Subscribe to RSS
DOI: 10.1055/s-0043-105077
National German Audit of Diagnosis, Treatment, and Teaching in Secondary Adrenal Insufficiency
Publication History
received 29 November 2016
accepted 28 February 2017
Publication Date:
28 March 2017 (online)
![](https://www.thieme-connect.de/media/hmr/201708/lookinside/thumbnails/2016-11-0364_10-1055-s-0043-105077-1.jpg)
Abstract
Great heterogeneity seems to exist regarding diagnosis, therapy, and teaching of patients with secondary adrenal insufficiency (SAI) across Germany resulting in different diagnosis and treatment strategies. The aim of the work was to present the first national audit on diagnosis, treatment, and patient teaching of SAI reflecting common clinical practice in Germany. A self-designed questionnaire was sent via e-mail to all members of the German Endocrine Society (approx. 120 centers). Returned questionnaires (response rate 38.3%) were checked for duplicity of institutions and analyzed. Diagnostic testing focuses on those patients with relevant risk for adrenal insufficiency. Basal serum cortisol is mostly used as screening test. Short synacthen and CRH tests are the preferred confirmatory tests, however, cut-off values vary due to different assays used. Patients with radiation, second surgery, progressive disease or new symptoms are followed by serial re-testing. Perioperative management and frequency of postoperative re-evaluations differ among centers. Hydrocortisone is the preferred glucocorticoid for replacement therapy, but daily doses vary considerably (10–30 mg/day). Some centers perform hormone measurements for dose adjustment of glucocorticoid replacement therapy whereas others rely on clinical judgement. Patients’ teaching is done in 84% of centers, but only half of the centers include patients’ relatives. Homogeneity exists in patients’ teaching regarding intercurrent illnesses (fever, diarrhoea). Recommendations regarding dose adaptations in situations such as sport-activities, dental-procedures, or coughing are highly variable. This first national audit reveals great heterogeneity among German centers and could improve patients’ care in SAI, for example, by initiating new trials and developing clinical practice guidelines.
Key words
adrenal insufficiency - pituitary - hydrocortisone - glucocorticoid therapy - patient’s teaching* These authors contributed equally to this work
Supporting Information
- Supporting Information for this article is available online at
http://www.thieme-connect.de/products
- Supporting Information
-
References
- 1 Arlt W, Allolio B. Adrenal insufficiency. Lancet 2003; 361: 1881-1893
- 2 Reynolds RM, Stewart PM, Seckl JR, Padfield PL. Assessing the HPA axis in patients with pituitary disease: a UK survey. Clin Endocrinol (Oxf) 2006; 64: 82-85
- 3 Bornstein SR, Allolio B, Arlt W, Barthel A, Don-Wauchope A, Hammer GD, Husebye ES, Merke DP, Murad MH, Stratakis CA, Torpy DJ. Diagnosis and treatment of primary adrenal insufficiency: an endocrine society clinical practice guideline. J Clin Endocrinol Metab 2016; 101: 364-389
- 4 Deutschbein T, Unger N, Mann K, Petersenn S. Diagnosis of secondary adrenal insufficiency: unstimulated early morning cortisol in saliva and serum in comparison with the insulin tolerance test. Horm Metab Res 2009; 41: 834-839
- 5 Petersenn S, Quabbe HJ, Schofl C, Stalla GK, von WK, Buchfelder M. The rational use of pituitary stimulation tests. Dtsch Arztebl Int 2010; 107: 437-443
- 6 Simon N, Castinetti F, Ouliac F, Lesavre N, Brue T, Oliver C. Pharmacokinetic evidence for suboptimal treatment of adrenal insufficiency with currently available hydrocortisone tablets. Clin Pharmacokinet 2010; 49: 455-463
- 7 Mah PM, Jenkins RC, Rostami-Hodjegan A, Newell-Price J, Doane A, Ibbotson V, Tucker GT, Ross RJ. Weight-related dosing, timing and monitoring hydrocortisone replacement therapy in patients with adrenal insufficiency. Clin Endocrinol (Oxf) 2004; 61: 367-375
- 8 Johannsson G, Nilsson AG, Bergthorsdottir R, Burman P, Dahlqvist P, Ekman B, Engstrom BE, Olsson T, Ragnarsson O, Ryberg M, Wahlberg J, Biller BM, Monson JP, Stewart PM, Lennernas H, Skrtic S. Improved cortisol exposure-time profile and outcome in patients with adrenal insufficiency: a prospective randomized trial of a novel hydrocortisone dual-release formulation. J Clin Endocrinol Metab 2012; 97: 473-481
- 9 Harbeck B, Brede S, Witt C, Sufke S, Lehnert H, Haas C. Glucocorticoid replacement therapy in adrenal insufficiency – a challenge to physicians?. Endocr J 2015; 62: 463-468
- 10 Inder WJ, Hunt PJ. Glucocorticoid replacement in pituitary surgery: guidelines for perioperative assessment and management. J Clin Endocrinol Metab 2002; 87: 2745-2750
- 11 Tohti M, Li J, Zhou Y, Hu Y, Yu Z, Ma C. Is peri-operative steroid replacement therapy necessary for the pituitary adenomas treated with surgery? A systematic review and meta analysis. PLoS One 2015; 10: e0119621
- 12 Wentworth JM, Gao N, Sumithran KP, Maartens NF, Kaye AH, Colman PG, Ebeling PR. Prospective evaluation of a protocol for reduced glucocorticoid replacement in transsphenoidal pituitary adenomectomy: prophylactic glucocorticoid replacement is seldom necessary. Clin Endocrinol (Oxf) 2008; 68: 29-35
- 13 Arlt W, Rosenthal C, Hahner S, Allolio B. Quality of glucocorticoid replacement in adrenal insufficiency: clinical assessment vs. timed serum cortisol measurements. Clin Endocrinol (Oxf) 2006; 64: 384-389
- 14 Rousseau E, Joubert M, Trzepla G, Parienti JJ, Freret T, Vanthygem MC, Desailloud R, Lefebvre H, Coquerel A, Reznik Y. Usefulness of time-point serum cortisol and acth measurements for the adjustment of glucocorticoid replacement in adrenal insufficiency. PLoS One 2015; 10: e0135975
- 15 Jung C, Greco S, Nguyen HH, Ho JT, Lewis JG, Torpy DJ, Inder WJ. Plasma, salivary and urinary cortisol levels following physiological and stress doses of hydrocortisone in normal volunteers. BMC Endocr Disord 2014; 14: 91-94
- 16 Hahner S, Spinnler C, Fassnacht M, Burger-Stritt S, Lang K, Milovanovic D, Beuschlein F, Willenberg HS, Quinkler M, Allolio B. High incidence of adrenal crisis in educated patients with chronic adrenal insufficiency: a prospective study. J Clin Endocrinol Metab 2015; 100: 407-416
- 17 Quinkler M, Beuschlein F, Hahner S, Meyer G, Schofl C, Stalla GK. Adrenal cortical insufficiency – a life threatening illness with multiple etiologies. Dtsch Arztebl Int 2013; 110: 882-888
- 18 Quinkler M, Hahner S, Johannsson G, Stewart PM. Saving lives of patients with adrenal insufficiency: a pan-European initiative?. Clin Endocrinol (Oxf) 2014; 80: 319-321
- 19 Quinkler M, Dahlqvist P, Husebye ES, Kampe O. A European emergency card for adrenal insufficiency can save lives. Eur J Intern Med 2015; 26: 75-76
- 20 Husebye ES, Allolio B, Arlt W, Badenhoop K, Bensing S, Betterle C, Falorni A, Gan EH, Hulting AL, Kasperlik-Zaluska A, Kampe O, Lovas K, Meyer G, Pearce SH. Consensus statement on the diagnosis, treatment and follow-up of patients with primary adrenal insufficiency. J Intern Med 2014; 275: 104-115
- 21 Repping-Wuts HJ, Stikkelbroeck NM, Noordzij A, Kerstens M, Hermus AR. A glucocorticoid education group meeting: an effective strategy for improving self-management to prevent adrenal crisis. Eur J Endocrinol 2013; 169: 17-22
- 22 Grossman A, Johannsson G, Quinkler M, Zelissen P. Therapy of endocrine disease: Perspectives on the management of adrenal insufficiency: clinical insights from across Europe. Eur J Endocrinol 2013; 169: R165-R175
- 23 Allolio B. Extensive expertise in endocrinology. Adrenal crisis. Eur J Endocrinol 2015; 172: R115-R124
- 24 Yanase T, Tajima T, Katabami T, Iwasaki Y, Tanahashi Y, Sugawara A, Hasegawa T, Mune T, Oki Y, Nakagawa Y, Miyamura N, Shimizu C, Otsuki M, Nomura M, Akehi Y, Tanabe M, Kasayama S. Diagnosis and treatment of adrenal insufficiency including adrenal crisis: a Japan Endocrine Society clinical practice guideline [Opinion]. Endocr J 2016; 63: 765-784
- 25 Dorin RI, Qualls CR, Crapo LM. Diagnosis of adrenal insufficiency. Ann Intern Med 2003; 139: 194-204
- 26 Schmidt IL, Lahner H, Mann K, Petersenn S. Diagnosis of adrenal insufficiency: Evaluation of the corticotropin-releasing hormone test and Basal serum cortisol in comparison to the insulin tolerance test in patients with hypothalamic-pituitary-adrenal disease. J Clin Endocrinol Metab 2003; 88: 4193-4198
- 27 Alaioubi B, Mann K, Petersenn S. Diagnosis of adrenal insufficiency using the GHRP-6 Test: comparison with the insulin tolerance test in patients with hypothalamic-pituitary-adrenal disease. Horm Metab Res 2010; 42: 198-203
- 28 Berg C, Meinel T, Lahner H, Yuece A, Mann K, Petersenn S. Diagnostic utility of the glucagon stimulation test in comparison to the insulin tolerance test in patients following pituitary surgery. Eur J Endocrinol 2010; 162: 477-482
- 29 de Miguel NP, Vela ET, Garcia NP, Rodriguez MM, Guerras IS. Martinez de Salinas Santamaria Mde, Maso AA. Guidelines for the diagnosis and treatment of adrenal insufficiency in the adult. Endocrinol Nutr 2014; 61 (Suppl. 01) 1-35
- 30 Erturk E, Jaffe CA, Barkan AL. Evaluation of the integrity of the hypothalamic-pituitary-adrenal axis by insulin hypoglycemia test. J Clin Endocrinol Metab 1998; 83: 2350-2354
- 31 Pfeifer M, Kanc K, Verhovec R, Kocijancic A. Reproducibility of the insulin tolerance test (ITT) for assessment of growth hormone and cortisol secretion in normal and hypopituitary adult men. Clin Endocrinol (Oxf) 2001; 54: 17-22
- 32 Vestergaard P, Hoeck HC, Jakobsen PE, Laurberg P. Reproducibility of growth hormone and cortisol responses to the insulin tolerance test and the short ACTH test in normal adults. Horm Metab Res 1997; 29: 106-110
- 33 Agha A, Tomlinson JW, Clark PM, Holder G, Stewart PM. The long-term predictive accuracy of the short synacthen (corticotropin) stimulation test for assessment of the hypothalamic-pituitary-adrenal axis. J Clin Endocrinol Metab 2006; 91: 43-47
- 34 Deutschbein T, Unger N, Mann K, Petersenn S. Diagnosis of secondary adrenal insufficiency in patients with hypothalamic-pituitary disease: comparison between serum and salivary cortisol during the high-dose short synacthen test. Eur J Endocrinol 2009; 160: 9-16
- 35 Deutschbein T, Broecker-Preuss M, Flitsch J, Jaeger A, Althoff R, Walz MK, Mann K, Petersenn S. Salivary cortisol as a diagnostic tool for Cushing’s syndrome and adrenal insufficiency: improved screening by an automatic immunoassay. Eur J Endocrinol 2012; 166: 613-618
- 36 Minniti G, Scaringi C, Poggi M, Jaffrain Rea ML, Trillo G, Esposito V, Bozzao A, Enrici MM, Toscano V, Enrici RM. Fractionated stereotactic radiotherapy for large and invasive non-functioning pituitary adenomas: long-term clinical outcomes and volumetric MRI assessment of tumor response. Eur J Endocrinol 2015; 172: 433-441
- 37 Xu Z, Lee VM, Schlesinger D, Sheehan JP. Hypopituitarism after stereotactic radiosurgery for pituitary adenomas. Neurosurgery 2013; 72: 630-637
- 38 Jahangiri A, Wagner J, Han SW, Zygourakis CC, Han SJ, Tran MT, Miller LM, Tom MW, Kunwar S, Blevins Jr. LS, Aghi MK. Morbidity of repeat transsphenoidal surgery assessed in more than 1000 operations. J Neurosurg 2014; 121: 67-74
- 39 Arafah BM. Reversible hypopituitarism in patients with large nonfunctioning pituitary adenomas. J Clin Endocrinol Metab 1986; 62: 1173-1179
- 40 Webb SM, Rigla M, Wagner A, Oliver B, Bartumeus F. Recovery of hypopituitarism after neurosurgical treatment of pituitary adenomas. J Clin Endocrinol Metab 1999; 84: 3696-3700
- 41 Berg C, Meinel T, Lahner H, Mann K, Petersenn S. Recovery of pituitary function in the late-postoperative phase after pituitary surgery: results of dynamic testing in patients with pituitary disease by insulin tolerance test 3 and 12 months after surgery. Eur J Endocrinol 2010; 162: 853-859
- 42 Esteban NV, Loughlin T, Yergey AL, Zawadzki JK, Booth JD, Winterer JC, Loriaux DL. Daily cortisol production rate in man determuned by stable isotope dilution/mass spectrometry. J Clin Endocrinol Metab 1991; 72: 39-45
- 43 Bleicken B, Hahner S, Loeffler M, Ventz M, Decker O, Allolio B, Quinkler M. Influence of hydrocortisone dosage scheme on health-related quality of life in patients with adrenal insufficiency. Clin Endocrinol (Oxf) 2010; 72: 297-304
- 44 Quinkler M, Ekman B, Marelli C, Uddin S, Zelissen P, Murray RD. Prednisolone is associated with a worse lipid profile than hydrocortisone in patients with adrenal insufficiency. Endocr Connect 2017; 6: 1-8
- 45 Quinkler M, Miodini NR, Zopf K, Ventz M, Oksnes M. Modified-release hydrocortisone decreases BMI and HbA1c in patients with primary and secondary adrenal insufficiency. Eur J Endocrinol 2015; 172: 619-626
- 46 Agha A, Liew A, Finucane F, Baker L, O’Kelly P, Tormey W, Thompson CJ. Conventional glucocorticoid replacement overtreats adult hypopituitary patients with partial ACTH deficiency. Clin Endocrinol (Oxf) 2004; 60: 688-693
- 47 Bhattacharyya A, Kaushal K, Tymms DJ, Davis JR. Steroid withdrawal syndrome after successful treatment of Cushing's syndrome: a reminder. Eur J Endocrinol 2005; 153: 207-210
- 48 Nieman LK, Biller BM, Findling JW, Murad MH, Newell-Price J, Savage MO, Tabarin A. Treatment of cushing's syndrome: an endocrine society clinical practice guideline. J Clin Endocrinol Metab 2015; 100: 2807-2831
- 49 Hahner S, Hemmelmann N, Quinkler M, Beuschlein F, Spinnler C, Allolio B. Timelines in the management of adrenal crisis – targets, limits and reality. Clin Endocrinol (Oxf) 2015; 82: 497-502
- 50 Simunkova K, Jovanovic N, Rostrup E, Methlie P, Oksnes M, Nilsen RM, Henno H, Tilseth M, Godang K, Kovac A, Lovas K, Husebye ES. Effect of a pre-exercise hydrocortisone dose on short-term physical performance in female patients with primary adrenal failure. Eur J Endocrinol 2016; 174: 97-105