Chronic Adrenocortical Insufficiency

Overview
  • Chronic Adrenocortical Insufficiency is the clinical syndrome associated with a slow, progressive decline in adrenocortical hormone synthesis leading to deficient adrenocortical hormone levels.
Etiologies
  • Overview
    • Chronic Adrenocortical Insufficiency can be caused by a variety of etiologies. These etiologies may be primary, referring to defects of the adrenal cortex itself , or secondary, referring to insufficient stimulation of an otherwise normal adrenal cortex by pituitary-derived ACTH.
  • Primary Adrenal Insufficiencies (AKA: Addison Disease)
    • Primary adrenal insufficiencies are referred to as "Addison Disease" and involve direct pathology of the adrenal cortices leading to defects in corticosteroid synethesis. It should be pointed out that the adrenal cortices possess signficiant functional reserve and over 90% of the endocrine organs must be destroyed for an individual to reach a clinical threshold. The most common etiology of primary adrenal insufficiency is autoimmune destruction of the adrenal cortices which typically occur with other autoimmune processes such as Hashimoto Thyroiditis, Type I DM, or pernicious anemia.
    • Destruction of the adrenal glands by metastatic neoplasms may also be responsible. Addison disease may also arise from infectious destruction of adrenal cortex by a variety of microorganisms. Mycobacterium tuberculosis-mediated destruction is usually associated with active infection and was historically the most common cause. Disseminated infections with endemic mycoses, especially Histoplasma and Coccidioides can also be a cause of adrenal destruction, although rarely. Finally, in AIDS Patients HIV itself is not to blame but other viruses such as CMV or Cryptococcus neoformans may infectiously destroy the adrenal cortices.
  • Secondary Adrenal Insufficiencies
    • Secondary adrenal insufficiencies arise due to deficient ACTH secretion typically caused by sources of hypopituitarism such as Sheehan Syndrome.
Laboratory Findings
  • Primary versus secondary etiologies of chronic adrenal insufficiency can be distinguished by assaying the levels of circulating ACTH. In primary etiologies plasma ACTH levels are typically high as the absence of adrenocortical cortisol lifts negative feedback on pituitary ACTH secretion. Secondary etiologies are characterized by low ACTH levels as destruction of the anterior pituitary naturally results in reduced ACTH secretion.
Clinical Consequences
  • The symptomology of chronic adrenal insufficiency begins insidiously and is progressive in course. Common non-specific symptoms include fatigue and weakness as well as nausea, vomiting, anorexia, and weight loss. Deficiencies in cortisol synthesis typically lead to hypoglycemia. Deficiencies in aldosterone synthesis leading to hypotension arise only late in the course as maintenance of aldosterone secretion requires only very low levels of ACTH.
  • A characteristic sign of adrenal insufficiency observed only in addisonian patients is a tan hyper-pigmentation of the skin. This arises because the ACTH peptide possess a small fragment that can stimulate melanocytes to produce pigment. This only occurs at very high, nonphysiological levels of ACTH and likely reflects an vestigial molecular function of ACTH that is no longer. Notably, the US president J.F. Kennedy suffered from Addison Disease and this is thought to be the source of his year-round tan.