OBJECTIVE -The presence of an enhanced cortisol secretion in patients with type 2 diabetes is debated. In type 2 diabetic subjects, cortisol secretion was found to be associated with the complications and metabolic control of diabetes. We evaluated cortisol secretion in 170 type 2 diabetic subjects and in 71 sex-, age-, and BMI-matched nondiabetic subjects. RESEARCH DESIGN AND METHODS-In all subjects, we evaluated ACTH at 8:00 A.M. in basal conditions and serum cortisol levels at 12:00 P.M. (F24) and at 9:00 A.M. after a 1-mg overnight dexamethasone suppression test and 24-h urinary free cortisol (UFC). In diabetic patients, we evaluated the presence of chronic complications (incipient nephropathy, asymptomatic neuropathy, background retinopathy, and silent macroangiopathy). Patients were subdivided according to the absence (group 1, n ϭ 53) or presence (group 2, n ϭ 117) of diabetes complications.RESULTS -In group 2, UFC (125.2 Ϯ 4.6 nmol/24 h) and F24 (120.6 Ϯ 4.1 nmol/l) were higher than in group 1 (109.2 Ϯ 6.8 nmol/24 h, P ϭ 0.057, and 99.7 Ϯ 6.1 nmol/l, P ϭ 0.005, respectively) and in nondiabetic patients (101.7 Ϯ 5.9 nmol/24 h, P ϭ 0.002, and 100.3 Ϯ 5.3 nmol/l, P ϭ 0.003, respectively). In diabetic patients, the number of complications was associated with F24 (R ϭ 0.345; P Ͻ 0.0001) and diabetes duration (R ϭ 0.39; P Ͻ 0.0001). Logistic regression analysis showed that the presence of diabetes complications was significantly associated with F24, sex, duration of diabetes, and glycated hemoglobin.CONCLUSIONS -In type 2 diabetic subjects, hypothalmic-pituitary-adrenal activity is enhanced in patients with diabetes complications and the degree of cortisol secretion is related to the presence and number of diabetes complications. Diabetes Care 30:83-88, 2007I n patients with type 2 diabetes, glucocorticoid secretion has been suggested to be a possible link between insulin resistance and the features of the metabolic syndrome (hypertension, obesity, coronary heart disease, hyperlipidemia, and type 2 diabetes) (1-4). In fact, while glucocorticoid excess (overt or subclinical) has been demonstrated to lead to diabetes or to worsen metabolic control (5-7), the relationship between cortisol levels, insulin resistance, and chronic complications in type 2 diabetic patients without hypercortisolism is still a matter of debate.In past years, the hypothalamicpituitary-adrenal (HPA) axis secretion in patients with type 2 diabetes has been extensively investigated (8 -14). In particular, some studies reported in these subjects an elevation of ACTH (10,12), basal (9 -11) and after dexamethasone test serum cortisol (13,14), and late-night salivary cortisol levels (15). In contrast, other previous studies (16 -17) did not show any alteration of pituitary-adrenal axis secretion. The presence of chronic complications of type 2 diabetes (i.e., macroangiopathy, retinopathy, and neuropathy) has been associated to with HPA axis activity (9,18 -23), and an association between the degree of severity of several clinical measures of d...

Objective: Subclinical hypercortisolism (SH) may play a role in several metabolic disorders, including diabetes. No data are available on the relative prevalence of SH in type 2 diabetes (T2D). In order to compare the prevalence of SH in T2D and matched non-diabetic control individuals, we performed a case-controlled, multicenter, 12-month study, enrolling 294 consecutive T2D inpatients (1.7% dropped out the study) with no evidence of clinical hypercortisolism and 189 consecutive age-and body mass index-matched non-diabetic inpatients (none of whom dropped out). Design and methods: Ascertained SH (ASH) was diagnosed in individuals (i) with plasma cortisol after 1 mg overnight dexamethasone suppression .1.8 mg/dl (50 nmol/l), (ii) with more than one of the following: (a) urinary free cortisol .60.0 mg/24 h (165.6 nmol/24 h), (b) plasma ACTH , 10.0 pg/ml (2.2 pmol/l) or (c) plasma cortisol . 7.5 mg/dl (207 nmol/l) at 24:00 h or .1.4 mg/dl (38.6 nmol/l) after dexamethasone-CRH (serum cortisol after corticotrophin-releasing hormone stimulus during dexamethasone administration) test, and (iii) in whom the source of glucocorticoid excess was suggested by imaging and by additional biochemical tests (for ACTH-dependent ASH). Results: Prevalence of ASH was higher in diabetic individuals than in controls (9.4 versus 2.1%; adjusted odds ratio, 4.8; 95% confidence interval, 1.6-14.1; P ¼ 0.004). In our population the proportion of T2D which is statistically attributable to ASH was approx. 7%. Among diabetic patients, the presence of severe diabetes (as defined by the coexistence of hypertension, dyslipidaemia and insulin treatment) was significantly associated with SH (adjusted odds ratio, 3.8; 95% confidence interval, 1.4 -10.2; P ¼ 0.017). Conclusions: In hospitalized patients, SH is associated with T2D.European Journal of Endocrinology 153 837-844

Stereotactic radiosurgery by gamma-knife (GK) is an attractive therapeutic option after failure of microsurgical removal in patients with pituitary adenoma. In these tumors or remnants of them, it aims to obtain the arrest of cell proliferation and hormone hypersecretion using a single precise high dose of ionizing radiation, sparing surrounding structures. The long-term efficacy and toxicity of GK in acromegaly are only partially known. Thirty acromegalic patients (14 women and 16 men) entered a prospective study of GK treatment. Most were surgical failures, whereas in 3 GK was the primary treatment. Imaging of the adenoma and target coordinates identification were obtained by high resolution magnetic resonance imaging. All patients were treated with multiple isocenters (mean, 8; range, 3-11). The 50% isodose was used in 27 patients (90%). The mean margin dose was 20 Gy (range, 15-35), and the dose to the visual pathways was always less than 8 Gy. After a median follow-up of 46 months (range, 9-96), IGF-I fell from 805 micro g/liter (median; interquartile range, 640-994) to 460 micro g/liter (interquartile range, 217-654; P = 0.0002), and normal age-matched IGF-I levels were reached in 7 patients (23%). Mean GH levels decreased from 10 micro g/liter (interquartile range, 6.4-15) to 2.9 micro g/liter (interquartile range, 2-5.3; P < 0.0001), reaching levels below 2.5 micro g/liter in 11 (37%). The rate of persistently pathological hormonal levels was still 70% at 5 yr by Kaplan-Meier analysis. The median volume was 1.43 ml (range, 0.20-3.7). Tumor shrinkage (at least 25% of basal volume) occurred after 24 months (range, 12-36) in 11 of 19 patients (58% of assessable patients). The rate of shrinkage was 79% at 4 yr. In no case was further growth observed. Only 1 patient complained of side-effects (severe headache and nausea immediately after the procedure, with full recovery in a few days with steroid therapy). Anterior pituitary failures were observed in 2 patients, who already had partial hypopituitarism, after 2 and 6 yr, respectively. No patient developed visual deficits. GK is a valid adjunctive tool in the management of acromegaly that controls GH/IGF-I hypersecretion and tumor growth, with shrinkage of adenoma and no recurrence of the disease in the considered observation period and with low acute and chronic toxicity.

Contrary to that observed in patients with MPHD, rhGH replacement therapy does not induce central hypothyroidism in children with idiopathic isolated GHD, further supporting the view that in children with MPHD, as in adults, GHD masks the presence of central hypothyroidism. Slow growth (in spite of adequate rhGH substitution and normal IGF-I levels) is an important clinical marker of central hypothyroidism, therefore a strict monitoring of thyroid function is mandatory in treated children with MPHD.