What are adrenal glands and what is their function?
The Adrenal glands are very important glands in our body. Each of the two adrenal glands rests on top of each kidney.
Adrenal glands produce a number of very important hormones including: Cortisol, Aldosterone and Sex steroids (also produced in the testes and ovaries).
What is adrenal insufficiency?
Adrenal insufficiency occurs when there is significant decrease in the level of these hormones especially cortisol and aldosterone.
There are two types of adrenal insuficiency:
1. Primary Adrenal Insufficiency
This is also known as Addison's disease. This disease is caused by the near total destruction of both of the adrenal glands. Therefore, these patients have a very low level of cortisol and aldosterone.
Because sex steroids are also produced in the testes and ovaries, these patients continue to have an adequate level of sex steroids.
In the majority of patients, this disease happens due to an autoimmune disease process. Often there is evidence of some other autoimmune disease such as Hashimoto's thyroiditis, Type 1 diabetes or pernicious anemia.
In third world countries, tuberculosis is also a major cause of this disease.
2. Secondary Adrenal Insufficiency
Secondary Adrenal Insufficiency is due to diseases of the pituitary or hypothalamus, which are endocrine organs found in the brain. This results in decrease in ACTH (AdrenoCorticoTropic Hormone) from the pituitary gland.
ACTH regulates the production of cortisol by the adrenal gland. A decrease in ACTH results in decrease in the production of cortisol by the adrenal glands. In these patients, Aldosterone production is spared as it is primarily under control of another hormonal mechanism, known as Renin Angiotensin Aldosterone axis.
Secondary Adrenal Insufficiency often occurs in patients with a tumor in the pituitary or hypothalamic area of the brain. The tumor itself or its treatment by surgery or radiation causes secondary adrenal insufficiency.
These patients also develop deficiencies of several other hormones, especially thyroid hormones, sex hormones and growth hormone.
Symptoms of Adrenal Insufficiency
Fatigue is the main symptom and is often the only symptom. Patients also usually have low blood pressure. Sometimes, patients may also develop darkening of their skin and a craving for salt.
If Adrenal insufficiency is not diagnosed in time, then more severe symptoms such as severe low blood pressure and shock can develop.
Diagnosis of Adrenal Insufficiency
Unfortunately, adrenal insufficiency is usually not suspected by primary care physicians. Patients are told that their fatigue is due to depression or stress. Phrases such as "it's all in your head" are used.
The best way to diagnose Addison's disease is by doing a Cortrosyn Stimulation test.
Cortrosyn Stimulation Test
In this test, a baseline blood sample for cortisol level is drawn from the patient. Then, an injection of Cortrosyn is given to the patient and another blood sample for cortisol is drawn after 60 minutes.
Treatment of Adrenal Insufficiency
Treatment of Addison's disease is very effective. Drugs such as Prednisone or Hydrocortisone and Florinef are used to replace the adrenal hormones.
A 38 year old female came to see me complaining of progressive fatigue for several months. She had seen several doctors during this period and was told that everything was fine on her blood work-up and this fatigue was "something in her head."
She had also developed nausea, vomiting and lost about 30 lbs. in the past two months. Two weeks earlier, she had developed vague abdominal pain and was operated on for suspected diagnosis of appendicitis, but her appendix was found to be normal on the pathology report.
She denied any fever, chills, night sweats, cough or dysuria. She complained of shortness of breath upon walking only 5-10 feet, but no chest pain.
Past medical history was remarkable for premature ovarian failure at age 27.
Blood pressure=70/40, Pulse= 80, Respiration=24, Temp= 98 F
She appeared sick, malnourished and dehydrated. The rest of the examination was unremarkable. I admitted her to the hospital for further management.
Serum electrolytes: Na=132, K=5.5, BUN=19 , Creatinine=1.0
I made a clinical diagnosis of Addison's disease and started aggressive intravenous hydration. A cortrosyn stimulation test was performed upon admission. Then the patient was started on intravenous hydrocortisone 100 mg every 6 hours.
Within 24 hours, the patient showed remarkable improvement. Her blood pressure came up to 105/60; her shortness of breath and anorexia resolved and fatigue started improving. Her low serum sodium (Na) and high serum potassium (K) resolved within 24 hours.
A CT scan of her abdomen did not visualize the adrenal glands indicating her adrenal glands were atrophied.
Three days later, the results of her cortrosyn stimulation test came back. Her baseline serum cortisol was low as 1 mcg/dl and at 60 minutes after 0.25 mg of cortrosyn injection, her serum cortisol was still 1 mcg/dl. This result confirmed the diagnosis of primary adrenal insufficiency or Addison's disease.
She was discharged home on the following medications: Hydrocortisone 10 mg every morning and 5 mg at lunch time. Florinef 0.075 mg every morning.
Addison's disease (Primary Adrenal Insufficiency) was unfortunately not suspected in this case until she came to see me. At that time, she was in an Addisonian Crisis. Fortunately, proper treatment was started without any further delay and she responded very well to the treatment.
Premature ovarian failure was an important feature in her history that made me highly suspicious of the diagnosis of Primary Adrenal Insufficiency. These two diseases are part of Polyglandular Autoimmune Syndrome (PGA) and tend to occur together.
Other components of PGA include autoimmune thyroid disease such as Hashimoto's thyroiditis or Graves disease, Type 1 diabetes, pernicious anemia, vitiligo and other autoimmune disorders such as collagen vascular diseases.
The important message from this case is that physicians should suspect the diagnosis of Addison's disease in patients with unexplained fatigue especially if they also have other autoimmune diseases such as Hashimoto's thyroiditis, Type 1 diabetes or premature ovarian failure.
In a severely sick patient, you do not even have to do a Cortrosyn stimulation test (We did this test because it was readily available). All you need to do is to draw a serum cortisol level before starting the patient on Hydrocortisone. Under the stress of acute illness, serum cortisol should be more than 25 mcg/dl. A value below this level is consistent with the diagnosis of Addison's disease in these patients.
This article was written by Sarfraz Zaidi, MD, FACE. Dr. Zaidi specializes in Diabetes, Endocrinology and Metabolism.
Dr. Zaidi is a former assistant Clinical Professor of Medicine at UCLA and Director of the Jamila Diabetes and Endocrine Medical Center in Thousand Oaks, California.
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