Idiopathic intracranial hypertension (IIH) is diagnosed when the intracranial pressure (ICP) is elevated without a secondary cause [1]. ICP is determined by the production and absorption of cerebrospinal fluid (CSF). IIH is much more common in women and obesity. The authors describe a patient with androgen insensitivity syndrome (AIS) who developed IIH following sex hormone therapy. This report was approved by the Institutional Review Board of Chuncheon Sacred Heart Hospital (No. 2023-01-004), with a waiver for informed consent. The requirement for informed consent was waived based on the low risk to the patient, given the de-identification of records.

A 21-year-old Asian woman (weight, 85.0 kg; height, 163.0 cm; body mass index [BMI], 31.99 kg/m²; blood pressure, 120/87 mmHg) visited the Department of Ophthalmology, Chuncheon Hallym Sacred Heart Hospital (Chuncheon, Korea) for horizontal diplopia, eye pain, and photopsia. She presented with a 1-month history of headache and pulsatile tinnitus. She had visited the gynecologist 8 years ago with ambiguous genitalia and amenorrhea. Pelvic magnetic resonance imaging (MRI) revealed an absence of the uterus and both ovaries. Hormonal test showed elevated 3.6 ng/mL of serum testosterone (the normal range for adolescent female, 0.20-0.38 ng/mL), and karyotype analysis showed 46,XY. She was diagnosed with partial AIS and had started to take conjugated estrogen. The ophthalmic examination revealed best-corrected visual acuities of 20/20 and intraocular pressure of 19 mmHg for both eyes. Her pupil sizes were equal and reactive without relative afferent papillary defect. Color vision tested with the Hardy-Rand-Rittler test was normal in both eyes. The alternating prism cover test revealed 10 prism diopters (PDs) esotropia in the primary position, 6 PDs esotropia in the left gaze, and 12 PDs esotropia in the right gaze. Ductions and versions showed a limitation in abduction in the left eye of grade −2. Fundus photography and optical coherence tomography (OCT) revealed bilateral optic disc swelling (Fig. 1A, 1B). The Humphrey visual field analyzer (Carl Zeiss Meditec Inc) revealed enlarged blind spots in both eyes (Fig. 1E, 1F).

At the neurology department, brain MRI and venography results were normal. Diagnostic lumbar puncture revealed an opening pressure of >50 cmH₂O (normal range, 10-25 cmH₂O), colorless, a glucose level of 74 mg/dL (normal range, 50-75 mg/dL), and a total protein level of 16 mg/dL (normal range, 5-45 mg/dL) without red or white blood cells. She received 400 mL of 20% intravenous mannitol and 500 mg of oral acetazolamide for 7 days after being diagnosed with IIH without discontinuing estrogen treatment. After 7 days, she complained of metamorphopsia. Macular OCT showed subtle subretinal fluid (SRF) and interdigitation zone disruption in her right eye (Fig. 1I). After 1 month of acetazolamide, diplopia, and lateral gaze limitation disappeared. After 7 months, on the same dosage, papilledema in both eyes decreased (Fig. 1C, 1D), SRF and interdigitation zone disruption in the right eye improved (Fig. 1J), and visual field tests returned to normal (Fig. 1G, 1H). Macular OCT showed stable state in her right eye (Fig. 1J). Her weight and BMI remained unchanged throughout treatment. Even 1 month after discontinuing the acetazolamide, no change was observed, but subsequent follow-up was lost.

Men account for about 9% of IIH cases [2]. Cases related to sex hormones have been reported. An obese man with prostate cancer diagnosed with IIH during androgen deprivation therapy has been reported [2]. Nguyen et al. [1] reported six cases of IIH during cross-sex hormone therapy, including five cases of female-to-male transition treated with testosterone and one case of male-to-female transition treated with conjugated estrogen, indicating that estrogen or testosterone use may cause IIH.

Some mechanisms have been proposed to cause IIH. Serum estradiol levels are significantly influenced by the aromatization of androstenedione to estrone by adipocytes, which may explain the association between IIH and obesity [3]. Elevated estrone levels have been detected in the CSF of patients with IIH [3]. It is hypothesized that estrone stimulates the choroid plexus secretory cells to produce more CSF [3]. Some chorioretinal changes account for an incidence of approximately 7% in IIH [4]. A review [4] revealed that choroidal folds were the most common manifestation (67%), followed by choroidal neovascular membrane (15%), and peripapillary SRF (10%). Peripapillary SRF occurs due to disruption of the intermediary tissue of Kuhnt, allowing fluid to migrate between the retina and the retinal pigment epithelium [5]. In our case, macular SRF might have been caused by the contiguous extension of peripapillary SRF into the macula [5].

In summary, IIH was successfully treated with acetazolamide treatment in AIS patients. Thus, it is necessary to check not only obesity, but also the history of taking exogenous sex hormones when treating patients with IIH. Further experimental research will be needed to determine how sex hormones affect the development of IIH.