ESPE Yearbook of Paediatric Endocrinology

To read the full abstract: Horm Res Paediatr. 2018; 90(5): 314

This single-centre, retrospective study analyzes the screening role of low IGF-1 levels in the diagnosis of growth hormone deficiency (GHD) in a cohort of 158 childhood cancer survivors (CCS) and in a selected sub-cohort of 117 CCS who received radiation for tumours not directly involving the hypothalamic-pituitary (HP) area (RT-NHP group).

The aim of the study was to assess the value of IGF-1 levels in predicting GH status, both at childhood GHD diagnosis and at final height retesting. IGF-1 levels <−2 SDS showed a low sensitivity for GHD (31.9%); test sensitivity was higher (45.6%) in patients with severe GHD, defined as GH peak < 3 mcg/l on stimulation tests. A significant negative correlation was found between pituitary radiation dose and GH peak on stimulation testing. IGF-1 levels showed no correlation with the number of hormonal defects in patients with multiple pituitary deficiencies. Conversely, when patients with childhood GHD in the RT-NHP group were retested after final height achievement, an IGF-1 level <–2 SDS predicted adulthood GHD in 100% of cases.

Previous reports on GHD in irradiated patients (1–6) seem to confirm that IGF-1 does not represent a suitable tool for screening purposes in irradiated patients. An overall poor sensitivity of IGF-1 levels <−2 SDS is reported in radiation-induced GHD. Sensitivity is higher in patients with severe GHD, while normal plasma IGF-1 concentrations despite a diagnosis of GHD are frequently found after low radiation doses to the HP area. According to the recommendation jointly provided by the European Endocrine Society and the Pediatric Endocrine Society there is a potential diagnostic reliability of low IGF-1 levels only in CCS with severe GHD (7).

The strengths of this interesting, well-designed study are its large, homogeneous cohort and its value in clinical practice. The limitations are instead related to its retrospective nature and to the lack of a control group of non-oncological GHD patients, which could provide more information about the role of IGF-1 in irradiation-dependent GHD.

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2. Tillmann V, Shalet SM, Price DA, Wales JK, Pennells L, Soden J, Gill MS, Whatmore AJ, Clayton PE. Serum insulin-like growth factor-I, IGF binding protein-3 and IGFBP-3 protease activity after cranial irradiation. Horm Res. 1998; 50: 71–77.

3. Achermann JC, Hindmarsh PC, Brook CG. The relationship between the growth hormone and insulin-like growth factor axis in long-term survivors of childhood brain tumours. Clin Endocrinol (Oxf). 1998; 49: 639–645.

4. Blum WF, Ranke MB, Kietzmann K, Gauggel E, Zeisel HJ, Bierich JR. A specific radioimmunoassay for the growth hormone (GH)-dependent somatomedin-binding protein: its use for diagnosis of GH deficiency. J Clin Endocrinol Metab. 1990; 70: 1292–1298.

5. Rosenfeld RG, Wilson DM, Lee PD, Hintz RL. Insulin-like growth factors I and II in evaluation of growth retardation. J Pediatr. 1986; 109: 428–433.

6. Sfeir JG, Kittah NEN, Tamhane SU, Jasim S, Chemaitilly W, Cohen LE, Murad MH. Diagnosis of GH Deficiency as a Late Effect of Radiotherapy in Survivors of Childhood Cancers. J Clin Endocrinol Metab. 2018; 103: 2785–2793.

7. Sklar CA, Antal Z, Chemaitilly W, Cohen LE, Follin C, Meacham LR, Murad MH. Hypothalamic-Pituitary and Growth Disorders in Survivors of Childhood Cancer: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2018; 103: 2761–2784.