The diagnosis and treatment of adrenal insufficiency during childhood and adolescence

Abstract

The diagnosis and treatment of adrenal insufficiency in childhood and adolescence poses a number of challenges. Clinical features of chronic adrenal insufficiency are vague and non-specific, and mimic many other causes of chronic ill health. A range of diagnostic tests are available for the assessment of adrenal function, all of which have advantages and disadvantages. Cortisol responses to these tests may vary with age and between genders. Knowledge of normal cortisol levels during health and ill health in childhood is also limited, and the cortisol replacement therapies available in clinical practice enable only crude mimicry of physiological patterns of cortisol secretion. An awareness of the limitations of diagnostic tests and treatments is important, and critical clinical assessment, integrating clinical and biochemical data, is essential for the diagnosis and treatment of children with suspected adrenal insufficiency. The aim of this review is to draw on data from clinical studies to inform a pragmatic approach to the child presenting with symptoms of chronic adrenal insufficiency. Clinical features of primary and secondary adrenal insufficiency, and syndromes associated with these diagnoses are described. Factors to consider when selecting a diagnostic test of adrenal function and interpretation of test results are considered. Finally, the limitations of cortisol replacement therapy are also discussed.

Adrenal Crises in Children: Perspectives and Research Directions

“…These include hypotension, abdominal pain and vomiting, a reduced level of consciousness, weakness, and lethargy [1, 2, 13, 15]. A number of biochemical abnormalities, including hyponatraemia, hyperkalaemia (in PAI) and, occasionally, hypercalcaemia may also be found [13, 15, 37].…”

“…The cornerstone of AC prevention is the institution of a protocol of escalating doses of glucocorticoid (“stress dosing”) in the event of an intercurrent illness or injury, when the requirement for cortisol is greater than that in the circulation [1, 6, 13, 15]. All parents and older children should be educated about the need for stress dosing.…”

“…These events cause considerable morbidity and occasional mortality in both children [1-6] and adults with chronic AI [7-12]. While the precise incidence of ACs in childhood is unknown, estimates from data in mainly adult populations indicate an approximate frequency of 5–10 ACs/100 patient years (PY) [13-15].…”

Vanishing 17-Hydroxyprogesterone Concentrations in 21-Hydroxylase Deficiency

“…However, the boy grew well and had normal weight pointing against overtreatment with glucocorticoids. Adrenal suppression by steroid treatment is characterized by growth failure [5, 6], which could be observed in the boy only before the diagnosis of ulcerative colitis. Most importantly, steroid treatment leading to adrenal insufficiency is characterized by lack of ACTH production (secondary adrenal insufficiency) [5, 6] in contrast to our boy demonstrating a high increase in ACTH after withdrawal of hydrocortisone treatment.…”

“…An adrenal cortex insufficiency due to prednisolone treatment of ulcerative colitis or inhaled steroids for bronchial asthma [5, 6] seems unlikely since adrenal cortex insufficiency persisted in the boy years after the end of these treatments. Adrenal insufficiency has been reported to remain months after removal of glucocorticoid-producing tumors; however, an adrenal insufficiency 3 years after finishing prednisolone treatment or removal of a glucocorticoid-producing tumor has not been reported in the literature to the best of our knowledge [7, 8].…”