The relative frequency of sleep apnoea in patients with treated acromegaly is at least 21%. Parameters of predictive value for the presence of sleep apnoea in this population are neck and index-finger circumference as measures of soft tissue hypertrophy, age, GH and IGF-I levels, and whether or not operative therapy was applied.

Abstract. To further investigate the role of opioids in the regulation of the pituitary-adrenal axis we studied the effect of morphine and naloxone on human corticotropin-releasing hormone (hCRH)-induced ACTH, immunoreactive (ir) β-endorphine, and cortisol release in normal subjects. Protocols: 1. 30 mg of a slow-release preparation of morphine or placebo was given orally 3 h prior to administration of hCRH (0.1 mg iv) (N = 7). 2. Naloxone (4 mg as bolus iv) or placebo was given 5 min prior to hCRH (N = 7). 3. Naloxone (4 mg iv as bolus followed by a continuous infusion of 6 mg over 75 min) or placebo was started 15 min prior to hCRH (N = 6). hCRH was injected at 11.00 h (protocol 1, 2) or at 17.00 h (protocol 3). Oral morphine not only suppressed basal hormone levels (P <0.02), but also the peak response to hCRH compared with placebo (cortisol: 270 ± 50 vs 559 ± 80 nmol/l; ACTH: 5.1 ± 1.5 vs 13.1 ± 2.7 pmol/l; ir β-endorphin: 48.5 ± 8.7 vs 88 ± 14 pmol/l; mean ± sem, P <0.02). Similarly, the maximum incremental changes and the area under the curve were significantly reduced for all three hormones compared with placebo (P < 0.05). After 4 mg of naloxone in the morning, no significant hormonal changes in response to hCRH were observed. However, 10 mg of naloxone in the afternoon led to higher maximum hormone concentrations in response to hCRH compared with placebo (cortisol: 636 ± 30 vs 437 ± 63 nmol/l; ACTH: 19.6 ± 4.4 vs 8.7 ± 1.1 pmol/l; ir β-endorphin: 180 ± 44 vs 94 ± 18 pmol/l, P <0.05). The effect of high-dose naloxone on the hCRH-induced hormone release alone supports the concept of a physiologically significant inhibition of the ACTH release by endogenous opioids via receptors of relative naloxone resistance (δ- or κ-receptors) located at the pituitary level. The μ-agonist morphine may act at suprahypophyseal sites by inhibition of CRH potentiating factors.

Cytokines are important modulators of immunological reactions, but it has been postulated that they might act on other unrelated epithelial cells. We studied the effects of recombinant interferon-gamma (rIFN gamma) and recombinant tumor necrosis factor-alpha (rTNF alpha) on normal human thyroid cells. We found that the combination of these two cytokines enhanced HLA class II molecule expression on these cells compared with the effect of rIFN gamma alone. This was proven by both immunofluorescence as well as a more sensitive and quantitative RIA. rTNF alpha alone had no effect on HLA class II molecule induction on the same thyrocytes, suggesting a synergistic rather than an additive action in combination with rIFN gamma. The addition of 600 U/ml rTNF alpha to low dose rIFN gamma (10 U/mL) enhanced class II expression by 50%, as quantified by RIA. We also demonstrated that normal thyrocytes possess distinct receptors for the two cytokines and that rTNF alpha probably augments IFN gamma binding, since it increased when the cells were first incubated with rTNF alpha. This increased binding provides an explanation for the synergistic action of rTNF alpha in enhancing class II molecule expression by rIFN gamma. We conclude that the presence of receptors for these cytokines on human thyroid cells gives a direct demonstration of their potential biological action on cells normally not involved in the immunological circuit. The phenomenon might also explain their direct or indirect involvement in vivo, such as in influencing inappropriate HLA class II molecule expression in epithelial cells affected by autoimmunity.

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To elucidate further the role of histamine in the control of ACTH secretion we investigated the effect of the selective H1 receptor antagonist meclastine on the ACTH response to insulin hypoglycaemia and to metyrapone-induced hypocortisolaemia in normal subjects. Intravenous meclastine (4.8 mg/90 min) significantly inhibited the hypoglycaemia-induced ACTH and cortisol increase whereas serum GH and PRL concentrations were unaffected. Orally administered meclastine (3 X 2 mg) also reduced the ACTH feedback response to cortisol deficiency in a modified metyrapone test, compared to a placebo. Our findings support the concept of an excitatory influence of histamine upon ACTH secretion via H1 receptors, possibly by stimulation of CRF release.