Endocrine Abstracts

Case report: 24-year. old man presented with change in facial appearance and joint pain. His symptoms began at puberty with the thickening and folding of the skin on the forehead and scalp and thickening of his fingers. These changes progressed over the next 5 years with marked seborrhoea, hyperhidrosis and linear palmar–plantar keratosis. The lower legs and forearms are cylindrically thickened, hands and feet increased in size, the terminal phalanges of the fingers show pronounced clubbing. Change of appearance was accompanied by swelling and pain in the joints, particularly in the knees. The patient complained of diarrhoea and abdominal pain, a colonoscopy revealed ulcerative colitis. This state was maintained for 4–5 years. At the age 22 he noticed slight improvement in the joint pains. His younger brother presented with very similar symptoms and signs at the age of 17. The parents were not related to each other. Acromegaly, Sotos syndrome, McCune–Albright syndrome and Carney complex were ruled out with clinical tests.

We diagnosed hypertrophic osteoarthropathy (pachyder moperiostosis). Due to the familial nature of the disease and no other underlying disease we considered primary hypertrophic osteoarthropathy, which can be due to deficiency of the enzyme 15-hydroxyprostaglandin dehydrogenase (HPGD), but no mutations were detected in this gene. As the phenotype of these patients is slightly different (teenager rather than childhood-onset, severe cutis gyrate on the forehead, lack of acroosteolysis), another causative gene was sought. A novel gene SLCO2A1 (solute carrier organic anion-transporter family member-2A1), also part of the PDE-pathway, was found to have compound heterozygote mutations c.(838C>T)+(1693T>G), P.(R280X)+(W565G) in both subjects. SLCO2A1 is a transporter, which mediates active uptake of prostaglandins, prior to their intracellular degradation. Hypertrophic osteoarthropathy can develop due cancer-induced reactive osteoarthropathy or in response to therapy with PDE1. These findings implicate local prostaglandin excess as the stimulus to hypertrophic osteoarthropathy.

Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.

Funding: This work was supported, however funding details unavailable.