Abstract:
Disturbance of growth and development is one of the most frequent reasons for consulting a doctor during childhood.
There are manifold causes for such disturbances. In many cases, there is not an isolated defect of the growth hormone concerning pituitary axis and therefore not only a lack of growth hormone. Often, there are more pituitary axes affected.
Such a clinical picture is called combined pituitary hormone deficiency (CPHD).
One possible reason for CPHD can be found in the malfunction of pituitary transcription factors. The disease pattern belonging to such a malfunction shows a broad variety both in manifestation at a particular time and in severity of possible deficiencies.
This retrospective study of children developing secondary hypothyroidism while being substituted with growth hormone serves to demonstrate the clinical course of these children and adolescents on the one hand, on the other hand it should be ascertained if a mutation of pituitary paired-like homeodomain transcription factor gene PROP-1 was cause of pituitary failure.
To achieve this, detailed clinical evaluation and description of endocrinological tests were performed. To get a widespread clinical characterisation, neuro-imaging to show abnormal pituitary morphology or cerebral malformation was performed and lists of additional diseases were made. Moreover, there was DNA-sequencing of the three exons of PROP-1 in 31 probands.
In one child, a compound-heterozygous mutation in PROP-1 could be found (2,3 % of all probands).
Therefore, secondary hypothyroidism developing under therapy with growth hormone is not caused by defects in PROP-1 and new “candidate genes” whose mutations can cause the sequence named above, must be found und examined.