2021

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 2021

• I would appreciate any advice about adrenal insufficiency that is caused by opioid use, especially how it might affect treatment compared to other cases of AI.​

  Opioid-induced adrenal insufficiency is quite common. 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. This can produce a full spectrum of adrenal insufficiency symptoms, from negligible to full adrenal crisis if there is an acute precipitating illness or injury. The diagnosis is confirmed with a blunted cortisol stimulation test, but simply finding a low AM serum cortisol with a low ACTH level is sufficient. This is a form of secondary adrenal insufficiency, not Addison’s disease. The treatment is the same as other forms of secondary adrenal insufficiency: usually hydrocortisone, but prednisone would also work. There is no need for fludrocortisone. Some important notes: OIAD is more likely with higher doses of opioids and longer duration of usage. It is potentially reversible if opioids can be discontinued. Finally, since the need for replacement glucocorticoids will increase in times of stress, if pain is not controlled with the opioid use, a higher dose of glucocorticoids may be needed. 

• I have multiple conditions on top of adrenal insufficiency: Histamine intolerance, food intolerance, and mast cell activation. Are these related to my adrenal illness, and are there any worries for interference in treatments?

  Histamine intolerance/food intolerance and mast cell activation syndrome are not endocrine issues and have nothing to do with adrenal disease. They are syndromes that present with allergic symptoms and are evaluated and treated primarily by allergists. If confirmed by testing, treatment includes anti histamines and food avoidance diets. Adrenal function is not affected, and steroid hormones are not used in therapy.

• Humana is my insurance provider for Medicare Part D benefits. When I refilled my prescription recently, I learned that Solu-Cortef is not included in the drug formulary for my plan. Instead, they would cover methylprednisolone acetate. I talked to my endocrinologist and he was reluctant to recommend the substitution. I’m curious about a second opinion as I thought I might not be the only person to encounter this issue.

  I suggest that your endocrinologist ask the insurance company for an exception to their formulary. Solu-Cortef is the standard of care and they should approve it off formulary.

• I was recently diagnosed with endometriosis, on top of Addison’s, and my gynecologist is suggesting birth control and topical testosterone cream in response. My concern is that both of these will cause issues with my Addison’s since hydrocortisone and hormones could further deplete my bone density. What are your thoughts on this method, and do you think it will have any counterindications as an individual with AI?

  Birth control pills and testosterone cream will not affect Addison’s disease or the dosage of hydrocortisone. The estrogen in the birth control pills is designed to reduce your own estrogen stimulation to the endometriosis tissue, but will not reduce it to menopausal levels, so there will be no depletion of bone density. The treatment plan appears to be safe.

• My symptoms started 12 years ago but have gotten progressively worse over the last 3 years. Often, I find it hard to move and have to rest. I have a lot of symptoms such as fatigue, nausea, dizziness, 20-pound weight loss, vomiting, abdominal pain with no clear cause besides IBS, etc. I am on a high salt diet and have been prescribed a 0.05 mg dosage of fludrocortisone for a high heart rate due to POTS.

  With the diagnosis of POTS and chronic fatigue syndrome, the symptoms are typical, including the GI symptoms. It is not possible to make an actual diagnosis, but it would be useful to get a 21-OH adrenal antibody test. If positive, that would suggest Addison’s and should be followed by an ACTH stimulation test to assess adrenal reserve. If it is negative, a further GI evaluation may reveal the cause of the symptoms.​

Q&A from NADF NEWS® June 2021

• Should individuals with adrenal insufficiency stress dose prior to receiving the COVID-19 vaccine?

  I do not advise using extra glucocorticoids on the day before or on the day of vaccination. I suggest the individual with adrenal insufficiency wait to see if significant side effects occur, usually the day after the vaccine. If there is fever, significant muscle aches and pains, and especially nausea or any typical adrenal insufficiency symptoms, I would then add stress dose steroids in addition to treating any fever with acetaminophen or ibuprofen.
  I have spoken to many of my patients about their experiences, and many report no side effects at all. Those that did have significant symptoms were individuals who had a history of acute Covid-19 infection earlier in the year, and then had the vaccine.

• What if we’ve had both COVID-19 shots and want to travel? Thoughts? I also have Addison’s Disease.

  For the latest advice, look at: https://www.CDC.gov.

• I was on high-dose hydrocortisone, but stopped two months ago. I have heard it can weaken your immune system, so I’m wondering how long am I more susceptible to infections?

  The answer depends on the clinical situation. If you have adrenal insufficiency it is dangerous to stop the glucocorticoids because the adrenal insufficiency must be treated. Fear of viral infections is never a reason to stop steroid therapy altogether. It is always essential to take the best dose that prevents adrenal insufficiency symptoms. Avoiding viral infections requires the use of the usual measures, including masks, hand washing and social distancing. However, if you are without adrenal insufficiency but required a short-term use of hydrocortisone and are now off it for 2 months, then sensitivity to viral infections is probably back to normal. Two months should be adequate.

• I have never seen any guidance on what to do if we have a severe allergic reaction (anaphylaxis) to something. My guess is that we would need both SoluCortef (or equivalent) and epinephrine. Would there be a problem if we were given only epinephrine without the SoluCortef?

  The immediate treatment for anaphylaxis is epinephrine. If this were to occur in a person with adrenal insufficiency, I would recommend adding a stress dose of hydrocortisone 20 mg to cover the stress. IV or IM hydrocortisone would be appropriate only if there is a sustained allergic reaction after the use of epinephrine.

• I have primary adrenal insufficiency (PAI). Recently I was diagnosed with Valley Fever. What do you know about treating Valley Fever in people with PAI? Before the serology tests were known, my doctor mentioned the possibility of treating me with Fluconazole.

  Valley Fever is a fungal infection caused by coccidioides. It is often quite mild and may resolve without treatment. In its severe form, it can cause pneumonia and sometimes meningitis. Severe Valley Fever is treated with antifungal medications, most often fluconazole. Adrenal insufficiency is a risk factor for more severe disease and its complications. Therefore, if the diagnosis is confirmed, treatment is likely to be advised. Unfortunately, the common side effects from fluconazole include nausea, dizziness, vomiting and diarrhea, all symptoms that occur in poorly controlled adrenal insufficiency. Clearly, treatment must be closely monitored. Extra doses of hydrocortisone may be necessary to cover the side effects of the medication. 

• I’d like to start taking the minerals zinc and selenium daily; is this something that will disrupt my hydrocortisone or effect my Addison’s Disease? If not, how much is appropriate?

  Neither zinc nor selenium will have any effect on Addison’s disease management. I do not specifically recommend either, but if you want to take them, there is no harm. Zinc is being promoted for anti-viral properties, but the benefit is minor. Selenium is promoted for autoimmune thyroid disease. I don’t propose its use to patients because the studies showing a benefit were in people who lived in parts of the world with a deficiency of selenium. In the US, there really is no such deficiency.

• I have just been diagnosed with severe obstructive sleep apnea that affect my cortisol levels. Why do I have to keep updosing so much?

  Obstructive sleep apnea can be a significant cause of daytime fatigue. It is usually treated with CPAP, a device that prevents the obstruction and allows adequate sleep. It is not treated with more glucocorticoids. In fact, excess steroids may cause weight gain that can worsen the sleep apnea. The key is to work with a sleep specialist on finding the best device to treat the sleep apnea, but use a normal replacement dose of glucocorticoids.

• I was recently diagnosed with an adenoma. Who is the best kind of specialist to see for adenomas?

  Adrenal adenomas are quite common. The patient should be evaluated by an endocrinologist for adrenal function to determine if the adenoma is producing excess cortisol or any other adrenal hormone. The next issue is size and growth. Regardless of function, if the adenoma is bigger than 3.5 cm or is growing, surgical excision should be considered.

Q&A from NADF NEWS® September 2021

• My husband has primary adrenal insufficiency (since age 10) and is scheduled for a vasectomy. His endo suggested he up-dose that day. Should we be concerned about the chance for crisis? Is there anything special he or his doctor should do? Is he at “higher risk” during surgery or recovery?

  Vasectomy is a minor surgical procedure, usually performed under local anesthesia. A double dose of the usual morning hydrocortisone will probably be sufficient. To be safe about any possible adrenal insufficiency issues post-op, the endocrinologist should communicate with the urologist about the adrenal insufficiency and have IV hydrocortisone available if needed.

• Are those with Addison’s who have been vaccinated more susceptible to being part of the small percentage that get the “breakthrough” Covid anyway? Are we as covered by the vaccine as the general population?

  Individuals with Addison’s disease who are fully vaccinated have the same minor susceptibility to breakthrough Covid infection as anyone else. They have the same capacity to develop a robust antibody response. The groups that may have a less than adequate immune response are those with an organ transplant due to the immunosuppressive drugs they must take, those who have an underlying immune deficiency disease, and some people who take chemotherapy. The vaccine really works!

• Does the antibody number correlate with how bad/far destroyed the cortex is?

  If a person with Addison’s disease has a positive 21-hydroxylase antibody test, it proves the autoimmune cause of the disease. However, the actual titer of the antibody does not correlate with the degree of adrenal destruction. In addition, if Addison’s disease has been present for many years, the antibody test may become negative because the adrenal glands may have been completely destroyed a long time ago, and there may be nothing left to continue to make antibodies against.

• Does prednisone, even at doses of 2 mg, effect the muscles more than hydrocortisone in equivalent dosing of (4:1 ratio) 8mg of HC?

  The relative effect on the various tissues and organs in the body from the use of glucocorticoids will be the same with prednisone and hydrocortisone in the equivalent doses. Q:  I want to see the world. I once had a travel doctor tell me not to travel outside of North America or Europe because of not having adrenal glands (they were removed). My current endocrinologist says I can travel anywhere but I’m hesitant after having an adrenal crisis on vacation in Florida last year. My family wants to travel to Africa and I’m really nervous. What are your thoughts on world travel?

• I want to see the world. I once had a travel doctor tell me not to travel outside of North America or Europe because of not having adrenal glands (they were removed). My current endocrinologist says I can travel anywhere but I’m hesitant after having an adrenal crisis on vacation in Florida last year. My family wants to travel to Africa and I’m really nervous. What are your thoughts on world travel?

  Individuals with adrenal insufficiency can travel anywhere, it just takes a bit of planning. Make sure everyone with you knows about your condition and how to help you if you get sick. Have an emergency kit with extra hydrocortisone tablets and a Solu-Cortef emergency injection with a syringe. Have a NADF wallet card with instructions on how to treat a crisis. Have a Medic alert bracelet or necklace that identifies your adrenal insufficiency. Wherever you are in the world, make sure you know how to reach an American consulate in case you need local medical help. Always listen to your body for early clues that suggest you have adrenal insufficiency symptoms and promptly treat them with extra hydrocortisone. Finally, in our current age of the Covid pandemic, I would suggest you avoid countries that have a poor rate of Covid vaccination. Even if you are fully vaccinated (and you should be), you could get trapped in a country that goes into an emergency lockdown.

• Have you ever heard about Ivermectin’s anti-inflammation properties? I was just wondering if it would be a good way to improve the realities of being dependent on corticosteroids. Maybe be able to keep my total steroid to a minimum and help with recovery?

  Unfortunately, the drug Ivermectin has recently received inappropriate attention, resulting in a lot of confusion. It started with baseless claims about its usefulness in treating Covid 19. There are legitimate clinical trials using it, either by itself or in combination with hydroxychloroquine and antibiotics. So far, there is no evidence of its effectiveness, but that has not stopped some advocates from making claims about it. Ivermectin is a drug approved only to treat parasites—specifically roundworms in the intestine. It is also used topically to treat scabies. It is not an antiviral therapy, and it is not an anti-inflammatory therapy. Indeed, among its serious potential side effects are nausea, dizziness, postural hypotension, muscle aches and rapid pulse! All of these are typically seen in poorly controlled adrenal insufficiency. No one with adrenal insufficiency should consider taking this drug unless prescribed by a physician for intestinal parasites, and even then the patient must be closely monitored.

Q&A from NADF NEWS® December 2021

• I have a question about the diagnosis of non-classic congenital adrenal hyperplasia and am struggling to get clarity from our endocrine specialist. My daughter’s endocrine specialist suspected she may have had this condition a few years ago and sent her for 17 hydroxyprogesterone and DHEAS tests which were pretty low. Since then, she has developed additional symptoms including hirsutism and unsure whether this condition could still be a possibility. Would the 17 hydroxyprogesterone/DHEAS tests three years ago have ruled it out, since the condition is congenital or do new symptoms require them to be repeated?​

  Non-classic CAH can be diagnosed with a morning elevated 17OH progesterone. Usually, the DHEAS is elevated as well. It is important that the test be performed with a morning specimen. If it is done in the afternoon or evening, there can be a false negative. If it was normal 3 years ago, there is no need to repeat it. The clinical issues currently suggest possible androgen excess. The most common cause of this is PCOS (polycystic ovary syndrome). This is much more common than CAH. The blood tests will usually show a slightly elevated testosterone, DHEAS, and a high LH/FSH ratio. It can be treated with medications that reduce insulin sensitivity (metformin), and androgens (spironolactone) or oral contraceptives. 

• ​Question: I was diagnosed with Addison’s in 1970 and am now 81. I have been taking Cortisone Acetate 25mg in AM and 12.5 in PM. I was recently diagnosed with osteoarthritis in wrists and placed on a 4mg dose Methylprednisolone (6-days). The inflammation and pain in wrists were almost immediately relieved. However, pain and inflammation returned after dose pack was gone. Should I speak to my Endo about switching from Cortisone Acetate to methylprednisolone to treat both conditions? Would a combination of both work?

  The response to the methylprednisolone pack was due to the high dose anti-inflammatory activity of the steroid. This can temporarily relieve pain in osteoarthritis, but it is not useful long term because at a high dose, side effects will occur. The effect was not due to the type of steroid. It was due to the potency. If high dose cortisone had been used, the effect would have been similar, but cortisone has more mineralocorticoid activity and would have also caused fluid retention. Long term, high dose steroids are not useful in treating osteoarthritis. I suggest you talk to the doctor about trying a non-steroidal anti-inflammatory drug in addition to your normal maintenance dose of cortisone.

• I would like to know if anybody has had this problem with blood pressure? When I wake up it at 7 AM it’s 180/110, then by 9 to 10 AM it 80/60 or lower and I fall asleep or pass out? Then goes up then back down around 2 :30 PM the same thing at 7:30 PM when I go bed it’s 170/110. My doctor said it all hydrocortisone I been taking for pass 40 years. My endocrinologist said it’s neurological.

  The wild swings in blood pressure are not likely due to adrenal insufficiency alone, although it may contribute to some of the lows. Since the blood pressure swings are potentially harmful, a thorough evaluation with the neurologist and perhaps a cardiologist working with the endocrinologist is in order.

• I take 15 mg of hydrocortisone upon waking and 10 mg at noon. I am going for an epidural in my thoracic spine in 2 weeks. Should I double up my morning dose, or not take it at all?

  Epidural injections are usually high dose steroids meant to relieve back pain. The steroids generally persist for several days, whether they relieve the pain or not. The procedure itself is not very stressful, so there is no need to add stress dose hydrocortisone prior to the procedure unless the physician performing it suggests that there may be unusual discomfort for your particular case. Once the procedure is over, the actual duration of the extra steroid injected is highly variable. Therefore, it is appropriate to continue the usual maintenance dosing even though initially there will be a higher-than-normal total steroid level in the body. This way, you can be confidant that when the injectable steroid wears off, you will still be adequately covered for the adrenal insufficiency.

• Are bloating and GI issues side effects of AI?

  The major GI issues associated with adrenal insufficiency are nausea, vomiting, diarrhea and abdominal cramps. All of these tend to occur in undiagnosed or inadequately treated adrenal insufficiency, or as symptoms associated with an adrenal crisis. Anyone with adrenal insufficiency who has these symptoms should take extra stress doses of glucocorticoids. Bloating without these other symptoms would more likely be due to other GI disorders, such as irritable bowel syndrome, celiac disease, or lactose intolerance, any of which may coexist with adrenal insufficiency.

• I recently switched to an insulin pump and noticed that I spike each time I take my hydrocortisone. It is much more dramatic than when I would have a long-acting insulin as my basal rate. Is this something that other people with Adrenal Insufficiency and T1D on pump therapy also struggle with?

  The increase in blood glucose after a dose of hydrocortisone is perfectly normal. I suspect that now that you are using an insulin pump along with a constant glucose monitor, you are simply observing more accurately something that was happening all this time. With the previous long-acting insulin and bolus management of the diabetes, the control of glucose was not as strict as it is with the pump/CGM. I encourage you to use the effect to help you titrate your insulin coverage - both basal and bolus to minimize any spike in glucose that you observe. If the actual increase in glucose is not severe and if the HbA1c is normal, you may not need to treat it.

• Does a normal hydrocortisone replacement dose (15mg) impact blood sugar levels? Can you develop steroid-induced diabetes on a replacement therapy dose? If so, what can be done to minimize this spike? I’ve noticed an elevation in my HgA1c since starting hydrocortisone (diagnosed with Addison’s in March 2021) and I think this is due to the medication.

  Replacement doses of glucocorticoids, including hydrocortisone and prednisone do not cause steroid-induced diabetes. Susceptible individuals, especially those who are overweight or have a family history of type-2 diabetes can develop diabetes from high dose glucocorticoids. The likelihood of developing diabetes may be related to the dosage of steroids as well as the duration of use. The observation of an increase in HbA1c after the onset of therapy with replacement doses of hydrocortisone might reflect the transition from an untreated low cortisol state, where hypoglycemia is common, to a new metabolic state with mild glucose intolerance that may be normal for that individual. The management at this point should start with assessing the adequacy of the hydrocortisone regimen to control the signs and symptoms of Addison’s disease, and then adding attention to promoting good glucose control with diet and exercise. If HbA1c remains elevated, medication to treat type 2 diabetes may be necessary and is compatible with the therapy for adrenal insufficiency.

• I was recently prescribed Diclofenac to manage an injury but wasn’t sure if it was going to cause issues with Addison’s and my hydrocortisone. Do you know if they shouldn’t be mixed?

  Diclofenac is a non-steroidal anti-inflammatory drug. It does not interfere with steroid use and can be used in a person with adrenal insufficiency.​

• I am a woman with a question regarding low cortisol and would really appreciate your help. Since recently identifying the low cortisol, my endocrinology team have ruled out Addison’s disease. They suspected a hypothalamus issue in the past. My cortisol was taken at 9 AM and was low then. An ATCH simulation test was done which ruled out Addison’s and other pituitary hormones were broadly normal. I was wondering then would this be possible with a hypothalamus condition?

  If there was pituitary or hypothalamic disease, the ACTH level would be undetectable. If it was in the normal range and the ACTH stimulation test showed a normal response, with elevation in the serum cortisol, then it suggests that there is normal hypothalamic/pituitary/adrenal physiology. If that is the case, the “low cortisol” may be from a low cortisol binding globulin. You can measure this as well as a 24-hour urine free cortisol to establish that the low serum cortisol may be misleading. With the endocrinologist indicating that Addison’s disease has been ruled out, and the uncertainty about hypothalamic disease, there is a need for either more testing, or a better explanation from the endocrinologist. Sometimes a low cortisol value can simply be from taking blood in the afternoon or evening.​