• Determinants of IGF-I status in a large cohort of growth hormone-deficient (GHD) subjects: the role of timing of onset of GHD.

      Lissett, Catherine A; Jönsson, Peter J; Monson, John; Shalet, Stephen M; Christie Hospital, Manchester, UK. (2003-12)
      BACKGROUND: IGF-I standard deviation score (SDS) is widely used in clinical practice; however, factors determining IGF-I SDS in GH-deficient (GHD) individuals remain incompletely understood. Earlier studies have been limited by the small size of cohorts studied. We have used the KIMS database to examine if a true difference exists between subjects who developed GHD in adult life (AO), and those who developed GHD in childhood (CO). PATIENTS: A total of 1317 patients fulfilled the inclusion criteria, 1073 with AO GHD and 244 with CO GHD. METHODS: Serum IGF-I concentrations were determined by a hydrochloric acid-ethanol extraction radioimmunoassay method using synthetic IGF-I for labelling. The reference range was calculated using normative data from healthy Swedish individuals. RESULTS: A total of 86% of patients with CO GHD but only 52% of patients with AO GHD had IGF-I SDS below -2 SDS. The CO cohort had a lower IGF-I SDS (-4.69 vs. -2.24, P < 0.0001), a smaller body mass index (BMI; 26.6 vs. 28.6 kg/m2, P < 0.0001) and waist-hip ratio (WHR; 0.90 vs. 0.92 P < 0.001) than the AO cohort. A stepwise multiple linear regression was performed to examine the principal determinants of IGF-I SDS. Age at onset of GHD was the most important determinant of IGF-I SDS, contributing 17% towards the variability of IGF-I SDS. Timing of onset, gender, BMI, and number of pituitary hormone deficiencies other than GH deficiency were also significant determinants of IGF-I SDS. CONCLUSION: Whilst age at onset of GHD was the most important determinant of IGF-I SDS, individuals with CO GHD had values on average 1.43 lower than those with AO GHD, all other factors being equal. Potential explanations include differences in GH secretory patterns, variation in body composition, and/or suboptimal treatment of GHD in childhood.
    • Endocrine complications of neoplastic diseases in children and adolescents.

      Gleeson, Helena K; Shalet, Stephen M; Department of Endocrinology, Christie Hospital, Wilmslow Road, Withington, Manchester M20 4BX, UK. (2001-08)
      Because of the increasing population of childhood cancer survivors, there is a need to focus on the late effects of cancer therapy. After discharge by their pediatric oncologists, it is essential that patients are not lost to the health system but rather are under continued surveillance with access to the appropriate physicians. Endocrine and metabolic consequences may impact the life of the patient both soon after cancer treatment and for many years in the future. The purpose of this article is to explore the current literature in the following areas: growth hormone (GH) deficiency, gonadotropin-releasing hormone (GnRH) analogues with GH therapy in childhood, safety of GH replacement, cardiovascular risk factors, osteopenia, thyroid problems, and gonadal damage resulting in infertility.
    • Extensive expertise in endocrinology: UK stance on adult GH replacement: the economist vs the endocrinologist.

      Shalet, Stephen M; Department of Endocrinology, Christie Hospital NHS Trust, Wilmslow Road, Manchester M20 4BX, UK. (2013-10)
      In the UK, through the use of a forced economic model, endocrinologists are in the curious position of offering GH replacement to some patients with severe GH deficiency (GHD) but withholding it from other patients with even more severe GHD. This approach is counter-intuitive to endocrine practice in treating endocrine deficiency states. For all other endocrine deficiencies, one would opt for treating those with the most severe biochemical evidence of deficiency first. If this endocrine approach was applied to adult GH replacement in an era of rationing, one would start with the GHD patients with a pathologically low IGF1 level. Given that the prevalence of subnormal IGF1 levels in a GHD population is age-dependent, this would result in GH replacement being offered to more young adult onset (AO) GHD and childhood onset GHD adults, and less often to middle-aged and elderly AO GHD adults. This in itself has the added advantage that the skeletal benefits appear more real in the former cohort of patients.
    • GH releasing peptide 2 test: the holy grail of testing GH deficiency?

      Brabant, Georg E; Department of Endocrinology, Christie Hospital, University of Manchester, Manchester M20 4BX, UK. georg.brabant@manchester.ac.uk (2007-07)
    • Growth hormone and the transition from puberty into adulthood

      Attanasio, Andrea F; Shalet, Stephen M; Cascina del Rosone, Via Monsarinero 45, 14041 Agliano Terme, Italy (2007-03)
    • Growth hormone replacement therapy during transition of patients with childhood-onset growth hormone deficiency into adulthood: what are the issues?

      Shalet, Stephen M; Rosenfeld, R G; Department of Endocrinology, Christie Hospital NHS Trust, Manchester, UK. (1998-04)
    • Pathophysiology of radiation-induced growth hormone deficiency: efficacy and safety of GH replacement.

      Darzy, Ken H; Shalet, Stephen M; Department of Endocrinology, Christie Hospital NHS Trust, Wilmslow Road, Withington, Manchester M20 4BX, United Kingdom. (2006-07)
      Radiation-induced growth hormone deficiency (GHD) is primarily due to hypothalamic damage. GH secretion by the pituitary may be affected either secondary to some degree of quantitative deprivation of hypothalamic input or, if the radiation dose is high enough, by direct pituitary damage. As a consequence, the neurosecretory profile of GH secretion in an irradiated patient remains pulsatile and qualitatively intact. The frequency of pulse generation is unaffected, but the amplitude of the GH pulses is markedly reduced. Over the last 25 years, the final heights achieved by children receiving GH replacement for radiation-induced GHD have improved; these improvements are attributable to refinements in GH dosing schedules, increased use of GnRH analogues for radiation-induced precocious puberty, and a reduced time interval between completion of irradiation and initiation of GH therapy. When retested at the completion of growth, 80-90% of these teenagers are likely to prove severely GH deficient and, therefore, will potentially benefit from GH replacement in adult life. Such long-term GH treatment in patients treated previously for a brain tumor means that critical and continuous surveillance must be devoted to the risk of tumor recurrence and the possibility of second neoplasms.