Endocrine dysfunction in patients with Fabry disease

Antongiulio Faggiano, A. Pisani, F. Milone, M. Gaccione, M. Filippella, A. Santoro, G. Vallone, F. Tortora, M. Sabbatini, L. Spinelli, G. Lombardi, B. Cianciaruso, A. Colao

Research output: Contribution to journalArticlepeer-review


Background: Fabry disease (FD) is a genetic disorder caused by lysosomal α-galactosidase-A deficiency and is characterized by the systemic accumulation of globotriaosylceramide. All endocrine glands are susceptible to globotriaosylceramide accumulation because of their high vascularization and low cellular proliferation rate. Nevertheless, this endocrine system has never been investigated in detail. Objective: We aimed to investigate the function and morphology of the endocrine glands in FD. Patients: The thyroid, gonadal, adrenal, and GH/IGF-I axes were evaluated in 18 FD patients (nine females and nine males, aged 21-64 yr) and 18 sex- and age-matched healthy subjects. Study design: We conducted an observational, analytical, open, prospective study. Interventions: Ten of the 18 patients received enzyme replacement therapy (ERT) with recombinant human α-galactosidase-A (agalsidase β) at a dose of 1 mg/kg body weight every 2 wk. Results: FD patients had higher baseline TSH levels than controls (P <0.01). Three subjects were diagnosed with an early stage of subclinical primary hypothyroidism associated with negative antithyroid antibodies. A history of menses abnormalities, miscarriage, or assisted delivery was found in 89% of FD women. Asthenozoospermia, oligozoospermia, or both were found in all FD men through seminal fluid analysis. FD patients had significantly higher circulating ACTH and lower cortisol levels than controls (P <0.05). In patients under ERT, a suboptimal cortisol response to the 250-μg ACTH test was found in 10%, and the ACTH-stimulated cortisol peak was significantly correlated to the health status profile (P <0.05). Conclusion: A variety of latent endocrine dysfunctions, including life-threatening conditions, occur in patients with FD. Endocrine dysfunctions are also present in patients already receiving ERT and are in part related to their persistent poor quality of life. An endocrine work-up should be recommended in all FD patients. Adequate monitoring and hormonal therapy, when required, have to be performed in cases of subclinical endocrine dysfunction to avoid life-threatening events.

Original languageEnglish
Pages (from-to)4319-4325
Number of pages7
JournalJournal of Clinical Endocrinology and Metabolism
Issue number11
Publication statusPublished - Nov 2006

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology, Diabetes and Metabolism


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