Adrenal Insufficiency

What is adrenal insufficiency?

Adrenal insufficiency is a condition in which the adrenal glands do not make enough of certain hormones, most importantly cortisol. The adrenal glands are two small, triangular glands that sit on top of the kidneys. Cortisol is often called the “stress hormone” because the body releases more of it during illness, injury, or emotional stress. It helps regulate blood pressure, blood sugar, the immune response, and how the body uses energy. In many people with adrenal insufficiency, the glands also produce too little aldosterone, a hormone that helps control salt, potassium, and fluid balance.

Doctors usually describe three main types. Primary adrenal insufficiency, also known as Addison’s disease, happens when the adrenal glands themselves are damaged. Secondary adrenal insufficiency happens when the pituitary gland (a small gland at the base of the brain) does not release enough adrenocorticotropic hormone, or ACTH, which is the signal that tells the adrenal glands to make cortisol. Tertiary adrenal insufficiency occurs when the hypothalamus (the part of the brain that controls the pituitary) does not send the right signals, most often because a person has been taking steroid medicines for a long time.

Adrenal insufficiency can affect people of any age and any sex. Primary adrenal insufficiency is relatively uncommon, while secondary and tertiary forms related to long-term steroid use are seen more often. Because the adrenal glands sit close to the kidneys, patients sometimes assume the problem is a kidney problem, but it is a hormonal (endocrine) condition. Kidney disorders are managed by specialists such as those in the Nephrology Department, whereas adrenal insufficiency is usually cared for by an endocrinologist, a doctor who specializes in hormones and glands. At Acibadem, this condition falls under the endocrinology service.

Adrenal insufficiency symptoms

Adrenal insufficiency symptoms often develop slowly over months and can be vague at first, which is one reason the condition may take time to recognize. Many people are first told they have fatigue, depression, or a stomach problem before the hormone deficiency is identified. Common symptoms include:

• Persistent, often severe tiredness and weakness
• Loss of appetite and unintended weight loss
• Nausea, vomiting, or abdominal pain
• Dizziness or lightheadedness, especially when standing up (a sign of low blood pressure)
• Low blood sugar, which may cause shakiness, sweating, or confusion
• Muscle and joint aches
• Salt craving
• Low mood, irritability, or difficulty concentrating
• Darkening of the skin, particularly in skin creases, scars, gums, and areas exposed to pressure
• Loss of body hair and reduced sex drive, mainly in women

Some symptoms differ by type. Skin darkening (hyperpigmentation) and salt craving are typical of primary adrenal insufficiency. In this form, the pituitary gland produces large amounts of ACTH in an attempt to stimulate the failing adrenal glands, and ACTH shares a pathway with the hormone that stimulates skin pigment. Salt craving and low blood pressure reflect the lack of aldosterone. In secondary and tertiary adrenal insufficiency, aldosterone production is usually preserved because it is controlled by a different system, so salt craving and severe low blood pressure are less prominent, and the skin does not darken. People with a pituitary problem may also have symptoms of other hormone deficiencies, such as menstrual changes, cold intolerance, or excessive thirst.

The most serious presentation is an adrenal crisis (also called an Addisonian crisis). This is a life-threatening emergency in which the body cannot produce the surge of cortisol needed during a major stress such as infection, surgery, injury, or severe vomiting. Warning signs include sudden severe weakness, severe pain in the lower back, abdomen, or legs, vomiting and diarrhea leading to dehydration, very low blood pressure, confusion, and loss of consciousness. Adrenal crisis requires immediate emergency treatment.

Causes and risk factors

Adrenal insufficiency causes depend on which part of the hormone system is affected.

Primary adrenal insufficiency (Addison’s disease) is most often caused by an autoimmune reaction, in which the immune system mistakenly attacks the outer layer of the adrenal glands. Other causes include infections that damage the glands, such as tuberculosis, certain fungal infections, and HIV-related infections; bleeding into the adrenal glands, which can occur with severe infection or with blood-thinning medicines; cancer that has spread to the adrenal glands; surgical removal of both adrenal glands; and rare genetic conditions such as congenital adrenal hyperplasia or adrenoleukodystrophy. Some medicines, including certain antifungal drugs and some cancer immunotherapies, can also reduce adrenal hormone production.

Secondary adrenal insufficiency results from problems with the pituitary gland. These include pituitary tumors (which are usually noncancerous), surgery or radiation therapy to the pituitary area, head injury, inflammation of the pituitary, and reduced blood supply to the pituitary, for example after severe bleeding during childbirth.

Tertiary adrenal insufficiency is most commonly caused by long-term use of glucocorticoid medicines such as prednisone, prednisolone, dexamethasone, or hydrocortisone. These medicines are used for asthma, rheumatoid arthritis, inflammatory bowel disease, and many other conditions. When the body receives steroids from outside, the hypothalamus and pituitary reduce their own signals, and the adrenal glands gradually become less able to respond. If the medicine is then stopped suddenly, the glands may not be able to produce enough cortisol on their own. Inhaled, injected, and even strong topical steroids can occasionally have this effect. Some people who have been treated for Cushing’s syndrome (excess cortisol) may also develop temporary adrenal insufficiency afterwards.

Risk factors include having another autoimmune condition such as type 1 diabetes, autoimmune thyroid disease, vitiligo, or pernicious anemia; a family history of autoimmune disease or Addison’s disease; long-term or high-dose steroid treatment; a history of pituitary disease, surgery, or radiation; certain chronic infections; and the use of medicines known to affect adrenal or pituitary function.

Adrenal insufficiency diagnosis

Adrenal insufficiency diagnosis begins with a detailed medical history and physical examination. Your doctor may ask about fatigue, weight changes, dizziness, salt craving, skin changes, other autoimmune conditions, and any past or present steroid use, including creams and inhalers. Blood pressure may be measured lying down and standing to look for a drop on standing.

Blood tests are the main way the condition is confirmed. Commonly used tests include:

• Morning serum cortisol: cortisol levels are normally highest in the early morning, so a sample taken at this time gives useful information. A clearly low result raises suspicion, while a clearly normal result often makes the diagnosis unlikely. Borderline results usually need further testing.
• ACTH level: a high ACTH with low cortisol points toward a primary adrenal problem, whereas a low or normal ACTH with low cortisol suggests a pituitary or hypothalamic cause.
• ACTH stimulation test: a synthetic form of ACTH (cosyntropin) is injected and cortisol is measured before and after. In a healthy person, cortisol rises; in adrenal insufficiency, the rise is inadequate. This is often the key confirmatory test.
• Electrolytes and blood sugar: low sodium, high potassium, and low glucose are common in primary adrenal insufficiency.
• Renin and aldosterone: these help assess whether aldosterone production is also affected.
• Adrenal antibodies: antibodies against adrenal tissue support an autoimmune cause.

In some situations, your doctor may use additional tests, such as an insulin tolerance test or other specialized tests of the pituitary, though these are used selectively because they must be done under close supervision.

Imaging is chosen based on the suspected type. If a primary adrenal problem is suspected, a CT (computed tomography) scan of the adrenal glands may be performed to look for enlargement, shrinkage, bleeding, infection, or tumors. If a secondary cause is suspected, an MRI (magnetic resonance imaging) scan of the pituitary gland is usually recommended. When adrenal insufficiency is diagnosed, doctors often check for related conditions, such as thyroid disease, and may test for tuberculosis or other infections depending on the person’s history.

Adrenal insufficiency treatment options

Adrenal insufficiency treatment options focus on replacing the hormones the body can no longer make in sufficient amounts. Unlike many conditions, observation without treatment is generally not appropriate once cortisol deficiency has been confirmed, because the lack of cortisol can be life-threatening during illness or stress. The one exception is steroid-induced adrenal insufficiency, where the adrenal glands may gradually recover after the steroid medicine is carefully reduced; in this case, the treatment is a supervised tapering plan with monitoring rather than indefinite replacement.

Glucocorticoid replacement. Cortisol is usually replaced with hydrocortisone, which is chemically identical to natural cortisol, taken in divided doses through the day to mimic the body’s natural rhythm. Some people are prescribed prednisolone or, less commonly, dexamethasone, which are longer-acting. Doses are adjusted based on symptoms, weight, and how the person feels, since there is no single blood test that perfectly measures whether the dose is right. Too little replacement causes ongoing symptoms and increases crisis risk; too much may lead to weight gain, high blood pressure, bone thinning, and other side effects over time.

Mineralocorticoid replacement. People with primary adrenal insufficiency usually also need fludrocortisone to replace aldosterone. This helps maintain normal blood pressure and sodium and potassium levels. The dose is monitored using blood pressure, electrolytes, and renin levels. Adequate salt intake is often advised, especially in hot weather or during heavy exercise.

Androgen replacement. Some women with primary adrenal insufficiency may be offered DHEA (dehydroepiandrosterone), a weak male-type hormone normally produced by the adrenal glands, to help with energy, mood, or sex drive. Evidence for benefit is mixed, so this is decided case by case.

Sick-day rules and stress dosing. A central part of treatment is education. Because the body cannot increase cortisol on its own, people are taught to increase their usual dose during fever, infection, vomiting, injury, or before surgery and dental procedures, according to a plan agreed with their doctor. If tablets cannot be kept down because of vomiting, an injection of hydrocortisone is needed. Most patients are given an emergency injection kit and taught how to use it, along with family members.

Emergency treatment of adrenal crisis. Adrenal crisis is treated in hospital with intravenous hydrocortisone, fluids to correct dehydration and low blood pressure, glucose if blood sugar is low, and treatment of the underlying trigger such as an infection.

Treating the underlying cause. When adrenal insufficiency is due to a pituitary tumor, infection, or another identifiable condition, that condition is treated as well, which may involve medication, surgery, or radiation therapy. Surgery is not a treatment for adrenal insufficiency itself.

Regular follow-up with an endocrinologist is usual, typically including a review of symptoms, blood pressure, weight, electrolytes, and bone health, and a check that the emergency plan and medical alert identification are up to date.

Living with adrenal insufficiency and outlook

Adrenal insufficiency is generally a lifelong condition, except when it is caused by steroid medicines and the glands recover over time. With consistent hormone replacement and good understanding of sick-day rules, many people lead full and active lives, work, travel, exercise, and have children. Outcomes are not guaranteed, however, and the main ongoing risk is adrenal crisis, which is most likely to occur when doses are missed or not increased during illness.

Practical steps that doctors commonly recommend include taking medication at the same times each day, never stopping it suddenly, carrying a steroid emergency card or wearing medical alert jewelry, keeping an emergency hydrocortisone injection kit accessible, informing any healthcare professional, including dentists and anesthesiologists, about the condition before procedures, and having a plan for travel that includes extra medication and a letter explaining the diagnosis. Some people notice they tire more easily than before or need more time to recover from minor illnesses. Fatigue and mood changes can persist even with treatment, and it is reasonable to discuss these with your care team rather than assume they must simply be accepted.

Long-term monitoring may also include attention to bone density, cardiovascular health, and screening for associated autoimmune conditions, particularly thyroid disease and type 1 diabetes, since these may develop over time in people with autoimmune Addison’s disease.

Frequently asked questions

What is adrenal insufficiency in simple terms?

Adrenal insufficiency means the body does not produce enough cortisol, and sometimes not enough aldosterone. Cortisol helps the body cope with stress, maintain blood pressure, and regulate blood sugar. When levels are too low, a person may feel exhausted, dizzy, and unwell, and may become dangerously ill during infections or injuries unless the missing hormone is replaced.

What are the first adrenal insufficiency symptoms people notice?

Early symptoms are often nonspecific, such as ongoing tiredness, weakness, reduced appetite, weight loss, and lightheadedness when standing. In primary adrenal insufficiency, gradual darkening of the skin and craving for salty foods are frequently reported. Because these symptoms overlap with many other conditions, they are easily attributed to other causes at first.

What are the most common adrenal insufficiency causes?

The most common cause of primary adrenal insufficiency in many regions is an autoimmune reaction that damages the adrenal glands, while infections such as tuberculosis remain important in some parts of the world. Secondary and tertiary forms are most often caused by pituitary disease or by long-term use of steroid medicines that suppress the body’s own cortisol production.

How is adrenal insufficiency diagnosis confirmed?

Doctors usually start with an early-morning blood cortisol level, often alongside ACTH, sodium, potassium, and glucose. If results are low or borderline, an ACTH stimulation test is commonly used to confirm the diagnosis and help distinguish primary from secondary causes. Imaging of the adrenal glands or pituitary gland may then be arranged to look for the underlying reason.

What are the adrenal insufficiency treatment options if I have Addison’s disease?

Treatment for Addison’s disease involves lifelong replacement of cortisol, usually with hydrocortisone tablets taken two or three times a day, plus fludrocortisone to replace aldosterone. Patients are also taught when and how to increase doses during illness and how to use an emergency injection. Doses are reviewed regularly and adjusted based on symptoms and blood tests.

Can adrenal insufficiency go away?

Adrenal insufficiency caused by autoimmune damage, infection, or surgery is generally permanent and requires ongoing hormone replacement. When the condition is caused by steroid medicines, adrenal function may recover after the steroid is tapered slowly under medical supervision, although recovery can take months and does not happen in every case.

Is adrenal insufficiency dangerous?

Untreated or undertreated adrenal insufficiency can lead to adrenal crisis, which is a medical emergency involving severe low blood pressure, dehydration, and sometimes shock. With appropriate replacement therapy and prompt action during illness, the risk is greatly reduced, but it does not disappear entirely, which is why ongoing education and an emergency plan are considered essential.

When to see a doctor

Consider making an appointment with a doctor if you have unexplained, persistent tiredness together with weight loss, dizziness on standing, nausea, salt craving, or darkening of the skin, particularly if you have another autoimmune condition or have recently stopped or reduced long-term steroid medication. If you have already been diagnosed, contact your care team when you are unsure how to adjust your dose during an illness, when you are planning surgery or travel, or if you notice new symptoms such as swelling, high blood pressure, or worsening fatigue.

Seek emergency medical care immediately, or have someone call emergency services, if you or a person with known or suspected adrenal insufficiency has any of the following red-flag signs:

• Repeated vomiting or diarrhea that prevents taking or keeping down steroid tablets
• Sudden severe weakness or collapse
• Severe pain in the abdomen, lower back, or legs
• Confusion, extreme drowsiness, or loss of consciousness
• Very low blood pressure, fainting, or a rapid, weak pulse
• High fever with rapid worsening of general condition
• Symptoms of very low blood sugar, such as shaking, sweating, and confusion, that do not improve

In these situations, an emergency hydrocortisone injection should be given if one is available, and hospital treatment should not be delayed. Adrenal crisis is treatable, but outcomes depend on how quickly treatment begins.