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Idiopathic intracranial hypertension in a transgender female

  • Rohini R. Sigireddi
    Affiliations
    Department of Ophthalmology, Baylor College of Medicine, Houston, TX
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  • Lance J. Lyons
    Correspondence
    Corresponding author: Lance J. Lyons, MD, University of Texas Medical Branch, 700 University Blvd., Galveston, TX 77550
    Affiliations
    Department of Ophthalmology and Visual Sciences, University of Texas Medical Branch, Galveston, TX
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  • Andrew G. Lee
    Affiliations
    Department of Ophthalmology, Blanton Eye Institute, Houston Methodist Hospital, Houston, TX; Departments of Ophthalmology, Neurology, and Neurosurgery, Weill Cornell Medicine, New York, NY; Section of Ophthalmology, University of Texas MD Anderson Cancer Center, Houston, TX; Department of Ophthalmology, University of Iowa Hospitals and Clinics, Iowa City, IA
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      Introduction

      A 39-year-old morbidly obese African-American male-to-female transgender patient presented with acute-on-chronic vision loss in the right eye. She reported a 1-year history of a dim temporal field OD initially at night, which progressed acutely to include daytime as well. The patient was seen by an optometrist, who found bilateral optic disc edema and referred the patient to an outside hospital. A computerized tomography (CT) of the head was normal.
      She reported continued intermittent headaches, transient visual obscurations lasting seconds, bilateral tinnitus, and an episode of diplopia the night before presentation. She denied any recent weight change or new medications. She had no past ocular history. Past medical history included human immunodeficieny virus (HIV) with a CD4 count of 856, viral load undetectable, on abacavir/dolutegravir/lamivudine. During the gender transition process, she took estradiol, ethinylestradiol, spironolactone, and conjugated estrogen tablets, and has not taken these medications for an estimated 4–6 years. She had hypertension treated with hydrochlorothiazide and valsartan, and chronic atrial fibrillation treated with amiodarone. The patient was taking rivaroxaban for a prior deep venous thrombosis. She had a stable fusiform aneurysm of the left carotid artery terminus and morbid obesity (body mass index 45 kg/m2). Past surgical history included cosmetic facial procedures. She denied smoking, alcohol, or drug use, recent sexual activity, and recent travel.
      On presentation the patient was hypertensive to 155/85 mm Hg, and her pulse was 81 beats per minute and had a regular rate. The remainder of the nonocular physical examination was unremarkable.
      Best corrected visual acuity was 20/25 OD and 20/20 OS. Intraocular pressures were 14 mm Hg OU. There was a right relative afferent pupillary defect. Ishihara color plates were 7/14 OD and 14/14 OS. Extraocular movements were intact and the slit lamp exam was normal OU. Automated perimetry (Humphrey visual field testing 24-2) revealed a dense superior and inferior altitudinal field defect OD and a markedly enlarged blind spot with a superior and inferior nasal step OS (see Fig. 1). Optical coherence tomography revealed a retinal nerve fiber layer thickness of 157 microns OD and 173 OS (normal range 97.3 ± 9.6 microns) with evidence of macular edema OU.
      • Alasil T.
      • Wang K.
      • Keane P.A.
      • et al.
      Analysis of normal retinal nerve fiber layer thickness by age, sex, and race using spectral domain optical coherence tomography.
      A fundus exam revealed Frisen grade IV optic disc edema OU.
      Fig. 1
      Fig. 1Humphrey Visual Field Testing 24-2 preformed at the time of consult. This testing depicts a generalized restriction in the right eye and enlarged blind spot in the left eye.
      Bloodwork, including complete blood count (for a female reference range), hemoglobin A1c, vitamin B12, folate, and thyroid stimulating hormone levels were all normal. The estimated glomerular filtration rate (GFR) was artificially low at 47 mL/min/1.73 m2, given that it was calculated for a female (rather than a chromosomal male); upon recalculation for a patient of male sex, it was normal at 63 mL/min/1.73 m2. The basic metabolic panel was otherwise normal.
      Magnetic resonanance imaging (MRI) of the brain revealed a partially empty sella, compression of the globes, and perineural optic nerve fluid accumulation bilaterally (Fig. 2). Severe narrowing of the distal right transverse sinus was noted on magnetic resonance venography, which was deemed congenital on subsequent CT angiogram; no sinus thrombosis was noted. Lumbar puncture (LP) opening pressure was 40 cm H2O; cerebrospinal fluid (CSF) IgG synthesis rate, glucose, white blood cells, and protein were all normal. CSF cultures and cryptococcal antigen testing were negative. A diagnosis of idiopathic intracranial hypertension (IIH) was made based upon the modified Dandy criteria.
      Fig. 2
      Fig. 2MRI images illustrating the radiographic findings indicative of increased intracranial pressure. A) T1-weighted image of the sagittal view illustrating an empty sella turcica (white arrow) from excess CSF accumulation and compression of the underlying pituitary gland. B) T1-weighted image of the coronal view of the empty sella (white arrow). C) T2-weighted image of the axial view with fluid accumulation in the optic nerve sheath (short white arrows) and flattening of the globes bilaterally (long white arrows).
      The patient underwent a right optic nerve sheath fenestration, tolerated the procedure well, and was started on 2 grams of acetazolamide per day by mouth. On post-operative day 1 the patient had subjective improvement in vision and has not since returned to the ophthalmology clinic.

      Discussion

      IIH is largely a condition of obese women of childbearing age. Given the disease’s unique association with this population, it has been postulated that sex hormones contribute to the development of IIH.
      • Chen J.
      • Wall M.
      Epidemiology and risk factors for idiopathic intracranial hypertension.
      Patients with physiologically elevated estrogen levels, such as pregnant women whose estrogen levels are increased from pregnancy and those taking estrogens, are known to be at higher risk for IIH.
      • Bagga R.
      • Jain V.
      • Gupta K.R.
      • Gopalan S.
      • Malhotra S.
      • Das C.P.
      Choice of therapy and mode of delivery in idiopathic intracranial hypertension during pregnancy.
      It is proposed that elevated estrogren levels result in thrombophilia and thrombosis in the dural venous sinuses, thus resulting in decreased CSF absorption and elevated intracranial pressure (ICP).
      • Bagga R.
      • Jain V.
      • Gupta K.R.
      • Gopalan S.
      • Malhotra S.
      • Das C.P.
      Choice of therapy and mode of delivery in idiopathic intracranial hypertension during pregnancy.
      • Glueck C.J.
      • Aregawi D.
      • Goldenberg N.
      • Golnik K.C.
      • Sieve L.
      • Wang P.
      Idiopathic intracranial hypertension, polycystic-ovary syndrome, and thrombophilia.
      Additionally, androgen levels (including testosterone, dehydroepiandrosterone sulfate, and androstenedione) have also been studied in the development of IIH. Elevated androgen levels were found to correlate with an earlier onset of IIH.
      • Klein A.
      • Stern N.
      • Osher E.
      • Kliper E.
      • Kesler A.
      Hyperandrogenism is associated with earlier age of onset of idiopathic intracranial hypertension in women.
      Polycystic ovarian syndrome (PCOS), a disease of hyperandrogenism known to also exist alongside obesity, was found in 39% of women with IIH in one case series.
      • Glueck C.J.
      • Iyengar S.
      • Goldenberg N.
      • Smith L.-S.
      • Wang P.
      Idiopathic intracranial hypertension: associations with coagulation disorders and polycystic-ovary syndrome.
      Increased circulating androgen levels were similarly found in 4 reported cases of female-to-male transgender patients with IIH who were receiving intramuscular testosterone to aid in their gender transition.
      • Park S.
      • Cheng C.P.
      • Lim L.T.
      • Gerber D.
      Secondary intracranial hypertension from testosterone therapy in a transgender patient.
      • Buchanan I.
      • Hansen K.
      • Bedolla J.
      Idiopathic intracranial hypertension in a transgender male on hormone therapy.
      • Mowl A.D.
      • Grogg J.A.
      • Klein J.
      Secondary pseudotumour cerebri in a patient undergoing sexual reassignment therapy.
      • Hornby C.
      • Mollan S.P.
      • Mitchell J.
      • et al.
      What do transgender patients teach us about idiopathic intracranial hypertension?.
      A detailed comparision of reported female-to-male transgender patients who received hormonal therapy and developed IIH can be found in Hornby et al.
      • Hornby C.
      • Mollan S.P.
      • Mitchell J.
      • et al.
      What do transgender patients teach us about idiopathic intracranial hypertension?.
      It may be that IIH in transgender and PCOS patients represents a neuro-metabolic complication of an abnormal circulating androgen range (elevated for females, but decreased for males).
      • Hornby C.
      • Mollan S.P.
      • Mitchell J.
      • et al.
      What do transgender patients teach us about idiopathic intracranial hypertension?.
      Utilizing the Naranjo algorithm for evaluating adverse drug reactions, another author identifed a “possible” relationship between testosterone and IIH development in transgender individuals.
      • Kapoor K.G.
      Regarding secondary intracranial hypertension from testostereone therapy in a transgender patient.
      The role that obesity plays in the development of IIH may be similarly mediated through hormonal influences. Excess adipose tissue allows for the increased peripheral aromatization of testosterone to estrogen, increased levels of cortisol, and aldosterone production, all of which raise ICP by stimulating CSF production via mineralocorticoid receptors in the choroid plexus.
      • Salpietro V.
      • Polizzi A.
      • Bertè L.F.
      • et al.
      Idiopathic intracranial hypertension: a unifying neuroendocrine hypothesis through the adrenal-brain axis.
      Adipocytes produce the hormone leptin, which stimulates a receptor on the epithelial choroid plexus resulting in sodium and water movement into the CSF.
      • Markey K.A.
      • Uldall M.
      • Botfield H.
      • et al.
      Idiopathic intracranial hypertension, hormones, and 11β-hydroxysteroid dehydrogenases.
      Obesity is a known association with IIH in men, though not as often as when compared to women with IIH.
      • Digre K.B.
      • Corbett J.J.
      Pseudotumor cerebri in men.
      This study interestingly suggested that among IIH patients, African-American men with hypertension are at a greater risk for vision loss and may need to be treated surgically more acutely than others, as in the case of our patient.
      • Digre K.B.
      • Corbett J.J.
      Pseudotumor cerebri in men.

      Conclusion

      To our knowledge this is the first known case of IIH in a male-to-female transgender patient in the English-language ophthalmic literature. In transgender patients, sex hormone disequilibrium can disrupt the normal balance of CSF production and absorption, resulting in elevated ICP and development of IIH. In this patient, there is a complex relationship between altered hormone levels, obesity, African-American race, chromosomal male sex, and existing hypertension. The special clinical challenges of diagnosing and treating transgender patients with IIH include: 1) adjustment of gender-based normal control data for the transgender state (e.g., hematocrit, GFR calculations); 2) the inadvertent misclassification of demographic risk factors for IIH (e.g., a transgender obese male mistakenly not known to have been obese female, PCOS in a transgender female); and 3) use of exogenous hormone therapy. We encourage clinicians to report the development of IIH in transgender patients to better understand and address the unique medical challenges faced by this demographic.

      Disclosure

      The authors have no proprietary or commercial interest in any materials discussed in this article.

      Conflicts of interest

      none.

      Acknowledgments

      No one other than the authors listed helped write or revise this manuscript. All authors contributed equally.

      References

        • Alasil T.
        • Wang K.
        • Keane P.A.
        • et al.
        Analysis of normal retinal nerve fiber layer thickness by age, sex, and race using spectral domain optical coherence tomography.
        J Glaucoma. 2013; 22: 532-541https://doi.org/10.1097/IJG.0b013e318255bb4a
        • Chen J.
        • Wall M.
        Epidemiology and risk factors for idiopathic intracranial hypertension.
        Int Ophthalmol Clin. 2014; 54: 1-11https://doi.org/10.1097/IIO.0b013e3182aabf11
        • Bagga R.
        • Jain V.
        • Gupta K.R.
        • Gopalan S.
        • Malhotra S.
        • Das C.P.
        Choice of therapy and mode of delivery in idiopathic intracranial hypertension during pregnancy.
        Med Gen Med. 2005; 7: 42
        • Glueck C.J.
        • Aregawi D.
        • Goldenberg N.
        • Golnik K.C.
        • Sieve L.
        • Wang P.
        Idiopathic intracranial hypertension, polycystic-ovary syndrome, and thrombophilia.
        J Lab Clin Med. 2005; 145: 72-82https://doi.org/10.1016/j.lab.2004.09.011
        • Klein A.
        • Stern N.
        • Osher E.
        • Kliper E.
        • Kesler A.
        Hyperandrogenism is associated with earlier age of onset of idiopathic intracranial hypertension in women.
        Curr Eye Res. 2013; 38: 972-976https://doi.org/10.3109/02713683.2013.799214
        • Glueck C.J.
        • Iyengar S.
        • Goldenberg N.
        • Smith L.-S.
        • Wang P.
        Idiopathic intracranial hypertension: associations with coagulation disorders and polycystic-ovary syndrome.
        J Lab Clin Med. 2003; 142: 35-45https://doi.org/10.1016/S0022-2143(03)00069-6
        • Park S.
        • Cheng C.P.
        • Lim L.T.
        • Gerber D.
        Secondary intracranial hypertension from testosterone therapy in a transgender patient.
        Semin Ophthalmol. 2014; 29: 156-158https://doi.org/10.3109/08820538.2013.788678
        • Buchanan I.
        • Hansen K.
        • Bedolla J.
        Idiopathic intracranial hypertension in a transgender male on hormone therapy.
        Arch Emerg Med Crit Care. 2017; 2: 1019
        • Mowl A.D.
        • Grogg J.A.
        • Klein J.
        Secondary pseudotumour cerebri in a patient undergoing sexual reassignment therapy.
        Clin Exp Optom. 2009; 92: 449-453https://doi.org/10.1111/j.1444-0938.2009.00404.x
        • Hornby C.
        • Mollan S.P.
        • Mitchell J.
        • et al.
        What do transgender patients teach us about idiopathic intracranial hypertension?.
        Neuro-Ophthalmology. 2017; 41: 326-329https://doi.org/10.1080/01658107.2017.1316744
        • Kapoor K.G.
        Regarding secondary intracranial hypertension from testostereone therapy in a transgender patient.
        Semin Ophthalmol. 2015; : 241-242
        • Salpietro V.
        • Polizzi A.
        • Bertè L.F.
        • et al.
        Idiopathic intracranial hypertension: a unifying neuroendocrine hypothesis through the adrenal-brain axis.
        Neuro Endocrinol Lett. 2012; 33: 569-573
        • Markey K.A.
        • Uldall M.
        • Botfield H.
        • et al.
        Idiopathic intracranial hypertension, hormones, and 11β-hydroxysteroid dehydrogenases.
        J Pain Res. 2016; 9: 223-232https://doi.org/10.2147/JPR.S80824
        • Digre K.B.
        • Corbett J.J.
        Pseudotumor cerebri in men.
        Arch Neurol. 1988; 45: 866-872https://doi.org/10.1001/archneur.1988.00520320056015