Alzheimer’s Disease: A Power Failure?

Like Willy Sutton, the bank robber famed for his explanation of why he robbed banks (because that’s where the money is), Alzheimer’s disease researchers have aimed most of their efforts at the well-known, visible pathology of the disease, the collections of debris scattered among the dying cells in the brains of patients suffering from the dementing illness. Made of a protein known called beta-amyloid, these plaques are the cause of the progressive death of brain cells and consequent loss of mental function – or so it has been thought. Research focus on amyloid plaques has been disappointing, though, yielding neither effective treatments nor preventive strategies. Moreover, the dramatic rise in the incidence of Alzheimer’s disease (AD), from 2% of people over age 85 in 1960 to 50% in 2000 indicates that something else is in play, something other than bad genetic luck that supposedly causes beta-amyloid to accumulate and nerve cells to die.

Energy production in the brain

As attention has turned to other potential causes of AD, older research findings seemingly unrelated to AD have assumed new importance, particularly discoveries related to brain energy metabolism. The preferred fuel for the brain is glucose. Until the 1980s, researchers thought that the brain, unlike other organs, did not need use the hormone insulin to allow glucose to enter its cells. But in the 1970s insulin receptors were discovered in brain cells and insulin was found in the spinal fluid, implying that the brain did indeed use the hormone. Because progressive resistance to insulin and difficulty getting glucose into cells to provide energy are the hallmarks of type 2 diabetes, and because the rise in AD incidence paralleled rising rates of type 2 diabetes in the last few decades, researchers began to wonder if AD might be rooted in insulin resistance and impaired energy production in brain cells. Insulin resistance in the brain might also explain the results of glucose metabolism studies in the brains of people at high genetic risk for AD, showing as much as 25% decrease in the use of glucose in areas concerned with memory and learning – long before any symptoms suggestive of AD have appeared.

Insulin resistance

By 2005, the idea that insulin resistance in the brain plays a significant role in the development of AD gained traction. Since not all type 2 diabetics get AD and not all AD patients have type 2 diabetes, insulin resistance cannot be the sole cause of AD. But a high blood insulin level is one of the two biggest risk factors for the disease. The other is a genetic factor – the gene for the E4 version of a protein called apolipoprotein B (apoB). Like insulin, apoB’s function is moving the building blocks for energy production into place in the various cells of the body. ApoB is like a delivery vehicle, packed with fats and cholesterol which are necessary for building the cellular machinery in the brain and providing fatty fuel for use when glucose is unavailable.

The tie between glucose, insulin and amyloid

Does impairment of glucose metabolism in the brain have any relationship to the classic pathological components of the disease – the amyloid plaques littering the brain, the destruction of nerve cell architecture, and the non-specific inflammatory changes? There are tantalizing clues. In the brain amyloid protein is a normal waste product. What is not normal is its accumulation in clumps around nerve cells. Beta-amyloid is usually broken down by an enzyme called IDE, insulin destroying enzyme. IDE breaks down insulin much more readily than it does amyloid proteins and when insulin is present in high amounts, the amyloid waits longer to be cleaned up and precipitates out of solution, forming clumps. Uncleared amyloid also prevents insulin from attaching to nerve cells to let more glucose in, depriving them of fuel.

Competition for IDE may not explain beta-amyloid accumulation completely, but it is a link between insulin, glucose metabolism and AD. In addition, high levels of glucose in all parts of the body prompt the development of abnormal collections of proteins/glucose combinations called advanced glycation products which trigger inflammatory damage to tissues in all organs. The brain is no exception.

A link between poor sleep and AD?

Sleep is another subject beginning to gain attention in the prevention and treatment of AD. Lack of good sleep contributes to the development of the metabolic syndrome, including type 2 diabetes, though disruption of normal hormonal rhythms. In normal people and in people with sleep apnea, sleep deprivation produces measurable impairments in working memory, thinking speed, attention, vigilance, and higher cognitive functions – the same functions affected by dementing illnesses such as AD.

Reasons for optimism

Do changing theories about AD have any practical consequences? Indeed. First, there is more reason for optimism about the future. If AD rates have risen because of changing dietary habits and lifestyles, we can change them again. The factors known to produce the metabolic syndrome are weight gain, lack of exercise and poor diet. Regular exercise is recognized as a deterrent to the development of AD. Some people are beginning to feel that the low fat dietary recommendations must also be changed since they have resulted in diets high in processed foods and carbohydrates, and low in foods with high amounts of antioxidants which counter inflammation. Fat metabolism, abnormal in the metabolic syndrome, is also important in the brain, which contains 25% of the body’s cholesterol. It needs sufficient healthy fats in the diet for normal function.

The second practical implication of the changing view of AD is the application of known drug treatments for type 2 diabetes, both for attempted prevention and for treatment of AD. Clinical studies in AD patients are already under way, using medications that improve insulin resistance. Intranasal insulin has also been tried. It is delivered directly into the brain, without fear of lowering body glucose levels and has shown some promise in improving AD symptoms. These approaches are entirely new and evidence of shifting focus in research. If Willy Sutton were an AD researcher he would be changing his targets.

Terminal Lucidity and Lucid Intervals

Caregivers of Alzheimer’s patients have long reported episodes of the patient returning briefly to “themselves,” for periods of hours to days. Some dramatic cases of such returns have been reported in the terminal phases of life. All of these cases have fallen into the “we don’t know why that happens” category of clinical observations. The concept of brain cells failing to function because of lack of energy is one that fits the appearance of lucid intervals better than a theory of the disease that implicates cellular destruction alone as the underlying cause of symptoms.

Arch Gerontol Geriatr. 2012 Jul-Aug;55(1):138-42. doi: 10.1016/j.archger.2011.06.031. Epub 2011 Jul 20. Terminal lucidity: a review and a case collection.

Nahm M¹, Greyson B, Kelly EW, Haraldsson E.

Posted by medical plaintalk

Physician turned medical writer.

Holding the Line: Stop Gaining First

One of the most remarkable failures of modern medicine is its inability to combat obesity and its associated ills. Obesity is not a new human condition, nor will it ever completely disappear. But since the 1970s, something has changed in the environment and culture to make the condition epidemic, despite sophisticated medical research, a multi-billion dollar diet industry, and constant media attention. The most effective solution remains not gaining excess weight in the first place, but that is no longer an option for over 60% of the population, many of whom are veteran dieters.

The body wants to keep the fat

Diets depend on adherence to a long-term plan for eating that fails to meet the body’s need for energy. In response to this semi-starvation, the body mounts a defense. Hair and fingernails grow more slowly. Heat generation declines and the dieter feels cold and is less inclined to move around. Cells throughout the body ramp down their energy needs. Within a few days, even sleeping burns fewer calories. Caloric requirements remain suppressed long after the target weight is achieved. Upward weight creep begins as soon as vigilance about food intake and exercise declines, and happens at a lower calorie intake than in the pre-diet days. So begins the yo-yo dieting cycle, unless the dieter just gives up.

Stop the upward creep first

Giving up the attempt to starve away the pounds will eventually bring the metabolic rate back up, but only as the pounds re-accumulate. At this point a tactic other than a repeat diet attempt may be in order. The most reliable way to achieve weight loss that lasts is by burning slightly more energy than is consumed on a daily basis over a long period of time – a sneak attack rather than a frontal assault. Such long term daily commitment requires habit formation, and habit formation requires patient repetition of actions over long periods of time. Holding weight stable- just simply trying not to gain any more for at least 6-12 months- is the first preparation for mounting a sneak attack.

Going on defense

In contrast to the coordinated offense of a diet plan, not gaining any more weight requires defensive tactics. Mindfulness – thinking before eating – is the primary tool. Each day presents dozens of choices that might contribute to weight gain – or not. The only concern is reacting to choices presented. Reacting correctly to just a few of them every day adds up over time. At the end of 6-12 months of no weight gain, you are better off than at the end of another diet cycle that winds up on the upside of the starting weight. You’ll have the habits of a person who maintains stable weight, and you will be ready to lose weight slowly and permanently by undershooting energy requirements just a little each day – but not enough to put your body into energy conservation mode.

Learn from the people who succeed

People who maintain stable weight often have some sensible guidelines for themselves. A common behavior is refusal to buy larger clothing sizes. Another is the choice of clothes with zippers and buttons and belts. If clothing becomes uncomfortable, they cut the sweets and alcohol back and pay more attention to activity level. A weekly weight check keeps others on track. These people know better than to obsess about daily weight fluctuations, but 3-5pound gain in a week gets their attention. While a common mindfulness tactic is procrastination of eating to sort out true hunger from urges of emotional origin, people who maintain stable weight also do not go long periods without eating. The body begins to downshift into a lower energy gear if no food appears to break a fast of more than 6 hours.

Choices, choice, choices

Easily digestible carbohydrates in the modern diet, especially those combined with fats, make good targets for people seeking stable weight. Carbohydrates trigger surges in insulin. Insulin blocks fat usage for energy needs, and hunger recurs much sooner after a high carbohydrate snack or meal than after one containing more protein and fat. Choose to keep insulin levels down: eggs instead of cereal; one slice of bread on a sandwich instead of two; one M&M instead of a handful; nuts instead of M&Ms; half the normal spaghetti serving – or eat just the meat sauce; drink water instead of juices or soft drinks, even diet ones. (The taste of artificial sweeteners also triggers a burst of insulin, even though they have no caloric value.) Put off eating something that you really don’t need – distract yourself with an activity or task. Practice self-control in other areas of life. Self-control is a “transferable skill” and any practice helps build it.

Activity choices abound. Park far away from your destination. Walk if the trip is less than a mile (get a pull cart for groceries if you are lucky enough to live near the store). Skip the elevators. Make dates for walking instead of eating. Keep your hands busy and mind busy (mental activity takes energy too). Sit on an exercise ball instead of a desk chair. If you have a wireless printer, put it far away from the computer – on another floor if possible. Mow your own lawn. Shovel your own snow. Buy a pedometer and watch the steps add up. Engage in some strengthening activities to build high-energy demanding muscle tissue.

Stay in the present

Dieting to lose weight is always focused on the future. Weight maintenance is a present-moment task. There will never be a better time than now to go on the defense and begin to stop gaining weight. Now is the only time you have in which to take action – all the rest of time is either a memory or an imaginary future.

Posted by medical plaintalk

Physician turned medical writer.

The Problem with Sugar: Insulin

This article is about insulin, not diabetes. Diabetic or not, you need to know about insulin. My epiphany about the importance of this hormone occurred when one of my children brought Micah, a friend with Type 1 diabetes, home for dinner. We had a healthy “Mediterranean” dinner – pasta tossed with olive oil, chicken, fresh tomatoes, and cilantro, with accompanying salad and French bread. And birthday cake. Fresh from life in a college dorm, the young friend ate with gusto – at least two helpings of everything. We all did. Later, I found him groggy and in need of two to three times his normal insulin dose. The epiphany was this: all the non-diabetics at the table that night required a lot of insulin to cover hefty carbohydrate intakes, but we were blissfully unaware of the consequences of over-indulgence. We did not have to fill syringes with extra insulin. Our pancreases did the work behind the scenes.

Awash in Insulin

Why was this realization an epiphany? Because we live in an age of excess, consuming large amounts of refined carbohydrates and frequently eating more than our energy requirements demand. We are awash in insulin of our own making and need to understand this hormone’s central role in metabolism. More and more research links insulin to the chronic diseases of civilization: high blood pressure, heart disease, obesity, and Type II diabetes (the variety in which insulin is too plentiful and doesn’t work properly, as opposed to Type I, in which the pancreas fails to produce insulin).

How insulin works

Insulin is the hormone that moves sugar from the blood into all the body’s cells. Blood sugar comes from carbohydrates in food and from glycogen made by liver and muscles as a way to store a twelve-hour supply of sugar. When glycogen stores run out and little food is coming in, as in starvation or very low calorie diets, we make sugar, first from our muscle proteins and then from our fat. The main goal of all metabolism is to keep blood sugar in a tight range – just right for the brain’s needs, because sugar is the only fuel the brain uses under normal circumstances. (It will resort to using ketone bodies, formed from fat in the liver during prolonged fasting or total carbohydrate restriction, but if sugar is available it is the preferred fuel).

Incoming dietary sugar elicits a burst of insulin from the pancreas. Insulin’s job is ferry the needed sugar to cells and to squirrel away extra sugar as glycogen and fat. Insulin is a lipogenic, or fat-producing hormone. Every time we overindulge, insulin goes into high gear to produce fat. It also raises triglyceride levels and lowers high density lipoproteins, exactly the changes in blood lipids that are associated with heart disease.

When insulin fails to work

Insulin is also mysterious. For unknown reasons, many people – one in every three of us – have a tendency to become “resistant” to insulin’s effects. Their pancreases put out more and more insulin to handle routine blood sugar levels. No one knows what makes the insulin inefficient, though fat accumulation in muscle cells may be part of the problem. This stage of “insulin resistance” goes unnoticed for years because there are no symptoms. Blood insulin levels are expensive to measure and difficult to standardize, so they are not part of any kind of routine, preventive screening.

Insulin promotes fat storage

High levels of insulin make fat storage and weight gain easier. Weight gain, particularly around the middle, promotes insulin resistance, and the pancreas responds with yet more insulin. A vicious cycle is underway. Insulin resistance can become so pronounced that blood sugar escapes control and spills into the urine. Insulin resistance is now Type II diabetes, treated with medicines that help insulin work, and ultimately, with shots of yet more insulin. Before this happens, and even afterwards, weight loss and exercise can reverse insulin resistance, leading medical researchers to believe that insulin resistance has something to do with abnormal energy processing in muscle cells. They’ve found that the muscles of some lean, healthy relatives of Type II diabetics show insulin resistance long before there is any fat in muscle, or abnormality in blood insulin levels.

Epidemic

In our sedentary age of super-sized, sugar-laced, low fiber meals, we produce far more insulin than our ancestors did. In addition, the genetic make-up of many people, particularly Hispanics, Native Americans and some African-Americans makes their insulin less effective. We don’t measure insulin levels routinely. Instead, we concentrate on easily-measured cholesterol and fret about fat in the diet. At the same time we are in the middle of an epidemic of insulin resistance and on the verge of an epidemic of Type II diabetes, which is no longer just a disease of middle and older age. For the first time in history, type II diabetes is appearing regularly in children, teens and twenty year olds.

The average American fast food diet sets people on the road to obesity, insulin resistance and type II diabetes. Lack of exercise keeps them there.In a world of easily available food that requires little or no work, the only defense against overeating is mental. Education and self- discipline are the weapons. Insulin-requiring, Type I diabetics like Micah know how much insulin has to be paid out for a big meal. The rest of us have to visualize that syringe full of extra insulin and imagine tucking away excess calories as fat. We have to see ourselves requiring more and more insulin as time goes on and becoming unable to produce enough to meet the needs of an insulin resistant body. It’s enough to make that second helping seem less desirable and regular exercise more attractive.

Keeping insulin levels under control:

Avoid weight gain
Lose any extra weight
Exercise 30 minutes per day.
Eat regular, small, balanced meals, and 25-30gm/day of fiber
Avoid the “white stuff:” Flour, sugar, white rice
If you are overweight and/or have relatives who have diabetes do all the above, and see if your doctor thinks a glucose tolerance test is warranted.

Posted by medical plaintalk

Physician turned medical writer.

The Sweet Tooth: Pathway to a Broken Heart?

For the last half a century or more we have believed the dietary cholesterol theory about heart disease, a hypothesis (idea to be tested by experiment) that found favor with researchers, grant makers, doctors and drug makers. What if this theory is wrong? What if cholesterol in artery walls has less to do with dietary fat than with the way the body processes carbohydrates? What if refined sugars and grains are the dietary culprits? Could insulin, the master hormone at the center of all energy processing, be a better marker than cholesterol for heart disease?

What is blood sugar?

The first thing to understand about sugar is that the blood sugar is not the same thing as the sugar in your pantry. Or the sugar in soft drinks or the sugar in fresh fruit. Blood sugar is a simple molecule called glucose – a product of plants’ ability to convert the energy of the sun into starches, long chains of glucose linked together. When you eat a starch, the digestion process breaks down the chains into simple glucose molecules which circulate in your blood. Glucose is used by every cell in the body for energy, and is also made into glycogen for storage in liver and muscle.The sugar in your pantry is sucrose extracted from plants, specifically cane grasses and beets, by a refining process that concentrates and crystallizes it. Each sucrose molecule is a combination of one glucose molecule with another of fructose, a chemically different plant sugar molecule.

The taste for sweetness is innate and possibly addictive. Before the advent of refined sugar, indulging the sweet tooth was difficult. The only edible sources were berries and fruits and small amounts of honey guarded by nasty bees – all confined by climate and geography. Sugar made its way into the human diet slowly, spreading from the East to the West as the secret of this “liquid gold” made its way along routes of commerce.

Sugar and the diseases of civilization

With time and commerce, consumption of sugar and refined grains skyrocketed. The diseases of civilization – diabetes, heart disease and obesity – followed refined sugar, flour and rice around the world, appearing wherever old dietary staples were replaced by these “white” foods. By the 1920s, the Americans averaged 110-120 pounds of sugar per person per year. We inched up to 124 pounds by the late 1970s. Then came the Japanese chemical innovation that made high-fructose corn syrup (HFCS) a dietary staple. By 2000, HFCS bumped sugar consumption up to 150 lbs. per year, largely in the form of sweetened drinks.

High fructose corn syrup

HFCS differs from sucrose because the ratio of fructose to glucose in corn syrup is 10% higher than in table sugar – 55:45 instead of 50:50. Some scientists believe that it is the remarkable increase in fructose consumption in modern times that correlates with the appearance of the metabolic syndrome – abdominal obesity, high fasting blood sugar, high triglycerides, abnormal lipoprotein levels and high blood pressure. If so, a 10% increase in fructose combined with a recent, large jump in overall sugar consumption may spell real trouble.
How can fructose cause trouble? Isn’t it the primary sugar of fruits? Yes, but eating an apple with a small amount of fructose combined with absorption-slowing fiber hardly nudges blood sugar up – a far cry from the blood sugar spike after 20 ounces of an HFCS sweetened beverage. Drink a coke, and about 60% of the glucose in the HFCS goes directly into the blood for immediate use, and 40 % into the liver for storage as glycogen. The fructose all goes to the liver for conversion into fat – released into the blood as triglycerides. The higher the fructose in the diet, the higher the triglycerides in the blood. Fructose is a “lipogenic” or fat-producing sugar, and long term consumption also raises LDL or bad cholesterol.

The problems with too much sugar

Once sugar consumption exceeds the small amounts nature provides without refining techniques, trouble begins. The different ways the body processes fructose and glucose combine to produce very efficient fat production. A rise in blood glucose prompts the pancreas to put out insulin to help ferry glucose into cells for energy use or storage. Insulin, like fructose, is “lipogenic” because it helps move fats into storage depots in three areas – the liver, fat tissue, and the walls of arteries. And as triglycerides are formed from fructose, insulin busies itself shuttling them around the liver and out into the blood. The pancreas then produces even more insulin to take care of the glucose – this is the phenomenon known as insulin resistance, part of the metabolic syndrome associated with heart disease.

Is it the cholesterol or the sugar?

The theory that cholesterol in dietary fat is the direct cause of cholesterol deposits in arteries requires a leap over the metabolic pathways that process simple sugars and are intimately involved in fat formation and storage – and over the fact that many people with low cholesterol levels have heart disease. Over the last half century, many researchers and doctors made the leap because they believed the theory. Just as important to widespread acceptance, though, were less scientific influences like the cheap availability of a test for blood cholesterol, the difficulty and expense of measuring insulin, and the dominance of researchers devoted to the dietary cholesterol theory over those who questioned it.

Medical history books contain an embarrassing array of once-unassailable theories and practices that have fallen by the wayside. Despite a modern sense of scientific invincibility, current medical ideas are not immune from error. Sugar and refined carbohydrates are not yet the poster children for the scourge of heart disease, but they may be a far better target than cholesterol. If the dietary fat theory gives way to the sugar theory, the massive push to lower cholesterol by diet and drugs may go into the books as one of those once-unassailable ideas that eventually fell.

Posted by medical plaintalk

Physician turned medical writer.

Thyroid Failure:Hashimoto’s Disease

When I was a resident in medical training a woman arrived in the emergency room in a coma. She had been living alone and, according to neighbors, sitting in a chair in her apartment for weeks. Her clinical state was like one of hibernation, with very low pulse, blood pressure and temperature. Her hair was like thin and brittle, her skin scaly and dry, her face puffy and her legs thickened by a waxy swelling called myxedema. She was in the final stages of thyroid gland failure, myxedema coma. Early in the course of her illness, when symptoms were probably mild and ill-defined, no one had realized she was “hypothyroid.” Later, when thyroid hormone levels had fallen to dangerous lows, she was too slow mentally and physically to seek help. By the time she arrived in the ER she was on the brink of death from Hashimoto’s disease, an autoimmune inflammation of the thyroid gland, or thyroiditis. Hashimoto’s disease was the first recognized disease caused by the immune system attacking some part of the body, and is the most common cause of thyroid gland failure in the USA.

Hashimoto’s disease affects at least one in every 1000 people in the US, women more frequently than men. Though the thyroid disease was first described in 1912, and is now known to be caused by the production of antibodies against thyroid hormone producing enzymes and proteins, there is still no known way to prevent it. The only risk factor is a family history of a similar problem. Some environmental factors such as high iodine intake and viral infections may play a role in triggering the process in genetically susceptible individuals. In Hashimoto’s disease, the antibodies gradually destroy the gland’s hormone producing follicles. Most often, the thyroid gradually and irregularly enlarges as the follicles are replaced by inflammatory tissue. While the bumpy neck bulge created is similar to a goiter, the latter is smoother and more regular in shape and a sign of an overworking but non-inflamed thyroid gland which is getting insufficient dietary iodine.

In Hashimoto’s disease, subtle physical symptoms often precede the development of an enlarged thyroid gland. Since thyroid hormone facilitates all metabolism and energy production in every part of the body, inadequate amounts of the hormone cause a host of vague symptoms which are often excused as simply the byproduct of life style inadequacies such as too little sleep, poor diet, lack of exercise and stress. The symptoms include fatigue, weight gain, depression and anxiety, inability to stay warm, joint and muscle aches and pains, constipation, slow pulse, coarse and thinning hair, puffiness, irregular menstrual periods, and inability to conceive. In some people, gland enlargement never occurs. And though the underlying problem is inflammatory, the thyroid gland is not tender.

Because of the vague nature of the symptoms that bring a patient with Hashimoto’s thyroiditis to the doctor, because the thyroid gland may not be enlarged and because the screening blood test for total thyroid hormone level may fall within a normal range, many other diagnoses are often entertained before the correct one is made. These include depression, anxiety, chronic fatigue syndrome and subclinical infection. In addition, because hypothyroidism drives cholesterol and weight up, attention gets diverted to heart disease and other components of the metabolic syndrome.

But once suspicion of Hashimoto’s has been raised, the problem is easily identified by blood tests for antibodies to an enzyme called thyroid peroxidase and to a thyroid hormone binding protein called thyroglobulin and a test for a pituitary gland hormone called TSH, or thyroid stimulating hormone. TSH rises as thyroid function fails and the pituitary gland attempts to stimulate it to keep producing thyroid hormone.

Some patients need thyroid scans and biopsies of any suspicious gland areas to rule out the very rare possibility that a lump in the gland is cancerous. A general medical evaluation is also helpful since low thyroid hormone can accelerate cardiovascular disease and since the autoimmune dysfunction underlying Hashimoto sometimes occurs in association with other autoimmune disorders such as celiac disease, Type 1 diabetes, adrenal gland insufficiency, autoimmune gastritis with Vitamin B12 deficiency, rheumatoid arthritis, lupus, and some clotting disorders that may cause either bruising or clot formation in blood vessels.

If other autoimmune problems are not found, the therapy for Hashimoto’s thyroiditis is as easy as taking one pill a day, usually a synthetic thyroid hormone called levothyroxine. Prior to the development of synthetic thyroid hormone, a desiccated powder made from pig thyroid glands was the only treatment available and it is still preferred by a significant number of patients. A controlled study done in 2013 to determine whether there was any scientific evidence for treatment preference showed that both synthetic thyroid hormone and desiccated thyroid hormone are equally effective in raising thyroid hormone levels and returning TSH levels to normal, but that desiccated thyroid hormone resulted in slightly greater weight loss.

Our myxedema coma patient survived, though her management was difficult because of the severity of her hypothyroidism. Under the autoimmune attack of Hashimoto’s thyroiditis, the thyroid gland is a victim of a very slow war of attrition as more and more of its structure is replaced by inflammatory cells and scar tissue. The fall-off in hormone production is slow, and the body adapts to lower and lower levels of thyroid hormone until all systems finally begin shutting down. At that point, re-introducing high levels of thyroid hormone can be dangerous to heart function. The correction must occur gradually, as the decline did, underscoring the importance of detecting thyroid gland failure early, before it takes such a metabolic toll. Even when discovered early, the establishment of appropriate hormone dose and the reversal of symptoms may take some time and patience. The hormone must be taken for the rest of a long and otherwise normal life.

Posted by medical plaintalk

Physician turned medical writer.

Iodine: An Unfinished Story

In these days of high tech medicine it is easy to forget that some of the most effective and efficient health interventions are simple and cheap. One example is the addition of iodine to salt, an idea which began in the early 1900s with experimental trials in schoolchildren living in what was then known as the “goiter belt” of the USA. In that region surrounding the Great Lakes, many children developed enlarged thyroid glands called goiters. A goiter is a sign of iodine deficiency. So successful were the trials of iodine-supplemented diets that, by the 1930s, 90% of residents of the Great Lakes region used iodized salt and goiter rates in the region had plummeted. Now, 70% of the world’s population uses iodized salt.

Iodine as an essential element

When iodine is in short supply, thyroid glands grow large in an attempt to harvest as much of the vital element as possible from the blood. Iodine is necessary for making thyroid hormone and thyroid hormone is crucial for normal development and metabolism. Pregnant women who have low iodine levels and insufficient thyroid hormone often miscarry their babies or produce babies who are deaf, mentally-retarded and stunted in growth. In children and adults, iodine and thyroid hormone deficiencies cause fatigue, weight gain, lowered IQ levels, mental apathy and numerous metabolic abnormalities. Regular intake of iodine is a simple preventive measure for a host of serious problems.

Unequal distribution

Iodine exists in an inorganic form in soil and water and makes its way into the plants and animals that we consume by combining with larger carbon-containing molecules. In its inorganic form, iodine is a water-soluble salt which washes out of soil easily, especially in areas where the land is rocky and exposed. Where soil is iodine deficient, so are crops, unless supplemented with iodine containing fertilizers. In contrast to its variable presence in soil, iodine is much more uniformly distributed in salt water seas. Algae, kelp and other seawater plants, as well as saltwater fish and shell fish are the most reliable natural sources of dietary iodine, while iodine concentrations in land based plants depend on the amount of iodine in soil that supports them. Terrestrial animals supply iodine proportional to the iodine in their food sources. Egg yolks are a good iodine source, because, like people, chickens develop goiters, and chicken feed is supplemented with iodine. Dairy products are also good sources. Cattle feed was originally supplemented with iodine to prevent hoof rot, and and because of the supplemented feed, iodine is secreted in the milk the cows produce.

Iodine and breast tissue

Milk contains iodine because mammary gland tissue, like thyroid gland tissue, accumulates iodine. The fact that iodine is found in human breast tissue, where it has no known function, has prompted studies of the element’s relationship to breast health. Japanese women have low rates of breast cancer and fibrocystic breast disease compared to American women, and their regular iodine consumption via seaweed is high, perhaps 25x higher than the recommended daily iodine consumption in the US. Studies on the treatment of fibrocystic breast disease with iodine supplements have been promising but so far a direct relationship between breast disease and iodine consumption has not been proven.

Iodine supplementation?

Even if high dietary iodine content has something to do with low breast cancer rates among Japanese women, translating this information to attempts to prevent breast cancer is not a straightforward task. While it is clear that iodine supplementation prevents goiter, hypothyroidism and cognitive impairment, it is also clear that increasing iodine intake is not risk free, particularly in people who are accustomed to low levels of dietary iodine. The thyroid gland, when faced with insufficient iodine in the blood, becomes a ruthless scavenger, extracting every last iodine molecule it can find. When iodine levels in the blood suddenly increase because of supplementary iodine intake, some thyroid glands will actually grow in size, pump out excessive thyroid hormone and even develop cancerous nodules. It may be that Japanese women can tolerate high amounts of iodine because it has never been in short supply for them. Caution and careful follow-up are always advisable when supplementing the diet with iodine in the form of tablets, drops or multivitamins.

Dietary iodine in the age of dietary angst

Obtaining enough iodine through the diet should be possible in almost all circumstances, especially because of the wisdom of public health policies regarding iodine. Nevertheless, some eating trends in health in the closing decades of the 20^thC have again raised public health concerns about iodine intake. Assessments of body iodine content are made by measuring urinary iodine levels, since the body extracts as much iodine as it needs and excretes the rest in urine. But individual measurements are so variable that averages of all people tested are used to estimate the iodine status in a given geographic area. Between 1971 and 2001, American iodine intake dropped dramatically then leveled off at half of the 1971 levels.

What happened over the last few decades? Americans began getting much more of their salt in the form of the un-iodized salt in processed foods. Many people began avoiding salt altogether, some quite unnecessarily. Sea salt appeared on the grocery store shelves as part of the natural and organic food trends. It is also possible that the 1971 levels of iodine consumption were artificially high. Studies in the 1970s showed that iodine-containing sanitizers were raising iodine levels in cows’ milk. Practices changed and milk iodine levels returned to normal. Between the 1960s and 1980s, iodine was used in dough making and bread supplied 25% of the iodine consumed during that period.* Perhaps the baseline measurements of iodine intake in the early 1970s were unnecessarily high. Perhaps intakes in 2001 and since are adequate, at least to prevent goiters from developing. But the fact that Japanese people ingest far higher levels of iodine from whole food sources without ill effect suggests that we can tolerate more. Stay tuned.

*Note: Iodine in the Nuclear Age

In the wake of the atmospheric nuclear testing period, the government mandated the use of iodine containing oxidizing agents for dough conditioning in commercial baking. The iodine in the bread competed in the diet for uptake into the thyroid gland with radioactive iodine isotopes generated in the wake of atmospheric nuclear testing. Saturating the thyroid gland with normal iodine is standard practice when radioactive iodine in the atmosphere is a threat, as it was after the Chernobyl disaster. Taken within 8 hours after, or 48 hours prior to a nuclear disaster, iodine can prevent accumulation of radioactive iodine in the thyroid gland and thus prevent radiation damage to the gland. Pills to be taken in the event of a nuclear catastrophe are simply potassium iodide.

Posted by medical plaintalk

Physician turned medical writer.

Thyroid Ups and Downs

Early in her husband’s presidency, first lady Barbara Bush began to lose weight. Her eyes became, in her own words “horrible and puffy” looking.” She had developed an autoimmune thyroid gland problem called Graves’ Disease. A few months later, the Bush‘s dog Millie came down with another autoimmune disease – lupus. The next spring, the president became ill with weight loss and a rapid, irregular heartbeat. Like Barbara he had Graves’ disease. Conspiracy theorists blamed Saddam Hussein for this outbreak of autoimmune disease in the White House, but thyroid experts saw nothing but coincidence. They admit, though, that they do not know what triggers antibody attacks against the thyroid gland, the most common cause of thyroid disease.

The many and varied symptoms of thyroid disease
Symptoms of thyroid disease most often involve effects of the hormones the gland makes. Thyroid hormone stokes the fire of metabolism, setting the rate of energy usage in every cell of the body and determining the basal metabolic rate (number of calories burned at complete rest).
Too much thyroid hormone causes hyperthyroidism; too little creates hypothyroidism. Extreme cases of either problem are easy to diagnose, but milder excess or deficiency states are much trickier and more common (an estimated 7-10% of adults have thyroid abnormalities). Hyperthyroid patients lose weight, become intolerant of warm environments and sweat profusely. Hair becomes thin and fine. The heart beats too fast and blood pressure rises, while muscles feel weak and hands shake. Sleep becomes elusive. On the hypothyroid end of the spectrum, lack of thyroid hormone banks the metabolic fires and drops the heat. Patients feel cold and become constipated. Incoming energy gets stored as fat; weight and cholesterol levels climb. Lethargy encroaches on daytime hours, and ambition and mental quickness decline. Both under and overactive glands can be enlarged and even visible as swellings just under the Adam’s apple.

Diagnosis
The confirmation of the thyroid gland’s role in symptoms comes from blood tests that measure thyroid hormone levels. Extreme cases are easy to diagnose. Milder cases, with less impressive symptoms and “borderline” blood tests are trickier. Mild symptoms overlap many of life’s normal patterns that are unrelated to thyroid hormone: weight, blood pressure and cholesterol tend to go up with age; sedentary people frequently feel cold and constipated; women at menopause would sometimes like to abolish indoor heating, and physical and mental energy are always subject to lifestyle, happiness, and drug effects. The opinion of an endocrinologist is particularly helpful in interpreting borderline thyroid symptoms and lab values.
Thyroxin or T4 (with four iodine molecules) comes from the thyroid gland. Tri-iodothyronine (T3) comes from T4 when one iodine molecule is split off. Thyroid stimulating hormone (TSH), made in the pituitary gland, is like a thermostat that regulates how much T4 the thyroid gland makes. When T4 is too high, TSH goes down. When T4 is too low, TSH goes up. So hypothyroid patients have high TSH and low T4, and hyperthyroid patients have low TSH and high T4.
Symptoms suggesting hyperthyroidism, combined with high-normal T4 and T3 and low- normal TSH prompt further tests to look directly at the thyroid gland. Thyroid scans employ radioactive iodine and distinguish between glands that overproduce in all areas, ones that have nodules of overproduction, and enlarged glands that no longer make any hormone. Measurement of three different types of anti-thyroid antibodies further narrows the diagnosis.

The problems with the tests
Not all labs use the same ranges of normal values. Some rely on broad TSH ranges found in a random selection of apparently healthy people (0.32 -5.0 µIU/ml). Other labs use a much narrower range (.34-2.5µIU/ml) found in people who have been screened to rule out thyroid disease. So if you see a doctor who uses the first range and your TSH is 4.5, you might be told just to watch your weight, get better sleep, take a little blood pressure medicine and be rechecked in 6 months or a year. A doctor using the second might would give you a prescription for thyroid hormone. Treatment of hypothyroidism in these gray areas might normalize the blood tests without producing any clinically identifiable benefits. Nevertheless, it is wise to follow up on iffy test results because, over time, thyroid conditions may declare themselves further.

Autoimmune thyroid disease
Graves Disease and Hashimoto’s thyroiditis, caused by different types of antibodies, are the most common causes of thyroid problems and tend to run in families. In Graves ’ disease, the antibodies may also attack eye muscles and make them swell, producing the characteristic bulging eyes that Barbara Bush complained about. Graves disease most often begins with a hyperthyroid state that requires treatment to suppress overproduction of thyroid hormone or to obliterate the gland by radiation, producing hypothyroidism that requires treatment; sometimes Graves’ improves on its own but then goes on to hypothyroidism. Hashimoto’s disease most commonly bypasses the clinical hyperthyroid phase altogether and is the most common cause of hypothyroidism.

Iodine deficiency
Lack of dietary iodine once caused many cases of hypothyroidism. The word cretin (slang for dunce, idiot) originated in a mountainous French region where iodine deficient soil and lack of iodine-rich seafood resulted in a high incidence of mental and physical retardation from hypothyroidism in babies. Thyroid hormone and the dietary iodine required to make it are critical for normal growth and development, especially of the brain. In modern societies babies are screened and treated for hypothyroidism, and iodized salt makes this essential element easily available so this once frequent deficiency is much less common.

Treatment
Oral, synthetic versions of T3 and T4, or “natural” versions made from batches of pig thyroid glands make failing thyroid glands easily treatable. Synthetic versions are easier to regulate than are the natural ones. Finding the proper dose to return the blood tests to the normal range is often much easier than finding the dose and timing of pills that improves symptoms. The latter process is an inexact science that sometimes results in too much hormone effect.
Overactive glands are treated with medicines that shut them down, sometimes with radioactive iodine that kills the glandular cells and sometimes with surgery to remove the entire gland. The latter two treatments always produce hypothyroidism which then requires treatment with replacement hormones.
One study on thyroid disease prevalence estimates that there are 13,000,000 Americans with undiagnosed thyroid problems. Thyroid tests are now part of routine blood work, more problems will be caught and treated earlier, and more will be learned about triggers for autoimmune thyroid problems – eventually putting at least one conspiracy theory to rest.

Notes on less Common Thyroid Conditions

Lumps in the thyroid: These are common and most are benign nodules or cysts; sometimes they produce thyroid hormone and cause hyperthyroidism.

Viral thyroiditis (also known as sub-acute thyroiditis): self-limited illness with several weeks of hyperthyroidism, followed by several weeks of hypothyroidism, and then recovery of normal function.

Thyroid cancer: Uncommon. Rarely produces thyroid hormone so usually the diagnosis results from evaluation of lump in the neck or hoarseness; results from radiation exposure – as once was the practice for treating acne.

Pituitary Gland Tumors: Pituitary failure to produce TSH causes hypothyroidism; very rarely the pituitary overproduces TSH and causes hyperthyroidism.

Dietary Hyperthyroidism: At least one outbreak of hyperthyroidism came from meat contaminated with animal thyroid glands. Another rare cause is sudden, excessive iodine supplementation in a patient with underlying thyroid disease .

Posted by medical plaintalk

Physician turned medical writer.

The Problem with Stress: No Fighting or Fleeing

…grant me the serenity
to accept the things I cannot change;
courage to change the things I can;
and wisdom to know the difference….

from The Serenity Prayer, by Reinhold Niebuhr

Picture an early human moving through the quiet forest, intent on the prey he’s tracking. His pace is steady and his mind focused. Suddenly a bear bursts through the trees. Emotional centers in primitive parts the hunter’s brain fire off threat messages which race through the sympathetic nervous system to his adrenal glands—little thumb size organs buried in fat and sitting on top of the kidneys. Almost instantly, each gland responds with a burst of adrenalin from its central core, the adrenal medulla. Danger also prompts his pituitary gland to pour out a big dose of adrenocorticotropin (ACTH), a hormone that speeds through the blood to the adrenal cortex, the outer 80% of the gland. In response, the gland releases cortisol, a powerful glucocorticoid hormone involved in energy regulation.

The hunter’s pulse and blood pressure shoot up. His airways dilate and he breathes faster. His vision narrows and sharpens. Anticipating action, his muscles and liver free glucose and fat from storage. By the time he races to a nearby tree to haul himself to safety, the cascade of neural and hormonal events has shifted his metabolism from quiet homeostasis (maintenance of normal function) to an active state designed for fleeing….or for fighting if the bear climbs too. When the bear loses interest and wanders away, our early man’s activated physiology reverts to routine functioning. He climbs down, resumes his methodical hunt and cooks his game over an open fire. From sundown to sunup, he sleeps.

Now consider a modern man as he rushes through his urban environment. He becomes anxious and then angry when his train is late. As he hails a cab he narrowly misses being hit by an oncoming car. Horns blare. He flops down in the back seat of the cab, fumbling for his ringing cell phone, only to hear that his boss is angry because he is late. Inside our overweight modern man’s body, early hunter physiology whips his adrenal glands into action – over and over and over. But he does not get to fight or flee. Worse yet, the threats in his environment do not lose interest and wander away. He will be on edge all day, and perhaps late into the night. After a few drinks, a few smokes, a fast food meal and some paperwork, he falls asleep in front of the TV, finally stumbling into bed in the wee hours of the morning. By 6AM he’s starting over, sleep-deprived.

The adrenal gland connection

In both early and modern humans, the brain-adrenal connection is heavily influenced by environment, genetic makeup, lifestyle and memory of previous experiences. We learn fear and make habits of emotional responses. While animal research can’t take into account human mental components of stress, it has provided useful physical insights, especially about the adrenal connection to chronic stress. Experiments in “rat micro-societies” refined the fight-or-flight concept and divided it into aggressive defense and passive defeat responses, an important distinction because each type activates different parts of the adrenal glands.

Rats responded with passive defeat when a task like pushing a lever sometimes produced food, sometimes didn’t, sometimes in one place, sometimes in another, and sometimes not at all. The consequences of the rats’ actions were uncontrollable and feedback didn’t help them learn. In these circumstances the adrenal cortex overproduced cortisol. If you think the passive defeat experiments resemble average life, then you’ll guess, correctly, that chronic stress in people might also trigger elevated cortisol levels.

Aggressive defense responses to the rat equivalent of being mugged, in contrast, activated primarily the adrenal medulla, which takes charge of the immediate activity necessary to survive a threat by producing an adrenalin rush – a burst of the hormones epinephrine and norepinephrine. In states of fear and/or anger, we experience this rush as rapid pulse, elevated blood pressure, increased breathing rate, flushing, pallor and dry mouth.

In our early hunter these adrenal responses are sequential. First comes the adrenalin rush which helps him survive. Following just behind, the adrenal cortex ramps up hormone production to help restore normality–to restock energy supplies, dampen pain and divert resources from routine activities.The system is designed for short bursts of danger, not for chronic immersion in mental stress.

The metabolic syndrome connection

Beginning in 2002, researchers began to correlate adrenal hormone abnormalities with the modern plague of the metabolic syndrome—abdominal obesity, insulin resistance, diabetes and high blood pressure, all reliable side effects of exposure to excessive cortisol, whether it comes from drugs like prednisone or from pituitary or adrenal gland diseases. (See note on Cushing’s disease below). No one thinks cortisol and stress are wholly responsible for our metabolic epidemic, but many hope that the stress connection will help lead to a solution.

Counteracting the stress response

Stress researchers uniformly conclude that short of retreating from the world, the only major defense that counteracts the effects of stress is regular physical activity which dissipates some of the energy mobilized for action. The best results come from superimposing physical activity on a lifestyle that accommodates enduring human needs: sufficient sleep, diet suitable for an ancient physiology, good social network and engagement in focused activity that has personal value. Even then, coping strategies are necessary.

A Note on Cushing’s Disease

The most dramatic demonstration of the results of too much cortisol occurs in patients with Cushing’s disease, usually caused by a pituitary gland tumor which overstimulates the adrenal cortex. In these patients, muscles are thin and weak, and excess weight is concentrated in the trunk and face and neck. Patients have red, jowly faces and skin scored by purplish stretch marks and poorly healed wounds. Bones are robbed of calcium and osteoporotic upper backs round forward under the characteristic “buffalo hump” of fat. The adrenal cortex hormones also have weak male hormone effects causing male pattern baldness and excess facial hair in women. The immune system is weakened and health is further damaged by diabetes, high blood pressure and heart disease.

Posted by medical plaintalk

Physician turned medical writer.

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