ENDOCRINOLOGY BOARD REVIEW

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ENDOCRINOLOGYBOARD REVIEW

• THYROID DISORDERS
• Henri Godbold, MD

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General

• - Thyroid produces two related hormones
  thyroxine(T4) and triidothyronine (T3)
• - Function is through nuclear receptors playing
  a role in cell differentiation
• - Maintains thermogensis, and metabolic
  homeostasis
• - Disorders result from autoimmune processes
  that either stimulate overproduction of hormones
  (thyrotoxicosis) or glandular destruction and
  hormone deficiency (hypothyroidism)
• - Benign nodules and various forms of thyroid
  cancers

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Anatomy

• - Located anterior to trachea consist two lobes
• -  Weighs 12-20gm soft and highly vascular a
  posterior region gland contain four parathyroid
  gland that produce parathyroid hormone
• - Lateral borders of the gland is transversed by
  the recurrent laryngeal nerves
• - Develops from the floor of the primitive
  pharynx third week of gestation migrates from the
  foramen cecum, at the base of tongue along the
  thyroglossal duct to neck
• - Hormonal synthesis usually begin at about 11
  weeks gestation

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Thyroid Physiology

• - Thyroid releases (2) forms of hormones
• - Thyroxine (T4) and triiodothyroxine (T3) ratio
  141
• - T3 is 80 derived from peripheral tissue
• - T4 all within the thyroid gland
• - T3 is produced from T4 in liver, kidneys,
  pituitary gland and CNS
• - T3 is the physiologically active in almost all
  tissue binding to specific nuclear
  receptors regulating the transcription of thyroid
  hormone dependent genes
•  

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Drugs decreasing Peripheral conversion of T4 to
T3

•        Propranolol
•        Corticosteroids
•        Propylthiouracil (PTU)
•        Amiodarone
•  

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SYNTHESIS AND RELEASE
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• - TSH controls release under the influence TRH
• from the hypothalamus
• - TSH stimulate thyrocyte function resulting in
  
• iodide uptake actively on the basal surface
  of the
• thyroid follicle cell
• - Iodide undergoes oxidation to iodine which
• iodinates tyrosine residues catalyzed by
• peroxidase
• - Thyroglobulin coupling occurs to form mono-
• and diiodotyrosine (MIT and DIT
• - Two DITs coupling T4
• - One DIT and one MIT combine T3
• - If iodine scarce, the production of T3 is
  increase
• - Activity is dictated by iodines attached
• to tyrosine molecules and location
•  

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Secretion

• Degradation process with endocytosis of the
  follicular colloid containing MIT, T3,
• T4, DIT attached to thyroglobulin undergoes
  fusion with lyosome resulting in proteolysis
  release
• Deiodination occurs with the recycling iodide and
  secretion of T3 and T4
• Circulating thyroid hormones are more than 99
  protein bound, are thyroxine-binding globulin,
  albumin, and transthyretin.
• 80 of circulating T3 is derived from the
  conversion of T4 outside the thyroid
• Serum half-life of T3 is much shorter than that
  T4 (1day vs 8days)

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Storage

• - Iodine as iodinated tyrosine of
• thyroglobins 8000 micrograms total
• - T4 and T3 represent 600 micrograms
• each
• - Enough hormone is stored in the
• follicular colloid to last 2-3 months 

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Overveiw of Thyroid Fx Workup
1st Test 2nd Test 3rd Test
TSH FT4-I, FT4 Clinical Status
HIGH Low Prim hypothyrism N/A
HIGH Normal Subclinical hypothyism TRH to confirm
HIGH High Pituitary hyperthyrism N/A
LOW High Thyrotoxicosis RAIU
LOW Normal Subclinical hypothyrism TRH to confirm
LOW Low Pituitary hyperthyrism N/A
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Measurement RAIU
Levels Specific disorders
High Hyperfunction (Graves, multinodule goiter, toxic solitary nodule, hCG secreting tumor)
Normal Euthyroid
Low Thyroiditis, severe iodine excess, amiodarone induced thyrotoxicosis
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Drugs and condition that affect thyroid Function
Tests
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Increase TBG Decrease TBG Block peripheral conversion of T4 to T3 Blocks thyroidal release T4 and T3
Estrogen OCT, pregnancy Tamoxifen Clofibarate Narcotics Hepatitis Bililary cirrhosis Androgens Gluccorticoid Nephrotic syn Propranolol Glucorticoid PTU Amiodarone Lithium Iodine
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Thyroid Pathology

• A. Thyroid Gland
• 1. Multinodular goiter (nontoxic goiter)
  Presentation
• i. Females gt males
• ii. Frequently asymptornatic
• iii. Typically euthyroid
• iv. Goiter
• v. Plummer's syndromedevelopment of
• hyperthyroidism (toxic multinodular Goiter)
• late in course

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• B. GROSS
• enlarged thyroid gland with multiple colloid
  nodules
• C. MICROSCOPIC
• i. Nodules of varying sizes composed of colloid
  follicles
• ii. Calcification, hemorrhage, cystic
  degeneration, and fibrosis
• D. LAB normal T4, T3, and TSH

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• B Hyperthyroidism
• 1. General features of hyperthyroidism I
• a. Clinical features
• i. Tachycardia and palpitations
• ii. Nervousness and diaphoresis
• iii. Heat intolerance
• iv. Weakness and tremors
• v. Diarrhea
• vi. Weight loss despite a good appetite
• b. Labs
• i. Elevated free T4
  ii. Primary
  hyperthyroidism decreased TSH

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• Graves'disease
• a. Definition autoimmune diseases
  characterized by production of IgG
  autoantibodies to the TSH receptor
• b. Clinical features
• i. Females gt males age 20-40
• ii. Hyperthyroidism
• iii. Diffuse goiter
• iv. Ophthalmopathy exophthalmus
• v. Dermopathy pretibial myxcdema
• c. Micro hyperplastic follicles with
  scalloped
• colloid

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• Other causes of hyperthyroidism
• a. Toxic multinodular goiter
• b. Toxic adenoma functioning adenoma
• producing thyroid hormone
• c. Hashimotos and subacute thyroiditis
• (transient hyperthyroidism)

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Juvenile Graves Disease

• Diffuse hyperplasia
• Most common cause of thyrotoxicosis in children
  and adolescents
• Clinical manifestation
• - muscle weakness - behavior
  problems
• - anxiety -
  cardiomegaly
• - palpitations -
  tachycardia
• - appetite -
  widen pulse pressure
• - Tremor -
  Emotional liability
• - rapid DTR time - Excessive
  perspiration
• Opthalmopathy, dermopathy, pretibial myxedema
• rare in children

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• Test TSH suppressed and serum T4 high
• Treatment
• a. Blunting toxic effects circulating T3/T4
• b. Stop further increase in production
• B-blockers prior to Sx intervention
• RAI rarely used in children and adolescences
  potential risk leukemia, thyroid Ca, and genetic
  disorder.
• Medical management PTU and methimazole
• mechanism Both inhibit the coupling of
• iodotyrosines,
  oxidation and
• binding of iodide
  

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• PTU 5-10mg/kg PO div q8hr
• Methimazole 0.2 mg/kg PO daily
• Once gland cools off and decrease in size
• tapper drugs
• Give synthetic T4 once euthyroid adjust to
  maintain a euthyroid status

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Neonatal Thyrotoxicosis

• Due to TSH-receptor stimulating antibodies(TSH)
• Transmitted transplacentally in mother with
• inactive or active Graves or Hashimoto
  thyroiditis
• Presentation newborn irritability, flushing,
  tachycardia, HTN, thyromegaly
• High total T4, FT4, T3 postnatal blood, low TSH
• Treatment
• a. sedative and digitalis if needed
• b. Iodide
• c. Lugol (5 iodine and 10 K iodine)
• d. Methimazole

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Hypothyroidism

• a. Clinical features
• i. Fatigue
• ii. Sensitivity to cold temperatures
• iii. Decreased cardiac output
• iv. Myxedema
• - Facial and periorbital edema
• - Peripheral edema of the hands and
• feet
• - Deep voice
• - Macroglossia
• v. Constipation
• vi. Anovulatory cycles

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• b. Lab
• i. Decrease Free T4
• ii. Primary hypothyroidism elevated TSH
• Iatrogenic hypothyroidism
• Most common cause of hypothyroids in US
• Secondary to thyroidectomy or RAI rx
• Rx Levothyroxine 12.5-50mcg PO qd adjusting
• dose by 12.5-25mcg/d q4-8wks

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Congential Hypothyroidism(cretinism)

• a. Etiology
• i. Endemic region iodine deficiency during
  intrauterine and
• neonatal life ( worldwide)
• ii. Non endemic regions thyroid dysgenesis
• b. Presentation
• i. Failure to thrive
• ii. Stunted bone growth and dwarfism
• -Commonly absent distal femoral epiphysis
• iii. Spasticity and motor incoordination
• iv. Mental retardation
• v. Goiter (endemic cretinism)
• - Endemic goiter
• a. Uncommon in the US
• b. Etiology dietary deficiency of iodine

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Clinical Manifestation congenital Hypothyroidism

• Occurs in 1/4000 Worldwide
• Most infant are asymptomatic at birth because of
  transplacental passage of T4 (usu 3rd day of
  life)
• Most common cause is thyroid dysgenesis
• Presentation hypoglycemia, jaundice
• micropenis, midline
  facial
• anomalies, enlarge
  posterior
• fontanelle, macroglossia
• Rx Initial dose Sodium L-tyroxine 10-15
• microgrms/kg/day( should not be mixed soy
• protien or iron) Then, 4 micrgms/kg/day

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Thyroiditis

• Hashimoto's thyroiditis
• a. Definition chronic autoimmune disease
  characterized by immune destruction of
  the thyroid gland and hypothyroidism
• b. Most common noniatrogenic cause of
  hypothyroidism and Goiter in children gt 6yo and
  adults in US
• c. Clinical presentation
• i. Females gt males age 40-65
• ii. Painless goiter
• iii. Hypothyroid
• iv. Initial inflammation may cause transient
  hyperthyroidism.
• d. Gross pale enlarge gland
• e. Micro
• i. Lymphocytic inflammation with
  germinal centers
• ii. Epithelial "Harthle cell" changes
• f. May be associated with other autoimmune
  diseases (SLE, RA, SS Sjogren's syndrome,
  etc.)
• g. Complication increased risk of non-Hodgkin
  lymphoma (NHL) B-cell lymphoma

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• 2. Subacute thyroiditis
• a. Synonyms De Quervain's thyroiditis,
  granulomatous
• thyroiditis
• b. Clinical features
• i. Second most common form of
  thyroiditis
• ii. Females gt males age 30-50
• iii. Preceded by a viral illness
• iv. Tender, firm, enlarged thyroid gland
• v. May have transient hyperthyroidism
• c. Micro granulomatous thyroiditis
• d. Prognosis typically the disease follows a
  self-limited course
• e. Symptoms control with analgesics,
  prednisone very severe dx

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• Riedel's thyroiditis
• a. Definition rare disease of unknown etiology
  characterized by destruction of the thyroid gland
  by dense fibrosis and fibrosis of surrounding
  structures (trachea and esophagus)
• b. Clinical features
• i. Females gt males middle age
• ii. Irregular, hard thyroid that is adherent to
  adjacent structures
• iii. May mimic carcinoma and present with
  stridor, dyspnea, or dysphagia
• c. Micro
• i. Dense fibrous replacement of the thyroid
  gland
• ii. Chronic inflammation
• d. Associated with retroperitoneal
  and mediastinal fibrosis

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Thyroid Neoplasia

• Adenomas
• a. Follicular adenomas are the most common
• b. Clinical features
• i. Usually painless, solitary nodules
• In first 20 yrs life likely
  malignant than older person
• ii. "Cold nodule" on thyroid scans
• iii. May be functional and cause
  hyperthyroidism
• (toxic adenoma)
• 2. Papillary carcinoma
• a. Epidemiology
• i. Account for 80 of malignant thyroid
  tumors
• ii. Females gt males age 20-50
• iii. Risk factor radiation
  exposure
• b. Micro
• i. The tumor typically exhibits a papillary
  pattern.
• ii. Occasional psammoma bodies
• iii. Characteristic nuclear features Clear
  "Orphan Annie eye" nuclei Nuclear grooves

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• Intranuclear cytoplasmic inclusions
• c. Lymphatic spread to cervical nodes is common.
• d. Treatment
• i. Resection is curative in most cases.
• ii. Radiotherapy with iodine 131 is effective
  for metastases.
• e. Prognosis excellent 20-year survival 90
• Follicular carcinoma
• a. Accounts for 15 of malignant thyroid tumors
• b. Females gt males age 40-60
• c. Hematogenous metastasis to the bones or lungs
  is common.
• d. High mortality rate because most present with
  distant mets

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• Medullary carcinoma
• a. Accounts for 5 of malignant thyroid tumors
• b. Arises from C cells (parafollicular cells)
  and secretes
• calcitonin
• c. Micro nests of polygonal cells in an amyloid
  stroma
• d. Minority (25) are associated with MEN 2 and
  MEN
• 3 syndromes
• Treatment primarily surgical
• - Advance disease external RT and chemo

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• Anaplastic carcinoma
• a. Presentation
• i. Females gt males age gt 60
• ii. Firm, enlarging, bulky mass
• iii. Dyspnea and dysphagia
• iv. Tendency for early widespread
• metastasis and invasion
  of the
• trachea and esophagus
• b. Micro undifferentiated, anaplastic, and
• pleornorphic cells
• c. Prognosis very aggressive and rapidly
  fatal

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Diagnosis

• Fine needle aspirate vs. excision
• - Hx RT to neck or head
• - rapidly growing nodule
• - satellite LN and/or distant mets
• - Hoarseness or dysphagia
• Rx Well differentiated neoplasm should be
  excised
• - TSH suppression
• - RAI ablation

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• Q1 An 18yo old boy presents with a 1 month
  history of slowly enlarging neck mass. You
  palpate a 2-cm mass in the superior lobe of the
  rt. thyroid with no lymphadenopathy.
• Of the following, the BEST next step is to
• Begin therapy with RAI
• Obtain anteroposterior and lateral CXR
• Perform needle bx of the neck
• Perform total thyroidectomy
• Prescribe oral cephalexin

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• Q2. 15yo female presents with an asymptomatic
  goiter. She has type 1 diabetes that was
  diagnosed at age 7 years
• Of the following, study that is MOST likely to
  establish the diagnosis is
• Measurement of antiperoxidase antibodies
• Needle bx of thyroid
• Technetium thyroid scan
• Thyroid-binding globulin levels
• US of the thyroid

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• Q3. 44yo male involved in a MVA unresponsive
  intubated in ICU with multiple orthropedic
  injuries. He is stabilized medically on day 2
  undergoes open reduction and internal fixation of
  right femur and right humerus. After returning to
  the ICU, his TSH is 0.3mU/L and total T4 is
  normal. T3 is 0.6 micrograms/dl. What is the next
  appropriate step in the management of this
  patient?
• Start levothyroxine
• RAIU scan
• Thyroid US
• Observe patient
• Initiate prednisone

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• Q4. Which of the following statements regarding
  hypothyroidism is true?
• Hashimotos thyroiditis is the most common cause
  of hypothyroidism worldwide
• The annual risk of developing overt clinical
  hypothyroidism from subclinical hypothyroidism in
  patients with positive thyroid peroxidase
  antibodies is 20.
• Hashimotos is characterized by marked
  infiltration of thyroid with activated T and B
  cells
• Low TSH excludes the diagnosis of hypothyroidism
• Thyroid peroxidase antibodies are present in 50
  of patients with autoimmune hypothyroidism

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References

• American College of Physicians
• MKSAP 13
• MedStudy Pediatric Board Review
• Harrisons Principle of Internal Medicine