Cortisol is mainly a stress hormone and helps maintain blood volume & vascular tone (all for blood pressure), maintains blood glucose (by proteolysis n gluconeogenesis and glycogen breakdown) and produces RBCs for oxygen, so that brain gets enough blood to make nutrients available to brain for use during stress. Also promotes insulin resistance & fat breakdown so that rest of the body use fatty acid instead of glucose. Metabolically it’s receptors are present only in limb fat and hence mobilises fat to blood n central body.
It also suppresses immunity by suppressing lymphocytes n eiosinophils, whereas it cause demargination of neutrophils and promotes RBC synthesis from bone marrow. Cortisol related neutrophilia is not accompanied by thrombocytosis ( unlike infections etc which elevates both neutrophils n platelets).
Lack of cortisol would hence cause
1: Low BP not responding to other measures such as fluids and ionotropes unless we give cortisol.
2: Hypovolemia & electrolyte imbalance. Diarrhea, vomiting and abdominal pain etc due to increased inflammatory activity in GIT. Hence acute Addison can be confused with gastroenteritis but in this case patient’s BP usually doesn’t respond to fluid replacement.
3:Hypoglycemia along with low BP is very good clue to think of endocrinal cause for both and Addison or Hypopituitrism are on top of D/D.
4: Increased lymphocytes n Eisinophils
5: Weight loss & low grade fever to make it look like chronic inflammatory diseases such as chronic infections, malignancies or autoimmune diseases etc. This is due to increased inflammatory activity in body. Weight loss is more pronounced in chronic addison and is due to inflammation and dehydration.
6: Pale skin due to lack of ACTH in pituitary related disease or hyper pigmentation due to adrenal disease with causing high ACTH. Adrenal would also cause deficiency of Aldosterone causing hyperkalemia, Low Na and marked dehydration whereas pituitary related can have other features of hypopituitrism. When not clear, take blood samples and treat as pituitary disease and replace cortisol and thyroxine both till the time it’s obvious.
Most common cause of acute Addison is exogenous Cushing where either patient stop taking cortisol or the dose isn’t increased with stress. Patient looks Cushing but present with Addison’s.
Adrenal damage can be due to autoimmune damage (most common cause in the developed countries) & TB (most common in countries where TB is prevalent). Metastatic deposits can also present as Addison’s.
Other causes for acute include haemorrhage, acute infections such as bacteremia, surgical resection etc. Congenital adrenal hyperplasia (all types have Addison’s disease accompanied with either Hyper aldosteronism (17 hydroxylase) or Hyper androgenism (21 & 11 hydroxylase deficiency- 11 will have normal aldosterone functions despite low Aldosterone as 11 DOCA works as Aldosterone whereas 21 deficiey will have Aldosterone deficiency).
Hormonal levels (ACTH, cortisol, renin- Aldosterone ratio, DHEA-S and pituitary hormonal assays are needed in addition to electrolytes etc.
SynACHTin test can be used to diagnosis subclinical Addison’s disease or to check adrenal reserve.
Imaging with CT or MRI for adrenals and MRI for pituitary will be needed to identify any structural cause such as tumour or adenoma etc.
Replace cortisol. Increase the dose during stress. Hydrocortisone is the most structurally resemblance to cortisol.
Aldosterone replacement will be needed too if electrolytes deficiency isn’t corrected by cortisol replacement.