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Endocrine Alterations in Patients With Pachydermoperiostosis.

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Pachydermoperiostosis (PHO) patients often present with low IGF-1 and elevated estradiol, mimicking acromegaly. Genetic analysis revealed novel variants in HPGD and SLCO2A1 genes, clarifying PHO characteristics.

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Area of Science:

  • Endocrinology
  • Genetics
  • Rare Diseases

Background:

  • Pachydermoperiostosis (PHO), or primary hypertrophic osteoarthropathy, shares features with acromegaly, leading to endocrine referral.
  • Genetic causes typically involve biallelic loss-of-function variants in HPGD or SLCO2A1.
  • Endocrine assessment details for PHO patients are often lacking.

Purpose of the Study:

  • To investigate the genetic and endocrine profiles of PHO patients.
  • To differentiate PHO from acromegaly in patients referred for endocrine evaluation.

Main Methods:

  • Assessed 17 patients from 14 families with suspected acromegaly but normal IGF-1 and/or GH suppression.
  • Performed genetic analysis for HPGD and SLCO2A1 variants.
  • Conducted detailed endocrine assessments, including IGF-1 and estradiol levels.

Main Results:

  • All patients exhibited digital clubbing; most had periostosis, arthralgia, edema, pachydermia, and facial coarsening.
  • 53% had low IGF-1 levels, and others had levels in the lowest quartile.
  • Elevated estradiol was observed in 62% of male patients; biallelic HPGD or SLCO2A1 variants were identified in 12/14 kindreds, including novel SLCO2A1 variants.

Conclusions:

  • Low IGF-1 and elevated estradiol are common endocrine findings in PHO.
  • Identified nine novel and five known pathogenic/likely pathogenic variants in HPGD and SLCO2A1.
  • Genetic and endocrine characterization aids in diagnosing PHO and distinguishing it from acromegaly.