The A.G are two small sized glands(3-6 gm) located bilaterally above the kidney. Each gland is composed of a cortex and medulla. The medulla acts as a sympathetic ganglion that secretes epinephrine (mostly). The cortex comprises about 90% of gland which produces and secretes three steroids: Glucocorticoids. Mineralocorticoids. Androgens.
Zona gromerulosa (Aldosterone) Zona fasiculata (G.C) Zona reticularis (Androgens) All of these hormones are derived from cholesterol and share a common molecular nucleus.
Cortex
MedullaGlucocorticoids
Epinephrine
Cortisol
Nor-epinephrine
Corticosterone
Dopamine
Mineralocorticoids
Aldosterone
Deoxycorticosterone
Androgens
Dehydroepiandosterone
Androsteredione
Functions and effects Regulates carbohydrate, fat and protein synthesis. Maintains vascular reactivity Inhibits inflammation Maintains homeostasis during physical and emotional stress.
Increase blood levels and peripheral use of glucose Increase liver glucose output Initiates lipolysis Initiates proteolysis Gluconeogenic mechanisms
Glucose
AdipocytesMuscle Glycogen
Cortisol
Insulin
Adipocytes
Muscle Glycogen
This hormone inhibits: Lysosome release Prostaglandin production Eicosanoid and cytokine release Endothelial cell expression of intracellular and extracellular adhesion molecules that attract neutrophils Function of leukocytes
Circadian rhythm
Stress Surgery, sports,trauma, Illness, burns, fever, hypoglycemiaHypothalamus
CRH
Pituitary
Adrenal cortex
Cortisol 25MG
- Ve feed back
Compound
Anti-Infl. potencyM.C potency
Dose (mg)
Short acting (12hr)
Cortisol
1
2
20
Cortisone
0.8
2
25
Intermediate (12-36hr)
Prednisone
4
1
5
Prednisolone
4
1
5
Methylprednisolone
5
0
4
Triamcinilone
5
0
4
Long acting (36hr)
Paramethasone
10
0
2
Betamethasone
25
0
0.75
Dexamethasone
25
0
0.75
Aldosterone is the primary M.C secreted by the adrenal gland. Essential for Na and K balance and maintains extracellular fluid. Its action is on the distal tubule and collecting duct of kidney. Regulation is by the renin-angiotensin system,ACTH,Plasma Na and K levels.
Stimulation of secretion
Decrease in I.V. volume or Na imbalanceDecrease in renal B.P
Release of renin which activates angiotensin
Cortex
Aldosterone secretion
Rise in B.P
- ve feed back
Diminished R.A. release
Excess secretion Cushing Syndrome
Insufficient productionPituitary gland disease Hypothalamus disease Exogenous use
Primary (Addison's Disease)
Secondary Pituitary gland disease Hypothalamus disease Exogenous use
Primary Ad. Insufficiency (Addison's disease) is due to the destruction of the adrenal cortex: Idiopathic (autoimmune) Hemorrhage Sepsis Infectious disease (T.B., HIV, Fungal) Malignancy Drugs
THE SIGNS AND SYMPTOMS OF DISEASE RESULT FROM DEFICIENCY OF BOTH CORTISOL AND ALDOSTERONE. 2. CLINICAL EVIDENCE OCCURS WHEN 90% OF ADRENAL CORTICES HAVE BEEN DESTROYED
LACK OF CORTISOL
Impaired glucose, fat and protein metabolism Hypotension Increased ACTH secretion Impaired fluid excretion Excessive pigmentation Inability to tolerate stressResults in an inability to conserve Na and eliminate K and H ions leading to hypovolemia ,hyperkalemia and acidosis.
Secondary Ad. Insufficiency is more common. The secretion of cortisol is directly dependent on the level of circulating ACTH. Assessment of suppression is based on laboratory findings. Topical or inhaled C.S. are rare inducers of suppression. Once C.S administration ceases ,the HPA axis regains function. Time required ranges from days to months
Hypoadrenalism Addison's disease Clinical features are related to the def. of both cortisol and aldosterone. Common findings include weakness ,fatigue, hypotension, pigmentation of the skin and m.m, anorexia and weight loss. If the patient is challenged by stress (surgery, infection or illness) an Adrenal crisis may develop. Features include hypothermia ,severe hypotension ,hypoglycemia and circulatory collapse where the situation is fatal.
CLINICAL PRESENTATION
Hypoadrenalism (Secondary – Chronic use of steroids) Clinical features are related to the def. of cortisol. The patient does not develop symptoms unless stressed. An adrenal crisis is possible but rare and not so severe with seldom occurrence of hypotension , dehydration and shock.CLINICAL PRESENTATION
Hypoadrenalism (Cushing syndrome) Due to long term high dose of C.S. Findings include Hypertension ,Heart failure ,Osteoporosis ,Central type obesity ,Diabetes mellitus ,Infection and Impaired healing.Primary insufficiency Investigations Eliminate cause Replacement therapy: Daily replacement is 25-30mg of cortisol or prednisone in a dosage of 7.5 mg. In regard to MCS the replacement is fludrocortisone (0. 5-1 mg) +Na indigestion.
Medical Management
Secondary insufficiencyEliminate causeReplacement therapyIf the case is due to exogenous C.S then benefits over side effects are evaluated. Hydrocortisone 20mg ,prednisone 5mg and dexamethasone 0.5mg per day.The dose is best given as a morning dose which are less suppressive than higher and divided doses.The drugs are TAKEN either daily or alternate day (preferable) regimen (day off-day intake-day off……) Medical management
Supplementation may be necessary equivalent to the normal physiological response to stress. The risk of an adverse outcome depends on duration and severity of surgery and the overall health of the patient.
Surgery is known to increase C.S levels during and after operations. Levels peak to 2-10 fold above baseline between 4-10 hours after operation. The level is based on the degree of surgery and the use of G.A.
Studies estimate that adults secrete 50mg of cortisone a day in response to minor surgery and 75-150mg a day in response to major surgery (GA). Cortisol secretion in the first 24hrs rarely exceed 200mg. For prednisone, the maximum response to stress by a normal adrenal gland is about 60mg prednisone
Medical consultation for boost needed The endogenous secretion can be inhibited if the patient has taken steroids for 2 weeks or longer within the past 2 years. It takes 2 weeks to two years for endogenous secretion to normalize following exogenous use. Exogenous steroids will cause minimal endogenous suppression when the steroid dose is given before 9 a.m.
Always determine the maximum dose of steroid the patient has taken within the last 2 years The first patient in the morning Severity of surgery. Dental procedures do not stimulate cortisol levels comparable to surgery.
Major dental surgery such as impactions ,osteotomy , bone resection warrant the use of supplementation. The stress response has been noticed to be in the 1-5hrs postoperatively. The response is not predictable. Those at risk for crisis are who discontinue drug or do not take supplementation.
Blood loss (hypovolemia-hypotension) Hypoglycemia Stress free protocol (N2O)
Minor surgical stress : Daily equivalent on day of operation for e.g. an asthmatic patient who takes 5mg prednisone should also take the same dose. Moderate surgical stress : Hydrocortisone equivalent of 50-75mg (double dose) per day for up to 1-2 days. Major surgical stress : Hydrocortisone equivalent of 100-150mg (double to triple dose) per day for 2-3 days. The above protocol recommends that steroids is taken within 2 hrs. of surgery and the patient is returned to the usual dose upon completion of the regimen (step up-step down regime)
Blood and fluid volume should be taken into consideration. Fall in the BP is the first indicator of an Adrenal Crisis. If so happens IV 100mg of hydrocortisone is given or IV 4mg of dexamethasone, fluid and electrolyte replacement. Over the next 24hrs 100mg IV is given slowly every 6-8 hours and if needed fluid replacement and correction of hypoglycemia.