1. Diseases of thyroid gland
Dominika Kanikowska
Department of Pathophysiology
2016/2017
Diseases of thyroid gland
Bibliography:
1. Zarys patofizjologii narządowej. Breborowicz A. Poznań
2. Patofizjologia. Damjanow I. Wrocław
3. Choroby wewnętrzne. Szczeklik A. Kraków
4.Medical Physiology. Guyton and Hall th ed.

2. Thyroid gland

3. Thyroid hormones
Tetraiodothyronine, thyroxin (T4); accounts for about 90% of the hormones secreted by the thyroid gland, and has a half-life of 7 days.
Triiodothyronine (T3); is another biologically active form of the thyroid hormone, accounting for 10% of the total hormone secreted by the thyroid gland, with a half-life of 18 h.
In the circulation, thyroid hormones circulate predominantly (99%) bound to carrier proteins:
Thyroxin-binding globulin (TBG): 70% of the T3 + T4
Transthyretin: 10-15% of the T3 + T4
Albumin: 15-20% of the T3 + T4
Lipoproteins: 2% of the T3 + T4
Free T4 and T3 account for less than 1% of the total amount of thyroid hormone in the blood and represents the active form of both hormones. Free T4 and T3 also provide negative feedback to the pituitary gland and hypothalamus.

4. Organ-specific Effects of Thyroid Hormones
Tissue
Effects
Cardiovasular system
Cardiac inotropic and chronotropic effects,↑cardiac output and blood volume,↓systemic vascular resistance.
Fat tissue
White adipose tissue differentiation, lipogenic enzymes and intracellular lipid accumulation. Hyperthyroidism enhances lipolysis.
Muscles
Proteolysis.
Bone
Bone growth and development through activation of osteoclast and osteoblast activities. Deficiency/excess during childhood affects growth (dwarfism/giganticism). In adults, excess thyroid hormone levels leads to osteoporosis and acromegaly.
Nervous system
Essential for brain development and maturation in infancy and childhood.
Digestive system
Increased carbohydrate absorption.
Increased intestinal peristalsis.

5. Structure and function of the thyroid follicular cell
1. Follicular epithelial cells synthesize thyroglobulin (TG) and secrete it into the lumen of the follicles as a colloid. 2. The synthesis of the thyroid hormones requires iodine, which is taken up by the follicular cells from the interstitial fluid (“iodine trapping”). 3. Iodine is transported to the colloidal surface by a transport protein and “organified,” that is, attached to tyrosine to form monoiodotyrosine (MIT) and diiodotyrosine (DIT). 4. Coupling of these iodinated tyrosine derivatives leads to the formation of triiodothyronine (T3) and tetraiodothyronine (thyroxine,T4). 5–6. Thyroglobulin is then endocytosed into the cytoplasm of follicular cells and cleaved by proteolysis, ultimately resulting in the formation of free T4. This process also leads to removal of iodine from monoiodotyrosine and diiodotyrosine molecules. 7. The iodine is recirculated. 8 and 9. Thyroxine is partly converted to T3 by 5′-monodeiodinase, and both T3 and T4 are released into the blood
jod

6. Hyperthyroidism
Pituitary adenoma
Nodular goiter or solitary hyperfunctioning adenoma
Graves’ disease
Thyroiditis
Other causes

7. Pituitary hyperthyroidism
Pituitary hyperthyroidism - tumors secreting TSH.
Hyperactivity is accompanied by elevated levels of TSH in the blood.

8. Nodular Goiter or Solitary Hyperfunctioning Adenoma
Adenoma within the thyroid gland producing thyroid hormones; if unchecked leads gradually to hyperactivity.
Nodular goiter (15%).
Hyperfunctioning adenoma (5%)

9. Thyroiditis
Etiology: viral, bacterial, after radiotheraphy or post-traumatic.
Sudden onset of fever and local soreness.
Excessive, uncontrolled release of the hormones that have been stored in the gland hormones (bound to thyroglobulin).

10. Graves’ Disease
Hyperthyroidism – an autoimmune condition caused by stimulation by TSH-like antibodies of the TSH receptor.
The disease is caused by exposure to factors (e.g. bacterial or viral antigens) in those people with a genetic predisposition.
50% of patients have: goiter, exophthalmos, tachycardia.
Pretibial myxedema (5% of patients).

11. Proposed pathogenesis of Graves' disease
TSH, thyroid-stimulating hormone; T3, triiodothyronine; T4, thyroxine
CMAJ. Mar 4, 2003; 168(5): 575–585.

12. Pretibial myxedema Thyroid. Sep 2008; 18(9): 953–958.
Indian J Dermatol May-Jun; 57(3): 247–248.

13. Severe bilateral exophthalmos - Graves’ disease
The Canadian Journal of Plastic Surgery 2003;11(4):

14. Hyperthyroidism- Graves’ disease

15. Effects of hyperthyroidism on the cardiovascular system and possible outcomes.
TBV, total blood volume;
LVEDV, left ventricular end-diastolic volume;
LVESV, left ventricular end-systolic volume;
SV, stroke volume;
SVR, systemic vascular resistance;
CO, cardiac output;
↑ increased; ↓ decreased.
Solid arrows indicate
direction of effects, and
dashed arrows potential outcomes.
Heart. Oct 2000; 84(4): 455–460.

16. Electrocardiographic changes associated with hyperthyroidism.
BMJ. Jun 1, 2002; 324(7349): 1320–1323.

17. Other Causes of Hyperthyroidism
Increasing the supply of iodine in people with hypothyroid goiter.
Hyperthyroidism in pregnancy.
Drugs –e.g. Amiodarone.

18. Thyrotoxic Crisis
Severe symptoms of hyperthyroidism, resulting from short-term hyper-secretion of thyroid hormones (e.g. after surgery on hyperactive thyroid).
Strong CNS stimulation, ↑ body temperature, sweating and diarrhea, dehydration, supraventricular tachycardia, atrial fibrillation.

19. Hypothyroidism Hypothalamic insufficiency Hypopituitarism
Disorders of the thyroid gland:
A. Congenital (thyroid hypoplasia, metabolic defects).
B. Acquired.

20. Hypothyroidism
Disorders within the thyroid gland:
The destruction of the thyroid gland by inflammatory processes;
The presence of antibodies against the receptor for TSH;
Destruction of the thyroid gland as a result of radiotherapy or surgery in people treated for hyperthyroidism;
Iodine deficiency or excess;
Drugs which inhibit the synthesis of thyroid hormones (e.g. lithium salts).

21. Chronic Thyroiditis (Hashimoto’s thyroiditis)
The most common type of thyroiditis and the most common cause of hypothyroidism.
Familial predisposition.
Often coexists with other autoimmune diseases.
Diagnosis is based on the finding:
anti-thyroid peroxidase antibodies;
anti-thyroglobulin antibodies.
In fine-needle aspiration biopsy of the thyroid gland, inflamation with lymphocyte infiltration can be seen.

22. Possible pathogenic mechanism of Hashimoto's thyroiditis
J Autoimmune Dis. 2005; 2: 1.

23. Hypothyroidism

24. Electrocardiographic changes associated with hypothyroidism.
BMJ. Jun 1, 2002; 324(7349): 1320–1323.

25. Patients with: a. hyperthyroidism b. hypothyroidism