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Objective: Obstructive sleep apnoea syndrome (OSAS) is strongly associated with obesity (OB) and is characterized by several changes in endocrine functions, e.g. GH/IGF-I axis, adrenal and thyroid activity. It is still unclear whether these alterations simply reflect overweight or include peculiar hypoxia-induced hormonal alterations. Hormonal evaluations have been generally performed in basal conditions but we have recently reported that OSAS is characterized by a more severe reduction of the GH releasable pool in comparison to simple obesity. We aimed to extend our evaluation of anterior pituitary function to corticotroph, thyrotroph and lactotroph secretion under dynamic testing in OSAS in comparison with simply obese and normal subjects., Subjects and Methods: In 15 male patients with OSAS [age, mean +/- SEM 43.5 +/- 1.6 years; body mass index (BMI) 39.2 +/- 3.1 kg/m2; apnoea/hypopnoea index, (AHI) 53.4 +/- 8.7], 15 male patients with simple obesity (OB, age 39.7 +/- 1.2 years; BMI 41.2 +/- 2.0 kg/m2; AHI 3.1 +/- 1.2 events/h of sleep) and in 15 normal lean male subjects (NS, age 38.2 +/- 1.4 years; BMI 21.2 +/- 0.8 kg/m2; AHI 1.9 +/- 0.8 events/h of sleep) we evaluated: (a) the ACTH and cortisol responses to CRH [2 microg/kg intravenously (i.v.)] and basal 24 h UFC levels; (b) the TSH and PRL responses to TRH (5 microg/kg iv) as well as FT3 and FT4 levels., Results: Twenty-four-hour UFC levels in OSAS and OB were similar and within the normal range. Basal ACTH and cortisol levels were similar in all groups. However, the ACTH response to CRH in OSAS (Deltapeak: 30.3 +/- 3.8 pmol/l; DeltaAUC: 682.8 +/- 128.4 pmol*h/l) was markedly higher (P < 0.001) than in OB (Deltapeak: 9.3 +/- 1.4 pmol/l; DeltaAUC 471.5 +/- 97.3 pmol*h/l), which, in turn, was higher (P < 0.05) than in NS (Deltapeak: 3.3 +/- 0.9 pmol/l; DeltaAUC 94.7 +/- 76.7 pmol*h/l). On the other hand, the cortisol response to CRH was not significantly different in the three groups. Basal FT3 and FT4 levels as well as the TSH response to TRH were similar in all groups. Similarly, both basal PRL levels and the PRL response to TRH were similar in the three groups., Conclusions: With respect to patients with simple abdominal obesity, obese patients with OSAS show a more remarkable enhancement of the ACTH response to CRH but a preserved TSH and PRL responsiveness to TRH. These findings indicate the existence of a peculiarly exaggerated ACTH hyper-responsiveness to CRH that would reflect hypoxia- and/or sleep-induced alterations of the neural control of corticotroph function; this further alteration is coupled to the previously described, peculiar reduction of somatotroph function.

Objectives: Obstructive sleep apnoea syndrome (OSAS) is strongly associated with obesity and characterized by endocrine and metabolic changes including impairment of insulin sensitivity. The aim of this study was to further clarify the insulin dynamics and glucose metabolism in this condition., Design, Patients and Measurements: We studied 30 obese patients with OSAS [OSA, 21 males, 9 females; age, mean +/- SEM: 53.1 +/- 1.7 years; body mass index (BMI): 38.6 +/- 1.1 kg/m2; waist-to-hip ratio (WHR): 0.99 +/- 0.07; Apnoea/Hypopnoea Index (AHI): 40.5 +/- 5.8 events/h of sleep] by means of overnight polysomnography and oral glucose tolerance testing. Mathematical models were used to assess: (i) whole-body insulin sensitivity index (ISI composite); (ii) hepatic ISI; (iii) the first phase of insulin secretion (DeltaI30'-0'/DeltaG30'-0'). Results were compared with those in 27 weight-matched patients with simple obesity (OB, 12 males, 15 females; age: 48.1 +/- 2.8 years, BMI: 38.5 +/- 1.4 kg/m2, WHR: 0.94 +/- 0.09; AHI: 2.15 +/- 0.5 events/h of sleep) and with 20 normal subjects (NS, 15 females; 5 males, age: 40.4 +/- 2.9 years; BMI: 22.2 +/- 0.6 kg/m2)., Results: ISI composite value was significantly lower in OSAS (1.71 +/- 1.41) than in OB (3.08 +/- 0.27) and in NS (6.1 +/- 0.4) even after age-, BMI- and WHR-adjustment. Similarly, hepatic ISI was significantly different among the three groups (OB = 0.25 +/- 0.02, OSAS = 0.16 +/- 0.014 and NS = 0.55 +/- 0.04). Sex did not affect ISI indices. Insulin secretion estimates were not significantly different among the three groups., Discussion: Obese patients with obstructive sleep apnoea syndrome are more insulin resistant than patients with simple obesity independently of the degree and distribution of adiposity. The worsening in insulin sensitivity in obstructive sleep apnoea syndrome patients could reflect the hypoxic state and would account for the increased vascular risk in this condition.