外源性雌二醇对垂体功能不全女性促肾上腺皮质激素刺激过程中血浆皮质醇和唾液皮质醇的影响

Significance of Exogenous Estradiol on Plasma Cortisol and Salivary Cortisol During Adrenocorticotropic Hormone Stimulation in Women With Pituitary Insufficiency.

作者信息

Aagaard Laura S, Krogh Jesper, Perlman Signe, Klose Marianne, Andreassen Mikkel

机构信息

Department of Nephrology and Endocrinology, Rigshospitalet Copenhagen, Copenhagen, Denmark.

Department of Medicine, Clinic for Pituitary Disorders, Zealand University Hospital, Koge, Denmark.

出版信息

Clin Endocrinol (Oxf). 2025 Aug 17. doi: 10.1111/cen.70020.

DOI:10.1111/cen.70020

PMID:40820549

Abstract

OBJECTIVE

Oral estrogens increase the levels of cortisol binding globulin (CBG) potentially affecting test results for adrenal insufficiency. The objective was to evaluate the influence of oral and transdermal estradiol on total plasma (p) and salivary cortisol in hypogonadal women with secondary adrenal insufficiency or at risk of developing adrenal insufficiency. Furthermore, to determine if estradiol treatment can lead to a change in the diagnosis of adrenal insufficiency based on a Synacthen-test.

METHODS

Crossover study.

INTERVENTION

12 weeks oral estradiol (2 mg), 12 weeks transdermal estradiol (100 µg/day), and 12 weeks without estradiol. After each intervention plasma total cortisol (pTC), salivary cortisol and CBG were measured before and after a 250 ug Synacthen-test (30 min) (normal response pTC > 420 nmol/L, overt adrenal insufficiency pTC < 250 nmol/L).

RESULTS

Seventeen hypopituitary patients, mean age 42 ± 6 years were included. 30-min pTC did not change significantly according to intervention (no estradiol 401 (interquartile range: 55-495), oral estradiol 440 (74-600), and transdermal estradiol 304 (48-492) nmol/L). Based on pTC no patients with overt adrenal insufficiency crossed the cut-off for adrenal insufficiency between interventions whereas three patients with borderline adrenal insufficiency (pTC 390-559 nmol/L) crossed the cut-off. CBG was higher on oral estradiol compared to no estradiol (p < 0.001) and transdermal estradiol (p = 0.017) whereas 30-min salivary cortisol was lower on oral estradiol compared to no estradiol (6.6 (1.6-23.0) vs. 10.4 (3.6-25.5 nmol/L) p = 0.04) and transdermal estradiol (p = 0.07).

CONCLUSION

In patients with overt adrenal insufficiency pTC was not influenced by estradiol supplementation. However, salivary cortisol decreased on oral estradiol concomitant with an increase in CBG levels. Our data may support the use of transdermal estradiol and the use of salivary cortisol when evaluating the adrenal axis.

摘要

目的

口服雌激素会增加皮质醇结合球蛋白（CBG）水平，这可能会影响肾上腺功能不全的检测结果。本研究旨在评估口服和经皮雌二醇对继发性肾上腺功能不全或有肾上腺功能不全风险的性腺功能减退女性的血浆总皮质醇（p）和唾液皮质醇的影响。此外，确定雌二醇治疗是否会导致基于促肾上腺皮质激素（Synacthen）试验的肾上腺功能不全诊断发生变化。

方法

交叉研究。

干预措施

口服雌二醇（2mg）12周、经皮雌二醇（100μg/天）12周以及无雌二醇治疗12周。每次干预后，在250μg促肾上腺皮质激素试验（30分钟）前后测量血浆总皮质醇（pTC）、唾液皮质醇和CBG（正常反应pTC＞420nmol/L，明显肾上腺功能不全pTC＜250nmol/L）。

结果

纳入17例垂体功能减退患者，平均年龄42±6岁。根据干预措施，30分钟时的pTC无显著变化（无雌二醇组为401（四分位间距：55 - 495），口服雌二醇组为440（74 - 600），经皮雌二醇组为304（48 - 492）nmol/L）。基于pTC，在各干预措施之间，无明显肾上腺功能不全的患者未超过肾上腺功能不全的临界值，而3例临界肾上腺功能不全患者（pTC 390 - 559nmol/L）超过了临界值。与无雌二醇组相比，口服雌二醇组的CBG更高（p＜0.001），与经皮雌二醇组相比也更高（p = 0.017）；与无雌二醇组相比，口服雌二醇组30分钟时的唾液皮质醇更低（6.6（1.6 - 23.0）对10.4（3.6 - 25.5nmol/L），p = 0.04），与经皮雌二醇组相比也更低（p = 0.07）。