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ENDOCRINOLOGY (/ENDOCRINOLOGY/NOTES)

Thyroid physiology

OTES

Overview

The thyroid is an endocrine gland responsible for the production of thyroid hormones

T3 and T4.

he major functional cells of the thyroid are the follicular cells. These are arranged into hollowpheres that form a functional unit termed a follicle.

Within these follicles is a central lumen containing colloid; the extracellular storage site for

hyroid hormone. Colloid is composed largely of thyroglobulin (Tg) a glycoprotein involved in

hyroid hormone synthesis.

arafollicular C cells secrete calcitonin, a hormone involved in calcium regulation.

Hypothalamic-pituitary-thyroid axis

Thyroid hormone release is controlled by the hypothalamic-pituitary-thyroid axis.

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Thyrotropin releasing hormone

RH is secreted from the paraventricular nucleus of the hypothalamus. As the name suggests

is a tropic hormone i.e one that acts upon another endocrine gland.

reaches the anterior pituitary via the hypophyseal portal system. Here it causes the release

f  thyroid stimulating hormone.

. Thyroid stimulating hormone

SH, produced by the thyrotrophs of the anterior pituitary, is released following stimulation

y TRH.

ransported in the blood, TSH acts upon the thyroid gland promoting the synthesis and

elease of thyroid hormone.

. Triiodothyronine and thyroxine

he thyroid is stimulated to synthesise and release thyroid hormone by TSH. The thyroid

roduces two hormones, thyroxine (T4) and triiodothyronine (T3). 

hese thyroid hormones complete a negative feedback loop through the suppression of TRH

nd TSH release.

hough T3 is more biologically active than its counterpart T4, secreted thyroid hormone is

0% T4. Peripherally much of T4 is converted to T3.

oth are highly lipophilic, act on intracellular receptors and bind to thyroxine-binding globulin

TBG) in the blood. Only the ‘free pool’ is active: <0.1% T4 and <1% of T3.

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he e! ects to T3/T4 are numerous:

BMR: increases the basal metabolic rate.

Metabolism: it has anabolic e! ects at low serum levels and catabolic e! ects at higher levels.

Growth: increases release and e! ect of GH and IGF-1.

Cardiovascular: increases the heart rate and contractility through increasing sensitivity to

catecholamines.

Thyroid hormone synthesis

Thyroid hormone has two constituents, tyrosine and iodine.

ackground

hyroid hormone is made with two basic building blocks:

Tyrosine (amino acid) - synthesised by the body.

Iodine - obtained in the diet and reduced to iodide before being absorbed in the small

intestines.

hese building blocks are assembled on the glycoprotein thyroglobulin (Tg) and synthesis

ccurs in the central colloid.

Preparation

odide enters the cell across the basolateral membrane via a sodium symporter. This process is

riven by secondary active transport mediated by a Na /K -ATPase pump.

t the luminal membrane, iodide is activated by thyroperoxidase (TPO) before entering the

olloid via the ion exchanger Pendrin.

+ +

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hyroglobulin, containing tyrosine, is produced by Golgi complexes and the endoplasmic

eticulum in the follicular cells. The thyroglobulin/tyrosine complex is exocytosed across the

uminal membrane into the colloid.

. Synthesis

Within the colloid, one iodide may attach to a tyrosine (attached to a thyroglobulin) to form

monoiodotyrosine (MIT). This reaction is catalysed by TPO. A second iodide may attach toMIT to form di-iodotyrosine (DIT).

oupling of MIT and DIT yield the thyroid hormones. One MIT and one DIT gives

riiodothyronine (T3) while two DITs give thyroxine (T4).

. Release

When stimulated (by TSH) the surrounding follicular cells phagocytose a portion of theolloid. Once within the follicular cell, this vesicle is subject to lysosomes which act to release

he T3/T4 from Tg.

he thyroid hormones T3/T4 may then di! use into the blood stream. Any remaining MIT and

IT is deiodinated (a reaction catalysed by iodinase) and recycled.

alcitonin

Calcitonin is produced by the parafollicular C cells.

alcitonin release is stimulated by increases in serum calcium. It acts to lower calcium through

s action on numerous tissues:

Intestines: Reduces calcium absorption

Bones: Stimulates osteoblasts, inhibits osteoclastsKidneys: Inhibits phosphate reabsorption

is not an essential hormone, following thyroidectomy no hormonal replacement of calcitonin

required.

may be therapeutically to treat hypercalcaemia and osteoporosis. Furthermore, it can be

sed as a marker of recurrence in medullary thyroid cancer.

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