CORTICOSTEROIDS & ADRENAL DIABETES

The Adrenal Glands are composed of two distinct parts, the adrenal medulla & the adrenal cortex. The Adrenal medulla secretes two hormones EPINEPHRINE & 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 & 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

1) Aldosterone: It is very potent & accounts for 95% or more of Mineralocorticoid activity .It is secreted by ZONA GLOMERULOSA which is the outer most layer of Adrenal cortex.

2) Desoxycorticosterone: Is 1/15th as potent as Aldosterone & secreted in very small quantities.

3) Corticosterone : Has very slight activity

4) 9alpha –Flurocortisol: It is synthetic & has slightly more potent than Aldosterone.

5) Cortisol: Has very slight mineralocorticoid activity.

6) Cortisone: Is synthetic & has very slight activity.

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

1) Cortisol: Very potent & accounts for about 95% of all
Glucocorticoid activity .It is secreted by The ZONA FASCICULATA which is the middle layer of Adrenal cortex & the deepest layer – ZONA RETICULARIS.

2) Corticosterone: About 4 % of total glucocorticoid activity but much less potent than Cortisol.

3) Cortisone: Synthetic but as potent as Cortisol.

4) Prednisone: Synthetic but 4 times as potent as Cortisol.

5) Methylprednisone: Synthetic but 5 times as potent as Cortisol.

6) Dexamethasone: Synthetic but 30 times as potent as Cortisol.

**** It is clear from the above list that some of these hormones have both Glucocorticoid & Mineralocorticoid activities.


The level of Cortisol needs to be just right. Too much or too little can cause problems. The amount of Cortisol which is made in the adrenal glands is controlled by another hormone called Adreno-cortico-trophic hormone, or ACTH for short (and sometimes just called Corticotrophin). ACTH is made in the pituitary gland.

The pituitary gland lies just below the brain. It makes several hormones, including ACTH. The amount of ACTH made by the pituitary gland is largely controlled by another hormone called Corticotrophin releasing hormone (CRH). CRH is made in a small part of the brain called the hypothalamus, which is just above the pituitary gland. CRH 'stimulates' certain cells in the pituitary to make ACTH.

ACTH passes into the bloodstream, is carried to the adrenal glands, and 'stimulates' the adrenal gland to make Cortisol. If the level of ACTH increases in the bloodstream, the adrenals make more cortisol.But, Cortisol has a negative 'feedback' effect on the pituitary gland. As the level of Cortisol in the bloodstream rises above a certain level, it 'turns down' the amount of ACTH made by the pituitary. This means the adrenal is then stimulated less, and less Cortisol is made. So, the level of Cortisol is kept within a certain range - just enough as is needed by the body.

MAJOR FUNCTION OF GLUCOCORTICOIDS :

By far the best known metabolic effect of Cortisol & 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 six to ten 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 & 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:

1) 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 & the abnormal cells in the adenoma are not 'turned down' by feedback from the high levels of cortisol.

2) Non Cancerous or malignant tumor of Adrenal gland causes excessive production of Cortisol.

3) Hyperplasia of Adrenal gland also leads to more production of Cortisol.

4) Some malignant & 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

5) Excessive intake of Alcohol also increases Cortisol levels.

6) 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 than avoidance of alcohol will cure Adrenal diabetes. If it is due to tumor of Pituitary or Adrenal gland or other part of body than removal of tumor will cure the Diabetes.