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The Adrenal Gland is found superior to the kidneys and produces both Cortisol and Aldosterone.

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The Adrenal gland is found superior to the kidneys. The Adrenal gland is triangular shaped and has two main parts; the adrenal cortex and the adrenal medulla. The Cortex is the outer part of the Gland. The Medulla is the middle of the gland.

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Produced in the middle layer of the adrenal cortex

Cortisol is the long-term and primary stress hormone, increases the blood glucose levels and starts the storing of more glucose.

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Produced in the outer adrenal cortex

A mineralocorticoid, regulates the mineral content in the blood (sodium/ potassium ions). Also regulates water and electrolyte balance. (target organ is kidney)

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Addison's disease is caused by the hyposecretion of all adrenal cortex hormones. The symptoms of this disease are bronze skin tone, muscle weakness, burnout, and susceptibility to infection.

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Hyperaldosteronism is a condition caused by the hypersecretion of aldosterone which results in excess water and sodium to be retained leading to high blood pressure.

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This syndrome results from a tumor in the middle cortical area of the adrenal cortex. It can cause people to have a “Moon face”, or “buffalo hump” on the upper back. This can lead to high blood pressure, hyperglycemia, the weakening of bones, and depression.

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Adrenal glands and the Anterior Pituitary Glands

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Adrenal glands and the Anterior Pituitary Glands

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The adrenal glands interact with the hypothalamus and the pituitary glands in the brain in order to produce ACTH. ACTH, which comes from the pituitary glands and stimulates the corticosteroid hormones into the blood. (corticosteroids are both mineralocorticoids and glucocorticoids) The hypothalamus and the Pituitary glands can both detect the blood cortisone levels and decrease the amounts if needed by stopping the release of ACTH.

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https://www.acpjournals.org/doi/10.7326/0003-4819-35-3-652

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If the address matches an existing account you will receive an email with instructions to reset your password.

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The size and the secretory activity of the adrenal cortex are controlled to a major extent by the adrenocorticotropic hormone (ACTH) of the anterior pituitary.

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https://www.hopkinsmedicine.org/health/conditions-and-diseases/adrenal-glands#:~:text=

Adrenal%20glands%2C%20also%20known%20as,stress%20and%20other%20essential%20functions

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What You Need to Know

Anatomy of the Adrenal Glands

An adrenal gland is made of two main parts:

The adrenal cortex is the outer region and also the largest part of an adrenal gland. It is divided into three separate zones: zona glomerulosa, zona fasciculata and zona reticularis. Each zone is responsible for producing specific hormones.

The adrenal medulla is located inside the adrenal cortex in the center of an adrenal gland. It produces "stress hormones," including adrenaline.

The adrenal cortex and adrenal medulla are enveloped in an adipose capsule that forms a protective layer around an adrenal gland.

Hormones of the Adrenal Glands

The role of the adrenal glands in your body is to release certain hormones directly into the bloodstream. Many of these hormones have to do with how the body responds to stress, and some are vital to existence. Both parts of the adrenal glands - the adrenal cortex and the adrenal medulla - perform distinct and separate functions.

Each zone of the adrenal cortex secretes a specific hormone. The key hormones produced by the adrenal cortex include:

Cortisol

Cortisol is a glucocorticoid hormone produced by the zona fasciculata that plays several important roles in the body. It helps control the body's use of fats, proteins and carbohydrates; suppresses inflammation; regulates blood pressure; increases blood sugar; and can also decrease bone formation.

This hormone also controls the sleep/wake cycle. It is released during times of stress to help your body get an energy boost and better handle an emergency situation.

How Adrenal Glands Work to Produce Cortisol

Adrenal glands produce hormones in response to signals from the pituitary gland in the brain, which reacts to signaling from the hypothalamus, also located in the brain. This is referred to as the hypothalamic pituitary adrenal axis. As an example, for the adrenal gland to produce cortisol, the following occurs:

The hypothalamus produces corticotropin-releasing hormone (CRH) that stimulates the pituitary gland to secrete adrenocorticotropin hormone (ACTH).

ACTH then stimulates the adrenal glands to make and release cortisol hormones into the blood.

Normally, both the hypothalamus and the pituitary gland can sense whether the blood has the appropriate amount of cortisol circulating. If there is too much or too little cortisol, these glands respectively change the amount of CRH and ACTH that gets released. This is referred to as a negative feedback loop.

Excess cortisol production can occur from nodules in the adrenal gland or excess production of ACTH from a tumor in the pituitary gland or other source.

Aldosterone

This mineralocorticoid hormone produced by the zona glomerulosa plays a central role in regulating blood pressure and certain electrolytes (sodium and potassium). Aldosterone sends signals to the kidneys, resulting in the kidneys absorbing more sodium into the bloodstream and releasing potassium into the urine. This means that aldosterone also helps regulate the blood pH by controlling the levels of electrolytes in the blood.

DHEA and Androgenic Steroids

These hormones produced by the zona reticularis are weak male hormones. They are precursor hormones that are converted in the ovaries into female hormones (estrogens) and in the testes into male hormones (androgens). However, estrogens and androgens are produced in much larger amounts by the ovaries and testes.

Epinephrine (Adrenaline) and Norepinephrine (Noradrenaline)

The adrenal medulla, the inner part of an adrenal gland, controls hormones that initiate the flight or fight response. The main hormones secreted by the adrenal medulla include epinephrine (adrenaline) and norepinephrine (noradrenaline), which have similar functions.

Among other things, these hormones are capable of increasing the heart rate and force of heart contractions, increasing blood flow to the muscles and brain, relaxing airway smooth muscles, and assisting in glucose (sugar) metabolism. They also control the squeezing of the blood vessels (vasoconstriction), helping maintain blood pressure and increasing it in response to stress.

Like several other hormones produced by the adrenal glands, epinephrine and norepinephrine are often activated in physically and emotionally stressful situations when your body needs additional resources and energy to endure unusual strain.

Adrenal Gland Disorders

The two common ways in which adrenal glands cause health issues are by producing too little or too much of certain hormones, which leads to hormonal imbalances. These abnormalities of the adrenal function can be caused by various diseases of the adrenal glands or the pituitary gland.

Adrenal Insufficiency

Adrenal insufficiency is a rare disorder. It may be caused by disease of the adrenal glands (primary adrenal insufficiency, Addison's disease) or by diseases in the hypothalamus or the pituitary (secondary adrenal insufficiency). It is the opposite of Cushing syndrome and is characterized by low levels of adrenal hormones. The symptoms include weight loss, poor appetite, nausea and vomiting, fatigue, darkening of skin (only in primary adrenal insufficiency), abdominal pain, among other.

The causes of primary adrenal insufficiency may include autoimmune disorders, fungal and other infections, cancer (rarely), and genetic factors.

Although adrenal insufficiency usually develops over time, it can also appear suddenly as an acute adrenal failure (adrenal crisis). It has similar symptoms, but the consequences are more serious, including life-threatening shock, seizures, and coma. These may develop if the condition is left untreated.

Congenital Adrenal Hyperplasia

Adrenal insufficiency can also result from a genetic disorder called congenital adrenal hyperplasia. Children who are born with this disorder are missing an essential enzyme necessary to produce cortisol, aldosterone or both. At the same time, they often experience excess of androgen, which may lead to male characteristics in girls and precocious puberty in boys.

Congenital adrenal hyperplasia can remain undiagnosed for years depending on the severity of the enzyme deficiency. In more severe cases, infants may suffer from ambiguous genitalia, dehydration, vomiting and failure to thrive.

Overactive Adrenal Glands

Sometimes, adrenal glands may develop nodules that produce too much of certain hormones. Nodules 4 centimeters or larger and nodules that show certain features on imaging increase suspicion for malignancy. Both benign and cancerous nodules may produce excessive amounts of certain hormones, which is referred to as a functional nodule. Functional tumors, malignant tumors or nodules greater than 4 centimeters are recommended to be referred for surgical evaluation.

Excess of Cortisol: Cushing Syndrome

Cushing syndrome results from excessive production of cortisol from the adrenal glands. The symptoms may include weight gain and fatty deposits in certain areas of the body, such as the face, below the back of the neck called a buffalo hump and in the abdomen; thinning arms and legs; purple stretch marks on the abdomen; facial hair; fatigue; muscle weakness; easily bruised skin; high blood pressure; diabetes; and other health issues.

Excess cortisol production can also be triggered by overproduction of ACTH by a benign tumor in the pituitary gland or tumor elsewhere in the body. This is known as Cushing Disease. Another common cause of Cushing syndrome is excessive and prolonged consumption of external steroids, such as prednisone or dexamethasone, which are prescribed to treat many autoimmune or inflammatory diseases (e.g., lupus, rheumatoid arthritis, asthma, inflammatory bowel disease, multiple sclerosis, etc.)

Excess of Aldosterone: Hyperaldosteronism

Hyperaldosteronism results from overproduction of aldosterone from one or both adrenal glands. This is characterized by increase in blood pressure that often requires many medications to control. Some people can develop low potassium levels in the blood, which can cause muscle aches, weakness and spasms. When the cause is adrenal oversecretion, the disease is called Conn syndrome.

Excess of Adrenaline or Noradrenaline: Pheochromocytoma

Pheochromocytoma is a tumor that results in excess production of adrenaline or noradrenaline by the adrenal medulla that often happens in bursts. Occasionally, neural crest tissue, which has similar tissue to the adrenal medulla, may be the cause of overproduction of these hormones. This known as a paraganglioma.

Pheochromocytomas may cause persistent or sporadic high blood pressure that may be difficult to control with regular medications. Other symptoms include headaches, sweating, tremors, anxiety and rapid heartbeat. Some people are genetically predisposed to developing this type of tumor.

Adrenal Cancer

Malignant adrenal tumors (adrenal cancer), such as adrenocortical carcinoma, are rare and often have spread to other organs and tissues by the time they are diagnosed. These tumors tend to grow fairly large and can reach several inches in diameter.

Cancerous adrenal tumors can be functional and release excess of one or more hormones accompanied by corresponding symptoms, as listed above. Patients may also experience abdominal pain, flank pain or a feeling of abdominal fullness, especially when the adrenal tumor gets very large.

Not all cancers found in adrenal glands originate from the gland itself. The majority of adrenal tumors are metastasis, or cancer spread, from another primary tumor elsewhere in the body.

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Adrenal glands, also known as suprarenal glands, are small, triangular-shaped glands located on top of both kidneys.

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https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3736622/

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Case presentation

A 20-year-old female patient was admitted in October with a 3-month history of persistent vomiting between 5 and 15 times a day and weight loss. She was dehydrated and unable to tolerate oral intake due to nausea and vomiting. Her bowel motions were normal; she had no problems with micturition or symptoms of infection, however had noticed significant weight loss in the preceding few months.

She had known hypothyroidism and had previously been referred directly to the gastroenterologists for persistent vomiting. She underwent an oesophagogastroduodenoscopy (OGD) which showed gastritis and therefore, she was started on proton pump inhibitor therapy. A blood test showed negative tissue transglutaminase antibodies, positive gastric parietal cell antibodies and she was scheduled for a CT enterograph.

Given this history she was treated as ongoing gastritis with vomiting secondary to the above. She had a sodium level of 133 mmol/L and low blood pressure and this was felt to be secondary to dehydration. This was treated with intravenous fluids and she was subsequently discharged on antiemetics.

The patient presented again 4 months later with persistent vomiting with some fresh blood at the end due to a Mallory-Weiss tear. She mentioned ongoing weight loss from 50 kg in August to 41 kg currently and ongoing lethargy. She described some right-sided abdominal pain and a pregnancy test was negative. She denied thyroxine abuse or forced vomiting. The patient was unsure about any relevant family history. She was a social smoker and denied any alcohol intake.

On examination she was very thin, hypotensive and tachycardic. She was clinically dehydrated and was noted to have some mild skin pigmentation.

Discussion

The above case highlights the importance of reviewing previous admissions and to think of other differential diagnoses especially when the presenting symptom is similar. The patient had been initially referred to the gastroenterologists; therefore, subsequent admissions were put down to a gastrointestinal cause despite there being limited improvement in symptoms. However given the ongoing weight loss despite no underlying cause on previous investigations, it was important to rule out other diagnoses and eventually the diagnosis of Addison's disease was made almost 1 year after symptoms presented.

Addison's disease is a relatively rare condition with an annual incidence of 4 million in the western population. It can be very difficult to diagnose and easily missed due to its presentation with non-specific symptoms.

The delay in diagnosis is not uncommon and patients can be seen by various healthcare professionals including gastroenterologists or psychiatrists before being correctly diagnosed.

The wide variety in symptoms means that the diagnosis can be attributed to other conditions and the more cardinal features such as skin or mucous membrane pigmentation may be missed although these may not always be present.

Anorexia or hypotension may be relevant however are again non-specific as they be explained by alternative diagnoses such as an underlying infection.

Investigations can provide many clues to the clinician to make them suspect Addison's disease. On routine blood tests the patient may have hyponatraemia and/or hyperkalaemia, hypoglycaemia, eosinophilia.

Raised TSH may be a feature and sometimes Addison's disease can be worsened by starting thyroxine.

A clinician may then suspect the diagnosis and consider a random cortisol level. However, this can be inaccurate due to the circadian rhythm of cortisol production with peak levels in the morning and low levels at midnight and also an increase in production in times of stress. An unusually low cortisol in the presence of clinical features of Addison's disease should prompt a diagnosis and this may be confirmed by a trial of hydrocortisone.

The key test for diagnosis is a short synacthen test however this can be difficult in the crisis scenario as intravenous hydrocortisone should be started immediately. Cortisol and adrenocorticotropic hormone (ACTH) levels should also be taken prior to steroid administration.

In the non-acute setting, Synacthen or synthetic ACTH (also called tetracosactrin) can be administered either intravenously or intramuscularly. A typical test involves baseline cortisol levels taken (0 min) followed by administration of 250 μg tetracosactrin and then repeat cortisol levels taken at 30 min (and 60 min in some cases). The level suggesting intact adrenal gland function has varied from between 400 and 550 nmol/L but the generally agreed level is 525 nmol/L.

About half of the patients with Addison's disease are diagnosed only after an acute adrenal crisis. It is a medical emergency often precipitated by an infection or other forms of stress in an undiagnosed or inadequately treated patient with Addison's disease. In this condition, patients present acutely unwell with severe dehydration, hypotension or circulatory shock.

There are known autoimmune associations with Addison's disease. Thomas Addison described the presence of pernicious anaemia and vitiligo when describing his eponymous condition. Fifty per cent of patients with Addison's disease have an associated autoimmune disease with the most common being thyroid disease.

Addison's disease can be associated with other autoimmunity therefore if a past medical history reveals conditions such as vitiligo, thyroid disease, coeliac disease or atrophic gastritis then this raises the suspicion of another autoimmune diagnosis. The above patient had hypothyroidism and positive gastric cell antibodies. This also suggested the possibility of autoimmune polyendocrine syndrome (APS).

Autoimmune polyendocrine syndrome

APS refers to multiple endocrine gland insufficiency associated with autoimmune disease; however, it is also used to describe syndromes characterised by the association of two or more organ specific disorders.

There is also the presence of genetic inheritance such as autoimmune regulator (AIRE) gene in APS type I or polygenic inheritance in APS type II. Neufeld and Blizzard further classified this syndrome into four main types based on clinical findings, however the main two syndromes are APS types I and II.

APS type I is an autosomal recessive condition and is characterised by the associations including mainly Addison's disease, hypoparathyroidism and chronic candidiasis. However, other associated features include pernicious anaemia, atrophic gastritis, hepatitis, vitiligo and type 1 diabetes mellitus.

APS type II (AKA Schmidt's syndrome) is more common than type I and is associated with conditions including Addison's disease, insulin dependant diabetes mellitus and autoimmune thyroid disease. It is associated with human leucocyte antigen (HLA)-HLA DR3 and HLA DR4.

Pernicious anaemia is also found but is more common in APS type I.

below summarises the key associations with Addison's disease and APS.

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Case Report: Addison's disease and its associations

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A 20-year-old female patient was admitted in October with a 3-month history of persistent vomiting between 5 and 15 times a day and weight loss. She was dehydrated and unable to tolerate oral intake due to nausea and vomiting.

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https://www.urmc.rochester.edu/encyclopedia/content.aspx?contenttypeid=85&contentid=p00399

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Anatomy of the adrenal glands

Adrenal glands are small, triangular glands that sit on top of each kidney. An adrenal gland is made of 2 parts. The outer region is called the adrenal cortex. The inner region is called the adrenal medulla. Both parts have distinct functions.

Function of the adrenal glands

Adrenal glands interact with the hypothalamus and pituitary gland in the brain. For example, for the adrenal gland to make corticosteroid hormones:

Both the hypothalamus and the pituitary gland can sense whether the blood has the right amount of cortisol (a hormone) in it. If there is too much or too little cortisol, these glands change the amount of CRH and ACTH they release.

What is the adrenal cortex?

The adrenal cortex secretes hormones that have an effect on the body's metabolism. The hormones also affect chemicals in the blood, and certain body characteristics. The adrenal cortex secretes hormones into the bloodstream. The hormones made by the adrenal cortex include:

Cortisol. This hormone helps control the body's use of fats, proteins, and carbohydrates. It suppresses allergic and inflammatory reactions in the body and also affects the immune system in other ways. Cortisol is needed to maintain blood pressure in times of stress.

Aldosterone. This hormone acts in the kidney to control the level of sodium and potassium in the body. It also helps maintain blood volume and blood pressure. Aldosterone is regulated by complex feedback mechanisms involving sodium and potassium levels as well as blood volume.

Androgen hormones. These hormones are converted elsewhere in the body to female hormones (estrogens) and male hormones (androgens). But, these steroid hormones are made in much larger amounts by the ovaries (estrogen) in women and testes (androgens) in men.

What is the adrenal medulla?

The adrenal medulla is the inner part of the adrenal gland. It helps a person cope with physical and emotional stress. The adrenal medulla secretes these hormones:

Epinephrine (adrenaline). This hormone helps the body respond to a stressful situation by increasing the heart rate and force of heart contractions. It also directs blood flow to the muscles and brain, causes smooth muscles to relax, and helps convert glycogen to glucose in the liver for energy, as well as other activities. People with asthma uses inhalers with epinephrine to open their breathing passageways.

Norepinephrine (noradrenaline). This hormone leads to squeezing of the blood vessels (vasoconstriction). This helps maintain blood pressure and increases it in response to sudden stress.

Medical Reviewers:

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Adrenal Glands - Health Encyclopedia - University of Rochester Medical Center

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Adrenal glands are small, triangular glands that sit on top of each kidney. An adrenal gland is made of 2 parts. The outer region is called the adrenal cortex. The inner region is called the adrenal medulla. Both parts have distinct functions. Adrenal glands interact with the hypothalamus and pituitary gland in the brain.

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https://www.mayoclinic.org/diseases-conditions/addisons-disease/diagnosis-treatment/drc-20350296

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Diagnosis

Your doctor will talk to you first about your medical history and your signs and symptoms. You may undergo some of the following tests:

Blood test. Tests can measure your blood levels of sodium, potassium, cortisol and adrenocorticotropic hormone (ACTH), which stimulates the adrenal cortex to produce its hormones. A blood test can also measure antibodies associated with autoimmune Addison's disease.

ACTH stimulation test. ACTH signals your adrenal glands to produce cortisol. This test measures the level of cortisol in your blood before and after an injection of synthetic ACTH.

Insulin-induced hypoglycemia test. You may be given this test if doctors think you may have adrenal insufficiency as a result of pituitary disease (secondary adrenal insufficiency). The test involves checking your blood sugar (blood glucose) and cortisol levels after an injection of insulin. In healthy people, glucose levels fall and cortisol levels increase.

In certain situations doctors may do alternative tests for secondary adrenal insufficiency, such as a low-dose ACTH stimulation test, prolonged ACTH stimulation test or glucagon stimulation test.

Imaging tests. You may undergo a computerized tomography (CT) scan of your abdomen to check the size of your adrenal glands and look for other abnormalities. You may also undergo an MRI scan of your pituitary gland if testing indicates you might have secondary adrenal insufficiency.

Treatment

All treatment for Addison's disease involves medication. You will be given hormone replacement therapy to correct the levels of steroid hormones your body isn't producing. Some options for treatment include oral corticosteroids such as:

Hydrocortisone (Cortef), prednisone or methylprednisolone to replace cortisol. These hormones are given on a schedule to mimic the normal 24-hour fluctuation of cortisol levels.

Fludrocortisone acetate to replace aldosterone.

You will need to get plenty of salt (sodium) in your diet, especially during heavy exercise, when the weather is hot or if you have gastrointestinal upsets, such as diarrhea.

Your doctor will also suggest a temporary increase in your medication dosage if your body is stressed, such as from an operation, an infection or a minor illness. If you're ill with vomiting and can't keep down oral medications, you may need injections of corticosteroids.

Other treatment recommendations include:

Carry a medical alert card and bracelet at all times. A steroid emergency card and medical alert identification will let emergency medical personnel know what kind of care you need. Also have a written action plan.

Keep extra medication handy. Missing even one day of medication may be dangerous, so keep a small supply of medication at work and with you whenever you travel.

Carry a glucocorticoid injection kit. The kit contains a needle, syringe and injectable form of corticosteroids to use in case of emergency.

Stay in contact with your doctor. Keep an ongoing relationship with your doctor to make sure that the doses of replacement hormones are adequate, but not excessive. If you're having ongoing problems with your medications, you may need adjustments in the doses or timing of the medications.

Have annual checkups. See your doctor or an endocrinology specialist at least once a year. Your doctor may recommend annual screening for a number of autoimmune diseases.

Treatment for an addisonian crisis, which is a medical emergency, typically includes intravenous injections of:

Corticosteroids

Saline solution

Sugar (dextrose)

Potential future treatments

Researchers are working to develop delayed-release corticosteroids, which act more like the human body. They are also working on pumps implanted under the skin that can deliver steroids in more-accurate doses.

Future treatment may eventually involve using adrenocortical stem cells combined with immunomodulatory treatment - modifying the immune response or the immune system - as well as gene therapy.

Clinical trials

Explore Mayo Clinic studies testing new treatments, interventions and tests as a means to prevent, detect, treat or manage this condition.

Coping and support

Support groups are available through the National Adrenal Diseases Foundation.

Preparing for your appointment

You're likely to start by seeing your family doctor or a general practitioner. However, when you call to set up an appointment, you may be referred to an endocrinologist.

Because appointments can be brief, and because there's often a lot of ground to cover, it's a good idea to be well-prepared for your appointment. Here's some information to help you get ready for your appointment, and what to expect from your doctor.

What you can do

Be aware of any pre-appointment restrictions. At the time you make the appointment, be sure to ask if there's anything you need to do in advance, such as restrict your diet.

Write down any symptoms you're experiencing, including any that may seem unrelated to the reason for which you scheduled the appointment.

Write down key personal information, including any major stresses or recent life changes.

Make a list of all medications, vitamins or supplements that you're taking.

Take a family member or friend along, if possible. Sometimes it can be difficult to recall all the information provided to you during an appointment. Someone who accompanies you may remember something that you missed or forgot.

Write down questions to ask your doctor.

Your time with your doctor is limited, so preparing a list of questions will help you make the most of your time together. List your questions from most important to least important in case time runs out. For Addison's disease, some basic questions to ask your doctor include:

What is likely causing my symptoms or condition?

Other than the most likely cause, what are possible causes for my symptoms or condition?

What kinds of tests do I need?

Is my condition likely temporary or chronic?

What is the best course of action?

What are the alternatives to the primary approach you're suggesting?

I have other health conditions. How can I best manage them together?

Are there any restrictions I need to follow?

Should I see a specialist?

Is there a generic alternative to the medicine you're prescribing me?

Are there any brochures or other printed material I can take home with me? What websites do you recommend?

In addition to the questions you've prepared to ask your doctor, don't hesitate to ask questions during your appointment.

What to expect from your doctor

Your doctor is likely to ask you a number of questions. Being ready to answer them may reserve time to go over any points you want to spend more time on. Your doctor may ask:

When did you first begin experiencing symptoms?

Have your symptoms been continuous or occasional?

How severe are your symptoms?

What, if anything, seems to improve your symptoms?

What, if anything, appears to worsen your symptoms?

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Your doctor will talk to you first about your medical history and your signs and symptoms. You may undergo some of the following tests: Blood test. Tests can measure your blood levels of sodium, potassium, cortisol and adrenocorticotropic hormone (ACTH), which stimulates the adrenal cortex to produce its hormones.