full lecture of thyroid gland

1. THYROID GLAND
DISORDERS
By Sara Sami
Yuzuncu Yil University
2015

2. THYROID GLAND DISORDERS
• 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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4. Thyroid GlandThyroid Gland

5. THYROID DISORDERS
• GRAVE’S DISEASE
• THYROID STORM
• TOXIC THYROID NODULEHYPERTHYROIDISM
• HASHIMOTOS THYROIDITIS
• CRETINISM
• MYXOEDEMA
• POSTPARTUM THYROIDITIS
• SUBACUTE THYROIDITIS
• SICK EUTHYROIDISM
HYPOTHYROIDISM

7. 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)

8. THYROID GLAND DISORDERS
• 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 “

9. 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

10. Chemistry of thyroid hormone productionChemistry of thyroid hormone production

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12. 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.

13. • 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.

14. • 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.

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

17. NEGATIVE FEEDBACK
Thyroid hormones on pituitary
T3 & T4
TSH
T3 & T4
TSH

18. 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 hormonethyroid-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
hormonehormone (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.

19. 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.

20. 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)

21. 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

22. 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

23. THYROID GLAND DISORDERS
• 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

24. THYROID GLAND DISORDERS
• THYROID HORMONE EFFECTS
– 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

25. THYROID GLAND DISORDERS
• THYROID HORMONE EFFECTS
- FAT & PROTEIN METABOLISM
• Increase lipolysis and lipid mobilization with:
– Cholesterol
– Triglicerides
– Free fatty acids
– MUSCLE METABOLISM
• Modulates;
– Strength & velocity of contraction

26. THYROID GLAND DISORDERS
• THYROID HORMONE EFFECTS
– ELECTROLYTE BALANCE
• Low Thyroid hormones could induce hyponatremia
– VITAMIN METABOLISM
• Modulates vitamin consumption
– HEMATOPOIETIC SYSTEM
• Could induce anemia

27. THYROID GLAND DISORDERS
• THYROID HORMONE EFFECTS
– 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

28. THYROID GLAND DISORDERS
• DIVIDED INTO:
– THYROTOXICOSIS (Hyperthyroidism)
• Overproduction of thyroid hormones
– HYPOTHYROIDISM (Gland destruction)
• Underproduction of thyroid hormones
– NEOPLASTIC PROCESSES
• Beningn
• Malignant

29. 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)

30. THYROID GLAND DISORDERS
• THYROTOXICOSIS:
–is defined as the state of thyroid hormone
excesss
• HYPERTHYROIDISM:
–is the result of excessive thyroid gland
function

31. THYROID GLAND DISORDERS
• Abnormalities of Thyroid Hormones
– Thyrotoxicosis
• Primary
• Secondary
• Without Hyperthyroidism
• Exogenous or factitious
– Hypothyroidism
• Primary
• Secondary
• Peripheral

32. 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

33. 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

34. 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)

35. 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”

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

37. THYROID GLAND DISORDERS
• HYPOTHYROIDISM
–Secondary
• Pituitary gland destruction
• Isolated TSH deficiency
• Bexarotene treatment
• Hypothalamic disorders
–Peripheral:
• Rare, familial tendency

38. 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.

39. Thank You For
Washing