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Title: Thyroid Disorders


1
Thyroid Disorders
  • Hasan AYDIN, MD
  • Yeditepe University Medical Faculty
  • Department of Endocrinology and Metabolism

2
Thyroid Regulation
TSH -R
3
Thyroid Hormones
  • THEY ARE NOT ESSENTIAL FOR LIFE, BUT ARE
    EXTREMELY HELPFUL

4
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

5
Thyroid Gland Disorders
  • Overproduction of thyroid hormones
  • Underproduction of thyroid hormones
  • Thyroid nodules
  • Thyroiditis
  • Thyroid neoplasms

6
Hyperthyroidism
7
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 (Steroids-dopamine)

8
Thyroid Gland Disorders
  • THYROTOXICOSIS
  • is defined as the state of thyroid hormone
    excesss
  • HYPERTHYROIDISM
  • is the result of excessive thyroid gland function

9
Abnormalities of Thyroid Hormones
  • Thyrotoxicosis
  • Primary
  • Secondary
  • Without Hyperthyroidism
  • Exogenous or factitious
  • Hypothyroidism
  • Primary
  • Secondary
  • Peripheral

10
Causes of Thyrotoxicosis
  • Primary Hyperthyroidism
  • Graves disease
  • Toxic Multinodular Goiter
  • Toxic adenoma
  • Functioning thyroid carcinoma metastases
  • Activating mutation of TSH receptor
  • Struma ovary
  • Drugs Iodine excess

11
Causes of Thyrotoxicosis
  • Thyrotoxicosis without hyperthyroidism
  • Subacute thyroiditis
  • Silent thyroiditis
  • Other causes of thyroid destruction
  • Amiodarone, radiation, infarction of an adenoma
  • Exogenous/Factitia
  • Secondary Hyperthyroidism
  • TSH-secreting pituitary adenoma
  • Thyroid hormone resistance syndrome
  • Chorionic Gonadotropin-secreting tumor
  • Gestational thyrotoxicosis

12
Thyrotoxicosis
  • Signs
  • Tachycardia
  • Atrial fibrillation
  • Tremor
  • Goiter
  • Warm, moist skin
  • Muscle weakness, myopathy
  • Lid retraction or lag
  • Gynecomastia
  • Exophtalmus
  • Pretibial myxedema
  • Symptoms
  • Hyperactivity
  • Irritability
  • Dysphoria
  • Heat intolerance sweating
  • Palpitations
  • Fatigue weakness
  • Weight loss with increased appetite
  • Diarrhea
  • Polyuria
  • Sexual dysfunction

13
Manifestations of Thyrotoxicosis
14
Differential Diagnosis
  • Panic attacks
  • Psychosis
  • Mania
  • Pheochromocytoma
  • Hypoglycemia
  • Occult malignancy

15
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)

16
Treatment Special Considerations
  • Thyrotoxic crisis or Thyroid storm
  • Its a life-threatening exacerbation of
    thyrotoxicosis, acompanied by fever, delirium,
    seizures, coma, vomiting, diarrhea, jaundice.
  • Mortality rate reachs 30 even with treatment
  • Its usually precipitated by acute illness, such
    as
  • Stroke, infection,trauma, diabetic ketoacidosis,
    surgery, radioiodine treatment
  • Propylthyouracil IV or Nasogastric tube
  • Radioiodine (131I)
  • Propranolol
  • Glucocorticoids
  • Benzodiazepines
  • Iodide (Large oral or IV dosage) (Wolf-Chaikoff
    effect)

17
HYPOTHYROIDISM
18
Definition
  • A deficiency of thyroid hormones, which in turn
    results in a generalized slowing down of
    metabolic processes.
  • In infants and children gt marked slowing of
    growth and development, with serious permanent
    consequences including mental retardation.
  • In adulthood gt a generalized slowing down of the
    organism, with the clinical picture of myxedema.

19
Causes of Hypothyroidism
  • Primary
  • Congenital
  • Acquired
  • Transient
  • Secondary
  • Pituitary
  • Hypothalamic

20
Hypothyroidism
  • Symptoms
  • Tiredness
  • Weakness
  • Dry skin
  • Sexual dysfunction
  • 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.

21
Hypothyroidism
22
Special Considerations
  • Myxedema coma
  • Reduced level of consciousness, seizures
  • Hypotension/shock
  • Hypothermia
  • Hyponatremia
  • Usually in elderly hypothyroid pts.
  • Usually precipitated by intercurrent illnesses
    that impairs ventilation
  • Its an Emergency with a high mortality rate
  • Treatment Lyotironine(T3) or T4, Hydrocortisone,
    external warming, IV fluids

23
Many Causes, One Treatment
  • Goal Normalize TSH level regardless of cause of
    hypothyroidism
  • Treatment Once daily dosing with Levothyroxine
    sodium (1.6 µg/kg/day)
  • Monitor TSH levels at 6 to 8 weeks, after
    initiation of therapy or dosage change

24
Treatment Special Considerations
  • Elderly patients
  • Coronary Artery Disease
  • Poor adrenal gland reserve
  • Childrens
  • Pregnancy
  • Emergency surgery (Non thyroid related)

25
Goiter and Thyroid Cancer
26
Definitions
Goiter is a diffuse or nodular enlargement of
the thyroid gland resulting from excessive
replication of benign thyroid epithelial cells.
A thyroid nodule is a discrete lesion within the
thyroid gland that is palpably and/or ultrasonog-
raphically distinct from the surrounding thyroid
parenchyma
27
Etiology of Nontoxic Goiter
  • Iodine deficiency
  • Goitrogen in the diet
  • Hashimoto's thyroiditis
  • Subacute thyroiditis
  • Inherited defect in thyroidal enzymes necessary
    for T 4 and T 3 biosynthesis
  • Generalized resistance to thyroid hormone (rare)
  • Neoplasm, benign or malignant

28
Multinodular Goiter Clinical Issues
  • Hyperthyroidism
  • Suspicion of malignancy
  • Compressive/obstructive symptoms
  • Cosmetic concerns

29
MULTINODULAR GOITERPresentation
  • Asymptomatic
  • Neck mass discovered by patient or physician
  • Abnormal CXR
  • Symptomatic
  • Pressure symptoms
  • Hoarseness
  • Thyrotoxicosis

30
NODULAR GOITERSuspicious Nodule or Goiter
  • High suspicion
  • Family history of medullary thyroid carcinoma
  • Rapid tumor growth
  • A nodule that is very firm or hard
  • Fixation of the nodule to the adjacent structures
  • Paralysis of the vocal cord
  • Regional lymphadenopathy
  • Distant metastasis
  • Moderate suspicion
  • Age of eitherlt20 or gt70 years
  • Male sex
  • History of head and neck irradiation
  • A nodule gt4 cm in diameter or partially cystic
  • Symptoms of compression, including dysphagia,
    dysphonia, hoarseness, dyspnea, and cough

31
Ultrasound
  • Ultrasonographic Cancer Risk Factors for a
    Thyroid Nodule
  • hypoechogenicity,
  • microcalcifications,
  • irregular margins,
  • increased nodular flow visualized by Doppler,
  • the evidence of invasion or regional
    lymphadenopathy

32
Multinodular Goiter Evaluation
  • TSH
  • FT4, T3
  • Radionuclide Scan / RAIU
  • US
  • CT Scan (without contrast)
  • FNA biopsy

33
Multinodular Goiter Fine Needle Aspiration
Evaluation
  • Biopsy all accessible nodule(s)
  • Biopsy suspicious nodule(s) cold on scan firm by
    palpation growing in size
  • Results less reliable in large goiters
  • Most common diagnosis is colloid nodule

34
Fine Needle Aspiration Evaluation
35
FNA results
  • Malignant- pt needs to have surgical management
  • Benign- observation with interval ultrasounds and
    clinical examinations
  • Indeterminate- radioisotope scan- perform
    suppression scan and if cold proceed to surgical
    management- if hot nodule consider observation
  • Non diagnostic- repeat FNA or U/S guided FNA

36
Thyroid Cancers
37
Benign Neoplasms of the Thyroid
  • Thyroid adenoma is a benign neoplastic growth
    contained within a capsule.

Embrional adenoma Fetal adenoma Microfollicular
adenoma Macrofollicular adenoma Papillary
cystadenoma Hurtle cell adenoma
38
Thyroid Cancer
  • Papillary (mixed papillary and follicular) 75
  • Follicular carcinoma 16
  • Medullary carcinoma 5
  • Undifferentiated carcinomas 3
  • Miscellaneous (lymphoma, fibrosarcoma, 1
    squamous cell carcinoma, malignant
    hemangioendothelioma, teratomas, and
    metastatic carcinomas)

39
Papillary Carcinoma
  • very slowly grow and remain confined to the
    thyroid gland and local lymph nodes for many
    years.
  • In older patients, more aggressive and invade
    locally into muscles and trachea.
  • in later stages, they can spread to the lung.
  • Death is usually due to local disease, with
    invasion of deep tissues in the neck less
    commonly, death may be due to extensive pulmonary
    metastases..

40
Follicular Carcinoma
  • is characterized by the presence of small
    follicles, colloid formation is poor.
  • capsular or vascular invasion.
  • more aggressive and local invasion of lymph nodes
    or by blood vessel invasion with distant
    metastases to bone or lung.
  • often retain the ability to concentrate
    radioactive iodine, to form thyroglobulin, and,
    rarely, to synthesize T3 and T4.

41
Follicular Carcinoma
  • rare ''functioning thyroid cancer'' is almost
    always a follicular carcinoma.
  • more likely to respond to radioactive iodine
    therapy.
  • In untreated patients, death is due to local
    extension or to distant bloodstream metastasis
    with extensive involvement of bone, lungs, and
    viscera.

42
Medullary Carcinoma
  • a disease of the C cells (parafollicular cells)
    derived
  • calcitonin, histamin, prostaglandins, serotonin,
    other peptides
  • more aggressive , but not undifferentiated
    thyroid cancer.
  • locally into lymph nodes and into surrounding
    muscle and trachea.
  • lymphatics and blood vessels and metastasize to
    lungs and viscera.
  • Calcitonin and CEA clinically useful markers for
    diagnosis and follow-up.

43
Medullary Carcinoma
  • About 80 are sporadic
  • the remainder are familial. four familial
    patterns
  • without associated endocrine disease (FMTC)
  • MEN 2a medullary carcinoma, pheochromocytoma, and
    hyperparathyroidism
  • MEN 2B, medullary carcinoma, pheochromocytoma,
    and multiple mucosal neuromas
  • MEN 3 with cutaneous lichen amyloidosis, a
    pruritic skin lesion located on the upper back.

44
Undifferentiated (Anaplastic) Carcinoma
  • small cell, giant cell, and spindle cell
    carcinomas.
  • usually occur in older patients with a long
    history of goiter in whom the gland suddenly
    -over weeks or months- begins to enlarge and
    produce pressure symptoms, dysphagia, or vocal
    cord paralysis.
  • Death from massive local extension usually occurs
    within 6-36 months These tumors are very
    resistant to therapy .

45
Lymphoma
  • only type of rapidly growing thyroid cancer that
    is responsive to therapy
  • as part of a generalized lymphoma or may be
    primary in the thyroid gland.
  • occasionally with long-standing Hashimoto's
    thyroiditis
  • characterized by lymphocyte invasion of thyroid
    follicles and blood vessel walls, which helps to
    differentiate thyroid lymphoma from chronic
    thyroiditis.
  • If there is no systemic involvement, the tumor
    may respond dramatically to radiation therapy

46
Cancer metastatic to the thyroid
  • Cancers of the breast and kidney, bronchogenic
    carcinoma, and malignant melanoma.
  • The primary site of involvement is usually
    obvious,
  • Occasionally , the diagnosis is made by needle
    biopsy or open biopsy of a rapidly enlarging cold
    thyroid nodule.
  • The prognosis is that of the primary tumor,

47
Management of Thyroid Cancer
  • Papillary and Follicular Carcinoma
  • Low-risk group under age 45 with primary lesions
    under 1 cm and no evidence of intra- or
    extraglandular spread.
  • For these patients, lobectomy is adequate therapy
  • All other patients high-risk, and for these total
    thyroidectomy and-if there is evidence of
    lymphatic spread -a modified neck dissection are
    indicated.
  • Prophylactic neck dissection is not necessary.
  • For the high-risk group, postoperative
    radioiodine ablation

48
Management of Thyroid Cancer
  • Follow-up at intervals of 6-12 months should
    include careful examination of the neck for
    recurrent masses.
  • If a lump is noted, needle biopsy is indicated to
    confirm or rule out cancer.
  • Serum TSH should be checked
  • Serum Tg should be lt 1 ng/ml .

49
Thyroiditis
50
Definition
  • Infectious or autoimmune inflammatory
  • diseases of thyroid gland

51
Classification
  • Hashimoto thyroiditis
  • Subacute granulomatous thyroiditis
  • Infectious thyroiditis
  • Radiation Trauma induced thyroiditis
  • Subacute Lymphocytic thyroiditis
  • Postpartum thyroiditis
  • Drug induced thyroiditis
  • Riedels thyroiditis

52
HASHIMOTOs THYROIDITIS Chronic Lymphocytic
Thyroiditis
  • Is the most prevalent form of thyroid autoimmune
    disease
  • (3-4 of popul.) and most common cause of
    hypothyroidism
  • Is characterized by gradual thyroid failure,
    goitre or both
  • Is more common in middle age
  • Clusters in families
  • May be associated with other autoimmune
    disorders

Dr. Hakaru Hashimoto
53
Subacute Granulomatous (de Quervains)
Thyroiditis
  • Most frequent cause of thyroid pain and
    tenderness
  • Postviral inflammatory process
  • (Coxsackievirus, mumps, measles, adenovirus,
    other)
  • Strongly associated with HLA-B35, most common in
    40-50 years old women
  • Transient thyroiditis (thyrotoxic for 2-6 wks)

54
Clinical Presentation
  • Previous viral infection (in 1-3 weeks)
  • Pain over thyroid,upper neck, jaw, throat,ears
  • Hoarseness,dysphagia
  • Fever, palpitation, nervousness, lassitude
  • Tender, enlarged, firm and often nodular

55
Treatment of DeQuervains Thyroiditis
  • A nonsteroidal antiinflammatory drug
  • Aspirin 2.4-3.6 g in divided doses
  • Naproxen 1.0-1.5 g in divided doses
  • Prednisone 30-40 mg qd
  • A beta blocker
  • Propranolol 40-120 mg
  • Atenolol 25-50 mg

56
Infectious Thyroiditis
  • Acute (with abscess formation)
  • Gram-positive or negative organisms (via blood or
    a fistula from the piriform sinus adjacent to the
    larynx)
  • Chronic
  • Mycobacterial
  • Fungal
  • Pneumocystis

57
Infectious Thyroiditis
  • Acute
  • Usually unilateral neck pain and tenderness
  • Fever, chills, a unilateral neck mass (fluctuant)
  • USG, FNAB, drainage and antibiotics
  • Chronic
  • Bilateral, less prominent neck pain
  • Some patients have hypothyroidism
  • FNAB

58
Radiation and Trauma-Induced Thyroiditis
  • Radiation Thyroiditis
  • Radioiodine treatment of Graves disease
  • Develops 5-10 days later and is mild
  • Trauma-induced Thyroiditis
  • Palpation, thyroid biopsy, surgery, car seat belt

59
Subacute Lymphocytic Thyroiditis(Painless,
Silent, Lymphocytic)
  • A variant form of Hashimotos thyroiditis
  • Associated with HLA-DR3
  • Postulated initiating factors
  • Excess iodine intake
  • Various cytokines

60
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61
Treatment of Subacute Lymphocytic
Thyroiditis
  • Most patients need no treatment
  • Symptomatic treatment during the hyperthyroid
    phase propranolol or atenolol
  • T4 ( 50-100 µg daily) given for 8-12 wks,
    discontinued and reevaluated 4-6 wks later

62
Postpartum Thyroiditis
  • Occurs in 3-16 of pregnancies (25 in T1DM)
  • Is seen within 1 year after parturition
  • Is likely to recur after subsequent pregnancies
  • Thyrotoxicosis is mild and transient
  • Antithyroid antibodies are elevated
  • RAIU is low
  • Slightly increased ESR

63
Presentation of Postpartum Thyroiditis
  • Transient hyperthyroidism (2-8 wks) followed by
    hypothyroidism (2-8 wks) and then recovery
    20-30
  • Transient hyperthyroidism alone 20-40
  • Transient hypothyroidism alone 40-50

64
Drug-Induced Thyroiditis
  • Interferon-alpha thyroiditis
  • Interleukin-2 thyroiditis
  • Amiodarone

65
Riedels Thyroditis
  • Is a fibrotic process associated with a
    mononuclear cell inflammation that extends beyond
    the thyroid into soft tissue
  • Can involve the parathyroids, the recurrent
    laryngeal nerve, trachea, mediastinum, ant. chest
    wall
  • Fibrosclerosis may involve the retroperitoneal
    space, mediastinum, retroorbital space, the
    biliary tract

66
Treatment of Riedels Thyroiditis
  • Thyroxine
  • Surgery
  • Glucocorticoids
  • Tamoxifen
  • Methylprednisone pulse therapy azathioprine or
    penicillamine

67
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