Brief Answer: Adrenal insufficiency Detailed Answer: 1 It can lead to very low blood pressure and cause shortness of breath. There are other ways it can do so too 2 Cortisol is typically highest in the morning when one wakes up and then declines as the day progresses such that it is lowest at midnight. This applies to normal sleep wake cycle. In shift workers this is reverses 3 Yes it can if the adrenal deficiency occurs rapidly. A surge of adrenaline or any stress can precipitate sudden adrenal deficiency in a person who has insufficiency of cortisol Let me tell you more about this condition The adrenal glands are located on top of each kidney and normally produce three classes of hormones: glucocorticoids, mineralocorticoids, and androgens. Adrenal insufficiency occurs when the adrenal glands produce an insufficient amount of one or more of these classes of hormones. Early detection of adrenal insufficiency can be difficult, although treatment is usually successful once it is initiated. Treatment is tailored to the underlying cause and, in most cases, lifelong treatment is necessary. With appropriate treatment and a few added precautions, people with adrenal insufficiency can lead active lives and have a normal life expectancy. TYPES OF ADRENAL HORMONES Glucocorticoids — Cortisol is the main glucocorticoid produced by the adrenal gland. Adrenocorticotropin hormone (ACTH) is made in the pituitary and stimulates the adrenal gland to produce cortisol. Cortisol has many important functions including: Helping to regulate glucose (blood sugar) levels Increase fat in the body Help to defend the body against infection Help the body respond to stress Mineralocorticoids — Aldosterone is the main mineralocorticoid produced by the adrenal glands. It helps to regulate the body's sodium and potassium levels, blood volume, and blood pressure. Androgens — Androgen hormones, including testosterone, dehydroepiandrosterone (DHEA), and DHEA sulfate, are present in both men and women. In women, androgens are produced in the adrenal glands and the ovaries. In women, adrenal androgens promote the development of sex characteristics such as underarm and pubic hair. In men, most androgens (eg, testosterone) are produced in the testes. Androgens made by the adrenal glands are not as important for normal sexual function. ADRENAL GLAND PRODUCTION OF HORMONES — Cortisol levels are normally regulated by the hypothalamus and pituitary gland. The hypothalamus sends corticotropin releasing hormone (CRH) to the pituitary gland. The pituitary gland responds by producing several hormones, one of which is ACTH (adrenocorticotropin hormone). ACTH stimulates the adrenal gland to produce cortisol. Cortisol levels help to control the pituitary's production of ACTH. PRIMARY ADRENAL INSUFFICIENCY — Primary adrenal insufficiency, also known as Addison's disease, occurs when the adrenal glands cannot produce an adequate amount of hormones despite a normal or increased ACTH level. This is a rare disease, occurring in about 35 to 120 people in every one million people. Most patients with Addison's disease experience fatigue, generalized weakness, loss of appetite and weight loss. The type and severity of symptoms depends upon the speed with which the condition develops, the severity of the hormone deficiency, the underlying cause of the condition, and other stresses on the body. Other common symptoms include: Darkening of the skin, especially on the face, neck, and back of hands Gastrointestinal symptoms such as nausea and vomiting (vomiting and abdominal pain may be a sign of an adrenal crisis) (see 'Adrenal crisis' below) Low blood pressure with lightheadedness after standing or sitting up Muscle and joint pain Salt cravings In women, decreased hair in the armpits and pubic area, and decreased sexual desire SECONDARY AND TERTIARY ADRENAL INSUFFICIENCY — In secondary adrenal insufficiency, an insufficient amount of ACTH is produced by the pituitary gland. In tertiary adrenal insufficiency, an insufficient amount of CRH is produced by the hypothalamus. Symptoms — The symptoms of secondary and tertiary adrenal insufficiency are similar to those of primary insufficiency, with a few exceptions: Darkening of the skin and dehydration do not occur Gastrointestinal symptoms are less common Symptoms of hypoglycemia (low blood sugar) are more common, including sweating, anxiety, shaking, nausea, or heart palpitations A tumor or other growth in the pituitary or hypothalamus can cause other symptoms, including headaches and difficulty seeing objects in the periphery of vision (to the far left and right). Also, low levels of pituitary hormones can develop and may cause infertility, impotence, fatigue, hoarseness, constipation, or a delay in beginning puberty or short stature in children. ADRENAL INSUFFICIENCY DIAGNOSIS — The diagnosis of adrenal insufficiency is a four part process: The blood cortisol level is measured Other tests are usually needed to confirm the diagnosis of adrenal insufficiency The level of the defect is determined (primary versus secondary/tertiary) by measuring ACTH Once the level of the defect is known, further evaluation is done to determine the cause of the defect or to evaluate for other associated problems Cortisol and ACTH level testing — To determine a person's cortisol and ACTH level, a blood sample is taken early in the morning, usually at around 8 AM. If the cortisol level is very low, the person is likely to have adrenal insufficiency. If the cortisol level is above a certain normal level, the person is very unlikely to have adrenal insufficiency. Many patients have cortisol results in an intermediate zone and need to have additional testing. A variety of other tests can be done to confirm the diagnosis of adrenal insufficiency. Most often, an ACTH stimulation test is done to establish the diagnosis. To perform this test, a blood sample is taken at any time of day to measure the "baseline" cortisol level. A high dose of ACTH is then given into a vein. A blood sample is then taken again 30 to 60 minutes later to measure the cortisol level. A low cortisol level after a dose of ACTH confirms that the person has adrenal insufficiency. Measurement of a blood ACTH level helps to determine if the problem lies within the adrenal gland (causing primary adrenal insufficiency) or in the pituitary or hypothalamus (causing secondary adrenal insufficiency): If the ACTH level is high, the person probably has primary adrenal insufficiency. If the ACTH level is low, the person probably has secondary or tertiary adrenal insufficiency. Determine the underlying cause For primary adrenal insufficiency — To determine the cause of primary adrenal insufficiency, the clinician must consider the patient's age, gender, and other medical problems. Most clinicians recommend an abdominal CT scan to evaluate the adrenal glands. In some cases, blood tests or a chest x-ray will also be recommended. In the past, tuberculosis was the most common cause of primary adrenal insufficiency. Currently, the most common cause of Addison's disease is autoimmune adrenalitis (a disease that causes the body to develop antibodies against the adrenal gland, eventually destroying it). For secondary/tertiary adrenal insufficiency — Possible causes of secondary and tertiary adrenal insufficiency include: An abnormal growth in the pituitary or hypothalamus Some people have deficiencies in ACTH and possibly other pituitary hormones (partial or panhypopituitarism) at birth; these are called congenital deficiencies Long-term treatment with glucocorticoid medications (eg, taking prednisone for asthma); this can interfere with normal pituitary function and is the most common cause of secondary adrenal insufficiency The clinician will usually obtain a MRI scan of the pituitary gland as well as blood tests of pituitary hormones. The scan provides a detailed image, to determine if a mass or abnormal growth is present. ADRENAL INSUFFICIENCY TREATMENT — The treatment of adrenal insufficiency includes replacement of the deficient hormones. The goal of treatment is to relieve the symptoms of hormone deficiency without developing signs of hormone excess. Treatment usually requires lifelong hormone replacement. Correct use of these hormone medications is essential to minimize symptoms and the chance of adrenal crisis. Primary insufficiency — Treatment of adrenal insufficiency requires a daily dose of a glucocorticoid and mineralocorticoid pill, usually for life. Androgen replacement may be recommended for women. The goal of treatment is to stabilize hormone levels and relieve symptoms. Hormone levels must remain balanced to minimize symptoms and the chance of adrenal crisis (see 'Adrenal crisis' below). Fatigue and nausea usually begin to disappear within days of starting treatment. Glucocorticoids — Several options are available for replacing glucocorticoids; a clinician will work with the patient to determine the regimen that is most effective, convenient, and that causes minimal side effects. Many clinicians prescribe the short-acting preparation oral hydrocortisone (similar to cortisol produced normally), with two or three doses per day. The largest dose is taken in the early morning and a smaller dose is taken in mid morning and mid- afternoon; this mimics the normal variation in blood cortisol levels. Because hydrocortisone is available in a variety of doses, the amount of hydrocortisone can be adjusted easily, which may be an advantage over the longer acting glucocorticoids. A longer acting glucocorticoid like prednisone is sometimes preferred because it can be taken once per day. Occasionally, a small additional dose is needed in the afternoon. It may be difficult to adjust the dose of these medications to avoid over-treatment. Monitoring during treatment — The development of weight gain or a puffy face is a sign of possible overtreatment and the glucocorticoid dose is usually decreased as a result. Higher doses of glucocorticoids are of no benefit and may increase the risk of bone thinning (osteoporosis). A clinician will monitor closely for these complications. Dosing — The dose of any of glucocorticoids is tailored to the patient's body weight and age; obese people may need a higher dose, while children and small adults may need a lower dose. Adjustments in dose are often necessary when starting treatment. Mineralocorticoids — Mineralocorticoids are replaced with an oral, synthetic mineralocorticoid drug called fludrocortisone (Florinef®). The dose of this medication is tailored to manage blood pressure and fluid balance. When the dose is adequate, there should be no problems with lightheadedness or dizziness when standing up. If the dose is too high, the person may notice swelling in the ankles, and the clinician may note hypertension (high blood pressure) or low blood potassium levels. In this case, the dose of fludrocortisone would be decreased. Androgens — Androgen replacement is sometimes recommended for women with primary adrenal insufficiency. A daily dose of dehydroepiandrosterone (DHEA) may improve libido and provide an improved overall sense of well-being. However, there are potential side effects associated with DHEA that are related to elevated androgen levels (eg, acne, facial hair, deepened voice). In addition, DHEA is only available as a dietary supplement in the United States. Because it is not regulated by the Food and Drug Administration, there are concerns about quality control and safety. Secondary and tertiary insufficiency — People with secondary and tertiary adrenal insufficiency require only glucocorticoid replacement (not mineralocorticoid or androgen replacement). Doses may be adjusted frequently in the beginning. Treatment may also include replacement of other deficient pituitary hormones. ADRENAL CRISIS — Adrenal crisis refers to overwhelming and life-threatening adrenal insufficiency. The most common signs of adrenal crisis are shock (very low blood pressure with a loss of consciousness), dehydration, and an imbalance of sodium and potassium levels in the body. In some cases, shock is preceded by fever, nausea, vomiting, and abdominal pain, weakness or fatigue, and confusion. Adrenal crisis usually occurs after an infection, trauma, or another stressor. Adrenal crisis is a life-threatening condition that requires emergency medical treatment. The patient or a family member or friend should immediately give an emergency injection of a glucocorticoid at the first signs of adrenal crisis (see 'Emergency precautions' below). In the emergency department or ambulance, treatment usually includes giving several liters of a salt solution (saline) and an injection of a glucocorticoid (dexamethasone or another form of cortisol) into a vein. Mineralocorticoid treatment (if needed) is usually started at a later time, when the saline treatment is completed. Following treatment, it is important look for and treat any factors that may have triggered the crisis, such as infection. ADRENAL INSUFFICIENCY PRECAUTIONS AND SPECIAL SITUATIONS — People with adrenal insufficiency should learn as much as possible about their condition and should be aware of early warning signs of hormone deficiency. It is also wise to share this information with family, friends, and any caregivers, so that they can also identify signs of trouble and be prepared to act in case of adrenal crisis. General precautions — People with adrenal insufficiency should wear a medical alert bracelet or necklace. They should also carry an emergency medical information card that lists the names and doses of their daily medications and the clinician and family member(s) to call in case of emergency. It is extremely important to identify early symptoms of adrenal deficiency and adrenal crisis; a clinician can describe subtle symptoms that should not be ignored. Emergency precautions — Even with careful use of medications and medical monitoring, some people with primary adrenal insufficiency will experience adrenal crisis. As a safety measure, the patient should always carry a syringe and a vial of dexamethasone (or another glucocorticoid). This system should be stored at home, at work or school, and in the patient's handbag or backpack. The patient or a family member or friend should give the injection into a muscle (usually the thigh) if any of the following occurs: After a major injury with substantial blood loss, fracture, or shock During an episode of nausea and vomiting if oral medications are thrown up If there are any signs or symptoms of adrenal crisis If a person is found unconscious Most people with adrenal insufficiency go years without needing an injection. However, the injection is recommended if there is any reason to believe it might be needed. There is little to no risk of being given an extra dose of a glucocorticoid while there are significant risks of having a low glucocorticoid level. After the injection is given, the patient should seek medical care immediately. After a major injury or if the person is found unconscious, it is best to call for emergency medical services. In the United States, most people can access emergency care by calling 911. Illnesses, medical procedures, and surgery — The adrenal glands normally increase cortisol output when the body is stressed by illness, major medical procedures, or surgery. People with adrenal insufficiency do not have this ability. The risk of adrenal crisis can be minimized by adjusting the dose of medications. During symptoms of a cold or flu, it is safe to double or triple the daily dose of glucocorticoid for three days without calling the doctor. However, if symptoms become worse during that time, or if it is not possible to return to the usual glucocorticoid dose on the fourth day, the healthcare provider should be called for advice. It is important to call the provider if there are any signs of a stomach illness with nausea, diarrhea, or vomiting. It is also important to call before any medical procedures or surgery. The provider will usually recommend temporarily increasing the glucocorticoid dose for these types of stresses. Pregnancy — Most women who have primary adrenal insufficiency are able to have a healthy pregnancy, labor, and delivery. During this time, it is important to take medications on schedule and have careful monitoring of the growing fetus as well as the woman's adrenal insufficiency. Some women require changes in glucocorticoid doses, especially during the third trimester and during labor. Women who have severe morning sickness may need to switch from oral medication to injected medication until the morning sickness subsides. ADRENAL INSUFFICIENCY PROGNOSIS — The long term outlook is good for most people with adrenal insufficiency who are treated and monitored. Most people can lead an active life, and have a normal life expectancy. Children with adrenal insufficiency who are treated and monitored carefully can grow normally and experience puberty without difficulty.