Running On Reserves: Understanding Adrenal Insufficiency

There seems to be a lot of mainstream media articles lately highlighting a medical condition called adrenal insufficiency. But exactly what is it?

First, it’s helpful to know what the adrenals are and what their function is. The human body has two adrenals, triangle-shaped glands located on the top of each kidney like a cap. Each adrenal gland is composed of two distinct parts: the outer part called the adrenal cortex and the inner adrenal medulla. The adrenal glands produce and secrete several hormones which act as a chemical “messengers,” traveling through the bloodstream and acting on various body tissues to enable them to function correctly, including glucocorticoids involved in the metabolism of carbohydrates, proteins and fats; mineralocorticoids that help maintain the body’s salt and water levels which, in turn, regulates blood pressure; and adrenal androgens, which play a role in early development of the male sex organs in childhood and female body hair during puberty.

Normally, the hormones produced and released by the adrenals are very carefully regulated to maintain the necessary balance that the body requires for optimal function. This regulation includes signals produced by the pituitary gland – a pea-sized structure located at the base of the brain – that stimulate adrenal hormone production and, in turn, receive feedback that sufficient levels of adrenal hormone are present. A small portion of the brain called the hypothalamus plays a further role by regulating the function of the pituitary.

With such intricate feedback loops, there can be several ways that systems affecting adrenal function can fail to work as they should. For example, dysfunction or destruction of the adrenal gland can result from infections. In the past, tuberculosis – a serious infectious disease that mainly affects the lungs – was recognized as a major culprit. But other infections such as those produced by bacteria or fungus have also been reported as affecting the adrenals’ ability to produce hormones. More recently, it has been recognized that the body can produce antibodies against its own adrenal tissue (referred to as an autoimmune response), which causes destruction of adrenal cells.

Other potential causes of adrenal function loss include medications, such as select anti-coagulants (commonly referred to as blood thinners) that can cause bleeding into the adrenal, resulting in the inability of the adrenals to maintain normal hormone production; cancer (usually metastasized from other organs); HIV infection; and congenital adrenal hyperplasia, a group of inherited genetic disorders.

Sometimes adrenal destruction affects only the adrenal cortex, whereas other times the entire adrenal can be affected. This is called primary adrenal insufficiency, as the problem is in the adrenal gland.

If the problem originates in the pituitary because there is not enough “message” hormone being sent to the adrenal (deficient ACTH secretion), then this is called secondary or central adrenal insufficiency. ACTH is released into the bloodstream in intermittent pulses throughout the day. When ACTH reaches the adrenal glands, it causes them to secrete more cortisol, a steroid hormone best known as the “stress” hormone, which allows your body to respond to stress or danger, increases your body’s metabolism of glucose, helps control your blood pressure and reduces inflammation.

Whether primary or secondary adrenal insufficiency, the symptoms are mostly similar, with a few exceptions. Common symptoms include weakness, fatigue, weight loss without trying to lose weight, abdominal pain, nausea and, at times, vomiting.

Patients might also have low blood sugar (hypoglycemia), low blood pressure (hypotension) and abnormally low levels of sodium in the blood (hyponatremia).

Primary adrenal insufficiency patients can have hyperpigmentation (darkening) of the skin, much like an overall suntan, except the darkening can affect areas of the body that aren’t typically exposed to the sun such as mucous membranes. An example is along the inner cheeks of your mouth where your teeth meet; chewing traumatizes this skin, which sets the stage for the darkening. Sometimes there is also darkening along the gums or tooth line and at elbows and knees. With long-lasting primary adrenal insufficiency, there can be darkening of the creases of the palm, along fingernail rims and nipples. Also, scars that form after a person has developed primary adrenal insufficiency may be darker than previous scars. In addition, those with primary adrenal insufficiency may experience dizziness when sitting or standing and salt cravings – a condition called hyperkalemia, which describes a potassium level in your blood that’s higher than normal.

Certain conditions can lead to rapid onset of symptoms, such as bleeding into the adrenal gland, which can lead to an adrenal crisis (also known as Addisonian crisis), a medical emergency requiring immediate treatment. Other causes result in a more gradual onset of symptoms. Symptoms of primary adrenal insufficiency occur only after loss of about 90 percent of both adrenal cortices, so there is considerable reserve available to protect normal body function.

Secondary adrenal insufficiency usually results from a decrease in ACTH, which then causes low cortisol (glucosteroid) levels. Other causes of secondary adrenal insufficiency are the presence of a pituitary mass leading to underproduction of pituitary hormones, or surgical removal of a pituitary mass. But the most common reason people develop secondary adrenal insufficiency is from long-term use of steroids, a substance found in medications for conditions such as rheumatoid arthritis and asthma. While there is a decreased response by the body to stress in secondary adrenal insufficiency, darkening of the skin is not seen and potassium blood levels are usually normal.

Both primary and secondary adrenal insufficiency are initially screened for with a test called the rapid ACTH stimulation test. Also called the cosyntropin, tetracosactide, or Synacthen test, the test is performed in a clinic setting with a blood draw. The test checks to determine what the adrenal gland can produce after it is stimulated by either an intramuscular or intravenous dose of synthetic ACTH; those results are compared to the patient’s ACTH level before the synthetic hormone is administered. The ACTH hormone level can help differentiate between primary and secondary adrenal insufficiency. At times, test results can be difficult to interpret, such as when there might be only partial adrenal insufficiency. More specialized testing can be done in this circumstance.

Once a diagnosis is confirmed, treatment for adrenal insufficiency consists of replacing the hormones the glands are no longer producing. There are maintenance doses of oral steroids meant for long-term daily intake and doses used to prevent adrenal crisis that can occur when the patient is experiencing stress or illness. The most commonly used steroids are hydrocortisone or cortisone acetate taken in two or three divided doses. The highest dose is given in the morning shortly after awakening, and the second dose is given around lunchtime or early afternoon. A third dose is needed occasionally even later in the day. A higher dose is given in the morning because steroids are normally produced in a circadian rhythm, the body’s 24-hour internal clock that is running in the background of your brain and cycles between sleepiness and alertness at regular intervals.

A typical medication regimen might be 15 milligrams oral hydrocortisone taken in the morning and either 5 milligrams or 10 milligrams taken in the afternoon. If the patient has difficulty remembering to take multiple doses, oral prednisolone or prednisone can be used once daily.

In those diagnosed with primary adrenal insufficiency, another hormone is needed to replace mineralocorticoids because there is a deficiency of aldosterone hormone production. Replacement is typically with a medication called fludrocortisone. In persons diagnosed with secondary adrenal insufficiency caused by steroid use, full recovery of their own production of adrenal steroid hormones is expected, but this may take weeks to years to occur. In primary adrenal insufficiency, patients will be on lifelong steroids and fludrocortisone.

Since an impaired adrenal gland is deficient in making appropriate amounts of cortisol, patients will need to take larger doses of hydrocortisone (the name for the hormone cortisol when supplied as a medication) to compensate for the body’s higher steroid needs during times of illness or stress. What is considered stress can vary from person to person, but there are some general principles to keep in mind. If the patient has a fever, a double or triple dose of hydrocortisone replacement is recommended until recovery, which is usually about two to three days. They should also increase their intake fluids rich in electrolytes that are essential for normal function of our cells and our organs. Examples are Gatorade, electrolyte-enhanced drink tab Nuun, or a homemade concoction made of mixed fruit juice such as citrus juice or tart cheery juice and honey, water and a pinch or two of table salt.

If patients develop nausea and can’t take in pills or fluids, or start vomiting, prompt medical help should be sought. Keeping intramuscular hydrocortisone on a hand as an emergency supply is recommended, as this allows for time to get to an urgent care center or emergency room after the intramuscular dose is given. But don’t delay seeking medical help – this is a critical situation.

Another stressful condition is when a patient is undergoing a surgical procedure. Major surgical procedures (trauma, delivery of a baby, those requiring general anesthesia) require stress-dose steroids be administered and monitored by the patient’s medical team. For more minor procedures, it is recommended that the steroid dose be doubled the day of the procedure and for one to two days following the procedure. Discuss with your endocrinologist the specific recommendations for maintaining adrenal health in a variety of situations.

Overall, the prognosis for someone diagnosed with adrenal insufficiency is very good, as proper diagnosis and treatment can lead to a healthy life. However, be careful not to attribute symptoms of the condition that we can all experience from time to time – fatigue and weakness, for example – to a possible adrenal issue when there’s no other indication that the adrenals aren’t functioning normally.