Glucocorticoids inhibit somatic growth in man and laboratory animals, and have long been regarded as suppressors of both stimulated GH secretion and insulin-like growth factor (IGF) activity. Recent evidence suggests, however, that glucocorticoids can be potent GH secretagogues in their own right with concomitant increases in circulating IGF-I levels. IGFs circulate tightly bound to a group of high-affinity binding proteins (IGFBPs) which modulate their actions. In order to investigate the effects of glucocorticoids on serum levels of IGFs and IGFBPs, normal male volunteers were sampled over 24-h periods before and directly after treatment with dexamethasone (2 mg twice daily) for 96 h. Following dexamethasone administration, all volunteers showed a marked increase in mean +/- S.E.M. IGF-I levels over the 24-h sampling period (292.2 +/- 31.8 before dexamethasone, 425.9 +/- 37 micrograms/l after dexamethasone, P < 0.005); there was no change in mean IGF-II levels. Integrated mean insulin levels were raised by dexamethasone treatment (50 +/- 4.6 before dexamethasone, 117 +/- 13.4 mU/l after dexamethasone, P = 0.002) and IGFBP-1 was significantly suppressed (42.9 +/- 8.2 before dexamethasone, 28.0 +/- 7.9 micrograms/l after dexamethasone, P < 0.001). IGFBP-2 levels were similarly suppressed after dexamethasone (319.5 +/- 24.5 before dexamethasone, 214.8 +/- 8.5 micrograms/l after dexamethasone, P = 0.002), and there was a significant increase in IGFBP-3 levels from 3.24 +/- 0.25 to 3.67 +/- 0.32 mg/l (P = 0.0153). Mean IGF bioactivity over the sampling period after dexamethasone was reduced by approximately 60% (0.93 +/- 0.39 before dexamethasone, 0.39 +/- 0.05 U/ml after dexamethasone, P < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

After major surgery there are complex and diverse changes in the IGFs and IGFBPs. The effect of these changes on IGF bioavailability may significantly affect the therapeutic potential of IGF-I in this setting.

The purpose of this study was to evaluate the relative merits of the postural stimulation test, adrenal computed tomography (CT) and venous sampling in the differential diagnosis of patients presenting with primary hyperaldosteronism. The records of 20 patients presenting with primary hyperaldosteronism were reviewed retrospectively. There were 15 patients with a unilateral aldosterone-producing adenoma (APA), four patients with idiopathic hyperaldosteronism (IHA) and one patient with primary adrenal hyperplasia (PAH). The postural stimulation test was based on measurements of plasma aldosterone and renin activity at 08.00 h and at noon after 4 h of ambulation. The CT scans of the adrenals were reviewed by a single radiologist. Bilateral venous sampling of adrenal veins was attempted in all patients and blood collected for aldosterone and cortisol assay. Plasma aldosterone concentration increased after 4 h of standing in all cases of hyperplasia but was also demonstrated in 10/15 patients with a surgically-proven APA. If one defines a significant postural rise as being greater than 30%, then 8/15 patients with APA can be considered as being posturally responsive. Computed tomography scanning correctly identified all 15 cases of APA and also classified correctly the remaining five cases of hyperplasia (four cases of IHA and one case of PAH). Venous sampling failed technically in 4/15 cases of APA and in one case of IHA: a total of 5/20 (25%,). A correct diagnosis of APA or IHA was established in all the remaining cases. However, the one case of PAH was treated successfully by adrenalectomy following venous sampling, which suggested a unilateral adrenal lesion: this one result was the only instance where venous sampling altered clinical decision-making. Computed tomography scanning may be used alone to confirm the cause of hyperaldosteronism where postural studies suggest an adrenal adenoma, and such patients may be considered for early surgery. Venous catheterization studies are not necessary routinely. but may still be useful in selected patients, particularly when CT scanning shows no clear lesion.

The diagnosis of Cushing's Disease during pregnancy is complex because the biochemical features are obscured by changes in the normal hypothalamo-pituitary-adrenal axis that occur during gestation. To date, treatment has not been successful and there is a high incidence of maternal and fetal complications. We report the case of a 24-year-old woman with Cushing's disease who presented during her 16th week of pregnancy. Diagnosis was confirmed by the finding of elevated serum and urinary free cortisol levels with loss of the normal circadian rhythm of serum cortisol. Cortisol levels failed to suppress after a low-dose dexamethasone test but suppressed after a high-dose test. There was an exaggerated serum cortisol and plasma adrenocorticotrophin (ACTH) response to corticotrophin-releasing hormone (CRH). Magnetic resonance (MR) scanning demonstrated a pituitary tumour and cure was effected by transsphenoidal surgery where tumour immunostaining for ACTH was removed. Postoperatively the patient made an uncomplicated recovery; serum cortisol and plasma ACTH levels were undetectable at 9 days following surgery and recovery of the hypothalamo-pituitary axis occurred at 99 days after surgery. Caesarean section was performed at 38 weeks of pregnancy and a healthy but small female infant was delivered. This case illustrates the biochemical features of Cushing's disease during pregnancy and is the first report of the use of CRH testing and MR scanning in this clinical situation. The cure by surgery and successful outcome for mother and infant, with preservation of normal anterior pituitary function, suggest that transsphenoidal surgery may be the treatment of choice.

Sepsis, surgery and critical illness are associated with an increased catabolic rate, which if prolonged delays recovery and increases morbidity and mortality. There is evidence that changes in the GH/IGF-I axis are permissive to protein catabolism. Critically ill, septic patients have high basal levels of GH, low levels of IGF-I and its carrier binding protein IGFBP-3, high levels of an inhibitory binding protein, IGFBP-I, and increased serum protease activity which reduces the affinity of IGFBP-3 for IGF-I. Overall there is a reduction in the indirect IGF-I-mediated anabolic actions of GH and an increase in the direct catabolic actions of GH. These physiological changes may be adaptive when a sick patient is fasting; however, the availability of modern intensive care means that these changes are no longer an advantage. GH and IGF-I, in pharmacological doses, promote positive nitrogen balance, in both animal models and man. Preliminary studies with IGF-I in postsurgical patients suggest that it may provide a practical therapy. Future studies need to focus on outcome measures in relation to the use of GH and IGF-I as anabolic therapies.