Growth and growth hormone secretion in paediatric Cushing's disease.
Although paediatric Cushing's disease is rare, it is associated with severe morbidity in childhood and presents a major diagnostic and therapeutic challenge for the paediatric endocrinologist. Growth failure remains an important feature of paediatric Cushing's disease, both at diagnosis and after successful treatment. However, the development of specific diagnostic tests and important therapeutic advances has contributed significantly to the current management. Transsphenoidal pituitary surgery (TSS) is now accepted as first-line therapy for both adult and paediatric Cushing's disease, offering the best opportunity for cure while preserving normal pituitary function. The cure rate following TSS in our centre is currently 62%; therefore, a significant proportion of children following TSS will remain uncured. Our favoured second-line therapy is pituitary radiotherapy, which is effective, rapid and appears to spare anterior pituitary function, with the exception of GH secretion. Growth failure was a symptom at diagnosis in 74% of patients; mean height SDS -1.81 (-0.28 to -4.17) compared with mean BMI SDS 2.29 (1.72-5.06). Height velocity (HV) was also subnormal; range 0.9-3.8 cm/yr. Chronic hypercortisolaemia suppresses linear growth and a history of symptoms for >2 years was obtained in 72% of our paediatric patients with Cushing's disease. In our series, 9 out of 10 patients did not demonstrate catch-up growth 0.64 years after TSS or pituitary radiotherapy and peak serum GH level to glucagon/ITT stimulation was 0.5-20.9 mU/l. Assessment of GH secretion over a period of 6 to 108 months after cure of paediatric Cushing's disease suggests that impaired GH secretion may persist into adult life. Investigation of possible GHD is performed in our unit in all post-cure patients who do not show optimal catch-up growth. If GH secretion is subnormal, GH replacement is started early and continued until final height, when GH secretion is reassessed. In our series of 10 patients, 9 received GH therapy, combined in 3 with a GnRH analogue to arrest puberty. The results of this treatment were satisfactory with mean height deficit compared with target height improving significantly from mean -1.72 +/- 1.26 SDS at diagnosis to -0.93 +/- 1.13 SDS (p=0.005) at final height or latest assessment, indicating that a favourable final height can be achieved.
Savage
Martin O
MO
Department of Endocrinology, St Bartholomew's and The Royal London School of Medicine and Dentistry, London, UK.
Storr
Helen L
HL
Grossman
Ashley B
AB
Krassas
Gerasimos E
GE