Tertiary Adrenal Insufficiency

Tertiary adrenal insufficiency is a condition where the brain, especially the hypothalamus, does not send enough signals to tell the adrenal glands to make cortisol, an important stress hormone. In this condition, the adrenal glands themselves are usually normal, but they are “switched off” because the signals from the brain are too low. The brain hormone that is low is called corticotropin-releasing hormone (CRH). When CRH is low, the pituitary gland makes less ACTH (adrenocorticotropic hormone), and the adrenal glands then make less cortisol. This is why tertiary adrenal insufficiency is sometimes called “central” adrenal insufficiency, because the problem is in the brain rather than in the adrenal glands. NCBI+1

Tertiary adrenal insufficiency happens when the brain’s hypothalamus does not make enough corticotropin-releasing hormone (CRH). CRH normally tells the pituitary gland to release ACTH, which then tells the adrenal glands to make cortisol. In tertiary adrenal insufficiency, this chain is “turned down,” so cortisol levels fall.NCBI+1

The most common cause is long-term or high-dose steroid medicines (such as prednisone or dexamethasone) taken for other illnesses. These medicines replace or exceed the body’s own cortisol for months, so the hypothalamus and pituitary reduce their signals and the adrenal glands “go to sleep.” When steroids are stopped or reduced too quickly, the body cannot increase its own cortisol, and symptoms of adrenal insufficiency appear.Cleveland Clinic Journal of Medicine+2Endocrine Society+2

Symptoms can include severe tiredness, weight loss, low blood pressure, dizziness on standing, nausea, vomiting, low blood sugar, and in serious cases, adrenal crisis, which is a medical emergency. Treatment focuses on safe steroid tapering, hormone replacement when needed, and strong education about “sick-day rules” and emergency management.NCBI+2endocrinology.org+2

Normally, the hypothalamus in the brain releases CRH, which travels a very short distance to the pituitary gland. The pituitary responds by releasing ACTH into the blood. ACTH then reaches the adrenal glands, which sit on top of the kidneys, and tells them to make cortisol. Cortisol helps control blood pressure, blood sugar, immune function, and the body’s response to stress. When cortisol levels are high enough, they send a “negative feedback” message back to the hypothalamus and pituitary to reduce CRH and ACTH, so the system stays in balance. In tertiary adrenal insufficiency, the hypothalamus does not produce enough CRH, so this chain reaction is weak, and cortisol levels fall. NCBI+1

Other names for tertiary adrenal insufficiency

Tertiary adrenal insufficiency has several other names that doctors and researchers may use. It is often called “glucocorticoid-induced adrenal insufficiency” when it is caused by long-term steroid treatment. Some articles use the term “GC-induced adrenal insufficiency (GI-AI)” or “exogenous steroid-induced adrenal suppression.” It can also be grouped under “central adrenal insufficiency,” which describes adrenal failure due to problems in the hypothalamus or pituitary. In practice, many doctors talk about secondary and tertiary adrenal insufficiency together as “central adrenal insufficiency,” because both involve low ACTH and low cortisol, while mineralocorticoid (aldosterone) production is usually normal. NCBI+3addisonsdisease.org.uk+3Endocrine Society+3

Types and clinical patterns of tertiary adrenal insufficiency

There are several useful ways to think about types or patterns of tertiary adrenal insufficiency, even though there is no single universal classification. One pattern is glucocorticoid-induced tertiary adrenal insufficiency, where long-term use of steroid medicines such as prednisone, prednisolone, dexamethasone, or hydrocortisone suppresses the HPA axis. Another pattern is tertiary adrenal insufficiency due to hypothalamic disease or injury, where tumors, surgery, radiation, or trauma affect the hypothalamus and reduce CRH production. A third pattern is transient tertiary adrenal insufficiency, which can happen after successful treatment of Cushing disease or after stopping long-term glucocorticoids; in this case, the HPA axis can slowly recover over months or sometimes years. Finally, some people have partial tertiary adrenal insufficiency, where cortisol production is enough for daily life but not enough for serious illness, surgery, or severe stress, so they develop symptoms mainly during stress. SpringerLink+3PMC+3Endocrine Society+3

Causes of tertiary adrenal insufficiency

Below are 20 important causes, each explained in simple language.

1. Long-term oral glucocorticoid tablets
   Taking steroid tablets such as prednisone, prednisolone, dexamethasone, or methylprednisolone for many weeks or months is the most common cause of tertiary adrenal insufficiency. These medicines mimic cortisol in the body, and high or long-term doses tell the brain that there is enough cortisol. As a result, the hypothalamus reduces CRH release, the pituitary reduces ACTH, and over time the adrenal glands “rest” and produce less natural cortisol. Endocrine Society+2NIDDK+2

2. High-dose steroid bursts, especially repeated
   Even shorter courses of high-dose steroids, especially if repeated often, can suppress the HPA axis in some people. For example, frequent “steroid bursts” for asthma or severe inflammation may lead to partial or temporary tertiary adrenal insufficiency, especially if the total dose over months is high. Endocrine Society+1

3. Long-term inhaled glucocorticoids for asthma or COPD
   Inhaled steroids used for asthma or chronic obstructive pulmonary disease can also suppress the HPA axis, especially at high doses and over long periods. Although less risky than high-dose oral steroids, strong inhaled steroids still enter the bloodstream and can reduce CRH and ACTH signals and lead to tertiary adrenal insufficiency in some patients. SpringerLink+1

4. Strong topical steroid creams and ointments
   Potent steroid creams used over large body areas or under occlusive dressings for long periods can be absorbed through the skin. This can cause systemic steroid effects, including suppression of the hypothalamus and pituitary. Over time, this may result in tertiary adrenal insufficiency, especially in children or people with thin or damaged skin. Ovid+1

5. Intranasal steroid sprays
   Steroid sprays for allergic rhinitis or sinus problems usually have low systemic absorption, but high doses, frequent use, or combined use with other steroids can still suppress the HPA axis. In some sensitive individuals, this can contribute to tertiary adrenal insufficiency. Ovid+1

6. Repeated intra-articular or soft-tissue steroid injections
   Steroid injections into joints or soft tissues (for arthritis, bursitis, or tendonitis) can enter the systemic circulation. If injections are repeated or the doses are large, they can suppress CRH and ACTH release, leading to tertiary adrenal insufficiency. JSTOR+1

7. Chronic intravenous or intramuscular glucocorticoids
   Some patients receive steroids by injection for autoimmune diseases, cancer, or other conditions. Long-term injected steroids have strong systemic effects and can cause marked HPA axis suppression, resulting in tertiary adrenal insufficiency when the steroids are reduced or stopped. Endocrine Society+1

8. Sudden stopping of long-term steroid therapy
   If someone has taken steroids for weeks or months and then stops them suddenly, the HPA axis may not have had time to recover. Because CRH and ACTH remain low and the adrenal glands are “sleepy,” the person can develop acute symptoms of adrenal insufficiency. This is why gradual tapering of long-term glucocorticoids is important. Endocrine Society+2NIDDK+2

9. Hypothalamic tumors
   Tumors involving the hypothalamus can damage CRH-producing cells or interrupt their blood supply. This reduces the CRH signal to the pituitary, leading to low ACTH and low cortisol, which is tertiary adrenal insufficiency. Examples include craniopharyngioma, hypothalamic glioma, and metastatic tumors. Children’s Hospital of Philadelphia+1

10. Brain radiation therapy affecting the hypothalamus
    Radiation therapy to treat brain tumors, leukemia, or other cancers can injure the hypothalamus and pituitary over time. Months or years after treatment, patients may develop central adrenal insufficiency, including tertiary adrenal insufficiency if the hypothalamus is mainly affected. Children’s Hospital of Philadelphia+1

11. Neurosurgery near the hypothalamic–pituitary region
    Operations in or near the sellar and suprasellar region may disturb blood flow or directly damage the hypothalamus. This can reduce CRH production and cause tertiary adrenal insufficiency after surgery, sometimes together with other pituitary hormone deficiencies. Children’s Hospital of Philadelphia+1

12. Infiltrative diseases (sarcoidosis, histiocytosis, hemochromatosis)
    Some systemic diseases deposit abnormal cells or materials in the hypothalamus and pituitary. Examples include sarcoidosis, Langerhans cell histiocytosis, and iron overload (hemochromatosis). These conditions can interfere with CRH production and lead to tertiary adrenal insufficiency. UpToDate+1

13. Traumatic brain injury (TBI)
    Moderate or severe head injury can damage the hypothalamic–pituitary region through bleeding, swelling, or shearing forces. Months after the injury, some patients develop central adrenal insufficiency due to reduced CRH or ACTH, which can present as tertiary adrenal insufficiency when the hypothalamus is mainly affected. NCBI+1

14. Subarachnoid hemorrhage or stroke affecting the hypothalamus

15. Bleeding around the brain or stroke involving the hypothalamic area can disrupt hormone-producing cells or their connections. This may lead to persistent reduction in CRH release and tertiary adrenal insufficiency, sometimes together with other pituitary hormone problems. UpToDate+1

15. Genetic or congenital hypothalamic defects
    Rare genetic disorders that affect development or function of the hypothalamus can also reduce CRH production. Children with these conditions may present with central adrenal insufficiency, including tertiary adrenal insufficiency, along with other hormonal and developmental problems. Children’s Hospital of Philadelphia+1

16. Chronic opioid therapy
    Long-term use of opioid medicines such as morphine, oxycodone, or methadone can suppress the HPA axis. Opioids act on receptors in the hypothalamus and pituitary, lowering CRH and ACTH release and sometimes causing tertiary adrenal insufficiency, especially in high doses or prolonged use. NCBI+1

17. Megestrol acetate and some other hormonal drugs
    Certain hormonal medicines, such as megestrol acetate used for appetite stimulation or cancer care, can suppress ACTH and cortisol production by acting on the HPA axis. This suppression is central and may behave like tertiary adrenal insufficiency. NCBI+1

18. Prolonged critical illness and intensive care
    Some very ill patients in intensive care develop a functional state where the HPA axis is blunted. In some cases, reduced hypothalamic drive contributes to low cortisol levels. This “critical illness–related corticosteroid insufficiency” can overlap with tertiary adrenal insufficiency, particularly when illness and drugs together suppress CRH and ACTH. NCBI+1

19. Post-treatment of Cushing disease or Cushing syndrome
    After surgery or medical treatment for Cushing disease or other causes of high cortisol, the hypothalamus and pituitary may remain suppressed for a long time. During this period, patients can have tertiary adrenal insufficiency and need temporary cortisol replacement until the HPA axis recovers. NCBI+1

20. Cranial irradiation in childhood
    Children who receive radiation to the brain for leukemia or brain tumors are at risk of late endocrine effects. Years later, they may develop impaired growth hormone, gonadal hormones, and central adrenal insufficiency due to hypothalamic damage, which includes tertiary adrenal insufficiency. Children’s Hospital of Philadelphia+1

Symptoms of tertiary adrenal insufficiency

1. Chronic fatigue and low energy
   The most common symptom is feeling very tired and weak, even after rest. Low cortisol means the body cannot respond well to normal physical and mental stress, so everyday tasks feel exhausting. This fatigue often develops slowly and may be misinterpreted as stress, depression, or “just being unfit.” NCBI+1

2. Muscle weakness
   People often notice that their muscles feel weak, heavy, or easily tired. Climbing stairs, lifting objects, or exercising becomes harder. Cortisol helps maintain muscle function and blood sugar; when it is low, muscles do not get enough energy during activity. NCBI+1

3. Loss of appetite
   Many patients with tertiary adrenal insufficiency lose their desire to eat. Food seems less appealing, and meal sizes become smaller. This lack of appetite is related to low cortisol, low energy, and sometimes low blood sugar and nausea. NCBI+1

4. Unintentional weight loss
   Because appetite is poor and the body cannot store and use energy normally, people may lose weight without trying. Clothes become looser, and the weight loss may be gradual over months. This weight loss is often one of the warning signs that leads doctors to test for adrenal insufficiency. NCBI+1

5. Nausea and sometimes vomiting
   Low cortisol can disturb digestion and the balance of salts and fluids in the body. As a result, people may feel sick to their stomach, especially in the morning or when stressed. In more severe cases, they may vomit, which further reduces fluid and blood volume and can make adrenal crisis more likely. NCBI+1

6. Abdominal pain or discomfort
   Some patients report vague stomach pain, cramping, or discomfort that has no clear cause on examination or imaging. This may come from slow gut movement, mild inflammation, and changes in blood flow to the intestines associated with low cortisol. NCBI+1

7. Dizziness or feeling faint, especially when standing up
   Cortisol helps blood vessels respond to adrenaline and maintain blood pressure. When cortisol is low, blood pressure may drop, especially when moving from lying to standing. This can cause dizziness, light-headedness, or a feeling that one might faint. In tertiary adrenal insufficiency, aldosterone is usually normal, so the drop may be milder than in primary adrenal disease, but it can still be very disturbing. NCBI+1

8. Headaches
   Frequent or persistent headaches may occur, sometimes related to low blood pressure, low blood sugar, or underlying brain conditions such as tumors or previous surgery that caused the tertiary adrenal insufficiency. Headaches can also reflect associated pituitary or hypothalamic problems. Children’s Hospital of Philadelphia+1

9. Low blood sugar episodes (hypoglycemia)
   Cortisol helps maintain normal blood sugar by supporting the release of glucose from the liver and by balancing insulin action. When cortisol is low, blood sugar can drop, especially during fasting, exercise, or illness. People may feel shaky, sweaty, hungry, confused, or irritable during these episodes. NCBI+1

10. Joint pain and body aches
    Generalized aches, pains, and stiffness in joints and muscles are common but non-specific symptoms. They may be due to inflammation, low energy availability in tissues, and coexisting autoimmune or inflammatory diseases that required steroid therapy in the first place. NCBI+1

11. Mood changes, depression, or irritability
    Cortisol has important effects on mood and brain function. Low cortisol may cause low mood, apathy, irritability, anxiety, or difficulty concentrating. Patients may be misdiagnosed with depression or chronic fatigue syndrome before adrenal insufficiency is discovered. NCBI+1

12. Poor stress tolerance
    People with tertiary adrenal insufficiency often say they “cannot handle stress.” Even minor infections, work stress, or emotional problems can make them feel extremely unwell. This happens because their bodies cannot raise cortisol levels quickly and strongly in response to stress, as a healthy HPA axis would do. NCBI+1

13. Changes in menstrual periods or sexual function
    In women, central adrenal insufficiency may occur together with other pituitary hormone problems. Menstrual periods may become irregular, lighter, or stop. In all genders, reduced energy, low blood pressure, and associated pituitary hormone changes can lead to low libido and reduced sexual function. Children’s Hospital of Philadelphia+1

14. Pale skin without darkening
    Unlike primary adrenal insufficiency, tertiary adrenal insufficiency usually does not cause darkening of the skin (hyperpigmentation). This is because ACTH levels are low or inappropriately normal, not high. The skin often looks pale or normal, which can make the diagnosis less obvious. NCBI+2Wikipedia+2

15. Adrenal crisis symptoms during severe stress
    If tertiary adrenal insufficiency is not recognized, a serious illness, surgery, or accident can trigger an adrenal crisis. Symptoms include severe vomiting, very low blood pressure, severe weakness, confusion, and possible loss of consciousness. This is a medical emergency and needs urgent hospital care and steroid treatment. NCBI+2NIDDK+2

Important: If someone has known adrenal insufficiency or is on long-term steroids and develops severe vomiting, very low blood pressure, or confusion, they need emergency medical help. Do not change or stop prescribed steroid medicines without a doctor’s advice.

Diagnostic tests for tertiary adrenal insufficiency

Physical examination tests

1. General physical examination and vital signs
   The doctor first checks overall appearance, weight, heart rate, blood pressure, and temperature. They look for signs such as low blood pressure, fast heart rate, weight loss, and dehydration. Although these findings are not specific, they raise suspicion of adrenal insufficiency, especially in someone who uses or recently stopped steroids. NCBI+2NIDDK+2

2. Orthostatic blood pressure and pulse test
   The doctor measures blood pressure and pulse while the person is lying down, and again after standing for one and three minutes. A significant drop in blood pressure or rise in pulse suggests that the body cannot maintain blood pressure when standing. This can occur in adrenal insufficiency because cortisol helps blood vessels respond to stress. NCBI+1

3. Body weight and growth assessment
   In adults, repeated weight measurements may show gradual weight loss. In children, doctors also check height and growth charts. Poor weight gain or slowed growth over time may suggest chronic under-replacement of cortisol or central hormone problems, including tertiary adrenal insufficiency. Children’s Hospital of Philadelphia+1

4. Skin, hair, and mucous membrane examination
   The doctor examines the skin for color changes, scars, bruising, and signs of long-term steroid use such as thin skin or stretch marks. In tertiary adrenal insufficiency, the skin is usually not darkened, which helps distinguish it from primary adrenal insufficiency. They also check the mouth and gums for pigmentation or pallor. NCBI+2Wikipedia+2

Manual examination tests

5. Abdominal palpation
   The doctor gently presses on the abdomen to look for tenderness, masses, or organ enlargement. In tertiary adrenal insufficiency, findings are often normal, but abdominal discomfort or pain without clear cause may support the clinical picture when combined with other signs and test results. NCBI+1

6. Manual muscle strength testing
   The doctor asks the person to push or pull against resistance with arms and legs. Muscle strength may be reduced, especially in the thigh and shoulder muscles, because long-term steroids can cause muscle wasting and low cortisol leads to poor energy supply during activity. NCBI+1

7. Neurological examination
   A brief neurological exam assesses reflexes, coordination, and sensation. This helps rule out other causes of fatigue, weakness, or dizziness, such as nerve disease or brain lesions. In some patients with hypothalamic or pituitary tumors, neurological signs (visual field loss, eye movement problems) can point to the underlying cause of tertiary adrenal insufficiency. Children’s Hospital of Philadelphia+1

8. Joint and spine examination
   The doctor moves the joints and spine to check for pain, swelling, or stiffness. This is important because many people with tertiary adrenal insufficiency are being treated for inflammatory or autoimmune diseases. Examining the joints helps balance the need for steroid treatment with the risk of adrenal suppression. NCBI+1

Laboratory and pathological tests

9. Early morning serum cortisol level
   A blood test is taken early in the morning, usually between 7 and 9 a.m., when cortisol should be highest. A clearly low cortisol level suggests adrenal insufficiency. However, in people on or recently off steroids, interpretation is complex, and further tests are usually needed to confirm tertiary adrenal insufficiency. NCBI+2Endocrine Society+2

10. Plasma ACTH level
    A blood test measures ACTH at the same time as cortisol. In tertiary adrenal insufficiency, cortisol is low or low-normal and ACTH is low or inappropriately normal, showing that the problem is central rather than in the adrenal glands themselves. This helps distinguish tertiary from primary adrenal insufficiency, where ACTH is high. NCBI+2Wikipedia+2

11. Short ACTH (Synacthen) stimulation test
    In this test, synthetic ACTH is injected, and cortisol levels are measured before and after (usually at 30 and 60 minutes). If the adrenals have been suppressed for a long time, they may not respond well, and cortisol will not rise adequately. This indicates adrenal insufficiency, which can be due to tertiary causes when ACTH and CRH have been low. NCBI+2Endocrine Society+2

12. Insulin tolerance test (ITT)
    In specialized centers, the insulin tolerance test is considered a “gold standard” for assessing the entire HPA axis. Insulin is given to cause controlled low blood sugar, which should strongly stimulate cortisol release if the axis is healthy. Failure of cortisol to rise appropriately suggests central adrenal insufficiency, including tertiary adrenal insufficiency. This test carries risks and must be done under close supervision. NCBI+2Endocrine Society+2

13. Metyrapone test
    Metyrapone blocks a step in cortisol production, which should cause the pituitary to increase ACTH if the HPA axis is intact. Measuring cortisol precursors after metyrapone helps assess whether the hypothalamus and pituitary can respond. A poor response suggests central adrenal insufficiency and can help diagnose tertiary adrenal insufficiency. NCBI+1

14. Serum electrolytes, glucose, and kidney function tests
    Blood tests measure sodium, potassium, glucose, urea, and creatinine. In tertiary adrenal insufficiency, sodium and potassium are often normal because aldosterone is usually preserved, but low sodium and low glucose may still occur. These tests help assess severity, dehydration, and the presence of adrenal crisis. NCBI+2NIDDK+2

15. Comprehensive pituitary hormone panel
    Because tertiary adrenal insufficiency can be part of a broader central hormone problem, doctors often test thyroid-stimulating hormone (TSH), free T4, prolactin, luteinizing hormone (LH), follicle-stimulating hormone (FSH), growth hormone (GH) or IGF-1, and sometimes others. Abnormalities suggest a pituitary or hypothalamic disorder and support the diagnosis of central (secondary or tertiary) adrenal insufficiency. Children’s Hospital of Philadelphia+2UpToDate+2

16. Tests for underlying systemic or infiltrative diseases
    Depending on the clinical picture, doctors may order tests for sarcoidosis, tuberculosis, hemochromatosis, or other systemic diseases that can affect the hypothalamus. These tests might include inflammatory markers, serum ACE, iron studies, or specific infection tests. Finding such a disease can explain why tertiary adrenal insufficiency developed and guide treatment. UpToDate+1

Electrodiagnostic tests

17. Electrocardiogram (ECG)
    An ECG records the electrical activity of the heart. In adrenal insufficiency, ECG may show changes related to low blood pressure, low blood volume, or electrolyte abnormalities. Although ECG does not diagnose tertiary adrenal insufficiency directly, it is important for assessing overall heart status, especially in suspected adrenal crisis. NCBI+1

18. Continuous cardiac and blood pressure monitoring
    In hospital, people with suspected adrenal crisis or those undergoing stimulation tests may have continuous ECG and blood pressure monitoring. This allows doctors to detect dangerous drops in pressure or rhythm changes quickly and to treat them. These electrodiagnostic observations help keep testing and treatment safe in patients with adrenal insufficiency. NCBI+1

Imaging tests

19. MRI of the hypothalamus and pituitary
    Magnetic resonance imaging (MRI) of the brain, focused on the hypothalamus and pituitary, is the key imaging test for central adrenal insufficiency. It can show tumors, cysts, inflammation, scarring, or structural abnormalities that explain reduced CRH or ACTH production. A normal MRI does not rule out glucocorticoid-induced tertiary adrenal insufficiency, but an abnormal MRI can identify other important causes. Children’s Hospital of Philadelphia+2UpToDate+2

20. CT or MRI of the adrenal glands when needed
    Although tertiary adrenal insufficiency mainly involves the brain, sometimes doctors also image the adrenal glands with CT or MRI. This is done to rule out primary adrenal diseases like Addison’s disease, adrenal bleeding, or tumors, especially if the clinical picture or blood tests are unclear. Normal-appearing adrenal glands support the diagnosis of central (secondary or tertiary) adrenal insufficiency. NCBI+2Mayo Clinic+2

Non-pharmacological treatments

1. Patient education and “sick-day rules”
A key non-drug treatment is clear education about the disease, daily medicines, and what to do during illness, surgery, or major stress. “Sick-day rules” teach you to increase steroid dose during fever, vomiting, trauma, or operations to avoid adrenal crisis. Education also includes written plans, teaching family what to do, and rehearsing emergency steps. The purpose is to keep cortisol high enough during stress. The mechanism is simple: information plus practice means you act quickly when unwell so your body does not run out of cortisol.endocrinology.org+2European Society of Endocrinology+2

2. Wearing a medical alert bracelet or card
A visible medical ID bracelet, necklace, or card stating “Adrenal insufficiency – steroid dependent” helps emergency staff give life-saving steroid injections if you cannot speak. Many adrenal groups and endocrine societies recommend medical IDs for all steroid-dependent patients. The purpose is to avoid delay in diagnosis and treatment during accidents, surgery, or sudden illness. The mechanism is rapid communication: the bracelet tells paramedics and doctors that cortisol replacement is urgent, so they can start IV hydrocortisone and fluids immediately.medicalert.org+2adrenalinsufficiency.org+2

3. Emergency steroid injection training
People with adrenal insufficiency are often given an emergency hydrocortisone injection kit. They and their close family are trained to give the shot in the thigh if vomiting, severe diarrhoea, trauma, or collapse prevents swallowing tablets. The purpose is to prevent or treat adrenal crisis at home or in transit to hospital. The mechanism is fast delivery of a high steroid dose directly into the muscle or vein, raising cortisol quickly and supporting blood pressure and blood sugar until full medical care is available.endocrinology.org+2Worcestershire Acute Hospitals NHS Trust+2

4. Gradual tapering of long-term steroids
The safest way to prevent or improve tertiary adrenal insufficiency is slow, planned reduction of long-term glucocorticoid therapy rather than sudden stopping. Doctors reduce the dose step by step and sometimes switch from a very strong steroid to a weaker one like hydrocortisone before stopping. The purpose is to give the hypothalamus–pituitary–adrenal (HPA) axis time to wake up. The mechanism is that gradual dose reductions allow CRH and ACTH to rise again and stimulate the adrenal glands to restart cortisol production.Cleveland Clinic Journal of Medicine+2PMC+2

5. Regular follow-up with an endocrinologist
Seeing an endocrine specialist helps fine-tune steroid dose, tapering speed, and replacement needs. The doctor reviews symptoms, blood pressure, weight, and blood tests such as morning cortisol and ACTH. The purpose is to avoid both under-replacement (risk of crisis) and over-replacement (risk of weight gain, diabetes, and bone loss). The mechanism is continuous monitoring and dose adjustment based on clinical signs and test results, following evidence-based guidelines for adrenal insufficiency and glucocorticoid-induced adrenal suppression.NCBI+2Frontiers+2

6. Routine vaccination and infection prevention
Because infections are a major trigger for adrenal crisis, routine vaccines (for example influenza and pneumonia) and good hygiene are important. The purpose is to reduce serious infections that increase cortisol demand. The mechanism is immune priming: vaccines help the immune system recognise germs earlier, so illness is milder. With fewer or less severe infections, there are fewer episodes of high stress where the body may struggle to make enough cortisol, especially during steroid tapering.endocrinology.org+1

7. Stress management and mental health support
Chronic psychological stress raises cortisol needs and can worsen fatigue and mood symptoms in adrenal insufficiency. Relaxation techniques, breathing exercises, counselling, or cognitive behavioural therapy can reduce anxiety and improve coping. The purpose is to stabilise daily stress levels so the replacement steroid dose remains appropriate. The mechanism is lower sympathetic nervous system activation and more regular daily routines, reducing surprise spikes in cortisol demand and improving sleep quality and overall wellbeing.NCBI+1

8. Regular, moderate physical activity
Gentle to moderate exercise, such as walking, cycling, or swimming, improves cardiovascular fitness, muscle strength, mood, and sleep. For people with adrenal insufficiency, training must be gradual and paired with correct steroid timing and hydration. The purpose is to rebuild strength and reduce fatigue without provoking crisis. The mechanism is improved circulation, better insulin sensitivity, and stronger muscles, which together support blood pressure and energy. Having a predictable exercise routine also helps doctors match steroid doses to daily activity.NCBI+1

9. Optimised sleep routine
Good sleep helps regulate hormones including cortisol. Going to bed and waking at consistent times, limiting screens before bed, and having a quiet dark room can all help. The purpose is to support the body’s natural circadian rhythm, which guides normal cortisol peaks in the early morning and lower levels at night. The mechanism is improved brain control of the HPA axis, better mood, and reduced perception of fatigue, which is important in people who already have low cortisol reserve.Frontiers+1

10. Balanced, nutrient-dense diet
A diet rich in vegetables, fruits, lean protein, whole grains, and healthy fats supports energy and bone health, and helps manage blood sugar, blood pressure, and weight. Some people with adrenal insufficiency need more salt or more calcium and vitamin D, depending on the type of adrenal problem and the medicines they take. The purpose is to support long-term health and reduce complications such as osteoporosis. The mechanism is steady supply of micronutrients and stable blood sugar, which reduces stress on the body and complements steroid replacement.NIDDK+2Medical News Today+2

11. Avoiding unnecessary fasting and crash diets
Long gaps without food can lead to low blood sugar, especially in people with limited cortisol reserve. Very low-calorie diets or fasting plans can also cause stress and weight loss that mimic adrenal crisis. The purpose is to keep blood sugar steady and avoid extra strain on the HPA axis. The mechanism is regular intake of carbohydrates and protein, which provides fuel for the brain and muscles and reduces the need for the body to break down its own tissue, a process normally helped by cortisol.Healthline+1

12. Limiting alcohol
Alcohol can lower blood pressure, upset blood sugar, and irritate the stomach, which may worsen nausea or vomiting during illness. In heavy use, it can interfere with liver metabolism of steroids. The purpose is to prevent sudden drops in blood pressure and reduce the risk that vomiting will stop you from absorbing oral steroid tablets. The mechanism is simple: less alcohol means more stable cardiovascular and metabolic function, which is crucial when cortisol reserve is low.NCBI+1

13. Avoiding abrupt stopping of topical, inhaled, or injected steroids
Potent steroid creams, inhalers, joint injections, and eye drops can all suppress the HPA axis if used at high doses for long periods. Stopping them suddenly after months can contribute to tertiary adrenal insufficiency. The purpose of careful tapering or dose review is to prevent sudden cortisol withdrawal. The mechanism is similar to oral steroid tapering: dose reduction over time allows the hypothalamus and pituitary to restart CRH and ACTH production safely.endocrinology.org+1

14. Bone health strategies
Long-term steroid use increases the risk of osteoporosis and fractures. Non-drug bone strategies include weight-bearing exercise, fall-prevention plans at home, safe footwear, and enough dietary calcium and vitamin D. The purpose is to protect bones and reduce fracture risk while on steroid replacement. The mechanism is improved bone formation from mechanical loading and adequate minerals, plus lower fall risk through better balance and strength.Office of Dietary Supplements+2Office of Dietary Supplements+2

15. Blood pressure and salt management
In tertiary adrenal insufficiency, aldosterone is usually normal, but some patients still have low blood pressure, especially during tapering. Extra salt and fluids may be advised in hot weather, during exercise, or illness. The purpose is to support blood volume and prevent dizziness and fainting. The mechanism is improved sodium and water retention in the circulation, helping the heart maintain blood pressure when cortisol is low.NIDDK+2addisonsdisease.org.uk+2

16. Travel planning and emergency kits
Travel increases risk because of time-zone changes, lost luggage, and unfamiliar medical systems. Planning includes carrying double supplies of steroids, keeping an emergency hydrocortisone injection in hand luggage, and a doctor’s letter. The purpose is to ensure access to medicines and emergency treatment anywhere. The mechanism is risk reduction: even if bags are lost or you become ill on a plane or in a remote area, you still have access to life-saving steroids and clear written instructions for local doctors.Cambridge University Hospitals+1

17. Clear communication with all healthcare providers
Every doctor, dentist, or nurse you see should know you have adrenal insufficiency and are steroid-dependent. This includes before surgery, dental extractions, or imaging with contrast. The purpose is to ensure steroid “stress doses” are given when needed and steroid doses are not stopped suddenly. The mechanism is coordinated care: each provider adjusts their plan (for example IV hydrocortisone before anaesthesia) so your cortisol needs are met during procedures.endocrinology.org+2European Society of Endocrinology+2

18. Psychological and social support groups
Living with a chronic endocrine condition can cause anxiety, low mood, or fear of crisis. Patient support groups and counselling offer shared experience, practical tips, and emotional support. The purpose is to reduce isolation and improve adherence to treatment plans. The mechanism is improved mental health and self-efficacy, leading to better daily management of medicines, diet, exercise, and sick-day rules.nhs.uk+1

19. Education about drug interactions
Some medicines (for example certain antifungals, anti-seizure drugs, and HIV drugs) can change how the liver breaks down steroids. Others may change blood pressure or blood sugar. The purpose of education is to check all new medicines with the endocrinologist or pharmacist. The mechanism is prevention of under- or over-treatment, by adjusting steroid dose when interacting drugs are started or stopped.FDA Access Data+2FDA Access Data+2

20. Healthy weight management
Both long-term steroids and chronic fatigue can lead to weight gain and loss of muscle mass. Simple strategies include portion control, more vegetables and lean protein, and limiting sugary drinks and ultra-processed foods. The purpose is to protect heart health, blood sugar, and joints. The mechanism is reduced strain on the cardiovascular system and better insulin sensitivity, which in turn lowers overall stress on the body and may help symptoms such as tiredness and joint pain.HealthCentral+1

Drug treatments

Important safety note: The medicines below are examples used in adrenal insufficiency. Exact drug choice, dose, timing, and changes must always be decided by a qualified doctor who knows the individual patient. Never start, stop, or change steroid doses on your own.

Because tertiary adrenal insufficiency is mainly due to long-term glucocorticoid use, the key drugs are glucocorticoid replacements (such as hydrocortisone) and safe tapering regimens. There are only a limited number of core drugs with strong evidence; it is better to cover these accurately than to list many weak options.NCBI+2Frontiers+2

1. Hydrocortisone tablets (for daily replacement)
Hydrocortisone is a short-acting glucocorticoid that is closest to natural cortisol. FDA-approved products, such as Cortef, are indicated for adrenal insufficiency.FDA Access Data+1 Doctors usually split the daily dose into two or three doses, with the largest in the morning, to mimic the body’s rhythm. Guidelines suggest total daily adult replacement of about 15–25 mg in divided doses, adjusted to the person’s size and symptoms.Frontiers+1 The purpose is to replace missing cortisol for daily life. The mechanism is direct binding to glucocorticoid receptors, supporting blood pressure, blood sugar, and stress responses. Side effects, especially if the dose is too high, can include weight gain, high blood pressure, diabetes, mood changes, and bone loss.FDA Access Data+1

2. Hydrocortisone oral solution or granules (especially for children)
Newer oral hydrocortisone solutions and granules in capsules for opening allow very flexible small doses, useful in children and people who cannot swallow tablets. FDA-approved hydrocortisone oral products are indicated as replacement therapy in adrenal insufficiency.FDA Access Data+1 Doctors tailor the dose to body weight and age, often giving several small doses over the day. The purpose is accurate, child-friendly cortisol replacement with better growth and fewer side effects. The mechanism is the same as tablets but with more precise dosing. Possible side effects include growth slowing, Cushing-like features, and bone thinning if the dose is too high for too long.FDA Access Data+1

3. Hydrocortisone sodium succinate injection (emergency use)
Injectable hydrocortisone (often as hydrocortisone sodium succinate) is used in adrenal crisis or when patients cannot take tablets, such as during surgery or severe vomiting. FDA labeling states its use in adrenocortical insufficiency and as emergency therapy.FDA Access Data+1 In an adrenal crisis, doctors give a high IV or IM dose followed by repeated doses or continuous infusion, alongside IV fluids. The purpose is rapid rescue of blood pressure and blood sugar. The mechanism is immediate high-level cortisol replacement. Side effects can include high blood sugar, mood changes, fluid retention, and infection risk, especially if high doses are prolonged.endocrinology.org+1

4. Cortisone acetate
Cortisone acetate is another natural glucocorticoid that is converted to hydrocortisone in the liver. FDA labeling includes its use for adrenocortical insufficiency, often as an alternative to hydrocortisone.FDA Access Data+1 Its dose is usually slightly higher than hydrocortisone because of conversion steps and is given in divided daily doses. The purpose is to maintain adequate cortisol levels when hydrocortisone is unsuitable or unavailable. The mechanism is similar to hydrocortisone after conversion. Side effects are also similar: weight gain, metabolic changes, and bone loss if the dose is too high or taken for many years.FDA Access Data+1

5. Prednisone (oral)
Prednisone is a synthetic glucocorticoid often used for autoimmune and inflammatory diseases. FDA labels list treatment of various endocrine conditions and warn that long-term use can cause adrenal suppression.FDA Access Data+2FDA Access Data+2 In tertiary adrenal insufficiency, prednisone may be the drug that originally caused suppression. Doctors then gradually reduce the dose and sometimes use low-dose prednisone or switch to hydrocortisone while the HPA axis recovers. The purpose is safe anti-inflammatory treatment while preventing abrupt cortisol withdrawal. Mechanistically, prednisone binds glucocorticoid receptors strongly and is long-acting. Side effects include weight gain, high blood pressure, diabetes, mood and sleep changes, and osteoporosis.FDA Access Data+2FDA Access Data+2

6. Prednisolone (oral)
Prednisolone is the active form related to prednisone and is widely used as an anti-inflammatory steroid. FDA-approved products such as Orapred ODT are indicated for many allergic, respiratory, and other inflammatory conditions, including endocrine disorders.FDA Access Data Like prednisone, long-term prednisolone at moderate or high doses can cause tertiary adrenal insufficiency, so careful tapering is essential. Some guidelines use low-dose prednisolone as an alternative to hydrocortisone for replacement (for example 3–5 mg per day) in stable adults.Frontiers+1 Side effects are similar to other glucocorticoids: metabolic changes, mood effects, and bone loss, especially at higher doses or over many years.FDA Access Data+1

7. Methylprednisolone (Medrol)
Methylprednisolone is a potent glucocorticoid with FDA approval for many inflammatory diseases and for primary or secondary adrenocortical insufficiency, though hydrocortisone or cortisone are preferred for pure replacement.FDA Access Data+1 In practice, high-dose methylprednisolone courses (for example in autoimmune flares) can significantly suppress the HPA axis and lead to tertiary adrenal insufficiency if stopped suddenly. The purpose of using it in this context is usually to treat the underlying inflammatory disease, with planned taper and later switch to safer long-term options. Mechanistically it is long-acting and strongly anti-inflammatory. Side effects include fluid retention, mood changes, infection risk, and bone thinning.FDA Access Data+1

8. Dexamethasone (Decadron)
Dexamethasone is a very strong, long-acting glucocorticoid. FDA labeling includes its use in primary or secondary adrenocortical insufficiency, though hydrocortisone or cortisone are preferred for routine replacement.FDA Access Data Because of its long half-life, dexamethasone is often used in testing (for example the dexamethasone suppression test) and in high doses for conditions such as brain swelling or chemotherapy-induced nausea. Long-term use at moderate doses can strongly suppress the HPA axis. The purpose in tertiary insufficiency is usually testing or short-term treatment, not chronic replacement. Side effects include very high risk of Cushing-like changes, weight gain, mental changes, and bone loss if misused.FDA Access Data+1

9. Fludrocortisone (mineralocorticoid – limited role in tertiary disease)
Fludrocortisone is a synthetic mineralocorticoid used mainly in primary adrenal insufficiency to replace aldosterone and help the body retain salt and water.Endocrine Society+1 In tertiary adrenal insufficiency, aldosterone production is usually normal, so fludrocortisone is rarely needed. It may have a role if there is mixed or uncertain adrenal damage with low blood pressure and high potassium that do not respond to salt and glucocorticoid alone. The mechanism is activation of mineralocorticoid receptors, increasing sodium and water reabsorption in the kidneys. Side effects include high blood pressure, swelling, and low potassium if the dose is too high.Endocrine Society+1

10. Short-acting insulin and glucose (supportive in crisis)
In adrenal crisis, blood sugar can be low or, occasionally, high because of stress or steroid injections. IV dextrose (glucose) solutions are standard to correct hypoglycaemia, and insulin may be used if very high sugars occur with high-dose steroids. The purpose is to stabilise blood glucose while hydrocortisone treatment is started. The mechanism is direct correction of low or high glucose levels, protecting the brain and other organs during the acute phase. Side effects can include rebound hypoglycaemia if insulin is over-given, which is why all of this is done in hospital under close monitoring.endocrinology.org+1

(Other medicines such as anti-nausea drugs, blood pressure medicines, or proton pump inhibitors may be used, but they treat symptoms or complications, not the adrenal insufficiency itself.)

Dietary molecular supplements

Always discuss supplements with your doctor or dietitian. Doses below are general examples for adults and may not fit everyone, especially younger people like you.

1. Vitamin D
Vitamin D helps your intestines absorb calcium and supports bone health, immune function, and muscle strength. Many people using long-term steroids have low vitamin D and higher fracture risk. Typical recommended intakes for most teens and adults are around 600 IU per day, with an upper safe limit of 4,000 IU unless a doctor prescribes more for deficiency.Office of Dietary Supplements+2Office of Dietary Supplements+2 The purpose is to protect bones and muscles while on steroids. Mechanistically, vitamin D helps regulate calcium and phosphate levels, promoting normal mineralisation of bone and supporting immune cells.

2. Calcium
Calcium is the main mineral in bones and teeth. Long-term steroid therapy can thin bones, so adequate calcium intake from food or supplements is important. Most adults need about 1,000–1,200 mg per day from food and supplements combined, often taken in divided doses of 500–600 mg for best absorption.Office of Dietary Supplements+2Office of Dietary Supplements+2 The purpose is to maintain bone density and lower fracture risk. The mechanism is straightforward: calcium provides the raw material for bone and supports muscle and nerve function.

3. Omega-3 fatty acids (fish oil or plant sources)
Omega-3 fatty acids (EPA, DHA, and ALA) are healthy fats found in oily fish, flaxseed, and walnuts. They may help lower inflammation, support heart health, and improve triglyceride levels, which can be worsened by steroids.Office of Dietary Supplements+2Office of Dietary Supplements+2 Typical supplemental intakes for general heart health are a few hundred milligrams of EPA+DHA per day, but exact doses vary. The purpose is to support cardiovascular health and possibly reduce steroid-related metabolic risks. Mechanistically, omega-3s are incorporated into cell membranes and can reduce production of inflammatory molecules.

4. Vitamin B12
Vitamin B12 is essential for red blood cell production and nerve function. Some people on long-term steroids or with chronic illness have low B12 intake or absorption, which worsens fatigue. Most adults need about 2.4 micrograms per day, with higher doses used in deficiency.Office of Dietary Supplements+2Office of Dietary Supplements+2 The purpose is to support energy levels and nerve health. Mechanistically, B12 is a co-factor in DNA synthesis and in pathways that keep nerves and blood cells healthy, so correcting deficiency can improve tiredness and cognitive function.

5. Folate (folic acid)
Folate works with B12 in making red blood cells and DNA. Low folate can worsen anaemia and fatigue in adrenal insufficiency. Usual supplemental doses are around 400 micrograms daily for adults, unless higher doses are prescribed for deficiency or pregnancy.e-lactancia.org The purpose is to support normal blood cell production and lower homocysteine levels. Mechanistically, folate is involved in one-carbon metabolism and DNA synthesis, so adequate intake helps tissues repair and renew properly.

6. Magnesium
Magnesium supports muscle and nerve function, heart rhythm, and bone strength. Steroids, vomiting, diarrhoea, or poor diet can lower magnesium levels, causing cramps or weakness. Typical supplemental doses range from about 200–400 mg per day in adults, often taken with food to reduce stomach upset.Office of Dietary Supplements+1 The purpose is to support muscle function and reduce cramps. Mechanistically, magnesium is a cofactor in many enzyme reactions, especially those involving energy (ATP), so normal levels improve neuromuscular stability.

7. Zinc
Zinc is important for immune function, wound healing, and taste. Chronic illness, poor appetite, or restricted diets can reduce zinc intake. Common supplemental doses are about 8–11 mg per day for adults, sometimes higher short-term if deficiency is present.Office of Dietary Supplements+1 The purpose is to support immune defence and healing in a body already stressed by low cortisol. Mechanistically, zinc is involved in many enzymes and in gene expression in immune cells, helping them respond properly to infections.

8. Vitamin C
Vitamin C is an antioxidant that supports immune function and helps the body absorb iron. It may help reduce the severity or duration of common infections, although evidence is modest. Typical supplemental doses are 75–120 mg per day for adults, with higher amounts used short-term during illness.Office of Dietary Supplements+1 The purpose is to support immune health and reduce oxidative stress. Mechanistically, vitamin C helps regenerate other antioxidants, supports collagen production, and may help white blood cells work better.

9. Probiotics
Probiotics are “good bacteria” found in yoghurt, fermented foods, or supplement capsules. They may help prevent antibiotic-associated diarrhoea and support gut health, which is important when you rely on oral steroid tablets. Evidence is still developing, and strains and doses vary widely.nutrition.ucdavis.edu The purpose is to support a healthy gut microbiome and possibly improve immune balance. Mechanistically, probiotics can compete with harmful bacteria, produce beneficial short-chain fatty acids, and interact with immune cells in the gut lining.

10. Multivitamin tailored for bone and immune health
A carefully chosen multivitamin with adequate vitamin D, calcium, B vitamins, and trace minerals can simplify supplement routines. It should not exceed upper limits without medical advice.Office of Dietary Supplements+2Office of Dietary Supplements+2 The purpose is to cover small dietary gaps that may develop during chronic illness and treatment. Mechanistically, regular intake of multiple micronutrients supports enzyme systems across the body, including those in bone, blood, and immune cells.

Immunity-supporting and regenerative / stem-cell approaches

At present, there are no FDA-approved “immunity booster,” regenerative, or stem-cell drugs specifically approved to cure tertiary adrenal insufficiency. Research is ongoing, mainly focused on primary adrenal insufficiency and adrenal tissue regeneration.PMC+2Cell+2 Below are six areas related to immunity or regeneration, described for information only, not as routine treatments.

1. Optimised steroid replacement as “immune support”
The safest way to support immunity in tertiary adrenal insufficiency is neither too little nor too much steroid. Under-replacement increases infection risk and crisis; over-replacement suppresses immune responses and raises infection risk in a different way.NCBI+2FDA Access Data+2 The purpose is to keep cortisol in a near-normal range. Mechanistically, physiological doses of glucocorticoids help the immune system respond appropriately to stress without the damaging over-suppression seen with high pharmacologic doses.

2. Vaccination programmes as immune protection
Routine vaccines (influenza, COVID-19, pneumococcal, and others based on national guidelines) reduce the risk of serious infections that could trigger adrenal crisis.endocrinology.org+2Cambridge University Hospitals+2 The purpose is to give targeted immune preparation against key pathogens. Mechanistically, vaccines train specific immune cells to respond quickly and strongly, lowering the chance that an infection overwhelms a person with limited cortisol reserve.

3. DHEA supplementation in selected adults (not routine in teens)
Some adult guidelines discuss using low-dose DHEA (a weak androgen) in women with adrenal insufficiency who have low energy, low libido, and low mood despite good glucocorticoid replacement. Evidence is mixed, and this is specialist care only.National Adrenal Diseases Foundation+1 The purpose is to improve quality of life where adrenal androgen production is low. Mechanistically, DHEA can be converted to sex hormones in tissues and may affect mood and energy, but it is not a cure and is not standard for tertiary adrenal insufficiency.

4. Experimental adrenal stem-cell and organoid therapies
Scientists are developing adrenal organoids (mini-glands grown from stem cells) and studying how to regenerate adrenal cortex tissue.ScienceDirect+2Cell+2 Preclinical studies show that stem-cell-derived steroidogenic cells and bioprinted adrenal tissues can make cortisol and respond to ACTH in animals.PMC+2PMC+2 The purpose is to create future cell-based therapies that might one day replace damaged adrenal glands. Mechanistically, transplanted cells or tissues would produce cortisol and other steroids in response to ACTH, potentially restoring a more natural rhythm. These treatments are experimental and not available in routine care.

5. Adrenal gland transplantation (rare and experimental)
There are rare case reports of adrenal gland transplantation (for example combined kidney–adrenal transplants) and experimental animal studies using adrenal spheroids.Frontiers+1 These are done in highly specialised centres. The purpose is to provide new adrenal tissue capable of cortisol and aldosterone production. Mechanistically, donor adrenal tissue is implanted and supplied with blood so it can secrete hormones. Because of rejection risks, immunosuppression, and technical difficulty, this is not standard therapy for tertiary adrenal insufficiency.

6. Regenerative research into adrenal stem cell niches
Basic science research explores how adrenal stem cells renew adrenal tissue and how signals like ACTH and Sonic hedgehog pathways control this.Frontiers+2e-enm.org+2 The purpose is to understand how to safely stimulate or replace adrenal cells in disease. Mechanistically, this research studies how stem cells differentiate into steroid-producing cells and how this process might be harnessed or repaired. At present, this information guides lab experiments and future therapies, not clinical treatment today.

Surgeries

Tertiary adrenal insufficiency is usually caused by medicines, so surgery is rarely used to treat it directly. Surgery can be important for underlying brain conditions that disturb the hypothalamus or pituitary.

1. Transsphenoidal pituitary surgery
Benign pituitary tumours such as ACTH-secreting adenomas (Cushing disease) are often removed by transsphenoidal surgery (through the nose and sphenoid sinus).NCBI+1 After surgery, cortisol levels may fall sharply, and temporary secondary or tertiary adrenal insufficiency can occur, needing hydrocortisone replacement until the axis recovers. The procedure is done to remove the tumour, relieve pressure, and normalise hormone production.

2. Craniotomy for hypothalamic or pituitary region tumours
Some larger or complex tumours in the hypothalamic–pituitary region need open skull surgery (craniotomy).UpToDate Surgery can damage or disrupt CRH and ACTH pathways, leading to long-term tertiary adrenal insufficiency that needs replacement steroids. The operation is done to control tumour growth, preserve vision, and protect brain structures, accepting that lifelong hormone replacement may be needed.

3. Radiotherapy to the pituitary region
Targeted radiotherapy is sometimes used when pituitary tumours cannot be fully removed or recur. Over time, radiation can reduce pituitary hormone output, including ACTH.UpToDate+1 This can cause or worsen tertiary adrenal insufficiency. Radiotherapy is done to control tumour growth and reduce hormone over-secretion; doctors then monitor and replace deficient hormones, including cortisol.

4. Surgery for underlying diseases requiring chronic steroids
Sometimes surgery for the primary illness (for example severe inflammatory bowel disease or some autoimmune conditions) allows doctors to reduce or stop long-term high-dose steroids, giving the HPA axis a chance to recover.OUP Academic+1 The purpose is to treat the root cause so less steroid is needed long term. The mechanism is that once inflammation is controlled by surgery, steroid doses can be tapered more safely, lowering the risk of continued tertiary adrenal insufficiency.

5. Experimental adrenal transplant procedures
As noted earlier, a few experimental or highly specialised surgeries transplant adrenal tissue along with other organs.Frontiers+1 These are not standard care and are reserved for very rare cases in research or combined organ transplant settings. The purpose is to attempt full hormonal replacement via donor adrenal tissue, but the need for strong immunosuppressive medicines limits widespread use.

Preventions (10 key strategies)

1. Use the lowest effective steroid dose for the shortest time – For inflammatory diseases, guidelines advise using the minimum glucocorticoid dose that controls disease and considering steroid-sparing drugs when possible. This lowers the chance of HPA axis suppression and tertiary adrenal insufficiency.Cleveland Clinic Journal of Medicine+2OUP Academic+2

2. Avoid abrupt stopping of steroids after more than 3–4 weeks of use – Expert guidance states that courses longer than 3–4 weeks, even at moderate doses, should be tapered rather than stopped suddenly.Endocrine Society+2PMC+2

3. Educate every steroid-treated patient about adrenal suppression risk – Patients on chronic steroids should receive clear information about adrenal insufficiency symptoms and crisis risk, so they know when to seek help.European Society of Endocrinology+1

4. Provide and use steroid “sick-day rules” – Written instructions on dose increases during illness, surgery, or injury significantly reduce adrenal crisis risk.endocrinology.org+2addisonsdisease.org.uk+2

5. Issue medical alert ID and steroid emergency cards – Wearing medical ID and carrying emergency cards makes correct emergency treatment more likely and faster.adrenalinsufficiency.org+2National Adrenal Diseases Foundation+2

6. Routine monitoring during tapering – Gradual dose reduction with regular review of symptoms, blood pressure, and morning cortisol helps detect adrenal suppression early and adjust tapering plans.adrenalinsufficiency.org+2OUP Academic+2

7. Limit use of multiple steroid forms at the same time – Using high-dose tablets together with potent creams, inhalers, or injections increases suppression risk. Clinicians are advised to consider the total steroid “load” when prescribing.endocrinology.org+1

8. Treat infections quickly and appropriately – Early treatment of infections with fluids and appropriate antimicrobials reduces prolonged stress on the body and lowers the chance of adrenal crisis in suppressed patients.endocrinology.org+1

9. Support bone and metabolic health during steroid therapy – Managing diet, exercise, and sometimes using bone-protective medicines lowers some of the long-term complications that might otherwise require more steroids or hospitalisation.Office of Dietary Supplements+2Office of Dietary Supplements+2

10. Regular specialist follow-up and updated care plans – Long-term endocrine follow-up ensures that as the underlying disease or life situation changes, steroid doses, sick-day plans, and emergency kits stay up to date, preventing gaps in protection.NCBI+2Worcestershire Acute Hospitals NHS Trust+2

When to see a doctor

You should see a doctor, preferably an endocrinologist, if you have been on steroids for more than a few weeks and notice severe tiredness, weight loss, dizziness on standing, stomach pain, nausea, vomiting, or darkening of the skin, especially when the steroid dose is reduced.NCBI+2Wikipedia+2

Seek urgent or emergency care immediately if you or someone you are with has symptoms of possible adrenal crisis: extreme weakness, confusion, fainting, severe vomiting or diarrhoea, very low blood pressure, or collapse. This is life-threatening and needs immediate hydrocortisone injection and IV fluids.endocrinology.org+2Worcestershire Acute Hospitals NHS Trust+2

Also see your doctor promptly if you are planning surgery, dental procedures, major travel, or pregnancy, or if any new doctor wants to change or stop your long-term steroid. They can adjust doses and update your sick-day and emergency plan to keep you safe.European Society of Endocrinology+2Cambridge University Hospitals+2

What to eat and what to avoid

1. Eat regular, balanced meals – Include complex carbohydrates, protein, and healthy fats at each meal to keep blood sugar stable and prevent energy crashes.Healthline+1

2. Focus on calcium- and vitamin-D-rich foods – Dairy products, fortified plant milks, leafy greens, and fish with bones support bone health, which is important on long-term steroids.NIDDK+2Medical News Today+2

3. Include lean protein sources – Fish, poultry, beans, lentils, tofu, and eggs help maintain muscle mass, especially when steroids and low cortisol affect muscle strength.NIDDK+1

4. Use healthy fats (olive oil, nuts, seeds) – These support heart health and help absorb fat-soluble vitamins like A, D, E, and K, while avoiding the trans-fats found in many processed snacks.Office of Dietary Supplements+1

5. Limit very salty processed foods unless advised otherwise – In tertiary adrenal insufficiency, aldosterone is usually normal, so very high salt from processed foods (chips, fast food, instant noodles) may raise blood pressure unnecessarily. Your doctor will tell you if extra salt is needed.NIDDK+2addisonsdisease.org.uk+2

6. Avoid high-sugar and highly processed foods – Sugary drinks, sweets, and refined grains can worsen weight gain, blood sugar spikes, and cholesterol, which are already risks with steroids.HealthCentral+1

7. Limit caffeine and energy drinks – Too much caffeine can cause palpitations, anxiety, and sleep problems that may be confused with adrenal symptoms. Moderate tea or coffee is usually fine, but avoid large amounts and late-night energy drinks.Healthline+1

8. Avoid heavy alcohol use – Alcohol can lower blood pressure, irritate the stomach, and interfere with blood sugar control, making adrenal crisis harder to manage.HealthCentral+1

9. Stay well hydrated – Drinking enough water is important, especially in hot climates, during exercise, or when unwell. Mild dehydration can worsen dizziness and low blood pressure in adrenal insufficiency.NIDDK+1

10. Discuss grapefruit and other interacting foods with your doctor – Grapefruit can affect liver enzymes that metabolise some medicines; although data on hydrocortisone itself are limited, it is safest to ask your doctor or pharmacist about possible interactions with your full medicine list.FDA Access Data+1

Frequently asked questions

1. Is tertiary adrenal insufficiency permanent?
Often it is temporary, especially when caused by long-term steroid treatment. The HPA axis may recover over months to a few years if steroids are tapered slowly and safely. Some people, particularly those with brain surgery or radiation, may have longer-lasting or permanent insufficiency and need life-long replacement. Regular testing and follow-up help your doctor see whether recovery is happening.NCBI+2OUP Academic+2

2. How is tertiary adrenal insufficiency diagnosed?
Doctors look at your history of steroid use, symptoms, and blood tests such as morning cortisol and ACTH. Sometimes stimulation tests with synthetic ACTH are used. In tertiary adrenal insufficiency, ACTH may be low or normal and cortisol low. A careful review is needed because tests can be affected by recent steroid doses.NCBI+2UpToDate+2

3. What is the difference between primary, secondary, and tertiary adrenal insufficiency?
In primary insufficiency (Addison disease), the adrenal glands themselves are damaged. In secondary, the pituitary does not make enough ACTH. In tertiary, the hypothalamus does not make enough CRH, often because long-term steroids or high cortisol levels have suppressed the system. The symptoms overlap, but aldosterone is usually normal in secondary and tertiary forms.NCBI+2Wikipedia+2

4. Can I ever stop taking steroid tablets completely?
Many people with steroid-induced tertiary adrenal insufficiency can eventually stop replacement, but only after very slow tapering and careful testing. Others with permanent hypothalamic or pituitary damage may need life-long treatment. Never stop steroid tablets suddenly without medical advice; this can trigger adrenal crisis.Cleveland Clinic Journal of Medicine+2PMC+2

5. How long does HPA axis recovery usually take?
Recovery is very variable. Some people recover in a few months after steroids are stopped; others may take a year or more, and some never fully recover. Factors include how high the steroid dose was, how long it was taken, the specific drug, and individual differences. Regular reviews and, sometimes, repeated stimulation tests guide decisions.Cleveland Clinic Journal of Medicine+2OUP Academic+2

6. What is an adrenal crisis, and how can I avoid it?
An adrenal crisis is a severe lack of cortisol causing very low blood pressure, shock, and risk of death. It can be triggered by infection, surgery, trauma, or sudden stopping of steroids. Prevention includes daily steroid adherence, using sick-day rules, carrying emergency hydrocortisone, and wearing medical ID.endocrinology.org+2addisonsdisease.org.uk+2

7. Can exercise make my adrenal insufficiency worse?
Moderate exercise is usually helpful and recommended, but over-exertion without proper steroid timing, food, and fluids can cause symptoms like dizziness or extreme fatigue. Start slowly, increase intensity gradually, and discuss with your endocrinologist how to time your doses around activity.choendocrine.com.sg+1

8. Do I need extra salt if I have tertiary adrenal insufficiency?
Most people with tertiary adrenal insufficiency do not need a high-salt diet because their aldosterone is normal. However, during hot weather, heavy exercise, or illness with vomiting or diarrhoea, extra fluids and some extra salt may be advised. Your doctor will tailor salt advice based on your blood pressure, blood tests, and other hormones.NIDDK+2addisonsdisease.org.uk+2

9. Can tertiary adrenal insufficiency affect growth in children or teens?
Yes, both the condition and its treatment can affect growth. Too little cortisol can cause poor wellbeing and appetite, while too much steroid can slow growth and thin bones. Paediatric endocrine teams use special hydrocortisone formulations and careful dosing to balance these risks and monitor growth and puberty closely.FDA Access Data+2Frontiers+2

10. Is it safe to get pregnant with adrenal insufficiency?
Many people with adrenal insufficiency have successful pregnancies, but close specialist care is needed. Steroid doses may need adjustment during pregnancy, labour, and after birth. Good control before pregnancy reduces risks for both parent and baby. Anyone planning pregnancy should discuss this early with their endocrinologist and obstetric team.nhs.uk+2National Adrenal Diseases Foundation+2

11. Are “adrenal support” herbal products a good idea?
Most “adrenal support” supplements sold online are not well regulated, may contain hidden steroids or hormones, and have little scientific proof. They can interfere with tests and real medicines. Major endocrine and safety organisations advise against using them. Always show your doctor any supplement you are considering.NCBI+1

12. Does tertiary adrenal insufficiency shorten life expectancy?
With good education, proper steroid replacement, sick-day rules, and medical ID, many people live normal lifespans. The main risks are unrecognised adrenal crisis and long-term complications of high steroid doses such as heart disease and osteoporosis. Regular specialist care greatly reduces these risks.NCBI+2Worcestershire Acute Hospitals NHS Trust+2

13. Can I fast for religious or cultural reasons?
Fasting can be risky in adrenal insufficiency because of low blood sugar and dehydration, especially in hot climates. If fasting is important to you, plan ahead with your endocrinologist. Sometimes shorter fasts, extra evening fluids, or exemptions may be recommended for safety.Healthline+1

14. Do I always need to double my steroid dose when stressed?
Not for small stresses like mild school stress or a short walk, but for fever, significant vomiting, dental surgery, or accidents, dose increases are usually needed according to your sick-day rules. Your individual plan will explain when and how to increase doses.endocrinology.org+2addisonsdisease.org.uk+2

15. What is the single most important thing I can do today?
The most important step is to learn and follow your personal adrenal emergency plan: know your daily dose, have written sick-day rules, carry an emergency hydrocortisone kit if prescribed, and wear medical ID. Then, make sure at least one trusted person knows how to help you in an emergency. These simple steps save lives.endocrinology.org+2adrenalinsufficiency.org+2

Disclaimer: Each person’s journey is unique, treatment plan, life style, food habit, hormonal condition, immune system, chronic disease condition, geological location, weather and previous medical  history is also unique. So always seek the best advice from a qualified medical professional or health care provider before trying any treatments to ensure to find out the best plan for you. This guide is for general information and educational purposes only. Regular check-ups and awareness can help to manage and prevent complications associated with these diseases conditions. If you or someone are suffering from this disease condition bookmark this website or share with someone who might find it useful! Boost your knowledge and stay ahead in your health journey. We always try to ensure that the content is regularly updated to reflect the latest medical research and treatment options. Thank you for giving your valuable time to read the article.

The article is written by Team RxHarun and reviewed by the Rx Editorial Board Members

Last Updated: December o2 , 2025.