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Acute Endocrinology:: From Cause to

Consequence
edited by Greet Van den Berghe
Water and sodium homeostasis: mineralocorticoid
and anti -diuretic hormone

Aldosterone is regulated by the renin-angiotensin-aldosterone system. The major


trigger for renin release is a fall in perfusion pressure, from hemorrhage,
hypotension, or a contraction of extracellular water volume after sodium loss.
Aldosterone enhances sodium reabsorption in the distal convoluted tubule in
exchange for potassium. Aldosterone insufficiency therefore results in inappropriate
natriuresis and potassium retention. The loss of salt and water may be catastrophic
during vomiting or diarrhoeal illness, with rapid deterioration to coma and death.
Anti -diuretic hormone (ADH) regulates free water excretion by increasing the
permeability of the collecting tubule to water. Its secretion is stimulated by
hyperosmolality and hypovolemia. In patients with chronic aldosterone insufficiency,
sodium depletion impairs the counter -current mechanism essential to establish a
hyperostomotic interstitium in the renal medulla, reducing ADH- medicated water
reabsorption and accelerating volume depletion.

Although adrenocortical hormone (ACTH) acutely stimulates aldosterone release, it


plays a minor role in the regulation of aldosterone secretion (3). Aldosterone
deficiency is not a feature of secondary adrenal failure and explains why acute
adrenal crisis is less frequently observed in secondary adrenal failure.
Glueocorticoid

Cortisol is required for the functioning of all tissues. It exerts important roles on
cardiovascular function, appetite, and on the immune system, properties that are
particularly relevant in understanding the pathophysiology of adrenal crisis.
CARDIOVASCULAR STABILITY

Vascular tone is maintained by 3 factors: adequate circulatory volume, cardiac

Acute Endocrinology:: From Cause to


Consequence
edited by Greet Van den Berghe
contractility, and peripheral vascular tone. Glucocorticoids and catecholamines
interact positively to maintain hemodynamic stability in human, by enhancing
catecholamine action in vascular smooth muscle (4).
A better understanding of the mechanism of their interactions has come from
animal studies. Glucocorticolds potentiate the response of catecholamines by
enhancing affinity to their receptors (5-8). The synthesis of major vasodilators by
endothelium, including prostacyclin and nitric oxide, is suppressed by
glucocorticoids (9-10).
Glucocorticoids stimulate cardiac function by enhancing contractility. Animal (1 1 )
and human (12) studies showed cardiac contractility to be markedly impaired in
glucocorticoid deficient state.
Glucocorticoids are also required for the normal functioning of chromaffin cells and
their capacity to produce adrenaline. Activity of phenylethanolamine Nmethyltransferase (PNMT), a rate -limiting enzyme in adrenaline synthesis, has been
shown (in animal studies) to be dependent on glucocorticoids trans- ported via the
intra-adrenal portal system (8). This dependency is evident in patients with isolated
glucocorticoid deficiency who manifest reduced synthesis of adrenaline both in
resting and stressed clinical states (13).
Glucocorticoid deficiency leads to circulatory collapse, reduced catecholamine
synthesis, vascular desensitisation to circulating catecholamines, inappropriate
vasodilation, and impaired cardiac contractility, which together with water and
sodium repletion due to aldosterone deficiency, represents the hallmark of adrenal
crisis.

APPETITE
Glucocorticoids play a central role in glucose metabolism, and regulate
energy storage and utilisation through interaction with the sympathetic nervous
system. An underappreciated effect of glucocorticoids is its potent orexigenic
property ( 14). The appetite stimulating effect of glucocorticoids may involve
mediation by the endocannabinoid system (/5). Both animal ( 16 ) and human (17)
studies have demonstrated an increase in appetite and high -fat food ingestion in

Acute Endocrinology:: From Cause to


Consequence
edited by Greet Van den Berghe
response to increased cortisol secretion from stress. The opposite occurs in
glucocorticoid deficient states. Patients lose their appetite; weight loss and cachexia
ensue as a consequence of advanced anorexia, impaired hepatic gluconeogenesis,
and defective mobilisation of substrates from peripheral fat and muscle stores.
Glucocorticoids such as dexamethasone, are sometimes used as appetite stimulants
in cachectic patients with advanced malignancy in the palliative care setting
IMMUNITY
Glucocorticoids are a potent suppressor of the immune system. Endogenous
glucocorticoids play an important role in the maintenance of host 'inflammatory'
homeostasis. The immune system is constitutively active (18); immune cells,
cytokines, and neuropept ides accumulate in injured tissue, forming
microinflammatory foci that facilitate tissue healing and regeneration (19).
Glucocorticoids exert important actions on leukocyte traffic 20), cytokines actions
(21), and adhesion molecule expression (22).
Equilibrium is maintained by the anti-inflammatory actions of glucocorticoids in
areas of tissue damage to facilitate healing.
The absence of glucocorticoids result in an enhanced state of inflammation,
causing an array of symptoms, which may be local or systemic. These symptoms