TY - JOUR
T1 - Endocrine alterations in patients with pachydermoperiostosis
AU - Stelmachowska-Banaś, Maria
AU - Barry, Sayka
AU - Angurala, Ishita
AU - Rice, Tom
AU - Magid, Kesson
AU - Carreira, Ana
AU - Rai, Ashutosh
AU - Evans, Amy
AU - Bollington, Mark
AU - Kaur, Vaishali
AU - Singhmar, Shallu
AU - Silaghi, Cristina Alina
AU - Mandisodza, Kudakwashe
AU - McGregor, Alan
AU - Sahoo, Jayaprakash
AU - Gupta, Rahul
AU - Behera, Kishore Kumar
AU - Roy, Ayan
AU - Carr, Ian
AU - Loughrey, Paul Benjamin
AU - Dutta, Pinaki
AU - Korbonits, Márta
N1 - © The Author(s) 2025. Published by Oxford University Press on behalf of the Endocrine Society.
PY - 2025/1/29
Y1 - 2025/1/29
N2 - 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.
AB - 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.
KW - Pseudoacromegaly
KW - Acromegaly
KW - IGF-I
KW - HPGD
KW - SLCO2A1
KW - Pachydermoperiostosis
KW - Primary hypertrophic osteoarthropathy
KW - Endocrinology
U2 - 10.1210/clinem/dgaf050
DO - 10.1210/clinem/dgaf050
M3 - Article
C2 - 39878145
SN - 0021-972X
JO - The Journal of clinical endocrinology and metabolism
JF - The Journal of clinical endocrinology and metabolism
ER -