Endocrine Alterations in Patients With Pachydermoperiostosis.

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 is often referred to endocrinologists. A detailed endocrine assessment is not available for these patients.

OBJECTIVE

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

METHODS

Seventeen patients from 14 families in which acromegaly was excluded based on lack of elevated insulin-like growth factor (IGF)-1 levels and/or growth hormone 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 ± SD, range 9-43). Digital clubbing was present in all patients. Periostosis (94%), arthralgia (88%), periarticular edema (77%), pachydermia (82%), and coarsened facial features resembling acromegaly (71%) were present in the vast majority of the patients, while eyelash trichomegaly, blepharoptosis, high-arched palate, gingival hypertrophy, gastrointestinal symptoms, and marfanoid habitus were 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. Estradiol concentration was increased above the normal range in 8 male patients (62%) with normal testosterone and prolactin levels. Biallelic HPGD (2/14 kindreds) or SLCO2A1 (8 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.

CONCLUSION

We establish that low IGF-1 and elevated estradiol levels are frequent features of PHO. Nine novel and 5 known pathogenic/likely pathogenic genetic variants were identified.