When I became an endocrinologist in 1981 I was truly excited about the field. At that time it seemed that the science of endocrinology was expanding rapidly and new discoveries were on the horizon particularly in regards to the way hormones effect the brain, mood and the immune system. Was I ever wrong! Itâ€™s thirty years later and none of those expectations were realized. In fact, I find that the field of endocrinology has barely budged since then and in some areas has actually lost ground.
Bringing on this round of pessimism on my part, is a recent â€œdevelopmentâ€ in the area of treatment for hyperthyroidism (over active thyroid). Ever since I was in training there have been two medicines, propylthiouracil (PTU) and methimazole (Tapazole), which are the mainstays of medical treatment for hyperthyroidism. Both medicines have been available since the 1940â€™s and show excellent efficacy and tolerability (and they are cheap!). Almost all endocrinologists I have met use these two drugs interchangeably although in pregnancy propylthyiouracil is favored due to rare birth defects in fetuses exposed to methimazole.
The â€œdevelopmentâ€ which I find so discouraging is the recent action by the FDA to place a very strict (black box) warning on the use of PTU due to the possible occurrence of a rare form of liver injury attributed to the drug. After almost 70 years of exemplary use, this has given rise to extensive debate in the endocrinology literature about how to restrict PTU use.
While it is true that methimazole is equally as effective as PTU to treat hyperthyroidism, I have personally seen numerous cases of fairly severe allergic reactions to methimazole. Fortunately it has been easy to continue medical treatment by simply switching to PTU. If we canâ€™t use PTU freely then the only other options are surgical removal of the thyroid or eradication of the thyroid using radioactive iodine, neither of which is free of potentially adverse outcomes.
I have never encountered severe liver injury with PTU nor has any of the colleagues I have polled. It has to be very, very rare. This is obvious because it has taken 70 years to get around to recognizing it formally. Can we really call it progress that we now have one less simple option for treating hyperthyroidism, a common and relatively benign disease? Let me take my cynicism to the next level. I wonâ€™t be surprised if a major pharmaceutical company soon announces the development of a new drug for treating hyperthyroidism. If Iâ€™m right the new drug will add nothing of real value that wasnâ€™t previously available but is many times more expensive then the drug it replaces.
So goes endocrinology into the new century, the stogy old lady of medicine.
Puberty occurs when areas within the brain awaken beginning a cascade of hormone signals which conclude with the gonads (ovaries and testicles) increasing their production of the female and male sex hormones estrogen and testosterone. Under the influence of these hormones a child begins the transition from childhood to sexual maturity. In boys puberty is associated with a growth spurt, the appearance of facial, axillary (arm pit) and pubic hair, acne, deepening of the voice, growth of the testicles and penis while girls undergo a growth spurt, develop breasts, acne, pubic and axillary hair, and growth of the clitoris.
Historical data shows the average age of puberty today is many years sooner than in previous generations. Most experts attribute earlier puberty to better nutrition. A recent article in metabolism.com reviewed how “over-nutrition” accelerates obese children into puberty sooner (referred to as precocious puberty) than normal weight children. The latest studies on causes of precocious puberty suggests that a child’s social environment also exerts an important influence on the timing of puberty. Researchers in Madrid publishing in The Journal of Clinical Endocrinology and Metabolism 95:4305 2010 analyzed the age of puberty in normal children, adopted children and children whose families immigrated (children not adopted but subject to high levels of personal stress) to Spain. Adopted children were 25 times more likely than other groups of children to undergo precocious puberty (breast development before the age of 8 years in girls, and boys under 9 years of age with testicular growth). Over-all girls were 11 times more likely than boys to demonstrate precocious puberty.
Researchers speculate that socio-emotional stresses early in life of children who are later adopted result in changes in the brain that cause premature maturation of vital nerve pathways. This early brain maturation later results in stimulation of the pituitary gland, turning on the hormone pathways that cause puberty. This seems strange to me because various forms of deprivation in childhood can also delay puberty. For example, girls who have anorexia remain child-like in their body development and may fail to menstruate even into their late teens. A decade ago I studied hormone levels in adults during the stress of illness and surgery and found this lowered the sex hormone levels in their blood. This makes sense from an evolutionary point of view because during stressful conditions nature wisely cuts off the reproductive hormones. Why make babies if the environment is hostile in some way? Why the opposite occurs in children under stress of adoption is an interesting but unanswered question.
Gary Pepper, M.D.,
It seems obvious that cutting away part of the stomach and intestine should cause weight loss. With a smaller stomach and less intestine fewer calories can be absorbed per day causing weight loss. Surgeons who perform gastric by-pass were puzzled however, by how fast their patients showed metabolic improvement after undergoing this procedure. They noticed many of their diabetic patients could be taken off diabetic medication immediately after surgery before weight had been lost. Scientists looking into this phenomena discovered unsuspected ways gastric by-pass improved metabolism.
The intestines produce hormones which regulate blood sugar and appetite. GLP-1 is among the best known of these intestinal hormones. GLP-1 is the basis of a whole new generation of medications used to treat diabetes such as Byetta, Victoza, Januvia and Onglyza. GLP-1 lowers blood sugar, stimulates the pancreas and reduces appetite. After gastric by-pass increased amounts of GLP-1 are produced by the remaining intestine. In a study published in the Journal of Clinical Endocrinology and Metabolism (95:4072-4076, 2010), researchers at St. Lukeâ€™s Hospital in New York discovered that levels of oxyntomodulin, another intestinal hormone that suppresses appetite and acts like GLP-1 on blood sugar levels, is doubled after gastric by-pass.
These exciting discoveries help explain why obese diabetics can often be sent home without any medication to control blood sugar immediately after undergoing gastric by-pass surgery. Although most insurance plans do not cover gastric by-pass surgery, dramatic improvements in patients after the procedure with greatly reduced medication costs may convince insurance companies that paying for the procedure will result in better outcomes and save them money in the long run.
Gary Pepper, M.D.
What comes to mind when considering the term “inflammation”? A festering pimple, or perhaps a high fever, an infected tooth, toe, abscess? These are typical examples of inflammation. Inflammation may exist in many other forms however, including possibly obesity.
Inflammation describes the immune system when it is activated. The presence of pus or fever are obvious forms of this. More subtle forms of inflammation can exist in the body. Recently, researchers from Australia, presented evidence that obesity itself is associated with abnormal activation of the immune system, or in other words, inflammation. This inflammation might in turn, cause type 2 diabetes. It is already becoming clear that the inflammation associated with obesity contributes to insulin resistance, the first step in the development of type 2 diabetes. In a study just published in the June volume of the Journal of Clinical Endocrinology and Metabolism (95:2845-2850, 2010), patients with either type 2 diabetes or pre-diabetes were evaluated for the distribution of inflammatory blood cells before and after gastric band surgery. Abnormal immune activation or inflammation was detected in this group. After an average of 13% weight loss following gastric surgery, the scientists found up to an 80% reduction in inflammatory blood cells. Many of the patients were able to significantly reduce their diabetic medications after the weight loss. The conclusion is that inflammation may result from obesity and is reversible when significant weight is lost. Metabolic problems like diabetes improve as the inflammation is reduced, as well. Therefore, inflammation may be part of the reason people develop diabetes as their weight increases.
Studies like this will provide new avenues for attacking the development of type 2 diabetes due to excessive weight gain, and possibly to help find ways of combating obesity, as well.
Gary Pepper, M.D.
Below, Mele describes her plight struggling to adjust to the disappearance of Armour from U.S. pharmacies. She discovered what was explained in my post, “Behind the Disappearance of Armour”. Forest Pharmaceuticals and Medicare are both responding in their own ways to the FDA decree that Armour Thyroid submit an application (NDA) as if it were any new drug seeking to come to market now. The FDA is charged with the responsibility to assure all prescription drugs in the U.S. demonstrate minimum levels of safety and efficacy. As a bureaucracy the FDA is unable (unwilling) to find a way to use the 50+ years of unblemished clinical experience unique to Armour, to satisfy this requirement. Rather than correct its own deficiency the FDA is forcing many thousands of hypothyroid patients on dessicated thyroid products to go through the difficult and potentially dangerous process of finding alternative thyroid hormone therapies. I am guessing that the FDA is receiving support for this policy from companies making synthetic t4 products and from medical organizations and their officers who receive funds from these same companies. Let’s not forget that Forest itself markets a generic t4 product, Levothroid, which will absorb some of the business lost by the withdrawal of Armour.
Mele submits her story to metabolism.com:
Iâ€™m just devastated. I could only get a seven day supply yesterday of Armour at Wal-Mart. They have no idea what the problem is and told me to come in Tuesday and they would have some again. I had no idea there was a problem again (last yearâ€™s nightmare made me assume everything would be ok after Forrest redid their manufacturinging plant) until I googled today.
I am 66 years old and have been on Armour Thyroid since I was 15 years old when I had a subtotal thyroidectomy for carcinoma. The only time I ever tried Synthroid was about 20 years ago when an endocrinologist convinced me that I was going to get osteoporosis if I continued using Armour. I only took it for two months, and when I walked into my family doctorâ€™s office at the end of the two months, he took haveone look me and said â€œwhWt is wrong? You are not youâ€. I wasnâ€™t me anymore (and the blood tests he ordered confirmed that I was very low on T3 and barely in the normal range for T4). That was probably the most terrifying experience I have ever had. I had no idea how totally entwined my personality, and feelings of well being, are dependent on Armour. I still find it scary that â€œmeâ€ is a product of a drug I take and when I take a different brand, I am no longer me. I felt like a stranger in my own skinâ€¦weak, no sparkly, dramatic personalityâ€¦ instead dull feeling, acting and cobwebs in my brain. My family doctor said that he was putting me back on Armour immediately and slowly I began to feel like me again.
Iâ€™m terrified now. I am in the middle of trying to prepare for a very complicated (nothing is ever simple or easy medically for me) cataract surgery in another city that I have fly to repeatedly for the presurgical appointments. If I have to go on Synthyroid againâ€¦how can I deal with this other upcoming surgery? It canâ€™t be put off as I can barely see to drive now.
Anyhow, I agree with others here that we have to organize and fight this. I find it very difficult to believe this is simply a shortage of the thyroid powder that Forrest is claiming is the problem. This is the FDA meddling, yet again, with patients very lives. I think I know an organization that will help us as they have fought bloody battles with the FDA for many years and have been victorious to a large extent. I am speaking of the Life Extension Foundation. Iâ€™ll be contacting them.
Two other things. For what it is worth, I have noticed no problems with the change in Armour but for the first time in many years, I have not done thyroid blood levels in two years. But I feel fine so I guess I donâ€™t have the absorbtion problem some mention with the new formula. I have had hair breakage though which I have puzzled over and that could well be due to the formula change.
As for Medicare and Armour, I have had Medicare since a drunk driver hit me many years ago so I have had Medicare long before I turned 65. When Medicare Part D first appeared Armour was on the Medicare forumulary. That was in mid 2006. Armour was on the Medicare formulary in 2007 also. Beginning Jan 2008, Armour was removed from the Medicare formulary. My physician I did a lot of research, calling, letter writing, etc. about it. My drug plan was and still is from AARP/United Health Care. United Health Care is angry about the Armour situation. However, they cannot make a special exception to cover it when a physician asks them to do so (as mine did) because their hands are tied. They are required by law to allow ONLY drugs that are approved and on the Medicare formulary.
AARP/United Health Care covers ALL drugs on the Medicare formulary and by law cannot cover any that are banned from the Medicare formulary. Armour was banned in 2008. I called Forest about it and was extremely puzzled by their lacksidasical response. My physician wrote Forrest also and they sent back a reply that had nothing to do with the question about Armour being removed from the Medicare formulary. My physician learned later that his, and my, suspicions were correct. It was removed because the FDA told Medicare that they could not cover a drug that had not gone through the NDA I believe it is calledâ€¦where a new drug has to undergo extensive clinical trials as per FDA regulations. We learned that the FDA was requiring Forrest to do this if they wanted Medicare coverage for Armour. Well, that is not possible. Forrest charges very little for Armour. Where are they supposed to get the money for the many years of clinical trials that the FDA has demanded? The FDA knew that demanding this would effectively kill Armour and that was their intent.
So, since Jan 2008, I have had to pay for a Medicare Part D plan that I canâ€™t use because the only drug I take (unless I need an antibiotic or something short term) is Armour. Wat is worse, most health insurance companies follow the Medicare formulary so if Medicare no longer covers Armour then most insurance plans will not cover it either.