Skip to main content

Advertisement

SpringerLink
Log in

Pregnancy-associated Cushing’s disease? An exploratory retrospective study

  • Published:
Pituitary Aims and scope Submit manuscript

Abstract

Purpose

In most clinical series of Cushing’s disease (CD), over 80% of patients are women, many of whom are of reproductive age. The year following pregnancy may be a common time to develop CD. We sought to establish the incidence of CD onset associated with pregnancy.

Methods

A retrospective review was conducted for patients with biochemically-proven CD. Demographics, clinical history, biochemistry, imaging, pathology, and outcomes were reviewed. Pregnancy-associated CD was defined as symptom onset within 1 year of childbirth.

Results

Over 10 years, 77 patients including 64 women (84%), with CD underwent endonasal surgery. Of the 64 women, 64% were of reproductive age (15–45 years) at the time of diagnosis, and 11 (27%) met criteria for pregnancy-associated CD. Of these 11 women, median number of pregnancies prior to onset of CD was 2 (range 1–4) compared to zero (range 0–7) for 30 other women with CD onset during reproductive age (p = 0.0024). With an average follow-up of 47 ± 34 months, sustained surgical remission rates for woman with pregnancy-associated CD, other women of reproductive age, and women not of reproductive age were 91%, 80% and 83%, respectively. The average lag-time from symptom onset to diagnosis for women with pregnancy-associated CD was 4 ± 2 years.

Conclusions

In this exploratory study, over one quarter of women of reproductive age with CD appeared to have symptomatic disease onset within 1 year of childbirth. This relatively high rate of pregnancy-associated CD suggests a possible causal relationship related to the stress of pregnancy and pituitary corticotroph hyperactivity in the peripartum period. This possible association suggests a heightened degree of clinical suspicion and biochemical testing for CD may be warranted after childbirth. Further study of this possible link between pregnancy and CD is warranted.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

Abbreviations

ACTH:

Adrenocorticotrophic hormone

CD:

Cushing’s disease

CRH:

Corticotroph releasing hormone

DNA:

Deoxyribonucleic acid

HPA:

Hypothalamic–pituitary–adrenal

IPSS:

Inferior petrosal sinus sampling

MRI:

Magnetic resonance imaging

References

  1. Etxabe J, Vazquez JA (1994) Morbidity and mortality in Cushing’s disease: an epidemiological approach. Clin Endocrinol (Oxf) 40:479–484. https://doi.org/10.1111/j.1365-2265.1994.tb02486.x

    Article  CAS  Google Scholar 

  2. Hammer GD, Tyrrell JB, Lamborn KR et al (2004) Transsphenoidal microsurgery for Cushing’s disease: initial outcome and long-term results. J Clin Endocrinol Metab 89:6348–6357

    Article  CAS  PubMed  Google Scholar 

  3. Lindholm J, Juul S, Jørgensen JOL et al (2001) Incidence and late prognosis of Cushing’s syndrome: a population-based study. J Clin Endocrinol Metab 86:117–123. https://doi.org/10.1210/jc.86.1.117

    Article  CAS  PubMed  Google Scholar 

  4. Mancini T, Kola B, Mantero F et al (2004) High cardiovascular risk in patients with Cushing’s syndrome according to 1999 WHO/ISH guidelines. Clin Endocrinol (Oxf) 61:768–777. https://doi.org/10.1111/j.1365-2265.2004.02168.x

    Article  Google Scholar 

  5. Pikkarainen L, Sane T, Reunanen A (1999) The survival and well-being of patients treated for Cushing’s syndrome. J Intern Med 245:463–468

    Article  CAS  PubMed  Google Scholar 

  6. Orth DN (1995) Cushing’s syndrome. N Engl J Med 332:791–803. https://doi.org/10.1056/NEJM199503233321207

    Article  CAS  PubMed  Google Scholar 

  7. Arnaldi G, Angeli A, Atkinson AB et al (2003) Diagnosis and complications of Cushing’s syndrome: a consensus statement. J Clin Endocrinol Metab 88:5593–5602

    Article  CAS  PubMed  Google Scholar 

  8. Dallapiazza RF, Oldfield EH, Jane JA (2015) Surgical management of Cushing’s disease. Pituitary 18:211–216. https://doi.org/10.1007/s11102-015-0646-5

    Article  PubMed  Google Scholar 

  9. Lindsay JR, Nieman LK (2005) The hypothalamic-pituitary-adrenal axis in pregnancy: challenges in disease detection and treatment. Endocr Rev 26:775–799. https://doi.org/10.1210/er.2004-0025

    Article  CAS  PubMed  Google Scholar 

  10. The American College of Obstetricians and Gynecologists Committee on Gynecologic Practice and American Society for Reproductive Medicine Practice Committee (2014) Female age-related fertility decline. Fertil Steril 101:633–634. https://doi.org/10.1016/j.fertnstert.2013.12.032

    Article  Google Scholar 

  11. Esposito F, Dusick JR, Fatemi N, Kelly DF (2007) Graded repair of cranial base defects and cerebrospinal fluid leaks in transsphenoidal surgery. Oper Neurosurg 60:295–304. https://doi.org/10.1227/01.NEU.0000255354.64077.66

    Article  Google Scholar 

  12. Lobo B, Zhang X, Barkhoudarian G et al (2015) Endonasal endoscopic management of parasellar and cavernous sinus meningiomas. Neurosurg Clin N Am 26:389–401. https://doi.org/10.1016/j.nec.2015.03.004

    Article  PubMed  Google Scholar 

  13. Dinç H, Esen F, Demirci A et al (1998) Pituitary dimensions and volume measurements in pregnancy and post partum. MR assessment. Acta Radiol 39:64–69

    PubMed  Google Scholar 

  14. Scheithauer BW, Sano T, Kovacs KT et al (1990) The pituitary gland in pregnancy: a clinicopathologic and immunohistochemical study of 69 cases. Mayo Clin Proc 65:461–474. https://doi.org/10.1016/S0025-6196(12)60946-X

    Article  CAS  PubMed  Google Scholar 

  15. Karaca Z, Tanriverdi F, Unluhizarci K, Kelestimur F (2010) Pregnancy and pituitary disorders. Eur J Endocrinol 162:453–475. https://doi.org/10.1530/EJE-09-0923

    Article  CAS  PubMed  Google Scholar 

  16. Nolten WE, Lindheimer MD, Rueckert PA et al (1980) Diurnal patterns and regulation of cortisol secretion in pregnancy. J Clin Endocrinol Metab 51:466–472. https://doi.org/10.1210/jcem-51-3-466

    Article  CAS  PubMed  Google Scholar 

  17. Carr BR, Parker CR, Madden JD et al (1981) Maternal plasma adrenocorticotropin and cortisol relationships throughout human pregnancy. Am J Obstet Gynecol 139:416–422

    Article  CAS  PubMed  Google Scholar 

  18. Mastorakos G, Ilias I (2003) Maternal and fetal hypothalamic-pituitary-adrenal axes during pregnancy and postpartum. Ann N Y Acad Sci 99:136–149

    Article  Google Scholar 

  19. Jornayvaz FR, Assie G, Bienvenu-Perrard M et al (2011) Pregnancy does not accelerate corticotroph tumor progression in Nelson’s syndrome. J Clin Endocrinol Metab 96:E658–E662. https://doi.org/10.1210/jc.2010-2235

    Article  CAS  PubMed  Google Scholar 

  20. World (2018) Fertility rate, total (births per woman). In: World Bank. https://data.worldbank.org/indicator/SP.DYN.TFRT.IN?

Download references

Acknowledgements

We would like to thank the John Wayne Cancer Institute at Providence Saint John’s Health Center in Santa Monica, CA for their ongoing support of our research.

Author information

Authors and Affiliations

  1. Pacific Neuroscience Institute, John Wayne Cancer Institute at Providence’s Saint John’s Health Center, 2125 Arizona Ave., Santa Monica, CA, 90404, USA

    Sheri K. Palejwala, Andrew R. Conger, Amy A. Eisenberg, Pejman Cohan, Chester F. Griffiths, Garni Barkhoudarian & Daniel F. Kelly

  2. Department of Neurosurgery, Geisinger Health System, Danville, PA, USA

    Andrew R. Conger

Authors
  1. Sheri K. Palejwala
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Andrew R. Conger
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Amy A. Eisenberg
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Pejman Cohan
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Chester F. Griffiths
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Garni Barkhoudarian
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Daniel F. Kelly
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Daniel F. Kelly.

Ethics declarations

Conflict of interest

All authors declare that they have no conflict of interest to disclose.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Palejwala, S.K., Conger, A.R., Eisenberg, A.A. et al. Pregnancy-associated Cushing’s disease? An exploratory retrospective study. Pituitary 21, 584–592 (2018). https://doi.org/10.1007/s11102-018-0910-6

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11102-018-0910-6

Keywords

Search

Navigation