The application of the combined corticotropin-releasing hormone plus desmopressin stimulation during petrosal sinus sampling is both sensitive and specific in differentiating patients with Cushing's disease from patients with the occult ectopic adrenocorticotropin syndrome.

CONTEXT: Although bilateral inferior petrosal sinus sampling (BIPSS) with CRH stimulation is the most accurate procedure for the differential diagnosis of ACTH-dependent Cushing's syndrome (CS), 4-15% of patients with Cushing's disease (CD) fail to demonstrate diagnostic gradients. Preliminary data suggest that a more potent stimulation by the combined administration of CRH plus desmopressin during BIPSS may provide some diagnostic advantage. A crucial issue, however, is whether such an amplified stimulation may affect the specificity of the procedure, and this was the main aim of the present study. OBJECTIVE: We investigated the diagnostic accuracy of BIPSS performed by CRH plus desmopressin stimulation. DESIGN AND SETTING: A retrospective analysis was conducted at a single tertiary care center. PARTICIPANTS: Fifty-four patients were admitted for the investigation of ACTH-dependent CS. CD was diagnosed in 47 patients; occult ectopic ACTH syndrome (oEAS) was histologically confirmed in seven patients. INTERVENTION(S): All patients underwent BIPSS with CRH plus desmopressin administration. Additional noninvasive tests included CRH test, high-dose dexamethasone suppression test, desmopressin test, and pituitary magnetic resonance imaging. MAIN OUTCOME MEASURES: Gradients of inferior petrosal sinus (IPS) to peripheral (IPS/P) ACTH were calculated before and after stimulation with CRH plus desmopressin. RESULTS: The sensitivity for a basal IPS/P gradient greater than 2 was 61.7%, with 100% specificity and a diagnostic accuracy of 66.7%. After stimulation with CRH plus desmopressin, receiver operating characteristic (ROC) curve analysis showed that a cutoff gradient of more than 2 offers the best test performance. In total, 46 of 47 patients with CD had an IPS/P gradient greater than 2, but none of the patients with oEAS, resulting in a sensitivity of 97.9%. The specificity was 100%, diagnostic accuracy was 98.2%, and the positive and negative predictive values were 100 and 87.5%, respectively. A subgroup of 18 patients (16 with CD and two with oEAS) had contradictory responses to routine tests with CRH and/or high-dose dexamethasone suppression test; sensitivity, specificity, and accuracy of BIPSS in this subgroup were 100%. CONCLUSIONS: The application of a combined stimulation with CRH plus desmopressin during BIPSS is associated with a high sensitivity but no loss of specificity.

Arterial stiffness in type 1 diabetes mellitus is aggravated by autoimmune thyroid disease.

OBJECTIVE: The aim of our study was to measure arterial stiffness in patients with Type 1 diabetes mellitus, its contributing factors and its relation to macrovascular arterial changes. MATERIALS AND METHODS: Thirty-one female Type 1 diabetic patients were studied; 11 had concomitant autoimmune thyroid disease although euthyroid during the study period. Stiffness was studied using applanation tonometry and pulse wave analysis for evaluation of systolic arterial pressure augmentation secondary to arterial stiffening and early wave reflection. Results were compared to 24 healthy individuals. In all patients, endothelium-related flow-mediated dilation (FMD) of the brachial artery and intima-media thickness (IMT) of the carotid artery were measured. RESULTS: Augmentation pressure (AP) and augmentation index (AI) were higher in Type 1 diabetic patients suggesting stiffer arteries compared to controls (AP: 5.8 +/- 3.6 vs 2.8 +/- 2.2 mmHg, p < 0.001; and AI:18.3 +/- 9 vs 11.1 +/- 8.8%, p = 0.004). The subgroup of diabetic patients with autoimmune thyroid disease presented stiffer arteries than those without (AP: 6.5 +/- 2.9 vs 5.5 +/- 3.9 mmHg, p < 0.05; and AI: 21.3 +/- 5.4 vs 16.7 +/- 10.3%, p < 0.05), though the two groups did not differ statistically by means of age, disease duration, hemoglobin A1c (HbA1c), lipid levels, FMD and IMT. In multiple regression analysis, variables independently associated to AI in the diabetes group were: age (p = 0.028), IMT of the carotid artery bifurcation (p = 0.045), disease duration (p = 0.031) and autoimmune thyroid disease (p = 0.015). No correlation was observed between AI and metabolic control, blood pressure, microalbuminuria, presence of retinopathy and endothelial function (FMD). CONCLUSIONS: Women with Type 1 diabetes have increased arterial stiffness, which indicates macroangiopathy. An independent correlation between these indices and carotid IMT was observed. Concomitant autoimmune thyroid disease seems to aggravate arterial compliance in these patients, a finding that merits further investigation.