Page 290 - Color Atlas Of Pathophysiology (S Silbernagl Et Al, Thieme 2000)

Causes of Hypothyroidism, Hyperthyroidism and Goitre
The hormones thyroxine (T 4 ) and triiodothyro- cess (inhibition of H 2 O 2 formation by exces-
–
nine (T 3 ) are formed in the epithelial cells sive I );
(thyrocytes) that surround the follicles of the 4. Abnormal breakdown of thyreoglobulin;
thyroid gland. Their synthesis is achieved in 5. Defective iodine incorporation (peroxidase
several steps, each of which can be disrupted. is involved in this, too);
Iodine is essential for the synthesis of the hor- 6. Defective coupling of two iodinated tyro-
mones and has to be supplied in food (→ A1). sine residues;
Iodine is taken from the blood into the follicu- 7. Inability to release thyroxine and triiodo-
lar epithelial cells by means of a transporter thyronine, from thyroglobulin (genetically
+
coupled to Na (→ A2). At the apical mem- determined or lithium);
brane of the cells it passes into the follicular 8. Lack of sensitivity of the target organs due
lumen by exocytosis and is oxidized there to receptor defects or inadequate conver-
(→ A3). sion into the more effective T 3 decreases T 3 /
A tyrosine-rich protein (thyroglobulin, TG) T 4 effectiveness even if T 3 /T 4 release is nor-
is formed in the epithelial cells (→ A4) and se- mal or even raised.
creted into the follicular lumen, too. Here the Furthermore, mutations of the TSH receptors
Hormones to the residues of diiodotyrosine (DIT) or of can be stimulatd by TSH. However, genetic de-
can change the degree to which the thyroid
tyrosine residues of the globulin are iodized
fects of receptors and enzymes of T 3 /T 4 syn-
monoiodotyrosine (MIT) (→ A6). The thyroid
in the follicular lumen. When stimulated to
Two very common causes of hypothyroid-
9 hormones are stored as thyroglobulin colloid thesis are rare.
do so by the thyroid-stimulating hormone ism are inflammatory damage to the thyroid
(TSH; see below), globulin is again taken up gland or surgical removal of the gland (due to
into the follicular epithelial cells and thyroxine thyroid cancer). More rarely hypothyroidism
and to a lesser extent triiodothyronine, is split is due to a deficiency of TSH (e.g., in pituitary
off from the globulin (→ A7). One iodine is re- insufficiency) or of TRH (e.g., in damage to the
moved from T 4 in the periphery by a deiodin- hypothalamus).
ating enzyme (deiodinase) and thus converted The most common cause of an increased re-
into the more active T 3 (→ A8). lease of thyroid hormone (hyperthyroidism) is
Regulation. Formation and release of T 3 and long-acting thyroid stimulator (LATS) or thy-
T 4 as well as growth of the thyroid gland are roid-stimulating immunoglobulin (TSI), an IgG
stimulated by thyrotropin (TSH) from the that apparently “fits” into the TSH receptor
anterior pituitary. Its release is, in turn, stimu- (Graves’ disease). This results, among other ef-
lated by thyroliberin (TRH) from the hypothal- fects, in stimulation of hormonal release and
amus. Stress and estrogens increase TSH re- thyroid enlargement. TSH release is suppress-
lease, while glucocorticoids, somatostatin, ed by a high T 3 /T 4 level. Other causes of hyper-
and dopamine inhibit it. thyroidism are orthotopic or ectopic thyroid
The causes of a lowered release of thyroid hormone–producing tumors, inflammation of
hormone (hypothyroidism) are usually found the thyroid (thyroiditis), increased release of
in the thyroid itself. Abnormal synthesis of thy- TSH, or excessive supply of thyroid hormones.
roid hormones can be brought about by any Enlargement of the thyroid gland (goitre) is
one of the following steps in their synthesis: the result of uncontrolled growth (tumor), or
1. Decreased iodine intake in food; of increased stimulation by TSH or TSI. In this
2. Impaired iodine uptake in the thyroid cells situation release of thyroid hormones can ei-
(genetically defective carrier or inhibition ther be reduced (e.g., in marked iodine defi-
of transport by perchlorate, nitrate, thiocya- ciency and the above-mentioned enzyme de-
nate (rhodanate); fects) or increased (e.g., in Graves’ disease).
3. Peroxidase deficiency (genetic) or peroxi-
280 dase inhibition by thiouracil or iodine ex-

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