Relative Adrenal Insufficiency

Chapter 75 Relative Adrenal Insufficiency



Jamie M. Burkitt, DVM, DACVECC



KEY POINTS



• Cortisol is an important hormone involved in modulation of inflammation and regulation of vascular tone.

• Relative adrenal insufficiency (RAI) is common in humans with sepsis and other types of critical illness.

• Human patients with RAI have poor vascular responsiveness and worse survival than those with normal hypothalamic-pituitary-adrenal axis (HPA) function.

• The best method for diagnosing RAI is unknown.

• Low dosages of hydrocortisone improve pressor responsiveness and survival in humans with RAI and septic shock.

• RAI likely occurs in a subpopulation of critically ill dogs and cats.

• Appropriate methods for the diagnosis and management of RAI in dogs and cats are unknown.


INTRODUCTION


Cortisol is a hormone released by the adrenal glands in small amounts in a circadian rhythm, and in larger amounts during times of physiologic stress. It has many important homeostatic functions including regulation of carbohydrate, lipid, and protein metabolism; immune system modulation; ensuring proper production of catecholamines and function of adrenergic receptors; and stabilizing cell membranes. A classic example demonstrating the importance of cortisol function is the patient with glucocorticoid-only hypoadrenocorticism. Patients with minimal endogenous corticosteroid production show clinical signs of gastrointestinal disturbance, weight loss, and collapse, particularly in stressful situations. These patients can be treated successfully with glucocorticoid supplementation.


Serum cortisol concentration is determined by the hormonal cascade and negative feedback mechanisms of the hypothalamic-pituitary-adrenal (HPA) axis. The hypothalamus produces corticotropin-releasing hormone (CRH), which stimulates the anterior pituitary to release adrenocorticotropic hormone (ACTH). ACTH in circulation stimulates the zona fasciculata and zona reticularis of the adrenal gland to produce and release cortisol. Cortisol has negative feedback action on both the hypothalamic release of CRH and the pituitary release of ACTH. Thus, when circulating cortisol concentration is low, CRH and ACTH will increase, stimulating the adrenal glands to produce more cortisol. The increased serum cortisol concentration inhibits the release of more CRH and ACTH.


Research over the past decade has shown that abnormalities of HPA axis function are common in human patients with severe sepsis and septic shock, conditions that frequently carry a mortality rate of 50% or more in both human and veterinary medicine.1-5 Many well-conceived and well-performed clinical studies have found RAI, also called critical illness-related corticosteroid insufficiency (CIRCI), in up to 77% of human patients with severe sepsis and septic shock.1,6-9 Unlike patients with classic hypoadrenocorticism, those with critical illness-associated RAI usually have normal to elevated basal serum cortisol concentration, but a blunted cortisol response to an ACTH stimulation test. Therefore their adrenal dysfunction truly is relative—it is believed that although the adrenal glands can make and release cortisol, the quantity is inadequate for the degree of physiologic stress. Following recovery from sepsis, HPA axis dysfunction resolves.10



ASSOCIATED PRIMARY ILLNESSES


Patients with relative adrenal insufficiency (RAI) include humans with severe sepsis and septic shock,1,6-9 severe hepatic disease,11 acute myocardial infarction,12 and hemorrhagic shock.13 It is important to note that although many illnesses are associated with RAI, all humans who have RAI are critically ill; RAI has not been documented in patients with localized infections, mild to moderate hepatopathy, or stable heart disease.



SUSPECTED PATHOPHYSIOLOGY


The underlying mechanisms of RAI are unknown. Studies have suggested that the inflammatory cytokines interleukin-614,15 or tumor necrosis factor,16,17 or corticostatin peptides produced by immune cells18 may interfere with HPA axis function. Also, there have been reports of RAI associated with adrenal hemorrhage in critically ill humans.19,20 Adrenal hypoperfusion and microvascular disease from disseminated intravascular coagulation may contribute. Even if glucocorticoids are produced in adequate amounts in critically ill patients, they may not be able to exert their effects. There is evidence that corticosteroid receptor numbers may be decreased in patients with hemorrhagic and septic shock.21 Cytokines may cause corticosteroid receptor dysfunction.22



SPECIES AFFECTED


It is widely accepted that RAI occurs in critically ill humans but strong evidence of RAI does not yet exist in veterinary medicine. One study of 20 dogs sequentially admitted to a veterinary intensive care unit failed to find HPA axis abnormalities in any patients,23 although another study in critically ill septic dogs found a 48% incidence of RAI.24 A study in cats admitted to an intensive care unit did not demonstrate RAI in septic cats, but did find HPA axis abnormalities in cats with neoplasia.25 Another study showed a decreased response to exogenous ACTH in septic cats compared with a group of normal cats.26 Thus it appears that RAI probably occurs in some subpopulations of critically ill dogs and cats. Clinical evidence in other species is unavailable.

Related posts:

  1. Deteriorating Mental Status
  2. Hyperthermia and Fever
  3. Ventilator-Associated Lung Injury
  4. Allergic Airway Disease in Dogs and Cats and Feline Bronchopulmonary Disease

Stay updated, free articles. Join our Telegram channel
Tags:
Sep 10, 2016 | Posted by in SMALL ANIMAL | Comments Off on Relative Adrenal Insufficiency

Full access? Get Clinical Tree
Get Clinical Tree app for offline access