Endocrine Abstracts

Background: Adrenal cortical carcinoma (ACC) in children is a rare and aggressive disease. Further characterisation of the presenting features and biochemical markers are needed to support earlier diagnosis. Refractory hypertension related to high cortisol concentrations at presentation, and post-operative decrease in cortisol can be challenging to manage. Focus on endocrine management has not been previously described.

Case Series: 34 patients (age 2 weeks–10 years (y), median 2.35y, 17 female) presenting with an ACC (1996-2021). Patients were either low (n = 15), borderline (n = 2), or high (n = 17) malignancy risk based on histology and tumour size. The most frequent presentations included virilisation (n = 29), hypertension (n = 20), cushingoid appearance (n = 15), and rarely gynaecomastia. 38% patients had an identified genetic mutation, either TP53 (n = 10, n = 8 high risk), or a mutation associated with Beckwith Wiedemann syndrome (n = 3, borderline n = 1 or high risk n = 2). Elevated cortisol concentrations were seen in most patients, with loss of circadian rhythm in one third. Androgen concentrations were frequently elevated (Androstenedione 88%, DHEA-S 61%, Testosterone 93%). Urine steroid profile pre-surgery revealed elevated androgen and cortisol metabolites. Refractory hypertension necessitated the use of metyrapone (n = 3) and ketoconazole (n = 3). All patients underwent surgical resection, a laparoscopic approach evolving over time, and 32% received adjuvant chemotherapy. Elevated biochemical markers resolved post-surgery, and most patients received intravenous hydrocortisone infusions post-operatively. All were discharged on hydrocortisone replacement (10 mg/m²/day; duration 0.1-8y, median 1y). Those treated with mitotane (n = 8) required a higher dose (15-17 mg/m²/day), with added fludrocortisone (n = 3), and thyroxine (n = 2). The mortality rate was 32% in this cohort, although comorbidities were contributing factors in at least two patients.

Conclusion: This series describes the most frequent presentations in this rare and aggressive disease, and highlights the essential role of genetic diagnosis in influencing disease progression and treatment. Our practice has evolved to include post-operative intravenous hydrocortisone infusion in all patients to mitigate the effect of the rapid fall in cortisol. The duration of hydrocortisone requirement in this cohort was highly variable. Future research is required into the use of newer agents such as pasireotide or mifepristone to decrease cortisol concentrations in those with refractory hypertension, as they may have fewer side-effects and reduce morbidity.