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Endocrinology2018; 159(11); 3791-3800; doi: 10.1210/en.2018-00726

Dysregulation of Cortisol Metabolism in Equine Pituitary Pars Intermedia Dysfunction.

Abstract: Equine Cushing disease [pituitary pars intermedia dysfunction (PPID)] is a common condition of older horses, but its pathophysiology is complex and poorly understood. In contrast to pituitary-dependent hyperadrenocorticism in other species, PPID is characterized by elevated plasma ACTH but not elevated plasma cortisol. In this study, we address this paradox and the hypothesis that PPID is a syndrome of ACTH excess in which there is dysregulation of peripheral glucocorticoid metabolism and binding. In 14 horses with PPID compared with 15 healthy controls, we show that in plasma, cortisol levels and cortisol binding to corticosteroid binding globulin were not different; in urine, glucocorticoid and androgen metabolites were increased up to fourfold; in liver, 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) expression was reduced; in perirenal adipose tissue, 11β-HSD1 and carbonyl reductase 1 expression was increased; and tissue cortisol levels were not measurably different. The combination of normal plasma cortisol with markedly enhanced urinary cortisol metabolite excretion and dysregulated tissue-specific steroid-metabolizing enzymes suggests that cortisol clearance is increased in horses with PPID. We infer that the ACTH excess may be compensatory and pituitary pathology and autonomous secretion may be a secondary rather than primary pathology. It is possible that successful therapy in PPID may be targeted either at lowering ACTH or, paradoxically, at reducing cortisol clearance.
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Publication Date: 2018-10-06 PubMed ID: 30289445PubMed Central: PMC6202856DOI: 10.1210/en.2018-00726Google Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This research investigates the dysregulation of cortisol metabolism in equine Cushing disease (pituitary pars intermedia dysfunction – PPID), which is a common condition in older horses. Interestingly, the disease is characterized by elevated plasma ACTH but not elevated plasma cortisol. This study offers evidence that cortisol clearance is increased in horses with PPID, suggesting it might be possible to treat PPID by reducing either ACTH or cortisol clearance.

Understanding Pituitary Pars Intermedia Dysfunction (PPID)

  • PPID, also known as equine Cushing disease, is a common condition in older horses. It involves the pituitary gland, which is responsible for releasing hormones like ACTH (adrenocorticotropic hormone).
  • Unlike other forms of hyperadrenocorticism, where cortisol (a stress hormone) levels are high, horses with PPID have elevated plasma ACTH levels but not elevated plasma cortisol levels. This breaks from the typical pattern and suggests a different underlying pathophysiology for PPID.

Methods and Findings of the Study

  • The study compared 14 horses with PPID to 15 healthy horses. It measured several variables related to cortisol metabolism and ACTH levels in different body fluids and tissues.
  • Despite the elevated ACTH in horses with PPID, plasma cortisol levels and cortisol binding to corticosteroid binding globulin were not different in comparison to healthy horses. This suggests that ACTH’s usual role in elevating cortisol levels may be disrupted in horses with PPID.
  • Researchers noted a fourfold increase in glucocorticoid and androgen metabolites in the urine of horses with PPID and found a reduced expression of an enzyme (11β-HSD1) in the liver.
  • The expression of 11β-HSD1 and carbonyl reductase 1 was found to be increased in perirenal adipose tissue of PPID-affected horses, indicating abnormal tissue-specific steroid metabolism. However, tissue cortisol levels remained the same.

Implications of the Findings

  • The observed evidence points towards increased cortisol clearance in horses with PPID, which could help explain the simultaneous finding of high ACTH levels and normal cortisol levels.
  • The researchers propose that the excess ACTH may be a compensatory response, trying to stimulate more cortisol production in the face of increased cortisol clearance.
  • This finding shifts the perspective on the pituitary pathology in PPID, suggesting it might be a secondary rather than primary pathology.
  • In terms of treatment strategies, the researchers suggest that successful therapy may be achieved by aiming to lower ACTH or, paradoxically, reducing cortisol clearance.

Cite This Article

APA
Morgan RA, Keen JA, Homer N, Nixon M, McKinnon-Garvin AM, Moses-Williams JA, Davis SR, Hadoke PWF, Walker BR. (2018). Dysregulation of Cortisol Metabolism in Equine Pituitary Pars Intermedia Dysfunction. Endocrinology, 159(11), 3791-3800. https://doi.org/10.1210/en.2018-00726

Publication

Endocrinology
ISSN: 1945-7170
NlmUniqueID: 0375040
Country: United States
Language: English
Volume: 159
Issue: 11
Pages: 3791-3800

Researcher Affiliations

Morgan, Ruth A
  • University/British Heart Foundation Centre for Cardiovascular Science, The Queen's Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom.
  • Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush Campus, Midlothian, United Kingdom.
Keen, John A
  • Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush Campus, Midlothian, United Kingdom.
Homer, Natalie
  • University/British Heart Foundation Centre for Cardiovascular Science, The Queen's Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom.
Nixon, Mark
  • University/British Heart Foundation Centre for Cardiovascular Science, The Queen's Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom.
McKinnon-Garvin, Anna M
  • Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush Campus, Midlothian, United Kingdom.
Moses-Williams, Jodie A
  • Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush Campus, Midlothian, United Kingdom.
Davis, Sarah R
  • Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush Campus, Midlothian, United Kingdom.
Hadoke, Patrick W F
  • University/British Heart Foundation Centre for Cardiovascular Science, The Queen's Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom.
Walker, Brian R
  • University/British Heart Foundation Centre for Cardiovascular Science, The Queen's Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom.
  • Institute of Genetic Medicine, Newcastle University, International Centre for Life, Newcastle upon Tyne, United Kingdom.

MeSH Terms

  • 11-beta-Hydroxysteroid Dehydrogenase Type 1 / metabolism
  • Adipose Tissue / metabolism
  • Adrenocorticotropic Hormone / metabolism
  • Androgens / metabolism
  • Androgens / urine
  • Animals
  • Carbonyl Reductase (NADPH) / metabolism
  • Case-Control Studies
  • Glucocorticoids / metabolism
  • Glucocorticoids / urine
  • Horse Diseases / metabolism
  • Horses
  • Hydrocortisone / metabolism
  • Hydrocortisone / urine
  • Liver / metabolism
  • Pituitary ACTH Hypersecretion / metabolism
  • Pituitary ACTH Hypersecretion / veterinary
  • Pituitary Gland, Intermediate / metabolism
  • Transcortin / metabolism

Grant Funding

  • 206587/Z/17/Z / Wellcome Trust
  • ISSF2 / Wellcome Trust
  • R42126/82976 / Biotechnology and Biological Sciences Research Council
  • Wellcome Trust
  • FS/18/20/33449 / British Heart Foundation
  • RG/11/4/28734 / British Heart Foundation

References

This article includes 53 references
  1. McGowan TW, Pinchbeck GP, McGowan CM. Prevalence, risk factors and clinical signs predictive for equine pituitary pars intermedia dysfunction in aged horses.. Equine Vet J 2013 Jan;45(1):74-9.
    pubmed: 22594955doi: 10.1111/j.2042-3306.2012.00578.xgoogle scholar: lookup
  2. Orth DN, Holscher MA, Wilson MG, Nicholson WE, Plue RE, Mount CD. Equine Cushing's disease: plasma immunoreactive proopiolipomelanocortin peptide and cortisol levels basally and in response to diagnostic tests.. Endocrinology 1982 Apr;110(4):1430-41.
    pubmed: 6277607doi: 10.1210/endo-110-4-1430google scholar: lookup
  3. Dybdal NO, Hargreaves KM, Madigan JE, Gribble DH, Kennedy PC, Stabenfeldt GH. Diagnostic testing for pituitary pars intermedia dysfunction in horses.. J Am Vet Med Assoc 1994 Feb 15;204(4):627-32.
    pubmed: 8163420
  4. Heinrichs M, Baumgärtner W, Capen CC. Immunocytochemical demonstration of proopiomelanocortin-derived peptides in pituitary adenomas of the pars intermedia in horses.. Vet Pathol 1990 Nov;27(6):419-25.
    pubmed: 2177580doi: 10.1177/030098589902700606google scholar: lookup
  5. Sojka-Kritchevsky JE, Johnson PJ. Current status and future directions: equine pituitary pars intermedia dysfunction and equine metabolic syndrome.. Equine Vet J 2014 Jan;46(1):99-102.
    pubmed: 24329586doi: 10.1111/evj.12194google scholar: lookup
  6. Orth DN, Nicholson WE. Bioactive and immunoreactive adrenocorticotropin in normal equine pituitary and in pituitary tumors of horses with Cushing's disease.. Endocrinology 1982 Aug;111(2):559-63.
    pubmed: 6284484doi: 10.1210/endo-111-2-559google scholar: lookup
  7. Cordero M, Shrauner B, McFarlane D. Bioactivity of plasma ACTH from horses with PPID compared to normal horses. J Vet Intern Med 2011;25(3):664.
  8. Gayrard V, Alvinerie M, Toutain PL. Interspecies variations of corticosteroid-binding globulin parameters.. Domest Anim Endocrinol 1996 Jan;13(1):35-45.
    pubmed: 8625614doi: 10.1016/0739-7240(95)00042-9google scholar: lookup
  9. Edwards CR, Stewart PM, Burt D, Brett L, McIntyre MA, Sutanto WS, de Kloet ER, Monder C. Localisation of 11 beta-hydroxysteroid dehydrogenase--tissue specific protector of the mineralocorticoid receptor.. Lancet 1988 Oct 29;2(8618):986-9.
    pubmed: 2902493doi: 10.1016/s0140-6736(88)90742-8google scholar: lookup
  10. Shackleton CH. Profiling steroid hormones and urinary steroids.. J Chromatogr 1986 Jun 20;379:91-156.
    pubmed: 3525596doi: 10.1016/s0378-4347(00)80683-0google scholar: lookup
  11. Morgan RA, Beck KR, Nixon M, Homer NZM, Crawford AA, Melchers D, Houtman R, Meijer OC, Stomby A, Anderson AJ, Upreti R, Stimson RH, Olsson T, Michoel T, Cohain A, Ruusalepp A, Schadt EE, Björkegren JLM, Andrew R, Kenyon CJ, Hadoke PWF, Odermatt A, Keen JA, Walker BR. Carbonyl reductase 1 catalyzes 20β-reduction of glucocorticoids, modulating receptor activation and metabolic complications of obesity.. Sci Rep 2017 Sep 6;7(1):10633.
    pmc: PMC5587574pubmed: 28878267doi: 10.1038/s41598-017-10410-1google scholar: lookup
  12. Livingstone DE, Di Rollo EM, Yang C, Codrington LE, Mathews JA, Kara M, Hughes KA, Kenyon CJ, Walker BR, Andrew R. Relative adrenal insufficiency in mice deficient in 5α-reductase 1.. J Endocrinol 2014 Aug;222(2):257-66.
    pmc: PMC4104038pubmed: 24872577doi: 10.1530/joe-13-0563google scholar: lookup
  13. Carroll CL, Huntington PJ. Body condition scoring and weight estimation of horses.. Equine Vet J 1988 Jan;20(1):41-5.
    pubmed: 3366105doi: 10.1111/j.2042-3306.1988.tb01451.xgoogle scholar: lookup
  14. Beech J, Boston RC, McFarlane D, Lindborg S. Evaluation of plasma ACTH, alpha-melanocyte-stimulating hormone, and insulin concentrations during various photoperiods in clinically normal horses and ponies and those with pituitary pars intermedia dysfunction.. J Am Vet Med Assoc 2009 Sep 15;235(6):715-22.
    pubmed: 19751169doi: 10.2460/javma.235.6.715google scholar: lookup
  15. Miller MA, Pardo ID, Jackson LP, Moore GE, Sojka JE. Correlation of pituitary histomorphometry with adrenocorticotrophic hormone response to domperidone administration in the diagnosis of equine pituitary pars intermedia dysfunction.. Vet Pathol 2008 Jan;45(1):26-38.
    pubmed: 18192571doi: 10.1354/vp.45-1-26google scholar: lookup
  16. Stirrat LI, Just G, Homer NZM, Andrew R, Norman JE, Reynolds RM. Glucocorticoids are lower at delivery in maternal, but not cord blood of obese pregnancies.. Sci Rep 2017 Aug 31;7(1):10263.
    pmc: PMC5579291pubmed: 28860525doi: 10.1038/s41598-017-10266-5google scholar: lookup
  17. Upreti R, Naredo G, Faqehi AM, Hughes KA, Stewart LH, Walker BR, Homer NZ, Andrew R. Simultaneous pharmacokinetic and pharmacodynamic analysis of 5α-reductase inhibitors and androgens by liquid chromatography tandem mass spectrometry.. Talanta 2015 Jan;131:728-35.
    pmc: PMC4196769pubmed: 25281165doi: 10.1016/j.talanta.2014.07.087google scholar: lookup
  18. Homer N, Kothiya S, Rutter A, Walker BR, Andrew R. Gas chromatography tandem mass spectrometry offers advantages for urinary steroids analysis.. Anal Biochem 2017 Dec 1;538:34-37.
    pmc: PMC5713679pubmed: 28887174doi: 10.1016/j.ab.2017.09.002google scholar: lookup
  19. Hammond GL, Lähteenmäki PL. A versatile method for the determination of serum cortisol binding globulin and sex hormone binding globulin binding capacities.. Clin Chim Acta 1983 Jul 31;132(1):101-10.
    pubmed: 6193907doi: 10.1016/0009-8981(83)90237-1google scholar: lookup
  20. Hart KA, Barton MH, Ferguson DC, Berghaus R, Slovis NM, Heusner GL, Hurley DJ. Serum free cortisol fraction in healthy and septic neonatal foals.. J Vet Intern Med 2011 Mar-Apr;25(2):345-55.
    pubmed: 21281351doi: 10.1111/j.1939-1676.2010.0667.xgoogle scholar: lookup
  21. nRRID:nAB_631572.
  22. Morgan R. Dysregulation of cortisol metabolism in equine pituitary pars intermedia dysfunction. figshare 2018. Accessed 8 June 2018.
  23. Bustin SA. Quantification of mRNA using real-time reverse transcription PCR (RT-PCR): trends and problems.. J Mol Endocrinol 2002 Aug;29(1):23-39.
    pubmed: 12200227doi: 10.1677/jme.0.0290023google scholar: lookup
  24. Silberzahn P, Rashed F, Zwain I, Leymarie P. Androstenedione and testosterone biosynthesis by the adrenal cortex of the horse.. Steroids 1984 Feb;43(2):147-52.
    pubmed: 6395450doi: 10.1016/0039-128x(84)90033-3google scholar: lookup
  25. Wake DJ, Strand M, Rask E, Westerbacka J, Livingstone DE, Soderberg S, Andrew R, Yki-Jarvinen H, Olsson T, Walker BR. Intra-adipose sex steroid metabolism and body fat distribution in idiopathic human obesity.. Clin Endocrinol (Oxf) 2007 Mar;66(3):440-6.
    pubmed: 17302881doi: 10.1111/j.1365-2265.2007.02755.xgoogle scholar: lookup
  26. Walker BR. Activation of the hypothalamic-pituitary-adrenal axis in obesity: cause or consequence?. Growth Horm IGF Res 2001 Jun;11 Suppl A:S91-5.
    pubmed: 11527096doi: 10.1016/s1096-6374(01)80015-0google scholar: lookup
  27. Hart KA, Wochele DM, Norton NA, McFarlane D, Wooldridge AA, Frank N. Effect of Age, Season, Body Condition, and Endocrine Status on Serum Free Cortisol Fraction and Insulin Concentration in Horses.. J Vet Intern Med 2016 Mar-Apr;30(2):653-63.
    pmc: PMC4913614pubmed: 26860336doi: 10.1111/jvim.13839google scholar: lookup
  28. van der Kolk JH, Nachreiner RF, Schott HC, Refsal KR, Zanella AJ. Salivary and plasma concentration of cortisol in normal horses and horses with Cushing's disease.. Equine Vet J 2001 Mar;33(2):211-3.
    pubmed: 11266074doi: 10.1111/j.2042-3306.2001.tb00604.xgoogle scholar: lookup
  29. Hart KA, Kitchings KM, Kimura S, Norton NA, Myrna KE. Measurement of cortisol concentration in the tears of horses and ponies with pituitary pars intermedia dysfunction.. Am J Vet Res 2016 Nov;77(11):1236-1244.
    pubmed: 27805438doi: 10.2460/ajvr.77.11.1236google scholar: lookup
  30. Chandler KJ, Dixon RM. Urinary cortisol:creatinine ratios in healthy horses and horses with hyperadrenocorticism and non-adrenal disease.. Vet Rec 2002 Jun 22;150(25):773-6.
    pubmed: 12135071doi: 10.1136/vr.150.25.773google scholar: lookup
  31. van der Kolk JH, Kalsbeek HC, Wensing T, Breukink HJ. Urinary concentration of corticoids in normal horses and horses with hyperadrenocorticism.. Res Vet Sci 1994 Jan;56(1):126-8.
    pubmed: 8146446doi: 10.1016/0034-5288(94)90210-0google scholar: lookup
  32. Lassourd V, Gayrard V, Laroute V, Alvinerie M, Benard P, Courtot D, Toutain PL. Cortisol disposition and production rate in horses during rest and exercise.. Am J Physiol 1996 Jul;271(1 Pt 2):R25-33.
    pubmed: 8760200doi: 10.1152/ajpregu.1996.271.1.r25google scholar: lookup
  33. Lottenberg SA, Giannella-Neto D, Derendorf H, Rocha M, Bosco A, Carvalho SV, Moretti AE, Lerário AC, Wajchenberg BL. Effect of fat distribution on the pharmacokinetics of cortisol in obesity.. Int J Clin Pharmacol Ther 1998 Sep;36(9):501-5.
    pubmed: 9760012
  34. Andrews RC, Herlihy O, Livingstone DE, Andrew R, Walker BR. Abnormal cortisol metabolism and tissue sensitivity to cortisol in patients with glucose intolerance.. J Clin Endocrinol Metab 2002 Dec;87(12):5587-93.
    pubmed: 12466357doi: 10.1210/jc.2002-020048google scholar: lookup
  35. Tomlinson JW, Finney J, Hughes BA, Hughes SV, Stewart PM. Reduced glucocorticoid production rate, decreased 5alpha-reductase activity, and adipose tissue insulin sensitization after weight loss.. Diabetes 2008 Jun;57(6):1536-43.
    pubmed: 18340018doi: 10.2337/db08-0094google scholar: lookup
  36. Strain GW, Zumoff B, Kream J, Strain JJ, Levin J, Fukushima D. Sex difference in the influence of obesity on the 24 hr mean plasma concentration of cortisol.. Metabolism 1982 Mar;31(3):209-12.
    pubmed: 7078409doi: 10.1016/0026-0495(82)90054-3google scholar: lookup
  37. Gambineri A, Forlani G, Munarini A, Tomassoni F, Cognigni GE, Ciampaglia W, Pagotto U, Walker BR, Pasquali R. Increased clearance of cortisol by 5beta-reductase in a subgroup of women with adrenal hyperandrogenism in polycystic ovary syndrome.. J Endocrinol Invest 2009 Mar;32(3):210-8.
    pmc: PMC4425940pubmed: 19542736doi: 10.1007/bf03346454google scholar: lookup
  38. Vinson GP, Whitehouse BJ, Dell A, Bateman A, McAuley ME. alpha-MSH and zona glomerulosa function in the rat.. J Steroid Biochem 1983 Jul;19(1B):537-44.
    pubmed: 6310242doi: 10.1016/0022-4731(83)90215-7google scholar: lookup
  39. Stimson RH, Mohd-Shukri NA, Bolton JL, Andrew R, Reynolds RM, Walker BR. The postprandial rise in plasma cortisol in men is mediated by macronutrient-specific stimulation of adrenal and extra-adrenal cortisol production.. J Clin Endocrinol Metab 2014 Jan;99(1):160-168.
    pmc: PMC4392802pubmed: 24092834doi: 10.1210/jc.2013-2307google scholar: lookup
  40. Keenan DM, Roelfsema F, Veldhuis JD. Endogenous ACTH concentration-dependent drive of pulsatile cortisol secretion in the human.. Am J Physiol Endocrinol Metab 2004 Oct;287(4):E652-61.
    pubmed: 15186998doi: 10.1152/ajpendo.00167.2004google scholar: lookup
  41. Keenan DM, Roelfsema F, Carroll BJ, Iranmanesh A, Veldhuis JD. Sex defines the age dependence of endogenous ACTH-cortisol dose responsiveness.. Am J Physiol Regul Integr Comp Physiol 2009 Aug;297(2):R515-23.
    pmc: PMC2724232pubmed: 19535673doi: 10.1152/ajpregu.00200.2009google scholar: lookup
  42. Rask E, Olsson T, Söderberg S, Andrew R, Livingstone DE, Johnson O, Walker BR. Tissue-specific dysregulation of cortisol metabolism in human obesity.. J Clin Endocrinol Metab 2001 Mar;86(3):1418-21.
    pubmed: 11238541doi: 10.1210/jcem.86.3.7453google scholar: lookup
  43. Mariniello B, Ronconi V, Rilli S, Bernante P, Boscaro M, Mantero F, Giacchetti G. Adipose tissue 11beta-hydroxysteroid dehydrogenase type 1 expression in obesity and Cushing's syndrome.. Eur J Endocrinol 2006 Sep;155(3):435-41.
    pubmed: 16914598doi: 10.1530/eje.1.02228google scholar: lookup
  44. Hughes KA, Manolopoulos KN, Iqbal J, Cruden NL, Stimson RH, Reynolds RM, Newby DE, Andrew R, Karpe F, Walker BR. Recycling between cortisol and cortisone in human splanchnic, subcutaneous adipose, and skeletal muscle tissues in vivo.. Diabetes 2012 Jun;61(6):1357-64.
    pmc: PMC3357308pubmed: 22511204doi: 10.2337/db11-1345google scholar: lookup
  45. Rönquist-Nii Y, Edlund PO. Determination of corticosteroids in tissue samples by liquid chromatography-tandem mass spectrometry.. J Pharm Biomed Anal 2005 Feb 23;37(2):341-50.
    pubmed: 15708676doi: 10.1016/j.jpba.2004.10.044google scholar: lookup
  46. Hughes KA, Reynolds RM, Andrew R, Critchley HO, Walker BR. Glucocorticoids turn over slowly in human adipose tissue in vivo.. J Clin Endocrinol Metab 2010 Oct;95(10):4696-702.
    pmc: PMC4394154pubmed: 20631029doi: 10.1210/jc.2010-0384google scholar: lookup
  47. Nixon M, Mackenzie SD, Taylor AI, Homer NZ, Livingstone DE, Mouras R, Morgan RA, Mole DJ, Stimson RH, Reynolds RM, Elfick AP, Andrew R, Walker BR. ABCC1 confers tissue-specific sensitivity to cortisol versus corticosterone: A rationale for safer glucocorticoid replacement therapy.. Sci Transl Med 2016 Aug 17;8(352):352ra109.
    pubmed: 27535620doi: 10.1126/scitranslmed.aaf9074google scholar: lookup
  48. Rabbitt EH, Ayuk J, Boelaert K, Sheppard MC, Hewison M, Stewart PM, Gittoes NJ. Abnormal expression of 11 beta-hydroxysteroid dehydrogenase type 2 in human pituitary adenomas: a prereceptor determinant of pituitary cell proliferation.. Oncogene 2003 Mar 20;22(11):1663-7.
    pubmed: 12642869doi: 10.1038/sj.onc.1206293google scholar: lookup
  49. Alpañés M, Fernández-Durán E, Escobar-Morreale HF. Androgens and polycystic ovary syndrome. Expert Rev Endocrinol Metab 2012;7(1):91–102.
  50. Rasmuson S, Andrew R, Näsman B, Seckl JR, Walker BR, Olsson T. Increased glucocorticoid production and altered cortisol metabolism in women with mild to moderate Alzheimer's disease.. Biol Psychiatry 2001 Mar 15;49(6):547-52.
    pubmed: 11257240doi: 10.1016/s0006-3223(00)01015-5google scholar: lookup
  51. Hedberg Y, Dalin AM, Forsberg M, Lundeheim N, Sandh G, Hoffmann B, Ludwig C, Kindahl H. Effect of ACTH (tetracosactide) on steroid hormone levels in the mare. Part B: effect in ovariectomized mares (including estrous behavior).. Anim Reprod Sci 2007 Jul;100(1-2):92-106.
    pubmed: 16860499doi: 10.1016/j.anireprosci.2006.06.007google scholar: lookup
  52. van der Kolk JH, Kalsbeek HC, van Garderen E, Wensing T, Breukink HJ. Equine pituitary neoplasia: a clinical report of 21 cases (1990-1992).. Vet Rec 1993 Dec 11;133(24):594-7.
    pubmed: 8116170
  53. Cozzolino M, Brancaccio D, Gallieni M, Galassi A, Slatopolsky E, Dusso A. Pathogenesis of parathyroid hyperplasia in renal failure.. J Nephrol 2005 Jan-Feb;18(1):5-8.
    pubmed: 15772917

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