Monday, October 31, 2016

Introduction to Endocrine Pathophysiology

Another topic test, another series of posts!

Overview of endocrine systems

Here's a couple of old posts that might help you brush up on this:
There's just a couple more random points to make that I haven't covered on those two posts. And trust me, I'm not kidding when I say they're pretty random.
  • Another name for indirect responses for hormone is "trophic response." (An indirect response is when one hormone stimulates another which stimulates a response, as opposed to a direct response where the first hormone stimulates a response all on its lonesome.)
  • Negative feedback isn't always caused by hormones. For example, calcium can inhibit parathyroid hormone and glucose can inhibit glucagon.

Understand hormone regulation and how hormone measurements are used to diagnose pathology

The main concept you need to understand here is negative feedback, where products of some system can inhibit the original hormones that caused them to be produced in the first place.

Okay, that was probably a shit explanation, so let's use an example: release of thyroid hormones. The hypothalamus secretes TRH (thyrotropin-releasing hormone), which causes the pituitary to release TSH (thyroid-stimulating hormone), which causes the thyroid gland to release the thyroid hormones T3 and T4. T3 and T4 feed back to inhibit further TSH release from the pituitary. This is an example of negative feedback. (As an aside, iodine is an essential part of T4, which is why it's important to have iodine in your diet.)

Examining whether negative feedback is working appropriately or not can help to differentiate between primary and secondary endocrine diseases. A primary disease is where the endocrine organ isn't producing its hormone (e.g. the thyroid isn't producing T3 and T4), whereas a secondary disease is generally where the endocrine organ is totally capable of producing its hormone but for whatever reason isn't receiving stimulation to do so. Here's some examples and explanations of how measuring hormone levels can help distinguish between the two:

  • Hyperthyroidism (elevated T4) in which TSH is low is an example of primary hyperthyroidism. There's nothing wrong with the pituitary, because it's producing less TSH in response to elevated T4, as it damn well should. T4 remains high because there's something wrong with the thyroid.
  • Primary hypothyroidism (low T4), on the other hand, has elevated TSH. Here negative feedback is also working appropriately: a lack of T4 is causing the pituitary to produce more TSH. However, the problems within the thyroid are causing a lack of T4.
  • Secondary hyperthyroidism often has increased TSH as well as increased T4. In this case, negative feedback is not working correctly. Increased T4 should decrease TSH, but in this case it isn't.
  • Similarly, secondary hypothyroidism has both decreased TSH and decreased T4.

Now just a few notes on endocrine disorders more generally! Endocrine disorders generally fall into two categories: one where too much hormone is being produced, and one where too little is being produced. Too much hormone could be due to a tumour or some sort, ectopic production of the hormone or exogenously added hormone (for example, taking corticosteroids). Too little could be produced by autoimmune responses, destruction by a tumour or the organ being overworked. Diagnosis can be done through measuring hormones (often multiple are required to account for natural fluctuations) and imaging to locate tumours etc.

Appreciate that pituitary tumours can produce a variety of pathologies

As I mentioned in my PHYL2001 post about the endocrine system, the pituitary is responsible for a helluva lot of hormones. The anterior pituitary releases FSH (follicle-stimulating hormone), LH (luteinising hormone), growth hormone, TSH (thyroid-stimulating hormone), prolactin and ACTH (adrenocorticotropic hormone). The posterior pituitary releases oxytocin and vasopressin (a.k.a. ADH- antidiuretic hormone). Therefore, although adenomas (pituitary tumours) are "benign" in that they don't tend to metastasise, they can cause a lot of nasty effects.

First let's have a look at what happens when hormones are produced in excess! The most common type of this is hyperprolactinaemia, which, as the name implies, is an excessive production of prolactin. It can result in galactorrhoea (inappropriate lactation- can occur in both men and women) as well as amenorrhoea (loss of menstruation due to inhibitory effects of prolactin). ACTH can be produced in excess too, which is one cause of Cushing's disease, which I've spoken about here. Excessive growth hormone can lead to gigantism if this happens prior to puberty, or acromegaly (enlargement of some tissues even after the growth plates have closed) if this happens later on.

So how can this be treated? Some drugs may be of help: bromocriptine, a dopamine agonist, may be of help in treating hyperprolactinaemia. This is because dopamine normally inhibits prolactin, so adding a dopamine agonist will inhibit excess secretion of prolactin. Androgen antagonists may also help in patients who are suffering from hirsutism (excessive hair) or alopaecia (baldness). Sometimes the tumour might have to be removed entirely via surgery. Tumours of other glands can be treated similarly: some tumours might be androgen- or oestrogen-dependent, so drugs that inhibit these pathways can help, and radiation might also help for some other tumours. For example, radioactive iodine can destroy a thyroid gland tumour.

Now let's look at how pituitary tumours can cause a deficiency of hormones! Firstly, tumours can actually end up destroying the pituitary, as they can compress their own blood supply. At the same time, they are disrupting the flow of hormones from the hypothalamus to the pituitary. This can be treated via hormone replacement, just as insulin can treat diabetes or exogenous T4 can treat hypothyroidism.

There are also other causes of hypopituitarism that you should know about. In Sheehan's Syndrome, the vascular system supplying the piutitary collapses following an obstetrical haemorrhage. This causes pan-hypopituitarism, or lack of all hormones from the anterior pituitary. Another cause of hypopituitarism is pituitary stalk transection, where a blunt force trauma can cause the pituitary stalk to tear. This also causes pan-hypopituitarism, with one exception: prolactin is elevated as it's no longer being suppressed by dopamine.

And that's lecture 1 done!

No comments:

Post a Comment