Abstract
The most frequent cause nowadays is autoimmune adrenalitis, which can be confirmed by the presence of 21-hydroxylase-antibodies (Oelkers 1996). When suspected on clinical grounds, adrenal insufficiency has to be confirmed by inappropriately low serum cortisol with elevated adrenocorticotropin (ACTH) (in case of primary adrenal insufficiency). A morning plasma cortisol ≤3 μg/dl is indicative for adrenal failure, whereas a cortisol ≥19 μg/dl rules out the disorder (Grinspoon and Biller 1994) if corticosterone-binding globulin (CBG) is normal. All other patients need dynamic testing (short ACTH stimulation test). A low ACTH in the presence of low cortisol points to secondary adrenal failure, in which case ACTH stimulation might be less reliable, especially when of recent onset.
Keywords
- Glucocorticoid Receptor
- Adrenal Insufficiency
- Congenital Adrenal Hyperplasia
- Mineralocorticoid Receptor
- Adrenal Failure
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
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- 11b-HSD2:
-
11β-hydroxysteroid-dehydrogenase
- ACTH:
-
Adrenocorticotropin
- BCRP1:
-
Breast cancer-resistance protein
- BETA:
-
Betamethasone
- CAH:
-
Congenital adrenal hyperplasia
- CBG:
-
Corticosterone-binding globulin
- DEX:
-
Dexamethasone
- DHEA:
-
Dehydroepiandrosterone
- GR:
-
Glucocorticoid receptor
- MR:
-
Mineralocorticoid receptor
- sGC:
-
Synthetic glucocorticoid
References
Alkatib AA, Cosma M, Elamin MB, Erickson D, Swiglo BA, Erwin PJ, Montori VM (2009) A systematic review and meta-analysis of randomized placebo-controlled trials of DHEA treatment effects on quality of life in women with adrenal insufficiency. J Clin Endocrinol Metab 94:3676–3681, doi: jc.2009-0672 [pii] 10.1210/jc.2009-0672
Arlt W (2008) Adrenal insufficiency. Clin Med 8:211–215
Avent ND, Chitty LS (2006) Non-invasive diagnosis of fetal sex; utilisation of free fetal DNA in maternal plasma and ultrasound. Prenat Diagn 26:598–603. doi:10.1002/pd.1493
Baumgartner-Parzer SM, Nowotny P, Heinze G, Waldhausl W, Vierhapper H (2005) Carrier frequency of congenital adrenal hyperplasia (21-hydroxylase deficiency) in a middle European population. J Clin Endocrinol Metab 90:775–778, doi: jc.2004-1728 [pii] 10.1210/jc.2004-1728
Beitins IZ, Bayard F, Ances IG, Kowarski A, Migeon CJ (1973) The metabolic clearance rate, blood production, interconversion and transplacental passage of cortisol and cortisone in pregnancy near term. Pediatr Res 7:509–519
Benediktsson R, Calder AA, Edwards CR, Seckl JR (1997) Placental 11 beta-hydroxysteroid dehydrogenase: a key regulator of fetal glucocorticoid exposure. Clin Endocrinol (Oxf) 46:161–166
Blumenstein I, Herrmann E, Filmann N, Zosel C, Tacke W, Bock H, Dignass A, Hartmann F, Zeuzem S, Stein J, Schroder O (2011) Female patients suffering from inflammatory bowel diseases are treated less frequently with immunosuppressive medication and have a higher disease activity: a subgroup analysis of a large multi-centre, prospective, internet-based study. J Crohns Colitis 5:203–210, doi: S1873-9946(11)00027-4 [pii] 10.1016/j.crohns.2010.12.012
Brown RW, Chapman KE, Kotelevtsev Y, Yau JL, Lindsay RS, Brett L, Leckie C, Murad P, Lyons V, Mullins JJ, Edwards CR, Seckl JR (1996) Cloning and production of antisera to human placental 11 beta-hydroxysteroid dehydrogenase type 2. Biochem J 313(Pt 3):1007–1017
Brucato A, Astori MG, Cimaz R, Villa P, Li Destri M, Chimini L, Vaccari R, Muscara M, Motta M, Tincani A, Neri F, Martinelli S (2006) Normal neuropsychological development in children with congenital complete heart block who may or may not be exposed to high-dose dexamethasone in utero. Ann Rheum Dis 65:1422–1426, doi: ard.2005.049866 [pii] 10.1136/ard.2005.049866
Carmichael SL, Shaw GM, Ma C, Werler MM, Rasmussen SA, Lammer EJ (2007) Maternal corticosteroid use and orofacial clefts. Am J Obstet Gynecol 197(585):e581–e587, discussion 683–684, e581–587. doi: S0002-9378(07)00715-6 [pii] 10.1016/j.ajog.2007.05.046
Charmandari E, Hindmarsh PC, Johnston A, Brook CG (2001) Congenital adrenal hyperplasia due to 21-hydroxylase deficiency: alterations in cortisol pharmacokinetics at puberty. J Clin Endocrinol Metab 86:2701–2708
Claahsen-van der Grinten HL, Stikkelbroeck NM, Otten BJ, Hermus AR (2011) Congenital adrenal hyperplasia–pharmacologic interventions from the prenatal phase to adulthood. Pharmacol Ther 132:1–14, doi: S0163-7258(11)00115-X [pii] 10.1016/j.pharmthera.2011.05.004
Clifton VL, Murphy VE (2004) Maternal asthma as a model for examining fetal sex-specific effects on maternal physiology and placental mechanisms that regulate human fetal growth. Placenta 25(Suppl A):S45–S52, doi: 10.1016/j.placenta.2004.01.004 S0143400404000189 [pii]
Corry DB, Tuck ML (1995) Secondary aldosteronism. Endocrinol Metab Clin North Am 24:511–529
Dalziel SR, Walker NK, Parag V, Mantell C, Rea HH, Rodgers A, Harding JE (2005) Cardiovascular risk factors after antenatal exposure to betamethasone: 30-year follow-up of a randomised controlled trial. Lancet 365:1856–1862, doi: S0140-6736(05)66617-2 [pii] 10.1016/S0140-6736(05)66617-2
David M, Forest MG (1984) Prenatal treatment of congenital adrenal hyperplasia resulting from 21-hydroxylase deficiency. J Pediatr 105:799–803
Duma D, Collins JB, Chou JW, Cidlowski JA (2010) Sexually dimorphic actions of glucocorticoids provide a link to inflammatory diseases with gender differences in prevalence. Sci Signal 3(143):ra74, doi: 3/143/ra74 [pii] 10.1126/scisignal.2001077
Dunn E, Kapoor A, Leen J, Matthews SG (2010) Prenatal synthetic glucocorticoid exposure alters hypothalamic-pituitary-adrenal regulation and pregnancy outcomes in mature female guinea pigs. J Physiol 588:887–899, doi: jphysiol.2009.182139 [pii]. 10.1113/jphysiol.2009.182139
Elabida B, Edwards A, Salhi A, Azroyan A, Fodstad H, Meneton P, Doucet A, Bloch-Faure M, Crambert G (2011) Chronic potassium depletion increases adrenal progesterone production that is necessary for efficient renal retention of potassium. Kidney Int 80:256–262, doi: 10.1038/ki.2011.15. ki201115 [pii]
Gow R, Koren G, Rieder M, Van Uum S (2011) Hair cortisol content in patients with adrenal insufficiency on hydrocortisone replacement therapy. Clin Endocrinol (Oxf) 74:687–693, doi: 10.1111/j.1365-2265.2011.04001.x
Grinspoon SK, Biller BM (1994) Clinical review 62: laboratory assessment of adrenal insufficiency. J Clin Endocrinol Metab 79:923–931
Hirvikoski T, Nordenstrom A, Lindholm T, Lindblad F, Ritzen EM, Lajic S (2008) Long-term follow-up of prenatally treated children at risk for congenital adrenal hyperplasia: does dexamethasone cause behavioural problems? Eur J Endocrinol 159:309–316, doi: EJE-08-0280 [pii]. 10.1530/EJE-08-0280
Hodyl NA, Wyper H, Osei-Kumah A, Scott N, Murphy VE, Gibson P, Smith R, Clifton VL (2010) Sex-specific associations between cortisol and birth weight in pregnancies complicated by asthma are not due to differential glucocorticoid receptor expression. Thorax 65:677–683, doi: thx.2009.123091 [pii]. 10.1136/thx.2009.123091
Hodyl NA, Stark MJ, Osei-Kumah A, Bowman M, Gibson P, Clifton VL (2011) Fetal glucocorticoid-regulated pathways are not affected by inhaled corticosteroid use for asthma during pregnancy. Am J Respir Crit Care Med 183:716–722, doi: 201007-1188OC [pii]. 10.1164/rccm.201007-1188OC
Hui L, Bianchi DW (2011) Prenatal pharmacotherapy for fetal anomalies: a 2011 update. Prenat Diagn 31:735–743. doi:10.1002/pd.2777
Jarukamjorn K, Sakuma T, Yamamoto M, Ohara A, Nemoto N (2001) Sex-associated expression of mouse hepatic and renal CYP2B enzymes by glucocorticoid hormones. Biochem Pharmacol 62:161–169, doi: S0006-2952(01)00656-6 [pii]
Katz FH, Duncan BR (1975) Letter: entry of prednisone into human milk. N Engl J Med 293:1154
Kreider ML, Levin ED, Seidler FJ, Slotkin TA (2005) Gestational dexamethasone treatment elicits sex-dependent alterations in locomotor activity, reward-based memory and hippocampal cholinergic function in adolescent and adult rats. Neuropsychopharmacology 30:1617–1623, doi: 1300716 [pii] 10.1038/sj.npp.1300716
Lajic S, Nordenstrom A, Hirvikoski T (2011) Long-term outcome of prenatal dexamethasone treatment of 21-hydroxylase deficiency. Endocr Dev 20:96–105, doi: 000321228 [pii]. 10.1159/000321228
Lekarev O, New MI (2011) Adrenal disease in pregnancy. Best Pract Res Clin Endocrinol Metab 25:959–973, doi: S1521-690X(11)00101-1 [pii]. 10.1016/j.beem.2011.08.004
Liu S, Wen SW, Demissie K, Marcoux S, Kramer MS (2001) Maternal asthma and pregnancy outcomes: a retrospective cohort study. Am J Obstet Gynecol 184:90–96, doi: S0002-9378(01)36348-2 [pii]. 10.1067/mob.2001.108073
Lovas K, Gjesdal CG, Christensen M, Wolff AB, Almas B, Svartberg J, Fougner KJ, Syversen U, Bollerslev J, Falch JA, Hunt PJ, Chatterjee VK, Husebye ES (2009) Glucocorticoid replacement therapy and pharmacogenetics in Addison’s disease: effects on bone. Eur J Endocrinol 160:993–1002, doi: EJE-08-0880 [pii]. 10.1530/EJE-08-0880
Mah PM, Jenkins RC, Rostami-Hodjegan A, Newell-Price J, Doane A, Ibbotson V, Tucker GT, Ross RJ (2004) Weight-related dosing, timing and monitoring hydrocortisone replacement therapy in patients with adrenal insufficiency. Clin Endocrinol (Oxf) 61:367–375, doi: 10.1111/j.1365-2265.2004.02106.x. CEN2106 [pii]
Makol A, Wright K, Amin S (2011) Rheumatoid arthritis and pregnancy: safety considerations in pharmacological management. Drugs 71:1973–1987, doi: 10.2165/11596240-000000000-00000. 3 [pii]
Merke DP (2008) Approach to the adult with congenital adrenal hyperplasia due to 21-hydroxylase deficiency. J Clin Endocrinol Metab 93:653–660, doi: 93/3/653 [pii]. 10.1210/jc.2007-2417
Merke DP, Bornstein SR (2005) Congenital adrenal hyperplasia. Lancet 365:2125–2136, doi: S0140-6736(05)66736-0 [pii]. 10.1016/S0140-6736(05)66736-0
Merz CJ, Tabbert K, Schweckendiek J, Klucken T, Vaitl D, Stark R, Wolf OT (2010) Investigating the impact of sex and cortisol on implicit fear conditioning with fMRI. Psychoneuroendocrinology 35:33–46, doi: S0306-4530(09)00235-2 [pii]. 10.1016/j.psyneuen.2009.07.009
Moritz KM, Dodic M, Jefferies AJ, Wintour EM, DeMatteo R, Singh RR, Evans RG (2009) Haemodynamic characteristics of hypertension induced by prenatal cortisol exposure in sheep. Clin Exp Pharmacol Physiol 36:981–987, doi: CEP5180 [pii]. 10.1111/j.1440-1681.2009.05180.x
National Center for Biotechnology Information. PubChem Compound Database (CID 31378) Fludrocortisone – Compound Summary http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=31378#x94. Accessed 9 Jan 2012
Neary N, Nieman L (2010) Adrenal insufficiency: etiology, diagnosis and treatment. Curr Opin Endocrinol Diabetes Obes 17:217–223, doi: 10.1097/MED.0b013e328338f608
New MI (2006) Extensive clinical experience: nonclassical 21-hydroxylase deficiency. J Clin Endocrinol Metab 91:4205–4214, doi: jc.2006-1645 [pii]. 10.1210/jc.2006-1645
O’Brien K, Sekimoto H, Boney C, Malee M (2008) Effect of fetal dexamethasone exposure on the development of adult insulin sensitivity in a rat model. J Matern Fetal Neonatal Med 21:623–628, doi: 903250622 [pii]. 10.1080/14767050802213073
Oelkers W (1996) Adrenal insufficiency. N Engl J Med 335:1206–1212, doi: 10.1056/NEJM199610173351607
Office of Rare Diseases (ORD). (2008) Long-Term Outcome in Offspring and Mothers of Dexamethasone-Treated Pregnancies at Risk for Classical Congenital Adrenal Hyperplasia Owing to 21-Hydroxylase Deficiency. ClinicalTrials.gov Identifier: NCT00617292. http://clinicaltrials.gov/ct2/show/NCT00617292
Ostensen M, Lockshin M, Doria A, Valesini G, Meroni P, Gordon C, Brucato A, Tincani A (2008) Update on safety during pregnancy of biological agents and some immunosuppressive anti-rheumatic drugs. Rheumatology (Oxford) 47(Suppl 3):iii28–31, doi: ken168 [pii]. 10.1093/rheumatology/ken168
Owen D, Matthews SG (2003) Glucocorticoids and sex-dependent development of brain glucocorticoid and mineralocorticoid receptors. Endocrinology 144:2775–2784
Padidela R, Hindmarsh PC (2010) Mineralocorticoid deficiency and treatment in congenital adrenal hyperplasia. Int J Pediatr Endocrinol 2010:656925. doi:10.1155/2010/656925
Parasrampuria J, Schwartz K, Petesch R (1998) Quality control of dehydroepiandrosterone dietary supplement products. JAMA 280:1565, doi: jlt1111 [pii]
Paris JJ, Frye CA (2011) Juvenile offspring of rats exposed to restraint stress in late gestation have impaired cognitive performance and dysregulated progestogen formation. Stress 14:23–32. doi:10.3109/10253890.2010.512375
Petropoulos S, Gibb W, Matthews SG (2011) Breast cancer-resistance protein (BCRP1) in the fetal mouse brain: development and glucocorticoid regulation. Biol Reprod 84:783–789, doi: biolreprod.110.088468 [pii]. 10.1095/biolreprod.110.088468
Reinisch JM, Simon NG, Karow WG, Gandelman R (1978) Prenatal exposure to prednisone in humans and animals retards intrauterine growth. Science 202:436–438
Speake PF, Glazier JD, Greenwood SL, Sibley CP (2010) Aldosterone and cortisol acutely stimulate Na+/H + exchanger activity in the syncytiotrophoblast of the human placenta: effect of fetal sex. Placenta 31:289–294, doi: S0143-4004(10)00003-2 [pii]. 10.1016/j.placenta.2009.12.025
Speiser PW, Azziz R, Baskin LS, Ghizzoni L, Hensle TW, Merke DP, Meyer-Bahlburg HF, Miller WL, Montori VM, Oberfield SE, Ritzen M, White PC (2010) Congenital adrenal hyperplasia due to steroid 21-hydroxylase deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 95:4133–4160, doi: 95/9/4133 [pii]. 10.1210/jc.2009-2631
Traish AM, Kang HP, Saad F, Guay AT (2011) Dehydroepiandrosterone (DHEA)–a precursor steroid or an active hormone in human physiology. J Sex Med 8:2960–2982. doi:10.1111/j.1743-6109.2011.02523.x, quiz 2983
Trapp CM, Oberfield SE (2011) Recommendations for treatment of nonclassic congenital adrenal hyperplasia (NCCAH): an update. Steroids, doi: S0039-128X(11)00354-0 [pii]. 10.1016/j.steroids.2011.12.009
Turner BB (1990) Sex difference in glucocorticoid binding in rat pituitary is estrogen dependent. Life Sci 46:1399–1406
U.S. Food and Drug Administration. (2007) Code of Federal Regulations 21CFR201 Labeling. Revised as of 1 Apr 2007
Verma S, Vanryzin C, Sinaii N, Kim MS, Nieman LK, Ravindran S, Calis KA, Arlt W, Ross RJ, Merke DP (2010) A pharmacokinetic and pharmacodynamic study of delayed- and extended-release hydrocortisone (Chronocort) vs. conventional hydrocortisone (Cortef) in the treatment of congenital adrenal hyperplasia. Clin Endocrinol (Oxf) 72:441–447, doi: CEN3636 [pii]. 10.1111/j.1365-2265.2009.03636.x
Vos AA, Bruinse HW (2010) Congenital adrenal hyperplasia: do the benefits of prenatal treatment defeat the risks? Obstet Gynecol Surv 65:196–205, doi: 0006254-201003000-00023 [pii]. 10.1097/OGX.0b013e3181d61046
Warrell DW, Taylor R (1968) Outcome for the foetus of mothers receiving prednisolone during pregnancy. Lancet 1:117–118
Weinstock M (2011) Sex-dependent changes induced by prenatal stress in cortical and hippocampal morphology and behaviour in rats: an update. Stress 14:604–613. doi:10.3109/10253890.2011.588294
White PC, Mune T, Agarwal AK (1997) 11 beta-Hydroxysteroid dehydrogenase and the syndrome of apparent mineralocorticoid excess. Endocr Rev 18:135–156
Wu W, Kocarek TA, Runge-Morris M (2001) Sex-dependent regulation by dexamethasone of murine hydroxysteroid sulfotransferase gene expression. Toxicol Lett 119:235–246, doi: S0378427401002636 [pii]
Wyrwoll CS, Holmes MC (2011) Prenatal excess glucocorticoid exposure and adult affective disorders: a role for serotonergic and catecholamine pathways. Neuroendocrinology, doi: 000331345 [pii]. 10.1159/000331345
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Gessl, A., Lemmens-Gruber, R., Kautzky-Willer, A. (2013). Adrenal Disorders. In: Regitz-Zagrosek, V. (eds) Sex and Gender Differences in Pharmacology. Handbook of Experimental Pharmacology, vol 214. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-30726-3_16
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