin, B Catargi, V Rigalleau, E Rullier, P Roger and A Tabarin

Surgical removal is the treatment of choice for insulinomas. Definitive biochemical diagnosis of organic hyperinsulinism has to be established before surgery. These tumors are sometimes undetected by preoperative imaging investigations and, in addition, surgical management may also be complicated by the absence of palpable tumors or the presence of multiple tumors. We report the value of the euglycemic clamp technique for diagnosis and surgical treatment in 21 patients with confirmed insulinomas. Data were compared with 12 controls, and nine patients were retested after surgery. During the euglycemic hyperinsulinic clamp, the mean C-peptide value was 3.6+/-2.2 ng/ml and it remained high (3.8+/-2.5 ng/ml), despite exogenous hyperinsulinemia (1762.7+/-233.2 microU/ml for the highest plateau). In contrast, the C-peptide concentration declined in 12 control patients (0.3+/-0.1 ng/ml, P < 0.001) and after successful surgery in nine retested patients (0.3+/-0.2 ng/ml, P < 0.01). During continuous glucose monitoring, successful removal of the insulin-secreting tumor was accompanied by an increase in plasma glucose concentrations and a loss of requirement for endogenous glucose within 36 min (range 28-43 min). The continuing requirement for glucose after the ablation of the tumor revealed the existence of additional and initially undetected tumors in four patients, among whom two had the multiple endocrine neoplasia type I (MEN I) syndrome. We conclude that the euglycemic hyperinsulinic clamp is a reliable and convenient diagnostic test for insulinoma, as it is both safe (no hypoglycemia) and relatively brief (3 x 90 min). Glucose monitoring and glucose clamping provide a reliable indicator of complete removal of insulin-hypersecreting tissue, especially in patients with occult or multiple tumors.

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B Catargi, F Leprat, M Guyot, N Valli, D Ducassou and A Tabarin

The best approach to radioiodine dose selection in the treatment of Graves' hyperthyroidism remains highly controversial. The formula to calculate the individual dose of (131)I to be delivered has been used for half a century and takes into account the thyroid mass, the effective half-life and the maximum uptake of (131)I. The objective of the present study was to evaluate the accuracy of this formula by determining the relationship between the administered dose of (131)I calculated to deliver a target dose of 50Gy to the thyroid and the actual exact organ dose. We further analyzed if therapeutic success, defined by euthyroidism following the individually calculated dose, can be predicted by different pretreatment parameters and particularly by organ dose. One hundred patients with a first episode of Graves' disease and who had received optimal thyroid irradiation after precise dosimetry were retrospectively reviewed. The patients were categorized according to their thyroid function (plasma free thyroxine (T(4)) serum concentration) as eu-, hyper- or hypothyroid during and 1 year after treatment. The relationship between the administered dose and organ dose was assessed by simple regression. We compared free T(4), free tri-iodothyronine, thyroid weight, the number of patients with antithyroperoxidase antibodies and TSH receptor autoantibodies, 24h urinary iodine excretion, (131)I uptake, and the exact dose of (131)I delivered to the thyroid as pretreatment variables. Although we found a correlation between administered dose (mCi) and organ dose (Gy) (r=0.3, P=0.003), the mean coefficient of variation for organ dose was 45%. Individualized radioiodine therapy enabled euthyroidism in 26% of patients and failed in 74% of patients (33% had persistent or recurrent hyperthyroidism and 41% permanent hypothyroidism). (131)I uptake was significantly higher in the hyperthyroidism group in comparison with the euthyroid group. However, organ dose and other pretreatment variables did not differ among the three groups. In conclusion, these results confirm the low performance of individual dosimetry using what are established ratios, since the delivered dose to the gland, although correlated to the intended dose, is highly variable. The finding that other usual pretreatment variables are not different between groups, gives little hope for improving the way of calculating the ideal dose of radioiodine. We suggest to those not yet ready to give a standard or an ablative dose for Graves' hyperthyroidism that they abandon this way to calculate the (131)I dose.

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N Valli, B Catargi, N Ronci, V Vergnot, F Leccia, JM Ferriere, G Chene, N Grenier, F Laurent and A Tabarin

OBJECTIVE: Biochemistry and I-6beta-iodomethyl norcholesterol scintigraphy (IMS) have both been used to assess cortisol secretion by adrenocortical incidentalomas. However, which biochemical abnormalities indicate subclinical corticoid excess is still debatable whilst IMS is expensive and cumbersome. The aim of the study was to evaluate prospectively patients with adrenal incidentalomas using both IMS and biochemical methods to examine whether the IMS pattern is associated with biochemical abnormalities and, if this is so, to find a biochemical parameter that could be used as a screening test to identify a subset of patients on whom IMS could subsequently be performed. METHODS: Thirty-one patients with benign cortical adenomas were recruited from 43 consecutive patients with adrenal incidentalomas. All 31 patients underwent IMS and measurement of (i) 0800 h serum cortisol, ACTH, dehydroepiandrosterone and 17-hydroxyprogesterone; (ii) midnight serum cortisol; (iii) 2400 h excretion of urinary free cortisol; (iv) cortisol after the overnight 1 mg dexamethasone (DEX) suppression test; (v) cortisol after an i.v. 4 mg DEX test; (vi) determination of the diurnal variation in serum cortisol. RESULTS: Sixty-one per cent of patients displayed unilateral uptake during IMS and 39% showed bilateral uptake. Patients with unilateral uptake exhibited significantly lower ACTH concentrations (P=0.0005), higher midnight cortisol concentrations (P=0.02), disrupted diurnal variation of serum cortisol (P=0.02) and higher cortisol concentrations after DEX suppression tests (P=0.01). Cortisol concentrations following the two DEX suppression tests correlated closely (r=0.80, P=0.0001). The i.v. 4 mg DEX test was clearly more sensitive for the diagnosis of unilateral uptake than the overnight 1 mg DEX test (76 vs 52%). Using various thresholds of cortisol concentration following the overnight 1 mg DEX test, it was found that the sensitivity of the test could be improved to 100% if the threshold was set at 60 nmol/l rather than the classical value of 138 nmol/l. All patients but one with post-test serum cortisol concentrations above 60 nmol/l as against none of patients with cortisol below 60 nmol/l exhibited at least one associated biochemical abnormality indicating subclinical glucocorticoid excess. CONCLUSION: In adrenocortical incidentalomas, unilateral uptake during IMS suggests subclinically excessive and/or autonomous cortisol secretion. A cortisol concentration above 60 nmol/l following the overnight 1 mg DEX test is highly correlated with unilateral uptake and is associated with biochemical abnormalities indicating subclinical glucocorticoid excess. Our results favour the use of the 1 mg overnight DEX test with revised criteria of interpretation as a screening test for subclinical hypercortisolism among patients with adrenocortical incidentalomas.