2023

Written by Paul Margulies, MD, FACE, FACP, Medical Director, NADF. Retired Clinical Associate Professor of Medicine, Zucker School of Medicine at Hofstra/Northwell.

Q&A from NADF NEWS® March 2023

• Is there a connection between ADHD, ADD and Addison’s Disease?​

  I am not aware of any connection between ADHD, ADD and Addison's disease, and I have not encountered it in my clinical practice. Since these disorders are quite common, it would be expected that some individuals with Addison's might have this as well.

• Is it possible to have taken too much sodium in a diet (popcorn and olives) and resultant equilibrium changes and elevated blood pressure. I stopped Florinef x2 days then started to feel better. Third day did a 1/2 of normal dose. Been on Florinef for 20 years. Never had this where I had to hold on to walls, furniture etc. to stand. It took me 5 days to get back to normal. I drink lots of water routinely.

  It is possible to consume too much sodium, causing high blood pressure. Since the fludrocortisone tells the kidneys to retain sodium, temporarily reducing the dose will correct it. One concern, however, is this may be a sign that you are developing essential hypertension, perhaps as a familial risk. I suggest that you monitor BP on your normal dose of fludrocortisone for any trends toward higher readings. If BP is often higher than in the past, discuss options with your endocrinologist. When hypertension does develop in Addison's, the usual first approach is to reduce the maintenance dose of fludrocortisone. Sometimes a non-diuretic antihypertensive medication is added.

• My endocrinologist told me that I'm unable to build muscle tissue and get stronger from disciplined exercise. Is that true?

  Glucocorticoids do contribute to wasting and atrophy of muscles, especially the proximal muscles (closer to the body) in the arms and legs. This is called steroid atrophy. It will occur when there is prolonged exposure to doses above the normal physiologic dose. In treating adrenal insufficiency, we try to keep the replacement dose below that level, so there is a smaller risk of atrophy. If there is atrophy from previous exposure, but the dose is now stable, there is the potential to regain strength in these muscles over time. If there is a lot of atrophy, it can take many months to regain the strength with exercise and good nutrition, including adequate protein. There may be other factors in your situation that may contribute to a lack of muscle recovery, such as other diseases or medications and age. Older people have a much harder time regaining muscle. Discuss this with your endocrinologist.

• Do you know if it's very common for someone to get Addison's Disease as a result of immunotherapy for treating cancer? I assume there have been few, if any, clinic trials with patients like me because all my doctors have been unable to answer 90 percent of my questions.

  Yes, we do know that immunotherapy that is used for a variety of cancers can cause adrenal insufficiency. It can actually cause primary or secondary adrenal insufficiency. When the medications activate the immune system, they can induce autoimmune adrenal insufficiency that injures the adrenal glands - Addison's disease. Another pathway is to cause autoimmune hypophysitis. This is inflammation in the pituitary. That inflammation may reduce the production of ACTH, leading to secondary adrenal insufficiency, plus disruption of other pituitary hormones, including thyroid and gonadal function. The most common endocrine effect from these medications is thyroid changes - either hyperthyroidism or hypothyroidism. Sometimes these effects may resolve over time.

• Would it be appropriate for someone with primary adrenal insufficiency to get the pneumococcal vaccine?

  I do recommend that anyone with adrenal insufficiency get the pneumonia vaccination. The current one is the Prevnar 20.

• Can long term steroids cause stomach ulcers? If so, how do individuals with Addison’s continue to take their medication without causing further damage?

  Oral glucocorticoids can cause acid-peptic symptoms and an increased risk of ulcers. It is usually seen in people who take high doses, especially over a long time. The doses used for adrenal insufficiency are lower, replacement doses. These doses are much less likely to contribute to stomach symptoms and injury. However, some individuals may be more sensitive. If acid peptic symptoms do occur, adding antacid medications or taking the medication with food can prevent the symptoms and damage.

• My son has Addison's disease. When should he take his medications in preparation for lab tests?

  The timing of lab tests will vary depending on what the clinician is looking for. If you are trying to assess the baseline adrenal function, the AM fasting cortisol and ACTH levels are useful, and must be obtained before any medication. If you want to assess the adequacy of replacement medications, blood tests for electrolytes and plasma renin may be taken anytime during the day after the normal dosing of medications in the morning and afternoon. This would not include serum cortisol or ACTH. If an ACTH stimulation test is performed, it must be before any glucocorticoid is taken.

Q&A from NADF NEWS® June 2023

• I am having trouble obtaining Greenstone hydrocortisone, and my doctor is prescribing prednisone instead. What are your thoughts?​

  Before switching to prednisone, I suggest trying to get Cortef brand hydrocortisone while waiting for the Greenstone supply.  Prednisone can be used, but it has a different duration of action and has very little mineralocorticoid activity. If you do use it, you may need to increase the dose of fludrocortisone.

• When I go to the gym, sometimes after about 20 minutes I get nauseous and need to sit for a few minutes and it passes. Does this mean I need more steroids?

  Nausea after exercise may be a sign of relative glucocorticoid insufficiency, especially if accompanied by lightheadedness and fatigue. If the symptoms are consistent, try adding an extra 2.5 or 5 mg of hydrocortisone before starting the exercise.

• My labs show I have positive anti-parietal cell antibodies, but my vitamin B-12 is normal. Does this mean I have pernicious anemia?

  Positive anti-parietal cell antibodies means you do have the underlying autoimmune mechanism of pernicious anemia. You should check B12 levels every 6 to 12 months. If it drops. then add B12 therapy.

• I have secondary AI from inhaled steroids. How soon after my diagnosis can I try to wean off the hydrocortisone?

  Secondary adrenal insufficiency is difficult to predict. Recovery is highly variable, depending on the dose of steroid that had been used and the length of time. If inhaled steroids are still necessary, tapering off the hydrocortisone may not be feasible. Read the NADF article about SAI. Coordinate with your pulmonologist and endocrinologist.

• I have had almost constant painless muscle twitching/spasms on my upper abdomen where my stomach is. Does this have anything to do with Addison's disease?

  Addison's disease can cause muscle cramping, especially in the abdominal area. Painless twitching is probably not related. It is worthwhile trying an extra dose of hydrocortisone at a time when the symptoms are worse to see if it subsides. If it doesn't help, consider a neurology consultation.

• Why would someone with Addison's wind up with critically low potassium?

  A very low potassium in an Addisonian may be from overtreatment with glucocorticoids or fludrocortisone, or the use of a diuretic or laxatives.

• Can you sweat excessively with Addison's disease? I can hardly bear the warm weather as I get very hot very quickly and sweat profusely. Even in the winter I sweat.​

   Excessive sweating is not a feature of Addison's disease. Many people have this as an annoying trait, without any disease. One should rule out hyperthyroidism, though it would typically cause other symptoms as well, such as rapid pulse, tremors and weight loss. Obesity can contribute to excessive sweating due to the extra fat.

Q&A from NADF NEWS® September 2023

• The 2nd and 3rd players of the adrenal cortex are dependent on the stimulation of ACTH. How much does ACTH stimulate the1st layer of the cortex? The Aldosterone/ Electrolyte and water balance? Or is the 1st layer dependent on another route, i.e.: working with the kidneys? Thank you.​

  The second and third layers of the adrenal cortex are dependent on stimulation from ACTH to produce cortisol and adrenal androgens. The first layer, producing aldosterone, is stimulated by ACTH, but is not dependent on ACTH. It is also stimulated by kidney function and blood pressure changes.

• It is my understanding that if you are taking 20 or more mg of HC daily your adrenal cortex is completely suppressed. Is this true? If you take less than 20mgs does your adrenal produce some cortisol? I would assume some natural would be better than a pill.

  Adrenal cortisol production is completely suppressed if you take a dose of glucocorticoid that is equal to or greater than the normal production of cortisol in that individual. That dose may vary from person to person, depending on weight, age, level of fitness, and use of medications that may affect absorption of steroids or metabolism of steroids. On average, we usually consider 25 mg of hydrocortisone or 5 mg of prednisone daily to be equivalent to normal production, but clearly that may vary. If one takes less than the equivalent daily production dose, the adrenals will still make some cortisol, but less than normal. Prolonged use of the dose that causes complete suppression will lead to secondary adrenal insufficiency.

• Is it wise to get Synthroid from a mail-order pharmacy? I was told that Synthroid is temperature-sensitive and should only be bought at a local retail pharmacy.

  I routinely prescribe Synthroid by mail order. It is safe and affordable. Just don't let the package sit in direct summer sunlight. It takes prolonged exposure to heat to affect the potency.

• My PCP is retesting my glucose, A1C and Insulin Resistance. Should I take my morning dose of HC before I have the labs drawn? I know steroids spike blood sugar, but is the spike in blood sugar an immediate thing, or does the spike stay higher than normal continually?

  Unless your doctor has a specific reason to have you hold the morning dose of hydrocortisone, you should take your usual dose at the usual time. That will provide the normal replacement glucocorticoid that your body would usually have if you did not have adrenal insufficiency. The blood studies will then reflect your usual glucose pattern.

• I have pituitary gland lymphocytic hypophysitis which causes central adrenal Insufficiency. I have been on 15mg hydrocortisone and 5mg stress dose since with stress dose at triple dose since 2014. Can you develop avascular necrosis from long term steroids? I am 44 years old and in 7 months have had a total Right hip and left knee replacement. I don’t have osteoporosis. The suspicion by the orthopedic surgeons is steroid use. He said that it does not matter how little a dose you are on. Is this correct?

  Yes, avascular necrosis can occur from steroid use, regardless of the dosage or length of use. Although we most commonly see it in people given high doses for various diseases, it can occur with replacement doses for primary or secondary adrenal insufficiency. There is no way to anticipate this unfortunate complication. I have also seen it in individuals who never took steroids, so the precipitating factors are complicated. Obviously, no one should avoid taking steroids when indicated because of fear of this fairly unusual disorder.

• I use budesonide as a treatment for my adrenal insufficiency, as prescribed by my endocrinologist, due to some other complications. Perhaps you can add it to your roster sometime.

  Budesonide is a glucocorticoid that has two clinical uses - inflammatory bowel diseases (Crohn's disease and ulcerative colitis) and asthma. When taken orally, it treats inflammatory bowel disease within the intestine. It is very poorly absorbed into the bloodstream, which makes it attractive as a gastrointestinal therapy because it has much less glucocorticoid effect on the body while suppressing the GI inflammation within the bowel. It has been used for many years, touted as a safer alternative to prednisone for these diseases. Similarly, budesonide has been used in inhalers for asthma because it is poorly absorbed and less likely to have significant steroid side effects.

  Budesonide should not be used to treat adrenal insufficiency. For primary and secondary adrenal insufficiency, you need a potent, consistent, and rapid absorption of the glucocorticoid. Budesonide does not do this.

• Does anyone have any thoughts on whether semiglutide (Ozempic, Wegovy, Monjourno) could benefit Addison's, etc., could it help regulate cortisol levels better in any way? I have Addison’s and started semiglutide for weight loss and my occasional Addison's symptoms have disappeared.

  These drugs are in a category called GLP-1 agonists. They work predominantly on the brain receptors that affect appetite. They tend to reduce hunger, resulting in decreased food intake and weight loss. They also improve glucose metabolism, so they can help to control type 2 diabetes. Unfortunately, the major side effect is nausea. Vomiting is common, as well as fatigue and dizziness. A more serious  side effect is pancreatitis. It does not improve cortisol metabolism, so there is no direct benefit to people with Addison's disease. With the potential side effect profile, I am concerned about the overlap with adrenal insufficiency symptoms.  I consider it risky.

• I have frequent urination. Sometimes I will make several trips to the bathroom, and it seems like within seconds. Could this be symptoms of low cortisol?

  Frequent urination is not a symptom of adrenal insufficiency. Causes can include urinary tract infection, bladder dysfunction in older people, diabetes, use of diuretics, and enlarged prostate in men. Talk to your primary doctor. If it is new, start with a urinalysis and urine culture.​

Q&A from NADF NEWS® December 2023

• Does adrenal insufficiency cause memory decline?​

  There is very little research on this topic. The few articles published have tried to summarize the results of several small studies of cognitive function in individuals with Addison's disease. They found an increase in attention deficit patterns and temporary reduction in episodic memory, but no evidence of long-term permanent memory decline or dementia. There is a review article of memory disorders in a variety of glucocorticoid disorders, but it includes diseases of glucocorticoid excess as well as adrenal insufficiency. I found no significant data pertaining to adrenal insufficiency.
  
  Keep in mind that memory decline is usually complicated. So many factors will affect memory, including age, overall health, neurologic disorders, medication, and genetics. In my clinical experience, I have not seen adrenal insufficiency to be a significant primary cause of memory decline or dementia.

• I have Addison’s and my recent labs show that I am also prediabetic. Is this a common occurrence for those with Addison’s, and what is the best way I can prevent getting diabetes?

  The blood test indicating prediabetes is the HbA1c. This test is very useful for screening for diabetes as well as managing the disease once it is diagnosed. It measures the average blood glucose level over the previous few weeks. Measuring fasting glucose along with the HbA1c provides even more information. For most laboratories, a level of HbA1c above 6.4 indicates a diagnosis of diabetes. Between 5.7 and 6.4 suggests glucose intolerance, now called prediabetes as a warning that type 2 diabetes (also known as adult-onset diabetes) is anticipated in the near future. People who develop type 1 diabetes have a rapid onset, usually in childhood or early adulthood, without a prediabetes phase.

  Prediabetes and type 2 diabetes are very common and are becoming more prevalent around the world. Risk factors include family history, overweight, lack of exercise and other medical conditions and medications that lead to insulin resistance and elevated blood glucose levels. Glucocorticoids will tend to increase glucose levels and increase fat tissue. However, individuals with Addison's disease, who must take glucocorticoids, should take replacement doses for their adrenal insufficiency and try to avoid excessive doses except for short term management of acute illness. Using replacement glucocorticoids will minimize the risk of inducing diabetes. Assuming that an individual with Addison's disease is consistent with a stable replacement dose, the coincidence of prediabetes should be dealt with using the same means as individuals without adrenal insufficiency. If overweight, lose weight. Decrease intake of sugar and other simple carbohydrates. Exercise more. Make sure the HbA1c is monitored regularly. With an optimal lifestyle, many individuals can maintain an improved or stable level over many years.

• I am awaiting diagnosis as a routine blood test showed very low cortisol and had to be admitted to the hospital for steroids. I am on 30 mg a day hydrocortisone but am now suffering with burning feet and numbness in my face; I would say, peripheral neuropathy symptoms. Is it a symptom of low cortisol? I did not have this before taking steroids.

  The sense of burning feet and numbness in the face is not a specific symptom of a low cortisol level. It is also unlikely to be due to the use of 30 mg of hydrocortisone. Since the underlying diagnosis is still pending, I suggest that you discuss these symptoms with the doctors involved with your work up. There certainly may be a neuropathy component as a factor, but it would be useless for me to speculate about what is going on.

• I have been on hydrocortisone 12.5mg in the morning and 10 mg at 2 PM for Addison's. Last month I got shingles and doubled my dosage as required and seemed to do well. I still have postherpetic neuralgia and persistent pain in the affected area. After seeing a neurologist, I was prescribed more antivirals and gabapentin. Should I continue to updose until pain subsides? Are there any other things we should know about having shingles with Addison's?

  There is no direct interaction between hydrocortisone and antiviral therapies or gabapentin. The dose of hydrocortisone was appropriately increased to help deal with the stress of the acute shingles infection and the pain. Stress doses of hydrocortisone should be continued, tapered, or discontinued depending on the level of pain. If the gabapentin and any other medication relieves the pain, the dose of hydrocortisone may return to your baseline dosage. The dose of hydrocortisone will have no effect on the healing of the shingles lesions or the length of time the neuralgia will persist.

• What is the recommended up-dosing for a tattoo, with Addison’s Disease?

  The issue is coverage for the stress from pain caused by the tattoo process. Extra hydrocortisone dosing of 5 to 10 mg should be enough. If you have a high tolerance for pain, you may not need any extra. Some Tylenol can be helpful. Avoid aspirin or ibuprofen to avoid bleeding into the skin. Most important: make sure it is a reputable tattoo parlor and new needles are used. Repeat use of needles has been associated with causing hepatitis C.

• My neuroendocrinologist's NP wants to know if a metyrapone test or CRH stim test for adrenal insufficiency are acceptable tests for accurate diagnosis.

  Testing for adrenal insufficiency varies according to the baseline condition being investigated. For the most common situation where one is trying to rule out primary adrenal insufficiency, a baseline cortisol and ACTH level, plus, if needed, an ACTH stimulation test is sufficient. Since you are inquiring about a neuroendocrine condition where there may be a component of secondary adrenal insufficiency, the work up is different. The typical issue is the evaluation of either baseline function of the hypothalamic-pituitary-adrenal axis after discovery of a pituitary tumor or hypothalamic tumor, or the evaluation of the axis immediately after removing a tumor. In both situations, the metyrapone test gives the best information. The CRH stimulation test may give a falsely normal result if performed too soon after a tumor is removed. The CRH test is most useful in a totally different scenario as a test for localization of the cause of Cushing's syndrome.

• Is menopause different for someone with primary adrenal insufficiency? I had surgical menopause last year at age 40, due to severe endometriosis and have not taken estrogen. I have always heard that surgical menopause causes more severe symptoms, such as more severe hot flushes. I have hot flushes, but I think they are milder to moderate. I wondered if my Addison's disease impacted this. Also, does menopause impact hydrocortisone dosing or cause more instances of needing minor stress dosing?

  The symptoms caused by menopause are highly variable - from devastating hot flushes, insomnia and mood changes to no symptoms at all. It is true that surgical menopause tends to be associated with more severe symptoms due to the sudden loss of all estrogen production in contrast to the normal prolonged and intermittent reduction in hormone levels in natural perimenopause and menopause that may take many months or years. But, again, there is a wide range in an individual's experience. Addison's disease generally has little effect on the age of menopause or the severity of symptoms. If symptoms are severe and lead to inadequate sleep, there may be a sense of extra stress that may benefit from an occasional extra dose of hydrocortisone. However, it is unlikely to require a chronic change in the steroid regimen. If symptoms remain severe and have a dramatic effect on quality of life, I recommend a discussion about hormone replacement therapy with your endocrinologist and gynecologist. Adrenal insufficiency is not a contraindication for hormone replacement. The risks and benefits are the same as for women without adrenal disease. If hormone replacement is needed, both estrogen and progesterone would be used for women with an intact uterus. After a hysterectomy, with the uterus removed, there is no need for the progesterone. Most doctors recommend the lowest dose that prevents the symptoms.

• Should I be concerned about elevated enzyme liver levels with Addison’s disease?

  Liver enzymes can be elevated for a variety of reasons. It can be a sign of serious liver disease or sometimes just a reaction to a recent viral illness. It is very important to discuss the significance with your primary doctor to understand if it requires further evaluation. The elevation itself is simply a sign, not a diagnosis. The underlying cause must be established. Regardless of the liver diagnosis, Addison's disease would not cause the enzyme elevation. However, if there is a serious liver disease, it may have an impact on your sense of wellbeing, including appetite and energy. This might affect your need for stress doses of hydrocortisone. Start with a thorough discussion with your doctor.