Pathology Student

Okay, so this post is more about being a student than it is about the study of pathology. Bear with me: there is important information here!

Of the two hormones produced by the posterior pituitary (oxytocin and antidiuretic hormone), the more interesting by far is oxytocin. Called the “cuddle hormone,” it has been shown to mediate trust, connection, monogamy, and basically any other good emotion that occurs in relationship with others. On Tuesday, the New York Times published an article entitled “Evidence That Little Touches Do Mean So Much” which suggests that oxytocin has another very important effect that may have implications for students in classrooms.

The article talks at length about research showing how small, physical interactions (a touch on the arm, a high-five, etc.) have a positive effect on both the toucher and the touchee. Some of the positive effects are what you’d expect: small touches have been shown to ease pain, soothe depression, deepen a relationship. But here’s something interesting: small touches can also improve performance! A soon-to-be-published study of professional basketball players came to this startling conclusion:

“Players who made contact with teammates most consistently and longest tended to rate highest on measures of performance, and the teams with those players seemed to get the most out of their talent.”

It probably has to do with – you guessed it – oxytocin. The article states: “If a high five or an equivalent can in fact enhance performance, on the field or in the office, that may be because it reduces stress. A warm touch seems to set off the release of oxytocin, a hormone that helps create a sensation of trust, and to reduce levels of the stress hormone cortisol.”

How could oxytocin (a “relationship” hormone) have anything to do with personal performance? The article offers an interesting suggestion:

“In the brain, prefrontal areas, which help regulate emotion, can relax, freeing them for another of their primary purposes: problem solving. In effect, the body interprets a supportive touch as ‘I’ll share the load.’”

So: let’s see more high-fives, more touches on the arm, more secret handshakes. It can’t hurt – especially around exam time!

Image credit: Carina Ice (http://www.flickr.com/photos/carinaice/4089444469/), under cc license

Q. I have been trying to figure out the two basic thyroid lab tests, TSH and T4. If you have a high TSH and a low T4 does that mean that the pituitary gland is going crazy to reach homeostasis but the thyroid is not responding? And inversely, if the T4 is high and the TSH is low does that mean for some reason the thyroid is working overtime due to a disease like Graves disease, and the pituitary is trying to compensate by not producing TSH?

A. Yes! That’s exactly right. When the two (TSH and T4) are opposite of each other – high T4/low TSH or low T4/high TSH – that means that the problem is intrinsic to the thyroid gland (Graves disease or Hashimoto thyroiditis, for example) and the pituitary is trying to control the thyroid by producing more or less TSH. Those are the most common types of thyroid disease – those that are intrinsic, or primary to the thyroid gland itself.

On the other hand, if both TSH and T4 are either low or high – high T4/high TSH or low T4/low TSH – that means that the process is being driven by TSH. Either there’s a pituitary adenoma making a ton of TSH, or the pituitary is not working well for whatever reason (it’s been radiated, or has undergone necrosis) and it’s not making enough TSH.

Image credit: akay (http://www.flickr.com/photos/akay/245002004/), under cc license.

Might as well admit it: the histology of the parathyroid glands is highly forgettable. I’m not sure why this is – perhaps because we don’t talk about it very often, perhaps because it’s so banal – but I do know that it’s one of those things that needs a lot of repetition to become permanent.

The parathyroid glands are four dinky little things (3-4 mm, about 35 mg each) usually located on the posterior surface of the thyroid gland. They exist in two pairs; the upper pair is derived from the fourth branchial cleft and descends with the thyroid gland, and the lower pair is derived from the third branchial cleft and descends with the thymus.  Their main function is the regulation of serum calcium levels. They do this by secreting a hormone called parathormone (or PTH) when serum calcium levels go down. PTH does all kinds of things (it activates osteoclasts to chew up bone, increases renal reaborption of calcium, increases renal conversion of vitamin D to its active form, and increases calcium absorption from the gut) but the bottom line is that it raises the serum calcium.

It’s the histology that’s like a blank spot in most medical students’ (and physicians’) minds. The parathyroid is composed of two types of cells: chief cells (small, round, bland cells) and oxyphil cells (large cells with abundant eosinophilic cytoplasm). The chief cells are the secretors of PTH, and they make up the bulk of the cellularity of the parathyroid. Scattered throughout are small islands of oxyphil cells (you can see one at 12 o’clock in the image above). There is a varying proportion of fat, too, that increases with age (like every other part of the body, it seems).

That’s it! Now go memorize it! Maybe this is the final repetition of parathyroid histology that will stick in your brain forever.

Q. What is the difference between a thyroid nodule, a multinodular goiter and a toxic multinodular goiter?

A. A thyroid nodule is simply what it sounds like: a lump in the thyroid, usually one that’s felt by the patient or the clinician. The term “thyroid nodule” doesn’t indicate anything about the underlying pathology, it is simply a clinical, descriptive term. Lumps or nodules in the thyroid can be caused by many different things, including multinodular goiter, other benign conditions such as thyroiditis or Graves disease, and thyroid neoplasms, such as adenoma and carcinoma. A nodule always needs to be investigated (the best way is with a fine-needle biopsy) because of the possibility (though small) that it could be caused by carcinoma.

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.

We talked a bit about thyroiditis yesterday (see 4/27/09 post). Here’s another kind of thyroiditis: fibrosing (or Riedel) thyroiditis. This one is totally different than subacute granulomatous thyroiditis. In fibrosing thyroiditis, the thyroid becomes overrun by fibrous tissue (guess that’s why they picked that name). For some unkown reason, fibroblasts just start proliferating and laying down collagen. In the picture above, there is one pathetic-looking residual follicle, surrounded by lymphocytes, in a sea of fibrotic tissue. As the disease progresses, the thyroid becomes a rock-hard, woody mass. If it gets big enough, it can compress some of the important structures in the neck, like the trachea, and it may need to be removed.

“Thyroiditis” means “inflammation of the thyroid gland” (any time you see “-itis,” think “inflammation”). There are four main types of thyroiditis: Hashimoto thyroiditis, subacute granulomatous (aka DeQuervain) thyroiditis, lymphocytic (aka silent) thyroiditis, and fibrosing (aka Riedel) thyroiditis. We’ll cover each of these in separate posts, starting today with subacute granulomatous thyroiditis.

Subacute granulomatous thyroiditis is a self-limiting inflammatory disorder of the thyroid that occurs following a viral upper respiratory tract infection (usually adenovirus or coxsackievirus). Several days after the infection begins, the patient develops severe neck pain, sometimes radiating to the ear. Some antigen in the virus stimulates production of CD8+ (cytotoxic) T cells which, for unclear reasons, begin to attack the thyroid follicles. As the follicles are damaged, colloid leaks out. The body sees this as foreign material, and it sends macrophages in to eat it up.

The microscopic picture looks like a foreign body giant cell reaction – because that is, in effect, what is happening. There are lots of macrophages, and you can see them ingesting colloid. Sometimes they form loose granulomas, and sometimes they become multinucleated (as in the multinucleated giant cell in the above photo).

The good news is that this process, though painful and scary-looking microscopically,  resolves on its own within a few weeks. Patients return to normal thyroid function, with no residual symptoms.

There are four types of thyroid carcinoma: papillary, follicular, medullary, and anaplastic carcinoma. One of these types, follicular thyroid carcinoma, can look very much like a benign thyroid adenoma. Both follicular carcinoma and thyroid adenoma are composed of follicles (resembling normal thyroid follicles). The only way to tell apart follicular thyroid carcinoma (which is malignant) from thyroid adenoma (which is benign) is to take out the entire nodule and examine the entire thing very carefully. If you see tumor cells invading the capsule, or if you see them within vessels (as in the photo above), that means it’s follicular carcinoma. Malignant tumor cells invade; benign ones do not.

Papillary thyroid carcinoma has a number of unique morphologic features. I mentioned psammoma bodies a few days ago (see 4/14/09 post). Illustrated above is another characteristic feature: Orphan Annie nuclei. These are so named because they have a “cleared-out” appearance, similar to Little Orphan Annie’s eyes. In fact, you can think of papillary thyroid carcinoma as the Little Orphan Annie tumor because:

1. It stays around for years and years without getting any bigger (papillary carcinoma is slow growing).
2. It is well-behaved and seldom kills people (overall, the 10-year survival for papillary carcinoma is >90%, which is better than the prognosis of any of the other types of thyroid carcinoma).
3.  The nuclei resemble Little Orphan Annie’s eyes.
4.  It often has psammoma bodies (derived from the Greek psammos, or sand): Annie’s dog is named Sandy.

I wish I could say I came up with this, but it comes from Ed’s Pathology Notes, a really wonderful pathology site for students (and anyone interested in pathology) at www.pathguy.com.