Yanovski J A, Friedman T C, Nieman L K, Chrousos G P, Cutler G B, Doppman J L, Kalogeras K T
Department of Diagnostic Radiology, Warren Grant Magnuson Clinical Center, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892-1862, USA.
Clin Endocrinol (Oxf). 1997 Aug;47(2):199-206. doi: 10.1046/j.1365-2265.1997.2301038.x.
In both normal volunteers and patients with Cushing's disease, one dominant inferior petrosal sinus (IPS) contains higher concentrations of AVP and ACTH than the contralateral (non-dominant) IPS, but ovine corticotrophin-releasing hormone (oCRH)-stimulated AVP in the petrosal sinuses is greater in Cushing's disease than in normal volunteers. To distinguish whether greater oCRH-releasable AVP might be specifically related to the presence of a pituitary corticotrophinoma, or be due to hypercortisolism per se, we compared IPS AVP in patients with Cushing's disease with those of patients with other causes of Cushing's syndrome.
Twenty-three patients with Cushing's disease, 16 patients with the syndrome of ectopic ACTH and seven patients with Cushing's syndrome of adrenal origin.
AVP and ACTH, measured both before and 3, 5 and 10 minutes after oCRH in the petrosal sinuses, and in a peripheral vein.
In all three groups, AVP concentrations were lateralized such that most of the AVP was found in one, dominant IPS. oCRH significantly increased IPS ACTH only in patients with Cushing's disease (p < 0.001), whereas it significantly increased dominant IPS AVP levels in all three patient groups (P < 0.01). However, neither dominant nor non-dominant IPS AVP (basal or oCRH-stimulated) were significantly different among patients with Cushing's disease, ectopic ACTH or Cushing's syndrome of adrenal origin. Basal and oCRH-stimulated IPS AVP were negatively correlated with urine free cortisol.
Inferior petrosal sinus AVP levels are similar in all forms of Cushing's syndrome, and thus the higher inferior petrosal sinus AVP levels in patients with Cushing's disease compared with normal volunteers are unlikely to be related specifically to the presence of the pituitary corticotrophinoma. While AVP may play a role in pituitary corticotroph tumourigenesis or may be secreted by some pituitary corticotroph tumours, the observation that CRH-stimulated inferior petrosal sinus AVP levels are higher in Cushing's disease than in normal volunteers appears most likely to be related to the low endogenous CRH levels induced by hypercortisolism, rather than a consequence of Cushing's disease itself. We hypothesize that low endogenous CRH leads to increased sensitivity of central nervous system CRH receptors to exogenous CRH, and thus to greater ovine CRH-stimulated AVP.
在正常志愿者和库欣病患者中，一条优势岩下窦（IPS）中抗利尿激素（AVP）和促肾上腺皮质激素（ACTH）的浓度高于对侧（非优势）IPS，但在库欣病患者中，岩下窦中羊促肾上腺皮质激素释放激素（oCRH）刺激的AVP水平高于正常志愿者。为了区分oCRH可释放的AVP增加是否与垂体促肾上腺皮质激素瘤的存在有特异性关系，还是由于高皮质醇血症本身所致，我们比较了库欣病患者与其他病因所致库欣综合征患者的IPS AVP水平。
23例库欣病患者、16例异位ACTH综合征患者和7例肾上腺源性库欣综合征患者。
在岩下窦和外周静脉中，分别于oCRH给药前、给药后3、5和10分钟测量AVP和ACTH。
在所有三组患者中，AVP浓度均偏向一侧，即大部分AVP存在于一条优势IPS中。oCRH仅在库欣病患者中显著增加IPS ACTH水平（p<0.001），而在所有三组患者中均显著增加优势IPS AVP水平（P<0.01）。然而，库欣病、异位ACTH或肾上腺源性库欣综合征患者的优势或非优势IPS AVP（基础或oCRH刺激后）均无显著差异。基础和oCRH刺激后的IPS AVP与尿游离皮质醇呈负相关。
在所有形式的库欣综合征中，岩下窦AVP水平相似，因此与正常志愿者相比，库欣病患者较高的岩下窦AVP水平不太可能与垂体促肾上腺皮质激素瘤的存在有特异性关系。虽然AVP可能在垂体促肾上腺皮质激素肿瘤发生中起作用，或可能由某些垂体促肾上腺皮质激素肿瘤分泌，但库欣病患者中CRH刺激的岩下窦AVP水平高于正常志愿者这一观察结果，似乎最有可能与高皮质醇血症诱导的内源性CRH水平降低有关，而非库欣病本身的结果。我们推测，内源性CRH水平降低导致中枢神经系统CRH受体对外源性CRH的敏感性增加，从而使羊CRH刺激的AVP增加。
