Abstract
Objective: Paediatric Cushing's syndrome (CS) remains a challenge to diagnose and exclude. We assessed the accuracy of 24-hour urinary free cortisol (UFC) determination in children referred for suspected CS. Design: We conducted a retrospective study of paediatric patients referred to our centre with suspected CS between 1982 and 2014. Patients: Of 66 subjects (mean age 12.9 years; range 4.4-16.9), there were 47 cases of CS (29 males), which included Cushing's disease (CD; 39 patients, 25 males), primary pigmented nodular adrenocortical disease (8 patients, 4 males) and 19 ‘controls' (6 males) in whom the diagnosis of CS was excluded. Measurements: The subjects had between one and five 24-hour UFC collections analysed by radioimmunoassay, chemiluminescent immunoassay or liquid chromatography-mass spectrometry. The data were normalised, corrected for body surface area (m2) and assessed using receiver operating characteristic analysis and an independent two-tailed t test. Results: The diagnostic accuracy of 24-hour UFC for CS was excellent (area under the curve 0.98, 95% CI 0.946-1.00, sensitivity 89%, specificity 100%). Conclusions: Twenty-four-hour UFC is a reliable and practical investigation with high diagnostic accuracy for paediatric CS. However, further investigations may be required if the UFC is normal but there is a high diagnostic suspicion of CS.
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References
1.
Chan LF, Storr HL, Grossman AB, Savage MO: Pediatric Cushing's syndrome: clinical features, diagnosis, and treatment. Arq Bras Endocrinol Metabol 2007;51:1261-1271.
[PubMed]
2.
Kanter AS, Diallo AO, Jane JA Jr, Sheehan JP, Asthagiri AR, Oskouian RJ, et al: Single-center experience with pediatric Cushing's disease. J Neurosurg 2005;103(suppl 5):413-420.
[PubMed]
3.
Lissau I: Overweight and obesity epidemic among children. Answer from European countries. Int J Obes Relat Metab Disord 2004;28(suppl 3):S10-S15.
[PubMed]
4.
Biller BM, Grossman AB, Stewart PM, Melmed S, Bertagna X, Bertherat J, et al: Treatment of adrenocorticotropin-dependent Cushing's syndrome: a consensus statement. J Clin Endocrinol Metab 2008;93:2454-2462.
[PubMed]
5.
Storr HL, Alexandraki KI, Martin L, Isidori AM, Kaltsas GA, Monson JP, et al: Comparisons in the epidemiology, diagnostic features and cure rate by transsphenoidal surgery between paediatric and adult-onset Cushing's disease. Eur J Endocrinol 2011;164:667-674.
[PubMed]
6.
Magiakou MA, Mastorakos G, Oldfield EH, Gomez MT, Doppman JL, Cutler GB Jr, et al: Cushing's syndrome in children and adolescents. Presentation, diagnosis, and therapy. N Engl J Med 1994;331:629-636.
[PubMed]
7.
Shah NS, George J, Acharya SV, Lila AR, Sarathi V, Bandgar TR, et al: Cushing disease in children and adolescents: twenty years' experience in a tertiary care center in India. Endocr Pract 2011;17:369-376.
[PubMed]
8.
Stratakis CA: Cushing syndrome in pediatrics. Endocrinol Metab Clin North Am 2012;41:793-803.
[PubMed]
9.
Bista B, Beck N: Cushing syndrome. Indian J Pediatr 2014;81:158-164.
[PubMed]
10.
Nieman LK, Biller BM, Findling JW, Newell-Price J, Savage MO, Stewart PM, et al: The diagnosis of Cushing's syndrome: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metabolism 2008;93:1526-1540.
[PubMed]
11.
Guignat L, Bertherat J: The diagnosis of Cushing's syndrome: an Endocrine Society Clinical Practice Guideline: commentary from a European perspective. Eur J Endocrinol 2010;163:9-13.
[PubMed]
12.
Kageyama K, Oki Y, Sakihara S, Nigawara T, Terui K, Suda T: Evaluation of the diagnostic criteria for Cushing's disease in Japan. Endocr J 2013;60:127-135.
[PubMed]
13.
Lila AR, Sarathi V, Jagtap VS, Bandgar T, Menon P, Shah NS: Cushing's syndrome: stepwise approach to diagnosis. Indian J Endocrinol Metab 2011;15(suppl 4):S317-S321.
[PubMed]
14.
Invitti C, Pecori Giraldi F, de Martin M, Cavagnini F: Diagnosis and management of Cushing's syndrome: results of an Italian multicentre study. Study Group of the Italian Society of Endocrinology on the Pathophysiology of the Hypothalamic-Pituitary-Adrenal Axis. J Clin Endocrinol Metab 1999;84:440-448.
[PubMed]
15.
Joshi SM, Hewitt RJ, Storr HL, Rezajooi K, Ellamushi H, Grossman AB, et al: Cushing's disease in children and adolescents: 20 years of experience in a single neurosurgical center. Neurosurgery 2005;57:281-285; discussion 285.
[PubMed]
16.
Elamin MB, Murad MH, Mullan R, Erickson D, Harris K, Nadeem S, et al: Accuracy of diagnostic tests for Cushing's syndrome: a systematic review and metaanalyses. J Clin Endocrinol Metab 2008;93:1553-1562.
[PubMed]
17.
Batista DL, Riar J, Keil M, Stratakis CA: Diagnostic tests for children who are referred for the investigation of Cushing syndrome. Pediatrics 2007;120:e575-e586.
[PubMed]
18.
Martinelli CE, Sader Milani S, Previato JK, Figueira M, Rangel Montenegro AP, Miraki-Moud F, et al: Final height in patients with idiopathic short stature and high growth hormone responses to stimulation tests. Horm Res 2007;67:224-230.
[PubMed]
19.
Savage MO: The combined pituitary function test is not indicated in the routine investigation of short stature. Clin Endocrinol 2000;52:679.
[PubMed]
20.
Odeniyi IA, Fasanmade OA: Urinary free cortisol in the diagnosis of Cushing's syndrome: how useful? Niger J Clin Pract 2013;16:269-272.
[PubMed]
21.
Pecori Giraldi F, Ambrogio AG, De Martin M, Fatti LM, Scacchi M, Cavagnini F: Specificity of first-line tests for the diagnosis of Cushing's syndrome: assessment in a large series. J Clin Endocrinol Metab 2007;92:4123-4129.
[PubMed]
22.
Elias PC, Martinez EZ, Barone BF, Mermejo LM, Castro M, Moreira AC: Late-night salivary cortisol has a better performance than urinary free cortisol in the diagnosis of Cushing's syndrome. J Clin Endocrinol Metab 2014;99:2045-2051.
[PubMed]
23.
Alexandraki KI, Grossman AB: Is urinary free cortisol of value in the diagnosis of Cushing's syndrome? Curr Opin Endocrinol Diabetes Obes 2011;18:259-263.
[PubMed]
24.
Falkner B, Daniels SR: Summary of the Fourth Report on the Diagnosis, Evaluation, and Treatment of High Blood Pressure in Children and Adolescents. Hypertension 2004;44:387-388.
[PubMed]
25.
Newell-Price J, Trainer P, Besser GM, Grossman A: The diagnosis and differential diagnosis of Cushing's and pseudo-Cushing's states. Endocr Rev 1999;19:647-672.
[PubMed]
26.
Storr HL, Chan LF, Grossman AB, Savage MO: Paediatric Cushing's syndrome: epidemiology, investigation and therapeutic advances. Trends Endocrinol Metab 2007;18:167-174.
[PubMed]
27.
Newell-Price J, Morris DG, Drake WM, Korbonits M, Monson JP, Besser GM, et al: Optimal response criteria for the human CRH test in the differential diagnosis of ACTH-dependent Cushing's syndrome. J Clin Endocrinol Metab 2002;87:1640-1655.
[PubMed]
28.
Lienhardt A, Grossman AB, Dacie JE, Evanson J, Huebner A, Afshar F, et al: Relative contributions of inferior petrosal sinus sampling and pituitary imaging in the investigation of children and adolescents with ACTH-dependent Cushing's syndrome. J Clin Endocrinol Metab 2001;86:5711-5714.
[PubMed]
29.
Cameron N: The methods of auxological anthropometry; in Faulkner F, Tanner JT (eds): Human Growth. 2. Postnatal Growth. New York, Plenum Press, 1978, pp 35-90.
30.
Marshall WA, Tanner JM: Variations in the pattern of pubertal changes in boys. Arch Dis Child 1970;45:13-23.
[PubMed]
31.
Marshall WA, Tanner JM: Variations in pattern of pubertal changes in girls. Arch Dis Child 1969;44:291-303.
[PubMed]
32.
Raff H, Raff JL, Findling JW: Late-night salivary cortisol as a screening test for Cushing's syndrome. J Clin Endocrinol Metab 1998;83:2681-2686.
[PubMed]
33.
Gafni RI, Papanicolaou DA, Nieman LK: Nighttime salivary cortisol measurement as a simple, noninvasive, outpatient screening test for Cushing's syndrome in children and adolescents. J Pediatr 2000;137:30-35.
[PubMed]
34.
Arnaldi G, Angeli A, Atkinson AB, Bertagna X, Cavagnini F, Chrousos GP, et al: Diagnosis and complications of Cushing's syndrome: a consensus statement. J Clin Endocrinol Metab 2003;88:5593-5602.
[PubMed]
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