Corticosteroids and Adrenal Diabetes

The Adrenal Glands are composed of two distinct parts, the adrenal medulla and the adrenal cortex. The adrenal medulla secretes two hormones Epinephrine and Norepinephrine in response to sympathetic stimulation. The adrenal cortex secretes an entirely different group of hormones called corticosteroids. There are two types of corticosteroids:

  1. Mineralocorticoids
  2. Glucocorticoids.

Both, glucocorticoids and mineralocorticoids, are steroid compounds.

Mineralocorticoids: The mineralocorticoids have gained this name because they especially affect electrolytes of the extra cellular fluids (sodium & potassium). Below are names of some important mineralocorticoids:

  • Aldosterone: It is very potent and accounts for 95% or more of mineralocorticoid activity. It is secreted by Zona Glomerulosa, which is the outer most layer of adrenal cortex.
  • Desoxycorticosterone: Is 1/15th as potent as aldosterone and secreted in very small quantities.
  • Corticosterone : Has very slight activity
  • 9 Alpha-Fluorocortisol: It is synthetic and has slightly more potent than aldosterone.
  • Cortisol: Has very slight mineralocorticoid activity.
  • Cortisone: Is synthetic and has very slight activity.

Glucocorticoids: The glucocorticoids have gained their name because they exhibit an important effect in increasing blood Glucose concentration. They also affect protein and fat metabolism. Below are names of some important glucocorticoids:

  • Cortisol: Very potent an accounts for about 95% of all glucocorticoid activity. It is secreted by The zona fasciculata which is the middle layer of adrenal cortex and the deepest layer – Zona Reticularis.
  • Corticosterone: About 4 % of total glucocorticoid activity but much less potent than cortisol.
  • Cortisone: Synthetic, but as potent as cortisol.
  • Prednisone: Synthetic, but four times as potent as cortisol.
  • Methylprednisone: Synthetic, but five times as potent as cortisol.
  • Dexamethasone: Synthetic, but 30 times as potent as cortisol.

It is clear from the above list that some of these hormones have both glucocorticoid and mineralocorticoid activities.

By far the best known metabolic effect of cortisol and other glucocorticoids on metabolism is their ability to stimulate gluconeogenesis (a metabolic process in which glucose is formed from non-carbohydrate carbon substrates such as lactate , glycerol , and glucogenic amino acids by the liver). Cortisol often increases the rate of gluconeogenisis as much as 6-10 folds. Cortisol causes gluconeogenesis by increasing all the enzymes in the liver cell which are required to convert amino acids to glucose. Also, Cortisol causes mobilization of amino acids from the extra hepatic tissues (mainly muscles). As a result, more amino acids become available in the plasma to enter into the gluconeogenisis process of the liver and thereby to promote the formation of glucose. Not only this Cortisol causes a moderate decrease in the rate of glucose utilization by the cells every where in the body.

ADRENAL DIABETES:
Excessive production of cortisol leads to Adrenal Diabetes. Adrenal Diabetes has many similarities with Pancreatic Diabetes. In Adrenal Diabetes, the blood glucose concentration is 50 % or more above normal levels. Administration of insulin lowers the blood glucose concentration only to a moderate amount. Therefore, it said that Adrenal Diabetes is moderately sensitive to insulin.

Causes of Excessive Production of Cortisol:

  • Non-cancerous tumor of Pituitary Gland (Pituitary Adenoma). In this condition, the pituitary gland produces more ACTH (corticotrophin) which stimulates the adrenal gland to produce more cortisol and the abnormal cells in the adenoma are not ‘turned down’ by feedback from the high levels of cortisol.
  • Non-cancerous or malignant tumor of adrenal gland causes excessive production of cortisol.
  • Hyperplasia of adrenal gland also leads to more production of cortisol.
  • Some malignant and non-cancerous tumors in other parts of body sometimes cause excessive production of cortisol by producing ectopic ACTH. ACTH is a hormone which stimulates the adrenal glands to produce cortisol. Normally, ACTH is produced by pituitary gland. However, some rare tumors like that of lung cancer produce ectopic ACTH which stimulates the Adrenals to produce cortisol.
  • Excessive intake of alcohol also increases cortisol levels.
  • Depression is also responsible for higher production of cortisol.

Treatment:
Depends upon the cause of excessive production of cortisol. If it is due to excessive intake of alcohol, then avoidance of alcohol will cure adrenal diabetes. If it is due to tumor of pituitary or adrenal gland or other part of body, then removal of tumor will cure the diabetes.

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