The article “Cushing Syndrome in Childhood” by Drs Parish et al in the January issue of Pediatrics in Review (10.1542/pir.2022-005732) discusses a clinical diagnosis that I find personally intriguing for four challenging themes that play off one another.
Theme number one. I begin with a literary digression. Recently a Wall Street Journal editorial on bankruptcy mentioned the character Bill in author Ernst Hemingway’s first published novel, The Sun Also Rises. When asked how he became bankrupt, Bill responds, “Two ways. Gradually and then suddenly.” Well, that is how Cushing syndrome behaves. The classic pattern described by Parish et al of “central adiposity with increased dorsocervical fat pads and moon facies… acne, hirsutism…plethora, bruising, skin atrophy, fungal infections, and in cases of ACTH-dependent Cushing syndrome, skin darkening and purple striae from high ACTH levels” may take months to years before becoming recognizable. Cushing syndrome is clandestine, sneaking up on you… gradually and then suddenly. (How many times have you cared for a patient who had persistent symptoms, knowing there was a cause but never finding it, when suddenly the answer was obvious? Yep, gradually then suddenly.)
Theme number two. Drs Parish et al in “Cushing Syndrome in Childhood” mention that, “endogenous Cushing syndrome is extremely rare in the pediatric population with an overall incidence of 0.7–2.4 per million adults.” I don’t think I have taken care of 1 million patients over the years, yet in my career, both in private practice and in academics, I encountered four patients with endogenous Cushing syndrome, ranging in age from infancy to adolescence. In clinical practice, we approach each day expecting common illnesses to occur commonly. But the unexpected does occur. Cushing syndrome reminds me that numbers do not always apply.
Theme number three. Numbers do apply. In the case of suspected endogenous Cushing syndrome, the patient’s age most likely indicates the source of pathology. If a patient with suspected Cushing syndrome is less than 6 years of age, an adrenal tumor is the likely cause. If the patient is greater than 6 years of age, excess pituitary ACTH secretion is the culprit. Sure enough, the infant and the toddler with suspected Cushing syndrome that I cared for had adrenal adenomas, and the two adolescents with suspected Cushing syndrome had pituitary adenomas.
Theme number four. The clock is ticking. As Drs Parish et al state, “early detection and treatment are essential to reduce associated acute and long-term morbidity and potential death.” While Cushing syndrome and its cause take time to declare, complications due to prolonged exposure to excessive glucocorticoids are also developing. Obesity, hypertension, cognitive delay, anxiety, depression, and emotional lability come to mind. Drs Parish et al also state, “Post-treatment challenges include optimization of growth and pubertal development, normalization of metabolism and body composition, and promotion of psychosocial health.” Better to treat before complications arise. But to catch Cushing syndrome early, you have to be looking for it, which gets back to theme number one of “gradually then suddenly.” One should shorten that time between gradual and sudden.
Cushing syndrome is a great exemplar for clinical reasoning, reminding me that pediatrics is practiced in part by keen observation, intuition, experience, judgement, and use of evidence-based medicine in a race to prevent harm. So when you see that anxious, hypertensive, slightly overweight patient, could you, by chance, be seeing someone with Cushing syndrome?