Thyroid Disorders

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Thyroid Disorders

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

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Thyroid Regulation
TSH -R
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Thyroid Hormones

• THEY ARE NOT ESSENTIAL FOR LIFE, BUT ARE
  EXTREMELY HELPFUL

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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

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Thyroid Gland Disorders

• Overproduction of thyroid hormones
• Underproduction of thyroid hormones
• Thyroid nodules
• Thyroiditis
• Thyroid neoplasms

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Hyperthyroidism
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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)

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Thyroid Gland Disorders

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

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Abnormalities of Thyroid Hormones

• Thyrotoxicosis
• Primary
• Secondary
• Without Hyperthyroidism
• Exogenous or factitious
• Hypothyroidism
• Primary
• Secondary
• Peripheral

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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

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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

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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

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Manifestations of Thyrotoxicosis
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Differential Diagnosis

• Panic attacks
• Psychosis
• Mania
• Pheochromocytoma
• Hypoglycemia
• Occult malignancy

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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)

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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)

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HYPOTHYROIDISM
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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.

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Causes of Hypothyroidism

• Primary
• Congenital
• Acquired
• Transient
• Secondary
• Pituitary
• Hypothalamic

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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.

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Hypothyroidism
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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

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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

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Treatment Special Considerations

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

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Goiter and Thyroid Cancer
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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
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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

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Multinodular Goiter Clinical Issues

• Hyperthyroidism
• Suspicion of malignancy
• Compressive/obstructive symptoms
• Cosmetic concerns

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MULTINODULAR GOITERPresentation

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

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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

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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

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Multinodular Goiter Evaluation

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

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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

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Fine Needle Aspiration Evaluation
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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

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Thyroid Cancers
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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
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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)

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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..

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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.

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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.

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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.

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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.

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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 .

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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

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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,

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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

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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 .

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Thyroiditis
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Definition

• Infectious or autoimmune inflammatory
• diseases of thyroid gland

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Classification

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

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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
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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)

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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

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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

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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

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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

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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

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Subacute Lymphocytic Thyroiditis(Painless,
Silent, Lymphocytic)

• A variant form of Hashimotos thyroiditis
• Associated with HLA-DR3
• Postulated initiating factors
• Excess iodine intake
• Various cytokines

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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

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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

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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

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Drug-Induced Thyroiditis

• Interferon-alpha thyroiditis
• Interleukin-2 thyroiditis
• Amiodarone

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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

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Treatment of Riedels Thyroiditis

• Thyroxine
• Surgery
• Glucocorticoids
• Tamoxifen
• Methylprednisone pulse therapy azathioprine or
  penicillamine

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