An audit of the management of childhood-onset growth hormone deficiency during young adulthood in Scotland

Our data confirm that a high proportion (82 %) of the retested patients with CO-GHD continue to have GHD as adults. The majority (80 %) of those who remain GH deficient opted to resume adult GH treatment, however it is unknown whether they complied with therapy and for how long they continued with the treatment. It may also be the case that those adults who were GHD initially declined to restart rhGH during transition, but later reconsidered GH therapy. Factors influencing this decision would be an important area for future studies.

Previous published studies have reported variable estimates of persistent GHD in adulthood ranging from 12.5–90 % [ 13, 14] but the high incidence of ongoing GHD in adulthood in our cohort may be attributed to the large proportion of patients with organic causes for their GHD. Some of our subjects with MPHD who had no structural abnormalities on MRI continued to have GHD, raising the possibility of an underlying genetic disorder. Similarly, the majority of idiopathic IGHD who were re-evaluated were GH deficient which may also indicate an underlying genetic predisposition. These findings suggest the importance of follow up and regular assessment of pituitary function in those with a low probability of persistent GHD, as they may develop other pituitary hormone deficiencies as previously demonstrated [ 15, 16]. On the other hand, some patients who would be considered as having a moderate to high probability of persistent GHD (IGHD with structural abnormalities, patients with MPHD or those with a history of cranial irradiation) were no longer GH deficient. These findings demonstrate the limitations in using “at risk” groups to determine who require re-evaluation of their GH axis and those who do not.

Our data confirm that while there are no unequivocal auxological or clinical signs that predict the transiency or the persistence of GHD, a history of organic disease, the presence of two or more additional PHDs [ 17, 18], presence of hypothalamic-pituitary structural abnormalities and tumour related organic GHD are strong indicators of persistence GHD [ 19– 22].

In terms of timing of retesting, the current guidelines suggest that a period from one to three months off rhGH is sufficient for retesting [ 9]. Our data show a variable interval between stopping treatment and reassessment, with only 28 % of patients off rhGH for less than 3 months. It is not clear for those who were off rhGH for longer duration before reassessment whether their stopping rhGH was for reasons other than re-testing. However, this prolonged period off rhGH may be associated with detrimental effects on somatic bone and body composition development during transition [ 23, 24], with recommendations for prompt resumption of rhGH in individuals with clinical evidence of persistent GHD [ 25]. Furthermore, a longer interval off rhGH may increase the risk of being lost to follow up in these already vulnerable patients and continued follow up around this time is essential [ 26]. We recommend that in patients who are under the care of paediatric services, the evaluation of GHD in transition should be undertaken by the paediatric clinic, ideally in the context of a joint transition service to improve the follow up and smooth transfer of adolescents with chronic endocrine conditions to the adult services as previously suggested [ 27].

The principle of offering rhGH during transition for those who have ongoing severe deficiency was variable between centres as the cut-offs chosen are variable, though the majority were in keeping with the guidance suggesting a GH peak <5 μg/l constituting severe GHD in transition [ 9, 10]. Few patients in our cohort declined restarting adult rhGH, they may be asymptomatic and therefore reluctant to restart rhGH therapy. Approximately one third of our subjects were considered to be very likely to have permanent GHD and therefore continued rhGH uninterrupted, apart from adjustment to an adult GH dose. This is in line with current guidelines which recommend that patients with severe congenital or acquired panhypopituitarism with three or more pituitary hormone deficiencies or identified genetic mutations may not require re-evaluation of their GH status; otherwise all patients with CO-GHD require biochemical re-evaluation and reconfirmation of GHD during transition before reinstituting adult GH replacement therapy [ 9, 12]. However, of the 34 patients who continued adult rhGH without formal retesting, nine had structural abnormalities on MRI probably were at high risk of ongoing GHD, but three had unexplained GHD and probably should have been retested. Furthermore, some centres still retested those with a high likelihood of permanent GHD, by checking their IGF1 levels, although all were reconfirmed GHD and resumed rhGH. On these grounds, it seems that no clear consensus has been reached as to whether or not to withdraw treatment and retest those at high risk of permanent GHD. It is also unclear whether those who continued rhGH without biochemical re-testing were re-evaluated at a later stage. For those who restarted rhGH, according to the current guidelines, at completion of somatic growth (approximately 25–30 years old) further re-evaluation should be undertaken with the offer of adult GH replacement therapy and monitoring in accordance with National Institute for Health and Care Excellence guidance (NICE) (TA 64 August 2003).