A number of patients with adrenal incidentaloma are exposed to a slight degree of cortisol excess resulting from functional autonomy of the adrenal mass (usually a cortical adenoma). At present, there are only scant data on the unwanted effects of this endocrine condition referred to as subclinical Cushing's syndrome. The aim of the present study was to look for some features of the metabolic syndrome in patients with incidental adrenal adenoma. Forty-one patients (9 men and 32 women) bearing adrenal incidentaloma with typical computed tomography features of cortical adenoma were studied. For both patients and controls, exclusion criteria were age equal to 70 yr or greater, previous history of fasting hyperglycemia, or impaired glucose tolerance (IGT), severe hypertension, current use of medication or concomitant relevant illnesses, and body mass index (BMI) equal to 30 kg/m(2) or greater. Forty-one patients with euthyroid multinodular goiter accurately matched for sex, age, and BMI served for a 1:1 case-control analysis. The study design included an oral glucose tolerance test (75 g) and an endocrine workup aimed at the study of the hypothalamic-pituitary-adrenal axis. Age and BMI were fully comparable between patients (54.0 +/- 10.7 yr, 23.8 +/- 2.4 kg/m(2)) and controls (52.2 +/- 11.6 yr, 23.5 +/- 2.8 kg/m(2)). Fasting glucose and fasting insulin levels were not different between the two groups (4.96 +/- 0.61 mmol/liter vs. 4.88 +/- 0.58 mmol/liter; 67 +/- 34 pmol/liter vs. 59 +/- 32 pmol/liter), but the 2-h postchallenge glucose was significantly higher in patients than in controls (7.43 +/- 2.49 mmol/liter vs. 6.10 plus minus 1.44 mmol/liter, P = 0.01). Fifteen patients (36%) reached the World Health Organization criteria for IGT and two other patients (5%) reached those for diabetes, and 14% of the controls qualified for IGT (P = 0.01). No difference in the lipid pattern was seen between the two groups, but either systolic or diastolic blood pressure were higher in patients (135.4 +/- 15.5 mm Hg vs. 125.0 +/- 15.6 mm Hg, P = 0.003; 82.9 +/- 9.1 mm Hg vs. 75.3 +/- 6.6 mm Hg, P < 0.0001). We calculated the whole-body insulin sensitivity index derived from the oral glucose tolerance test that was significantly reduced in the patients (4.3 +/- 1.7 vs. 5.7 +/- 2.5, P = 0.01). In a multiple regression analysis, 2-h glucose was associated with BMI and midnight cortisol values (r(2) = 0.36, P = 0.002). The comparison of the patients with nonfunctioning adenoma (n = 29) with those with subclinical Cushing's syndrome (n = 12) yielded significant differences as to 2-h glucose and triglyceride levels, which were significantly higher in the second group (7.02 +/- 1.76 mmol/liter vs. 8.72 +/- 3.17 mmol/liter, P = 0.03; 1.06 +/- 0.4 mmol/liter vs. 1.73 +/- 0.96 mmol/liter, P = 0.002), but the insulin sensitivity index was conversely reduced (5.2 +/- 1.4 vs. 2.9 +/- 1.2, P < 0.0001). In conclusion, many patients with incidental adrenal adenoma display altered glucose tolerance, that may be explained by reduced insulin sens...

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Our data in a large and modern day pHPT series, with a preponderance of asymptomatic patients, confirm increased insulin resistance and pre-valence of IGT and undiagnosed diabetes.

In this review we propose an integrated neuro-endocrine-metabolic point of view on the alterations (adaptations?) of GHaIGF-1 axis in obesity, summarizing the evidence from the literature, particularly focusing the data on humans and adding where possible results from our studies in this ®eld. It is well-known that GH secretion is deeply impaired in overweight patients: we reviewed the multiple mechanisms underlying this issue, considering either central (CNS-related, such as impairment of GHRH tone or increased somatostatin release) or peripheral (ie metabolic: insulin, free fatty acids, glucose) factors. A central point of the debate about GH insuf®ciency in obesity is if it represents a simple adaptive phenomenon or re¯ects a true impairment of the axis activity. Evaluation of IGF-I levels and generation in obesity was the mean used to address this question: a bulk of evidence on IGF-I balance in human obesity has been provided, but the matter is still uncertain and unsolved.

To investigate the mechanism underlying the GH-releasing effect of arginine (ARG), we studied the interactions of ARG (0.5 g/kg infused i.v. over 30 min) with GHRH (1 microgram/kg i.v.) and with pyridostigmine (PD, 60 mg orally) on GH secretion in 15 children and adolescents with familial short stature (5.1-15.4 years). In a group of eight subjects ARG induced a GH increase not statistically different to that observed after GHRH (peak, mean +/- SEM: 38.0 +/- 10.4 vs 64.0 +/- 14.4 mU/l). The combined administration of ARG and GHRH led to GH levels (101 +/- 15.2 mU/l) higher than those observed after GHRH (P less than 0.025) or ARG alone (P less than 0.001) and overlapping with those recorded after combined PD and GHRH administration (111 +/- 22.4 mU/l). In the other seven subjects, ARG and PD administration induced a similar GH response either when administered alone (25.2 +/- 13.6 and 27.8 +/- 4.0 mU/l, respectively) or in combination (33.8 +/- 5.4 mU/l). In conclusion, our results show that in children ARG administration potentiates GHRH- but not PD-induced GH increase. These findings agree with the hypothesis that the GH-releasing effect of both ARG and PD is mediated via the same mechanism, namely, by suppression of endogeneous somatostatin release. Combined administration of either ARG or PD with GHRH has a similar striking GH-releasing effect which is clearly higher than that of GHRH alone.

OBJECTIVE: To compare insulin-like growth factor-I (IGF-I) concentrations in obese and normal subjects, and evaluate the possible relationships between IGF-I concentrations and demographic, anthropometric, metabolic and hormonal variables in obese patients. SUBJECTS AND METHODS: 286 obese outpatients (OB, 234 female and 52 male; age 18 ± 71 y, body mass index (BMI) b 27 kgam 2 ) were recruited. MEASUREMENTS: BMI, waist-to-hip ratio (WHR), serum basal and oral glucose tolerance test (OGTT)-stimulated glucose and insulin concentrations, IGF-I, basal growth hormone (GH), prolactin (PRL), androgens, thyrotropin (TSH), free triiodothyronine (fT 3 ), free thyroxine (fT 4 ), free fatty acids (FFA), triglycerides, total and high density lipoprotein (HDL)-cholesterol, 24h-urinary cortisol levels and blood pressure (BP) values were measured. IGF-I concentrations were also evaluated in a large population of 326 age-matched controls (controls, 228 women, 98 men; age 20 ± 86 y, BMI`25 kgam 2 ). RESULTS: IGF-I concentrations were lower in OB than in controls (age-adjusted mean: 21.6 vs 23.6 nmolaL, P`0.03). However, individual IGF-I concentrations in OB were within the age-adjusted normal range. In both groups, IGF-I concentrations were gender-independent, and showed a simple negative correlation with age (r À0.47). In OB, univariate analysis also shows that IGF-I concentrations were negatively correlated with BMI (r À0.33), but not WHR, with both basal (r À0.16) and OGTT-stimulated glucose levels (r À0.17), as well as FFA levels (r À0.19), and with both diastolic and systolic BP (both r À0.17). In OB women, IGF-I concentrations positively correlated with PRL (r 0.31), testosterone (r 0.30), androstenedione (r 0.30), and dehydroepiandrosterone-sulfate (DHEAS) concentrations (r 0.41). No correlation was found with other variables. The multiple regression analysis showed that IGF-I concentrations were inversely and independently related to age and BMI only. CONCLUSIONS: In obesity, IGF-I concentrations are slightly reduced, but generally within the age-adjusted normal range. IGF-I concentrations in obesity show independent and negative relationships with age and BMI, but are not associated with fat distribution, insulin secretion, glucose tolerance, BP or risk indices for cardiovascular disease (CVD).

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The derangement of glucose metabolism is found frequently in all forms of hyperparathyroidism. Both in primary (PHPT) and secondary hyperparathyroidism (SHPT) PTH excess is thought to be involved in deteriorating insulin sensitivity and secretion though their different clinical and pathophysiological conditions. In PHPT these abnormalities are related to a high frequency of Type 2 diabetes mellitus and also impaired glucose tolerance according to recent clinical studies, without differences between symptomatic and asymptomatic clinical presentation. In chronic renal failure (CRF), the disorders of glucose metabolism due to SHPT do not bear an increased risk for diabetes whereas they seem to be involved in the progression of atherosclerotic vascular damage which connotes CRF. Moreover, clinical and experimental studies have shown that vitamin D deficiency associated with glucose metabolism abnormalities favors the development of the metabolic syndrome. The potential for metabolic and cardiovascular harm related to hyperparathyroidism, especially PHPT, is the most interesting issue for clinical endocrinologists. This short review of the clinical and pathophysiological data of literature on glucose homeostasis disorders in hyperparathyroidism focuses on its potential clinical and therapeutic impact, particularly in the management of PHPT.