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Pituitary size fluctuation in long-term MR studies of PROP1 deficient patients: A persistent pathophysiological
A Voutetakis1, A Sertedaki, S Livadas
1First Pediatric Department, Athens University School of Medicine, Aghia Sophia Children's Hospital, Greece. avouteta@nidcr.nih.gov
Abstract:
Inactivating PROP1 gene alterations are responsible for over 50% of familial combined pituitary hormone deficiency cases. Pituitary enlargement followed by regression and subnormal pituitary size has been documented in a number of PROP1 deficient patients. Data derived from PROP1 deficient mice (Ames dwarfs) have revealed some of the underlying cellular mechanisms. Nevertheless, long-term magnetic resonance imaging (MRI) findings in two PROP1 deficient patients suggest the evolution of pituitary pathology as more complex and persistent than previously described. Patient A had enlarged pituitary gland (pituitary height: 9-10 mm), demonstrated by serial MRI carried out from age 5 to 8.5 yr, small pituitary gland (4 mm) at age 10 yr and pituitary enlargement (11 mm) at age 19 yr. Patient B had a pituitary gland of normal size at age 7 yr (5 mm), whereas at age 14.3 and 16.3 yr, an enlarged pituitary gland was disclosed (10 and 11 mm, respectively). Both series of events are suggestive of a persistent pathophysiological mechanism in the pituitary gland of patients with PROP1 gene defects. Therefore, long-term pituitary follow-up by MRI in such patients may be necessary even in the case of a small or normal pituitary gland. It must be noted that current data from the Ames dwarf mouse cannot fully explain the observed pituitary size fluctuation.
Insights
Prophet-1 (PROP1) gene mutations cause combined pituitary hormone deficiency. Long-term MRI in PROP1-deficient patients reveals complex pituitary size fluctuations, challenging existing models.
Area of Science:
- Genetics
- Endocrinology
- Radiology
Background:
- Prophet-1 (PROP1) gene inactivating alterations are a primary cause of familial combined pituitary hormone deficiency (CPHD).
- Previous studies, including those on Ames dwarf mice, suggested PROP1 deficiency leads to pituitary enlargement followed by regression.
- The cellular mechanisms underlying PROP1-related pituitary pathology are not fully understood.
Observation:
- Serial magnetic resonance imaging (MRI) in two PROP1-deficient patients demonstrated dynamic pituitary size changes.
- Patient A exhibited pituitary enlargement, subsequent regression, and a later re-enlargement.
- Patient B showed a normal pituitary size initially, followed by significant enlargement over time.
Findings:
- Long-term MRI findings indicate a more complex and persistent pituitary pathology in PROP1 deficiency than previously recognized.
- Observed pituitary size fluctuations in patients suggest ongoing pathophysiological processes.
- Current data from PROP1-deficient mouse models do not fully account for the observed pituitary size variability in humans.
Implications:
- Long-term pituitary monitoring using MRI is crucial for patients with PROP1 gene defects, irrespective of initial pituitary size.
- These findings highlight the need for revised understanding of PROP1's role in pituitary development and function.
- Further research is warranted to elucidate the mechanisms driving persistent pituitary size fluctuations in PROP1 deficiency.
