Obese patients with obstructive sleep apnoea syndrome show a peculiar alteration of the corticotroph but not of the thyrotroph and lactotroph function

2004 
Summary 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 µg/kg intravenously (i.v.)] and basal 24 h UFC levels; (b) the TSH and PRL responses to TRH (5 µg/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 (Δpeak: 30·3 ± 3·8 pmol/l; ΔAUC: 682·8 ± 128·4 pmol*h/l) was markedly higher (P < 0·001) than in OB (Δpeak: 9·3 ± 1·4 pmol/l; ΔAUC 471·5 ± 97·3 pmol*h/l), which, in turn, was higher (P < 0·05) than in NS (Δpeak: 3·3 ± 0·9 pmol/l; ΔAUC 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.
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