ESPE Yearbook of Paediatric Endocrinology

Clinical Endocrinology. 2020;93:305–311. doi: 10.1111/cen.14264. PMID: 32521075

This study analyzed retrospectively GH content in newborn screening cards of 20 children with clinical features suggestive of GH deficiency (such as recurrent hypoglycemia) compared to screening cards from 281 healthy newborns, and determined 7 ng/ml to be the optimal a cut off value for the diagnosis of GH deficiency (GHD).

Congenital hypopituitarism in neonates is a rare disease (estimated incidence < 1:20 000 newborns) and may be associated with developmental defects such as ocular, midline and genital abnormalities or be initially asymptomatic but at risk of developing multiple pituitary hormone deficiencies over time. Mutations in genes involved in pituitary development underlie congenital hypopituitarism, which is characterized by the deficiency of one or more pituitary hormones (1). Early diagnosis of GHD is crucial for preventing recurrent severe hypoglycemia in newborns and infants. GH stimulation tests are not feasible in neonatal age and IGF1 measurement is not helpful for diagnosis due to the physiological low blood concentrations at this age.

In this study, according to the clinical, endocrine and brain MRI characteristics, the newborns were classified as having severe GHD (recurrent hypoglycemia with either a significant cerebral MRI morphology or two additional pituitary hormone deficiencies), and without severe GHD (no recurrent hypoglycemia or recurrent hypoglycemia but no morphological or additional functional defects of the pituitary gland). A detailed questionnaire was sent to the physicians of each newborn with the tentative diagnosis of severe GHD, asking for clinical, endocrine, biochemical and radiological data of the patients. GH levels from 20 term newborns with severe GHD were compared with 441 term and 151 preterm healthy newborns. ROC plot analysis revealed 7 ng/ml as the cut-off value with the best predictive value (90% sensitivity and 98.7% specificity).

The conclusion was that a single measurement of GH concentrations in screening cards may confirm the clinical diagnosis of neonatal GHD. It is noteworthy that GH immunoreactivity in newborn screening cards shows a progressive time-dependent decay when stored at 6 °C indicating the need of adjusting the measured GH content by the storage time. In addition, GH levels vary with the assay method. For instance, another recent study has reported a cut-off value of 4.5 ng/ml having a 100% sensitivity and 85% specificity for diagnosing neonatal GH deficiency (3). Though the potential clinical impact of this study is beyond question, the retrospective design, the small number of patients with GHD and the dependence of diagnosis on the questionnaire responses may limit its value. A thorough clinical evaluation remains the basis for the suspicion of GHD which can be then confirmed by neuroradiology and GH measurement.

Reference: 1. Alatzoglou KS, Dattani MT. Genetic forms of hypopituitarism and their manifestation in the neonatal period. Early Hum Dev. 2009;85(11):705–712.2. Binder G, Weidenkeller M, Blumenstock G, Langkamp M, Weber K, Franz AR. Rational approach to the diagnosis of severe growth hormone deficiency in the newborn. J Clin Endocrinol Metab. 2010;95(5):2219–2226. 3. Mamilly L, Pyle-Eilola AL, Chaudhari M, Henry RK. The utility of a random growth hormone level in determining neonatal growth hormone sufficiency. Clin Endocrinol (Oxf). 2021;94(3):392–398.