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
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Measurement RAIU
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Drugs and condition that affect thyroid Function
Tests
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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