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GH and TSH deficiency
R W Pfäffle1, R Martinez, C Kim
1Dept. of Pediatrics RWTH Aachen, Germany. pfaeffle@alpha.imib.rwth-aachen.de
Insights
Growth hormone (GH) therapy can cause hypothyroidism in children due to pituitary development issues. Prop-1 gene mutations are a potential cause of combined pituitary hormone deficiency when Pit-1 gene mutations are absent.
Area of Science:
- Endocrinology
- Genetics
- Developmental Biology
Background:
- Hypothyroidism is a known complication of growth hormone (GH) therapy in GH-deficient children.
- The anterior pituitary gland's development involves complex interactions between cell lines and transcription factors.
- Pit-1 is a key transcription factor regulating pituitary development, and its mutations cause combined pituitary hormone deficiency (CPHD).
Purpose of the Study:
- To investigate the role of transcription factors in combined pituitary hormone deficiency (CPHD).
- To explore potential genetic causes for CPHD in patients lacking Pit-1 gene mutations.
Main Methods:
- Review of existing literature on pituitary development and transcription factors.
- Analysis of genetic data from families with CPHD.
- Clinical presentation analysis of patients with GH deficiency and hypothyroidism.
Main Results:
- Mutations in the Pit-1 gene lead to deficiency in GH, Prolactin (Prl), and TSH, causing severe growth and developmental retardation.
- Over half of families with CPHD do not show Pit-1 gene abnormalities.
- Prop-1, a transiently expressed fetal anterior pituitary transcription factor, is emerging as a candidate gene for CPHD in Pit-1-negative cases.
Conclusions:
- Pit-1 gene mutations are a significant cause of CPHD, but not the sole genetic factor.
- Prop-1 gene mutations represent a likely alternative cause for CPHD in patients without Pit-1 abnormalities.
- Understanding these genetic factors is crucial for diagnosing and managing GH deficiency and hypothyroidism in children.
Abstract:
Hypothyroidism is a recognised complication of GH therapy in GH deficient children. The mechanisms involved include direct effects on thyroid function but also result from the close interrelationship of pituitary cell-lines that differentiate during embryonic development of the anterior pituitary gland. Among numerous pituitary transcriptionfactors that orchestrate pituitary organogenesis Pit-1 was the first to be recognised and is the most extensively studied. Mutations in the Pit-1 gene account for a form of combined pituitary hormone deficiency for GH, Prolactin (Prl) and TSH (CPHD). Despite the variability of the clinical presentation of this syndrome at the time of initial diagnosis, all forms finally result in severe retardation of growth and development due to GH-deficiency and hypothyroidism. More than half of the families with a combined pituitary hormone deficiency have not disclosed any Pit-1 abnormalities. Evidence is accumulating that Prop-1, a transcriptionfactor expressed temporarily in the fetal anterior pituitary, could be a candidate for patients with a Pit-1 phenotype without any Pit-1 gene abnormalities.