RESUMO
The cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) gene on 2q33 is associated with autoimmune thyroid diseases (AITDs). Our earlier study in 56 families showed linkage of 2q33 to the presence of thyroid antibodies (TAbs). The goals of this study were to confirm the linkage of the 2q33 region to TAbs, to fine map this region, and study the ICOS gene. We performed a linkage study in an expanded data set of 99 multiplex AITD-TAb families (529 individuals). The highest two-point LOD score of 2.9 was obtained for marker D2S325 on 2q33. To fine map this locus, we genotyped 238 Caucasian AITD patients and 137 controls for five additional markers in the linked locus, which contained the CTLA-4, CD28, and ICOS genes. The A/G single-nucleotide polymorphism at position 49 of CTLA-4 was associated with AITD (P=0.01, OR=1.5), while markers inside CD28 and ICOS were not. Functional studies have shown that the G allele was associated with reduced inhibition of T-cell proliferation by CTLA-4. We concluded that: (1) the AITD gene in the 2q33 locus is the CTLA-4 gene and not the CD28 or ICOS genes; and (2) the G allele is associated with decreased function of CTLA-4.
Assuntos
Antígenos de Diferenciação de Linfócitos T/genética , Antígenos de Diferenciação/genética , Antígenos CD28/genética , Cromossomos Humanos Par 2/genética , Tireoidite Autoimune/genética , Alelos , Antígenos CD , Antígeno CTLA-4 , Mapeamento Cromossômico , Feminino , Genótipo , Humanos , Proteína Coestimuladora de Linfócitos T Induzíveis , Funções Verossimilhança , Escore Lod , Masculino , Repetições de Microssatélites/genética , Polimorfismo de Nucleotídeo Único/genética , Linfócitos T/imunologia , Tireoidite Autoimune/imunologia , População BrancaRESUMO
OBJECTIVE: To review the patient profiles, laboratory data, and diagnostic approaches in factitious administration of glucocorticoids. METHODS: Four cases of surreptitious use of glucocorticoids are presented. Clinical and laboratory data as well as imaging studies are summarized. Pertinent case reports in the literature are reviewed. RESULTS: We report four cases of surreptitious use of glucocorticoids encountered within a 2-year period. All four patients were women without significant psychiatric histories. In three patients, the question of factitious Cushing's syndrome was suspected because of physical evidence or symptoms of Cushing's syndrome (or both) in the setting of suppressed cortisol levels. The fourth patient had undetectable cortisol levels in both serum and 24-hour urine samples but did not have signs or symptoms of adrenal insufficiency. In three cases, the diagnosis was confirmed by direct measurement of synthetic glucocorticoids in the patient's urine or serum. The fourth case was diagnosed by correlating increased cortisol levels with decreased precursor adrenal steroids. CONCLUSIONS: Exogenous corticosteroid use in the absence of a medical indication poses a serious risk to a patient. This possibility should be considered in patients with signs and symptoms consistent with Cushing's syndrome but with low serum and urinary cortisol levels. Similarly, this diagnosis should be suggested in patients without symptoms of adrenal insufficiency and with low cortisol levels. Laboratory measurement of synthetic steroids can be helpful in confirming the diagnosis.
