2024
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 2024
Q: Is it safe for those with adrenal insufficiency to get multiple vaccines in one day, for example flu, COVID and or RSV? Should there be a few days spaced out between them?
A: I do recommend all 3 of the current virus immunizations - the influenza, RSV and new covid vaccine for individuals with adrenal insufficiency. Although the CDC indicates that all 3 can be given in one day, my personal opinion is that it is prudent to take no more than 2 at a time.
Q: Is it possible to have both PAI & SAI?
A: Primary adrenal insufficiency is due to damage, destruction or removal of both adrenal glands, leading to deficiency of both glucocorticoids (cortisol) and mineralocorticoids (aldosterone) and is treated with replacement hydrocortisone and fludrocortisone. Secondary adrenal insufficiency is due to a suppression or absence of secretion of ACTH from the pituitary gland in the head. The lack of ACTH stimulation to the adrenal glands leads to a deficiency of cortisol, but usually does not affect aldosterone production. Therefore, treatment is usually with glucocorticoids alone. The most common cause of SAI is the prolonged use of high dose steroids for other diseases, suppressing ACTH. If that is the cause, recovery may be possible if the steroid treatment can be tapered and discontinued. When ACTH deficiency is due to pituitary or hypothalamic disease or tumors, recovery is less likely. The possibility of PAI and SAI at the same time is unlikely, but not impossible. One scenario is SAI from steroid use and then a coincidental development of autoimmune adrenal disease or bilateral adrenal hemorrhage causing destruction of the adrenal glands. The most important issues in management are understanding whether there is a need for mineralocorticoid replacement and whether there is a potential for recovery.
Q: Has an Addisonian ever reported reflex syncope on the morning after vaccination. I had this even though I doubled the dose of hydrocortisone. Also, last year I had a fever and fainted without losing complete consciousness.
A: Reflex syncope, better known as vasovagal syncope, is a very common phenomenon. It is not due to Addison’s disease. Usually, it is in response to a trigger, such as seeing blood, fear of pain or any emotional distress. Sometimes a heavy meal with alcohol can trigger it. The vagus nerve to the stomach is stimulated, leading to a slowing of the heart rate and a sudden drop in blood pressure. This results in decreased blood flow to the brain and ultimately fainting. Typical early symptoms are pale skin, lightheadedness, blurry vision, nausea, a warm feeling in the face followed by a cold sweat. If caught early, loss of consciousness may be prevented by quickly lying on the floor to increase blood flow to the head. If loss of consciousness does occur, there may be twitching movements. The whole episode usually lasts less than a minute. The only danger is injury from hitting your head on furniture or the floor. Since in this case it did not occur immediately after the vaccination (that could have triggered it from fear of needles), the episode one day later was a coincidence. It was not necessary to take extra steroids, only fluids. It is not appropriate to avoid vaccinations. If you had an episode at the time of a vaccination, I would recommend that you recline for several minutes after the next shot, just as we recommend for some people who faint when giving a blood sample.
Q: I’m supposed to have a Botox injection on a muscle, and I wanted to make sure there was no contraindication for Addison’s Disease. Can you help with that?
A: Botox acts as a local long-acting muscle relaxant. The injections are not very painful and the effect is not stressful. There is no contraindication for anyone with adrenal insufficiency and no need to take extra glucocorticoids.
Q: I have been treated for Addison’s since 2005 when I almost died from hyponatremia. I have been taking hydro/fludro since then with zero problems. A family member needs a kidney. Could I donate?
A: Addison’s disease is not an absolute contraindication for live kidney donation. However, since kidney transplants are handled regionally, each region and hospital facility may reject you based on their own criteria and aversion to risk. In addition to the Addison’s disease, they will evaluate other medical issues, including age, other illnesses, kidney function and medication use. If they feel that the surgical removal of one of your kidneys presents an excessive risk to you, they will turn you down.
Q&A from NADF NEWS® June 2024
Q: Is it okay to use topical hydrocortisone to support during a crisis?
A: Topical steroids should never be used to treat adrenal insufficiency - neither acute or chronic. Topical steroids are used to treat skin diseases and inflammation only. It does not provide a significant blood level of glucocorticoid that would substitute for oral or injectable steroids.
Q: What is happening in the body during emotional stress if the body is not naturally producing cortisol?
A: Stress, whether physical or emotional, will prompt an increase in cortisol production to increase blood pressure, blood glucose and help with mood stability. In the absence of an automatic surge in cortisol, the remaining physiologic responses to stress still provide a significant safety net. There will be a dramatic increase in catecholamines - epinephrine and norepinephrine (adrenalin) as well as growth hormone and glucagon. These hormones also increase blood pressure and glucose. There may be an increase in heart rate from the epinephrine. Of course, if the emotional stress is recognized, you should add an extra amount of glucocorticoid to supplement the usual dose, providing what the adrenal glands can no longer do.
Q: How should medication be managed with time zone changes when traveling and should you stress dose?
A: I recommend trying to take the doses of medication according to the time where you are. If you are travelling east, the next dose will be needed sooner than usual, but will be rebalanced with the following dose. When travelling west, there will be a longer interval. If you are going more than 3 time zones west, it would be helpful to add a small extra dose of hydrocortisone in the middle of the journey.
Q: How long do I wait to run renin activity, after changing my dose of Florinef? My renin continues to be going up, regardless of my dosing, so I need the time frame in which I can measure renin activity after I’ve changed my dose.
A: Reduction in plasma renin after an increase in fludrocortisone dose is fairly slow. Usually, it is rechecked at the next clinical visit, but if you are concerned about it, I suggest waiting a month before repeating the renin level.
Q: I had Cushing’s disease and a macroadenoma pituitary tumor removal in 2011. With Cushing’s, I stopped my cycle in my late 30s and experienced menopause symptoms in my late 40s, including horrible hot flashes. Post surgery, my pituitary gland is not functioning, and I take thyroid and hydrocortisone. Just recently, I started getting hot flashes again! I am very confused by this, I am 60 years old.
A: The recurrence of hot flushes at this time in your life is, indeed, confusing. I suggest a visit with your endocrinologist to get some new baseline hormone levels. You should be menopausal at this age, and the hypopituitarism caused by the surgery 13 years ago would likely eliminate the normal pituitary gonadotropin (FSH and LH) increase typical of a woman of 60. One possibility is a partial recovery of residual pituitary production of FSH and LH. Another possibility is excess thyroid hormone dosing causing hyperthyroidism that may mimic menopausal heat intolerance.
Q&A from NADF NEWS® September 2024
Q: I have Cushing’s and am scheduled to get my right adrenal gland out. Will I need a medical alert bracelet after?
A: If the Cushing's syndrome is caused by an adrenal adenoma, removal has the potential to cure the Cushing's. Usually, the remaining adrenal is intact, but chronically suppressed by the cortisol excess from the adenoma. Once the adenoma is removed, the remaining adrenal should gradually recover function. Initially, glucocorticoid replacement will be needed, but it will then be tapered slowly. If the remaining adrenal does fully recover, glucocorticoids may be discontinued. In this scenario, the benefit of an alert bracelet may be temporary, but it is inexpensive and harmless.
Q: In the early stages, can your cortisol level be normal? I have on and off lower back and abdominal pain, on and off headaches, salt craving, red rashes, white spots on skin, and extreme fatigue. I took a cortisol morning blood test, and they said it was normal. This is the 3 time in 2 years I’ve felt this way, this time has lasted the longest.
A: Yes, the cortisol level can be normal in the early stages. The most important first step in diagnosing adrenal insufficiency is to think that it might be the cause of the problem. Then it is time to consult a physician, ultimately an endocrinologist, if the initial work-up, signs and symptoms are suggestive. A morning cortisol by itself can be misleading. A normal value should not be considered reliable without other testing. At the very least, I would recommend a morning fasting cortisol with a plasma ACTH level, CBC, electrolytes, BUN, creatinine and measurement of 21-OH adrenal antibodies. If these tests are not diagnostic, the next step is an ACTH (Cortrosyn) stimulation test by an endocrinologist.
Q: I had Cushing’s disease and a macroadenoma pituitary tumor removal in 2011. With Cushing’s, I stopped my cycle in my late 30s and experienced menopause symptoms in my late 40s, including horrible hot flashes. Post surgery, my pituitary gland is not functioning, and I took thyroid meds and hydrocortisone. Just recently, I started getting hot flashes again! I am very confused by this, I am 60 years old.
A: The recurrence of hot flushes at this time in your life is, indeed, confusing. I suggest a visit with your endocrinologist to get some new baseline hormone levels. You should be menopausal at this age, and the hypopituitarism caused by the surgery 13 years ago would likely eliminate the normal pituitary gonadotropin (FSH and LH) increase typical of a woman of 60. One possibility is a partial recovery of residual pituitary production of FSH and LH. Another possibility is excess thyroid hormone dosing causing hyperthyroidism that may mimic menopausal heat intolerance.
Q: Can people with Adrenal Insufficiency take Tylenol? Drink green tea? Do these lower cortisol? Are there foods or beverages that we should avoid that do affect people with AI?
A: Acetaminophen (Tylenol) does not lower the cortisol. In pain medications, like Percocet and Ultracet acetaminophen is combined with opioids. Opioids do lower cortisol, but not the acetaminophen. Also, green tea is good for you and will not affect cortisol levels.
Follow Up Questions
Q: Can you clarify if opioids lower cortisol absorption, or cortisol produced by the body? Should patients with adrenal insufficiency avoid taking opioids, or should they increase the dose of hydrocortisone? Is Tylenol better than Advil?
A: Chronic opioid users develop some degree of adrenal insufficiency. The mechanism is suppression of the hypothalamic-pituitary responsiveness to the need for cortisol, so there is a relative deficiency of ACTH stimulation to the adrenals, resulting in inadequate cortisol production.
It has been estimated that between 9 to 29% of chronic opioid users develop some degree of adrenal insufficiency. The mechanism is suppression of the hypothalamic-pituitary responsiveness to the need for cortisol, so there is a relative deficiency of ACTH stimulation to the adrenals, resulting in inadequate cortisol production.
Those with primary adrenal insufficiency or secondary adrenal insufficiency are already on replacement doses of glucocorticoids. They can take opioids if needed for pain and do not need to adjust their hydrocortisone doses unless the stress of pain is excessive. Tylenol (acetaminophen) and Advil (ibuprofen) in the usual doses are equivalent as pain medications, but ibuprofen has more anti-inflammatory effects. Neither one is an opioid and neither has an effect on cortisol.
Q: Have you ever seen high blood pressure in someone with Addison’s? I have had Addison’s for 48 years, and my BP always ran low. But over the past decade (and especially since I had Covid 2 years ago) it has gotten high, to the point where I am now on propranolol to control it. Are there any other Addisonians who have this problem, and is there any guidance on how to deal with it?
A: People with Addison’s disease can have hypertension, usually essential hypertension as a familial tendency, or due to kidney disease. When this occurs, medications such as beta blockers or calcium channel blockers can be used, and the dose of mineralocorticoid is usually lowered or eliminated as long as the serum potassium is not elevated. Diuretics should not be used in Addisonians. If the potassium is elevated, low dose fludrocortisone can be added, with adjustments in the antihypertensive drugs to compensate. There is no reason to allow the blood pressure to stay high.
Q: Are ACE inhibitors contraindicated for Addison’s Disease?
A: ACE inhibitors are not contraindicated in the management of hypertension in most people with Addison's disease. They can be used along with calcium channel blockers and beta blockers. Most diuretics should be avoided. One precaution with ACE inhibitors is that they are inappropriate if there is significant kidney failure. At the onset of hypertension in Addisonians, a reduction in the dose of fludrocortisone may be sufficient to reduce the blood pressure. If that is inadequate, the addition of one or more of the antihypertensive medications can be considered.
Q&A from NADF NEWS® December 2024
Q: If my ACTH, taken 8am after the recommended fasting time, is very high, 143pg/ml, but my cortisol is 15.2 does that signify Cushing’s syndrome? I experienced very sudden weight gain in my upper body and face and extreme fatigue also. The test was taken this July. I've also had hypothyroidism, Hashimoto’s, for 13 years. I also had a pituitary adenoma in 2022 that gave me high prolactin, but after a course of cabergoline, I no longer have high prolactin and the MRI of the pituitary as of October 2023 was good, showing no adenoma.
A: The ACTH and cortisol values could be consistent with Cushing’s syndrome but are not diagnostic. The physical changes you describe warrant a thorough evaluation. I assume the studies were ordered by an endocrinologist. By this time, I would expect that other tests are being ordered. The next basic test would be an overnight dexamethasone suppression test to see if your cortisol production can be suppressed. If it is not suppressed, then more extensive studies of cortisol production from blood and urine tests and more definitive suppression tests are useful. The history of a prolactin-secreting pituitary adenoma may be significant but could be a coincidence. Cushing’s disease with pituitary ACTH excess can occur along with prolactin.
Q: I was diagnosed with Addison's Disease (PAI) last month and have been put on hydrocortisone. I am finding that it is causing mild depression. I have complication with heart issues having 2 stents. I do not want an antidepressant that causes weight gain - that would only add to my depression. Any suggestions?
A: Depression is a very common disorder and should be addressed with your physician. Medication and psychotherapy can be very effective. Although some of the antidepressants can contribute to weight gain, that should not be the only factor to consider. I will not make specific suggestions. Discuss your concerns with your physician or psychiatrist.
Q: Can long-term use of Budesonide cause adrenal insufficiency? I have eosinophilic gastritis and have been on budesonide for 6 yrs. I stopped but did not taper right and went into an adrenal crisis.
A: Budesonide is a potent glucocorticoid used to treat a variety of illnesses that respond to local rather than systemic steroid therapy. It is used in many inhalers for asthma and other pulmonary disorders. It is also used as a long-acting oral medication for chronic inflammatory bowel diseases like Crohn's disease, ulcerative colitis and eosinophilic gastritis. Usually, it is given for a fairly short course of 8 to 12 weeks, then tapered. Although it is poorly absorbed into the circulation, there is some systemic effect that is directly related to the dose and length of time it is used. I would expect that anyone who used it for 6 years would be likely to have suppression of the hypothalamic-pituitary-adrenal axis resulting in some degree of secondary adrenal insufficiency. That would mandate the need for a slow taper and monitoring for signs and symptoms of SAI. A rapid taper would raise the risk of an acute adrenal crisis.
Q: Are there any clinical trials or evidence testing the validity of using both Hydrocortisone and Prednisone to treat Addison’s? My endocrinologist has not found any, and discounts "anecdotal" evidence cited in forums. I believe I can benefit from the addition of a small amount of Prednisone overnight to avoid blood glucose lows.
A: There are no clinical trials documenting the combination of prednisone and hydrocortisone, but there is no contraindication to trying it. Prednisone has a long duration of effect, in contrast to the shorter effect of hydrocortisone, and has little mineralocorticoid effect, so it is rarely used by itself in managing Addison's disease. Usually, divided doses of hydrocortisone, with the larger dose in the early morning and one or two doses in the afternoon or evening are adequate. If morning hypoglycemia does occur before the AM dose, an evening small dose of prednisone is reasonable. If it works, and the combined dose of glucocorticoid does not cause signs of steroid excess, that is fine.
Q: How does THC interact with Addison’s Disease?
A: THC is the active cannabinoid that causes a "high" from marijuana. It is now available in oral forms mixed with other cannabinoids. Studies have shown that THC can cause a temporary increase in cortisol release in normal people. Chronic use of THC will blunt that response. Measurements of cortisol during the day in individuals who chronically use marijuana as a source of THC have variable levels that do not indicate significant adrenal insufficiency. Since those with Addison's disease cannot increase their cortisol levels in response to THC, there is no direct effect from THC. Dosing of replacement hydrocortisone in Addisonians will probably not be affected by THC. As usual, it is important to monitor for any adrenal insufficiency symptoms that might be due to an individual's particular response or sensitivity. If these symptoms occur, a slight increase in hydrocortisone may be needed, or just stop using THC.
Other Questions
Q: How can we balance sodium intake without raising BP?
A: Undiagnosed or inadequately treated primary adrenal insufficiency leads to an imbalance in electrolytes in the blood, with a low sodium and a high potassium along with a tendency for low blood pressure. Once the diagnosis is made and replacement therapy with hydrocortisone and fludrocortisone is initiated and maintained, the sodium and potassium levels and blood pressure return to normal. An acute stress will require extra hydrocortisone to prevent a shift in electrolytes and low blood pressure, and the addition of extra sodium from salty food and fluids is very important. Although there is a risk that excessive amounts or salt may raise blood pressure, it is only a problem in those with underlying essential hypertension. If high blood pressure persists on a normal salt intake, you should consult your physician about slightly reducing the fludrocortisone dose or adding a non-diuretic antihypertensive medication.
Q: I got blood results today and have more questions. ACTH was 600+ pg/mL (above normal). Based on your knowledge of Addison's, what ACTH level would allow me to lower my HC dose from 20mg to 15mg? Renin was normal (green zone), and I'm half-dosing fludro. My leg is still slightly swollen. Does Xanax have any medical benefit for Addison’s? Does it reduce cortisol burn?
A: The level of ACTH is a useful test in making the diagnosis of Addison's disease, but it is not very useful in guiding the replacement dose of hydrocortisone. I recommend that you work with your doctor in monitoring the signs and symptoms of adrenal insufficiency as you adjust the timing and dosing. Aim for the lowest dose that prevents symptoms. In contrast, the plasma renin level is very helpful in adjusting the fludrocortisone dose, along with observing for leg swelling, blood pressure and serum potassium. Xanax is a short acting anti-anxiety medication. It has no direct benefit or risk for people with Addison's disease. The doctor prescribing it should control the dosing and refills.
Q: What is your recommendation for timing for divided doses of hydrocortisone? Specifically, what is the latest time you recommend for the final hydrocortisone dose of the day? My current dosing is 12.5 / 5 / 2.5 mg of hydrocortisone upon waking (usually 6:30am), noon, and 5pm. I also take .2 mg of fludrocortisone upon waking. I feel well on this regimen, except that I sleep lightly, wake frequently, and never feel rested when I get up in the morning. I notice that I sleep much more soundly when I occasionally forget my 5pm dose. However, when this happens, I sometimes feel sluggish and slow in the morning. Is there a way I can better time my medication to allow for improved sleep while avoiding the risk of adrenal crisis?
A: The observation that deleting the 5 PM dose seems to provide better quality sleep is a useful tip. I suggest trying a 2 dose regimen of 12.5 mg at 6:30 AM and 7.5 mg at 4 or 4:30 PM. This will give the same total daily dose of 20 mg and hopefully prevent the mild morning symptoms of adrenal insufficiency. Also, look for other factors that might be affecting sleep, like caffeine in the afternoon or evening, late night eating, and the use of electronic devices before going to sleep. Remember that the dosing can be changed to fit changes in lifestyle and personal stresses.
Q: Are there long term effects on the HPA axis due to SSRIS and is there a link between SSRI and SAI?
A: SSRI medications are safe and appropriate when prescribed for depression and anxiety. As with any medication, the benefits and side effects would be monitored by each patient and provider. Over the years, there has been quite a bit of research on cortisol levels and the hypothalamic-pituitary-adrenal axis. Many people with depression have altered patterns of cortisol production. SSRI medications have been shown to have minor short term and long term effects on cortisol levels. However, there is no evidence of long term injury to the HPA. SSRI medication does not cause clinically significant secondary adrenal insufficiency.
Q: Colonoscopies can be a terror to many. Dehydration and nausea are big factors, and prevents many from going through with them. I’m very concerned about the effects of both the preparation and procedure causing someone with adrenal insufficiency to go into crisis. What sort of precautions can patients take to help them?
A: The cleanout protocols have changed and are now gentler. There is no need for inpatient colonoscopy unless there are other significant medical problems, like severe heart disease or a history of complications from previous colonoscopies. As always, I recommend individualization of steroid management, so if the prep causes nausea or severe cramps, extra hydrocortisone should be used to cover those symptoms on the prep day. However, if the cleanout just causes the usual diarrhea, and appropriate fluids are used to avoid dehydration, a normal steroid dose that day will be sufficient. My recommendation for a slight extra dose on the morning of the procedure stands, although even that is probably not needed in most cases. But again, a higher dose can be used if there are other stressors. I continue to recommend that the anesthesiologist be prepared to give IV hydrocortisone if needed.
Q: I have Cushing’s and am scheduled to get my right adrenal gland out. Will I need a medical alert bracelet after?
A: If the Cushing's syndrome is caused by an adrenal adenoma, removal has the potential to cure the Cushing's. Usually, the remaining adrenal is intact, but chronically suppressed by the cortisol excess from the adenoma. Once the adenoma is removed, the remaining adrenal should gradually recover function. Initially, glucocorticoid replacement will be needed, but it will then be tapered slowly. If the remaining adrenal does fully recover, glucocorticoids may be discontinued. In this scenario, the benefit of an alert bracelet may be temporary, but it is inexpensive and harmless.
Q: I have had Addison’s Disease for 36 years. I am now experiencing signs and symptoms of gluten insufficiency. Are there published studies on long term hydrocortisone replacement therapy?
A: Hydrocortisone does not cause celiac disease or gluten sensitivity. Most people with mild symptoms just deal with them by staying on a gluten free diet. In case of severe celiac crisis, temporary use of high dose corticosteroids may be useful.