The influence of Graves’ orbitopathy treatment with intravenous glucocorticoids on adrenal function
Abstract
Introduction: Graves’ orbitopathy (GO) is the commonest extrathyroidal feature of Graves’ disease. For active, moderate to severe GO intravenous glucocorticoid pulse therapy (ivGCS) is the first-line treatment, which might be followed by oral glucocorticoid therapy. Glucocorticoid treatment, especially in the time of withdrawal, carries a risk of adrenal insufficiency. The aim of this study was to assess the pituitary-adrenal axis function in patients with GO before and at the cessation of ivGCS, and after further oral glucocorticoid therapy.
Material and methods: Twenty patients received treatment in accordance with the EUGOGO protocol (500 mg methylprednisolone once a week for six weeks, then 250 mg once a week for another six weeks) followed by oral prednisone at a gradually decreasing dose from 30 mg/day over a three-month period. Adrenal function was evaluated directly before the ivGCS, before the last pulse, and after oral glucocorticoid intake. The assessment consisted of clinical evaluation, and measurements of morning total serum cortisol (TSC) and plasma adrenocorticotropic hormone (ACTH). Patients with decreased cortisol level underwent ACTH stimulation test with TSC measurements before, and 30 minutes and 60 minutes after the administration of synthetic ACTH.
Results: All patients before and at the cessation of ivGCS treatment demonstrated intact adrenal function. One patient after prednisone therapy presented decreased adrenal reserve. TSC concentration was significantly lower after the ivGCS (p = 0.025) and oral glucocorticoid therapy (p = 0.0006) in comparison to evaluation before therapy.
Conclusions: Therapy with ivGCS for GO does not lead to secondary adrenocortical insufficiency. Further low-dose oral glucocorticoid therapy may result in secondary adrenocortical insufficiency in some patients.
Keywords: glucocorticoidsmethylprednisoloneGraves’ orbitopathyadrenal insufficiencycortisol
References
- Bahn RS, Heufelder AE. Pathogenesis of Graves' ophthalmopathy. N Engl J Med. 1993; 329(20): 1468–1475.
- Bartalena L, Baldeschi L, Boboridis K, et al. European Group on Graves' Orbitopathy (EUGOGO). The 2016 European Thyroid Association/European Group on Graves' Orbitopathy Guidelines for the Management of Graves' Orbitopathy. Eur Thyroid J. 2016; 5(1): 9–26.
- Laurberg P, Berman DC, Bülow Pedersen I, et al. Incidence and clinical presentation of moderate to severe graves' orbitopathy in a Danish population before and after iodine fortification of salt. J Clin Endocrinol Metab. 2012; 97(7): 2325–2332.
- Tanda ML, Piantanida E, Liparulo L, et al. Prevalence and natural history of Graves' orbitopathy in a large series of patients with newly diagnosed graves' hyperthyroidism seen at a single center. J Clin Endocrinol Metab. 2013; 98(4): 1443–1449.
- Bednarczuk T, Bar-Andziak E, Hubalewska-Dydejczyk A, et al. [Management of Graves' orbitopathy. Comments on the EUGOGO consensus statement]. Endokrynol Pol. 2009; 60(4): 312–330.
- Dinsen S, Baslund Bo, Klose M, et al. Why glucocorticoid withdrawal may sometimes be as dangerous as the treatment itself. Eur J Intern Med. 2013; 24(8): 714–720.
- Todd GRG, Acerini CL, Ross-Russell R, et al. Survey of adrenal crisis associated with inhaled corticosteroids in the United Kingdom. Arch Dis Child. 2002; 87(6): 457–461.
- Zöllner EW, Lombard CJ, Galal U, et al. Hypothalamic-pituitary-adrenal axis suppression in asthmatic school children. Pediatrics. 2012; 130(6): e1512–e1519.
- Giotaki Z, Fountas A, Tsirouki T, et al. Adrenal reserve following treatment of Graves' orbitopathy with intravenous glucocorticoids. Thyroid. 2015; 25(4): 462–463.
- Jespersen S, Nygaard B, Kristensen LØ. Methylprednisolone Pulse Treatment of Graves' Ophthalmopathy Is Not Associated with Secondary Adrenocortical Insufficiency. Eur Thyroid J. 2015; 4(4): 222–225.
- Furst DE, Saag KG. Glucocorticoid withdrawal. In: Post TW. UpToDate, Waltham, MA 2016.
- Miśkiewicz P, Kryczka A, Ambroziak U, et al. Is high dose intravenous methylprednisolone pulse therapy in patients with Graves' orbitopathy safe? Endokrynol Pol. 2014; 65(5): 402–413.
- Buttgereit F, Saag KG, Cutolo M, et al. The molecular basis for the effectiveness, toxicity, and resistance to glucocorticoids: focus on the treatment of rheumatoid arthritis. Scand J Rheumatol. 2005; 34(1): 14–21.
- Gupta G, Jain A, Narayanasetty N. Steroid pulse therapies in dermatology. Muller Journal of Medical Sciences and Research. 2014; 5(2): 155.
- Willenberg HS, Bornstein SR. Adrenal Insufficiency. In: Lang F, eds. Encyclopedia of Molecular Mechanisms of Disease. Springer-Verlag GmbH Berlin, Heidelberg. ; 2009: 41–44.
- Hägg E, Asplund K, Lithner F. Value of basal plasma cortisol assays in the assessment of pituitary-adrenal insufficiency. Clin Endocrinol (Oxf). 1987; 26(2): 221–226.
- Khan MI, Habra MA, McCutcheon IE, et al. Random postoperative day-3 cortisol concentration as a predictor of hypothalamic-pituitary-adrenal axis integrity after transsphenoidal surgery. Endocr Pract. 2011; 17(5): 717–726.
- Mitchell J, Barbosa G, Tsinberg M, et al. Unrecognized adrenal insufficiency in patients undergoing laparoscopic adrenalectomy. Surg Endosc. 2009; 23(2): 248–254.
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