Thyroid gland disorder

THYROID GLAND DISORDERS

By Sara Sami Yuzuncu Yil University

2015


• GENERAL ASPECTS OF THYROID GLAND

– Anatomy: weight range from 12 to 30g

– Located in the neck, anterior to the traquea

– Produces: T4 & T3 (active hormone)

– Regulation: “negative Feed-back” axis

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Thyroid GlandThyroid Gland

THYROID DISORDERS

• GRAVE’S DISEASE• THYROID STORM• TOXIC THYROID NODULEHYPERTHYROIDISM

• HASHIMOTOS THYROIDITIS• CRETINISM• MYXOEDEMA• POSTPARTUM THYROIDITIS• SUBACUTE THYROIDITIS• SICK EUTHYROIDISM

HYPOTHYROIDISM

THYROID GLAND DISORDERS– THYROID GLAND REGULATION

“negative Feed-back” axis

– Hypothalamus

– (TRH positive effect)

– Pituitary glan

– (TSH, positive effect)

– Thyroid gland

T3 & T4

(negative effect)


• Thyroid hormones:The thyroid gland maintains the metabolic level of almost

all cells in the body by producing, in its follicular cells, two thyroid hormones: triiodothyronine (T3), and tetraiodothyronine (T4) or thyroxine– T4: (Thyroxine) is made exclusively in thyroid gland

• Ratio of T4 to T3 ; 5::1

• Potency of T4 to T3; 1::10

• T4 is the most important source of T3 by peripheral tissue deiodination “ T4 to T3 “

Hormones of the Thyroid GlandHormones of the Thyroid Gland

• Thyroxine (T4)• Principle hormone• Increases energy and protein metabolism

rate• Triiodothyronine (T3)• Increases energy and protein metabolism

rate• Calcitonin• Regulates calcium metabolism• Works with parathyroid hormone and

vitamin D

Chemistry of thyroid hormone productionChemistry of thyroid hormone production


The synthesis in the thyroid gland takes place in the following way:

• A. Dietary iodine (I2) is reduced to iodide (I-) in the stomach and gut is rapidly absorbed and circulates as iodide.

• B. Follicular cells in the thyroid gland possess an active iodide trap that requires and concentrates iodide from the circulating blood. Iodide is transported into the cell against an electrochemical gradient (more than 50 mV) by a Na+-I--symport. The iodide pump is linked to a Na+-K+-pump, which requires energy in the form of oxidative phosphorylation (ATP) and is inhibited by ouabain. The thyroid absorption of iodide is also inhibited by negative ions (such as perchlorate, pertechnetate, thiocyanate and nitrate), because they compete with the iodide at the trap. In the follicular cell, iodide passes down its electrochemical gradient through the apical membrane and into the follicular colloid. Iodide is instantly oxidised – with hydrogen peroxide as oxidant - by a thyroid peroxidase to atomic or molecular iodine (I0 or I2) at the colloid surface of the apical membrane. Thiouracil and sulfonamides block this peroxidase.

• C. The rough endoplasmic reticulum synthesises a large storage molecule called thyroglobulin. This compound is build up by a long peptide chain with tyrosine units and a carbohydrate unit completed by the Golgi apparatus. Iodide-free thyroglobulin is transported in vesicles to the apical membrane, where they fuse with the membrane and finally release thyroglobulin at the apical membrane.

• D. At the apical membrane the oxidised iodide is attached to the tyrosine units (L-tyrosine) in thyroglobulin at one or two positions, forming the hormone precursors mono-iodotyrosine (MIT), and di-iodotyrosine (DIT), respectively. This and the following reactions are dependent on thyroid peroxidase in the presence of hydrogen peroxide -both located at the apical membrane. As MIT couples to DIT it produces tri-iodothyronine (3,5,3`-T3), whereas two DIT molecules form tetra-iodothyronine (T4), or thyroxine. These two molecules are the two thyroid hormones. Small amounts of the inactive reverse T3 (3,3`,5`- T3) is also synthesised.

• E. Each thyroglobulin molecule contains up to 4 residues of T4 and zero to one T3. Thyroglobulin is retrieved back into the follicular cell as colloid droplets by pinocytosis. Pseudopods engulf a pocket of colloid. These colloid droplets pass towards the basal membrane and fuse with lysosomes forming phagolysosomes.

• F. Lysosomal exopeptidases break the binding between thyroglobulin and T4 (or T3). Large quantities of T4 are released to the capillary blood. Only minor quantities of T3 are secreted from the thyroid gland.

• G. The proteolysis of thyroglobulin also releases MIT and DIT. These molecules are deiodinated by the enzyme deiodinase, whereby iodide can be reused into T4 or T3. Normally, only few intact thyroglobulin molecules leave the follicular cells.

• H. TSH stimulates almost all processes involved in thyroid hormone synthesis and secretion.


The hypothalamic-pituitary-thyroid feedback system, which regulates the body levels of thyroid hormone.

NEGATIVE FEEDBACK

Thyroid hormones on pituitary

T3 & T4

TSH

T3 & T4

TSH

Control of thyroid gland activity• The hypothalamic-pituitary-thyroid axishypothalamic-pituitary-thyroid axis controls the thyroid gland

function and growth.•• a.a. The production and release of thyroid hormone is controlled by

thyroid-releasing hormone thyroid-releasing hormone (TRH)(TRH) from the hypothalamus.•• TRHTRH reaches the anterior pituitary via the portal system, where the

thyrotropic cells are stimulated to produce thyroid-stimulating hormone hormone (TSH) or (TSH) or thyrotropinthyrotropin.

• TSH is the only known regulator of thyroid hormone secretion in humans. TSH is released to the systemic blood, by which it travels to the thyroid gland. Here, TSH stimulates the uptake of iodide, and all other processes that promote formation and release of T4 (and T3).

• TSH activates adenylcyclase bound to the cell membranes of the follicular cells and increases their cAMP.

• T3 has a strong iinhibitory effect on TRH secretion, as well as on the expression of the gene for the TRH precursor.

Control of thyroid gland activity• b. Almost all circulating T3 is derived from T4. TSH also stimulates the

conversion of T4 to the more biologically active T3. • Most of the circulating thyroid hormones are bound to plasma

proteins, whereby the hormone is protected during transport. There is an equilibrium between the pool of protein-bound thyroid hormone and the free, biologically active forms (T3 and T4) that can enter the body cells.

• Thyroid hormones are lipid-soluble and they can easily cross the cellular membrane by diffusion.

• c. Inside the cell, T3 binds to nuclear receptors and stimulates cellular metabolism and increases metabolic rate.

• d. The concentrations of T3 and T4 in the blood are recorded by pituitary and hypothalamic receptors.

• This negative feedback system keeps the blood concentrations within normal limits, and there is only a minimal nocturnal increase in TSH secretion and T4 release.

Disorders of the Thyroid Gland

• Goiter is enlargement of thyroid gland• Simple goiter• Adenomatous or nodular goiter

• Hypothyroidism• Infantile hypothyroidism (cretinism)

• Myxedema• Hyperthyroidism• Graves disease• Thyroid storm

• Thyroiditis• Hashimoto disease

vHypothyroidism (Hashimoto’s disease, Goiter) and vHyperthyroidism (Graves’ disease)

THYROID GLAND DISORDERS• THYROID HORMONE EFFECTS:

– Affects every single cell in the body

–Modulates:

–Oxygen consumption

–Growth rate

–Maturation and cell differentiation

– Turnover of Vitamins, Hormones, Proteins, Fat, CHO

THYROID GLAND DISORDERS• THYROID HORMONE EFFECTS

– CALORIGENESIS– GROWTH & MATURATION RATE– C.N.S. DEVELOPMENT & FUNCTION– CHO, FAT & PROTEIN METABOLISM– MUSCLE METABOLISM– ELECTROLYTE BALANCE– VITAMIN METABOLISM– CARDIOVASCULAR SYSTEM– HEMATOPOIETIC SYSTEM– GASTROINTESTINAL SYSTEM– ENDOCRINE SYSTEM– PREGNANCY


• THYROID HORMONE EFFECTS

– CALORIGENESIS• Controls the Basal Metabolic Rate (BMR)

– CHO METABOLISM

• Increases:–Glucose absorption of the GI tract–Glucose consumption by peripheral tissues–Glucose uptake by the cells–Glycolysis–Gluconeogenesis– Insulin secretion



– GROWTH & MATURATION RATE

– C.N.S. DEVELOPMENT & FUNTION

• “ESSENTIAL” in the newborn to prevent development of “CRETINISMS” & to a normal “IQ”

• Modulation of brain cerebration

• Mood modulation


- FAT & PROTEIN METABOLISM

• Increase lipolysis and lipid mobilization with:

–Cholesterol– Triglicerides– Free fatty acids

– MUSCLE METABOLISM

• Modulates;

– Strength & velocity of contraction



– ELECTROLYTE BALANCE

• Low Thyroid hormones could induce hyponatremia

– VITAMIN METABOLISM

• Modulates vitamin consumption

– HEMATOPOIETIC SYSTEM

• Could induce anemia


– CARDIOVASCULAR SYSTEM• Hyperthyroidism, increases:

– Heart rate & myocardial strenght – Cardiac output– Peripheral resistances (Vasodilatation)– Oxygen consumption– Arterial pressure

• Hypothyroidism, reduces:– Heart rate & myocardial strenght– Cardiac output– Peripheral resistances (Vasodilatation)– Oxygen consumption– Arterial pressure

THYROID GLAND DISORDERS• DIVIDED INTO:

– THYROTOXICOSIS (Hyperthyroidism)• Overproduction of thyroid hormones

– HYPOTHYROIDISM (Gland destruction)• Underproduction of thyroid hormones

– NEOPLASTIC PROCESSES• Beningn• Malignant

THYROID GLAND DISORDERS• TSH High usually means Hypothyroidism

– Rare causes:• TSH-secreting pituitary tumor• Thyroid hormone resistance• Assay artifact

• TSH low usually indicates Thyrotoxicosis

– Other causes• First trimester of pregnancy• After treatment of hyperthyroidism• Some medications (Esteroids-dopamine)


• THYROTOXICOSIS: –is defined as the state of thyroid hormone

excesss • HYPERTHYROIDISM: –is the result of excessive thyroid gland

function

THYROID GLAND DISORDERS• Abnormalities of Thyroid Hormones

– Thyrotoxicosis • Primary• Secondary• Without Hyperthyroidism• Exogenous or factitious

– Hypothyroidism• Primary• Secondary• Peripheral

THYROID GLAND DISORDERS• Causes of Thyrotoxicosis:–Primary Hyperthyroidism• Grave´s disease• Toxic Multinodular Goiter• Toxic adenoma• Functioning thyroid carcinoma metastases• Activating mutation of TSH receptor• Struma ovary•Drugs: Iodine excess

THYROTOXICOSIS

• Symptoms:– Hyperactivity– Irritability– Dysphoria– Heat intolerance &

sweating– Palpitations– Fatigue & weakness– Weight loss with

increased appetite– Diarrhea– Polyuria– Sexual dysfunction

• Signs:– Tachycardia– Atrial fibrillation– Tremor– Goiter– Warm, moist skin– Muscle weakness,

myopathy– Lid retraction or lag– Gynecomastia– * Exophtalmus– * Pretibial myxedema

THYROID GLAND DISORDERS• Treatment:

– Reducing thyroid hormone synthesis:• Antithyroid drugs (Methimazole, Propylthyouracil)• Radioiodine (131I)• Subtotal thyroidectomy

– Reducing Thyroid hormone effects:• Propranolol• Glucocorticoids• Benzodiazepines

– Reducing peripheral conversion of T4 to T3• Propylthyouracil• Glucocorticoids• Iodide (Large oral or IV dosage) (Wolf-Chaikoff effect)

Thyrotoxicosis results in an increase in metabolic rate. This may result in: Smooth, moist, warm skin Flushing of face and hands Overgrown nails (acropachy, clubbing), which may lift off the nail bed (onycholysis) Fine soft thinned scalp hair Generalized itching (pruritus) Urticaria Increased skin pigmentation “Pretibial myxedema”

http://dermnetnz.org/vascular/flushing.html

http://dermnetnz.org/hair-nails-sweat/onycholysis.html

http://dermnetnz.org/systemic/itch.html

http://dermnetnz.org/reactions/urticaria.html


• HYPOTHYROIDISM– Primary• Autoimmune (Hashimoto´s)• Iatrogenic Surgery or 131I•Drugs: amiodarone, lithium• Congenital (1 in 3000 to 4000)• Iodine defficiency• Infiltrative disorders


• HYPOTHYROIDISM

– Secondary• Pituitary gland destruction• Isolated TSH deficiency• Bexarotene treatment• Hypothalamic disorders

–Peripheral:• Rare, familial tendency

HYPOTHYROIDISM

• Symptoms:– Tiredness– Weakness– Dry skin Sexual

dysfunction– Dry skin– Hair loss– Difficulty

concentrating

• Signs:– Bradycardia– Dry coarse skin– Puffy face, hands and

feet– Diffuse alopecia– Peripheral edema– Delayed tendon reflex

relaxation– Carpal tunel

syndrome– Serous cavity

effusions.

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Thyroid gland disorder

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