What is the role of exogenous substances in the etiology of idiopathic intracranial hypertension (IIH)?

Updated: Jan 02, 2019
  • Author: Mark S Gans, MD; Chief Editor: Andrew G Lee, MD  more...
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Answer

The list of exogenous substances associated with IIH is extensive. Although the association between these substances and this disorder is generally considered well established, the exact causal relation has not been fully clarified in the literature.

Exogenous substances reportedly associated with IIH include amiodarone, antibiotics (eg, nalidixic acid, penicillin, and tetracycline), carbidopa, levodopa, chlordecone, corticosteroids (topical and systemic), cyclosporine, danazol, growth hormone, indomethacin, ketoprofen, lead, leuprolide acetate, levonorgestrel implants, lithium, oxytocin, perhexiline, phenytoin, and vitamin A (>100,000 U/day)/retinoic acid. [4, 6] However, the Idiopathic Intracranial Hypertension Treatment Trial compared serum and CSF levels of vitamin A metabolites in patients with IIH and controls. No differences were found in patients with IIH and controls prior to treatment, leading the study to conclude that vitamin A does not affect the development of IIH. [16] Although many potential associations have been reported, few have been proven to be causal using typical causation criteria (eg, World Health Organization criteria).

According to the 1994 review by Radhakrishnan et al and numerous subsequent reports, [24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40] medication risk factors that meet minimal criteria but have not been confirmed in case-controlled studies include the following:

  • Cimetidine, corticosteroids, danazol, isotretinoin, levothyroxine, lithium, [41] minocycline, nalidixic acid, nitrofurantoin, tamoxifen, tetracycline, and trimethoprim-sulfamethoxazole
  • All- trans-retinoic acid (ATRA) used in the treatment of promyelocytic leukemia, cyclosporine, levonorgestrel implant, pancreatin
  • Recombinant human growth hormone/natural growth hormone (somatotropin)
  • Vitamin A in infants

However, a case-control study [42] found that several of the conditions that were thought to be associated with IIH were not more common than in the control patients, including iron deficiency anemia, thyroid disease, pregnancy, antibiotic intake, and use of oral contraceptives. [42] No direct causation has ever been established in cases of contraceptives, including birth control pills and drug-eluting intrauterine devices. It is believed that rapid weight gain after starting the contraceptives, rather than direct hormonal influence, is probably the trigger.

In some instances, although a patient may present with IIH after exposure to a certain medication, the disorder can continue despite discontinuance of the presumed offending agent.

Withdrawal from corticosteroids may result in IIH. [4] If corticosteroids are used for the treatment of IIH, their withdrawal may lead to a rebound increase in ICP. [2]


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