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ENDOCRINOLOGY BOARD REVIEW

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ENDOCRINOLOGY BOARD REVIEW THYROID DISORDERS Henri Godbold, MD General - Thyroid produces two related hormones thyroxine(T4) and triidothyronine (T3) - Function is ... – PowerPoint PPT presentation

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Title: ENDOCRINOLOGY BOARD REVIEW


1
ENDOCRINOLOGYBOARD REVIEW
  • THYROID DISORDERS
  • Henri Godbold, MD

2
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

3
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

4
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
  •  

8
SYNTHESIS AND RELEASE
9
  • - 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
17
Measurement RAIU
18
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

21
  • 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

22
  • 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

23
  • 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

24
  • Other causes of hyperthyroidism
  • a. Toxic multinodular goiter
  • b. Toxic adenoma functioning adenoma
  • producing thyroid hormone
  • c. Hashimotos and subacute thyroiditis
  • (transient hyperthyroidism)

25
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

26
  • 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

27
  • 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

28
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

29
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


30
  • 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

31
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

32
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

33
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

34
  • 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

35
  • 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

36
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

37
  • 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

38
  • 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

39
  • 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

40
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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42
  • 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

43
  • 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

44
  • 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

45
  • 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

46
References
  • American College of Physicians
  • MKSAP 13
  • MedStudy Pediatric Board Review
  • Harrisons Principle of Internal Medicine
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