Pediatric Rheumatology Unit, Children's Institute, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Av. Dr. Eneas Carvalho Aguiar, 647 - Cerqueira César, Sao Paulo, SP, 05403-000, Brazil.
Internal Medicine Department, Faculdade de Medicina, Universidade Federal de Pelotas, Pelotas, Rio Grande do Sul, Brazil.
Clin Rheumatol. 2021 Sep;40(9):3651-3658. doi: 10.1007/s10067-021-05677-9. Epub 2021 Mar 13.
To assess overall adrenal mineralocorticoid/glucocorticoid/androgen steroidogenesis in childhood-onset systemic lupus erythematosus (cSLE) patients and the possible effect of prednisone on adrenal hormones and ovarian reserve.
Fifty-one adult cSLE (ACR criteria) patients and 23 healthy controls were evaluated for adrenal steroidogenesis including mineralocorticoid (progesterone, deoxycorticosterone, aldosterone), glucocorticoid (17-OHprogesterone, 11-desoxycortisol, cortisol), and androgen (dehydroepiandrosterone-sulfate, androstenedione, total testosterone, and dihydrotestosterone) hormones. Ovarian reserve assessment included follicle-stimulating hormone (FSH), estradiol, anti-Müllerian hormone, ovarian volumes, and antral follicle count.
The median of current age [29.11 (19-39.8) vs. 30.8 (19.6-42.1) years, p = 0.502] was similar in adult cSLE and controls. Regarding mineralocorticoid/glucocorticoid, the median of progesterone (p = 0.003), 17-OH progesterone (p < 0.001), and 11-desoxycortisol (p = 0.036) were significantly lower in patients compared to controls. All androgen steroidogenesis hormones were reduced in the former group [dehydroepiandrosterone-sulfate (p < 0.001), androstenedione (p = 0.001), total testosterone (p = 0.005), and dihydrotestosterone (p < 0.001)]. Further comparison of patients with and without current use of prednisone and controls revealed a predominant impact on adrenal glucocorticoid and androgen steroidogenesis with reduced levels of 17-OH progesterone [0.17 (0-0.5) vs. 0.27 (0.1-2.9) vs. 0.33 (0.1-0.8) ng/mL, p < 0.001], dehydroepiandrosterone-sulfate [0.155 (0-0.6) vs. 0.49 (0.1-1.6) vs. 1.11 (0.1-2.6) μg/mL, p < 0.001], androstenedione [0.56 (0.2-4.4) vs. 1.7 (0.5-4.5) vs. 2.33 (0.3-3.8) ng/mL, p < 0.001], total testosterone [12 (12-167) vs. 16 (12-28) vs. (16.5 (0-50) ng/d, p = 0.002], and dihydrotestosterone [92.68 (11.8-198.5) vs. 160.62 (37.9-842.1) vs. 188.3 (71.3-543.9) pg/ml, p < 0.001] in patients under this drug. In addition, patients with this therapy had reduced median ovarian volumes [4.14 (2-12) vs. 7.13 (2-25.7) vs. 5.18 (2.4-17.3) cm, p = 0.028) that was not associated with cyclophosphamide cumulative dose (p > 0.05). The median prednisone dose was 15/mg/day (2.5-40).
We provided novel evidence that cSLE patients have an overall androgen/glucocorticoid/mineralocorticoid adrenal suppression. Furthermore, low/moderate prednisone use seems to underlie these abnormalities and may also adversely affect ovarian reserve, independently of immunosuppressants. Key Points • cSLE patients have an overall androgen/glucocorticoid/mineralocorticoid adrenal suppression. • Low/moderate prednisone use may affect ovarian reserve, independently of immunosuppressants.
评估儿童起病系统性红斑狼疮(cSLE)患者的肾上腺糖皮质激素/盐皮质激素/雄激素类固醇生成的整体情况,并探讨泼尼松对肾上腺激素和卵巢储备的可能影响。
评估 51 例成人 cSLE(ACR 标准)患者和 23 例健康对照者的肾上腺类固醇生成情况,包括糖皮质激素(孕酮、脱氧皮质酮、醛固酮)、盐皮质激素(17-羟孕酮、11-去氧皮质醇、皮质醇)和雄激素(硫酸脱氢表雄酮、雄烯二酮、总睾酮、二氢睾酮)激素。卵巢储备评估包括卵泡刺激素(FSH)、雌二醇、抗苗勒管激素、卵巢体积和窦卵泡计数。
成人 cSLE 患者与对照组的中位年龄[29.11(19-39.8)与 30.8(19.6-42.1)岁,p=0.502]相似。关于盐皮质激素/糖皮质激素,与对照组相比,患者的孕酮(p=0.003)、17-羟孕酮(p<0.001)和 11-去氧皮质醇(p=0.036)中位数显著降低。所有雄激素类固醇生成激素均减少[硫酸脱氢表雄酮(p<0.001)、雄烯二酮(p=0.001)、总睾酮(p=0.005)和二氢睾酮(p<0.001)]。进一步比较有和无当前使用泼尼松的患者与对照组,发现肾上腺糖皮质激素和雄激素类固醇生成的主要影响,17-羟孕酮水平降低[0.17(0-0.5)与 0.27(0.1-2.9)与 0.33(0.1-0.8)ng/mL,p<0.001],硫酸脱氢表雄酮[0.155(0-0.6)与 0.49(0-1.6)与 1.11(0-2.6)μg/mL,p<0.001],雄烯二酮[0.56(0.2-4.4)与 1.7(0.5-4.5)与 2.33(0.3-3.8)ng/mL,p<0.001],总睾酮[12(12-167)与 16(12-28)与(16.5(0-50)ng/d,p=0.002]和二氢睾酮[92.68(11.8-198.5)与 160.62(37.9-842.1)与 188.3(71.3-543.9)pg/ml,p<0.001]在接受该药物治疗的患者中降低。此外,接受这种治疗的患者卵巢体积的中位数[4.14(2-12)与 7.13(2-25.7)与 5.18(2.4-17.3)cm,p=0.028)]降低,与环磷酰胺累积剂量无关(p>0.05)。泼尼松的中位剂量为 15/mg/天(2.5-40)。
我们提供了新的证据,表明 cSLE 患者存在整体的雄激素/糖皮质激素/盐皮质激素肾上腺抑制。此外,低/中等剂量的泼尼松使用似乎是这些异常的基础,并且可能独立于免疫抑制剂,对卵巢储备产生不利影响。关键点:cSLE 患者存在整体的雄激素/糖皮质激素/盐皮质激素肾上腺抑制。低/中等剂量的泼尼松使用可能独立于免疫抑制剂,对卵巢储备产生不利影响。