Endocrine Abstracts

The diagnosis of GHD in young adults is not straightforward and represents a major clinical challenge. The key predictors of persistent GHD are the severity of the original GH deficiency, the presence of additional pituitary hormone deficits, severely low IGF1 concentrations, and structural hypothalamic–pituitary (HP) abnormalities. We have demonstrated that patients with GHD and congenital HP may not require re-evaluation of GH secretion, whereas patients with isolated GHD and normal or small pituitary gland should be retested well before the attainment of adult height. MRI findings of the HP area in patients with GHD may be the most important criterion upon which the decision to re-evaluate a patient can be based, as opposed to response to pharmacological stimulation.

Two recent consensus statements on the management of young adults with childhood onset GHD during transition phase state that there are various groups of patients have a high likelihood of permanent GHD after adult height attainment; these include those with severe GHD in childhood with or without two or three additional hormone deficits possibly due to a defined genetic cause, those with severe GHD due to structural HP abnormalities and with CNS tumors, and patients having received high-dose cranial irradiation.

A subgroup of subjects with idiopathic GHD of childhood onset presenting with congenital structural HP abnormalities confirms that GHD patients – defined ‘a priori’ as those with GH response <5 μg/l and with anterior pituitary hypoplasia, pituitary stalk agenesis and posterior pituitary ectopia at the level of the median eminence – are likely candidates for permanent GHD in adult life, while those with less severe MRI features have an uncertain diagnosis or a likelihood of normal GH response after stimulation tests. These findings have important clinical implications in the diagnosis and prognosis of GHD after adult height achievement.

The comparison between a cohort of subjects with a high likelihood of permanent GHD and a control group showed that the lowest values observed in normal subjects of peak GH after insulin tolerance test (ITT) of 6.1 μg/l and IGF1 of −1.7 SDS could identify GHD subjects with a sensitivity of 96 and 77% respectively and a specificity of 100% for both groups. Another recent study that compared two groups of subjects with high and low likelihood of permanent GHD confirmed that a peak GH response after insulin tolerance test of less than 5.62 μg/l can distinguish between the two groups, correctly classifying 87.34% of subjects (with sensitivity of 77.42% and specificity of 93.75%). Indeed, IGF1 measurement is a useful marker of the degree of GHD, ensuring an accurate classification of patients with severe GHD for cut-off levels of ≤ −2.8 SDS (40). Pituitary function should be periodically assessed in subjects with pituitary stalk agenesis and IGHD or CPHD, as they may develop additional pituitary hormone deficiencies and deterioration of metabolic parameters. In our recent study, ACTH deficiency characterized a subset of patients with idiopathic GHD and pituitary stalk abnormalities, revealing that several of them had undiagnosed subclinical ACTH deficiency.