Correspondence

Anaphylactic Reaction to Gonadotropin-Releasing Hormone

N Engl J Med 1993; 328:815March 18, 1993

Article

To the Editor:

Anaphylactic reactions in patients receiving pulsatile gonadotropin-releasing hormone (GnRH) are rare.1 We describe a patient who had such a reaction when given GnRH intravenously after having received pulsatile subcutaneous GnRH therapy for 10 weeks.

The patient was a 31-year-old man with infertility due to severe oligospermia. His sexual development and physical examination were normal. The plasma follicle-stimulating hormone, luteinizing hormone, and testosterone concentrations were 8 mIU per milliliter, 10 mIU per milliliter, and 450 ng per deciliter (15.6 nmol per liter), respectively. The patient underwent an intravenous GnRH stimulation test with 100 μg of GnRH and then was treated with GnRH (Lutrelef, Ferring) in a dose of 50 μg given subcutaneously every 129 minutes with a computerized pump. Nine weeks later, he had a transient episode of generalized urticaria that responded to chlorpheniramine maleate. Treatment with GnRH was continued for an additional week, at which time the intravenous GnRH test was repeated.

Within seconds after the injection, the patient reported having dizziness, blurred vision, and palpitations. These symptoms were followed by hypotension, perspiration, and loss of consciousness. He was treated successfully with fluids and oxygen. Intradermal skin tests with GnRH at concentrations of 100 and 320 μg per milliliter (corresponding to the test and treatment doses, respectively) were positive in the patient, but negative in four normal subjects. Skin tests were also positive with doses of 0.01 and 1.0 μg of GnRH per milliliter (corresponding to the test and treatment doses, respectively). Three additional patients who received the same treatment with GnRH but who had no allergic reactions had negative skin tests. The vehicle was identified as pure mannitol; the possibility of hypersensitivity to mannitol was excluded after an intradermal skin test with mannitol at a concentration of 1000 μg per milliliter was negative.

The absence of an allergic response to the initial intravenous and subsequent subcutaneous injections of GnRH suggests the occurrence of acquired hypersensitivity leading to an anaphylactic reaction in this patient; this possibility was confirmed by the results of the skin tests performed later. Although rare, the possibility of acquired hypersensitivity to GnRH during long-term therapy should be considered when this treatment is prescribed.

Gad Potashnik, M.D.
Eitan Lunenfeld, M.D.
Edward Spitz, M.D.
Marek Glezerman, M.D.
Soroka University Hospital of Kupat Holim, Beer-Sheba 84101, Israel

1 References

1. 1

   Popovic V, Milosevic Z, Djukanovic R, et al. Hypersensitivity reaction with intravenous GnRH after pulsatile subcutaneous GnRH treatment in male hypogonadotrophic hypogonadism. Postgrad Med J 1988;64:245-246
   CrossRef | Web of Science | Medline

Citing Articles (5)

Citing Articles

1. 1

   Annemarie B. Lüchinger, Velja Mijatovic, Thomas Rustemeyer, Peter G.A. Hompes. (2011) Anaphylactic Reaction to Different Gonadotropin-Releasing Hormone Agonists for the Treatment of Endometriosis. The American Journal of the Medical Sciences 341:3, 240-242
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2. 2

   Elizabeth M. Stringer, Ryan S. De Voe, Michael R. Loomis. (2011) Suspected Anaphylaxis to Leuprolide Acetate Depot in Two Elf Owls (Micrathene whitneyi). Journal of Zoo and Wildlife Medicine 42:1, 166-168
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3. 3

   Catherine Lam, James Tjon, Jill Hamilton, Alexandra H Ahmet. (2006) Recurrent Anaphylaxis Associated with Gonadotropin-Releasing Hormone Analogs: Case Report and Review of the Literature. Pharmacotherapy 26:12, 1811-1815
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4. 4

   Johannes Mayr, Reingard Aigner. (1995) Hypersensitivity reaction to intranasal gonadotropin-releasing hormone. European Journal of Pediatrics 154:3, 248-248
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5. 5

   &NA;. (1993) Gonadorelin. Reactions Weekly &NA;:445, 8
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