Written by Paul Margulies, M.D, F.A.C.E., F.A.C.P. Medical Director, NADF.
Clinical Associate Professor of Medicine, New York University Medical School.
Q&A from March, 2012
Question: I am a provider with an Addison’s patient. She has been doing well on the Hydrocortisone 10mg three tablets daily when she developed hot flashes, mood swings and night sweats. We placed her on a low dose Combipatch and this has alleviated her symptoms however has caused her to blow up secondary to the potentiation of the estrogen on the Hydrocortisone, so we are reducing her Hydrocortisone and expect this edema to resolve. My questions: 1 Do we have more cases of Addison’s then are recognized, as they may present with menopause symptoms and in giving these women HRT, we are increasing the endogenous cortisol levels, thus masking a diagnosis of Addison’s? 2 Would repeating the cortisol levels now, with having a baseline, help us to make adjustments to her current dose of steroids?
Answer: Estrogen does not increase the production of cortisol, it only increases the level of cortisol binding globulin, making the serum cortisol level appear higher. I do not think we are missing patients with adrenal insufficiency. Adding estrogen to a woman with adrenal insufficiency will not relieve the symptoms of adrenal insufficiency, only the vasomotor symptoms. Adjusting for any fluid retention might necessitate a decreased dose of mineralocorticoid, not the glucocorticoid.
Question: My endo once told me that some people can’t tolerate prednisone or they don’t process it right…is that true?
Answer: Although fairly rare, some people lack the enzyme that converts prednisone to the active form, prednisolone. These people can use prednisolone instead of prednisone. Prednisolone is actually the preferred preparation in the UK, where prednisone is not available.
Question: Can you give us some information on the interaction between prednisone (as well as other corticosteroids) and calcium (acid neutralizing agents)? How much AI patients be concerned?
Answer: The interaction of glucocorticoids and calcium has several facets. Many people take calcium antacids with their steroids because they think they need it to reduce the incidence of heartburn from the steroids. In fact, that is rarely needed. Glucocorticoids are known to cause calcium loss leading to osteoporosis, but research has shown that the replacement doses used to treat Addison’s disease do not increase that risk. I do recommend calcium supplements for postmenopausal Addisonian women, but the dose is the same as other women. Vitamin D is important to assess in all postmenopausal women, and vitamin D supplementation to achieve blood levels above 30 is important. High doses of glucocorticoids may suppress vitamin D levels as well as activity, but normal replacement doses should not effect vitamin D.
Question: Is it true that fludrocortisone acetate (a.k.a. Florinef®) builds up in a person’s system over time?
Answer: Fludrocortisone does not build up over time. It is a synthetic mineralocorticoid with a fairly long duration of action, so it can be taken every other day and still work. If too high a dose is given, it will raise blood pressure, cause fluid retention and suppress potassium. Reducing the dose will relieve these effects. Some Addisonians need only a tiny dose, especially if they also have a family pattern of essential hypertension. Sometimes it is used in a small dose along with an antihypertension drug (but not a diuretic) to keep things in balance. This adjustment in balancing mineralocorticoid and blood pressure medication is a normal part of the treatment of Addison’s disease.
Q&A from June, 2012
Question: I have always wondered what might be physically wrong with me as a result of (my mother) getting steroid shots when she was pregnant with me. Please let me know. I appreciate your time and effort and my mother always enjoyed getting your newsletter. Thank you.
Answer: Don’t worry. It turns out that steroids given to pregnant women do not hurt the fetus and have no long term side effects.
Question: My husband has pheochromocytoma. There was a tumor in 1994. His right adrenal gland was removed. It was benign. It is back, but there is no tumor to be found. They see lesions on ths spine and scull. They want to do Chemo. But everyone is just guessing. He is on Beta Blockers, Alpha Blockers, and Demser. Do you have any information regarding this disease and information regarding when there is no tumor?
Answer: Most of the time when there is evidence of a return of laboratory studies showing a pheochromocytoma, there is visible tumor seen on one or more imaging techniques. In addition to CT and MRI, two other types of studies can be used: radioiodine labelled MIBG scanning, and PET/CT using a special type of agent that goes to neuroendocrine tissues. If all these are negative, I would suggest just controlling the blood pressure with medications alone.
Question: Hello, I had a question regarding Fludrocortisone. I just found out I am pregnant and my endocrinologist told me to stop taking my Fludrocortisone. I was under the impression it was okay to take while pregnant. Do you have any information regarding this. Thanks.
Answer: Fludrocortisone is safe in pregnancy. Generally, there is no reason to change the hydrocortisone and fludrocortisone regimen unless complications occur. If there is severe morning sickness, extra hydrocortisone may be needed. If there is significant hypertension late in the pregnancy, a reduction in the dose of fludrocortisone may be useful.
Question: What does it mean when the cortisol level is lower in the morning, and higher in the late afternoon-evening?
Answer: Normal people have a peak cortisol level just before they wake up in the morning and the level gradually decreases through the day, usually reaching near zero by midnight. Typically, people with adrenal insufficiency have lower than normal cortisol levels all the time, but the values may overlap with normal, so an ACTH stimulation test is more accurate in sorting out whether there is a normal reserve. People with Cushing’s syndrome have cortisol levels higher than normal, but again it can overlap with normal. However, in Cushings there is usually a lack of variation during the day, and the midnight cortisol is elevated rather than zero. As to why someone might have an inverted cycle, it depends. There may be a missleading inversion if that person is taking any steroid preparation, which may supress the morning value. If there is much stress, normal people can increase their cortisol production in the afternoon. It is important to look at the clinical context, the use of medications that might affect the values, and the absolute numbers for that time of day.
Q&A from September, 2012
Question: What is the most optimal form of cortisone and optimal dosing for a person who has cortisone induced Addison’s, or is it called another name because it was drug-induced?
Answer: Steroid induced adrenal insufficiency is a form of secondary adrenal insufficiency and should not be called Addison’s disease. That name refers to primary adrenal insufficiency due to destruction of the adrenals. The major difference is the need for replacement of both glucocorticoid and mineralocorticoid hormones in Addison’s versus the need for only glucocorticoids in most people with secondary adrenal insufficiency.There is no perfect treatment dose. Each person needs individual monitoring. For secondary adrenal insufficiency, I would often start with prednisone 5 mg every morning and then adjust upward or downward as needed.
Question: I have read over and over again that Florinef should be kept refrigerated, however every time I get my script filled … florinef is being stored on the pharmacy shelf (i.e. being stores at room temp) and multiple pharmacist insist the medication does not need to be refrigerated at the pharmacy or at home. I have been told by at least one pharmacist that if I refrigerate the meds it will cause condensation and destruction of the medicine. I am emailing hoping you may know the answer. Please, please advise if you have any personal advice or know the manufactures recommendations in the US.
Answer: As others have noted, the two generic preparations of fludrocortisone available in the United States have the old formulation that is stable at room temperature. Only the new formulation that is being sold in Europe and Canada as a brand (to be eligible for a patent) requires refrigeration. So, no one in the US needs to worry.
Question: The Addison’s Disease Self Help Group in the United Kingdom has a set of surgical guidelines on their website (http://www.addisons.org.uk). What do you think of them?
Answer: I don’t like it at all. They advise too much hydrocortisone for minor procedures and I don’t like IM hydrocortisone. Don’t use it.
Question: I have Addison’s Disease. I came off Estrogen 5 months ago. I have been having a lot of trouble with the Addison’s since then. Two very close ER visits, low on cortisol all the time. I remember a previous flier from NADF stating that people who are off Estrogen need more cortisol. It seems true for me. I am thinking of going back on Estrogen because I was so stable then. I took myself off the Estrogen. Is this a common problem with Addisonians? Do you know if most Addisonians go back on Estrogen or take more cortisone?
Answer: Estrogen increases the amount of a protein (cortisol binding globulin) that carries cortisol in the blood. With increased levels of this protein, there is actually a minor need for higher doses of hydrocortisone to allow a normal free, or active hydrocortisone blood level while on estrogen. That means that if estrogen is withdrawn, free hydrocortisone levels are higher, not lower. In most postmenopausal women these differences are very minor, so adjustments in hydrocortisone dose is usually not necessary. Another effect of estrogen that can be important is the slight salt retaining effect. Withdrawal of estrogen might necessitate a slight increase in need for fludrocortisone to make up for the difference. In any case, with major changes apparently occurring after withdrawal of estrogen, it is a good time to see your endocrinologist to review all medical issues, check for possible changes in thyroid status (this can change with estrogen and can have a major impact on steroid sensitivity) and initiate appropriate changes in hormone dosages.
Q&A from December, 2012
Question: How quickly can an adrenal insufficient patient die from adrenal crisis?
Answer: No good answer to the question. Death in the setting of an adrenal crisis depends on what is going on in the patient, not just the absence of adrenal function. Most deaths in adrenal crisis occur because there is shock related to an infection or loss of blood volume because of an accident or injury. Hypoglycemia may also occur and contribute to loss of consciousness, as can arrhythmias from high potassium and low sodium levels. The rate of change in a person’s function ending in death depends on how fast any of these factors are progressing, the underlying health of the individual, and the ability of heath providers to reverse them.
Question: Have you encountered anyone with Addison’s who also has Graves Ophthalmopathy (Thyroid Eye Disease)?
Answer: Autoimmune thyroid disease is very common in association with autoimmune Addison’s disease. In our NADF survey we found 76.7% had thyroid disease (69.6% hypothyroid and 7.1% hyperthyroid). We presumed that the hyper people had Graves’ disease. The incidence of thyroid eye disease, with exophthalmos and eye symptoms is probably the same in individuals with only Graves’ vs those with both Graves’ disease and Addison’s, but no one has actually published data on this. In my personal experience, I have seen a few who have both and did develop thyroid eye disease. The management of the eye disease varies with the severity. Most stabilize and slowly improve over time once the hyperthyroidism is treated. Severe cases require high dose steroids, radiation, surgery, or a combination of these treatments.
Question: For people who have autoimmune Addison’s disease, is it dangerous or otherwise not recommended to take immune system boosting drugs and supplements, such as Airborne? Do people with Addison’s naturally have a weaker immune system?
Answer: People who develop autoimmune Addison’s disease have a gene that signals their immune system to create antibodies that go to the adrenal cortex and destroy it, leaving those individuals with a deficiency of cortisol and aldosterone. They do not have an immune deficiency disorder. They can make antibodies against viruses and bacteria just like everybody else. Taking any nutrient that might benefit their immune responsiveness is just fine (though be careful about trusting the hype on most supplements out there). People who have diseases that require high dosages of glucocorticoid medications may have a suppression of their immune responsiveness, but this does not apply to the replacement doses for Addison’s disease.
Question: I know woman who had her Cushing’s syndrome treated by the removal of one of her adrenal glands, and is hoping to keep the other gland by taking medication. Is it possible for a woman with Cushing’s to this extent to become pregnant and carry to full term?
Answer: The clinical situation is not very clear. If the Cushing’s syndrome was due to a benign tumor of one adrenal gland, and that was removed, then the medication would likely be a replacement glucocorticoid such as prednisone taken while waiting for the other suppressed adrenal to return to normal function. If that is the case, pregnancy is possible while still on the prednisone, but will require close monitoring. If, however, the diagnosis is really Cushing’s disease due to a pituitary ACTH producing tumor, then the adrenal surgery would not cure the Cushing’s and the medication is suppressing adrenal function. In that case, pregnancy would not be feasible because the medication would affect ovarian and placental function.