Diamantina Health Partners: integrating leadership in research, research translation, education and clinical care.

Many have asked "what is the benefit of the DHP over the current situation?" We believe that the responsiveness of research to community health needs and the balance of research and teaching outcomes in academic institutions can be improved, and stronger incentives to integrate research outcomes into clinical practice can be provided. The DHP is thus set up differently to a clinical research centre. The aim of our DHP is to improve health outcomes by means of coordinated excellence in teaching, research and clinical care. Technical efficiencies and excellence in care mean that financial efficiencies will occur. Joint clinical, research and teaching initiatives are underway, and plans are being developed to teach future clinical staff the science of clinician-directed, rational use of medical resources. These include pathology, imaging services, pharmaceuticals and patient referrals, assisted by published expert guidelines. There are significant administrative and personnel issues to surmount, but planning for integration has begun, and plans for turning research outcomes into clinical care plans are already emerging.

Hypothalamic/pituitary morbidity in skull base pathology.

In this article the epidemiology, pathophysiology, clinical presentation, investigation, management, and prognosis of hypopituitarism and hypothalamic dysfunction, arising from skull base pathologies and treatment of these conditions, are reviewed and discussed. The clinical question: "What is the consequence of pituitary hypofunction in young patients (ie, craniopharyngioma)?" is answered based on information provided in the review.

Paracrine regulation of growth hormone secretion by estrogen in women.

CONTEXT: Paracrine regulation is emerging as a discrete control mechanism in the endocrine system. In hypogonadal men, stimulation of GH secretion by testosterone requires prior aromatization to estradiol, a paracrine effect unmasked by central estrogen receptor blockade with tamoxifen. In hypogonadal women, estrogen replacement via a physiological non-oral route fails to enhance GH secretion, indicating an absence of an endocrine effect. The aim was to investigate whether local estrogens produced from aromatization regulate GH secretion. DESIGN: We conducted an open-label, two-phase, crossover study. PATIENTS AND INTERVENTION: We compared the effects on GH secretion of tamoxifen with estradiol valerate in postmenopausal women. Ten women were treated with tamoxifen (10 and 20 mg/d) and estradiol valerate (2 mg/d) via oral route for 2 wk each, with a washout period of at least 6 wk. MAIN OUTCOME MEASURES: We measured the GH response to arginine and circulating levels of IGF-I and SHBG, markers of hepatic estrogen effect. RESULTS: The GH response to arginine was reduced by 10- and 20-mg tamoxifen in a dose-dependent manner and potentiated significantly (P<0.05) by estradiol valerate. Mean IGF-I concentration was reduced significantly with high-dose tamoxifen (P<0.01) and estradiol valerate treatment (P<0.05), whereas mean SHBG levels rose with both (P<0.01). CONCLUSIONS: Blunted GH response to stimulation occurring in the face of reduced IGF-I feedback inhibition with tamoxifen indicates that GH secretion was suppressed by estrogen receptor antagonism. Because circulating estradiol was unaffected, these data indicate a significant role of local estrogen in the central control of GH secretion. We conclude that aromatase mediates the paracrine control of GH secretion in women.

Independent and combined effects of testosterone and growth hormone on extracellular water in hypopituitary men.

CONTEXT: Symptoms of fluid retention in GH-deficient patients during GH replacement are greater in men than in women, suggesting that testosterone may augment or estradiol may attenuate the antinatriuretic actions of GH. The mechanisms underlying the sodium-retaining effects of GH are poorly understood. AIM: The aim of this study was to investigate the effects of GH and testosterone, alone and in combination, on extracellular water (ECW) and the hormonal mechanisms involved. DESIGN: Two separate, open-label, randomized, two-period, crossover studies were performed; the first compared the effects of GH alone with those of GH and testosterone, and the second compared the effects of testosterone alone with those of GH and testosterone. PARTICIPANTS: Twelve hypopituitary men with GH deficiency and hypogonadism were studied. INTERVENTION: During the weeks of intervention, GH (0.5 mg/d) and testosterone enanthate (250 mg) were administered by im injection. OUTCOME MEASURES: The outcome measures were ECW, IGF-I, plasma renin activity (PRA), aldosterone (Aldo), and atrial natriuretic peptide (ANP). RESULTS: GH treatment significantly increased (P < 0.05) both IGF-I and ECW, and these changes were enhanced by cotreatment with testosterone (P = 0.07 for both). PRA, Aldo, and ANP levels did not change. Testosterone treatment alone did not change the IGF-I concentration, whereas cotreatment with GH induced a marked increase. Testosterone alone increased (P < 0.05) ECW, and the effect was augmented (P < 0.01) by cotreatment with GH. Although PRA and ANP did not change, plasma Aldo decreased after single and combined treatments. CONCLUSION: GH and testosterone exerted independent and additive effects on ECW. The mechanisms of fluid retention for both hormones are likely to be exerted on the renal tubules. This is the first direct evidence that testosterone increases ECW.