Thyroid Disorders - PowerPoint PPT Presentation

Title: Thyroid Disorders


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Thyroid Disorders

• Eric J Milie, D.O.

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Objectives

• Understand basic interactions of the
  hypothalamic-pituitary-thyroid axis
• Recognize the various causes of hypo- and
  hyperthyroid
• Differentiate between acute, subacute, and
  chronic thyroiditis in terms of clinical picture
  and treatment
• Explain the work-up required for a patient with a
  solitary thyroid nodule

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Thyroid Anatomy

• Small gland located in anterior portion of neck
• Attached to larynx
• Two halves (lobes) connected by isthmus
• Resembles a butterfly or bow-tie
• From Greek word meaning shield
• Each lobe roughly 4cm long, 1-2cm wide
• Cannot normally be seen, barely palpable in
  healthy adult

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Thyroid Anatomy continued
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Function of Thyroid Gland

• Secretes thyroid hormones, which regulate
  metabolism throughout the body
• Two hormones secreted Thyroxine (T4) and
  Triiodothyronine (T3)

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Thyroid Hormones

• T4, the major hormone produced by the thyroid,
  has only slight effect on controlling bodys
  metabolism
• T4 converted to T3 (active thyroid hormone)
  mainly in the liver and kidney
• Many factors effect conversion rate, including
  bodys need from moment to moment and presence or
  absence of illness

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Chemical Structure
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Thyroid Hormones continued

• T4 de-iodinated in liver and kidney, resulting in
  T3 and reverse T3 (inactive)
• Thyroid hormones poorly soluble in water, so 99
  protein bound
• Principle carrier is thyroxine binding globulin,
  a glycoprotein synthesized by the liver

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Some Thyroid Hormone Responsibilities

• Heart rate
• Respiratory rate
• Rate of caloric consumption
• Skin maintenance
• Growth
• Fertility
• Digestion
• Heat regulation

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Role of Iodine

• Chief component of thyroid hormones, essential
  for their production
• Iodine concentrated from blood via the
  Sodium-iodide symporter, so-called iodine trap
• In areas where there is not sufficient levels of
  iodine (Great Lakes, Swiss Alps, Tasmania),
  iodine must be supplimented
• In U.S., salt iodized, so iodine deficiency is
  rare

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Sodium-Iodine Symporter
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Thyroid Stimulating Hormone

• Chief stimulator of thryoid hormone synthesis is
  TSH (Thyroid Stimulating Hormone), released from
  anterior pituitary
• Most important controller of TSH secretion is
  Thyrotropin Releasing Hormone (TRH) from
  hypothalamic neurons
• Secretion of TRH, and hence TSH, inhibited by
  high blood levels of thyroid hormones (negative
  feedback loop)

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TRH-TSH-Thyroid Hormone Feedback Loop
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Hypothalamic-Pituitary Axis

• Feedback loop pat of so-called hypothalamic
  pituitary axis
• As thyroid hormone levels in blood increase,
  negative feedback to hypothalamus and pituitary
• Leads to shut-down of thyroid producing follicles
• When circulating levels of thyroid hormone
  stabilize, process begins anew
• Axis influenced by other factors, including
  environmental factors (cold exposure leads to
  increase in thyroid hormone production in rodent
  models)

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Hypothalamic-Pituitary-Thyroid Axis
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Goiter Formation as Dysfunction of
Hypothalmic-Pituitary-Thyroid Axis

• Insufficient dietary intake of iodine leads to
  insufficient production of T3 and T4
• Hypothalamus responds with increasing levels of
  circulating TRH
• Causes pituitary to release more TSH
• Secondary function of TSH is thyroid cell growth
• Prolonged exposure to high levels of TSH results
  in goiter

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Goiter
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Thyroid Gland- Diagnostic Studies

• No single test is 100 accurate in diagnosing
  thyroid disease, so usually combination of two or
  more tests ordered
• TSH level is most common test ordered for
  monitoring of thyroid function
• High levels of TSH usually indicative of under
  active thyroid gland (hypothyroid)
• Low levels usually indicative of over active
  thyroid gland (hyperthyroid)

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Diagnostic Tests continued

• Measurement of T4 by radioimmunoassay (RIA)
  reflects the amount of T4 circulating in the
  blood.
• Usually combined with T3 uptake to give a free
  T4 level, which corrects for other medications
  which influence the routine T4 test

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Diagnostic Tests continued

• Thyroid Binding Globulin may be ordered for
  patients with unexplained elevations or
  deficiency of T4 and T3
• Excess or deficiency of TBG will alter the
  measurement of T3 and T4, but not the action of
  the hormones
• Hereditary trait can cause excessive or deficient
  levels of TBG

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Iodine Uptake Scan

• Radioactive iodine administered to patient
• Iodine concentrated in the thyroid or excreted in
  the urine
• Uptake measured at various time intervals
• Does not measure hormone levels, merely avidity
  of thyroid for iodine and clearance rate relative
  to kidney function
• Diseases resulting in excessive production of
  thyroid hormone generally associated with
  increased RAIU, diseases resulting in decreased
  production generally show decreased RAIU

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RAIU continued
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Thyroid Scan

• Usually done at same time as RAIU
• Useful in identifying nodules and defining if
  they are hot or cold
• Measuring size of goiter prior to treatment
• Follow-up in thyroid cancer patients after
  surgery
• Locating thyroid tissue outside of neck, such as
  at base of tongue or in the chest

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Thyroid Scan

• Two types, camera scan and Computerized
  Rectilinear Thyroid scan
• Camera scan most common, takes 5-10 minutes
• CRT developed in the 1990s, improves clarity,
  more precisely identifies nodules, and provides
  information on both function and size

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Camera Scan
Camera scan images showing hot nodule (left)
and cold nodule (right)
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CRT
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Thyroid Ultrasound

• Screening tool for suspected thyroid nodule
• Can identify if nodule is cystic or solid, but
  provides little help determining if it is benign
  or malignant
• Can detect changes in nodules size
• Useful in assisting with needle biopsy of thyroid

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Thyroid Ultrasound
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Ultrasound Characteristics Suggesting Benign
Nodule

• Sharp edges around entire nodule (well
  circumscribed)
• Nodule filled with fluid and not live tissue
  (cystic)
• Multiple nodules throughout the thyroid
• No blood flowing through nodule on Doppler
  (suggest cystic lesion)

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Fine Needle Biopsy

• Most reliable test to determine whether cold
  nodule cancerous or benign
• Provides definitive diagnosis in up to 75 of
  biopsies
• Further discussion later in presentation

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Euthyroid Sick Syndrome Definition

• Clinical condition in which patients suffering
  from severe non-thyroid illness are clinically
  euthyroid but biochemically dysthyroid

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Euthyroid Sick Syndrome Precipitating Factors

• Fasting
• Starvation
• Anorexia nervosa
• Protein malnutrition
• Surgical trauma
• Hyperthermia

• Myocardial infarction
• Chronic renal failure
• Diabetic ketoacidosis
• Cirrhosis
• Sepsis

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Euthyroid Sick Syndrome Lab Findings

• T4 concentration is normal or decreased
• T4-binding to TBG is decreased
• T3 concentration is decreased
• rT3 concentration is increased
• TSH concentration is normal
• Thyroid scans usually normal

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Euthyroid Sick Syndrome Pathogenesis

• When people are sick or malnourished or have had
  surgery, the thyroid hormone T4 is not converted
  normally to the active T3 hormone
• Large amounts of reverse T3 accumulate
• Despite this abnormal conversion, the thyroid
  functions normally
• No treatment is necessary, as thyroid function is
  preserved
• Laboratory tests normalize once the underlying
  illness resolves

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Hyperthyroid Definition

• Condition of excess functional activity of the
  thyroid gland
• Characterized by increased basal metabolism,
  goiter, and disturbances of the autonomic nervous
  system
• Affects women 31 more than men

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Hyperthyroid Types

• Graves disease
• Toxic nodular goiter (Plummers disease)
• Toxic adenoma
• Therapeutic induced hyperthyroid (Lugols,
  amiodarone, etc.)
• Thyroiditis
• Primary and/or metastatic follicular carcinoma
• TSH producing tumor of the hypophysis

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Hyperthyroid Common Symptoms and Signs

• Heat intolerance, excessive sweating, and moist
  skin
• Hyperactivity and tenseness
• Weight loss (unintentional)
• Fine tremors, palpitations, and tachycardia
• Infiltrative dermopathy
• Ocular signs, including lid lag, exophthalmus,
  and conjunctival injection
• Generalized pruritis

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Hyperthyroid Diagnostic Work-up

• History and physical
• Blood chemistries, including hormone levels and
  specific antibodies
• Ultrasound
• Thyroid scan
• Fine needle biopsy (particularly with
  hyperthyroidism associated with nodularity)

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Graves Disease

• Autoimmune disease associated with the production
  of antibodies that bind to TSH receptors in the
  follicular cells of the thyroid and activate
  these cells to produce T4 and T3.
• These antibodies therefore simulate TSH - TSH has
  no part in this hyperfunctioning

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Graves Disease Pathophysiology

• Most common form of adult hyperthyroidism
• Peaks in 3rd and 4th generations
• Clinical presentation includes all aforementioned
  signs and symptoms ocular and dermatological
  signs pathognomonic
• Bilateral exophthalmos occurs in 40-50 of
  Graves patients- unilateral involvement is rare

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Graves Disease continued

• T3 and T4 concentrations increased
• TSH level decreased
• Autoimmune antibodies to TSH receptors
• RAI and Tc-99m studies are increased
• Scans usually show mildly enlarged thyroid which
  concentrates isotope evenly and intensely

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Graves Disease- Therapy (Conservative)

• Treatment with antithyroid drugs (Propranolol,
  propylthiouricil, methimazole)
• Long term remission rate with conservative
  treatment is low (30-50)
• Propranolol ß-blocker makes patient eumetabolic
  but not euthyroid
• Other drugs block iodothyronine hormone synthesis

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Graves Disease- Therapy Surgery

• Treatment of choice if patient younger than 21
  years of age, is sensitive to iodine, or who have
  very large goiters
• In good hands, recurrence rate is low (2-9)with
  a 3 incidence of hypothyroidism
• Side effects vocal cord paralysis and
  hypoparathyroidism

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Graves Disease- Therapy Radioactive Iodine-131

• Therapy of choice for women past childbearing
  years and adult males
• No proven increase in incidence of carcinoma,
  leukemia, etc.
• 25 of patients will be hypothyroid one year
  after treatment incidence increases 2/year for
  the next 20 years

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Graves Ophthalmopathy

• Most frequent extrathyroidal manifestationof
  Graves disease
• Fortunately, most patients with only minor
  involvement, amenable to non-aggressive treatment

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Graves Exophthalmos Picture
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Management of Nonsevere Exophthalmos
Management of nonsevere Graves ophthalmopathy13 Management of nonsevere Graves ophthalmopathy13
Sign and/or symptom Therapeutic measure
Photophobia Foreign body sensation Eyelid retraction increased intraocular pressure Lag ophthalmos Mild diplopia Sunglasses Artificial tears and ointments ß-Blocking eyedrops Nocturnal taping of the eyes Prisms Correction of hyper- or hypothyroidism Elimination of risk factors (smoking) Reassurance on the natural history of the disease
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Management of Severe Exophthalmos
Management of severe Graves ophthalmopathy13
Established methods Glucocorticoidsa. Oralb. Intravenousc. Local Supervoltage orbital radiotherapy a. Rehabilitative surgeryb. Orbital decompressionc. Extraocular muscle surgeryd. Eyelid surgery Novel treatments under investigation 1. Somatostatin Analogues 2. Octreotide 3. Lanreotide 4. Intravenous immunoglobulins 5. Nonestablished methods 6. Cyclosporinea 7. Plasmapheresis 8. Anecdotal treatments 9. Cyclophosphamide 10. Bromocriptine 11. Metradinazole
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Infiltrative Dermopathy of Graves Disease
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Toxic Adenoma Definition

• Autonomous hyperfunctioning nodule surrounded by
  normal functioning tissue
• Rarely two or more adenomas exist in normally
  functioning thyroid
• No clear cause neither antibodies nor TSH
  involved
• Nodule must be 2.5-3cm in size to produce
  hyperthyroidism

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Toxic Adenoma Presentation

• Symptoms and signs of hyperthyroidism.
• No exophthalmos.
• No infiltrating dermopathy.
• The thyroid gland may be enlarged, but is
  generally of normal size.
• On palpation, a non-tender, mildly firm nodule is
  palpable.

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Toxic Adenoma Diagnosis

• T3 and T4 levels are elevated.
• The TSH concentration is decreased.
• Specific antibodies are absent.
• On Radioisotope scan, the thyroid gland is
  usually of normal size.
• One hot nodule - rest of the gland is cool

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Toxic Adenoma Treatment

• Unless contraindicated, radioactive iodine (131I)
  - higher doses are usually necessary.
• Production of hypothyroidism is rare.

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Toxic Adenoma Imaging
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Toxic Multinodular Goiter (Plummers Disease)

• enlarged multinodular goiter commonly found in
  areas of iodine deficiency in which patients with
  long-standing non-toxic goiter develop
  thyrotoxicosis
• One or more of the nodules begin to hyperfunction
  autonomously
• Encompasses a spectrum of different clinical
  entities ranging from a single hyperfunctioning
  nodule within an enlarged thyroid gland having
  additional non-functioning nodules to multiple
  hyperfunctioning areas (nodules) scattered
  throughout the gland barely distinguishable from
  non-functioning nodules and ordinary thyroid
  tissue

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Plummers Disease Clinical Presentation

• A middle-aged person with 10 - 15 years history
  of an enlarged gland.
• The general symptoms and signs of
  hyperthyroidism.
• Exophthalmos is absent.
• Infiltrative dermopathy is absent.
• The gland is enlarged and multinodular.

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Plummers Disease Diagnosis

• The serum T3 and T4 levels are raised.
• The TSH concentration is decreased.
• No auto-immune antibodies are present
• Scan shows an enlarged, multinodular gland.
• One, two or more nodules are hot (overactive) and
  in between cool and cold nodules

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Plummers Disease Treatment

• Similar to treatment for Graves disease
• Plummers disease is more resistant to 131I
  therapy than Graves - apparently because the
  areas (nodules) of low activity at the time of
  therapy become active as the hyperactive nodules
  are destroyed and more TSH is released.
• Induction of hypothyroidism is rare

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Plummers Disease Imaging
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Thyrotoxicosis Factitiae

• syndrome of hyperthyroidism that results from an
  overdosage of thyroid hormone - T3 or T4.
• Clinical signs and symptoms similar to other
  causes of hyperthyroidism
• No exophthalmos or dermopathy

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Thyrotoxicosis Factitiae Diagnosis

• T3 therapy serum concentration of T3 is
  increased, serum T4 is decreased, and TSH
  concentration is decreased.
• T4 therapy serum T3 concentration is increased,
  T4 concentration is increased, TSH level is
  decreased.
• RAI uptake by thyroid is decreased
• The thyroid gland is not enlarged.
• Scan image shows a cool thyroid

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Thyrotoxicosis Factitiae Treatment

• Reduce or suspend T4 therapy.
• Normalization may take 6 weeks or longer

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Hamburger Thyrotoxicosis

• Several outbreaks of thyrotoxicosis have been
  attributed to a practice, now banned in the US,
  called "gullet trimming
• Meat in the neck region of slaughtered animals is
  ground into hamburger
• Thyroid glands are reddish in color and located
  in the neck, it's not unusual for gullet trimmers
  to get thyroid glands into hamburger or sausage
• Outbreak of thyrotoxicosis in Minnesota and South
  Dakota that was traced to thyroid-contaminated
  hamburger. A total of 121 cases were identified
  in nine counties, with the highest incidence in
  the county having the offending slaughter plant.
  The patients complained of sleeplessness,
  nervousness, headache, fatique, excessive
  sweating and weight loss

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Iodine-precipitated Hyperthyroidism

• With iodine deficiency production of T4 and T3
  decreases, so more TSH is released and thyroid
  stimulation increases, resulting in enlargement
  of the thyroid (goiter)
• If iodine intake is increased in such a patient
  the enlarged gland may produce excess amounts of
  T3 and T4, and hyperthyroidism develops.
• Excess iodine intake by euthyroids and
  hyperthyroids may suppress TSH secretion and thus
  produce hypothyroidism or it may produce
  hyperthyroidism by activating hormogenesis in
  patients with deranged special thyroidal systems,
  so-called Jod-Basedow phenomenon
• Lastly, it may elicit hyperactivity in normal
  thyroid glands by deranging the function of the
  cells

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Secondary Hyperthyroidism

• This term refers to hyperthyroidism precipitated
  by excess TSH secretion by a pituitary tumour or
  by other tumours (e.g. choriocarcinoma, struma
  ovarii, etc.)
• Clinical signs and symptoms same as other causes
  of hyperthyroidism, without exophthalmos
• The T3, T4 and TSH concentrations are raised
• The thyroid is enlarged and the isotope uptake is
  diffusely increased.

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Hypothyroidism

• condition where insufficient thyroid hormones are
  produced
• Two main types are distinguished,. primary and
  secondary hypothyroidism
• Primary hypothyroidism by far more common
• Primary Hypothyroidism can be subdivided into
  hypothalamic-pituitary causes vs. thyroidal causes

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Hypothyroidism Causes Primary
1. Primary (thyroidal) hypothyroidism          
1. Loss of functional thyroid tissue
                    1. chronic autoimmune
thyroiditis                     2. reversible
autoimmune hypothyroidism (silent and postpartum
thyroiditis, cytokine-induced thyroiditis).
                    3. surgery and irradiation
(131I or external irradiation)                   
  4. infiltrative and infectious diseases,
subacute thyroiditis                     5.
thyroid dysgenesis           2. Functional
defects in thyroid hormone biosynthesis and
release                     1. congenital
defects in thyroid hormone biosynthesis
                    2. iodine deficiency and
iodine excess                     3. drugs
antithyroid agents, lithium, natural and
synthetic goitrogenic chemicals
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Hypothyroidism Causes Secondary
2. Central (hypothalamic/pituitary) hypothyroidism           1. Loss of functional tissue                     1. tumors (pituitary adenoma, craniopharyngioma, meningioma, dysgerminoma, glioma, metastases)                    2. trauma (surgery, irradiation, head injury)                     3. vascular (ischemic necrosis, hemorrhage, stalk interrruption, aneurysm of internal carotid artery)                     4. infections (abcess, tuberculosis, syphilis, toxoplasmosis)                     5. infiltrative (sarcoidosis, histiocytosis, hemochromatosis)                     6. chronic lymphocytic hypophysitis                     7. congenital (pituitary hypoplasia, septooptic dysplasia, basal encephalocele)           2. Functional defects in TSH biosynthesis and release                     1. mutations in genes encoding for TRH receptor, TSHß, or Pit-                     2. drugs dopamine glucocorticoids L-thyroxine withdrawal 3. "Peripheral" (extrathyroidal) hypothyroidism                     1. Thyroid hormone resistance                    2. Massive infantile hemangioma

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Hypothyroidism Signs and Symptoms

• A dull facial expression, a hoarse voice, slow
  speech, a puffed face with swollen periorbital
  tissues. These changes are the result of
  mucopolysaccharide (hyaluronic acid and
  chondroitin sulphate) infiltration of the
  tissues.
• The patient is cold-intolerant due to low
  metabolic rate.
• Drooped eyelids and the hair is sparse the skin
  is coarse, dry, scaly and thick.
• Modest weight gain.
• Signs of intellectual impairment - frank
  psychosis (myxoedema madness) may develop.
• A yellowish colour of the skin due to
  carotenaemia, and pruritis.11
• Bradycardia, cardiac arrhythmia, etc.

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Hypothyroid Lab Studies

• Anemia normo-/micro-/macrocytic.
• T4 and T3 concentrations are low, and TSH
  concentration is high in the primary type.
• T4, T3 and TSH are low in the secondary type.
• TRH and/or TSH tests differentiate between
  primary and secondary hypothyroidism.

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Thyroiditis

• Inflammation of the thyroid gland
• Classified as chronic, subacute, and acute
• Can initially present as hyperthyroidism,
  ramification may result in hypothyroidism

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Hashimotos Thyroiditis

• A chronic inflammation of the thyroid with
  lymphocytic infiltration of the gland caused by
  autoimmune factors
• Most common cause of primary hypothyroidism in
  North America
• Women to men 81, rate increases in both sexes
  with age
• A family history of thyroid disorders is common,
  and incidence is increased in patients with
  chromosomal disorders, including Turner's, Down,
  and Klinefelter's syndromes

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Hashimotos Signs and Symptoms

• Painless enlargement of the thyroid gland
• Examination reveals a nontender goiter, smooth or
  nodular, firm, and more rubbery than the normal
  thyroid many patients have hypothyroidism when
  first seen
• Other forms of autoimmune disease are common
• There may be an increased incidence of thyroid
  neoplasia, particularly papillary carcinoma and
  thyroid lymphoma

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Hashimotos Diagnosis

• Laboratory findings early in the disease consist
  of normal T4 and TSH levels and high titers of
  thyroid peroxidase antibodies and less commonly
  anti-thyroglobulin antibodies
• The thyroid radioactive iodine uptake may be
  increased, perhaps because of a defect in
  organification of iodide in conjunction with a
  gland that continues to trap iodine
• Later in the disease, the patient develops
  hypothyroidism with decreased T4, decreased
  thyroid radioactive iodine uptake, and increased
  TSH

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Hashimotos Treatment

• usually requires lifelong replacement therapy
  with thyroid hormone to decrease goiter size and
  treat the hypothyroidism
• Occasionally, the hypothyroidism is transient
• The average oral replacement dose with
  L-thyroxine is 100-120 µg/day

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Hashimotos
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Subacute Thyroiditis (de Quervains Thyroiditis)

• Acute inflammatory disease of the thyroid,
  probably caused by a virus
• Frequently a history of mumps
• The gland shows giant cell infiltration but
  lymphocyte infiltration is absent
• Female patients outnumbered male patients in a
  ratio of 3-61
• Although the disease has been described at all
  ages, it is rare in children

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Subacute Thyroiditis Presentation

• Condition is characterized by sudden onset of
  sore throat, tenderness of the neck and low grade
  fever
• Disease may reach its peak within 3 to 4 days and
  subside and disappear within a week, but more
  typically, a gradual onset extends over 1 to 2
  weeks and continues with a fluctuating intensity
  for 3 to 6 weeks
• Thyroid gland is typically enlarged two or three
  times the normal size or larger and is tender to
  palpation
• The condition is often confused with pharyngitis
  or otitis media

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Subacute Thyroiditis Presentation continued

• Approximately one-half of the patients present
  during the first weeks of the illness, with
  symptoms of thyrotoxicosis, including
  nervousness, heat intolerance, palpitations,
  tremulousness, and increased sweating
• As the disease process subsides, transient
  hypothyroidism occurs in about one-quarter of the
  patients
• Ultimately thyroid function returns to normal and
  permanent hypothyroidism occurs in less than 10
  percent of the cases

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Subacute Thyroiditis Diagnosis

• History and clinical examination.
• An elevated erythrocyte sedimentation rate.
• The T4 level is elevated, the TSH is down.
• The 131I-uptake is down in the presence of
  elevated T4, and a radioisotope scan (99mTcO4-)
  shows a cool thyroid or the thyroid is not
  visualized.

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Subacute Thyroiditis Treatment

• In some instances, no treatment is required
• Mainstay of treatment is analgesia
• Initial therapy with Aspirin or NSAIDs
• May need to treat with corticosteroids
  (Typically, Prednisone 40mg daily to begin with,
  followed by a long taper of up to six weeks)
• Relief of symptoms with treatment almost
  diagnostic
• Alternatively oral cholecystographic agents (such
  as sodium ipodate or sodium iopanoate) may be
  used safely and effectively for the management of
  hyperthyroidism in these patients even when they
  have relapsed after corticosteroid therapy
• The recurrent rate of subacute thyroiditis after
  cessation of prednisone therapy is about 20 but
  no difference has been found in routine
  laboratory data between recurrent and
  non-recurrent groups of patients
• Levothyroxine administration may be useful in
  situations where the patient is not already
  hyperthyroid due to the release of thyroidal
  contents into the circulation

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Subacute Thyroiditis Prognosis

• In 90 or more of patients, there is a complete
  and spontaneous recovery and a return to normal
  thyroid function
• However, the thyroid glands of patients with
  subacute thyroiditis may exhibit irregular
  scarring between islands of residual functioning
  parenchyma, although the patient has no symptom
• Up to 10 of the patients may become hypothyroid
  and require permanent replacement with
  levothyroxine

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Acute (Infectious) Thyroiditis

• Thyroid extremely resistant to infection,
  therefore infectious thyroiditis rare
• However, in certain situations, particularly in
  children a persistent fistula from the pyriform
  sinus may make the left lobe of the thyroid
  particularly susceptible to abscess formation
• Occasionally, acute bacterial supporative
  thyroiditis occurs in children receiving cancer
  chemotherapy

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Acute Thyroiditis Etiology

• Virtually any bacteria can infect the thyroid
• Strep, Staph, pneumococcus, salmonella,
  bacteroides, t. pallidum, pasturella, and
  mycobacterium all documented
• In addition, fungal infections, including
  cryptococcus, have been reported
• Most commonly, however, especially in children,
  infection of the thyroid gland is a result of
  direct extension from an internal fistula from
  the pyriform sinus

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Acute Thyroiditis Etiology
91
Acute Thyroiditis Presentation

• The dominant clinical symptom is pain in the
  region of the thyroid gland which may
  subsequently enlarge and become hot and tender
• The patient is unable to extend the neck and
  often sits with the neck flexed in order to avoid
  pressure on the thyroid gland
• Swallowing is painful
• There are usually signs of infection in
  structures adjacent to the thyroid, local
  lymphadenopathy as well as temperature elevation
  and, if bacteremia occurs, chills
• Gas formation has been noted with suppurative
  thyroiditis
• Pediatric presentation more typical than adult
• In general, no sign of hypo- or hyperthyroidism

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Acute Thyroiditis Diagnosis

• History, physical, and clinical suspicion most
  important
• Patient more ill appearing than in subacute
• The T3, T4 and TSH levels are usually normal, and
  the rT3 is increased
• A radioisotope scan shows an enlarged gland with
  diffusely increased isotope uptake
• If lesion localized on ultrasound or scan, needle
  biopsy diagnostic

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Acute Thyroiditis Treatment

• Surgical removal of fistulous tract in pediatric
  patients with communication with pyriform sinus
• Systemic antibiotics with broad spectrum coverage
  needed for some patients
• Must add fungal coverage in immunocompromised
  patients

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Acute Thyroiditis Prognosis

• some patients with thyroiditis, the destruction
  may be sufficiently severe that hypothyroidism
  results
• Patients with a particularly diffuse thyroiditis
  should have follow-up thyroid function studies
  performed to determine that this has not occurred
  
• Surgical removal of a fistula or branchial pouch
  sinus is required to prevent recurrence when this
  is present

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Clinical Differences Between Thyroiditis Types
Subtype Etiology Neck Pain RAIU TSH T4 Autoantibodies
Chronic lymphocytic (Hashimoto's disease) Autoimmune No Present
Subacute granulomatous Viral Yes ? ? ? Absent
Microbial inflammatory Bacterial, fungal, parasitic Yes Normal Normal Absent
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Amiodarone and Thyroid

• Amiodarone used to treat cardiac arrythmias
• Structurally similar to thyroid hormone,
  comprised of 39 iodine
• Patients on amiodarone may become hypo- or
  hyperthyroid
• If hypothyroid, stop amiodarone and give T4

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Amiodarone Induced Hyperthyroid

• Two Types Type I and Type II
• Type 1 In this type underlying thyroid pathology
  is present, for example multinodular or diffuse
  goiter (thyroid enlarged) and in these patients
  amiodarone precipitates typical Jod-Basedow with
  increased blood T4 and T3 levels and a decreased
  blood TSH level
• Radioisotope studies show a diffusely or
  multinodular enlarged gland (goiter) with normal
  or increased 131I or 99mTc uptake
• Ultrasound shows a nodular or enlarged thyroid
  gland
• Improves with use of perchlorate, which promotes
  iodine expulsion from thyroid

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Amiodarone Induced Hyperthyroid continued

• Type II In this type there is no evidence of
  underlying thyroid pathology
• The gland is small and it may be tender
• Radioisotope studies (131I or 99mTc) show a small
  gland with low or absent radioisotope uptake
• Ultrasound images are normal
• The onset of the condition is often explosive
• The condition is treated by steroids, in addition
  to perchlorate

99
Thyroid Nodule

• One in 12 to 15 young women has a thyroid nodule
• One in 40 young men has a thyroid nodule
• More than 95 percent of all thyroid nodules are
  benign (non-cancerous growths)
• Some are actually cysts which are filled with
  fluid rather than thyroid tissue
• Most people will develop a thyroid nodule by the
  time they are 50 years old
• The incidence of thyroid nodules increases with
  age
• 50 of 50 year olds will have at least one
  thyroid nodule
• 60 of 60 year olds will have at least one
  thyroid nodule
• 70 of 70 year olds will have at least one
  thyroid nodule

100
Thyroid Nodule continued

• Ninety-five percent of solitary thyroid nodules
  are benign
• Thyroid cancers typically present as a dominant
  solitary thyroid nodule, cold nodule on scan
• Papillary carcinoma accounts for 60 percent,
  follicular carcinoma accounts for 12 percent, and
  the follicular variant of papillary carcinoma
  accounting for six percent
• Fine needle biopsy is a safe, effective, and easy
  way to determine if a nodule is cancerous

101
Features Favoring Benign Nodule

• Family history of Hashimoto's thyroiditis
• Family history of benign thyroid nodule or
  goiter
• Symptoms of hyperthyroidism or hypothyroidism
• Pain or tenderness associated with a nodule
• Soft, smooth, mobile nodule
• Multinodular goiter without a predominant nodule
  (lots of nodules, not one main nodule)
• Warm" nodule on thyroid scan (produces normal
  amount of hormone)
• Simple cyst on ultrasound

102
Factors Favoring Malignant Nodule

• Age less than 20
• Age greater than 70
• Male gender
• New onset of swallowing difficulties
• New onset of hoarseness
• History of external neck irradiation during
  childhood
• Firm, irregular and fixed nodule
• Presence of cervical lymphadenopathy (swollen
  hard lymph nodes in the neck)
• Previous history of thyroid cancer
• Nodule that is "cold" on scan (shown in picture
  above, meaning the nodule does not make hormone)
• Solid or complex on ultrasound

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104
Thyroid Disease Review
Condition TSH Free T4 Free T3 Other
Graves Disease ??? ? Usually ? Thyroid scan with diffuse isotope uptake
Toxic Adenoma ? ? or Normal ? or Normal thyroid scan shows functioning nodule and suppression of other thyroid tissue
Toxic Multi-nodular Goiter ? ? or Normal ? or Normal thyroid scan shows enlarged gland with multiple active nodules
Thyroiditis ? Variably ? Variably ? thyroid scan shows low radioiodine uptake, thyroglobulin level markedly raised.
Factitious Hyper-thyroidism ? ? ? or Normal low radioiodine uptake on thyroid scan and absent thyroglobulin levels
Pregnancy Normal ? total T4 Normal free T4 ? total T3 Norma free T3 positive pregnancy test
Steroid therapy, Severe Illness, etc. Normal or ? Normal Normal N/A
105
Question 1

• A 60 year old woman comes to your clinic for
  examination of a lump in her neck. On physical
  examination, a soft, smooth, mobile nodule is
  palpated in the left lobe of the thyroid.
  Thyroid scan ordered through your clinic shows a
  1cm hot nodule at the superior pole of the left
  thyroid lobe. Which of the following should you
  tell your patient when she asks about the results
  of her tests?
• A. This lesion most likely represents cancer and
  an urgent surgical referral must be sought
• B. Lesions such as these are exceedingly rare in
  patients her age
• C. 95 of these lesions are benign
• D. She most likely has an infection of the
  thyroid and will require inpatient antibiotic
  therapy

106
Question 2

• A 35 year old African American female presents to
  your clinic with a two week history of
  palpitations, excessive sweating, and a recent 15
  pound weight loss, though she is always eating.
  Also, she notices that the front of her neck is
  fuller than usual and her eyes bug-out. She
  has a history of Lupus, but has otherwise been
  healthy. Routine laboratory tests are ordered.
  Which of the following would you expect to find?
• A. Elevated level of TSH
• B. Decreased level of T4
• C. Decreased level of T3
• D. Auto-antibodies to TSH receptors
• E. Anti-thyroglobulin antibodies

107
Question 3

• While working in the Emergency Department of a
  local community hospital, a five year old boy is
  brought in by his parents because of a sore
  throat. The child has leukemia, and has received
  chemotherapy for the same two weeks prior to his
  presentation. On exam, the child appears
  lethargic. There is a noticeably enlarged lump
  in the area of the left lobe of the thyroid
  gland, which elicits a painful response when
  palpated. Upon further questioning, the parents
  state that he hasnt eaten well over the past 2-3
  days because of difficulty swallowing. Which of
  the following is the most likely diagnosis?
• A. Acute infectious thyroiditis
• B. Sick Euthyroid Syndrome
• C. Hamburger Thyrotoxicosis
• D. Hashimotos Thyroiditis
• E. Plummers Disease

108
References

• American Association of Clinical Endocrinologists
  medical guidelines for clinical practice for the
  evaluation and treatment of hyperthyroidism and
  hypothyroidism. Endocr Pract. 2002
  Nov-Dec8(6)457-69
• Bartalena L. Pinchera A, Macocci C. Management of
  Graves ophthalmopathy Reality and
  prespectives. Endocrine Reviews 2000 21168-199.
  
• Beers, Mark MD et al. The Merck Manual of
  Diagnosis and Therapy Seventh Edition. Merck,
  New York, 1995
• Braunwald, et al. Harrisons Principals of
  Internal Medicine, 15th Edition. McGraw, New
  York. 2001.
• Klopper JF. Diagnosis and management of
  amiodarone-induced hyperthyroidism. SA Med J
  1999 89453-454.
• Murray IPC and Ell PJ. (1998) Nuclear Medicine in
  Clinical Diagnosis and T reatment. 2nd Ed.
  Churchill Livingstone, Edinburgh 136-142.
• O'Reilly DS Thyroid function tests-time for a
  reassessment.BMJ 2000 May 13320(7245)1332-4.
• Student BMJ . Interpreting Thyroid Function
  Tests. 
• www.emedicine.com