GHD Diagnostics in Europe and the US: An Audit of National Guidelines and Practice

Abstract

<b><i>Introduction:</i></b> Almost 20 years after the first international guidelines on the diagnosis and treatment of GHD have been published, clinical practice varies significantly. The low accuracy of endocrine tests for GHD and the burden caused by ineffective treatment of individual patients were strong motives for national endocrine societies to set up national guidelines regarding how to diagnose GHD in childhood. This audit aims to review the current state and identify common changes, which may improve the diagnostic procedure. <b><i>Methods:</i></b> A group of eight German pediatric endocrinologists contacted eight pediatric endocrinologists from Spain, France, Poland, the UK, the Netherlands, Denmark, Italy, and the US. Each colleague responded as a representative for the own country to a detailed questionnaire containing 22 open questions about national rules, guidelines, and practice with respect to GHD diagnostics and GH prescription. The results were presented and discussed in a workshop and then documented in this study which was reviewed by all participants. <b><i>Results:</i></b> National guidelines are available in 7 of 9 countries. GH is prescribed by pediatric endocrinologists in most countries. Some countries have established boards that review and monitor prescriptions. Preferred GH stimulation tests and chosen cutoffs vary substantially. Overall, a trend to lowering the GH cutoff was identified. Priming is becoming more popular and now recommended in 5 out of 9 countries; however, with different protocols. The definition of pretest-conditions that qualify the patient to undergo GH testing varies substantially in content and strictness. The most frequently used clinical sign is low height velocity, but definition varies. Height, IGF-1, and bone age are additional parameters recommended in some countries. <b><i>Conclusions:</i></b> GHD diagnostics varies substantially in eight European countries and in the US. It seems appropriate to undertake further efforts to harmonize endocrine diagnostics in Europe and the US based on available scientific evidence.

Adolescent boys with constitutional delay of growth and puberty grow faster than patients with organic growth hormone deficiency

“…The high mean age at initiation of rhGH treatment in association with late puberty in rhGH postmarketing studies 16 is an additional hint that GHD is often not clearly distinguished from tempo variants of growth, which do not profit from rhGH treatment. The major clinical characteristic widely accepted to suggest GHD is decreased growth velocity based on the comparison with reference values 17 . Although height standards and height velocity references for infancy and childhood are unproblematic, age‐related reference data for adolescents always reflect the biology of normally maturing children and neglect the group of late maturers, who naturally grow slower due to lack of puberty.…”

Should Pediatric Endocrinologists Consider More Carefully When to Perform a Stimulation Test?

“…In an Italian single-center retrospective study conducted on 166 children with a first pathologic ATT test, GHD was confirmed in 80.2% of patients (27), thus resulting in accordance with our study. Therefore, in the Unites States and almost all the Europe, two stimulation tests are required in order to reduce the risk of false positive results (28). The ITT test is still considered the gold standard with a high power of discrimination.…”

Differential Diagnosis of the Short IGF-I-Deficient Child with Apparently Normal Growth Hormone Secretion

“…Finally, the reproducibility of a GHST is low [14], probably caused partially by the effect of a variable interval between the pharmacological agent and the foregoing spontaneous GH pulse (the refractory interval is estimated at 3 h [23, 24]). All these uncertainties have led to a large variation in clinical practice around the world with regard to GHSTs [25, 26].…”