Robert D Murray

Influences on quality of life in GH deficient adults and their effect on response to treatment

Studies of the effect of GH on quality of life (QOL) in growth hormone deficient (GHD) adults have reported conflicting results. Recently, however, we have demonstrated that by selecting only those patients with impaired QOL the efficacy of GH replacement on QOL can be greatly improved. The improvement in QOL was observed to correlate significantly with that recorded before commencing GH therapy. This study aims to assess if demographic variables affect QOL in untreated GHD adults or the improvement in QOL following GH therapy.

Dose titration and patient selection increases the efficacy of GH replacement in severely GH deficient adults

Previous studies of GH replacement in adults have used unselected cohorts of GH deficient (GHD) adults and weight‐based dosing regimens resulting in supraphysiological serum IGF‐I levels and a high frequency of side‐effects and withdrawal from these studies. By choosing patients with a high level of morbidity at baseline and using a low dose GH titration regimen we aimed to avoid over‐replacement and increase the efficacy of treatment.

The effect of long-term untreated growth hormone deficiency (GHD) and 9 years of GH replacement on the quality of life (QoL) of GH-deficient adults

background Quality of life (QoL) is reduced in GH‐deficient adults compared with the normal population. Further support for the role of GH in the maintenance of QoL is derived from short‐term studies of GH replacement in severely GH‐deficient adults; these have predominantly reported beneficial effects, although the degree of improvement has often been modest. To date, however, there are few data to demonstrate whether this beneficial effect on QoL is maintained in the long term.

Pre-treatment IGF-I level is the major determinant of GH dosage in adult GH deficiency

Severe GH deficiency in adults is a definite clinical entity, the effects of which can be reversed by administration of subcutaneous recombinant GH. The ideal dosing regimen and determinants of the maintenance dose have, however, yet to be elucidated.

Growth hormone: current and future therapeutic applications

The increased availability of growth hormone (GH) in the mid-1980s, as a result of advances in recombinant DNA techniques, has allowed research into the use of this hormone at physiological dosage, as replacement therapy for adults with GH deficiency (GHD) and at pharmacological dosages as a possible therapeutic agent, for a number of disease states. GHD adults have increased body fat and reduced muscle mass and consequently, reduced strength and exercise tolerance. In addition, they are osteopenic, have unfavourable cardiac risk factors and impaired quality of life. In these individuals, replacing GH reverses these anomalies, although it may not alter the reduced insulin-sensitivity. A proportion of adults with GHD perceive a dramatic improvement in their well-being, energy levels and mood following replacement. GH has protein and osteo-anabolic, lipolytic and antinatriuretic properties. GH has been considered for the therapeutic treatment of frailty associated with ageing, osteoporosis, morbid obesity, cardiac failure, major thermal injury and various acute and chronic catabolic conditions. Initial small, uncontrolled studies for many of these clinical problems suggested a beneficial effect of GH, although, later placebo-controlled studies have not observed such dramatic effects. Furthermore, with a recent publication demonstrating an approximate 2-fold increase in mortality in critically ill patients receiving large doses of GH, the use of GH should remain in the realms of replacement therapy and research, until there are significant advances in our understanding.

The diagnosis of growth hormone deficiency (GHD) in successfully treated acromegalic patients.

Due to persistent qualitative abnormali‐ties in GH secretion following treatment, and lack of a sensitive marker of GHD in mid‐adult life it is extremely difficult to diagnose GHD in treated acromegalic patients. The diagnosis of GHD in patients with pituitary disease relies on provocative tests of GH reserve. Arginine releases GH by reducing somatostatin inhibition of GH release, whereas GH secretagogues (GHS) affect GH release by direct stimulation of the GHS receptor, though an intact GH releasing hormone (GHRH) axis is a prerequisite. The peak GH response to insulin‐induced hypoglycaemia and arginine in acromegalic patients, in whom basal serum GH levels of less than 5 mU/l have been achieved, is greatly diminished in those treated by hypothalamo–pituitary irradiation. We aimed to study the response of successfully treated acromegalic patients to the growth hormone secretagogue hexarelin in view of its different putative mechanism of action, and in addition, to determine whether it has any value in the diagnosis of GH deficiency in this subset of patients.

Survivors of childhood cancer: long‐term edocrine and metabolic problems dwarf the growth distrubance

The long‐term effects of radiotherapy and chemotherapy are becoming increasingly reconginzed as the cure rates of certain childhood malignancies improve. The endocrine system is particularly sensitive to cancer therapies. Long‐term survivors of childhood cancer who received cranial irradiation have been shown to have lower than predicted height, an increased prevalence of obesity and redutions in strength, exercise tolerance, bone mineral density, quality of life and academic achievement. Growth hormone deficiency (GHD) is the most frequent endocrine deficiency observed following cranial irradiation. Adults with GHD resulting from primary hypothalamic‐pituitary disease during childhood have been shown to exhibit a clinical picture similar to that described in long‐term survivors of childhood cancer: increased fat mass and reduced lean mass, strength, exercise tolerance, bone mineral density and quality of life. This review considers the possible contributin of GHD to the adverse sequelae observed in long‐term survivors of childhood malignancy and includes our preliminary experience in treating 14 adults with GHD resulting from the treatment of childhood malignancies.

The diagnosis and management of inpatient hyponatraemia and SIADH

Hyponatraemia is a very common medical condition that is associated with multiple poor clinical outcomes and is often managed suboptimally because of inadequate assessment and investigation. Previously published guidelines for its management are often complex and impractical to follow in a hospital environment, where patients may present to divergent specialists, as well as to generalists.

Partial growth hormone deficiency is associated with an adverse cardiovascular risk profile and increased carotid intima‐medial thickness

Objective  To quantify the relative prevalence of surrogate markers of vascular risk in adults with partial GH deficiency (GH insufficiency, GHI).

Pituitary dysfunction following cranial radiotherapy for adult‐onset nonpituitary brain tumours

There are limited data concerning the evolution of radiation‐induced hypopituitarism in adult‐onset brain tumour (AO‐BT) survivors, in part the consequence of the limited survival of many of these individuals. We aim to characterize the pituitary‐related outcomes following cranial radiotherapy (cXRT) for adult‐onset primary nonpituitary brain tumours.