Adrenal Insufficiency General Overview

There are normally two adrenal glands, located one above each kidney, and each adrenal gland is composed of two parts.  The inner portion, or the medulla, produces adrenaline, and the outer portion, known as the cortex, makes two essential steroid hormones, cortisol and aldosterone. Adrenal Insufficiency disease is a severe or total deficiency of these hormones either caused by destruction of the adrenal cortex cortex or from a disturbance within the endocrine system such as the pituitary gland.  Cortisol, a glucocorticoid,  mobilizes nutrients, modifies the body's response to inflammation,  helps maintain metabolsim, and also helps to control the amount of water in the body. Cortisol production is regulated by another hormone, adrenocorticotrophic hormone (ACTH), made in the pituitary gland which is located just below the brain.  Aldosterone is a mineralcorticoid that regulates sodium, potassium, and water retention, and, in turn, blood volume and blood pressure.

Primary Adrenal Insufficiency, or Addison's disease, is the loss of cortisol and aldosterone due to damage to the adrenal gland themselves.  Seconday Adrenal Insufficiency occurs when ACTH is deficient, resulting in a lack of cortisol , although aldosterone may remain adequate. Secondary Adrenal Insufficiency is different but similar to Addison's disease, as both include a loss of cortisol.  Common causes of primary Adrenal Insufficiency include autoimmune destruction, which is the most common; tuberculosis; fungal infections; and metabolic failure from conditions such as congenital adrenal hyperplasiaor from certain medications.   Secondary adrenal insufficiency can be cause by hypopituitarism from either pituitary disease, such as a tumor, or the prolonged use of "steroid" medications, resulting in ACTH suppression and lack of cortisol production. Other causes for both types include surgery, trauma, volume loss, hypothermia, heart attack, hypoglycemia, fever and pain.

Symptoms of adrenal insufficiency are chronic and slowly progressive.  Symptoms are commonly missed or ignored until the body is stressed, such as contracting the flu or an accident, and causes the patient to enter Adrenal Crisis as a result of the deficient adrenal response. The most common symptoms include:

• Fatigue, including muscle weakness and spasm
• Skin darkening (or Vitiligo) with ACTH deficiency
• Weight loss and appetite changes
• Abdominal pain, diarrhea, and constipation
• Orthostatic hypotension with syncope

Adrenal Insufficiency Testing and Diagnosis

Tests specifically for adrenal insufficiency include Adrenocorticotropic hormone (ACTH) stimulation test, or Cortrosyn test, and the Insulin-Induced Hypoglycemia Test.  The ACTH Stim test is usually performed in a hospital and measures the amount of cortisol and aldosterone in the blood and urine.  A baseline reading for both hormones is taken, and after the administration the ACTH, or Cortrosyn, injection, repeat cortisol and aldosterone levels are obtained every 30-60 minutes after.  Little or no rise in cortisol levels are consistent with adrenal insufficiency, and elevated ACTH level may also be found.  The Insulin-induced Hypoglycemia test, or IIHT, evaluates the hypothalamic-pituitary-adrenal (HPA) axis, and first measures baseline blood glucose and cortisol levels, and after an insulin injection, glucose and cortisol levels are measured 30, 45 and 90 minutes afterwards.

 Correlating tests for adrenal insufficiency includes certain physiological changes, such as abnormal skin pigmentation, and abnormal lab tests such as elevated potassium levels, low sodium, white blood cell anomalies, low blood volume, and abnormal EKG or chest x-ray.  Calcium, BUN, creatinine, and thyroid hormone levels are also evaluated.

 Testing to determine the cause of the insufficiency may include evaluation for tuberculosis and other infections through skin tests and x-rays, and measurement of adrenal tissue antibodies specific to autoimmune disease. A CT scan of the adrenals may be and in cases of secondary adrenal insufficiency, head CT or MRI may show a lesion on the pituitary gland.

Adrenal Insufficiency TreatmentOnce the diagnosis is made, the treatment is predominantly composed of steroid replacement for the cortisol and, if needed aldosterone.  Most Cortisol and aldosterone replacements are taken orally and divided into morning and afternoon dosages to match the normal production during the day. Common cortisol (glucocorticoid) replacements and dosages are:

Hydrocortisone	15-25 mg/daily	2-3 divided doses daily
Prednisone	5-7.5 mg/daily	1 or 2 Divided doses daily
Cortisone Acetate	25-35 mg/day.	Divided doses every 8 hours
Dexamethasone	0.6-0.75 mg/daily	Divided doses every 6-12 hours
Recommended Mineralcoritoid replacement is:
Fludrocortisone	.05-0.1 mg/daily	1 dose daily

Equivalent dosing for the glucocorticoids are:

Hydrocortisone (Cortef)	20 mg
Prednisone	5 mg
Cortisone Acetate	25 mg
Dexamthasone	0.75 mg

Primary adrenal insufficiency requires life-long daily cortisol and/or aldosterone replacement; for those with secondary adrenal insufficiency, some adrenal function may return after a period of steroid replacement, and aldosterone replacement may not be necessary.

• Medication Recommendations and Guidelines

·                Medications must be taken everyday at the right time and dose!

·                 It can take several months to determine the type, dosage and timing of medication may take several months.  Medication requirements vary with each individual, and can change, temporarily or permanently, due to several factors. 

·                Monitor and report new symptoms to your doctor in case medications/treatments need to be modified

·                Order medication prescription refills early and often enough to ensure that the patient doesn’t run out of medication, and it is advisable to have at least 1 month’s supply in reserve

·                Take an extra supply of medication when traveling, and  documentation (i.e. doctor’s note or letter) to explain medication and supplies (syringes, needles, etc). 

• Preventing Adrenal Crisis: Stress Response Guidelines

Because the body can’t respond to stress with increased cortisol production, patients with adrenal insufficiency need additional cortisol during times of stress to prevent adrenal or Addisonian crisis, such as during an illness, after trauma or injury, or before any surgery.  Guidelines for increasing steroid medications are:

·                Extra 5 mg Hydrocortisone (or comparative medication and dose) for mild stress, fever, or injury

·                Extra 10 mg for mild infection with fever

·                Double the usual dose for significant fever or illness causing vomiting, diarrhea, or dehydration

·                If vomiting can’t be controlled or there is severe fever/illness or trauma, an emergency steroid injection should be given, and the patient should then receive

        IV steroids and fluids nearest medical facility.

Mineralocorticoid therapy does not need to be increased during periods of illness or physical stress.