The physiology of growth hormone (GH) in adults: translational journey to GH replacement therapy.

The fact that growth hormone (GH) plays an important role in health after the cessation of growth requiring replacement therapy in adult life has only been recognised in the last three decades. This has only been made possible by recombinant technology providing GH supplies required to undertake investigations in the physiology of GH action and the benefits of replacement therapy in patients identified by rigorously validated diagnostic tests for GH deficiency (GHD). Human studies have revealed important regulatory roles in substrate metabolism, sodium homeostasis, body composition, and physical function. GH-induced anabolism is achieved by stimulating amino acid incorporation into protein while reducing oxidative loss simultaneously enhancing lipid utilisation by stimulating fatty acid oxidation and reducing lipid storage. Sodium and fluid retention are enhanced by activating the renin-angiotensin system and distal renal tubular reabsorption. GH stimulates the aerobic and anaerobic energy systems that underpin muscle and cardiovascular function. These pleiotropic actions explain the clinical picture of increased adiposity, reduced lean mass, and impaired physical and psychological function in the GHD adult, all of which are reversed when GH is replaced. Women require a greater replacement dose of GH than men. This is because androgens enhance while oestrogens attenuate GH action. The oestrogen effect is route-dependent, occurring with oral delivery blunting the liver-mediated actions of GH by directly inhibiting GH receptor signalling, global experience spanning over 30 years has attested to the safety, efficacy, and benefits of replacement therapy for adults with GHD.

Longitudinal evaluation of the natural history of conservatively managed nonfunctioning pituitary adenomas.

CONTEXT: The optimal management of nonfunctioning pituitary adenomas presenting without symptomatic mass effect remains uncertain. The objective of this study was to elucidate the natural history of nonfunctioning pituitary adenomas managed conservatively. DESIGN: Volumetric evaluation of tumour growth in serial pituitary MRI scans by a single observer and retrospective review of changes in pituitary function. PATIENTS: Patients with nonfunctioning pituitary adenomas who underwent at least 2 serial pituitary MRI scans over ≥6 months between 2003 and 2013 prior to any intervention. MEASUREMENTS: Primary end-point was a ≥20% increase in volume or surgery. Secondary end-points were rate of pituitary dysfunction and pituitary apoplexy. RESULTS: Fifty nonfunctioning pituitary adenomas (23 macroadenomas and 27 microadenomas, mean age 49, range 17-85 years) were identified. Mean follow-up was 36 months (range 6-79). An increase in volume occurred in macroadenomas (P < 0·01) but not in microadenomas (P = 0·44). A ≥20% increase in volume occurred in nine of 23 macroadenomas compared with two of 27 microadenomas (P < 0·05). Five macroadenomas (one with new visual field defect) and one microadenoma proceeded to surgery (P = 0·08). Hormone deficiency was present in four of 24 macroadenomas vs 0 of 27 microadenomas (P < 0·05) at baseline, while new hormone deficiency developed in only two macroadenomas during follow-up. Pituitary apoplexy occurred in one microadenoma. A growth rate of >10 mm3 /month assessed at approximately 2 years of follow-up among the macroadenoma group was highly predictive (sensitivity and specificity of 90%) of a ≥20% increase in volume or surgery. CONCLUSIONS: Nonfunctioning pituitary macroadenomas have a greater tendency to grow and require surgical intervention while microadenomas rarely progress.