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Theme 2 : THYROID DISEASES
Study goals:

To recollect main points in physiology and anatomy relatively to thyroid
structure and function.

To acquaint students with aetiology, pathogenesis, clinical sighs, and specific
investigations of common thyroid diseases.

To learn general principles of treatment of thyroid diseases.
Duration of the lecture: 2 hours
Learning resources: schemes, multimedia, text books.
Plan of the lecture:
1. Core concepts in anatomy and physiology
2. Hyperthyroidism
3. Hypothyroidism
Learning resources: schemes, multimedia, text books.
1.

CORE CONCEPTS IN ANATOMY AND PHYSIOLOGY

Thyroid gland consists of two lobes (right and left) one on either side of the
trachea and isthmus which connects them together in the front of the neck
The thyroid gland produces three hormones: triiodothyronine (T 3), thyroxine
(T4) and thyrocalcitonin (calcitonin, TCT). Iodine is necessary in the thyroid hormone
synthesis. Adequate iodine intake should be 150-200 µg per day.
Thyroid hormones are involved in the regulation of the following physiological
processes:
 Growth and development
 Thermoregulation, calorigenesis
 Cardiovascular effect
 Metabolism of proteins, carbohydrates, and lipids
The secretion of T3 and T4 are under the control of thyroid-stimulating hormone
(TSH), which is in turn under thyrotropin-releasing hormone (TRH).
Iodine (organic and inorganic) is absorbed in gastrointestinal tract in the form of
iodide. Iodide following active transport enters the thyroid gland. The trapped iodide
is oxidised by peroxidase system to active iodine. Active iodine iodinates the tyrosine
residue of glycoprotein and forms monoiodotyrosine (MIT) and diiodotyrosine (DIT).
This process is called iodide organification. Two molecules of DIT form T4. whereas
MIT with DIT produces T3 (condensation process).
20 % of T3 volume comes from thyroid gland secretion. Another 80% are
derived from T4 deiodination in peripheral tissues (liver, kidneys). Normal T3 is three
to five times more potent than T4. That’s why T4 is considered as prohormone, while
T3 as hormone.

 Usual period of life when Graves' disease frequently appears is 4th-5th decades.2 Impaired deiodination of T4 produce two types of T3: normal T3 and reverse T3 (without feedback effect). Functional state may be divided into: hypothyroidism. Hyperthyroidism (thyrotoxicosis) is the syndrome resulting from the excessive production of thyroid hormones. liothyronine). Thyrotoxicosis is the term which mostly used to denote excessive ingestion of thyroid hormones or iodine.  Other names of Graves’ disease are: Diffuse toxic goiter. which is usually characterised by hyperthyroidism. Basedow-Graves’ disease. while iatrogenic thyrotoxicosis is caused by hormone overdosing (levothyroxine sodium. other). Primary toxic goiter. goiter.  Graves’ disease is characterised by recidivations and remissions.5 % of the population suffers from hyperthyroidism in adults. thyroiditis. hyperthyroidism. GRAVES’ DISEASE  0. exophthalmos. 2. HYPERTHYROIDISM Hyperthyroidism is a common clinical condition of various diseases (Graves’ disease. euthyroidism. This means that certain thyroid disease may induce different functional changes and that certain functional disorder may be caused by wide variety of thyroid diseases. toxic adenoma. Thyroid diseases may be accompanied by functional derangement or/and morphological changes. Definition. The majority of hormones bind to thyroid-binding proteins: thyroxine-binding globulin (TBG) and to much lesser extent – thyroid-binding prealbumin (TBPA). Pretibial myxedema is considered as nonpitting edema of the pretibial areas. Aetiology  Hereditary predisposing markers in whites is HLA-B8 or -DR3. Iodine-induced thyrotoxicosis appears following chronic intake of inorganic iodine (amiodarone.  Graves’ disease occurs five-eight times more often in females than in males. Graves’ disease is hereditary dependent an autoimmune disease. Treatment of iatrogenic hyperthyroidism should be directed toward cancellation of hormone intake. Plummer’s disease. in Asians HLA-BW35.  Graves’ disease is the most common cause of hyperthyroidism. nodular and mixed. Thyroid morphology can be denoted as diffuse. . Exophthalmos is the pathologic protrusion of the eyeballs. potassium iodide). Goiter means thyroid enlargement. and pretibial myxedema.

auscultation).  Physical examination (visual inspection.  Musculoskeletal system (lean and exhaustion appearance. moist palms). muscle weakness). T3.  Instrumental investigations (ultrasonography. inner tension. pregnancy. anxiety. poor concentration.  Inability of antigen-specific T-suppressor to inhibit T-helper activity results in the unregulated generation of TSH receptor antibodies. as suspected may be also originated from TSH receptor like antigens presented in some bacteria and viruses. antibodies to thyroid peroxidase). hyperdefecation with predisposition to diarrhoea). sweating.  Thyroid gland (usually enlargement).  The higher level of TSI the more severe is hyperthyroidism.  TSH receptor antibodies bind to TSH receptors presented on the thyroid follicular cell and stimulate thyroid hormone production.  Eyes (wide-eyed stare.  Triggering factors: viruses and bacterial infections (Spumaviruses.  Cardiac system (tachycardia). radioisotope studies). Mycoplasma).  TSH receptor antibodies. “angry look”). Yersinia enterocolitica.3  Defect of antigen specific T supressor. tremor).  Laboratory findings (TSH.  TSH receptor antibodies is considered as thyroid-stimulating immunoglobulins (TSI).  Skin (warm. T4. Clinical picture  Nervous system (nervousness. Pathogenesis  Thyrocytes express HLA and together with thyroid specific antigen bind T-helper through T-cell T3 receptor complex stimulating B cells to produce antibodies against TSH receptor.  Gastrointestinal system (hunger and weight loss. TSI. climbing. Diagnostic approach  Inquiry of the patient (anamnesis of the disease and life). palpation. emotional crisis. emotional lability. reduced muscles ability in walking. .

nitrate. pertechnetate. thiocyanate) in the different drug compositions competitively inhibit accumulation of iodide. or once a day in the morning.5-1 g per day q. myalgia. Used only if other treatment are contraindicated.i. nitrate. Medicamentous therapy Pathogenetic treatment Agents that inhibit iodide trapping  Potassium perchlorate and other monovalent anions such as pertechnetate. Propylthiouracil. jaundice. Adverse effects The usual side effects include fever.i.d. Onset of thionamides effect takes within 3-4 weeks until the thyroid stores of T3 and T4 become depleted. except Potassium perchlorate that may be administered in the treatment of Iodine-induced thyrotoxicosis. nausea. The most common problem is hypothyroidism as a result of long-lasting . These drugs are now obsolete and mostly no longer used. Cabbages contain thiocyanate and is called goitrogenic vegetable. skin rash. Dosage: 0. Dosage: 30-60 mg per day t.d. Subtotal thyroidectomy (surgery). Thiamazole. thionamides (Thiamazole and Propylthiouracil) suppress iodide organification and condensation. Radioiodine therapy (radical treatment). 2. They decrease the synthesis of T3 and T4 blocking iodide into tyrosine incorporation and condensation of monoiodotyrosine and diiodotyrosine. 3. Dosage: 300-600 mg per day q.4 Treatment approach 1. Medicamentous therapy (pathogenetic and symptomatic treatment ).d. Agents that inhibit the synthesis of thyroid hormones  Thiamazole (Mercazolilum)  Propylthiouracil (Propacil) In order to inhibit synthesis.i. arthralgia. It is suggested that both of them are able to inhibit synthesis of TSI. and thiocyanate in the different drug compositions Monovalent anions (perchlorate. Discontinuation of potassium perchlorate worsen thyrotoxicosis. Propylthiouracil additionally inhibit peripheral T 4 conversion into T3 or activate T4 transformation into inactive reverse T3. Potassium perchlorate. Effect of their action is reversible. Drug’s abolition causes immediate surge in T 3 and T4 with aggravation of clinical status. Adverse effects Aplastic anaemia which may be fatal is the main side effect.

anxiety.  Iopanoic acid (Telepaque). Large doses of dexamethasone also inhibit peripheral conversion of T4 to T3. High levels of iodide inhibit the synthesis of thyroid hormones while small doses. . are necessary in hormone synthesis.i. sweating). Its effect is reversible. Dosage: 8 mg per day. Symptomatic treatment  Beta-adrenergic blockers  Corticosteroids Beta-adrenergic blockers do not cure the thyroid gland but inhibit sympathetic reactions (tremor. Sodium ipodate and iopanoic acid are radiographic contrast agents. and headache. As the euthyroid state is obtained. Dexamethasone. Agents that decrease thyroid hormone release  Potassium or sodium iodide (Lugol’s Solution). 2-4 weeks therapy may be indicated for severe hyperthyroidism. It can be used when prepare patients for surgery. nervousness. on the contrary. They additionally possess potent property to inhibit peripheral conversion of T4 to T3 . Dosage: 80-120 mg per day t. because iodine reduces thyroid vascularity. Besides. Adverse effects The most common adverse effects are: rash.  Sodium ipodate (Oragrafin). Sodium ipodate and iopanoic acid. Adverse effects Beta-adrenergic blockers mask real patient feelings thus making clinical observation unusable. pruritus. the thyroid gland escapes the iodide press with large resulting concentration of iodide.d. Sudden withdrawal of iodides precipitates thyroid storm. Propranolol. hypersalivation.5 treatment. dose should be tapered and subsequently discontinued. Dosage: 5 drops (by 200 mg iodide) per day. Potassium iodide. Drug interactions Propylthiouracil can cause hypoprothrombinaemia. Thionamides cause thyroid enlargement because the negative feed-back effect to TSH is absent. sore gums. tachycardia. Agranulocytosis is reported rare. Nevertheless iodide suppression is not beneficial for long lasting treatment (more than 10 days). Dosage: 1 g per day. nonselective beta blockers produce modest reduction in serum T 3 level by blocking conversion T4 to T3. Subsequently.

It emits gamma (X-rays) and beta rays.  Lack of thyroid hormones in childhood produces cretinism (mental and physical retardation). in a pregnant patients with serious contraindications to other therapy. when Graves’ disease is accompanied by advancing ophthalmopathy. Subtotal thyroidectomy Surgery treatment should be considered in cases that suggest possible malignancy (nodule. Hypothyroidism is the syndrome that is characterised by thyroid hormone deficiency. HYPOTHYROIDISM  Hypothyroidism may occur as a result of thyroid and non-thyroid disorders. secondary. Definition. Another problem is hypothyroidism which develops at the rate of 10-15% in the first year after I 131 treatment. and peripheral causes. Radioiodine-131. while beta-radiation destroys overactive tissue.  Primary pathologic base includes Hashimoto disease.6 Radioiodine therapy Radical treatment  Radioactive iodide I131 (Iodotope) Radioactive iodide behaves like dietary iodide and accumulates in the storage follicles. hoarseness. tertiary. Adverse effects I131 therapy causes acute release of thyroid hormones usually about 5-10 days after ingestion as a result of ablation of thyroid tissue. . pain. Aetiology  Hypothyroidism may develop as a result of primary. because of the potential carcinogenic effect in young adults and children. 3. I 131 should be given only to people beyond their reproductive years. Dosage: usually 4-10 mCi (millicurie) in the correspondence to the following calculation – 60-80 µCi/g of the thyroid estimated weight. state after radioactive iodine or surgical treatment of Graves disease or in the late stages without such therapy.  Thyroid hormone deficiency is presented with myxedema which denotes specific nonpitting edema. X-rays alter thyroid growth and activity. rapid growth of the goiter).

swollen periorbital tissue).  Eyes (drooped eyelids. etc.7 different thyroiditis. high level of creatinine phosphokinase). nonpitting edema. slow speech. Pathogenesis  Pathogenesis depends on the type of hypothyroidism. hereditary inability to synthesise thyroid hormones. reduced voltage of the ECG and flat T waves).  Secondary and tertiary causes involve congenital or acquired pathologies of pituitary gland and hypothalamus respectively. etc. hypogonadism. ascites). pernicious anaemia. enlargement suggests Hashimoto thyroiditis with hypothyroid state). congenital aplasia. TSH stimulates thyroid enlargement. dry. Increased levels of peripheral hormones try to compensate tissue resistance. and T3 levels are high.  Reproductive system (amenorrhea. drowsiness. formation of cysts.  Thyroid gland (small as a result of hypoplasia or aplasia. cardiomegaly.  Cardiac system (bradycardia.  Skin (coarse features.  Primary hypothyroidism is characterised by decreased T4 and T3 concentration that causes elevation of TSH and prolactin (PRL). predisposition to obstipation.  Musculoskeletal system (joint effusions. scaly.  Secondary and tertiary hypothyroidism present with low TSH level that is usually accompanied with deficiency of other anterior pituitary hormones results in hypocorticism. T4. Diagnostic approach .  In peripheral hypothyroidism TSH. signs of intellectual and memory impairment.  Peripheral hypothyroidism may be presented following peripheral tissue resistance to effect of thyroid hormones or loss of hormones during nephritis or enterocolitis. depression). thick. severe lack of iodine in environment. adenomas. and cool skin. muscle cramps. arthralgia. achlorhydria.  Gastrointestinal system (weight gain. etc. yellowish colour due to carotenaemia). PRL causes galactorrhea and amenorrhea.  Mucopolysaccharide (hyaluronic acid and chondroitin sulphate) infiltration of the tissue is the base of specific clinical appearance of edema. galactorrhea). Clinical picture  Nervous system (myxedema madness.

growth and maturation.8  Inquiry of the patient (anamnesis of the disease and life). palpation. Adverse effects. Hypothyroidism General Treatment is directed at replacement of the thyroid hormone deficiency. intravenous beta-blocker. potassium iodide. It is a medical emergency. Elderly patients or those known to have ischaemic heart disease must receive low initial doses with slow increments since angina. infarction.  Laboratory findings (TSH. auscultation). (sodium levothyroxine) 2. magnetic resonance imaging scan). Two preparations are available: thyroxine (T4) and tri-iodothyronine (T3). Pharmacokinetics Both T4 and T3 are adequately absorbed following oral administration. Dosage: 50-200 µg/day Synthetic triiodothyronine (Liothyronine). FT4 . tachyarrhythmias or heart failure can be precipitated. Triiodthyronini hydrochloridum (Liothyronine) 3. fever.  Instrumental investigations (ultrasonography. radioisotope studies. hyperlipidemia). TRH tests. Dosage: Thyroid crisis Clinical features are delirium. Treat with: rehydration.  Physical examination (visual inspection. T4. Dosage: Synthetic T4–T3 combination (Liotrix). tachycardia. Both undergo liver conjugation and enterohepatic circulation. dehydration and diarrhoea. Synthetic T4–T3 combination (Liotrix) Synthetic thyroxine (Sodium levothyroxine). Excess dosage produces the features of hyperthyroidism. T4 has a half-life of about a week and T3 of about 2 days. although the latter is rarely used. Treatment approach  Replacement therapy 1. carbimazole and dexamethasone. These are related to physiological and pharmacological actions of thyroid hormone. Mechanism These preparations provide replacement therapy by stimulation of metabolism. anaemia. T3. Dose .

Diagnosis. Pathogenesis. Prohormone. Pathogenetic treatment. HYPOTHYROIDISM Cretinism. Adequate iodine intake. Condensation. Goiter.9 Thyroxine: Starting dose is 0. Pathogenesis. Pretibial myxedema. Diagnosis. HYPERTHYROIDISM Graves’ disease. Aetiology. Radioiodine therapy. Medicamentous therapy. Thyroid hormones. Clinical picture. Exophthalmos. Hypothyroidism. Agents that decrease thyroid hormone release. Myxedema. meanings and explanations given below in the order of their appearance: CORE CONCEPTS IN ANATOMY AND PHYSIOLOGY Thyroid gland. Physiological processes. Subtotal thyroidectomy. Thyrotoxicosis. Agents that inhibit iodide trapping. Iodine-induced thyrotoxicosis. After studying this chapter you should know the following terms. TBG. Organification. TRH. Clinical picture. Radical treatment. Symptomatic treatment. TSH.05 mg/day (0. Deiodination in peripheral tissues.025 mg/day if old or with heart disease) with dose increments every 2-3 weeks depending on thyroid function. Aetiology. . Agents that inhibit the synthesis of thyroid hormones. Iatrogenic hyperthyroidism.