Sex hormones, CSF and serum leptin in patients with idiopathic intracranial hypertension

Abstract

Background Idiopathic intracranial hypertension (IIH) is typically seen in females of childbearing period; therefore, it is possible that female sex hormones have a pathogenic role in IIH. Obesity is considered as a strong risk factor for IIH, Leptin levels in the serum and CSF were found to be positively correlated with anthropological measures of obesity. The role of leptin and sex hormones in the pathogenesis of idiopathic intracranial hypertension is not fully understood. The aim of this work was to assess CSF leptin, serum leptin, estradiol, testosterone, Dehydroepiandrosterone sulfate (DHEAS) levels in idiopathic intracranial hypertension (IIH) patients. Results This is a case control study which was conducted on 38 IIH female patients and 38 females as controls. IIH patients had significantly higher levels of serum Leptin, CSF Leptin, serum estradiol and serum testosterone than controls (P value < 0.001, < 0.001, 0.005 and < 0.001, respectively), whereas there was no statistically significant difference between IIH patients and controls in serum DHEAS (P value = 0.142). IIH patients with body mass index (BMI) ≥ 30 kg/m2 had significantly higher levels of serum Leptin, CSF Leptin, serum estradiol, serum testosterone, and serum DHEAS than IIH patients with BMI < 30 kg/m2 (P value < 0.001, < 0.001, 0.009, < 0.001, and < 0.001, respectively). Conclusions Patients with IIH express a characteristic elevation in CSF leptin, serum leptin, estradiol and testosterone levels. These hormones are significantly elevated in patients with high BMI.

Modelling idiopathic intracranial hypertension in rats: contributions of high fat diet and testosterone to intracranial pressure and cerebrospinal fluid production

“…To determine whether CSF extracted from the HFD-fed rats differed in testosterone levels compared to their lean counterparts, as observed for IIH patients [ 39 , 41 ], we performed liquid chromatography-mass spectrometry (LC–MS) analysis on CSF extracted from HFD-fed and control rats. HFD did not induce an elevated testosterone level in the rat CSF (HFD: 1.92 ± 0.03 nmol/l, n = 8 vs control: 1.99 ± 0.04 nmol/l, n = 5, p = 0.17, Fig.…”

“…While female sex and obesity are two of the cardinal characteristics of most IIH patients, the great majority of obese females do not have IIH. Striking among biomarkers distinguishing IIH patients from unaffected obese females is elevation of testosterone [ 39 , 41 ], which in all tested female IIH patients is increased to a level over double that of bodyweight-matched controls, but below that of male subjects. The HFD-fed rats did not mimic the elevated CSF testosterone levels, which may be due to their modest bodyweight gain and/or species difference in the response to overweight.…”

“…The HFD-fed rats did not mimic the elevated CSF testosterone levels, which may be due to their modest bodyweight gain and/or species difference in the response to overweight. Adjuvant testosterone treatment of lean female rats was then employed to mimic the elevated levels of testosterone in the IIH patients, resulting in greater increases in serum testosterone, but similar increases in CSF testosterone to those observed in IIH patients [ 39 , 41 ]. The elevated CSF levels of testosterone caused an increased ICP and increased rate of CSF production in these rats, which were, at least in part, associated with augmented activity of the choroid plexus transport protein, NKCC1, which has been demonstrated as a key contributor to CSF secretion in mice, rats, and dogs [ 45 , 49 , 57 , 96 ].…”

“…A range of factors of putative importance for disease etiology has been detected in IIH patients [ 38 – 40 ]. Most notably, analysis of IIH steroid hormone profiles revealed a unique phenotype of serum and CSF androgen excess, distinct from that driven by obesity alone [ 39 , 41 ]. The interplay between adiposity and androgen excess, both features of systemic metabolic dysregulation, and ICP elevation is not understood.…”

Idiopathic intracranial hypertension in two twin sisters

“…The pathophysiology of IIH remains unknown; however, multiple theories have been proposed. This includes cerebral oedema, stenosis of the distal portion of the transverse venous sinus, increased intra-abdominal pressure secondary to obesity impeding venous returns, excess retinol or retinol-binding protein interfering with CSF resorption, microthrombosis in sagittal sinus leading to the blockage of CSF resorption and changes in hormone levels, notably elevated levels of leptin, estradiol and testosterone 8 9…”