At what age does Cushing's syndrome typically present?

Age of Presentation in Cushing's Syndrome

Cushing's syndrome typically presents in the third to fourth decade of life in adults, but when it occurs in children, the mean age at presentation is 12.3 ± 3.5 years, with endogenous cases being extraordinarily rare before age 18. 1, 2

Age Distribution by Population

Pediatric Population

• Endogenous Cushing's syndrome is extraordinarily rare before age 18 years, with the disorder being much less common in children than adults 1
• The mean age at presentation in pediatric cases is 12.3 ± 3.5 years (range 5.7–17.8 years) 2, 3
• Only 2% of cases occur before age 11 years 1
• In a retrospective study of 855 patients, 7.7% reported onset before age 13 years, with early onset associated with stronger genetic susceptibility and more widespread disease 1
• Among 59 pediatric patients studied (ages 4-20 years), the presentation occurred predominantly in adolescence 4

Adult Population

• Classic Cushing's syndrome in adults has an estimated incidence of 1 case per 100,000 persons annually 5
• The incidence of endogenous Cushing's syndrome ranges from 2 to 8 per million people annually in the general population 6
• Subclinical Cushing's syndrome, which is much more common, has an estimated prevalence of 79 cases per 100,000 persons 5

Age-Related Clinical Differences

Prepubertal vs. Postpubertal Presentation

• In children over age 6, Cushing's disease (pituitary adenoma) is the most common cause of Cushing's syndrome (75-80%), while adrenal causes predominate in younger children 1, 2
• Prepubertal children show male predominance (71% male), contrasting sharply with the 79% female predominance seen in adults 2, 3
• Boys tend to present with more aggressive disease, including higher BMI, shorter height, and higher ACTH levels compared to girls 2, 3

Age-Specific Clinical Features

• The hallmark presentation in prepubertal children is growth failure combined with weight gain, making the disorder somewhat easier to detect than in post-pubertal adolescents or adults 1
• Mean age of patients presenting with striae was 15.2 ± 2.3 years, compared to 10.3 ± 3.3 years in those without striae, suggesting striae develop more commonly in older pediatric patients 7
• The youngest patient with CDKN1B-attributable disease (MEN4 syndrome) presented at age 30 with acromegaly 1

Critical Diagnostic Considerations by Age

Pediatric-Specific Screening

• Unexplained weight gain combined with declining height velocity or decreasing height standard deviation score (SDS) has high sensitivity for identifying Cushing's syndrome in children and avoids unnecessary testing in simple obesity 2
• Growth deceleration (subnormal growth velocity with height SDS below mean while BMI SDS rises above mean) is the critical distinguishing feature from common obesity 2
• Very few obese children actually have Cushing's syndrome, making the growth criterion essential for appropriate screening 2

Genetic Syndromes and Age

• Germline mutations (MEN1, RET, AIP, PRKAR1A, CDKN1B, DICER1, SDHx, CABLES1) may predispose children to Cushing's disease, though screening is usually reserved for cases with family history or syndromic features 1
• Early onset Cushing's syndrome (before age 13) is associated with stronger genetic susceptibility 1

Common Pitfalls

• Do not dismiss Cushing's syndrome in obese children without evaluating growth velocity, as this is the key discriminating feature 2
• Do not assume all pediatric cases present in adolescence, as 7.7% can present before age 13 and 2% before age 11 1
• Do not apply adult diagnostic criteria directly to children, as test performances and clinical presentations differ significantly 1
• Recognize the sex distribution reversal: prepubertal cases are predominantly male (71%), while adult cases are predominantly female (79%) 2, 3