Endocrine alterations in patients with pachydermoperiostosis

Maria Stelmachowska-Banaś, Sayka Barry, Ishita Angurala, Tom Rice, Kesson Magid, Ana Carreira, Ashutosh Rai, Amy Evans, Mark Bollington, Vaishali Kaur, Shallu Singhmar, Cristina Alina Silaghi, Kudakwashe Mandisodza, Alan McGregor, Jayaprakash Sahoo, Rahul Gupta, Kishore Kumar Behera, Ayan Roy, Ian Carr, Paul Benjamin LoughreyPinaki Dutta, Márta Korbonits*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

CONTEXT: Pachydermoperiostosis (primary hypertrophic osteoarthropathy, PHO) usually due to biallelic loss-of-function variants in HPGD and SLCO2A1, has some features overlapping with acromegaly and often referred to endocrinologists. A detailed endocrine assessment is not available for these patients.

OBJECTIVE: To assess the genetic and endocrine characteristics of PHO patients referred to endocrine centres with a possible diagnosis of acromegaly.

METHODS: Seventeen patients from 14 families in which acromegaly was excluded based on lack of elevated IGF-1 levels and/or GH suppression on an oral glucose tolerance test were assessed for HPGD and SLCO2A1 variants.

RESULTS: Age at diagnosis was 26.2±9.0 years (mean±standard deviation, range 9-43). Digital clubbing was present in all patients. Periostosis (94%), arthralgia (88%), periarticular oedema (77%), pachydermia (82%) and coarsened facial features resembling acromegaly (71%) was present in the vast majority of the patients, while eyelash trichomegaly, blepharoptosis, high-arched palate, gingival hypertrophy, gastrointestinal symptoms and marfanoid habitus was seen in some. Nine patients (53%) had low IGF-1 levels, the rest of the patients had IGF-1 levels in the lowest quartile of the reference range. Oestradiol concentration was increased above the normal range in eight male patients (62%) with normal testosterone and prolactin levels. Biallelic HPGD (2/14 kindreds) or SLCO2A1 (eight novel) variants (12/14 kindreds) were found. Two patients had no identifiable pathogenic/likely pathogenic variant in HPGD or SLCO2A1. Their phenotype was not different from the other patients.

CONCLUSIONS: We establish that low IGF-1 and elevated oestradiol levels are frequent features of PHO. Nine novel and five known pathogenic/likely pathogenic genetic variants were identified.

Original languageEnglish
JournalThe Journal of clinical endocrinology and metabolism
Early online date29 Jan 2025
DOIs
Publication statusEarly online date - 29 Jan 2025

Bibliographical note

© The Author(s) 2025. Published by Oxford University Press on behalf of the Endocrine Society.

Keywords

  • Pseudoacromegaly
  • Acromegaly
  • IGF-I
  • HPGD
  • SLCO2A1
  • Pachydermoperiostosis
  • Primary hypertrophic osteoarthropathy
  • Endocrinology

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism

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