ESPE Yearbook of Paediatric Endocrinology

Brief summary: Chemotherapy, radiotherapy and corticosteroids used to treat acute lymphoblastic leukemia (ALL) can have endocrine side-effects, such as adrenal insufficiency (AI). This cross-sectional single-centre study aimed to assess AI frequency after completion of ALL therapy, by comparison to healthy controls matched for age and sex, and to identify biomarkers of adrenal function and reserve.

Study patients were at least 16 months post-completion of steroid therapy. Patients and controls had a fasting blood sample collected for plasma cortisol, aldosterone, plasma renin activity (PRA), dehydroepiandrostendione-sulfate (DHEAS), adrenocorticotropic hormone (ACTH), anti-adrenal antibodies, fasting blood glucose, sodium and potassium. The diurnal profile of cortisol and 24-hour urinary excretion of free cortisol was also assessed. Additionally, patients with ALL underwent adrenal imaging and low-dose ACTH testing to assess their adrenal reserve. The study population was divided into 3 groups: 1) up to 2 years remission; 2) 2–5 years remission; 3) >5 years remission.

ACTH testing revealed impaired cortisol responses in 4/43 (9%) ALL survivors, two of whom needed hydrocortisone replacement therapy, and showed also low levels of free urinary cortisol, midnight cortisol and DHEAS. Antibodies against the adrenal cortex were negative and adrenal ultrasound was normal in the entire study population. Urinary free cortisol positively correlated with evening and midnight cortisol levels, DHEAS, systolic and diastolic blood pressure, without differences between groups with different remission time.

Of the treatment-related endocrinopathies, AI is certainly the most important to be diagnosed, due to the risk of adrenal crisis, a life-threatening event. Therefore, it would be very useful to identify a simple and inexpensive clinical screening modality for AI. It is well known that long-duration glucocorticoid therapy causes central AI, which is usually transient, even if the different impacts of dexamethasone and prednisolone on the severity of adrenal suppression and recovery time have not been clearly demonstrated.

These authors concluded that cortisol levels after ACTH testing, DHEAS, urinary free cortisol and midnight plasma cortisol were the essential indicators of HPA function. Of these, DHEAS levels seem the most practical marker, as it has been shown that DHEAS levels return to normal 2 weeks before complete HPA recovery, and they correlate with urinary free cortisol. The half-life of DHEAS is longer than that of cortisol and diurnal fluctuation is minimal, so that a single sample is sufficient, regardless time of the day or food intake.