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Death in pediatric Cushing syndrome is uncommon but still occurs

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Abstract

Cushing syndrome (CS) in children is rare. Delayed diagnosis and treatment of CS may be associated with increased morbidity and, unfortunately, mortality. We performed a retrospective review of all patients with CS under the age of 18 years referred to the National Institutes of Health (NIH) from 1998 to 2013 in order to describe deceased patients among cases of pediatric CS referred to the National Institutes of Health (NIH). The deaths of four children (three females and one male), aged 7.5–15.5 years (mean age 11.2 years) with length of disease 2–4 years, were recorded among 160 (2.5 %) children seen at or referred to the NIH over the last 15 years. All died at different institutions, prior to coming to the NIH (two) or after leaving NIH (two). Presenting symptoms included increasing weight and decreasing height gain, facial plethora, dorsocervical fat pad (webbed neck), striae, headache, vision disturbances, and depression and other mood or behavior changes; there were no differences between how these patients presented and the others in our cohort. The causes of CS in the deceased patients were also not different, in fact, they spanned the entire spectrum of CS: pituitary disease (one), ectopic corticotropin production (one), and primary adrenal hyperplasia (one). In one patient, the cause of CS could not be verified. Three died of sepsis and one due to residual disease and complications of the primary tumor.

Conclusions: Despite the advances in early diagnosis and treatment of pediatric CS, a 2.5 % mortality rate was identified in a large cohort of patients with this condition referred to an experienced, tertiary care referral center (although these deaths occurred elsewhere). Pediatricians need to recognize the possibility of death, primarily due to sepsis, in a patient with pediatric CS and treat accordingly.

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Abbreviations

ACTH:

Adrenocorticotropic hormone

ACC:

Adrenocortical carcinomas

ACT:

Adrenocortical tumors

CD:

Cushing disease

CS:

Cushing syndrome

CT:

Computerized tomography

GH:

Growth hormone

iMAD:

Isolated micronodular adrenocortical disease

IPSS:

Inferior petrosal sinus sampling

MRI:

Magnetic resonance imaging

NIH:

National Institutes of Health

oCRH test:

Ovine cortisol releasing hormone test

PPNAD:

Primary pigmented nodular adrenal dysplasia

RR:

Reference range

TSS:

Transsphenoidal surgery

yr:

Year

24 h UFC:

24 h urine free cortisol

1 mg DST:

Low-dose (1 mg) dexamethasone suppression test

8 mg DST:

High-dose (8 mg) dexamethasone suppression test or Liddle’s test

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Acknowledgments

This research was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health (NIH). We thank Diane Cooper, MSLS, NIH Library, for providing assistance in writing this manuscript. We also thank the families of the patients who so kindly provided us with data on the events surrounding their children's course before or after their hospitalization at the NIH. Finally we want to thank in particular Dr. William H. Lagarde, Raleigh, NC who worked relentlesly on the investigation of the cause of death of one of the patients reported in this article. We hope that their stories will lead to an ever decreasing mortality in Cushing syndrome.

Conflict of interest

All the authors have nothing to disclose.

Author information

Authors and Affiliations

  1. Section on Endocrinology and Genetics and Pediatric Endocrinology Inter-Institute Training Program, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health Clinical Research Center, 10 Center Drive, Building 10, Room 1-3330, MSC1103, Bethesda, MD, 20892, USA

    Alexandra Gkourogianni, Maya B. Lodish, Mihail Zilbermint, Charalampos Lyssikatos, Elena Belyavskaya, Margaret F. Keil & Constantine A. Stratakis

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  1. Alexandra Gkourogianni
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  2. Maya B. Lodish
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  3. Mihail Zilbermint
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  4. Charalampos Lyssikatos
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  5. Elena Belyavskaya
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  6. Margaret F. Keil
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  7. Constantine A. Stratakis
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Corresponding author

Correspondence to Maya B. Lodish.

Additional information

Communicated by Beat Steinmann

Authors’ summary

In a cohort of 160 patients with pediatric Cushing syndrome (CS) studied over 15 years, four patients died. Early diagnosis and treatment of complications of CS is vital to minimize mortality of this disease among children.

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Gkourogianni, A., Lodish, M.B., Zilbermint, M. et al. Death in pediatric Cushing syndrome is uncommon but still occurs. Eur J Pediatr 174, 501–507 (2015). https://doi.org/10.1007/s00431-014-2427-y

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  • DOI: https://doi.org/10.1007/s00431-014-2427-y

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