Secondary Adrenal Insufficiency

Secondary adrenal insufficiency is a condition where your adrenal glands do not make enough of the stress hormone cortisol because the pituitary gland in your brain is not sending enough ACTH (adrenocorticotropic hormone) to tell them to work. The adrenal glands themselves are usually normal, but they are “under-stimulated,” so cortisol levels fall. Aldosterone (the salt-controlling hormone) is usually normal in secondary adrenal insufficiency, which is one key difference from primary adrenal insufficiency (Addison’s disease). Low cortisol can cause tiredness, low blood pressure, low blood sugar, and a poor response to physical or emotional stress. Wikipedia+1

Other names for secondary adrenal insufficiency

Secondary adrenal insufficiency may also be called central adrenal insufficiency, pituitary adrenal insufficiency, ACTH deficiency–related adrenal insufficiency, or secondary Addison’s disease. When the problem is even higher in the brain, at the hypothalamus, some experts use the term tertiary adrenal insufficiency, but in real life secondary and tertiary forms often look very similar and are grouped together as “central” adrenal insufficiency. Wikipedia+1

Types of secondary adrenal insufficiency

1. Pituitary-tumor–related secondary adrenal insufficiency – A benign or cancerous tumor in the pituitary gland can press on the cells that make ACTH. When those cells are damaged or destroyed, ACTH levels fall and the adrenal glands do not get enough signal to make cortisol. Common tumors include pituitary adenomas and craniopharyngiomas. MSD Manuals+1

2. Post-surgical or post-radiation secondary adrenal insufficiency – Surgery to remove a pituitary tumor, or radiation to treat a pituitary or brain tumor, can accidentally damage ACTH-producing cells. Sometimes this damage appears months or years after treatment, so people need long-term follow up of adrenal function. MSD Manuals+1

3. Glucocorticoid-induced (treatment-related) adrenal insufficiency – Long-term use of steroid medicines such as prednisone, dexamethasone, or high-dose inhaled or injected steroids can “switch off” the hypothalamus and pituitary. When these drugs are stopped too quickly, the body may not be able to raise ACTH and cortisol in time, leading to secondary (or tertiary) adrenal insufficiency. Endocrine Society+1

4. Autoimmune or inflammatory ACTH deficiency – Sometimes the immune system attacks the pituitary (autoimmune hypophysitis) or inflammatory diseases such as sarcoidosis, tuberculosis, or other granulomatous diseases involve the pituitary. This can cause isolated ACTH deficiency or broader failure of the pituitary gland (panhypopituitarism), which then leads to low cortisol. MSD Manuals+2NIDDK+2

5. Genetic or congenital central adrenal insufficiency – In rare cases, babies are born with gene changes that affect ACTH production or pituitary development. These children may present with low blood sugar, poor feeding, or low blood pressure early in life due to chronic cortisol deficiency. UpToDate+1

Causes of secondary adrenal insufficiency

1. Long-term oral steroid therapy – Taking daily steroid tablets such as prednisone for weeks to months for conditions like asthma, rheumatoid arthritis, or lupus can suppress the hypothalamus–pituitary–adrenal (HPA) axis. When the dose is reduced or stopped, the pituitary may not restart ACTH production quickly, and cortisol can drop to unsafe levels. Endocrine Society+1

2. Frequent steroid injections – Repeated high-dose steroid injections into joints, the spine, or soft tissues can be absorbed into the bloodstream and suppress ACTH in the same way as oral steroids, especially when injections are repeated often or combined with other steroid forms. Endocrine Society+1

3. High-dose inhaled steroids – Strong inhaled steroids for severe asthma or COPD, especially at high doses over a long time, can enter the blood and partially shut down ACTH production, leading to central adrenal insufficiency in some people. Endocrine Society+1

4. Potent topical steroids on large skin areas – When powerful steroid creams or ointments are used on large or damaged skin areas for a long time, enough medicine can be absorbed to suppress ACTH and cortisol production. Endocrine Society+1

5. Pituitary adenoma – A benign tumor of the pituitary gland can compress normal pituitary tissue. As it grows, ACTH-producing cells may stop working, causing chronic low ACTH and secondary adrenal insufficiency, often along with other pituitary hormone problems. MSD Manuals+1

6. Craniopharyngioma and other sellar tumors – Tumors that grow near the pituitary stalk, such as craniopharyngiomas or metastatic cancers, can damage the pituitary or the connection from the hypothalamus, reducing ACTH release and lowering cortisol. MSD Manuals+1

7. Pituitary surgery – Operations to remove pituitary tumors can remove or injure normal ACTH-producing tissue. Even carefully done surgery can leave a person with long-term need for cortisol replacement because ACTH secretion never fully recovers. MSD Manuals+1

8. Pituitary radiation therapy – Radiation to treat pituitary or nearby brain tumors may damage hormone-producing cells over time. ACTH deficiency is a known late effect, and patients who have had brain or pituitary radiation are usually monitored for adrenal insufficiency. MSD Manuals+1

9. Pituitary apoplexy (sudden pituitary bleeding) – A sudden bleed into a pituitary tumor or gland can cause intense headache, visual loss, and rapid loss of ACTH and other hormones. This is an emergency and often causes abrupt secondary adrenal insufficiency. MSD Manuals+1

10. Traumatic brain injury – Head trauma can damage the pituitary stalk or gland, leading to partial or complete loss of pituitary hormones, including ACTH. Secondary adrenal insufficiency may appear months or years after the injury. NIDDK+1

11. Subarachnoid hemorrhage or brain bleeding – Bleeding around the brain can interrupt blood flow to the pituitary or hypothalamus, causing ACTH deficiency and central adrenal insufficiency in some survivors. NIDDK+1

12. Autoimmune hypophysitis – The immune system can mistakenly attack the pituitary gland. This autoimmune inflammation may damage ACTH-producing cells, giving secondary adrenal insufficiency, often with other pituitary hormone losses. UpToDate+1

13. Infections of the pituitary or hypothalamus – Tuberculosis, fungal infections, syphilis, or viral infections can involve the pituitary or hypothalamus and disrupt ACTH production, leading to chronic low cortisol. MSD Manuals+1

14. Infiltrative diseases (sarcoidosis, hemochromatosis, Langerhans cell histiocytosis) – Conditions where abnormal cells or iron deposit in the pituitary can slowly damage hormone-producing tissue, including ACTH cells, and cause gradual secondary adrenal insufficiency. MSD Manuals+1

15. Sheehan syndrome (post-partum pituitary necrosis) – Severe bleeding during or after childbirth can cut off the blood supply to the pituitary, leading to death of hormone-producing cells. ACTH deficiency with secondary adrenal insufficiency is a classic part of this condition. Wikipedia+1

16. Genetic defects of ACTH production – Rare mutations in genes that control ACTH production or pituitary development can lead to isolated ACTH deficiency or combined pituitary hormone deficiency and thus secondary adrenal insufficiency from birth or early life. UpToDate+1

17. Empty sella syndrome / idiopathic pituitary failure – In some people, the pituitary gland becomes flattened or small on imaging (empty sella), or pituitary failure occurs without a clear cause. This can include ACTH deficiency and low cortisol production. MSD Manuals+1

18. Pituitary metastases from other cancers – Cancers such as breast or lung cancer can spread to the pituitary region and damage hormone-producing cells, including those making ACTH, leading to secondary adrenal insufficiency. MSD Manuals+1

19. Chronic opioid use – Long-term use of strong opioid pain medicines can suppress the hypothalamus and pituitary. This can reduce ACTH and cortisol in some patients, giving a functional form of secondary adrenal insufficiency. Wikipedia+1

20. Long-term critical illness or severe chronic disease – Very prolonged severe illness, major surgery, or intensive care stays can disturb the HPA axis and sometimes lead to central adrenal insufficiency, especially when combined with steroid use. endocrinology.org+1

Symptoms of secondary adrenal insufficiency

1. Chronic fatigue and low energy – Many people feel deeply tired even after rest or sleep. Everyday tasks may feel heavy, and exercise tolerance is reduced because cells are not getting the normal cortisol support they need for energy metabolism. NIDDK+1

2. Muscle weakness – Patients may notice weak arms or legs, difficulty climbing stairs, lifting objects, or standing from a chair. Cortisol helps muscles respond to stress and low levels can make muscles feel weak and easily tired. NIDDK+1

3. Loss of appetite and early fullness – People often do not feel like eating and may feel full after only a small amount of food. This reduced appetite, together with nausea, contributes to weight loss. NIDDK+1

4. Unintentional weight loss – Because of poor appetite, nausea, and general illness, weight often falls slowly over months. Clothes may become loose even without trying to diet. NIDDK+1

5. Nausea, sometimes vomiting – Cortisol supports normal digestion and helps the body handle stress. When it is low, people commonly feel sick to the stomach, especially in the morning or during illness, and some may vomit. NIDDK+1

6. Abdominal or stomach pain – Dull, cramping, or vague stomach pain is common and can be mistaken for many other digestive problems. In an adrenal crisis, the pain may become severe and spread. NIDDK+1

7. Dizziness, especially when standing – Low cortisol can reduce blood pressure and affect the blood vessels. When a person stands up, blood pressure may drop too much, causing light-headedness, blurred vision, or even fainting. NIDDK+1

8. Low blood pressure – Blood pressure at rest is often lower than usual. Unlike primary adrenal insufficiency, severe salt loss is less common because aldosterone is usually preserved, but low cortisol still contributes to low pressure and poor stress tolerance. Wikipedia+1

9. Low blood sugar (hypoglycemia) – Cortisol helps keep blood sugar stable, especially during fasting. Low cortisol can lead to shakiness, sweating, confusion, or even loss of consciousness due to low blood sugar, particularly in children and very thin adults. NIDDK+1

10. Headache and visual changes – When a pituitary tumor or other mass is the cause, headache is common. If the tumor presses on the optic nerves, the person may lose part of their side vision or have blurred or double vision. MSD Manuals+1

11. Menstrual changes and fertility problems – Women with pituitary disease often have irregular or absent periods and may have trouble becoming pregnant because other pituitary hormones controlling the ovaries are also low, along with ACTH and cortisol. MSD Manuals+1

12. Low sex drive and reduced body hair – Men and women may notice lower interest in sex and reduced body or underarm hair because pituitary damage can also reduce sex hormone production. This often occurs together with low cortisol. MSD Manuals+1

13. Depression, irritability, or low mood – Cortisol and other hormones from the HPA axis affect brain function and mood. People with secondary adrenal insufficiency may feel sad, anxious, or “not themselves,” and this may be mistaken for purely psychological illness. Wikipedia+1

14. Joint and muscle aches – Aching muscles and joints are common and may be misdiagnosed as fibromyalgia or arthritis, especially if fatigue is also present. These pains often improve when cortisol is replaced to normal levels. NIDDK+1

15. Poor response to stress or illness and risk of adrenal crisis – During infections, surgery, or accidents, people with untreated or under-treated secondary adrenal insufficiency can become very sick with severe weakness, vomiting, low blood pressure, confusion, or collapse. This is called adrenal crisis and is a medical emergency that needs urgent injection of hydrocortisone and fluids. endocrinology.org+1

If someone has these symptoms, especially together or during stress, they should see a doctor or endocrinologist urgently and seek emergency care if they feel very unwell.

Diagnostic tests for secondary adrenal insufficiency

Physical exam

1. General physical examination – The doctor looks at overall appearance, weight, body build, and signs of long-term steroid use such as thin skin or bruising. They also look for signs of chronic illness or pituitary disease. This first step guides which hormone tests and scans are needed. NIDDK+1

2. Blood pressure and heart rate lying and standing – Measuring blood pressure and pulse when lying down and again after standing helps detect a drop in blood pressure (orthostatic hypotension). A big fall with symptoms supports the possibility of adrenal insufficiency, although it can also have other causes. NIDDK+1

3. Assessment for dehydration and volume status – The doctor checks skin turgor, mouth moisture, capillary refill, and neck veins to see if the person is dry or low in blood volume. While salt loss is less severe than in primary adrenal insufficiency, low cortisol and low intake can still cause dehydration. NIDDK+1

4. Examination for other pituitary hormone problems – The doctor looks for reduced body or facial hair, small testes, breast discharge, changes in body fat, or symptoms of thyroid problems. These signs suggest a broader pituitary problem (hypopituitarism) that often includes ACTH deficiency. MSD Manuals+1

Manual tests (bedside clinical maneuvers)

5. Visual field testing by confrontation – The doctor checks side vision by asking the patient to look straight ahead and report when they see fingers appearing at the edge. Loss of outer visual fields can suggest a large pituitary tumor pressing on the optic chiasm, a common structural cause of secondary adrenal insufficiency. MSD Manuals+1

6. Manual muscle strength testing – The doctor asks the patient to push and pull against resistance with arms and legs, and to stand up from a chair without using their hands. Generalized or proximal muscle weakness, together with other signs, supports a diagnosis of adrenal insufficiency or pituitary disease. NIDDK+1

7. Basic neurologic examination – Simple tests of reflexes, coordination, eye movements, and mental status help detect brain or pituitary lesions. Abnormal findings may point toward a central cause of adrenal insufficiency rather than a problem in the adrenal glands themselves. MSD Manuals+1

8. Functional postural and exercise tests – Asking the person to walk, climb one or two steps, or raise their arms repeatedly can show how quickly they tire or feel dizzy. Poor tolerance to mild exertion, together with low blood pressure or low blood sugar, raises suspicion for adrenal insufficiency. NIDDK+1

Laboratory and pathological tests

9. Early morning serum cortisol – A blood sample taken around 8 a.m. measures cortisol when it should be highest. Very low levels strongly suggest adrenal insufficiency, while clearly normal levels usually make the diagnosis unlikely. Borderline results need further dynamic testing. UpToDate+1

10. Plasma ACTH level – Measuring ACTH at the same time as morning cortisol helps separate primary from secondary adrenal insufficiency. In secondary adrenal insufficiency, ACTH is usually low or inappropriately normal despite low cortisol, because the pituitary is not responding properly. Wikipedia+1

11. Standard ACTH (cosyntropin) stimulation test – In this test, synthetic ACTH is injected, and cortisol is measured before and after the injection. A normal rise in cortisol suggests healthy adrenal glands. In long-standing secondary adrenal insufficiency, the adrenals may not respond well because they have been under-stimulated for a long time. Cleveland Clinic+1

12. Insulin tolerance test (ITT) – This dynamic test is considered a “gold standard” for central adrenal insufficiency. Insulin is given to safely lower blood sugar under close monitoring. In response to hypoglycemia, a healthy person should release ACTH and cortisol. In secondary adrenal insufficiency, cortisol fails to rise adequately. ITT must be done in a hospital because of the risk of severe low blood sugar. PMC+1

13. Metyrapone or glucagon stimulation tests – These are alternative dynamic tests used when ITT is not safe. Metyrapone blocks cortisol synthesis and should trigger an ACTH rise in healthy people, while the glucagon test indirectly stimulates the HPA axis. Abnormal responses can support a diagnosis of central adrenal insufficiency. PMC+1

14. Basic metabolic panel (electrolytes and kidney function) – Blood tests for sodium, potassium, bicarbonate, and creatinine help assess dehydration and metabolic status. In secondary adrenal insufficiency, sodium can be low but potassium is usually normal, which helps differentiate it from primary adrenal insufficiency. NIDDK+1

15. Glucose and HbA1c measurements – Fasting and random blood sugar tests, together with HbA1c, help detect low blood sugar episodes and overall glucose control. Hypoglycemia in someone with suggestive symptoms can point toward adrenal insufficiency or pituitary failure. NIDDK+1

16. Pituitary hormone panel – Tests for TSH, free T4, LH, FSH, prolactin, growth hormone or IGF-1, and sometimes vasopressin or its markers, help show whether there is a broader pituitary problem. Low levels of several pituitary hormones together with low ACTH strongly support a central cause of adrenal insufficiency. MSD Manuals+1

17. Autoimmune and infection-related blood tests – When hypophysitis or infiltrative diseases are suspected, doctors may order autoimmune markers, tuberculosis tests, or other infection screens. Positive results can support a specific cause of pituitary damage leading to secondary adrenal insufficiency. MSD Manuals+1

Electrodiagnostic tests

18. Electrocardiogram (ECG) – An ECG records the heart’s electrical activity. It is used to look for rhythm changes, signs of low blood potassium or other metabolic problems, and to monitor the heart during severe illness or dynamic tests like ITT. Abnormalities do not prove adrenal insufficiency but help guide safe management. NIDDK+1

19. Continuous heart rate and blood pressure monitoring – During adrenal crisis or dynamic tests, continuous monitoring (for example, via telemetry or blood pressure machines) is used to detect dangerous drops in blood pressure or heart rhythm problems early. This monitoring is part of safe testing and treatment in people with suspected adrenal insufficiency. endocrinology.org+1

Imaging tests

20. MRI of the pituitary and hypothalamus – Magnetic resonance imaging (MRI) of the brain, focused on the pituitary region, is the key imaging test to look for tumors, inflammation, bleeding, or other structural changes that can cause ACTH deficiency and secondary adrenal insufficiency. The MRI appearance often guides whether surgery, radiation, or medical treatment is needed. MSD Manuals+1

Non-pharmacological treatments (therapies and other approaches)

Non-pharmacological treatments do not replace steroid medicines in secondary adrenal insufficiency, but they make daily life safer and more stable. They help the body handle stress, protect bones, heart, and immune system, and reduce the risk of adrenal crisis.Endocrine Society+1

1. Education about the disease and “steroid rules”
   The first therapy is clear education. Patients learn what secondary adrenal insufficiency is, why they need daily steroid tablets, how to increase the dose during fever, surgery, or trauma, and when to seek emergency care. Good education lowers fear, improves treatment adherence, and reduces the chance of adrenal crisis by helping people act early when they become sick.National Adrenal Diseases Foundation+1

2. Sick-day rules and emergency action plan
   An emergency plan explains exactly what to do if there is vomiting, high fever, serious infection, or accident. The plan includes doubling or tripling oral glucocorticoid doses and using an emergency injection if tablets cannot be kept down. The goal is to prevent dangerous low cortisol during stress and to guide quick travel to hospital.associationofanaesthetists-publications.onlinelibrary.wiley.com+1

3. Medical alert bracelet or card
   Wearing a medical alert bracelet or necklace and carrying a steroid card tells doctors and paramedics that the person has adrenal insufficiency. In an emergency, staff can give IV hydrocortisone and fluids without delay. This simple tool protects life when the patient cannot speak for themselves.

4. Regular sleep and stress management
   Chronic stress, anxiety, and poor sleep put extra load on the body. Stress-management techniques like breathing exercises, mindfulness, gentle yoga, and cognitive behavioral strategies help calm the nervous system. This reduces fatigue, improves mood, and makes it easier for replacement steroids to meet the body’s daily needs.

5. Moderate, regular exercise program
   Safe, regular movement such as walking, cycling, or light resistance exercise strengthens muscles and bones, improves heart health, and supports mood. Exercise plans must be built slowly, with rest days and extra caution during heat or illness. The goal is to fight weakness and weight gain without triggering exhaustion.

6. Bone-health program (posture, weight-bearing work, fall prevention)
   Long-term glucocorticoid use can thin bones and raise fracture risk. Weight-bearing exercise, posture training, balance practice, and home safety checks lower the chance of falls and breaks. Combined with vitamin D, calcium, and medical care, this non-drug approach protects skeletal health in people who must take steroids.PMC+1

7. Fluid and salt management skills
   Although mineralocorticoid replacement is usually not needed in pure secondary adrenal insufficiency, some people still have low blood pressure, dizziness, and salt craving. Learning to drink enough fluids, spread intake through the day, and adjust salt under medical advice helps keep blood pressure and circulation stable, especially in hot weather or with exercise.Endocrine Society+1

8. Sensible heat and cold protection
   People with adrenal insufficiency may tolerate heat or cold poorly. Avoiding extreme temperatures, using fans or air-conditioning in hot climates, dressing in layers, and resting more on very hot days reduce strain on blood pressure and circulation. The aim is to avoid dehydration and collapse triggered by environmental stress.

9. Infection-prevention habits
   Good handwashing, staying up to date with vaccines (like influenza and COVID-19), avoiding close contact with people who are very sick, and quick treatment of minor infections all help. Because cortisol supports immune and stress responses, active infection can unmask low cortisol. Prevention lowers the need for high “stress doses” of steroids.Endocrine Society+1

10. Psychological counseling and support groups
    Living with a chronic hormone disease can cause fear, low mood, or feeling different from others. Talking with a counselor or joining an adrenal insufficiency support group helps people share experiences and coping skills. Emotional support improves adherence to treatment, self-care, and overall quality of life.

11. Work and school adjustments
    Some people need flexible hours, more rest breaks, or lighter physical tasks. Honest discussion with employers or teachers, supported by medical letters, can reduce over-exertion, episodes of near-collapse, and repeated sick leave. These adjustments help patients stay active and independent.

12. Travel planning
    Travel therapy means planning steroid doses across time zones, carrying more medicine than needed, keeping drugs in hand luggage, and knowing where to find emergency care. A written plan from the endocrinologist and translated medical letters can avoid missed doses and crisis when away from home.

13. Avoiding sudden steroid withdrawal
    A key non-drug measure is not stopping long-term glucocorticoids suddenly. Tapering slowly under medical supervision allows the hypothalamic-pituitary-adrenal axis to recover and prevents new or worse secondary adrenal insufficiency caused by abrupt withdrawal.Endocrine Society+1

14. Education for family and caregivers
    Relatives and close friends should learn how to recognize early symptoms of adrenal crisis (severe weakness, vomiting, low blood pressure, confusion) and how to give an emergency hydrocortisone injection if prescribed. Trained family support improves safety at home and shortens delays in reaching hospital.

15. Lifestyle measures to protect stomach and heart
    Because glucocorticoids can affect blood sugar, blood pressure, and stomach lining, simple habits like eating smaller, regular meals, avoiding heavy late dinners, limiting caffeine, and checking blood pressure at home help. These measures reduce side effects of long-term replacement therapy.

16. Weight management and nutrition counseling
    Some patients gain weight, especially around the abdomen, when steroids are not perfectly matched to their needs. A dietitian can help design a meal pattern rich in vegetables, lean proteins, whole grains, and controlled fats and sugars. This helps maintain healthy weight and metabolic profile.

17. Limit alcohol and stop smoking
    Alcohol and tobacco can worsen blood pressure, blood sugar, and bone loss and may mask early symptoms of crisis. Reducing or stopping these habits with professional help improves general health and reduces strain on organs already adapting to low cortisol and chronic steroid use.

18. Home monitoring tools
    Keeping a simple diary of blood pressure, pulse, weight, symptoms, and intercurrent illness days lets patients and doctors see patterns. Early rising dizziness, repeated nausea, or frequent infections in the diary may signal under-replacement or need for dose adjustment.

19. Patient smartphone apps and reminder tools
    Many people forget doses or sick-day changes. Using phone alarms, pill boxes, or adrenal-specific apps helps ensure medication is taken at the right time each day. Reliable timing keeps blood cortisol levels more stable and avoids highs and lows that cause fatigue and mood changes.

20. Regular specialist follow-up visits
    Scheduled visits with an endocrinologist or expert physician are themselves a form of non-pharmacological therapy. Doctors review symptoms, lab results, blood pressure, weight, and medications and adjust doses or plans early. Regular review lowers long-term complications and improves life expectancy.legeforeningen.no+1

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Drug treatments

Drug treatment for secondary adrenal insufficiency mainly means glucocorticoid replacement to copy normal cortisol rhythms and stress-dose steroids during illness. Hydrocortisone or equivalent steroids are the core therapy; mineralocorticoid is usually not required because aldosterone production is often normal in secondary disease.PMC+2National Adrenal Diseases Foundation+2

Important: Doses below are typical ranges from guidelines and product labels, but real prescriptions must always be individualized by a doctor.

1. Hydrocortisone oral tablets (e.g., CORTEF)
   Hydrocortisone is the first-line drug for adrenal insufficiency. It is a short-acting glucocorticoid taken 2–3 times daily, with most of the dose in the morning to mimic natural cortisol. Typical adult replacement is about 15–25 mg per day in divided doses, adjusted to symptoms, weight, and labs. Side effects include weight gain, high blood pressure, and bone loss if doses are too high.PMC+2FDA Access Data+2

2. Hydrocortisone granules or oral solutions (e.g., ALKINDI SPRINKLE, KHINDIVI)
   These child-friendly forms allow accurate small dosing, especially in children or people who cannot swallow tablets. Doses are calculated by body surface area and divided across the day. Labels warn that under-dosing or sudden stoppage can cause adrenal crisis, especially during stress. Common side effects mirror those of tablets when over-replaced.FDA Access Data+1

3. Prednisone immediate-release tablets
   Prednisone is an intermediate-acting glucocorticoid that can sometimes be given once each morning because of its longer effect. A common adult replacement is roughly 4–6 mg once daily, which equals about 15–25 mg hydrocortisone. It is useful for patients who prefer once-daily dosing but may slightly flatten normal daily cortisol patterns. Side effects include fluid retention, mood change, elevated sugar, and bone thinning.PMC+2OUP Academic+2

4. Prednisone delayed-release tablets (e.g., RAYOS)
   Delayed-release prednisone is designed to release steroid later in the night or early morning to match inflammatory peaks in some conditions. In secondary adrenal insufficiency, it may help certain patients who need once-daily dosing with better early-morning coverage. Doses generally match standard prednisone doses. Risks include the usual glucocorticoid side effects, plus rare allergic reactions listed in the label.FDA Access Data+1

5. Prednisolone oral solutions and tablets
   Prednisolone is the active metabolite of prednisone and is often used when liquid or pediatric dosing is required. Replacement doses are similar to prednisone, adjusted per kilogram body weight. It is taken 1–2 times daily. The mechanism is strong glucocorticoid action with almost no mineralocorticoid effect. Long-term use can increase infection risk, blood pressure, and blood sugar.FDA Access Data+1

6. Cortisone acetate
   Cortisone acetate is an older pro-drug converted to cortisol in the liver. It can still be used for adrenal replacement in some regions. It has slightly weaker glucocorticoid activity per milligram than hydrocortisone, so doses are numerically higher. Side effects and mechanisms are similar: anti-inflammatory and metabolic effects, with potential for Cushing-like features at excessive doses.FDA Access Data+1

7. Methylprednisolone
   Methylprednisolone is a more potent glucocorticoid with longer action. In secondary adrenal insufficiency it is mainly used when patients also need strong anti-inflammatory control, for example in autoimmune disease. Replacement doses are small (roughly 2–4 mg equal to 15–20 mg hydrocortisone) and given once daily. Side effects include higher risk of glucose intolerance and mood changes compared with hydrocortisone.

8. Dexamethasone
   Dexamethasone is a very potent, long-acting glucocorticoid. It strongly suppresses ACTH and cortisol production and is not usually chosen for routine daily replacement, but may be used in specific situations or tests. Very low doses (for example, 0.25–0.5 mg daily) can substitute for larger hydrocortisone doses. Because it has no mineralocorticoid effect and a long half-life, overdose has higher risk of Cushing-like symptoms.

9. Intravenous hydrocortisone for adrenal crisis
   During severe illness, surgery, trauma, or vomiting, oral tablets may not work. In these cases, guidelines advise IV hydrocortisone, commonly 100 mg at once, followed by continuous infusion or repeated doses plus saline. The purpose is rapid cortisol replacement to reverse shock, low blood pressure, and low blood sugar. Short-term side effects are usually small compared with the life-saving benefit.associationofanaesthetists-publications.onlinelibrary.wiley.com+1

10. Intramuscular hydrocortisone emergency injection
    Many patients are prescribed an emergency hydrocortisone kit for home or travel use. Family or the patient injects hydrocortisone into muscle at the first signs of severe vomiting, collapse, or confusion. It quickly raises blood steroid levels until IV treatment is available. Bruising and local pain are minor side effects compared with preventing adrenal crisis.

11. Fludrocortisone acetate tablets
    In pure secondary adrenal insufficiency, most patients do not need mineralocorticoid, because aldosterone comes mainly from the adrenal cortex under renin control. However, in some mixed cases or in children, low-dose fludrocortisone (often 0.05–0.2 mg once daily) may be used to support blood pressure and salt balance. Side effects include swelling, high blood pressure, and low potassium if dose is too high.DailyMed+1

12. Proton pump inhibitors (e.g., omeprazole)
    Long-term glucocorticoid therapy can irritate the stomach, especially when combined with NSAIDs. PPIs reduce acid production and protect the stomach lining. They are taken once daily, usually before breakfast. The goal is to lower gastric ulcer and bleeding risk. Possible side effects include headache, diarrhea, and, with long use, slightly lower magnesium or vitamin B12 levels.

13. Bisphosphonates (e.g., alendronate)
    If bone density scans show osteoporosis from chronic steroid therapy, doctors may add a bisphosphonate to slow bone loss. These drugs bind to bone and reduce breakdown by osteoclasts. Weekly or monthly dosing is common. They can cause stomach upset and rarely jaw bone problems, so dental health and correct intake instructions are important.

14. Calcium supplements (medicinal form)
    When diet alone does not supply enough calcium, tablets may be prescribed to reach about 1000–1200 mg elemental calcium per day from food plus supplement. Calcium supports bone mineralization in the setting of steroid-related bone loss. Excess supplementation can cause kidney stones or constipation, so doses must be balanced with diet and kidney function.

15. Vitamin D medicinal preparations
    Vitamin D3 drops or tablets are often given at 800–2000 IU daily (or as weekly higher doses) to support calcium absorption and bone strength. Replacement improves muscle function and reduces fracture risk, especially in people on chronic steroids. Very high uncontrolled doses can cause high calcium and kidney damage, so blood levels are monitored.

16. Anti-emetic drugs (e.g., ondansetron)
    Nausea and vomiting during infections can prevent patients from keeping steroid tablets down, triggering crisis. Short-term anti-emetic treatment lets patients tolerate oral glucocorticoids. It works by blocking serotonin receptors in the gut and brain. Side effects are usually mild (headache, constipation), though heart rhythm changes are possible at high doses.

17. Isotonic saline infusion (0.9% NaCl)
    In adrenal crisis, low cortisol combines with low blood pressure, low sodium, and dehydration. Rapid infusion of normal saline in hospital restores blood volume and supports circulation while hydrocortisone starts working. This IV fluid therapy is considered a medical “drug” and is dosed according to blood pressure, urine output, and heart status.

18. Dextrose solutions (e.g., 5–10% dextrose or 50% bolus)
    Low cortisol can cause low blood sugar, especially in children. IV dextrose corrects hypoglycemia quickly and protects the brain. It is given as a bolus or infusion and then adjusted based on glucose checks. Side effects mainly include temporary high blood sugar; careful monitoring is needed in people with diabetes.

19. Vaccines (e.g., inactivated influenza, pneumococcal vaccines)
    Vaccines are not adrenal drugs, but they are important medications to reduce infection risk in people who depend on steroids. Inactivated vaccines are generally safe and can reduce episodes needing stress-dose steroids. Live vaccines must be timed and chosen carefully, depending on steroid dose and immune status.

20. Drugs that allow glucocorticoid taper (e.g., steroid-sparing agents)
    In some patients, steroid-sparing immunosuppressants or biologics for the primary disease (such as rheumatoid arthritis) allow reduction of exogenous steroids, lowering the risk or severity of secondary adrenal insufficiency. Doses and choices are highly individual and require specialist supervision because these drugs have their own serious side effects.

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Dietary molecular supplements

Supplements do not replace prescribed glucocorticoids. They simply support general health, bones, muscles, and immunity. Always discuss them with a doctor or dietitian.

1. Vitamin D3 – Helps absorb calcium and supports bone and muscle health, especially important when on steroids that thin bones. Typical daily doses are 800–2000 IU, adjusted to blood levels. It works by binding vitamin D receptors and improving calcium transport in the gut and kidneys.

2. Calcium (citrate or carbonate) – Provides raw material for bone mineralization. Daily intake from food plus supplements often targets 1000–1200 mg elemental calcium. It supports normal nerve and muscle function and reduces osteoporosis risk from steroids, but excess doses can cause kidney stones and constipation.

3. Magnesium – Magnesium participates in hundreds of enzyme reactions, including energy production and muscle function. Steroids and PPIs may lower magnesium over time. Supplemental magnesium in moderate doses can improve cramps, fatigue, and sleep quality, but too much may cause diarrhea.

4. Omega-3 fatty acids (EPA/DHA) – These healthy fats from fish oil or algae support heart health, reduce low-grade inflammation, and may improve mood. Typical doses are about 500–1000 mg combined EPA/DHA daily from capsules or enriched foods. They work by altering cell membrane composition and inflammatory mediator production.

5. Vitamin B12 – B12 helps form red blood cells and maintain nerve function. Some people on long-term acid suppression or with autoimmune issues develop low B12, leading to fatigue and numbness. Oral or injectable B12 restores stores and helps energy metabolism by acting as a cofactor in DNA and myelin synthesis.

6. Folate (folic acid or methylfolate) – Folate supports DNA synthesis, cell division, and red blood cell formation. Inadequate folate can worsen anemia-related fatigue in chronic disease. Controlled supplement doses help correct deficiency and support overall tissue repair, but very high doses can hide B12 deficiency.

7. Vitamin C – Vitamin C supports collagen formation, immune defense, and antioxidant protection. Modest daily supplementation (for example, 100–500 mg) can help people with low fruit and vegetable intake. It donates electrons to neutralize free radicals and supports immune cell function, but high doses may cause stomach upset.

8. Zinc – Zinc is vital for immune function, wound healing, and hormone receptor function. Short courses of zinc at recommended doses may help if diet is poor. It acts in enzyme systems and transcription factors. Too much zinc can lower copper levels and cause nausea, so supervised use is important.

9. Probiotic preparations – Probiotics are beneficial bacteria taken as capsules or fermented foods. They can support gut health, reduce antibiotic-associated diarrhea, and may slightly modulate immune responses. A healthier gut may improve nutrient absorption and overall resilience in people with chronic hormone disease.

10. Coenzyme Q10 – CoQ10 is involved in mitochondrial energy production. Some patients with chronic fatigue find modest benefit from supplementation. It helps shuttle electrons in the respiratory chain and acts as an antioxidant. Doses vary; potential side effects are usually mild, like digestive discomfort.

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Immune-boosting and regenerative / stem-cell-related therapies

These therapies are adjuncts or experimental, not standard replacement for secondary adrenal insufficiency.

1. Standard vaccines as “immune training” drugs
   Inactivated vaccines for influenza, pneumococcus, and COVID-19 help the immune system prepare safely for common infections. They boost specific immune memory without causing disease. For people on steroids, this reduces severe infection risk and thus lowers episodes that demand high stress-dose glucocorticoids.

2. Immunoglobulin therapy (in selected immune disorders)
   Some patients with combined immune problems may receive intravenous or subcutaneous immunoglobulin. This pooled antibody product supports defense against infections while their own immunity is weak. It works by providing ready-made antibodies and modulating immune responses, which indirectly protects patients who also have adrenal failure.

3. Hematopoietic stem cell transplantation (for rare underlying diseases)
   A few rare underlying conditions that damage the pituitary or immune system may be treated with stem cell transplantation. This intensive therapy replaces the bone marrow with donor stem cells. It can cure some blood cancers or immune diseases, but adrenal insufficiency often remains, so steroids are still needed.

4. Mesenchymal stem-cell trials for autoimmune disease
   Experimental trials use mesenchymal stem cells to calm severe autoimmune disease. By lowering the need for high-dose steroids, they may reduce the risk of steroid-induced secondary adrenal insufficiency. Doses and schedules are strictly controlled within trials, and long-term safety is still being studied.

5. Biologic immune-modifying drugs
   Biologics targeting TNF, IL-6, or other pathways can control diseases such as rheumatoid arthritis or inflammatory bowel disease. When inflammation is controlled, doctors can taper oral steroids more safely, lowering the chance of adrenal suppression. These drugs have their own serious risks and require specialist supervision.

6. Future adrenal or pituitary regenerative therapies (research stage)
   Scientists are exploring the use of induced pluripotent stem cells, gene therapy, and tissue engineering to regenerate hormone-producing cells of the pituitary–adrenal axis. These ideas remain in early research or very small trials. For now, they are scientific hope, not standard care, and must not replace proven glucocorticoid replacement.

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Surgeries and procedures (why they may be done)

1. Transsphenoidal pituitary surgery
   This operation removes pituitary tumors (adenomas) through the nose and sphenoid sinus. It may be needed when a tumor compresses vision or secretes hormones. Surgery can improve the underlying problem but often causes or worsens secondary adrenal insufficiency, making careful steroid replacement essential afterward.

2. Pituitary radiotherapy or radiosurgery
   When surgery is not possible or does not fully control a tumor, targeted radiation may be used. Radiation shrinks tumor tissue over months or years. However, it frequently damages normal pituitary cells, leading to permanent need for glucocorticoid and other hormone replacement.

3. Neurosurgery for craniopharyngioma or other brain lesions
   Some childhood and adult brain tumors near the hypothalamus or pituitary are removed by open or endoscopic neurosurgery. The goal is to protect brain structures and vision. Because these areas regulate ACTH and cortisol, surgery almost always requires careful postoperative hormone assessment and long-term steroid replacement.

4. Surgery to treat Cushing’s disease or syndrome
   Cushing’s disease (ACTH-secreting pituitary tumor) or ectopic ACTH production is often treated with tumor removal. After successful surgery, the adrenal glands are small and suppressed from years of over-stimulation. Patients commonly go through a period of secondary adrenal insufficiency and need replacement until the axis recovers, if ever.

5. Bariatric or other major surgeries in steroid-dependent patients
   Major procedures are not used to treat adrenal insufficiency itself, but people with this condition may undergo them for other health reasons. Surgeons and anesthetists must give peri-operative stress-dose hydrocortisone to prevent crisis. Planning involves increased steroid doses, IV fluids, and close monitoring.

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Prevention strategies

1. Use the lowest effective glucocorticoid dose for the shortest time in other diseases, to reduce new cases of secondary adrenal insufficiency.Endocrine Society+1

2. Never stop long-term steroids suddenly; taper slowly under medical guidance.

3. Learn and follow sick-day rules and always keep written emergency instructions.

4. Wear a medical alert bracelet and carry a steroid card at all times.

5. Keep an emergency hydrocortisone injection kit and know how to use it.

6. Attend regular endocrine follow-up for dose review and education.

7. Keep vaccinations up to date and practice basic infection prevention.

8. Maintain healthy lifestyle habits: balanced diet, regular activity, no smoking, limited alcohol.

9. Plan ahead for travel and surgery, including extra steroid supply.

10. Share information with family, school, or workplace so others can help in emergencies.

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When to see a doctor

You should see a doctor or endocrinologist regularly for routine follow-up, and urgently if you notice warning signs. Make an early appointment if fatigue, dizziness, nausea, weight loss, or low blood pressure get worse, if you are often sick with infections, or if you think your steroid dose is either too high or too low. Seek emergency care immediately if you have severe vomiting or diarrhea, cannot keep tablets down, feel faint or confused, have severe abdominal pain, or collapse. These can be signs of adrenal crisis and require urgent IV hydrocortisone and fluids in hospital.legeforeningen.no+1

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What to eat and what to avoid

1. Eat regular, balanced meals with vegetables, fruits, whole grains, and lean protein to support steady energy and blood sugar.

2. Include some salt in the diet if you have low blood pressure or salt craving and your doctor agrees; avoid very low-salt fad diets.

3. Limit very salty processed foods (chips, instant noodles, fast food) if your blood pressure is high or if you take fludrocortisone.

4. Choose healthy fats like olive oil, nuts, seeds, and oily fish instead of deep-fried foods and trans fats to protect the heart.

5. Control added sugars by cutting back on sugary drinks, sweets, and desserts, which can worsen steroid-induced high blood sugar and weight gain.

6. Stay hydrated with water throughout the day, especially in hot weather or during exercise, to support blood pressure and kidney function.

7. Limit caffeine and energy drinks, which may worsen palpitations, anxiety, or sleep problems, especially when combined with steroids.

8. Avoid heavy alcohol use, which can lower blood sugar, irritate the stomach, and interfere with medication schedules.

9. Ensure enough protein from fish, eggs, dairy, beans, or tofu to support muscle mass and recovery from illness.

10. Work with a dietitian if you have diabetes, obesity, celiac disease, or kidney problems along with adrenal insufficiency, so your diet meets all needs safely.

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Frequently asked questions (FAQs)

1. Is secondary adrenal insufficiency the same as Addison’s disease?
   No. Addison’s disease is primary adrenal insufficiency, where the adrenal glands are damaged. In secondary adrenal insufficiency, the pituitary or hypothalamus does not signal the adrenals properly, usually due to long-term steroid use or pituitary disease. Treatment is similar but mineralocorticoid replacement is often not needed.

2. Can secondary adrenal insufficiency be cured?
   Sometimes. If it is caused by temporary suppression from long-term steroid therapy, the hypothalamic–pituitary–adrenal axis may recover slowly after steroids are tapered. In many pituitary or hypothalamic disorders, the problem is permanent, and life-long replacement is required. Regular testing helps doctors see if recovery is possible.Endocrine Society+1

3. Do I have to take steroid tablets for the rest of my life?
   Many people do, but not everyone. Your doctor may test your adrenal function after some time to see whether cortisol production has returned. Until tests clearly show recovery, you must continue replacement to avoid crisis. Never change doses on your own.

4. Are replacement doses of steroids dangerous?
   Replacement doses aim to copy what a healthy body would make. When carefully adjusted, they are much safer than the higher anti-inflammatory doses used in other diseases. Long-term risks like weight gain, high blood pressure, and bone loss mainly occur when doses are too high or not monitored.

5. Can I live a normal life with secondary adrenal insufficiency?
   Yes, many people live very full lives. Key steps are taking steroids exactly as prescribed, understanding sick-day rules, wearing medical identification, eating well, staying active, and having regular check-ups. With good self-management, complications and hospital visits can be greatly reduced.

6. What is an adrenal crisis?
   An adrenal crisis is a life-threatening state where cortisol is suddenly too low for the body’s needs, often during stress, infection, or vomiting. Symptoms include severe weakness, low blood pressure, abdominal pain, vomiting, and confusion. Treatment is urgent IV hydrocortisone and saline in hospital; early injection at home can save time and life.

7. Do I need fludrocortisone as well as hydrocortisone?
   Most people with pure secondary adrenal insufficiency do not need fludrocortisone because their aldosterone production is preserved. However, some mixed cases or children might benefit. The decision is based on blood pressure, electrolytes, and symptoms like salt craving or dizziness on standing.

8. Can I exercise or play sports?
   Yes, regular exercise is encouraged, but build up slowly and avoid dehydration and over-heating. Carry extra oral steroid doses as advised for strenuous events and know when to increase them. Always bring medical identification and make sure coaches or friends know about your condition.

9. What should I do if I forget a dose?
   If you remember within a few hours, take it as soon as possible. If it is almost time for the next dose, your doctor may advise skipping or adjusting rather than doubling. If you feel unwell, especially dizzy or nauseated, contact your healthcare provider for guidance.

10. Can pregnancy be safe with secondary adrenal insufficiency?
    Yes, many women with adrenal insufficiency have healthy pregnancies. Hydrocortisone doses are often adjusted during pregnancy and birth, and stress doses are used during labor and cesarean sections. Close coordination between endocrinologist and obstetrician is essential.

11. Will my children inherit this condition?
    Secondary adrenal insufficiency due to long-term steroid use is not inherited. If it is due to a specific pituitary tumor or genetic problem, an endocrinologist can explain the individual risk. In most cases, children do not automatically develop the same problem.

12. Is there a special time of day to take my steroids?
    Usually the largest dose is taken in the morning, with smaller doses at lunch or mid-afternoon, to copy natural cortisol rhythm. Taking late-evening doses is often avoided because it can disturb sleep. Your doctor will adjust timing based on your symptoms and daily routine.PMC+1

13. Can herbal or “adrenal support” supplements replace my medicine?
    No. Many “adrenal” products are unregulated and may even contain hidden steroids. They cannot safely replace prescribed glucocorticoids and may interfere with testing. Always show any supplement to your doctor before using it.

14. How often should my hormone levels be checked?
    Frequency depends on stability and underlying cause. Early after diagnosis or dose change, checks may be more frequent. Once stable, yearly reviews of symptoms, blood pressure, weight, and selected blood tests are common. Any new or severe symptoms should trigger earlier review.

15. What is the most important thing to remember about secondary adrenal insufficiency?
    The single most important point is never be without your steroid medicine and emergency plan. Carry tablets and an emergency card, know how to adjust doses when sick, and teach family or friends what to do. With these steps, you greatly reduce risk and can live an active, safe life.

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.