Metabolic Neurology, Institute of Metabolism and Systems Research, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.
Department of Neurology, University Hospitals Birmingham NHS Foundation Trust, Queen Elizabeth Hospital, Birmingham, UK.
Eur J Endocrinol. 2022 Jul 4;187(2):323-333. doi: 10.1530/EJE-22-0108. Print 2022 Aug 1.
Idiopathic intracranial hypertension (IIH) is a disease of raised intracranial pressure (ICP) of unknown etiology. Reductions in glucocorticoid metabolism are associated with improvements in IIH disease activity. The basal IIH glucocorticoid metabolism is yet to be assessed.
The objective of this study was to determine the basal glucocorticoid phenotype in IIH and assess the effects of weight loss on the IIH glucocorticoid phenotype.
A retrospective case-control study and a separate exploratory analysis of a prospective randomized intervention study were carried out.
The case-control study compared female IIH patients to BMI, age, and sex-matched controls. In the randomized intervention study, different IIH patients were randomized to either a community weight management intervention or bariatric surgery, with patients assessed at baseline and 12 months. Glucocorticoid levels were determined utilizing 24-h urinary steroid profiles alongside the measurement of adipose tissue 11β-HSD1 activity.
Compared to control subjects, patients with active IIH had increased systemic 11β-hydroxysteroid dehydrogenase (11β-HSD1) and 5α-reductase activity. The intervention study demonstrated that weight loss following bariatric surgery reduced systemic 11β-HSD1 and 5α-reductase activity. Reductions in these were associated with reduced ICP. Subcutaneous adipose tissue explants demonstrated elevated 11β-HSD1 activity compared to samples from matched controls.
The study demonstrates that in IIH, there is a phenotype of elevated systemic and adipose 11β-HSD1 activity in excess to that mediated by obesity. Bariatric surgery to induce weight loss was associated with reductions in 11β-HSD1 activity and decreased ICP. These data reflect new insights into the IIH phenotype and further point toward metabolic dysregulation as a feature of IIH.
特发性颅内高压（IIH）是一种病因不明的颅内压升高疾病。糖皮质激素代谢减少与 IIH 疾病活动的改善有关。基础 IIH 糖皮质激素代谢尚未得到评估。
本研究旨在确定 IIH 的基础糖皮质激素表型，并评估减肥对 IIH 糖皮质激素表型的影响。
进行了回顾性病例对照研究和前瞻性随机干预研究的单独探索性分析。
病例对照研究将女性 IIH 患者与 BMI、年龄和性别匹配的对照组进行比较。在随机干预研究中，不同的 IIH 患者被随机分配到社区体重管理干预或减肥手术组，患者在基线和 12 个月时进行评估。利用 24 小时尿类固醇谱和测量脂肪组织 11β-HSD1 活性来确定糖皮质激素水平。
与对照组相比，活动期 IIH 患者的全身 11β-羟甾脱氢酶（11β-HSD1）和 5α-还原酶活性增加。干预研究表明，减肥手术后体重减轻可降低全身 11β-HSD1 和 5α-还原酶活性。这些降低与 ICP 降低有关。与匹配的对照样本相比，皮下脂肪组织外植体显示出升高的 11β-HSD1 活性。
该研究表明，在 IIH 中，存在一种全身性和脂肪组织 11β-HSD1 活性升高的表型，超过了肥胖所介导的表型。减肥手术诱导体重减轻与 11β-HSD1 活性降低和 ICP 降低有关。这些数据反映了对 IIH 表型的新见解，并进一步指向代谢失调是 IIH 的一个特征。
