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Thyroid Gland Dr f. Golgiri Thyroid Gland.

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3 Thyroid Gland Dr f. Golgiri

4 Thyroid Gland

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6 THE THYROID GLAND OVER TRACHEA
TWO LARGE LATERAL LOBES CONNECTED BY AN ISTHMUS 15 to 20 g FUNCTIONAL UNIT IS THE FOLLICLE: EPITHELIAL CELLS AROUND A HOLLOW VESSICLE FILLED WITH THYROGLOBULIN

7 Anatomy

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9 Biosynthesis, Secretion, And Transport of Thyroid hormones
Iodine is the most important element in the biosynthesis of thyroid hormones. Thyroglobulin acts as a performed matrix containing tyrosyl groups to which the reactive iodine attaches to form the hydroxyl residues of monoiodotyrosine (MIT) and diiodotyrosine (DIT). The coupling of two DIT molecules forms T4 . The coupling of one DIT molecules and one MIT molecule results in the formation of T3 or reverse T3 (rT3) Almost all circulating T4 and T3 hormones are bound to serum proteins ( thyroid hormone-binding proteins )

10 Thyroid Hormone Synthesis
Iodide trapping Oxidation of iodide and iodination of thyroglobulin Coupling of iodotyrosine molecules within thyroglobulin (formation of T3 and T4) Proteolysis of thyroglobulin Deiodination of iodotyrosines Intrathyroidal deiodination of T4 to T3

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13 Only 0. 03 % of T4 and 0. 3 % of T3 are not bound to proteins
Only 0.03 % of T4 and 0.3 % of T3 are not bound to proteins . These fractions, called free T4 (FT4) and free T3 (FT3), are the physiologically active portions of the thyroid hormones . T3 is the most biologically active thyroid hormone and is three to four times more potent than T4. T3 is more active because it is not as tightly bound to the serum proteins as is T4, and has a greater affinity to target tissue receptors

14 Hypothalamic Pituitary Axis

15 Thyroid Evaluation

16 Thyroid function tests
TSH : The single most sensitive, specific and reliable test of thyroid status . In primary hypothyroidism, [TSH] is increased. In primary hyperthyroidism, [TSH] is decrease or undetectable Total T4 and Total T3 : More than 99% of T4 and T3 circulate in plasma bound to protein Both [total T4] and [total T3] change if [TBG] alters, e.g. in pregnancy Free T4 and Free T3 Free thyroid hormone concentrations are independent of changes in the concentration of thyroid-hormone binding proteins → more reliable for diagnosis of thyroid dysfunction

17 Interpreting results of thyroid function tests
Primary hyperthyroidism Plasma [TSH] : ↓ due to feedback inhibition on the pituitary Plasma free and total T4 and T3 concentrations : ↑

18 Primary hypothyroidism:
Plasma [TSH] : ↑ Plasma [free T4] and [total T4] : ↓ Plasma free T3 and total T3 measurements are of no value here, since normal concentrations are often observed .

19 Physical Exam

20 Evaluation of the Thyroid Disease(Ultrasonography)
Most sensitive procedure or identifying lesions in the thyroid (2-3mm) 90% accuracy in categorizing nodules as solid, cystic, or mixed (Rojeski, 1985) Best method of determining the volume of a nodule (Rojeski, 1985) Can detect the presence of lymph node enlargement and calcifications Noninvasive and inexpensive

21 Evaluation of the Thyroid Disease (Radioisotope Scanning)
Prior to FNA, was the initial diagnostic procedure of choice Performed with: technetium 99m pertechnetate or radioactive iodine Technetium 99m pertechnetate cost-effective readily available short half-life trapped but not organified by the thyroid - cannot determine functionality of a nodule

22 Normal scan of thyroid gland

23 Graves – Basedow disease

24 Autonomous adenoma Initial scan - euthyreosis
Repeat scan - hyperhyreosis

25 Cold nodule

26 (Fine-Needle Aspiration) Evaluation of the Thyroid Disease
Currently considered to be the best first-line diagnostic procedure in the evaluation of the thyroid nodule: Advantages: Safe Cost-effective Minimally invasive Leads to better selection of patients for surgery than any other test (Rojeski, 1985)

27 Effects of Thyroid Hormone
Fetal brain and skeletal maturation Increase in basal metabolic rate Inotropic and chronotropic effects on heart Increases sensitivity to catecholamines Stimulates gut motility Increase bone turnover Increase in serum glucose, decrease in serum cholesterol

28 Goiter

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30 Goiterogenesis Iodine deficiency results in hypothyroidism
Increasing TSH causes hypertrophy of thyroid (diffuse nontoxic goiter) Follicles may become autonomous; certain follicles will have greater intrinsic growth and functional capability (mult inodular goiter) Follicles continue to grow and function despite decreasing TSH (toxic mul tinodular goiter) Sporadic vs. endemic goiter

31 Simple (Colloid) Goiter
Diffuse goiter Usually euthyroid Peaks in puberty Endemic goiter Compensatory  TSH Follicular cell hypertrophy and hyperplasia Goiterogens (eg, cassava) Non endemic or sporadic less common Rare hereditary defects in thyroid hormone synthesis Note distension of follicles with colloid and flattening of epithelial cells

32 Multinodular Goiter Most simple goiters become transformed into multinodular goiters. Nontoxic or toxic (induce thyrotoxicosis) No ophthalmopathy or dermopathy May cause cosmetic disfigurement and tracheal compression May induce the superior vena caval syndrome Differentiation of a dominant nodule from a thyroid tumour may be difficult. Retrosternal extension

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35 Presentation Usually picked up on routine physical exam or as incidental finding Patients may have clinical or subclinical thyrotoxicosis Patients may have compressive symptoms: tracheal, vascular, esophageal, recurrent laryngeal nerve

36 Tracheal Compression

37 Note fibrosis and variation of follicular size
Multinodular Goitre Note fibrosis and variation of follicular size

38 Gross and Microscopic Pathology Multinodular Goiter

39 Figure 17-5. (A) Cross section of multinodular goiter
Figure (A) Cross section of multinodular goiter. (B) Gross radioautograph of the thyroid in part a. Observe the variation in 131I uptake in different areas.

40 Treatment of Diffuse or Multinodular Goiter
Suppressive Therapy Antithyroid Medications: Propylthiouracil and Methimazole I-131 Surgical Therapy

41 Tumours of Thyroid Gland

42 Tumours of Thyroid Gland
2-4% estimated incidence of palpable solitary nodules. Most are not neoplastic and 90% of neoplastic nodules are adenomas. Thyroid cancer is rare (30 per million per year). The younger the patient the greater the chance of neoplasia. A nodule in a male patient is more suspicious than in a female.

43 Thyroid Adenoma Most are follicular adenomas Encapsulated
Homogeneous, soft, fleshy cut surface Foci of haemorrhage Rarely cause hyperthyroidism Most are “cold” on isotope thyroid scan Cystic degeneration

44 Malignant Thyroid Tumours
Papillary carcinoma Follicular carcinoma Medullary carcinoma Anaplastic carcinoma Lymphoma Tumours metastatic to the thyroid

45 History Symptoms The most common presentation of a thyroid nodule, benign or malignant, is a painless mass in the region of the thyroid gland (Goldman, 1996). Symptoms consistent with malignancy Pain dysphagia Stridor hemoptysis rapid enlargement hoarseness

46 History (continued...) Risk factors Thyroid exposure to irradiation
low or high dose external irradiation (40-50 Gy [ rad]) especially in childhood for: large thymus, acne, enlarged tonsils, cervical adenitis, sinusitis, and malignancies 30%-50% chance of a thyroid nodule to be malignant (Goldman, 1996)

47 Risk factors (continued…)
History (continued...) Risk factors (continued…) Age and Sex Benign nodules occur most frequently in women years (Campbell, 1989) Men have a higher risk of a nodule being malignant

48 History (continued…) Family History
History of family member with medullary thyroid carcinoma History of family member with other endocrine abnormalities (parathyroid, adrenals)

49 Evaluation of the thyroid Nodule (Physical Exam)
Examination of the thyroid nodule: consistency - hard vs. soft size - < 4.0 cm Multinodular vs. solitary nodule multi nodular - 3% chance of malignancy (Goldman, 1996) solitary nodule - 5%-12% chance of malignancy (Goldman, 1996) Mobility with swallowing Mobility with respect to surrounding tissues Well circumscribed vs. ill defined borders

50 Evaluation of the Thyroid Nodule (Blood Tests)
Thyroid function tests thyroxine (T4) triiodothyronin (T3) thyroid stimulating hormone (TSH) Calcitonin Thyroglobulin (TG) Serum Calcium

51 Evaluation of the Thyroid Nodule (imaging)
Chest radiograph Computed tomography Magnetic resonance imaging Radioimaging usually not used in initial work-up of a thyroid nodule

52 Evaluation of the Thyroid Nodule (Ultrasonography)
Most sensitive procedure or identifying lesions in the thyroid (2-3mm) Best method of determining the volume of a nodule (Rojeski, 1985) Can detect the presence of lymph node enlargement and calcifications Noninvasive and inexpensive

53 Evaluation of the Thyroid Nodule (Radioisotope Scanning)
Prior to FNA, was the initial diagnostic procedure of choice

54 Evaluation of the Thyroid Nodule (Fine-Needle Aspiration)
Currently considered to be the best first-line diagnostic procedure in the evaluation of the thyroid nodule: Advantages: Safe Cost-effective Minimally invasive Leads to better selection of patients for surgery than any other test (Rojeski, 1985)

55 Fine-Needle Aspiration (continued…)
FNA halved the number of patients requiring thyroidectomy (Mazzaferri, 1993) FNA has double the yield of cancer in those who do undergo thyroidectomy (Mazzaferri, 1993)

56 Fine-Needle Aspiration (continued…)
Pathologic results are categorized as: positive, negative, or indeterminate

57 Thyroiditis

58 Chronic Thyroiditis Also known as Hashimoto’s disease
Probably the most common cause of hypothyroidism in United States Autoantibodies include: thyroglobulin antibody, thyroid peroxidase antibody, TSH receptor blocking antibody

59 Gross and Microscopic Pathology of Chronic Thyroiditis

60 Presentation and Course
Painless goiter in a patient who is either euthyroid or mildly hypothyroid permanent hypothyroidism May have periods of thyrotoxicosis Treat with levothyroxine

61 Subacute Thyroiditis Most common cause of thyroid pain and tenderness
Acute inflammatory disease most likely due to viral infection Transient hyperthyroidism followed by transient hypothyroidism; permanent hypothyroidism or relapses are uncommon

62 Subacute thyroiditis Tc-99m pertechnetate

63 Treatment of Subacute Thyroiditis
Symptomatic: NSAIDS or a glucocorticoid Beta-blockers indicated if there are signs of thyrotoxicosis Levothyroxine may be given during hypothyroid phase

64 Histopathology of Subacute Thyroiditis

65 Riedel’s Thyroiditis Rare disorder usually affecting middle-aged women
Likely autoimmune etiology Fibrous tissue replaces thyroid gland Patients present with a rapidly enlarging hard neck mass

66 Histopathology of Riedel’s Thyroiditis

67 ACUTE INFECTIOUS THYROIDITIS
Rare, serious, bacterial inflammatory disease of the thyroid.

68 Protective mechanisms of the thyroid gland:
very good perfusion efficient lymphatic drainage capsulation of the thyroid high concentration of iodine

69 Etiologic agents: Streptococcus pyogenes, Streptococcus pneumoniae, Escherichia coli, Pseudomonas aeruginosa, Salmonella typhi, anaerobes of the oropharyngeal cavity.

70 RARE FORMS OF INFECTIOUS THYROIDITIS:
the thyroid is rarely the seat of tuberculosis, syphilis, fungal infections (Aspergillus species), or parasites; Pneumocystis carinii infection of the thyroid has been reported in patients with AIDS.

71 TREATMENT OF INFECTIOUS THYROIDITIS
this type of thyroiditis requires the administration of appropriate antibiotics based on the findings of the culture from a fine-needle aspirate, and surgical drainage (or excision) of any area of fluctuance or abscess.

72 hematogenous seeding from distant foci Infection to the thyroid occurs by: direct trauma through a persistent thyroglossal duct extension from adjacent infected structures

73 CLINICAL PICTURE OF ACUTE INFECTIOUS THYROIDITIS
the skin over the infected area is erythematous and warm the white cell count and erythrocyte sedimentation rate are elevated thyroid antibodies are absent serum T4 and T3 levels are usually normal as well as thyroid RAIU

74 TREATMENT OF INFECTIOUS THYROIDITIS
this type of thyroiditis requires the administration of appropriate antibiotics based on the findings of the culture from a fine-needle aspirate, and surgical drainage (or excision) of any area of fluctuance or abscess.

75 Drug-Induced Thyroiditis
Patients receiving cytokines such as IFN- or IL-2 may develop painless thyroiditis Amiodarone

76 Hypothyroidism

77 Hypothyroidism Before treatment After treatment

78 Hypothyroidism Clinical syndrome resulting from a deficiency of thyroid hormones, which in turn results in generalized slowing down of metabolic processes

79 Classification of hypothyroidism
Primary (thyroid failure) Secondary (Central): pituitary TSH deficit hypothalamic deficiency Peripheral resistance to the thyroid hormones Goitrus Nongoitrus

80 Etiology of hypothyroidism
• Primary: 1. Hashimoto’s thyroiditis A/ with goiter B /thyroid atrophy end-stage autoimmune thyroid disease, following either Hashimoto’s thyroiditis or Graves’ disease 2. Subacute thyroiditis 3. Thyroidectomy or therapy for hyperthyroidism (drugs, 131I) 4. Excessive iodide intake 5. Other causes A/ Iodide deficiency B/ Goitrogens C/ Inborn errors of thyroid hormone synthesis

81 Etiology of hypothyroidism
Secondary(Central): Hypopituitarism due to pituitary adenoma, pituitary ablative therapy, or pituitary destruction Hypothalamic destruction Peripheral resistance to the action of thyroid hormones

82 Cretinism Main features: goiter, mental retardation, short stature , puffy appearance of the face and hands, neurologic signs

83 Cretinism Symptoms of hypothyroidism in newborns:
respiratory difficulty, cyanosis, jaundice, poor feeding, hoarse cry, umbilical hernia, marked retardation of bone maturation

84 Hypothyroidism in children
Retarded growth Mental retardation Precocious puberty enlargement of the sella turcica

85 Hypothyroidism in adults
Common features: Easy fatigability, coldness, weight gain, constipation, menstrual irregularities, muscle cramps Physical findings: cool,rough, dry skin, puffy face and hands, a hoarse, husky voice, slow reflexes, yellowish color of the skin (increased level of carotene)

86 Hypothyroidism in adults
Cardiovascular signs: Impaired muscular contraction,bradycardia, diminished cardiac output • Low voltage of ECG

87 Hypothyroidism in adults
Pulmonary function: Shallow, slow respirations Impaired ventilatory response to hypercapnia or hypoxia Renal function: Decreased glomerular filtration Impaired ability to excrete water load

88 Hypothyroidism in adults
Anemia: Impaired hemoglobin synthesis Iron deficiency (increased loss with menorrhagia, impaired absorption from intestine) Folate deficiency (imapired intestinal absorption) Pernicious anemia (vitamin B12 deficiency, autoimmune)

89 Hypothyroidism in adults
Neuromuscular system: Severe muscle cramps Paresthesias Muscle weakness Central nervous system: Chronic fatigue Lethargy Inability to concentrate

90 Diagnosis Check TSH---if it is >4.2 mU/L,
check free thyroxine: low free thyroxine indicates overt hypothyroidism; normal free thyroxine indicates sub-clinical hypothyroidism.

91 Diagnosis If TSH is low and hypothyroidism is still suspected, check the free thyroxine. If this is low the patient either has central (hypothalamic) hypothyroidism or is not hypothyroid. With hypothalamic hypothyroidism, there is always a deficiency of the other pituitary hormones---check cortisol

92 THERAPY OF HYPOTHYROIDISM
Treatmant of choice is L-thyroxine

93 THYROTOXICOSIS AND HYPERTHYROIDISM

94 Thyrotoxicosis Defined as the clinical,physiologic,and biochemical findings that result when the tissues are exposed to,and respond to,excess thyroid hormone. RAIU is subnormal

95 Hyperthyroidism Denotes only those conditions in which sustained hyperfunction of the thyroid gland leads to thyrotoxicosis. Increased RAIU is the hallmark.

96 Varieties of Thyrotoxicosis
Associated with thyroid hyperfunction: Excess production of TSH(rare) Abnormal thyroid stimulator-Eg:Graves’ disease Intrinsic thyroid autonomy-Eg:Hyperfunctioning adenoma, Toxic multinodular goitre Not associated with thyroid hyperfunction: Disorders of hormone storage-Eg:Subacute thyroiditis, chronic thyroiditis Extrathyroid source of hormone- Thyrotoxicosis factitia,ectopic thyroid tissue- struma ovarii, functioning follicular Ca.

97 Clinical features The clinical manifestations include those that reflect the associated thyrotoxicosis

98 Clinical features of thyrotoxicosis
Neuromuscular: Nervousness,irritability,emotional liability,psychosis Tremor Hyperreflexia Muscle weakness,proximal Reproductive:Amenorrhoea,Oligomenorrhoea Infertility,impotence

99 Thyrotoxicosis.. Gastrointestinal:
Weight loss despite increased appetite Diarrhea and steatorrhea Vomiting Cardiorespiratory: Palpitations,Sinus tachycardia,Atrial fibrillation Increased pulse pressure Angina,cardiomyopathy and heart failure

100 Thyrotoxicosis.. Others: Heat intolerance Increased sweating Fatigue
Gynaecomastia Palmar erythema, Onycholysis

101 Hyperthyroidism Graves’ disease
Also known as Basedow’s disease. Graves’ disease is a disorder with three major manifestations: 1)Hyperthyroidism with diffuse goiter 2)Ophthalmopathy 3)Dermopathy. These three manifestations may not appear together.

102 Incidence and prevalence
Relatively common disease that can occur at any age More common in the 3rd and 4th decade Disease is more frequent in women(7:1) Genetic factors play an important role An overlap exsists with other autoimmune diseases suggesting Graves is also a autoimmune thyroid disease

103 Etiology and Pathogenesis
Cause of Graves’ is unknown No single factor is responsible for the entire syndrome

104 Pathology Thyroid gland is diffusely enlarged,soft and vascular.
There is parenchymatous hyperplasia and hypertrophy with lymphocytic infilteration.

105 Pathology The ophthalmopathy is characterized by an inflammatory infilterate of the orbital contents The dermopathy of Graves’ disease is characterized by thickening of the dermis,which is infilterated by lymphocytes and mucopolysaccharides

106 Goiter Is diffuse and toxic and maybe asymmetric and lobular.
There may be presence of bruit over the goiter

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108 Ophthalmopathy Signs of Graves’s ophthalmopathy are divided into two components: 1) Spastic: Stare, lid lag and lid retraction which account for the “frightened” facies. 2) Mechanical: Proptosis of varying degrees,ophthalmoplegia,and congestive occulopathy characterized by chemosis,conjunctivitis,periorbital swelling and the potential complications of corneal ulceration,optic neiritis and optic atrophy.

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111 Dermopathy Usually occurs over the dorsum of the legs or feet and is termed localized or pretibial myxedema. The affected area is usually demarcated from the normal skin by being raised and thickened and having a peau d’ orange appearance;it may be pruritic and hyperpigmented. The most common presentation is non pitting oedema,but lesions maybe plaque like,nodular or polypoid. Clubbing of the fingers and toes accompanies and is termed thyroid acropachy

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115 Investigations Thyroid function test: TSH- Undetectable T4 - Raised
RAIU- Raised TSH-receptor antibodies(TRAb)-elevated in Graves’s disease Isotope scanning- Increased uptake

116 Treatment of Hyperthyroidism

117 Anti thyroid drugs Chemically block hormone synthesis
Methimazole-active metabolite of Carbimazole .propylthiouracil

118 Duration of treatment 18-24 months Side effects- Rash Leukopenia
Agranulocytosis

119 Ablative therapy (Surgery & Iodine)
Indications: Relapse or recurrance following drug therapy A large goiter Failure to follow medical regimen. Radioactive iodine is simple,effective and economical

120 Complications of ablative therapy
Immediate complications of surgery: Bleeding,injury to recurrant laryngeal nerve and thyroid crises. Other complications Hypothyroidism Radiation thyroiditis

121 Complications of thyrotoxicosis
1)Cardiac- Heart failure Atrial fibrillation 2)Thyrotoxic crises: or ‘storm’: Fulminating increase in signs and symptoms of thyrotoxicosis. Occurs in medically untreated or inadequately treated patients.May be precipitated by surgery or sepsis The syndrome is characterized by extreme irritability,delirium or coma,fever 41°C or more,tachycardia,restlessness,hypotension, vomiting and diarrhea.

122 Treatment of thyroid crisis
Provide supportive care; Treat dehydration Administer glucose and saline Vitamin B complex and glucocorticoids Digitalization is required in those with atrial fibrillation Immediate and large doses of anti thyroid agents(eg-propylthiouracil 100mg every 2h) Iodine intravenously or by mouth Propranolol 40-80mg every 6h Dexamethasone(2mg every 6h) and to be tapered later.

123 Treatment of ophthalmopathy and Dermopathy
Methylcellulose eye drops Tinted glasses Persistant diplopia can be corrected by surgery Papilloedema,loss of visual field or acuity requires urgent treatment with prednisolone 60 mg daily. Majority of patients require no treatment other than reassurance. Dermopathy of Graves rarely requires treatment

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