Hypothalamic–Pituitary–Thyroid Axis (HPT-Axis)

00:01 Before we begin the discussion of thyroid pathology, let’s first take a look at normal functioning and a review quickly of thyroid hormone synthesis.

00:12 Let’s begin.

00:15 HPT overview: hypothalamus, pituitary, thyroid axis… the classic prototype physiologically of your negative feedback mechanism.

00:28 Up until now, we’ve looked at one major positive feedback mechanism and that was in fact oxytocin.

00:37 Here, with hypothalamus releasing TRH; please do not forget that TRH is also responsible for also releasing prolactin from the anterior pituitary.

00:49 Now, we then land upon the anterior pituitary, released TSH.

00:55 TSH will then bind to a very important receptor on your thyroid gland known as your TSH receptor.

01:03 That becomes important to you pathologically in Graves’ disease where type II hypersensitivity type of thyroid stimulation immunoglobulin is then going to bind to the TSH receptor.

01:13 We’ll talk further when we get into details about thyroid hormone synthesis a very important symport called your sodium iodide symport.

01:25 From your thyroid, you are then going to release T4 in great quantity 20 to 1, 15 to 1 depends as to whom you speak to, but point being is T4 is released in much greater concentration of ratio than T3.

01:40 And then all of the different organs that your thyroid hormones then works upon it could be the liver, it could be the intestine, it could be the heart, it could be just about everything and anything including your bones.

01:55 In this picture, you have two columns.

02:02 On the left, you have stimulatory and on the right, inhibitory and as and when I can, I’ll go ahead and start putting in clinical applications.

02:12 We begin with stimulation with alpha-adrenergic agonists, the opposite of this would be alpha-adrenergic blockers.

02:21 Inhibitory… also keep in mind that you can have nodules within this thyroid gland and when you do remember that sometimes it could be a space occupying lesion and therefore, decreased release of your thyroid hormones or really anywhere up and down your axis, you could have a tumour that’s inhibiting the release as space occupying lesion.

02:43 Stimulatory… TRH, estrogen; inhibitory… somatostatin, dopamine for the most part, think of it as being or exhibiting inhibitory type of action on your thyroid gland.

02:57 Dopamine, however, in terms of inhibitory action would be with prolactin and perhaps shares a little bit of inhibition with growth hormones.

03:08 Glucocorticoids, chronic illnesses… chronic illnesses is very important for us.

03:12 How do you feel when you’re ill? Not too energetic, maybe if there were symptoms that you wanted to equate it to, it would be more so along the lines of hypothyroidism.

03:25 We’ll talk a little bit more about chronic illness.

03:29 Stimulatory… TSH, TSH receptor, stimulating antibodies is the full phrase there, Aby standing for antibodies whereas inhibitory… TSH receptor blocking antibodies and so, here, if you’re thinking about, once again, some type of autoimmune disease such as Hashimoto, then keep in mind that at any point during the thyroid hormone synthesis and release, you could have destruction of thyroid hormone synthesis.

04:04 We’ll talk more later.

04:06 Iodine could be both inhibitory or stimulatory, keep that in mind.

04:10 The way that it could be stimulatory is that if you required to synthesize thyroid hormone then iodine obviously will be responsible for the key element of creating a thyroid hormone or if there was too much iodine, at some point in time, you might have a negative feedback.

04:28 But, in both instances, keep in mind that you may result in goiters… iodine deficiency or iodine excess.

04:37 Lithium is a big one; lithium… two major organs that lithium is responsible for causing dysfunction and that you’re responsible for.

04:46 Number one, thyroid gland and number two, down the kidneys will bring in about a nephrogenic type of diabetes insipidus picture.

05:01 The thyroid gland itself and its histology.

05:03 What you’re seeing in the image is the middle area that is homogenously eosinophilic and pinkish then surrounded by a boundary of what’s known as your follicular epithelial cells.

05:21 Now, what we’ll do further is and what you’ve already done is take the follicular epithelial cell and have your basolateral side facing the blood… B basolateral, B blood… and then the apical membrane which is then facing the colloid, that homogenously pink region that is then responsible for housing or storing your thyroid hormones.

05:46 Thyroid hormones are made in the follicular epithelial cell, as we shall see, the key element there being iodine; regulated by TSH.

05:56 Remember, every single thyroid tissue or cell has a TSH receptor.

06:04 That TSH receptor will be incredibly important for us to stimulate or initiate thyroid hormone synthesis because it brings about sodium iodide symport, as we shall see.

06:15 Serum T3 and T4 are then bound, once they get into circulation.

06:20 Remember, these are lipid soluble, hmm? Prior to this, they were water soluble.

06:25 What do I mean? The TSH receptor on the thyroid gland… water soluble IG protein type of signal transduction.

06:34 But, when the thyroid hormone gets into circulation, you know darn well that its effects within the nucleus in transcription/translation and such is extremely, extremely critical and quite effective.

06:50 So, therefore, it will pass through the membrane; so, therefore, you-you need to make sure that you’re able to regulate that.

06:57 And so, therefore, the liver then produces what’s known as your binding globulin… liver; not inside my thyroid gland right now.

07:05 What I’ll show you in a little bit is your thyroglobulin and I’ve asked you a number of times do not get the two confused and you want to keep things… keep these separate clinically, as you shall see.