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Decreased bone mineral density in women with Sheehan’s syndrome and improvement following oestrogen replacement and nutritional supplementation

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Abstract

Sheehan’s syndrome (SS) is an important cause of pan-hypopituitarism in women. There is scanty information on bone mineral density (BMD) in this condition. We determined BMD and the changes in BMD after oestrogen (E2) replacement and nutritional supplementation in women with SS. In a cross-sectional study, BMD was measured by DEXA in 83 patients [age (mean ± SD) 42 ± 9.2 years] and compared with an equal number of matched controls. In a sub-set of 19 patients, we conducted an open-label, prospective study to determine changes in BMD after 1 year of replacement of E2, and calcium and vitamin D3 supplementation. All patients had low serum IGF-1 and E2, while 98% had ≥ 3 pituitary hormone deficiencies. Compared with Indian reference standards, 47% had decreased bone mass (Z-score ≤ − 2.0). BMD Z-scores were decreased at all sites, being most marked in the lumbar spine and femoral neck. At the lumbar spine, BMD was lowest among the age group 21–30 years. Women with SS also had significantly lower BMD Z-scores at all three sites on comparison with ethnic controls. On multivariate analysis, BMD Z-score was associated with weight, daily calcium intake and age (lumbar spine). In the prospective study, 1 year of therapy improved BMD Z-score at lumbar spine (− 1.4 ± 1.2 vs. − 1.1 ± 1.1, p = 0.02), but not at hip or femoral neck. In conclusion, patients with SS had significantly lower BMD compared to controls at all three sites. Replacement of E2 and supplementation with calcium/vitamin D3 lead to significant improvement in lumbar spine BMD.

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References

  1. Karaca Z, Laway BA, Dokmetas HS, Atmaca H, Kelestimur F (2016) Sheehan syndrome. Nat Rev Dis Primers 2:16092

    Article  PubMed  Google Scholar 

  2. Diri H, Tanriverdi F, Karaca Z, Senol S, Unluhizarci K, Durak AC, Atmaca H, Kelestimur F (2014) Extensive investigation of 114 patients with Sheehan’s syndrome: a continuing disorder. Eur J Endocrinol 17:1311–1318

    Google Scholar 

  3. Tessnow AH, Wilson JD (2010) The changing face of Sheehan’s syndrome. Am J Med Sci 340:402–406

    Article  PubMed  Google Scholar 

  4. Du GL, Liu ZH, Chen M, Ma R, Jiang S, Shayiti M, Zhu J, Yusufu A (2015) Sheehan’s syndrome in **njiang: clinical characteristics and laboratory evaluation of 97 patients. Hormones 14:660–667

    PubMed  Google Scholar 

  5. Gei-Guardia O, Soto-Herrera E, Gei-Brealey A, Chen-Ku CH (2011) Sheehan syndrome in Costa Rica: clinical experience with 60 cases. Endocr Pract 17:337–344

    Article  PubMed  Google Scholar 

  6. Zargar AH, Singh B, Laway BA, Masoodi SR, Wani AI, Bashir MI (2005) Epidemiologic aspects of postpartum pituitary hypofunction (Sheehan’s syndrome). Fertil Sterl 84:523–528

    Article  Google Scholar 

  7. Kristjansdottir HL, Bodvarsdottir SP, Sigurjonsdottir HA (2011) Sheehan’s syndrome in modern times: a nationwide retrospective study in Iceland. Eur J Endocrinol 164:349–354

    Article  CAS  PubMed  Google Scholar 

  8. Ramiandrasoa C, Castinetti F, Raingeard I, Fenichel P, Chabre O, Brue T, Courbière B (2013) Delayed diagnosis of Sheehan’s syndrome in a developed country: a retrospective cohort study. Eur J Endocrinol 169:431–438

    Article  CAS  PubMed  Google Scholar 

  9. Almeida M, Laurent MR, Dubois V, Claessens F, O’Brien CA, Bouillon R, Vanderschueren D, Manolagas SC (2017) Estrogens and androgens in skeletal physiology and pathophysiology. Physiol Rev 97:135–187

    Article  PubMed  Google Scholar 

  10. Tritos NA, Klibanski A (2016) Effects of growth hormone on bone. Prog Mol Biol Transl Sci 138:193–211

    Article  CAS  PubMed  Google Scholar 

  11. Barake M, Klibanski A, Tritos NA (2014) Effects of recombinant human growth hormone therapy on bone mineral density in adults with growth hormone deficiency: a meta-analysis. J Clin Endocrinol Metab 99:852–860

    Article  CAS  PubMed  Google Scholar 

  12. Tritos NA, Greenspan SL, King D, Hamrahian A, Cook DM, Jönsson PJ, Wajnrajch MP, Koltowska-Häggstrom M, Biller BM (2011) Unreplaced sex steroid deficiency, corticotropin deficiency, and lower IGF-I are associated with lower bone mineral density in adults with growth hormone deficiency: a KIMS database analysis. J Clin Endocrinol Metab 96:1516–1523

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Colao A, Di Somma C, Pivonello R, Loche S, Aimaretti G, Cerbone G, Faggiano A, Corneli G, Ghigo E, Lombardi G (1999) Bone loss is correlated to the severity of growth hormone deficiency in adult patients with hypopituitarism. J Clin Endocrinol Metab 84:1919–1924

    CAS  PubMed  Google Scholar 

  14. Rosén T, Wilhelmsen L, Landin-Wilhelmsen K, Lappas G, Bengtsson BA (1997) Increased fracture frequency in adult patients with hypopituitarism and GH deficiency. Eur J Endocrinol 137:240–245

    Article  PubMed  Google Scholar 

  15. Cartwright B, Robinson J, Seed PT, Fogelman I, Rymer J (2016) Hormone replacement therapy versus the combined oral contraceptive pill in premature ovarian failure: a randomized controlled trial of the effects on bone mineral density. J Clin Endocrinol Metab 101:3497–3505

    Article  CAS  PubMed  Google Scholar 

  16. Gotherstrom G, Bengtsson B-A, Bosæus I, Johannsson G, Svensson J (2007) Ten-year GH replacement increases bone mineral density in hypopituitary patients with adult onset GH deficiency. Eur J Endocrinol 156:55–56

    Article  CAS  PubMed  Google Scholar 

  17. Mo D, Fleseriu M, Qi R, Jia N, Child CJ, Bouillon R, Hardin DS (2015) Fracture risk in adult patients treated with growth hormone replacement therapy for growth hormone deficiency: a prospective observational cohort study. Lancet Diabetes Endocrinol 3:331–338

    Article  CAS  PubMed  Google Scholar 

  18. Acibucu Fettah, Kilicli F, Sebila Dokmetas H (2014) Bone mineral density in Sheehan’s syndrome. Gynecol Endocrinol 30:532–535

    Article  CAS  PubMed  Google Scholar 

  19. Gokalp D, Tuzcu A, Bahceci M, Arikan S, Ozmen CA, Cil T (2009) Sheehan’s syndrome and its impact on bone mineral density. Gynecol Endocrinol 25:344–348

    Article  CAS  PubMed  Google Scholar 

  20. Chihaoui M, Yazidi M, Chaker F, Belouidhnine M, Kanoun F, Lamine F, Ftouhi B, Sahli H, Slimane H (2016) Bone mineral density in Sheehan’s syndrome; prevalence of low bone mass and associated factors. J Clin Densitom 19:413–418

    Article  PubMed  Google Scholar 

  21. Tanriverdi F, Unluhizarci K, Kula M, Guven M, Bayram F, Kelestimur F (2016) Effects of 18-month of growth hormone (GH) replacement therapy in patients with Sheehan’s syndrome. Growth Horm IGF Res 15:231–237

    Article  CAS  Google Scholar 

  22. Shatrugna V, Kulkarni B, Kumar PA, Rani KU, Balakrishna N (2005) Bone status of Indian women from a low-income group and its relationship to the nutritional status. Osteoporos Int 16:1827–1835

    Article  PubMed  Google Scholar 

  23. Sheila C. Vir and Richa Malik, Nutrition Situation of Women in India (2015) Current status, implications on child undernutrition and challenges ahead. Statistics and applications {ISSN 2454-7395(online)} Volume 13, Nos. 1&2, (New Series), pp. 71–84 (http://ssca.org.in/media/8._Nutrition_Situation_of_WomenCurrent_StatusImplications_on_Child_Undernutrition.pdf. Accessed on 23 June 2017

  24. Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP, Murad MH, Weaver CM (2011) Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 96:1911–1930

    Article  CAS  Google Scholar 

  25. ISCD official position statement-adults. http://www.iscd.org/official-positions/2015-iscd-official-positions-adult/. Accessed on 23 June 2017

  26. Population based reference standards of peak bone mineral density of Indian males and females—an ICMR multi-centre task force study (2010) Indian Council of Medical Research New Delhi. (www.icmr.nic.in/final/ICMR%20Tech%20Report%20_BMDRefStds2010.pdf). Accessed on 23 June 2017

  27. Genant HK, Wu CY, van Kuijk C, Nevitt MC (1993) Vertebral fracture assessment using a semiquantitative technique. J Bone Miner Res 8:1137–1148

    Article  CAS  PubMed  Google Scholar 

  28. Kelestimur F, Jonsson P, Molvalilar S, Gomez JM, Auernhammer CJ, Colak R, Koltowska-Häggström M, Goth MI (2005) Sheehan’s syndrome: baseline characteristics and effect of 2 years of growth hormone replacement therapy in 91 patients in KIMS–Pfizer International Metabolic Database. Eur J Endocrinol 152:581–587

    Article  CAS  PubMed  Google Scholar 

  29. De Laet C, Kanis JA, Odén A, Johanson H, Johnell O, Delmas P, Eisman JA, Kroger H, Fujiwara S, Garnero P, McCloskey EV, Mellstrom D, Melton LJ 3rd, Meunier PJ, Pols HA, Reeve J, Silman A, Tenenhouse A (2005) Body mass index as a predictor of fracture risk: a meta-analysis. Osteoporos Int 16:1330–1338

    Article  PubMed  Google Scholar 

  30. Emaus N, Wilsgaard T, Ahmed LA (2005) Impacts of body mass index, physical activity, and smoking on femoral bone loss: the Tromsø study. J Bone Miner Res 29:2080–2089

    Article  Google Scholar 

  31. Warensjö E, Byberg L, Melhus H, Gedeborg R, Mallmin H, Wolk A, Michaëlsson K (2011) Dietary calcium intake and risk of fracture and osteoporosis: prospective longitudinal cohort study. BMJ 342:d1473

    Article  PubMed  PubMed Central  Google Scholar 

  32. Arya V, Bhambri R, Godbole MM, Mithal A (2004) Vitamin D status and its relationship with bone mineral density in healthy Asian Indians. Osteoporos Int 15:56–61

    Article  CAS  PubMed  Google Scholar 

  33. Popat VB, Calis KA, Vanderhoof VH, Cizza G, Reynolds JC, Sebring N, Troendle JF, Nelson LM (2009) Bone mineral density in estrogen-deficient young women. J Clin Endocrinol Metab 94:2277–2283

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Isotton AL, Wender MC, Casagrande A, Rollin G, Czepielewski MA (2012) Effects of oral and transdermal estrogen on IGF1, IGFBP3, IGFBP1, serum lipids, and glucose in patients with hypopituitarism during GH treatment: a randomized study. Eur J Endocrinol 166:207–213

    Article  CAS  PubMed  Google Scholar 

  35. Fazeli PK, Klibanski A (2014) Determinants of GH resistance in malnutrition. J Endocrinol 220:R57–R65

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Foo J-P, Hamnvik O-P, Mantzoros CS (2012) Optimizing bone health in anorexia nervosa and hypothalamic amenorrhea: new trials and tribulations. Metabolism 61:899–905

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

The financial support provided by Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, (PGI/DIR/RC/717/2011) as an intra-mural grant to Dr SB Yadav is acknowledged.

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  1. Purnima Agarwal and Ramesh Gomez contributed equally to this work.

Authors and Affiliations

  1. Department of Endocrinology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, 226014, India

    Purnima Agarwal, Ramesh Gomez, Eesh Bhatia & Subhash Yadav

Authors
  1. Purnima Agarwal
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  2. Ramesh Gomez
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  3. Eesh Bhatia
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  4. Subhash Yadav
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Correspondence to Subhash Yadav.

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The studies have been approved by the appropriate institutional and/or national research ethics committee and have been performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.

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Agarwal, P., Gomez, R., Bhatia, E. et al. Decreased bone mineral density in women with Sheehan’s syndrome and improvement following oestrogen replacement and nutritional supplementation. J Bone Miner Metab 37, 171–178 (2019). https://doi.org/10.1007/s00774-018-0911-6

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  • DOI: https://doi.org/10.1007/s00774-018-0911-6

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