The Adrenal Glands

The adrenal glands also known as the suprarenal glands sit on top of the kidneys. The right adrenal gland is triangular shaped, while the left suprarenal gland is semilunar shaped.

They are chiefly responsible for releasing hormones in response to stress through the synthesis of corticosteroids such as cortisol and catecholamines such as epinephrine. The synthesis of these hormones starts with cholesterol. The adrenal glands affect kidney function through the secretion of aldosterone, a hormone involved in regulating the osmolarity of blood plasma. The adrenal glands are separated into two distinct structures, the adrenal cortex and medulla, both of which produce hormones. The cortex mainly produces cortisol, aldosterone, and androgens, while the medulla chiefly produces epinephrine and norepinephrine.

The Adrenal Cortex

The adrenal cortex is devoted to the synthesis of corticosteroid hormones. Corticosteroids are synthesized from cholesterol within the adrenal cortex. Specific cortical cells produce particular hormones including cortisol, corticosterone, androgens such as testosterone, and aldosterone. Under normal unstressed conditions, the human adrenal glands produce the equivalent of 35–40 mg of cortisone per day. In contrast to the direct innervation of the medulla, the cortex is regulated by hormones secreted by the pituitary gland and the hypothalamus, as well as by the renin-angiotensin system.

The adrenal cortex is comprised of three zones, or layers. The anatomic zonation can be appreciated at the microscopic level, where each zone can be recognized and distinguished from one another based on structural and anatomic characteristics. The adrenal cortex exhibits functional zonation as well: by virtue of the characteristic enzymes present in each zone, the zones produce and secrete distinct hormones.

Zona glomerulosa (outer)

    The outermost layer, the zona glomerulosa is the main site for production of mineralocorticoids, mainly aldosterone, which is largely responsible for the long-term regulation of blood pressure and balancing of the electrolytes.

Zona fasciculata

    Situated between the glomerulosa and reticularis, the zona fasciculata is responsible for producing glucocorticoids, chiefly cortisol. The zona fasciculata secretes a basal level of cortisol but can also produce bursts of the hormone in response to adrenocorticotropic hormone (ACTH) from the pituitary gland.

Zona reticularis

    The inner most cortical layer, the zona reticularis produces androgens, mainly dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEA-S).

The Adrenal Medulla

The adrenal medulla is the core of the adrenal gland, and is surrounded by the adrenal cortex. The chromaffin cells of the medulla are the body’s main source of the circulating catecholamines adrenaline (epinephrine) and noradrenaline (norepinephrine). Derived from the amino acid tyrosine, these water-soluble hormones are major hormones underlying the fight-or-flight response.

To carry out its part of this response, the adrenal medulla receives input from the sympathetic nervous system through preganglionic fibers originating in the thoracic spinal cord. Because it is innervated by preganglionic nerve fibers, the adrenal medulla can be considered as a specialized sympathetic ganglion. Unlike other sympathetic ganglia, however, the adrenal medulla lacks distinct synapses and releases its secretions directly into the blood.

Cortisol also promotes epinephrine synthesis in the medulla. Produced in the cortex, cortisol reaches the adrenal medulla and at high levels, the hormone can promote the up regulation of phenylethanolamine N-methyltransferase (PNMT), thereby increasing epinephrine synthesis and secretion.

Cortisol is in a class of hormones called glucocorticoids, which affect every organ and tissue in the body. Cortisol has thousands of affects in the body. Cortisol’s most important job is to help the body respond to stress and to maintain glucose levels in the blood for energy.

The adrenal glands are responsible for the “fight or flight” reaction to stress as well as the longer actions of cortisol for illness and extended stressors. Briefly, there is a rapid increase in cortisol, to enable the body to cope. Among its other vital tasks, cortisol helps maintain blood pressure and heart function, helps slow the immune system’s inflammatory response, helps balance the effects of insulin in breaking down sugar for energy, helps regulate the metabolism of proteins, carbohydrates, and fats, helps maintain proper arousal and sense of well-being and with its diurnal rhythm and the help of melatonin, regulates the sleep/wake cycle.

It is the failure of this mechanism to work properly, in the presence of general stress, or the stress of illness, that we call low adrenal reserve, adrenal insufficiency or adrenal fatigue. Adrenal Fatigue is actually a misnomer which should be HPA Dysfunction (Hypothalamus, Pituitary, Adrenal Dysfunction). When the adrenals fail to function at all or the failure is caused by autoimmune disease, it is called Adrenal Failure or Addison’s Disease. When adrenals hyper function, for many reasons, it is called Cushings Syndrome.


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Low Cortisol

Overview

When the adrenal glands do not make enough cortisol, this is called adrenal insufficiency. Please see the section on adrenals.

Causes

  • Hypothyroidism
      This is the cause that we deal with most of the time and it’s due to taking T4 only thyroid meds, or under treating with Desiccated thyroid or other issues that interfere with the thyroid hormones getting into the cell. Such as RT3 or low iron. When thyroid hormones are not at an optimal level, the adrenals will excrete more cortisol in order to keep the body functioning, over time; this causes them to become fatigued. Also low thyroid in the body down-regulates every other gland and organ including the adrenals.
  • High stress lifestyle
      When the adrenals are asked to consistently pump out cortisol they eventually become tired and overworked. Then they are not able to produce enough cortisol on their own.
  • Bad eating habits
      This would cover yoyo and extreme dieting and eating and diet high in processed foods. A good balanced diet with good fats, lean meats, fish, fruits, vegetables, whole grains and proper mineral balance, will help to keep adrenals healthy.
  • Medications
    • SSRI Antidepressants (Effexor, Prozac, Cymbalta, Zoloft, Lexapro, Paxil)
    • Tricyclic Antidepressants
    • Benzodiazepines (Xanax, Ativan, Valium, Klonipin)
    • GABA (Lyrica, Gabapentin, Neurontin)
    • Sleeping Aids (Ambien, Sonata, Lunesta)
    • Prednisone Dose Packs
    • Medrol Dose Pack
    • Cortisone injections
    • Stimulants (Adderall, Provigil)
    • Most arthritis medications
    • Steroid Asthma medications
    • Steroid nasal sprays
    • Most blood pressure medications
    • Alpha and
    • Beta Blockers
    • Progesterone unless it is perfectly titrated and balanced with estrogen
    • HCG
  • Supplements that contribute to adrenal fatigue
    • Holy Basil
    • Ginseng
    • Eleuthero
    • Astragalus
    • Zinc
    • Phosphatidylserine
    • Melatonin
    • Bee Pollen and beeswax products
    • Alcohol
    • Phenibut
    • Valerian
    • Kava Kava
    • 5-HTP

 

 

Symptoms

  • Allergies getting worse
  • Body ache – all over
  • Clumsy
  • Confusion
  • Continuing hypothyroid symptoms with a high Free T3
  • Dark circles under eyes
  • Diarrhea
  • Dizziness
  • Emotionally hyper sensitive
  • Fatigue
  • Feeling better after 6 pm
  • Feeling of doom or panic
  • Flu like symptoms
  • Headache
  • Heart palpitations
  • Highly defensive
  • Hypoglycemia
  • IBS symptoms
  • Inability to focus
  • Inability to handle stress
  • Inability to interact with others
  • Inflammation that doesn’t go away
  • Irritable
  • Jittery or hyper feeling
  • Low back pain – in kidney/adrenal area
  • Motion sickness
  • Nausea
  • Rage or sudden angry outburst
  • Overreacting
  • Paranoid
  • No patience
  • Shaky hands, internal feeling of shakiness
  • Weakness – general or localized

Testing

The most reliable and accurate way to test for adrenal fatigue is the 24 hour adrenal saliva test. This will test cortisol levels either 4 or 6 times (depending on which lab) during the day and night. It is not only your cortisol levels that are important, but also the cortisol rhythm.

You cannot get accurate saliva results while on any kind of medication or supplement that will affect cortisol. Examples of this would be (this is not a complete list) Hydrocortisone, anti-anxiety meds, some anti-depressants, herbal adrenals supplements, asthma inhalers, prednisone.

Saliva testing tells you the level of cortisol that is free and available (unbound) for your body to use. A blood cortisol level tells you what is bound and unbound. It is the unbound cortisol that is we need to know about.

Herbal support will either extend your natural production or will help to raise or lower a low or high level of cortisol. Due to the herbal remedies interference with your own cortisol production you cannot test while taking these.

HC (hydrocortisone) will suppress your ACTH (which is the hormone that tells the adrenals to make cortisol) which in turn will suppress your own cortisol production.

Treatment

Your treatment should be based on the results of your 24 hour cortisol saliva test and your symptoms.

Hydrocortisone (HC) is a glucocorticoid. Glucocorticoids are adrenocortical steroids, both naturally occurring and synthetic, which are readily absorbed from the gastrointestinal tract. Hydrocortisone (HC) is the most commonly used steroid to treat adrenal fatigue. Although hydrocortisone is classified as a steroid it is also bio-identical. Hydrocortisone is basically cortisol and this is what your body makes when your adrenals are healthy and functioning properly. Hydrocortisone’s brand name is Cortef and is made by Pfizer. There are many pharmaceutical companies that make generic brands of hydrocortisone. These generic brands work just as well as the name brand with some variances in absorption that are titrated out as you adjust your doses.
When you receive your prescription for HC you will also receive a patient information sheet. This will list all kind of scary side effect of HC. But what you have to realize is that this information is based on pharmacologic doses of HC and what you will be taking to rest and heal your adrenals is a physiologic dose, which is a much lower dose. A pharmacologic dose would be approximately 100 mg or more. A physiologic dose would be 50 mg or less. Men will need more HC then women, so their doses will be slightly higher.

Methylprednisolone (medrol) is a glucocorticoid. Glucocorticoids are adrenocortical steroids, both naturally occurring and synthetic, which are readily absorbed from the gastrointestinal tract. Some patients find that HC is not strong enough or does not last long enough. These patients may have to switch completely or partially to Medrol. Medrol is 5 times more potent than HC.

Prednisone and Prednisolone are gluccocorticoid. Glucocorticoids are adrenocortical steroids, both naturally occurring and synthetic, which are readily absorbed from the gastrointestinal tract. These are not normally recommended for treating adrenal fatigue. Both Prednisone and Prednisolone are 4 times more potent than HC.

Isocort and Glandulars would be used to treat mild cases of Adrenal Fatigue. Although adrenals may not respond to these and HC may be needed.

Isocort is a Fermented Plant Derived Cortisol and Echinacea Purpurea. Some have trouble with Isocort due to the Echinacea as it belongs to the ragweed family. Isocort may be purchased over the internet and is available at many different sites.

Ashwagandha In Ayurveda ashwagandha is considered a rasayana herb. This herb is also considered an adaptogen which is an herb that works to normalize physiological function, working on the HPA axis and the neuroendocrine system. Ashwagandha has many beneficial elements, including flavonoids and members of the withanolide class. Numerous modern studies have found that ashwagandha shows great promise for being effective in reducing inflammation, decreasing stress, increasing mental activity, invigorating the body, and as an antioxidant. Ashwagandha will help to balance high and low cortisol levels with its activity that is similar to GABA, which explains why the plant is effective in reducing anxiety.

Rhodiola or Rhodiola rosea may be effective for improving mood and alleviating depression. Pilot studies on human subjects showed that it improves physical and mental performance, and may reduce fatigue. Rhodiola rosea’s effects potentially are related to optimizing serotonin and dopamine levels due to monoamine oxidase inhibition and its influence on opioid peptides such as beta-endorphins, although these specific neurochemical mechanisms have not been clearly documented with scientific studies. Rhodiola is included among a class of plant derivatives called adaptogens which differ from chemical stimulants, such as nicotine, and do not have the same physiological effects. In Russia and Scandinavia, Rhodiola rosea has been used for centuries to cope with the cold Siberian climate and stressful life. Such effects were provided with evidence in laboratory models of stress using the nematode C. elegans, and in rats in which Rhodiola effectively prevented stress-induced changes in appetite, physical activity, weight gain and the estrus cycle.

Most glandular products contain a combination of herbs and are not recommended. Glandulars in most cases contain the whole adrenal gland and therefore contain adrenaline. Products containing a combination of herbs usually contain some for both high and low cortisol and are counterproductive.

A  adrenal cortex supplement is the best choice for treating mild adrenal fatigue.

The following is a list of other supplements that should be taken to help support healthy adrenal function:

B-complex 100 Once a day. Either morning or night depending on how it affects you. Some will get energy from B vitamins and others will get a calming effect.
Vitamin Cat least 2000mg or to bowel tolerance
Sea salt it should be unrefined sea salt and we find that Celtic sea salt works the best.
B-12 Sublingual Methylcobalamin 2500mcg daily

It is very important to track your treatment. This is done by charting your temps. What this means is taking your temperature orally 3 times a day and getting an average temperature for that day. You will take your temp 3 hours after getting out of bed and then every three hours after that for a total of 3 temps for the day. For example if you get up at 6 am, you will take temps at 9am, noon and 3pm. It is best to take your temps at the same time every day. You are looking for 5 consecutive days of stable temperatures. Stable temps are within .2 degrees Fahrenheit of each other. For example 98.0, 98.1, 98.0, 98.2, 98.1. When your temps are stable this tells you that you are on enough adrenal support and that it is time to either raise or add thyroid medication.
An old fashion mercury thermometer is best for charting temps but if one is not available or you are not comfortable using a mercury thermometer, then a Geratherm Mercury Free Oral Thermometer will work.
Tracking your blood pressure and pulse are also helpful in tracking your treatment.
Remember that for both temps and blood pressure you should sit and rest for at least 15 minutes and not have anything to eat, drink or smoke in that time period.

Treatment for adrenal insufficiency takes at least six months and often a year or more. Lifestyle changes are very important in rest and healing adrenals and in resetting the HPA axis. See the section on lifestyle and adrenals.


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Addisons

Overview

Addison’s disease is a disorder that occurs when the adrenal glands do not produce enough adrenal hormones (glucocorticoid, mineralocorticoid, sex hormones). Addison’s disease results from damage to the adrenal cortex.

Causes

  • The immune system mistakenly attacking the gland (autoimmune disease)
  • Infections such as tuberculosis, HIV, or fungal infections
  • Hemorrhage, blood loss
  • Tumors
  • Use of blood-thinning drugs (anticoagulants)
  • Birth defect ( adrenals gland not forming properly during development)
  • Lack of cholesterol
  • Risk factors for the autoimmune type of Addison’s disease include other autoimmune diseases:
    • Chronic thyroiditis
    • Dermatitis herpetiformis
    • Graves’ disease
    • Hypoparathyroidism
    • Hypopituitarism
    • Myasthenia gravis
    • Pernicious anemia
    • Testicular dysfunction
    • Type I diabetes
    • Vitiligo
    • Certain genetic defects may cause these conditions.

Symptoms

  • Changes in blood pressure or heart rate
  • Chronic diarrhea
  • Darkening of the skin – patchy skin color
  • Unnaturally dark color in some places
  • Paleness
  • Fatigue
  • Loss of appetite
  • Mouth lesions on the inside of a cheek (buccal mucosa)
  • Vomiting
  • Salt craving
  • Slow, sluggish movement
  • Unintentional weight loss
  • Allergies getting worse
  • Body ache – all over
  • Clumsy
  • Confusion
  • Continuing hypothyroid symptoms with a high Free T3
  • Dark circles under eyes
  • Diarrhea
  • Dizziness
  • Emotionally hypersensitive
  • Feeling better after 6 pm
  • Feeling of doom or panic
  • Flu like symptoms
  • Headache
  • Heart palpitations
  • Highly defensive
  • Hypoglycemia
  • IBS symptoms
  • Inability to focus
  • Inability to handle stress
  • Inability to interact with others
  • Inflammation that doesn’t go away
  • Irritable
  • Jittery or hyper feeling
  • Low back pain – in kidney/adrenal area
  • Motion sickness
  • Nausea
  • Rage or sudden angry outburst
  • Overreacting
  • Paranoid
  • No patience
  • Shaky hands, internal feeling of shakiness
  • Weakness – general or localized
  • Sudden penetrating pain in the legs, lower back or abdomen
  • Syncope (loss of consciousness and ability to stand)
  • Hypoglycemia (reduced level of blood glucose)
  • Slurred speech
  • Severe lethargy
  • Hyponatremia(low sodium level in the blood)
  • Hyperkalemia (elevated potassium level in the blood)
  • Hypercalcemia (elevated calcium level in the blood)
  • Convulsions
  • Fever
  • Psychosis

Testing

You cannot get accurate saliva results while on any kind of medication or supplement that will affect cortisol. Examples of this would be (this is not a complete list) Hydrocortisone, anti-anxiety meds, some anti-depressants, herbal adrenals supplements, asthma inhalers, prednisone.

Saliva testing tells you the level of cortisol that is free and available (unbound) for your body to use. Where a blood cortisol level tells you what is bound and unbound. It is the unbound cortisol that is we need to know about.

    Aldosterone
    Renin
    CTH stimulation test
    Abdominal x-ray
    Abdominal CT scan

Tests may show:

  • Increased potassium
  • Low blood pressure
  • Low cortisol level
  • Low serum sodium
  • Normal sex hormone levels

This disease may also change the results of the following tests:

  • 17-hydroxycorticosteroids
  • 17-ketosteroids
  • 24-hour urinary aldosterone excretion rate
  • ACTH
  • Aldosterone
  • Blood eosinophil count
  • CO2
  • Cortrosyn stimulation test
  • Potassium test
  • Renin
  • Urine cortisol

Treatment

Treatment with replacement corticosteroids will control the symptoms of this disease. However, you will usually need to take these drugs for life. People often receive a combination of glucocorticoids (cortisone or hydrocortisone) and mineralocorticoids (fludrocortisone).

Never skip doses of your medication for this condition, because life-threatening reactions may occur.

The health care provider may increase the medication dose in times of:

  • Infection
  • Injury
  • Stress

During an extreme form of adrenal insufficiency, adrenal crisis, you must inject hydrocortisone immediately. Supportive treatment for low blood pressure is usually needed as well.

Some people with Addison’s disease are taught to give themselves an emergency injection of hydrocortisone during stressful situations. It is important for you to always carry a medical identification card that states the type of medication and the proper dose needed in case of an emergency. Additionally, your health care provider may advise you to always wear a Medic-Alert tag (such as a bracelet) alerting health care professionals that you have this condition in case of emergency.

Expectations (prognosis)

With hormone replacement therapy, most people with Addison’s disease are able to lead normal lives.

Complications

Complications can occur if you take too little or too much adrenal hormone supplement.

Complications also may result from the following related illnesses:

  • Diabetes
  • Hashimoto’s thyroiditis (chronic thyroiditis)
  • Hypoparathyroidism
  • Ovarian hypofunction or testicular failure
  • Pernicious anemia
  • Thyrotoxicosis
  • Celiac disease

A medical alert bracket should be worn.


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High Cortisol

Overview

High cortisol happens when your adrenal glands produce too much cortisol. This usually indicates the early stages of adrenal fatigue or adrenal exhaustion.

Causes

  • High stress lifestyle
      When the adrenals are asked to consistently pump out cortisol they eventually become tired and over worked. Then they are not able to produce enough cortisol on their own.
  • Bad eating habits
      This would cover yoyo and extreme dieting and eating a diet high in processed foods. A good balanced diet with good fats, lean meats, fish, fruits, vegetables, whole grains and proper mineral balance, will help to keep adrenals healthy.
  • Medications
      • HCG
      • Dextroamphetamine (Dexedrine)
      • Benzodiazepines (Xanax, Ativan, Valium, Klonipin)
      • SSRI Antidepressants
      • Toxin stress from environmental factors
      • Inflammatory conditions such as Hashimotos Thyroiditis
    • See the section on Cushings

Symptoms

    • Bruising easily
    • Fluid retention
    • High blood pressure
    • Moon-shaped face
    • Obesity
    • Severe fatigue
    • Spare Tire – increased belly fat
    • Weak muscles and deterioration
    • Increased fat in the back of the neck and upper back area (hump)
    • Purple stretch marks

Testing

The most reliable and most accurate way to test for adrenal fatigue is the 24 hour adrenal saliva test. This test will give you your cortisol levels either 4 or 6 times (depending on which lab) during the day and night. It is not only your cortisol levels that are important, but also the cortisol rhythm. You cannot get accurate saliva results while on any kind of medication or supplement that will affect cortisol. Examples of this would be (this is not a complete list) Hydrocortisone, anti-anxiety meds, some anti-depressants, herbal adrenals supplements, asthma inhalers, prednisone. Saliva testing tells you the level of cortisol that is free and available (unbound) for your body to use. Where a blood cortisol level tells you what is bound and unbound. It is the unbound cortisol that is we need to know about. Herbal support will either extend your natural production or will help to raise or lower a low or high level of cortisol. Due to the herbal remedies interference with your own cortisol production you cannot test while taking these.

Treatment

Which method of treatment is used will depend on the results of your 24-hour cortisol saliva test.

Holy Basil – Tulsi has been used for thousands of years in Ayurveda for its diverse healing properties. Tulsi is considered to be an adaptogen, balancing different processes in the body, and helpful for adapting to stress.

Phosphatidyl Serine

Melatonin – Circulating levels of the hormone melatonin vary in a daily cycle, thereby allowing the entrainment of the circadian rhythm of several biological functions. Taken 30 to 90 minutes before bedtime, melatonin supplementation acts as a mild hypnotic. It causes melatonin levels in the blood to rise earlier than the brains own production accomplishes. Melatonin should only be taken for a few weeks to a few months.

Zinc – zinc should only be taken for a short period of time as an excess of zinc is toxic. It can be taken in doses up to 50 mg a day.

DHEA – DHEA would only be taken in cases of very high cortisol and depending on your levels of DHEA and DHEA-S.

Tracking your treatment It is very important to track your treatment. This is done by what we call charting your temps. What this means is taking your temperature orally 3 times a day and getting an average temperature for that day. You will take your temp 3 hours after getting out of bed and then every three hours after that for a total of 3 temps for the day. For example if you get up at 6 am, you will take temps at 9am, noon and 3pm. It is best to take your temps at the same time every day. You are looking for 5 consecutive days of stable temperatures. Stable temps are within .2 of each others. For example 98.0, 98.1, 98.0, 98.2, 98.1. When your temps are stable this tells you that one you are on enough adrenal support and two that it is time to either raise or add thyroid medication. An old fashion mercury thermometer is best for charting temps but if one is not available or you are not comfortable using a mercury thermometer, then a Geratherm Mercury Free Oral Thermometer will work. Tracking your blood pressure and pulse are also helpful in tracking your treatment. Remember that for both temps and blood pressure you should sit and rest for at least 15 minutes and have not had anything to eat, drink or smoke in the time period.


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Cushings

Overview

Cushing’s syndrome is characterized by excessive cortisol production. The most common cause is an ACTH-secreting pituitary tumor. Since ACTH is the natural stimulator of cortisol production, too much ACTH causes the adrenal glands to grow (adrenal hyperplasia) and produce too much cortisol. Cushing’s can also be caused by a tumor on one or both of the adrenal glands.

Normally cortisol is secreted with a distinctive daily pattern called a circadian rhythm. Cortisol levels peak in the morning (usually between 7 and 8 AM) and decrease to substantially lower levels late at night. In Cushing’s syndrome, levels do not follow the normal circadian rhythm so cortisol levels are found to be high at all times during the day and night.

Cushing’s syndrome is fairly rare. It is more often found in women than in men and often occurs between the ages of 20 and 40.

Symptoms of Cushing’s syndrome:

  • Weight gain
  • Hypertension
  • Poor short term memory
  • Insomnia
  • Recurrent infections
  • Muscle weakness
  • Irritability
  • Excess hair growth in women
  • Thin skin
  • Purple stretch marks
  • Easy bruising
  • Depression
  • Red ruddy face
  • Extra fat around the neck
  • Weak bones
  • Acne
  • Round face
  • Fatigue
  • Hip and shoulder weakness
  • Poor concentration
  • Balding in women
  • Swelling of feet and/or legs
  • Menstrual irregularity
  • Diabetes

Testing

The 24-hour adrenal saliva test measures your free cortisol and also your circadian rhythm. This is the most informative test.

The Dexamethasone Suppression Test will show up certain types of Cushing’s syndrome. Dexamethasone is a steroid that can mimic cortisol. If the body is regulating cortisol correctly, the cortisol levels will decrease after taking a dexamethasone tablet. In someone with Cushing’s syndrome, the cortisol level will remain unchanged and high.

A 24-hour urine cortisol test can also be helpful and will show your total cortisol output in a 24- hour period.

ACTH blood test.

Inferior petrosal sinus sampling (IPSS) is the best test to distinguish an ACTH-producing tumor on the pituitary from one in another part of the body. This involves inserting small plastic tubes into both the right- and left-sided veins in the groin (or neck) and threading them up to the veins near the pituitary gland. Blood is then taken from these locations and also from a vein not connected to the pituitary gland. During the procedure, a medication that increases ACTH levels from the pituitary is injected. By comparing the levels of ACTH produced close to the pituitary gland in response to the medication with those produced by other parts of the body, a diagnosis can be made.

It is also possible to visualize the pituitary gland using a process called magnetic resonance imaging (MRI). This involves an injection of an agent that will help the tumor to show up on the MRI scan. However, up to 10% of healthy people have an abnormal area on their pituitary consistent with a tumor. Therefore, the presence of an abnormality alone is not diagnostic of Cushing’s disease. Also, in about 50% of patients with Cushing’s disease, the tumor is too small to be seen. Thus the absence of a tumor on a MRI scan does not necessarily exclude Cushing’s syndrome.

Treatment

Removal of Pituitary Tumor

Removal of the pituitary tumor by surgery is the best way to treat Cushing’s disease. This is recommended for those who have a tumor that does not extend into areas outside of the pituitary gland as long as they are well enough to tolerate anesthesia. This is usually carried out by going via the nose or upper lip and through the sphenoid sinus to reach the tumor. This is known as transsphenoidal surgery and avoids having to get to the pituitary via the upper skull. This route is less traumatic for the patient and allows for a quicker recovery.

Removing only the tumor leaves the rest of the pituitary gland intact so that it will eventually function normally. This is successful for 70–90% of people when performed by the best pituitary surgeons. The success rates reflect the experience of the surgeon performing the operation. However, the tumor can return in up to 15% of patients, probably because of incomplete tumor removal at the earlier surgery.

After successful pituitary surgery, cortisol levels will be very low. This can continue for 3–18 months after surgery. These low levels of cortisol can cause nausea, vomiting, diarrhea, aches and pains, and a flu-like feeling. These feelings are common in the first days and weeks after surgery as the body adjusts to the lower cortisol levels. Doctors give people a cortisol-like medicine until recovery of the pituitary and adrenal glands is either well under way or complete.

Hydrocortisone or prednisone is usually used for this purpose. Doctors monitor the recovery of the pituitary and adrenal glands by measuring morning cortisol values, or by testing the ability of the adrenal glands to secrete cortisol in response to an injected medication similar to ACTH.

Until the pituitary and adrenal glands recover, the body does not respond normally to stress such as illness by increasing cortisol production. As a result people who suffer with ‘flu’, fever or nausea may have to double the oral dose of the glucocorticoid when they are sick. However, this increased dosage should only be used for 1–3 days. On occasion, people can suffer vomiting or severe diarrhea that prevents them from absorbing the glucocorticoids taken by mouth.

In this situation, it may be necessary to receive injections of dexamethasone or another glucocorticoid, and seek emergency medical care. Patients should wear a Medic Alert bracelet until glucocorticoid replacement is stopped.

If it is necessary to have a prolonged increase in hydrocortisone, a doctor should evaluate this need, and a tapering regimen may be needed to reduce the dose back to the daily requirement.

Removal of Adrenal Gland

Removal of both adrenal glands also removes the ability of the body to produce cortisol. Since adrenal hormones are necessary for life, patients must then take a glucocorticoid cortisol-like hormone and the mineralocorticoid hormone fludrocortisone (Florinef), which controls salt and water balance, every day for the rest of their lives. This should only be done in extreme cases where all other treatment avenues have been exhausted.

There may be a concern that the pituitary tumor will enlarge, so MRI imaging of the pituitary gland may be done after this surgery. People whose adrenal glands have been removed may have initial symptoms that are similar to those after pituitary surgery, and they should take extra glucocorticoid during illness as described above, and wear a Medic-Alert bracelet.

It is important to note that if you are taking replacement cortisol there may be a number of occasions when you need additional replacement. This can include stressful situations, such as surgical procedures, dental procedures, and so on. You should discuss your specific condition with your doctor and ensure you know what situations to look out for and what action to take.

Radiosurgery

When the tumor is seen on MRI, radiosurgery is another option for treatment. Radiosurgery includes radiation therapy either to the entire pituitary gland or to specified target locations. This may be used as the only treatment or it may be given if pituitary surgery is not completely successful. These approaches can take up to 10 years to have full effect.

In the meantime patients take medicine to reduce adrenal gland production of cortisol. One important side effect of radiation therapy is that it can affect other pituitary cells that make other hormones. As a result, up to 50% of patients need to take other hormone replacement within 10 years of the treatment. This should only be done in extreme cases where all other treatment avenues have been exhausted.

Drug Treatment

While some promising drugs are being tested in clinical studies, when given alone, currently available medications to reduce cortisol levels do not work well as a long-term treatment. These medicines are most often used in conjunction with radiation therapy.


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Aldosterone

Aldosterone is a hormone that increases the reabsorption of sodium ions and water and the release (secretion) of potassium ions in the collecting ducts and distal convoluted tubule of the kidneys’ functional unit, the nephron. This increases blood volume and, therefore, increases blood pressure. Drugs that interfere with the secretion or action of aldosterone are in use as antihypertensives. Some of these drugs lower blood pressure by blocking the aldosterone receptor. Aldosterone is part of the renin-angistensin system. Aldosterone is a yellow steroid hormone (mineralocorticoid family) produced by the outer-section (zona glomerulosa) of the adrenal cortex in the adrenal gland. Corticosteroids are synthesized from cholesterol within the adrenal cortex. Aldosterone activity is reduced in Addison’s disease and increased in Conn’s syndrome.

Aldosterone synthesis is stimulated by several factors:

  • Increase in the plasma concentration of Angiotensin III, a metabolite of Angiotensin II
  • Increase in plasma angiotensin II ACTH, or potassium levels, which are present in proportion to plasma sodium deficiencies. (The increased potassium level works to regulate aldosterone synthesis by depolarizing the cells in the zona glomerulose, which opens the voltage-dependent calcium channels. The level of angiotensin II is regulated by angiotensin I, which is in turn regulated by the hormone renin. Potassium levels are the most sensitive stimulator of aldosterone.
  • The ACTH stimulation test, which is sometimes used to stimulate the production of aldosterone along with cortisol to determine whether primary or secondary adrenal insufficiency is present (However, ACTH has only a minor role in regulating aldosterone production; with hypopituitarism there is no atrophy of the zona glomerulosa.)
  • Plasma acidosis
  • The stretch receptors located in the atria of the heart. If decreased blood pressure is detected, the adrenal gland is stimulated by these stretch receptors to release aldosterone, which increases sodium reabsorption from the urine, sweat, and the gut. This causes increased osmolarity in the extracellular fluid, which will eventually return blood pressure toward normal.
  • Potassium. This is one of the main feedback loop controllers of aldosterone production. High potassium should cause high aldosterone when the adrenals are able to produce more aldosterone. In reverse, low potassium can depress aldosterone production.

The secretion of aldosterone has a diurnal rhythm.


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Hypoaldosterone

Hypoaldosterone is when the outer-section (zona glomerulosa) of the adrenal cortex does not produce enough aldosterone.

Causes

  • Adrenal insufficiency
  • Hypopituitarism
  • Addison’s
  • Renal dysfunction-most commonly diabetic nephropathy
  • Low Potassium
  • Medications
    • ACE inhibitors
    • NSAIDs
    • Cyclosporine
    • Diuretics
    • Progesterone
    • Estrogen
    • Spironolactone
    • Eplerenone
    • Beta Blockers
    • Angiotensin II receptor blockers
    • Renin inhibitors
    • Heparin
    • Opiates

Symptoms

  • Low blood pressure
  • Low blood volume
  • High pulse
  • Heart palpitations
  • Dizziness
  • Lightheadedness when you stand
  • Fatigue
  • Craving salt
  • Frequent urination
  • Getting up many times during the night to urinate
  • Sweating
  • Excessive Thirst

Testing

Testing should be done at 8am before any supplements/meds and you should have been out of bed and moving around for 2 hours. You should also be in a sitting position when the blood is drawn.
Fast after midnight.
Salt fast for 24 hours before testing. This means no sea salt, no food with salt added and no beverages with sodium.

Sodium, potassium and renin should be tested at the same time as Aldosterone.
Women who are pre-menopause: test during the first week of your cycle because aldosterone increases during the second half of your cycle. Day 3 is ideal but close to that is fine.
On the day of the test you can resume your meds & supplements and eat immediately after the blood draw.

In a normal person, plasma renin activity peaks at 60-120 minutes after getting up in the morning, with the aldosterone response lagging a little. Aldosterone and renin correlate at 120 minutes. For these reasons, aldosterone excretion and renin activity is best assessed at 120 minutes in an upright posture.

Medications, OTC products and other things that can effect aldosterone testing are as follows:

  • OTC pain relievers of the non-steroid class (such as Motrin and Advil)
  • Diuretics (water pills)
  • Beta blocker
  • Steroids
  • Angiotensin-converting enzyme (ACE) inhibitors
  • Oral contraceptives
  • Stress
  • Heavy Exercise
  • Illness
  • NSAIDs
  • Cyclosporine
  • Progesterone
  • Estrogen
  • Spironolactone
  • Eplerenone
  • Angiotensin II receptor blockers
  • Renin inhibitors
  • Heprain
  • Opiates

Treatment

How you treat low aldosterone will vary from person to person. Even those with low aldosterone many not need Florinef.
The most important factor in treating aldosterone is being able to get sodium and potassium labs done every 3 – 4 weeks. Supplementing with Celtic sea salt and usually slow release potassium are essential when treating low aldosterone.

Aldosterone affects the Diastolic Blood Pressure and often when systolic pressure is good (110-130) and diastolic pressure is low (below 70) it is caused by low aldosterone so this is also a measure of correct mineralcorticoids.
Fludrocortisone (Florinef) is started at a ¼ of a tab, as it is a very potent steroid and changes your body’s fluid balance. Increasing to 1/2 tab after 7-10 days depending on reactions and severity of problems. It is raised in this manner, 1/4 tab at a time, until the BP is normal and low aldosterone symptoms disappear. If at any time BP goes too high it should be reduced.
It can also cause fluid retention and pressure headaches, so these are signs of too much, or possibly it is lowering potassium too much so this is why electrolytes need to be checked often as you adjust this.


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Hyperaldosterone

Overview

Hyperaldosteronism is a condition where too much aldosterone is produced by the adrenal glands.

People with primary hyperaldosteronism have a problem with the adrenal gland that causes it to release too much aldosterone.
In secondary hyperaldosteronism, the excess aldosterone is caused by something outside the adrenal gland that mimics the primary condition.
Primary hyperaldosteronism used to be considered a rare condition, but some experts believe that it may be one of the causes of high blood pressure in some patients. Most cases of primary hyperaldosteronism are caused by a noncancerous (benign) tumor of the adrenal gland. The condition is most common in people ages 30 – 50.

Cause

  • Adrenal Insuffiency
  • Adrenal Tumor (benign or malignant)
  • Over activity of the rennin-angiotensin system
  • Cirrhosis of the liver
  • Heart failure
  • High or low potassium

Symptoms

  • High blood pressure
  • Low potassium
  • Weakness (caused by low potassium)
  • Tingling (caused by low potassium)
  • Muscle spasms (caused by low potassium)
  • Frequent urination
  • Fatigue
  • Headache
  • High sodium
  • Low Magnesium
  • Intermittent or temporary paralysis
  • Muscle spasms
  • Muscle weakness
  • Numbness
  • Excessive Thirst
  • Tingling
  • Metabolic alkalosis
  • Fluid retention

Testing

Testing should be done at 8am before any supplements/meds and you should have been out of bed and moving around for 2 hours. You should also be in a sitting position when the blood is drawn.
Fast after midnight.
Salt fast for 24 hours before testing. This means no sea salt, no food with salt added and no beverages with sodium.
Sodium, potassium and renin should be tested at the same time as Aldosterone.
And one note for women that are pre-menopause: test during the first 2-3 days of your cycle because aldosterone increases during the second half of your cycle.
On the day of the test you can resume your meds & supplements and eat immediately after the blood draw.

In blood testing if the aldosterone-to-renin ratio is abnormally increased this would point to primary hyperaldosteronism, and a decrease or normal, but with a high renin would point to secondary hyperaldosteronism.

CT scan to check for adrenal tumors.
Sometimes the health care provider needs to insert a catheter into the veins of the adrenal glands to determine which of the adrenals contains the growth.

This disease may also affect the results of the following tests:

  • CO2
  • Serum magnesium
  • Serum sodium
  • Urine potassium
  • Urine sodium

Treatment

Primary hyperaldosteronism caused by a tumor is usually treated with surgery. Removing adrenal tumors may control the symptoms. Even after surgery, some people still have high blood pressure and need to take medication. However, they can often reduce the number of medications or doses they take.

Medications used to treat hyperaldosteronism include:

  • Amiloride
  • Spironolactone (Aldactone; Aldactazide), a diuretic (“water pill”)
  • Triamterene

Medicines and diet (but not surgery) are used to treat secondary hyperaldosteronism.

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