Vitamin D metabolism in hypercorticism and acromegaly

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription Access



Due to the high prevalence of low vitamin D levels in the overwhelming majority of regions of the world and discovery of extra-skeletal effects of vitamin D, the issue of maintaining adequate levels of vitamin D in the blood remains extremely relevant, especially in people with high risk of severe deficiency. To date, few studies have been performed on the features of vitamin D metabolism in disorders such as hypercorticism and acromegaly. However, vitamin D deficiency in such patients, according to available literature, may be more widespread and more pronounced than in general population. It is now recommended to use standard prophylactic and therapeutic doses of vitamin D for the treatment of these diseases, which may not satisfy the therapeutic goals specific to each disease. This review provides information on normal vitamin D metabolism, as well as literature data on the possible relationship and mutual influence between these endocrinopathies and vitamin D metabolism.

Full Text

About the authors

Alexandra A. Povaliaeva

ФГБУ "НМИЦ эндокринологии" Минздрава России

Author for correspondence.
ORCID iD: 0000-0002-7634-5457
SPIN-code: 1970-2811

ассистент методического аккредитационно-симуляционного центра

Ekaterina A. Pigarova

ФГБУ "НМИЦ эндокринологии" Минздрава России

ORCID iD: 0000-0001-6539-466X
SPIN-code: 6912-6331

к.м.н, в.н.с. отделения нейроэндокринологии и остеопатий

Larisa K. Dzeranova

ФГБУ "НМИЦ эндокринологии" Минздрава России

ORCID iD: 0000-0002-0327-4619
SPIN-code: 2958-5555

д.м.н., г.н.с. отделения нейроэндокринологии и остеопатий

Liudmila Ya. Rozhinskaya

ФГБУ "НМИЦ эндокринологии" Минздрава России

ORCID iD: 0000-0001-7041-0732
SPIN-code: 5691-7775

д.м.н., профессор, г.н.с. отделения нейроэндокринологии и остеопатий

Galina A. Mel'nichenko

ФГБУ "НМИЦ эндокринологии" Минздрава России

ORCID iD: 0000-0002-5634-7877
SPIN-code: 8615-0038

д.м.н., профессор, академик РАН, директор Института клинической эндокринологии


  • Пигарова Е.А., Рожинская Л.Я., Белая Ж.Е. и др. Клинические рекомендации Российской ассоциации эндокринологов по диагностике, лечению и профилактике дефицита витамина D у взрослых // Проблемы эндокринологии. — 2016. — Т. 62. — №4. — C. 60–84. [Pigarova EA, Rozhinskaya LY, Belaya JE et al. Russian Association of Endocrinologists recommendations for diagnosis, treatment and prevention of vitamin D deficiency in adults. Problems of Endocrinology. 2016;62(4):60–84. (In Russ.)] doi: 10.14341/probl201662460-84.
  • Holick MF. Vitamin D deficiency. N. Engl. J. Med. 2007;357(3):266–281. doi: 10.1056/NEJMra070553.
  • Bikle DD. Vitamin D metabolism, mechanism of action, and clinical applications. Chem. Biol. 2014;21(3):319–329. doi: 10.1016/j.chembiol.2013.12.016.
  • Holick MF, editor. Vitamin D. Molecular biology, physiology and clinical applications. 2nd ed. New York: Humana Press; 2010. doi: 10.1007/978-1-60327-303-9.
  • Kugai N, Koide Y, Yamashita K et al. Impaired mineral metabolism in Cushing’s syndrome: parathyroid function, vitamin D metabolites and osteopenia. Endocrinol. Jpn. 1986;33(3):345–352. doi: 10.1507/endocrj1954.33.345.
  • Hahn TJ, Halstead LR, Baran DT. Effects of short term glucocorticoid administration on intestinal calcium absorption and circulating vitamin D metabolite concentrations in man. J. Clin. Endocrinol. Metab. 1981;52(1):111–115. doi: 10.1210/jcem-52-1-111.
  • Findling JW, Adams ND, Lemann J et al. Vitamin D metabolites and parathyroid hormone in Cushing’s syndrome: relationship to calcium and phosphorus homeostasis. J. Clin. Endocrinol. Metab. 1982;54(5):1039–1044. doi: 10.1210/jcem-54-5-1039.
  • Seeman E, Kumar R, Hunder GG et al. Production, degradation, and circulating levels of 1,25-dihydroxyvitamin D in health and in chronic glucocorticoid excess. J Clin Invest. 1980;66(10): 664–669. doi: 10.1172/JCI109902.
  • Corbee RJ, Tryfonidou MA, Meij BP et al. Vitamin D status before and after hypophysectomy in dogs with pituitary-dependent hypercortisolism. Domest. Anim. Endocrinol. 2012;42(1):43–49. doi: 10.1016/j.domaniend.2011.09.002.
  • Jiang P, Xue Y, Li H et al. Dysregulation of vitamin D metabolism in the brain and myocardium of rats following prolonged exposure to dexamethasone. Psychopharmacology (Berl). 2014;231(17):3445–3451. doi: 10.1007/s00213-014-3440-6.
  • Klein RG, Arnaud SB, Gallagher JC et al. Intestinal calcium absorption in exogenous hypercortisolism. J Clin Invest. 1977;60(10):253–259. doi: 10.1172/JCI108762.
  • Huybers S, Naber T, Bindels R et al. Prednisolone-induced Ca2+ malabsorption is caused by diminished expression of the epithelial Ca2+ channel TRPV6. Am. J. Physiol. 2007;292(1):92–97. doi: 10.1152/ajpgi.00317.2006.
  • Van Cromphaut SJ, Stockmans I, Torrekens S et al. Duodenal calcium absorption in dexamethasone-treated mice: functional and molecular aspects. Arch. Biochem. Biophys. 2007;460(2):300–305. doi: 10.1016/
  • Levi M, Shayman JA, Abe A et al. Dexamethasone modulates rat renal brush border membrane phosphate transporter mRNA and protein abundance and glycosphingolipid composition. J. Clin. Invest. 1995;96(1):207–216. doi: 10.1172/JCI118022.
  • Christakos S, Gill R, Lee S et al. Molecular aspects of the calbindins. J Nutr. 1992;122(S3):678–682. doi: 10.1093/jn/122.suppl_3.678.
  • Akeno N, Matsunuma A, Maeda T et al. Regulation of vitamin D-1-hydroxylase and -24-hydroxylase expression by dexamethasone in mouse kidney. J. Endocrinol. 2000;164:339–348. doi: 10.1677/joe.0.1640339.
  • Kurahashi I, Matsunuma A, Kawane T et al. Dexamethasone enhances vitamin D-24-hydroxylase expression in osteoblastic (UMR-106) and renal (LLC-PK 1) cells treated with 1a, 25-dihydroxyvitamin D3. Endocrine. 2002;17(2):109–118. doi: 10.1385/ENDO:17:2:109.
  • Khomenko AV. Cholecalciferol hydroxylation in rat hepatocytes under the influence of prednisolone. Ukr Biokhim Zh. 2013;85(3):90–95.
  • Dhawan P, Christakos S. Novel regulation of 25-hydroxyvitamin D3 24-hydroxylase (24(OH)ase) transcription by glucocorticoids: cooperative effects of the glucocorticoid receptor, C/EBPb, and the vitamin D receptor in 24(OH)ase transcription. J. Cell. Biochem. 2010;110(6):1314–1323. doi: 10.1002/jcb.22645.
  • Kim M, Lee G, Jung E et al. The negative effect of dexamethasone on calcium-processing gene expressions is associated with a glucocorticoid-induced calcium-absorbing disorder. Life Sci. Elsevier Inc. 2009;85(3–4):146–152. doi: 10.1016/j.lfs.2009.05.013.
  • Davidson ZE, Walker KZ, Truby H. Do glucocorticosteroids alter vitamin D status? A systematic review with meta-analyses of observational studies. J Clin Endocrinol Metab. 2014;97(3):738–744. doi: 10.1210/jc.2011-2757.
  • Holick MF, Binkley NC, Bischoff-Ferrari HA et al. Evaluation, treatment, and prevention of vitamin D deficiency: An Endocrine Society Clinical Practice Guideline. J. Clin. Endocrinol. Metab. 2011;96(7):1911–1930. doi: 10.1210/jc.2011-0385.
  • Grossman JM, Gordon R, Ranganath VK et al. American College of Rheumatology 2010 Recommendations for the prevention and treatment of glucocorticoid-induced osteoporosis. Arthritis Care Res. (Hoboken). 2010;62(11):1515–1526. doi: 10.1002/acr.20295.
  • Buckley L, Guyatt G, Fink HA et al. 2017 American College of Rheumatology Guideline for the prevention and treatment of glucocorticoid-induced osteoporosis. Arthritis Care Res. (Hoboken). 2017;69(8):1095–1110. doi: 10.1002/acr.23424.
  • Ortego-Jurado M, Ríos-Fernández R, González-Moreno J et al. Oral calcidiol is more effective than cholecalciferol supplementation to reach adequate 25(OH)D levels in patients with autoimmune diseases chronically treated with low doses of glucocorticoids : A ‘“real-life”’ study. J. Osteoporos. 2015;(2015):ID 729451. doi: 10.1155/2015/729451.
  • Shiraishi A, Takeda S, Masaki T et al. Alfacalcidol inhibits bone resorption and stimulates formation in an ovariectomized rat model of osteoporosis : distinct actions from estrogen. J. Bone Miner. Res. 2000;15(4):770–779. doi: 10.1359/jbmr.2000.15.4.770.
  • Shymanskyi I, Lisakovska O, Mazanova A et al. Vitamin D3 modulates impaired crosstalk between RANK and glucocorticoid receptor signaling in bone marrow cells after chronic prednisolone administration. Front. Endocrinol. (Lausanne). 2018;9(6):303. doi: 10.3389/fendo.2018.00303.
  • Bouillon R, Carmeliet G, Verlinden L et al. Vitamin D and human health : Lessons from vitamin D receptor null mice. Endocr. Rev. 2015;29(6):726–776. doi: 10.1210/er.2008-0004.
  • Lima GL, Paupitz JA, Aikawa NE et al. A randomized double-blind placebo-controlled trial of vitamin D supplementation in juvenile-onset systemic lupus erythematosus : positive effect on trabecular microarchitecture using HR-pQCT. Osteoporos. Int. 2018;29(3):587–594. doi: 10.1007/s00198-017-4316-5.
  • Ringe JD, Dorst A, Faber H et al. Superiority of alfacalcidol over plain vitamin D in the treatment of glucocorticoid-induced osteoporosis. Rheumatol Int. 2004;24:63–70. doi: 10.1007/s00296-003-0361-9.
  • Yamada S, Takagi H, Tsuchiya H et al. Comparative studies on effect of risedronate and alfacalcidol against glucocorticoid-induced osteoporosis in rheumatoid arthritic patients. Yakugaku Zasshi. 2007;127(9):1491–1496. doi: 10.1248/yakushi.127.1491.
  • Brown J, Zacharin M. Attempted randomized controlled trial of pamidronate versus calcium and calcitriol supplements for management of steroid-induced osteoporosis in children and adolescents. J. Paediatr. Child. Heal. 2005;41(11):580–582. doi: 10.1111/j.1440-1754.2005.00720.x.
  • Rianthavorn P, Pisutikul K, Deekajorndech T et al. Prevention of bone loss in children receiving long-term glucocorticoids with calcium and alfacalcidol or menatetrenone. J. Pediatr. Endocr. Met. 2012;25(3-4):307–312. doi: 10.1515/jpem-2011-0441.
  • Rooney M, Bishop N, Davidson J et al. The prevention and treatment of glucocorticoid-induced osteopaenia in juvenile rheumatic disease : A randomised double-blind controlled trial. EClinicalMedicine. 2019;(12):79–87. doi: 10.1016/j.eclinm.2019.06.004.
  • Warady BD, Lindsley CB, Robinson RG et al. Effects of nutritional supplementation on bone mineral status of children with rheumatic diseases receiving corticosteroid therapy. J. Rheumatol. 1994;3(21):530–535.
  • Buckley LM, Leib ES, Cartularo KS et al. Calcium and vitamin D3 supplementation prevents bone loss in the spine secondary to low-dose corticosteroids in patients with rheumatoid arthritis: A randomized, double-blind, placebo-controlled trial. Ann. Intern. Med. 1996;125(12):961–968. doi: 10.7326/0003-4819-125-12-199612150-00004.
  • Eskildsen PC, Lund B, Sorensen OH et al. Acromegaly and vitamin D metabolism: effect of bromocriptine treatment. J. Clin. Endocrinol. Metab. 1979;49(3):484–486. doi: 10.1210/jcem-49-3-484.
  • Brown DJ, Spanos E, MacIntyre I. Role of pituitary hormones in regulating renal vitamin D metabolism in man. Br. Med. J. 1980;280(6210):277–278. doi: 10.1136/bmj.280.6210.277.
  • Shah R, Licata A, Oyesiku NM et al. Acromegaly as a cause of 1,25-dihydroxyvitamin D-dependent hypercalcemia : case reports and review of the literature. Pituitary. 2010;(S1):S17–22. doi: 10.1007/s11102-010-0286-8.
  • Ueda M, Inaba M, Tahara H et al. Hypercalcemia in a patient with primary hyperparathyroidism and acromegaly: distinct roles of growth hormone and parathyroid hormone in the development of hypercalcemia. Intern. Med. 2005;44(4):307–310. doi: 10.2169/internalmedicine.44.307.
  • Lund B, Eskildsen PC, Lund B et al. Calcium and vitamin D metabolism in acromegaly. Acta Endocrinol. 1981;96(4):444–450. doi: 10.1530/acta.0.0960444.
  • White HD, Ahmad AM, Durham BH et al. Effect of active acromegaly and its treatment on parathyroid circadian rhythmicity and parathyroid target-organ sensitivity. J. Clin. Endocrinol. Metab. 2006;91(3):913–919. doi: 10.1210/jc.2005-1602.
  • Takamoto S, Tsuchiya H, Onishi T et al. Changes in calcium homeostasis in acromegaly treated by pituitary adenomectomy. J. Clin. Endocrinol. Metab. 1985;61(1):7–11. doi: 10.1210/jcem-61-1-7.
  • Ho PJ, Fig LM, Barkan АL et al. Bone mineral density of the axial skeleton in acromegaly. J. Nucl. Med. 1992;33(9):1608–1612.
  • Bijlsma JWJ, Nortier JWR, Researchgroupfor C et al. Changes in bone metabolism during treatment of acromegaly. Acta Endocrinol. (Copenh). 1983;104:153–159. doi: 10.1530/acta.0.1040153.
  • Fredstorp L, Pernow Y, Werner S. The short and long-term effects of octreotide on calcium homeostasis in patients with acromegaly. Clin Endocrinol. 1993;39(3):331–336. doi: 10.1111/j.1365-2265.1993.tb02373.x.
  • Cappelli C, Gandossi E, Agosti B et al. Long-term treatment of acromegaly with lanreotide: evidence of increased serum parathormone concentration. J. Endocr. 2004;51(6):517–520. doi: 10.1507/endocrj.51.517.
  • Fontaine O, Pavlovitch H, Balsan S. 25-hydroxycholecalciferol metabolism in hypophysectomized rats. Endocrinology. 1978;102(6):1822–1826. doi: 10.1210/endo-102-6-1822.
  • Wongsurawat N, Armbrecht HJ, Zenser TV et al. Effects of hypophysectomy and growth hormone treatment on renal hydroxylation of 25-hydroxycholecalciferol in rats. J. Endocr. 1983;101:333–338. doi: 10.1677/joe.0.1010333.
  • Brixen K, Nielsen HK, Bouillon R et al. Effects of short-term growth hormone treatment on PTH, calcitriol, thyroid hormones, insulin and glucagon. Acta Endocrinol. (Copenh). 1992;127:331–336. doi: 10.1530/acta.0.1270331.
  • Bianda T, Hussain MА, Glatz Y et al. Effects of short-term insulin-like growth factor-I or growth hormone treatment on bone turnover, renal phosphate reabsorption and 1,25 dihydroxyvitamin D3 production in healthy man. J. Intern. Med. 1997;241(2):143–150. 10.1046/j.1365-2796.1997.94101000.x.
  • Condamine L, Vztovsnik F, Friedlander G et al. Local action of phosphate depletion and insulin-like growth factor 1 on in vitro production of 1,25-dihydroxyvitamin D by cultured mammalian kidney cells. J. Clin. Invest. 1994;94(10):1673–1679. doi: 10.1172/JCI117512.
  • Wei S, Tanaka H, Seino Y. Local action of exogenous growth hormone and insulin-like growth factor-I on dihydroxyvitamin D production in LLC-PK1 cells. Eur. J. Endocrinol. 1998;139(4):454–460. doi: 10.1530/eje.0.1390454.



Abstract - 117

PDF (Russian) - 5



Copyright (c) Povaliaeva A.A., Pigarova E.A., Dzeranova L.K., Rozhinskaya L.Y., Mel'nichenko G.A.

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies