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Management of Cushing syndrome in children and adolescents: experience of a single tertiary centre

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Abstract

The diagnosis and management of paediatric Cushing syndrome (CS) is highly challenging. This study aims to characterise its presentation, diagnosis, management and outcome by a retrospective case review of 30 patients (14 females) followed at a single tertiary paediatric endocrinology centre over a 30-year period. At presentation, median age was 8.9 years (0.2–15.5) and the commonest manifestations were weight gain (23/30), hirsutism (17/30), acne (15/30) and hypertension (15/30). Growth retardation was present in 11/30. Median body mass index (BMI) was +2.1 standard deviation score (SDS) (−6.5 to +4.6). Urinary free cortisol (UFC) was abnormal in 17/18 (94 %), midnight cortisol in 27/27 (100 %) and low-dose dexamethasone suppression (LDDS) test in 20/20 (100 %). High-dose dexamethasone suppression (HDDS) test was abnormal in 6/6 (100 %) of adrenal tumours, 1/10 (10 %) of Cushing disease (CD) and 1/2 (50 %) of ectopic tumours. Bilateral inferior petrosal sinus sampling (IPSS) identified five CD cases and one ectopic tumour. All patients underwent surgery and subsequently required cortisol replacement. Final diagnoses were 16 CD, 11 adrenal disease, 2 ectopic ACTH-secreting lesions and 1 case of unidentified aetiology. One year post-diagnosis, median BMI was 0.5 SDS (−2.5 to +3.7), hypertension was present in 4/14 (28 %), and 43 % (12/30) of individuals were off hydrocortisone.

Conclusion: The prevalence of the clinical manifestations differs from that reported in other series. Screening tests were highly sensitive, with UFC, midnight cortisol and LDDS performing well. One year post-treatment, BMI and BP normalised in the majority of patients and almost half of them were able to discontinue replacement hydrocortisone.

What is Known:

•Cushing syndrome is an extremely rare entity in the paediatric and adolescent age groups, so not many cohort studies have been published in this population.

•Several tests can be employed to firstly diagnose hypercortisolaemia and secondly identify the source of origin of it. The efficacy and safety of these tests in children is still uncertain.

What is New:

•This study includes cases due to the different aetiologies of endogenous hypercortisolaemia (pituitary, adrenal and ectopic hypercortisolaemia) allowing us to compare the differences in presentation, diagnosis, management and long-term outcome between the groups.

•There is a difference in the prevalence of Cushing syndrome symptoms and in the performance of the tests in our cohort compared to previously published studies in the literature.

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Abbreviations

ACTH:

Adrenocorticotropic hormone

BMI:

Body mass index

BP:

Blood pressure

CD:

Cushing disease

CRH:

Corticotrophin-releasing hormone

CS:

Cushing syndrome

CT:

Computed tomography

DEXA:

Dual-energy X-ray absorptiometry

HDDS:

High-dose dexamethasone suppression

IPSS:

Inferior petrosal sinus sampling

LDDS:

Low-dose dexamethasone suppression

MIBG:

Metaiodobenzylguanidine

MRI:

Magnetic resonance imaging

PET:

Positron emission tomography

PPNAD:

Primary pigmented nodular adrenal disease

SDS:

Standard deviation scores

UFC:

Urinary free cortisol

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Authors’ contributions

M. Güemes, P. Murray and M. Dattani designed the study, collected the patients’ data and wrote the manuscript. The rest of the authors have significantly contributed to this study with patient data and writing up of the manuscript.

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Authors and Affiliations

  1. London Centre for Paediatric Endocrinology and Diabetes, Great Ormond Street Hospital for Children, London, UK

    Maria Güemes, Philip G Murray, Caroline E Brain, Helen A Spoudeas, Catherine J Peters, Peter C Hindmarsh & Mehul T Dattani

  2. Section of Genetics and Epigenetics in Health and Disease, Genetics and Genomic Medicine Programme, UCL Institute of Child Health, University College London, 30 Guilford Street, London, WC1N 1EH, UK

    Maria Güemes, Peter C Hindmarsh & Mehul T Dattani

Authors
  1. Maria Güemes
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  2. Philip G Murray
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  3. Caroline E Brain
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  4. Helen A Spoudeas
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  5. Catherine J Peters
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  7. Mehul T Dattani
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Corresponding author

Correspondence to Mehul T Dattani.

Ethics declarations

This study was conducted as part of a quality assessment audit and as such ethical approval was not required.

Conflict of interest

The authors declare that they have no competing interests.

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There is no source of funding or financial assistance to declare.

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Communicated by Beat Steinmann

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Güemes, M., Murray, P.G., Brain, C.E. et al. Management of Cushing syndrome in children and adolescents: experience of a single tertiary centre. Eur J Pediatr 175, 967–976 (2016). https://doi.org/10.1007/s00431-016-2727-5

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  • DOI: https://doi.org/10.1007/s00431-016-2727-5

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