In this paper, we present an infant with CS who had a large unilateral (left) adrenal mass. Pediatric adrenocortical tumors (ACTs) are rare in infancy and occur primarily in children between one to five years of age (60%), with a peak in incidence below 4 years of age (0.4 cases per million). Nearly half of these ACTs are adrenocortical carcinoma (2
). In a registry of 254 pediatric patients with ACTs, 55% presented with virilization alone. Only 5.5% of the children in this registry had isolated CS, and this tended to occur in older children (median age, 12.6 years) (13). Increased androgen production in infancy and early childhood ACTs can be explained by the structure of the adrenal gland at birth. At this time, the inner fetal zone constitutes 85-90% of the gland; the primary steroid product of the inner fetal zone is dehydroepiandrosterone sulphate (14
Our infant presented with isolated CS without any clinical or biochemical evidence of hyperandrogenism, which is rare. To the best of our knowledge, CS due to adrenal adenoma presenting early in infancy has not been reported previously. Also intriguing is the benign nature of the tumor despite its large size. To control the profound hypercortisolemic state and thus reduce the peri-operative morbidity and mortality, ketoconazole was administered to our patient pre-operatively. Ketoconazole is an imidazole derivative, originally used as an anti-fungal drug but is one of the most commonly used drugs in the medical management of both Cushing’s disease and CS, as well as in preparing these patients for surgery (15
). Ketoconazole inhibits several steps of adrenal steroidogenesis including the cholesterol side-chain cleavage enzyme, 17α-hydroxylase and 17,20-lyase, thus has a beneficial effect in CS. In addition, it has a direct inhibitory effect on ACTH release from the pituitary (15
). In adults, ketoconazole is used in doses of 400-1200 mg/day in divided doses (15). Common side effects are gastrointestinal upset and skin rash. Liver dysfunction in the form of mild reversible increase in transaminase levels can occur in about 10% of the patients (17
). However, serious hepatic injury is rare and can rarely be fatal (17
Post-operative hydrocortisone supplementation following surgery for adrenal adenoma causing CS is necessary as the contralateral adrenal gland is usually hypoplastic secondary to prolonged suppressed ACTH secretion from the pituitary due to CS. This explains the lack of visualization of the contralateral adrenal in our patient and the adrenal insufficiency state documented on the 8th post-operative day.
From the registry of a series consisting of 254 pediatric ACTs, those with completely resected tumors weighing less than 200 g and without metastasis had a five-year event-free survival rate of 91%. Age less than four years was independently associated with better prognosis. A multivariate analysis showed an adjusted odds ratio of 2.6 for patients aged less than four years (13
). Complete biochemical resolution of hypercortisolism post-operative with favorable histological features is probably predictive for a good prognosis in our patient.
To summarize, our patient who presented at age 4 months with obesity and growth retardation is possibly the youngest ever reported case of CS due to adrenal adenoma. Surgical removal of the mass resulted in rapid weight loss with biochemical and clinical resolution of CS.