Chapter 5: Adrenal Disorders

OVERVIEW

Disorders of adrenal function occur at all ages and may be an isolated problem or one of multiple organs involved in certain syndromes. Principles that are helpful in evaluating the most common pediatric clinical situations in which an adrenal disorder is suspected include the following:

1. Patients with early pubic hair development (premature pubarche) will have in order of frequency:

   1. Idiopathic premature adrenarche

   2. Central precocious puberty

   3. Nonclassical (late-onset) congenital adrenal hyperplasia (NC-CAH)

   4. Adrenal or gonadal tumor

   5. Exogenous testosterone exposure

2. Patients with “simple” obesity are distinguished from those with Cushing syndrome by the following clinical features:

   1. Cushing syndrome often develops rapidly.

   2. Children with Cushing syndrome do not grow well in height, whereas those with obesity often have accelerated height velocity.

   3. Patients with Cushing syndrome often have signs of androgen excess.

3. Patients with adrenocortical insufficiency will have either:

   1. Primary adrenal failure, usually with symptoms of both glucocorticoid and mineralocorticoid (ie, salt loss) deficiency. The most common causes are:

      1. CAH (ambiguous genitalia in females)

      2. Autoimmune Addison disease (often associated with other endocrinopathies)

      3. Adrenoleukodystrophy (ALD)

   2. Central adrenal insufficiency due to lack of adrenocorticotropic hormone (ACTH) stimulation of cortisol production, with symptoms of glucocorticoid deficiency alone. The most common causes:

      1. Suppression of the hypothalamic-pituitary-adrenal (HPA) axis following abrupt discontinuation of glucocorticoid treatment

      2. ACTH deficiency associated with multiple pituitary hormone deficiencies

GENERAL PRINCIPLES OF ADRENAL FUNCTION

The adrenal cortex secretes three classes of biologically active steroid hormones: glucocorticoids (cortisol), controlled by the HPA axis; mineralocorticoids (aldosterone), controlled by the renin-angiotensin system; and androgens (dehydroepiandrosterone [DHEA], DHEA sulfate, and androstenedione), controlled by an as yet uncharacterized trophic hormone.

Metabolic effects of steroid hormones are mediated by interaction with a specific cellular receptor. The ligand-activated steroid-receptor complex dimerizes, enters the nucleus of target cells, binds to various transcription factors, and forms stable complexes with specific “steroid-response elements” that then modulate transcription of specific target genes to exert the hormonal effects (see Chapter 1).

The embryologically and functionally distinct adrenal medulla secretes catecholamines, mainly epinephrine (adrenaline), stimulated by the sympathetic nervous system and by high cortisol levels from the adrenal cortex. The effects of epinephrine are mediated through adrenergic receptors, which produce tissue-specific effects.

THE ADRENAL GLAND

Anatomy

The adrenal glands lie at the upper pole of each kidney. Ectopic nodules (rests) of adrenocortical tissue derived from embryonic mesenchymal cells may be located in the broad ligaments of the female or in the testes or spermatic cords of the male. The size of the adrenal glands varies with age, mainly due to changes within the adrenal cortex (Figure 5-1). During gestation and at birth, the adrenal glands are much larger relative to body size than during adulthood, and at birth the weight of the glands is nearly that of adult glands (8-12 g). During the ...