Endocrine Abstracts

Fabry Disease (FD) is a rare X–linked metabolic storage disease characterized by a–galactosidase A deficiency and deficient lysosomal function. The patients suffer from diffuse organ manifestations due to the accumulation of the substrate globotriaosylceramide (Gb3), which are only partially reversed by the available enzyme replacement (ERT) therapies. Previous endocrinological studies in patients with FD included small patient numbers or focused on a certain organ. To investigate the function of the endocrine system in patients with FD, we conducted an observational prospective study and included 77 patients with genetically confirmed FD (26 men, 20/26 classic, 6/26 late–onset phenotype, 51 women, 41/51 and 10/51 respectively), who are systematically followed by our reference center. Within this cohort, 3/77 new cases of subclinical and 2/77 of manifest hypothyroidism were identified while no abnormalities in the GH/IGF-1 axis was found. All (77/77) patients had normal baseline ACTH and morning cortisol levels and unrestricted cortisol response upon short time synacthen testing (62/62). Several cases with altered renin–angiotensin–aldosterone system (RAAS) were detected but none of them included clinical or hormonal suspicion of primary aldosteronism and the discrepancies were explained in the context of chronic kidney disease (CKD) or antihypertensive medications. 11/77 patients were suffering from significant hypophosphatemia (P < 0.80 mmol/l), likely due to VitD deficiency. 25/77 patients had VitD deficiency (25(0H)VitD < 20 mg/l) and 25/77 had insufficiency (25(0H)VitD between 20 and 30 mg/l) despite the fact that 23/50 were substituted with cholecalciferol. In male patients, normal baseline testosterone, FAI and SHBG levels were documented with no indication of hypogonadism. In 1/33 women, primary infertility and estrogen substitution was reported and further 4/33 achieved pregnancy only following IVF. 5/33 patients had a history of miscarriages but all of them delivered children. One/33 women had clinical and biochemical features of PCOS. To our knowledge, this is the largest endocrine study in patients with FD. Our findings indicate presence of a range of endocrine conditions in patients with FD. Longitudinal and case/control studies will be required to provide indication whether these findings are caused by FD dependent mechanisms on endocrine organs or represent independent co-morbidities similar than in the general population. Overall, our study highlights the importance of actively seeking and diagnosing endocrine disorders in patients with FD with the goal to optimise their health care.