Endocrine dysfunction in patients with Fabry disease.
BACKGROUND
Fabry disease (FD) is a genetic disorder caused by lysosomal alpha-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.


METHODS
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.


METHODS
We conducted an observational, analytical, open, prospective study.


METHODS
Ten of the 18 patients received enzyme replacement therapy (ERT) with recombinant human alpha-galactosidase-A (agalsidase beta) 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-microg ACTH test was found in 10%, and the ACTH-stimulated cortisol peak was significantly correlated to the health status profile (P < 0.05).


CONCLUSIONS
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.
Faggiano
A
A
Department of Molecular, Federico II University of Naples, Via Sergio Pansini 5, 80131 Naples, Italy. afaggian@unina.it
Pisani
A
A
Milone
F
F
Gaccione
M
M
Filippella
M
M
Santoro
A
A
Vallone
G
G
Tortora
F
F
Sabbatini
M
M
Spinelli
L
L
Lombardi
G
G
Cianciaruso
B
B
Colao
A
A
D000307:Adrenal Gland Diseases / Q000453:epidemiology; D000328:Adult; D016022:Case-Control Studies; D015897:Comorbidity; D004703:Endocrine System / Q000502:physiology*; D004700:Endocrine System Diseases / Q000150:complications* / Q000453:epidemiology; D000795:Fabry Disease / Q000097:blood / Q000150:complications* / Q000378:metabolism; D005260:Female; D006058:Gonadal Disorders / Q000453:epidemiology; D013006:Growth Hormone / Q000378:metabolism / Q000502:physiology; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism / Q000502:physiology; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D013959:Thyroid Diseases / Q000453:epidemiology
D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone