Advertisement

An Audit of the Use of Gonadorelin Analogues to Prevent Recurrent Acute Symptoms in Patients with Acute Porphyria in the United Kingdom

  • Danja Schulenburg-BrandEmail author
  • Tricia Gardiner
  • Simon Guppy
  • David C. Rees
  • Penelope Stein
  • Julian Barth
  • M. Felicity Stewart
  • Michael Badminton
Research Report
Part of the JIMD Reports book series (JIMD, volume 36)

Abstract

Severe recurrent acute attacks of porphyria have traditionally been treated with either prophylactic human haemin or gonadorelin analogues (GnA) in females. Evidence on the most effective treatment for this patient subgroup is lacking. This audit surveyed the use of prophylactic GnA in the UK.

Twenty female patients (who experienced between 2 and 45 acute attacks of porphyria requiring hospitalisation and treatment with human haemin prior to GnA prophylaxis) were included in the audit. Data was retrospectively collected based on patient history and case review.

Twenty three treatment courses were given lasting a median period of 12 months. Monthly subcutaneous Goserelin was most commonly used. In three patients in whom timing with the menstrual cycle was not considered, an acute attack occurred after initiation of the first dose. The majority of patients experienced oestrogen deficiency symptoms during treatment. Fifty percent of the prescribed courses of GnA resulted in a degree of clinical benefit. This successfully treated group experienced between 3 and 20 acute attacks prior to and between 0 and 6 acute attacks during GnA treatment.

The audit revealed large variation in practice in the United Kingdom regarding indication, duration of treatment, specific drug used and management of side effects. In view of the limited treatment options available for this cohort and the mixed outcome successes reported, we believe it is reasonable for porphyria specialists to continue offering GnA treatment to women with severe recurrent debilitating acute attacks of porphyria associated with the menstrual cycle, and we propose best practice guidelines to standardise management.

References

  1. Anderson KE (1989) LHRH analogues for hormonal manipulation in acute intermittent poprhyria. Semin Hematol 26:10–15PubMedGoogle Scholar
  2. Anderson KE, Spitz IM, Bardin CW et al (1990) A gonadotropin releasing hormone analogue prevents cyclical attacks of porphyria. Arch Intern Med 150:1469–1474CrossRefPubMedGoogle Scholar
  3. Andersson C, Innala E, Bäckström T (2003) Acute intermittent porphyria in women: clinical expression, use and experience of exogenous sex hormones. A population-based study in northern Sweden. J Intern Med 254:176–183CrossRefPubMedGoogle Scholar
  4. Anderson KE, Spitz IM, Sassa S et al (1984) Prevention of cyclical attacks of acute intermittent porphyria with a long-acting agonist of luteinizing hormone-releasing hormone. N Engl J Med 311:643–645CrossRefPubMedGoogle Scholar
  5. Badminton MN, Whatley SD, Elder GH (2012) The porphyrias and other disorders of porphyrin metabolism. In: Burtis CA, Ashwood ER, Bruns DE (eds) Tietz textbook of clinical chemistry and molecular diagnostics. Elsevier Saunders, St. Louis, pp 1031–1055CrossRefGoogle Scholar
  6. BNF (2013) British national formulary, vol 66. BMJ Group and Pharmaceutical Press, LondonGoogle Scholar
  7. Dowman JK, Gunson BK, Mirza DF et al (2012) Liver transplantation for acute intermittent porphyria is complicated by a high rate of hepatic artery thrombosis. Liver Transpl 18:195–200CrossRefPubMedPubMedCentralGoogle Scholar
  8. Edwards AM, Elliot WH (1975) Induction of delta-aminolevulinic acid synthetase in isolated rat liver cells by steroids. J Biol Chem 250:2750–2755PubMedGoogle Scholar
  9. Elder G, Harper P, Badminton M et al (2013) The incidence of inherited porphyrias in Europe. J Inherit Metab Dis 36:849–857CrossRefPubMedGoogle Scholar
  10. Fraser HM, Baird DT (1987) Clinical applications of LHRH analogues. Baillieres Clin Endocrinol Metab 1:43–70CrossRefPubMedGoogle Scholar
  11. Herrick AL, McColl KE, Wallace AM et al (1990) LHRH analogue treatment for the prevention of premenstrual attacks of acute porphyria. Q J Med 175:355–363Google Scholar
  12. Hift RJ, Meissner PN (2005) An analysis of 112 acute porphyria attacks in Cape Town, South Africa. Medicine (Baltimore) 84:48–60CrossRefGoogle Scholar
  13. Innala E, Backstrom T, Bixo M et al (2010) Evaluation of gonadotropin-releasing hormone agonist treatment for prevention of menstrual-related attacks in acute porphyria. Acta Obstet Gynecol Scand 89:95–100CrossRefPubMedGoogle Scholar
  14. Kappas A, Song CS, Levere RD et al (1968) The induction of delta-aminolevulinic acid synthetase in vivo in chick embryo liver by natural steroids. Proc Natl Acad Sci U S A 61:509–513CrossRefPubMedPubMedCentralGoogle Scholar
  15. Lamon JM, Frykholm BC, Herrera W et al (1979) Danazol administration to females with menses-associated exacerbations of acute intermittent porphyria. J Clin Endocrinol Metab 48:123–126CrossRefPubMedGoogle Scholar
  16. Levit EJ, Nodine JH, Perloff WH (1957) Progesterone-induced porphyria; case report. Am J Med 22:831–833CrossRefPubMedGoogle Scholar
  17. Marsden JT, Guppy S, Stein P et al (2015) Audit of the use of regular haem arginate infusions in patients with acute porphyria to prevent recurrent symptoms. JIMD Rep 22:57–65. doi: 10.1007/8904_2015_411 CrossRefPubMedPubMedCentralGoogle Scholar
  18. Perlroth MG, Marver HS, Tschudy DP (1965) Oral contraceptive agents and the management of acute intermittent porphyria. JAMA 194:1037–1042CrossRefPubMedGoogle Scholar
  19. Peters TJ, Sarkany R (2005) Porphyria for the general physician. Clin Med 5:275–281CrossRefGoogle Scholar
  20. Soonawalla ZF, Orug T, Badminton MN et al (2004) Liver transplantation as a cure for acute intermittent porphyria. Lancet 363:705–706CrossRefPubMedGoogle Scholar
  21. Stein P, Badminton M, Barth J et al (2013) Best practice guidelines on clinical management of acute attacks of porphyria and their complications. Ann Clin Biochem 50:217–223CrossRefPubMedGoogle Scholar
  22. Stein P, Cox T (2011) Homecare delivery of haem arginate in acute porphyria. International Porphyrins and Porphyrias Meeting, Cardiff. Br J Dermatol 164:1125–1176CrossRefGoogle Scholar
  23. Studd J, Leather AT (1996) The need for add-back with gonadotrophin-releasing hormone agonist therapy. Br J Obstet Gynaecol 103:1–4CrossRefPubMedGoogle Scholar
  24. Thunell S (2006) (Far) Outside the box: genomic approach to acute porphyria. Physiol Res 55:S43–S66PubMedGoogle Scholar

Copyright information

© SSIEM and Springer-Verlag Berlin Heidelberg 2017

Authors and Affiliations

  • Danja Schulenburg-Brand
    • 1
    Email author
  • Tricia Gardiner
    • 1
  • Simon Guppy
    • 2
  • David C. Rees
    • 2
  • Penelope Stein
    • 2
  • Julian Barth
    • 3
  • M. Felicity Stewart
    • 4
  • Michael Badminton
    • 1
  1. 1.Department of Medical Biochemistry and ImmunologyUniversity Hospital of WalesCardiffUK
  2. 2.Department of Haematological MedicineKing’s College HospitalLondonUK
  3. 3.Department of Clinical ChemistryLeeds General InfirmaryLeedsUK
  4. 4.Manchester Academic Health Sciences Centre, Department of Clinical Biochemistry, Salford Royal NHS Foundation TrustUniversity of ManchesterSalfordUK

Personalised recommendations