Pathology Student

Atherosclerosis is responsible for half the deaths in the US today! If you get it in your coronary arteries, you’re at risk for myocardial infarction; if it’s in your carotid arteries, you’re at risk for stroke. And lest you think this is something you don’t need to worry about until you’re old, you should know that this process starts very, very early in life – somewhere during childhood – and you just can’t tell you have it until you suddenly start getting nasty symptoms (doctors call this the “clinical horizon,” which sounds strangely picturesque). Scary.

There are lots of risk factors for getting atherosclerosis. They are divided into two groups: major risk factors (which are known for sure to cause atherosclerosis) and lesser or uncertain risk factors (which have less of an effect, or are as yet unproven). Let’s take a look at both groups.

Major risk factors

Some of the major risk factors for atherosclerosis you are simply stuck with, and there is not a thing you can do about them. These include:

• increasing age (atherosclerosis is more common as people get older)
• gender (At younger ages, males are more at risk. Premenopausal women are relatively protected; after menopause the risk in women increases and eventually exceeds the risk in males.)
• family history
• genetic abnormalities (lots of these probably exist; many aren’t fully understood).

The good news is that there are several major risk factors that you can potentially do something about. These include:

• Hyperlipidemia (best thing to do is have a high level of HDL cholesterol, which actually scavenges lipids and removes them from atherosclerotic plaques, and a low level of LDL, which is the “bad” cholesterol that makes up part of the plaques.
• Hypertension (there’s no one right number, but it should be at least below 140 systolic and 90 diastolic)
• Cigarette smoking (smoking potentiates the other risk factors)
• Diabetes (patients with diabetes mellitus have an increased amount of atherosclerosis at a younger age)
• C-reactive protein level (this is a serum marker of inflammation; the higher the level, the greater the risk for atherosclerosis)

Lesser or uncertain risk factors

Then there are a bunch of other things that may be related to an increased risk, but the data is not yet conclusive. These include:

• Obesity
• Physical inactivity
• Stress
• Postmenopausal estrogen deficiency
• High carbohydrate intake
• Lipoprotein (a) (an altered form of LDL that seems to be independently associated with increased risk of atherosclerosis)
• Trans-fat intake
• Chlamydia pneumoniae infection (Chlamydia pneumoniae and other bugs have been detected in plaques but not in normal arteries, and there are increased antibody titers to C. pneumoniae in patients with more severe atherosclerosis. But a causal link hasn’t been established.)

So: don’t smoke; eat well (not too many carbs, no trans fats), exercise, and maintain a healthy weight; keep your blood pressure and lipids within the normal range; if you have diabetes, work to keep it as controlled as possible; don’t get Chlamydia pneumoniae. Oh, and don’t get all worried about it – stress is another potential risk factor!

Image credit: Hamed Masoumi (http://www.flickr.com/photos/hamedmasoumi/2266654041/), under cc license.

One of the things that researchers are studying like crazy is the process by which cancer takes root and grows in the body. Our diet plays a huge role in this process (witness the much lower incidence of cancers in India, for example, despite the much higher incidence of carcinogens!).  For your own health, and for the health of your future patients, I highly recommend David Servan-Schreiber’s book, Anticancer: A New Way of Life, which came out last year. David is an MD who developed brain cancer and went through successful medical treatment. However, his tumor recurred, and at that point he decided he needed to change his way of life. This book describes the effects diet and stress have on the growth of cancer – and before you blow that off as being too foofy or alternative, you should know that he backs up every point he makes with tons of research from accomplished scientists at respected places like Harvard and M.D. Anderson. Much of this post is from information described in David’s book.

The process of tumor growth is much like the growth of weeds. Tumors grow in three phases: 1) initiation, 2) promotion, and 3) progression. Initiation is the phase when a seed settles in the soil, promotion is the phase when the seed becomes a plant, and progression is the phase when the plant becomes a weed (developing beyond control, invading flower beds and growing right up to the sidewalk).

Initiation (the planting of the seed) depends largely on our genes and on toxins (radiation, carcinogens, etc.). But promotion (the growth of the seed) depends on having the right survival conditions: favorable soil, water, and sun. The cool thing is that promotion is reversible! If you can change the tumor’s environment, you can prevent it from spreading. Diet plays a role – probably a big role – in the creation of a favorable vs. unfavorable tumor environment.

Cancer “fertilizers”

Here are some dietary substances that create a fertile soil for cancers:

Refined sugars (drive up proinflammatory insulin and insulin-like growth factor, or IGF)
Insufficient omega-3s/excess omega-6s (favor inflammation)
Growth hormones in meat and non-organic dairy products (stimulate IGF)

Okay, what diet does this sound like? Lots of sugar, bad fats, and meat – the typical Western diet.

Cancer inhibitors

So, what should we eat? In addition to avoiding saturated fat, sugar, meat and non-organic stuff, a good cancer-fighting diet would include some/all of the following:

Catechins (in green tea) – inhibit angiogenesis

Phytoestrogens (in soy products) – block overstimulation of tumors by estrogen; prevent angiogenesis

Curcumin (in turmeric) – inhibits inflammation, inhibits angiogenesis, promotes apoptosis in tumor cells

Ellagic acid (in berries) – inhibits angiogenesis, blocks transformation of environmental carcinogens into toxic substances

Anthocyanidins (in blueberries, cranberries, cinnamon, dark chocolate) – promote apoptosis in tumor cells

Terpenes (in mint, thyme, marjoram, oregano, basil, rosemary) – inhibit tumor cell invasion, promote apoptosis in tumor cells, inhibit angiogenesis

Gingerol (in ginger) – inhibits inflammation and angiogenesis

Sulforaphane, indole-3-carbinol (in cruciform veggies) – prevent precancerous cells from becoming malignant; promote apoptosis of tumor cells, inhibit angiogenesis

Sulfur compounds (in garlic and onions) – reduce carcinogenic effects of nitrosamines (created in overgrilled meat and present in tobacco); promote apoptosis in tumor cells; help regulate blood sugar levels.

Lycopene (in carrots, yams, other bright colored veggies and fruits) – stimulates NK cells to become more aggressive; inhibits tumor cell growth

Long-chain omega-3 fatty acids (in fatty fish) – reduce cancer cell growth, prevent metastasis

Vitamin D (sun, cod liver oil, milk (tiny amount), vitamins) – dramatically reduces risk of several cancers

Polyphenols (red wine, chocolate) – block NF-kappa B (important in all three stages of cancer development: initiation, promotion, progression), limit angiogenesis

Photo credit: L’eau Bleue (http://www.flickr.com/photos/8175535@N05/3536354514/), under cc license.

Systemic lupus erythematosus is one of a few diseases that have earned the name “the great imitator.” It is a chronic, systemic illness with many, many possible symptoms in many different organ systems, and widely varying disease courses in different patients. We’ll go through a short summary of lupus here and save the more detailed information for other posts.

The underlying cause of lupus is not known. To manifest the disease, you most likely need have two things: 1) a genetic predisposition, and 2) some environmental trigger (sun exposure, drugs, etc.). Whatever the underlying cause, patients with lupus all have autoantibodies against self antigens. All patients with lupus have anti-nuclear antibodies (antibodies against some part of the cell nucleus – like DNA, histones, RNA-bound proteins, or nucleoli). Some patients also have anti-RBC, anti-lymphocyte, anti-platelet and/or anti-phospholipid antibodies as well.

The autoantibodies cause damage by forming immune complexes with their corresponding antigens (in the case of anti-nuclear antibodies, there must be some type of cell destruction to expose the corresponding nuclear antigens!), and circulating around the body lodging in places they should not be (like glomeruli, skin, joints, the pericardium, etc.). Remember what type of hypersensitivity reaction this is? (See the bottom of the post for the answer. But try to remember before you look!)

Organ systems commonly affected (with common manifestations) are:
1. Renal system (wide variation in manifestations, from painless hematuria, to lupus nephritis, to end-stage renal failure. One histologic hallmark is membranous glomerulonephritis with a “wire-loop” appearance due to immune complex deposition.)
2. Skin (the classic manifestation is a malar, or “butterfly,” rash, but scaly patches, ulcers, and other skin lesions can occur)
3. Nervous system (headache, mood disorders, seizures, psychosis, focal neurologic deficits)
4. Musculoskeletal system (arthritis of small joints of hands, muscle pain)
5. Cardiovascular system (pericarditis, endocarditis (called Libman-Sacks endocarditis), atherosclerosis)
6. Hematopoietic system (anemia, thrombocytopenia, leukopenia, antiphospholipid antibody syndrome)

There are two main forms of lupus: discoid lupus and systemic lupus erythematosus. Patients with discoid lupus have only skin (not systemic) involvement, and they do not have anti-DS DNA antibodies (an antinuclear antibody frequently present in patients with systemic lupus). Systemic lupus erythematosus is just what the name says: a systemic form of the disease. It is the more common form, unfortunately.

The prognosis is difficult to predict for individual patients. Some patients have very few symptoms; rarely, the disease course is acute and rapid. Most patients suffer a relapsing and remitting course over a period of many years (the overall 10 year survival is 80%). Acute flare-ups can be treated with steroids – but as of now, there is no cure.

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The type of hypersensitivity reaction that is characterized by immune complex deposition is type III.

Photo credit: NIH (http://www.niehs.nih.gov/health/topics/conditions/lupus/index.cfm), under cc license.

The MHC (major histocompatibility) complex is a collection of genes on chromosome 6. It’s organized into three regions: the class I region, the class II region, and the class III region. Class I genes encode glycoproteins expressed on the surface of nearly every nucleated cell in the body. These glycoproteins, called MHC I receptors, present antigens (proteins made within that particular cell) to CD8+ T cells. Class II genes encode glycoproteins expressed only on the surface of antigen-presenting cells (macrophages and dendritic cells). These glycoproteins, called MHC II receptors, present antigens (which that antigen-presenting cell has eaten and processed) to CD4+ T cells. The MHC III region encodes a bunch of things, including complement proteins and cytokines.

So what?

Well, your T cells can’t recognize antigen unless it’s shown to them by an MHC receptor (the books say “presented in the context of an MHC receptor” but I like simpler words better). Helper (CD4 +) T cells recognize antigens only when they are presented by MHC II receptors; cytotoxic (CD8 +) T cells recongize antigens only when they are presented by MHC I receptors.

How are you supposed to remember which cells have MHC I receptors and which have MHC II receptors, and which T cell subset recognizes each one? I think of it like this. The MHC I receptor is kind of a low-class, ordinary, run-of-the-mill receptor (hence the common-sounding “I” designation). It’s present on virtually all nucleated cells in the body. The MHC II receptor is a high-class, specialized, advanced kind of receptor (hence the higher “II” designation). Only certain kinds of cells (antigen presenting cells) get to have this receptor. I’m sure that’s not why they named them that – but it helps me remember the numbers if I think of them in this way.

As to the cells that recognize each type of receptor – if you can remember the above, then you can figure out which type of T cell will recognize each receptor. Cytotoxic T cells recognize that type of MHC that is present on all cells in the body: the type I MHC receptor. It has to be this way, because any cell in the body can become infected, and cytotoxic T cells need to have a way to recognize and kill these cells. Helper T cells, on the other hand, recognize only that type of MHC that is present on antigen presenting cells: the MHC II receptor. Which makes sense, because helper T cells need the cytokines released by antigen presenting cells to help them do their job. So they lock onto the MHC II receptor on antigen presenting cells, and while they’re there, they get nice cytokine signals telling them to grow and differentiate.

Image credit: NIH.

Sometimes we (okay, I) get so caught up in describing pathologic mechanisms that real-life examples get the short end of the stick. Let’s look at some real diseases in which the underlying problem is a hypersensitivity reaction.

Type I (allergic) hypersensitivity
The big example (obviously) of this type of hypersensitivity is allergy. Pollen, cat dander, peanuts – they all have the same mechanism and this is it.

Type II  (antibody-mediated) hypersensitivity
There are a ton of diseases that have an underlying type II hypersensitivity reaction going on. Here’s a partial list:

1. Autoimmune hemolytic anemia: the patient makes antibodies to red cell antigens for some reason (not a good thing to do) which end up causing hemolysis.
2. Pemphigus vulgaris: the patient makes antibodies against the proteins connecting epithelial cells together, resulting in epithelial cell discohesion and bullae formation.
3. Goodpasture syndrome: the patient makes antibodies that react against proteins in both the glomeruli and the alveoli, leading to nephritis and lung hemorrhage.
4. Myasthenia gravis: the patient makes antibodies that bind to the acetylcholine receptor (on the muscle end plate), preventing acetylcholine from binding and doing its job; the end result is muscle weakness.
5. Graves disease: the patient makes antibodies that bind to the TSH (thyroid-stimulating hormone) receptor on thyroid epithelial cells, causing excessive stimulation of the receptor (just the opposite of what happens in myasthenia gravis!), leading to excessive production of thyroid hormone (hyperthyroidism).

Type III (immune-complex-mediated) hypersensitivity
There are a ton of diseases in this category too.

1. Lupus: the patient makes antibodies that bind to certain nuclear antigens; complexes lodge anywhere they please but especially in the kidneys, skin, and joints.
2. Post-streptococcal glomerulonephritis: in fighting a strep infection, the patient makes an antibody that reacts against the strep bug but also cross-reacts with some antigen in the glomerulus; antigen-antibody complexes lodge there and cause nephritis.
3. Serum sickness: after injection of foreign proteins into the patient (e.g., like they did in the old days when they used horse serum in vaccines!), the patient makes antibodies against the foreign proteins, and the resulting complexes lodge anywhere they want, but especially in the joints, kidneys, and vessels.
4. Arthus reaction: after injection of foreign protein into the skin, the patient (the original patient in Arthus’ 1903 experiments was a poor little bunny – but the same thing happens in humans) makes antibodies against this protein, and the resultant complexes stay in the skin, eliciting a nasty localized vasculitis and a big owie on the skin.

Type IV (T-cell-mediated) hypersensitivity
There are two kinds of this one (after all, there are two kinds of T cells!).

Delayed-type hypersensitivity
A good example of this is poison ivy exposure (patient gets exposed to poison ivy, helper T cells respond and some become memory cells; upon repeat exposure the memory T cells rush to the site, activating macrophages and causing inflammation). Another example is the Mantoux test; same principle.

T-cell-mediated cytotoxicity
Type I diabetes is a good example of this one. In this disease, cytotoxic T cells kill pancreatic islet cells. That’s not very nice. They are supposed to be killing infected cells, or tumor cells – not the patient’s own normal cells.

Photo credit: Joe Shlabotnik (http://www.flickr.com/photos/joeshlabotnik/506346418/in/photostream/).

Here’s a summary of those four pesky hypersensitivity reactions you will definitely be asked questions on at some point.

Sometimes, the best way to remember things is to boil them down to as few words as possible. I think you can summarize each hypersensitivity reaction in a one or two words:

Type I – allergy
Type II – antibodies
Type III – immune complex
Type IV – T cells

Here’s a little more information:

Type I hypersensitivity is the mechanism underlying the classic allergic response. It’s also called “immediate” hypersensitivity, which makes sense to any allergy sufferer (as soon as you start petting the cat, you start sneezing). It’s caused by an antigen (from an allergen, like cat dander) binding to IgE antibodies that are bound to the surface of mast cells. The antigen bridges the IgE antibodies, triggering release of nasty mediators (like histamine) from the mast cell. The end result: vessels dilate, smooth muscle contracts, and inflammation comes in and makes itself at home.

Type II hypersenstivity is also called “antibody-mediated” hypersensitivity. Which is kind of misleading, becase it’s not the only type of hypersensitivity reaction that involves antibodies. Oh well. In this type of hypersensitivity antibodies bind to antigens on a cell surface (any cell surface). Macrophages come in and eat up the cells (they think the Fc fragments of antibodies are yummy). Complement gets activated, inflammation comes in (harming tissue) and cells end up dying. Examples of this type of hypersensitivity include: autoimmune hemolytic anemia, pemphigus vulgaris, Goodpasture syndrome, myasthenia gravis, and Graves disease.

Type III hypersensitivity is also called “immune-complex-mediated” hypersensitivity. In this one, antibodies bind to antigens, forming complexes. These antigen-antibody complexes circulate (either throughout the whole body, or within one area of the body), get stuck in vessels, and stimulate inflammation, the end result being inflammation-mediated tissue damage and necrotizing vasculitis. Examples of this type of hypersensitivity include: systemic lupus erythematosus, post-streptococcal glomerulonephritis, polyarteritis nodosa, serum sickness, and the Arthus reaction.

Type IV hypersensitivity is also called “T-cell-mediated” hypersensitivity. This type of hypersensitivity has two subtypes. In one subtype, called delayed-type hypersensitivity, helper T cells secrete cytokines that activate macrophages (which eat the antigen) and induce inflammation (which damages tissue). A good example of delayed-type hypersensitivity is poison ivy. The other subtype, called T-cell-mediated cytotoxicity, involves cytotoxic T cells coming and killing target cells (like the cells of a transplanted organ, or the pancreatic islet cells in a patient with type I diabetes).

The nice kitty image is from anomalous 4 at: http://www.flickr.com/photos/31333486@N00/2066349843/

We’re back after a nice long summer break! School is back in session and hopefully Pathology Student will give you a little help along the way in your study of pathology.

Here’s a general pathology concept that is important not only for boards but for real life: wound healing. Let’s take a look at wound healing in the skin. Whether the wound is a small kitty scratch or a huge burn, we have ways of repairing the damage and restoring function to the skin. There are two types of wound healing in the skin: healing by first intention and healing by second intention (weird names, I know, but whatever).

Healing by first intention occurs in small wounds that close easily – for example, paper cuts, or small surgical incisions in which the edges are easily approximated. In this type of healing, epithelial regeneration predominates over fibrosis. That’s a fancy way of saying that there is usually minimal scarring in this type of healing. Healing is generally fast. Here’s a summary of the timeline in most wounds healing by first intention:

By 24 hours: a clot forms, neutrophils arrive, and the epithelium begins to regenerate
By 3-7  days: macrophages arrive, granulation tissue is formed, collagen begins to bridge the incision, and the new epithelium increases in thickness.

Let’s stop right here for a moment. Granulation tissue is that stuff that forms when your body is filling in the gap between your remaining tissues. The contents of granulation tissue are 1) new, fragile blood vessels, 2) fibroblasts, and 3) a loose extracellular matrix holding it all together. The whole point of granulation tissue is to provide a place for the new structures to grow that will hold the tissue together (blood vessels and collagen). That’s it. Note: granulation tissue is not the same as a granuloma (which is a collection of macrophages) or chronic granulomatous disease (in which patients have neutrophils that don’t work right, so their macrophages are left with the job of killing bacteria, and they form little granulomas all over the place). So don’t get those terms mixed up.

Weeks later: the granulation tissue is gone, collagen has been remodeled (using little metalloproteinase enzymes like collagenase), and the epidermis is full and mature (though it lacks dermal appendages in the area of the healed wound). Eventually, a full-blown scar forms.

Healing by second intention occurs in larger wounds that have gaps between the wound margins. Examples of this type of wound are: areas of skin infarction, large burns and ulcers, and extraction sockets (where the dentist has pulled a tooth. Yes, this first- and second-intention healing applies to mucosal epithelium too!). In this type of healing, fibrosis predominates over epithelial regeneration. In other words, there’s gonna be a big scar that’s more prominent than any skin regrowth that occurs. Healing by second intention is slower. There is a lot more granulation tissue (because you have a huge gap to bridge) and more inflammation (neutrophils and macrophages coming in to clean up the dead cells and debris). Therefore, there’s a greater risk of infection and inflammation-related tissue injury. Also, the wound contracts as it heals (so you don’t have to make such a big scar). As far as a timeline goes, you can’t really make a universal timeline for second-intention healing, because it varies a lot depending on how big the wound is.

It all makes sense if you can just remember: first intention = small wounds, second intention = big wounds.

The strangely beautiful photo above, aptly titled “cat launchpad,” was taken by quinn.anya and can be found at: http://www.flickr.com/photos/quinnanya/2420314228/.

The second most common type of anemia (after iron-deficiency anemia) is anemia of chronic disease (ACD). This is a mild to moderate anemia accompanying infections, inflammatory disorders or malignant diseases that persist more than 1-2 months (examples include pulmonary infections endocarditis, rheumatoid arthritis, lupus, carcinoma, lymphoma, and myeloma). It’s characterized by low serum iron, despite lots of macrophage storage iron.

The pathogenesis of this anemia is multifactorial. Part of the problem is related to iron metabolism. For the most part, mucosal cells absorb iron okay, but they don’t release it into plasma (so the iron never makes it into red cell precursors!). Macrophages take up iron okay, but they release it very slowly. All of this is mediated, at least in part, by a substance called hepcidin, which is produced by the liver and released in response to inflammation (which, of course, you see in most chronic diseases).

In addition to the iron metabolism stuff, the red cells in this anemia have a shortened lifespan. The weird thing is that if you put cells from patients with ACD into normal patients, the red cells have a normal lifespan; but if you put cells from a normal patient into a patient with ACD, those red cells will die early! To top it all off, there is an impaired bone marrow response to anemia. There’s not enough iron available to make enough red blood cells; also, there’s not enough erythropoietin around, and bone marrow can’t respond to what little there is. Ugh. You’d think with all that stuff going on, the anemia would be severe – but it generally isn’t. Patients usually have no real symptoms related to the anemia; they have enough trouble with whatever chronic disease they suffer from.

The anemia is normochromic and normocytic, usually.  Some cases (about 25%) are microcytic (but MCV rarely gets below 72 fL). There is minimal anisocytosis and poikilocytosis. There’s really not a lot to look at under the microscope!

To make the diagnosis, you need to do iron studies. In ACD, you’ll see the following:
•    ↓ serum iron
•    ↓ TIBC (total iron binding capacity)
•    ↓ transferrin saturation
•    ↑ ferritin (remember: ferritin is an acute phase reactant! So it’s increased in these patients, because there is chronic inflammation present.)
•    ↑ bone marrow storage iron

This anemia usually is so mild that treatment is not necessary. The anemia develops during the first 2 months of the chronic disease, and it doesn’t progress thereafter. The important thing to remember is that you need to distinguish it from iron-deficiency anemia (use iron studies for this). You wouldn’t want to mix the two up, because anemia of chronic disease requires no further treatment, whereas a diagnosis of iron-defieciency anemia necessitates a search for possible sites of blood loss.

Photo credit: Ethan Hein (http://www.flickr.com/photos/ethanhein/2383172799/), under cc license.

The final member of the thyroiditis quartet is lymphocytic thyroiditis (also called silent thyroiditis). This type of thyroiditis is characterized histologically by – you guessed it – a ton of lymphocytes (as in the image above). Just lymphocytes. No germinal centers, plasma cells, or Hurthle cells (like you see in Hashimoto thyroiditis). 

The pathogenesis of lymphocytic thyroiditis is unresolved. There may be an inherited component (there is a high frequency of both HLA-DR3 and HLA-DR5 in patients with this type of thyroiditis) and/or an autoimmune component (patients often make anti-thyroglobulin and anti-peroxidase antibodies).

Whatever the pathogenesis is, the disorder itself is mild. Some patients are asymptomatic (hence the name “silent”); others present with a painless, slightly enlarged thyroid. Mild, transient hyperthyroidism may develop over the first few weeks after onset, but by two months, the disease has usually run its course.

We’ve been discussing thyroiditis lately (see posts from 4/27/09 and 4/28/09). There are four kinds of thyroiditis: Hashimoto, subacute granulomatous, lymphocytic, and fibrosing. The most common of these, by far, is Hashimoto thyroiditis.

Hashimoto is an autoimmune disease in which the patient’s own immune system attacks and slowly destroys the thyroid gland. It’s much more common in women (as is typical of autoimmune diseases), and it is the most common cause of hypothyroidism in parts of the world where there is enough iodine. It typically presents with an enlarged, non-tender thyroid gland. Patients gradually lose thyroid function and eventually become hypothyroid.

The main problem in this disorder is that the T cells (for some unknown reason) recognize the patient’s own thyroid antigens as foreign. The T cells are cytotoxic to thyroid epithelial cells (not good), and they stimulate B cells to make anti-thyroid antibodies (also not good), such as anti-peroxidase antibody, anti-thyroglobulin antibody, and anti-TSH-receptor antibody. The most sensitive and specific of these antibodies is anti-peroxidase antibody (the other antibodies can also be present in Graves disease). The most interesting (I think) is anti-TSH-receptor antibody. It blocks the action of TSH, leading to hypothyroidism!

Salient histologic features of Hashimoto disease include a whopping lymphoid infiltrate, often with germinal centers (as in the above image) and Hurthle cells, which are follicular epithelial cells with abundant, eosinophilic, granular cytoplasm (if you look closely, you can see some of these in the above image, especially around the perimeter at 2, 7, and 9 o’clock).

Patients with Hashimoto thyroiditis who are euthyroid may simply be observed clinically. Patients who are hypothyroid generally are given synthetic thyroid hormone (levothyroxine). Since the disease is a chronic, progressive, autoimmune process, treatment must continue for life.