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The spectrum of hypopituitarism caused by PROP1 mutations
Sushil Mody1, Milton R Brown, John S Parks
1Department of Pediatrics, Johns Hopkins School of Medicine, Baltimore, MD, USA.
Insights
PROP1 gene mutations cause combined anterior pituitary hormone deficiencies, often diagnosed later in childhood. Growth hormone deficiency typically appears before thyroid-stimulating hormone deficiency, with varied hormonal and physical outcomes.
Area of Science:
- Genetics
- Endocrinology
- Pediatrics
Background:
- Mutations in the PROP1 gene are a significant cause of combined anterior pituitary hormone deficiencies in humans.
- Affected individuals exhibit diverse physical and hormonal phenotypes, complicating early diagnosis.
Purpose of the Study:
- To review the clinical presentation and diagnostic considerations of PROP1 gene-related pituitary hormone deficiencies.
- To highlight the typical progression of hormonal deficits and variability in physical manifestations.
Main Methods:
- Literature review of clinical cases and genetic studies concerning PROP1 mutations.
- Analysis of reported hormonal profiles, physical examinations, and pituitary imaging findings.
Main Results:
- Diagnosis is rarely made in the first year of life, with growth failure often appearing later in childhood.
- Growth hormone (GH) deficiency usually precedes thyroid-stimulating hormone (TSH) deficiency. Some patients experience pubertal arrest with loss of gonadotropin responses.
- Partial corticotrophin (ACTH) deficiency is a late-onset finding. Pituitary imaging may show a small gland or an intrapituitary mass.
Conclusions:
- PROP1 mutations lead to a spectrum of anterior pituitary dysfunction with a characteristic, though variable, progression of hormone deficiencies.
- Further research is needed to understand the mechanisms behind delayed hormone loss and pituitary overgrowth in these patients.
Abstract:
Mutations in the PROP1 gene are responsible for a high proportion of cases of multiple or combined anterior pituitary hormone deficiencies in humans. The physical and hormonal phenotypes of affected individuals are not uniform. The diagnosis is seldom considered during the first year of life. Growth failure is usually evident later in childhood. Deficiency of growth hormone (GH) tends to precede deficiency of thyroid-stimulating hormone (TSH). While most affected individuals fail to enter puberty without sex hormone replacement, some enter puberty but then develop pubertal arrest with a loss of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) responses to GnRH. Partial deficiency of corticotrophin (ACTH) is a late finding. Imaging of the pituitary may disclose either a small anterior pituitary gland or an intrapituitary mass. The mechanisms responsible for delayed loss of hormone production and the occasional overgrowth of the pituitary represent important areas for future research.