Adrenal insufficiency is a serious condition in which the production or action of the glucocorticoids, mineralocorticoids and androgens made by the adrenal cortex is reduced or absent. Before synthetic glucocorticoids were introduced, it was a fatal condition.
The adrenal cortex is driven by a chain of signals: the hypothalamus supplies CRH (corticotropin-releasing hormone) and the anterior pituitary supplies ACTH (adrenocorticotropic hormone). Adrenal insufficiency is classified by the level at which this axis fails: primary when the adrenal gland itself is affected, secondary when the anterior pituitary cannot supply enough ACTH, and tertiary when the hypothalamus cannot supply enough CRH. That level organises most of what follows, because it decides which hormones are lost and therefore what the patient shows.
Choose a route through the topic
The first five notes follow adrenal insufficiency in general, and the pathophysiology is the place to start, because the later notes rely on how the three forms differ. Read them in this order:
- Pathophysiology of Adrenal Insufficiency explains why symptoms appear only once more than 90% of the adrenal cortex is destroyed, and why the secondary and tertiary forms keep normal mineralocorticoid secretion.
- Causes of Adrenal Insufficiency gives the epidemiology and the causes of the primary, secondary and tertiary forms.
- Clinical Manifestation of Adrenal Insufficiency covers the chronic signs and symptoms, the acute adrenal crisis and its precipitants, and the features that separate the secondary and tertiary forms from the primary one.
- Diagnosis of Adrenal Insufficiency covers the laboratory tests, the standard- and low-dose ACTH stimulation tests, the hormone patterns that separate the three forms, and the workup for the underlying cause.
- Treatment of Adrenal Insufficiency covers glucocorticoid and mineralocorticoid replacement, the prevention and emergency treatment of adrenal crisis, and the long-term outlook.
Congenital adrenal hyperplasia is a group of inherited defects in the same steroid pathway. Here the disorder lies in a single enzyme of hormone synthesis rather than in a level of the axis, so it is best read after the general notes, beginning with the overview:
- Congenital Adrenal Hyperplasia: Overview introduces congenital adrenal hyperplasia, its inheritance, and the two most common enzyme deficiencies.
- Congenital Adrenal Hyperplasia: Pathophysiology explains how a block in cortisol synthesis raises ACTH and shunts precursors into androgens, the classical and non-classical forms, and the origin of salt wasting.
- Congenital Adrenal Hyperplasia: Clinical Manifestation covers virilization of the external genitalia, the effects on puberty, fertility and stature, salt wasting, and the phenotypes of 21-hydroxylase deficiency.
- Congenital Adrenal Hyperplasia: Diagnosis covers when to suspect CAH in a newborn, the steroid assays and newborn screening, and the confirmatory test.
- Congenital Adrenal Hyperplasia: Treatment covers replacement therapy, monitoring, and the approach to non-classical disease.