Thyroid Physiology and Testing Quiz
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Questions and Answers

What is the primary physiological role of Free T4 and Free T3?

  • They are unbound hormones that are physiologically active. (correct)
  • They mainly circulate in a bound form.
  • They bind to receptors on cell membranes.
  • They exclusively regulate TSH levels.

    • What can be assessed using an I-123 Uptake Scan?

  • Thyroid metabolic activity. (correct)
  • Patient's free T4 levels.
  • Thyroid nodule composition.
  • TSH secretion levels.

    • During hyperthyroidism due to a primary thyroid disorder, what would TSH levels typically show?

  • Decreased TSH, increased T4, and increased T3. (correct)
  • Normal TSH, normal T4, and normal T3.
  • Increased TSH, decreased T4, and decreased T3.
  • Variable TSH, decreased T4, and increased T3.

    • Why is TSH considered the initial test of choice for assessing thyroid function?

    <p>It shows small changes in response to T4/T3 levels.</p> Signup and view all the answers

    What is the challenge with thyroid nodules in the US population?

    <p>8% of the population has thyroid masses, leading to diagnostic difficulty.</p> Signup and view all the answers

    What does more colloid in a fine needle aspiration typically indicate?

    <p>Higher likelihood of benign nature</p> Signup and view all the answers

    Which feature is NOT commonly associated with hyperthyroidism?

    <p>Cold intolerance</p> Signup and view all the answers

    What is a significant risk associated with excising a lingual mass?

    <p>Possible malignancy without prior examination</p> Signup and view all the answers

    Which age and gender group has the highest prevalence of hypothyroidism?

    <p>Women, especially elderly</p> Signup and view all the answers

    What are common symptoms of sympathetic hyperfunction seen in hyperthyroidism?

    <p>Anxiety and tremor</p> Signup and view all the answers

    What is a common clinical feature of a thyroglossal duct cyst?

    <p>Located midline, above the thyroid cartilage</p> Signup and view all the answers

    In cases of hyperthyroidism, which of the following is considered a significant cardiac complication?

    <p>Congestive heart failure</p> Signup and view all the answers

    The main concern when assessing 'might be malignant' in fine needle aspiration is what?

    <p>Low predictive value</p> Signup and view all the answers

    Which of the following statements about ectopic thyroid is true?

    <p>It may occur anywhere along the thyroglossal duct path</p> Signup and view all the answers

    What is NOT a clinical feature of hypothyroidism?

    <p>Increased sweating</p> Signup and view all the answers

    What is the most common cause of hypothyroidism?

    <p>Hashimotos/autoimmune thyroiditis</p> Signup and view all the answers

    What clinical feature is common in neonates with hypothyroidism?

    <p>Prolonged jaundice</p> Signup and view all the answers

    Which laboratory feature is indicative of primary hypothyroidism?

    <p>High TSH; Low T4</p> Signup and view all the answers

    What is a recognized long-term effect of untreated neonatal hypothyroidism?

    <p>Cognitive delays</p> Signup and view all the answers

    Which condition is characterized as an autoimmune disease leading to hyperthyroidism?

    <p>Grave's disease</p> Signup and view all the answers

    Which of the following conditions can lead to neonatal hypothyroidism due to iodine deficiency?

    <p>Cretinism</p> Signup and view all the answers

    What is the best approach to address misleading laboratory results in systemically sick patients?

    <p>Evaluating post-recovery</p> Signup and view all the answers

    What is the primary mechanism responsible for the altered thyroid function during Euthyroid Sick Syndrome?

    <p>Release of inflammatory mediators</p> Signup and view all the answers

    What is the primary type of immune destruction involved in Hashimoto Thyroiditis?

    <p>T-cell mediated immune destruction</p> Signup and view all the answers

    In Hashimoto Thyroiditis, what would you expect to find in serology during the disease progression?

    <p>Elevated Anti-TPO antibodies</p> Signup and view all the answers

    Which age group has the peak incidence of Hashimoto Thyroiditis?

    <p>Middle-aged adults (40-60 years)</p> Signup and view all the answers

    What is a common morphological finding in Hashimoto Thyroiditis?

    <p>Hurthle cell metaplasia</p> Signup and view all the answers

    What is a defining characteristic of Reidels Thyroiditis?

    <p>Slowly developing hypothyroidism</p> Signup and view all the answers

    What is the typical clinical course of Subacute Thyroiditis?

    <p>Transient hyperthyroidism followed by hypothyroidism</p> Signup and view all the answers

    Which condition is characterized by a decrease in thyroid uptake during diagnosis?

    <p>Hashimoto Thyroiditis</p> Signup and view all the answers

    Which type of goiter is associated with dietary iodine deficiency?

    <p>Endemic Goiter</p> Signup and view all the answers

    What type of nodule is most commonly associated with Follicular Adenoma?

    <p>Cold nodule</p> Signup and view all the answers

    Which thyroid carcinoma has the highest incidence among thyroid cancers?

    <p>Papillary Carcinoma</p> Signup and view all the answers

    Which of the following is a characteristic morphology of Papillary Carcinoma?

    <p>Presence of psammoma bodies</p> Signup and view all the answers

    What is a common clinical feature of Multinodular Goiter?

    <p>Usually asymptomatic with cosmetic issues</p> Signup and view all the answers

    Which mutation is commonly associated with poor prognosis in Papillary Carcinoma?

    <p>BRAFv600e mutation</p> Signup and view all the answers

    In what way do autoimmune conditions like Hashimoto's increase the risk of other diseases?

    <p>Increased risk of other autoimmune diseases due to shared mechanisms</p> Signup and view all the answers

    What defines a follicular carcinoma?

    <p>Presence of vascular or capsular invasion</p> Signup and view all the answers

    What is a characteristic histological feature of papillary carcinoma that correlates with a favorable prognosis?

    <p>Complete encapsulation</p> Signup and view all the answers

    In poorly differentiated carcinoma, what mutation is commonly involved?

    <p>p53 inactivation</p> Signup and view all the answers

    What distinguishes medullary carcinoma from other thyroid cancers?

    <p>It secretes calcitonin</p> Signup and view all the answers

    Which factor is associated with a better prognosis in medullary carcinoma?

    <p>Limited disease to the thyroid gland</p> Signup and view all the answers

    What clinical symptom might result from poorly differentiated carcinoma's invasion?

    <p>Vocal cord paralysis</p> Signup and view all the answers

    What is a common characteristic of follicular carcinoma in terms of morphology?

    <p>Similar architecture to follicular adenoma</p> Signup and view all the answers

    Which condition has the highest 1-year mortality rate among thyroid cancers?

    <p>Poorly differentiated carcinoma</p> Signup and view all the answers

    What is a common clinical presentation of patients with medullary carcinoma?

    <p>Diarrhea</p> Signup and view all the answers

    What is the risk factor related to the familial form of medullary carcinoma?

    <p>Presence of multiple thyroid masses</p> Signup and view all the answers

    Study Notes

    Hypothyroidism

    • 90% of hypothyroidism in regions of sufficient iodine is caused by Hashimoto Thyroiditis
    • Typically affects women more so than men
    • Peak Age 40-60 years
    • Incidence 4/1000 women; 1/1000 men

    Hashimoto Thyroiditis

    • Autoimmune destruction of thyroid gland
    • T-cell-mediated immune destruction of gland
    • Circulating autoantibodies are often present:
      • Anti-TSH (blocking usually)
      • Anti-TPO
      • Anti-thyroglobulin
      • May be elevated in any form of immune destruction of thyroid
    • Initial hormone release may occur, leading to transient hyperthyroidism
    • Gland shrinks and fibrosis occurs, resulting in a smaller fibrotic gland

    Hashimoto Thyroiditis - Clinical

    • Early Stages:
      • Chronic inflammation
      • Gland is enlarged, non-tender, firm
      • May be hyperthyroid, euthyroid, or hypothyroid
    • Late Stages:
      • Follicle destruction
      • Slow decrease in gland size +/- nodularity
      • Capsule remains intact; gland mobile
      • Hypothyroid

    Hashimoto Thyroiditis - Clinical Complications

    • Increased risk of other autoimmune diseases:
      • Diabetes
      • Vitiligo
      • Pernicious Anemia
      • Myasthenia gravis
    • Increased risk of MALToma due to continued immune stimulation

    Hashimoto Thyroiditis - Morphology

    • Early Stages:
      • Gland enlargement
      • Brisk lymphocytic inflammation
      • Germinal centers
      • Thyroid epithelium- - ->Hurthle cell metaplasia (big and pink)
    • Late Stages:
      • Gland atrophy
      • Gland fibrosis

    Hashimoto Thyroiditis - Diagnosis

    • Early Possible Diagnosis: High T4/T3, Low TSH with Decreased thyroid uptake
    • Primary hypothyroidism (if late enough)
      • High TSH
      • Low T4/T3
    • Serology
      • Anti-TPO
      • Anti-thyroglobulin
      • Anti-TSH blocking
    • Thyroid Iodine Scan:
      • Decreased uptake
      • Shrunken; May show nodularity

    Riedels Thyroiditis - Clinical

    • Slowly developing hypothyroidism
    • Most prominent: symptoms of compression:
      • Trachea
      • Nerves
      • Vessels
    • Painless
    • Fibrosis- - ->Rock hard gland
      • Asymmetric, fixed in place
    • Differential diagnosis: Cancer with invasion of adjacent structures

    Subacute Thyroiditis - Clinical

    • Typically follows URI
    • Painful thyroid on swallowing, neck motion, etc
    • Hyperthyroid
    • Then Hypothyroid as gland is depleted
    • Then restored to normal
    • CRP/ESR usually elevated
    • I-scan decreased uptake

    Subacute Thyroiditis - Morphology

    • Follicle depletion and rupture
    • Granulomatous reaction

    Subacute Painless Thyroiditis

    • Lymphocytic thyroiditis without Hurthle Cells or Germinal Centers
    • Usually self-limited
    • Usually women, often post-partum
    • Transient hyperthyroidism, then normalizes
    • Morphology: Similar to Hashimotos but no Hurthle Cells
    • Clinical: Similar to Subacute Granulomatous but lymphocytes, not granulomas
      • Autoimmune not viral
      • ESR/CRP normal; I-scan with decreased uptake

    Goiter

    • Term for thyroid enlargement
    • Includes some of today’s defined entities
    • Also due to intact feedback loops:
      • Hypothyroidism- - ->high TSH- - ->gland hyperplasia- - ->(hopefully euthyroid)
    • Causes:
      • Iodine Deficiency: (Endemic Goiter): Common worldwide (mountain, inland)
      • Inborn errors- - ->Dyshormonogenetic Goiter
      • Goitrogens: Dietary inhibitors of T4/T3 synthesis
        • Broccoli, Cauliflower, Kale, Brussels Sprouts, Cabbage, soy, others
      • Lithium
      • Sporadic: Unknown cause; usually young women

    Endemic Goiter

    • Geographic regions with >10% Iodine Deficient goiter
    • People usually euthyroid
    • Symmetric diffuse gland enlargement
    • Usually modest enlargement
    • Typical labs:
      • Normal T4, High TSH or High Normal TSH
    • Gradually form areas of involution- - -> “Colloid Goiter”
      • Zones of HIGH colloid content

    Multinodular Goiter

    • Evolution of multinodularity out of diffuse goiter
    • May arise in Endemic or Sporadic goiters, etc
    • Late complication so older age group.
    • May produce huge glands
    • May produce hyperfunctioning nodules
      • “Toxic Nodule” or “Hot Nodule”

    Multinodular Goiter - Pathogenesis

    • Compensatory hypertrophy and hyperplasia:
      • Dietary Iodine deficiency, Goitrogen, Sporadic
      • TSH response- - -> Euthyroid state
        • Severe deficiency may lead to goitrous hypothyroidism
    • Initial response results in diffuse enlargement
    • Over time, areas of involution develop
    • Other areas become hyperplastic
    • Development of zones of clonality
      • Areas of proliferation
      • Areas of involution- - ->cold nodules
      • May become autonomous T4 producers- - ->Toxic or “hot” nodule)

    Multinodular Goiter - Morphology

    • Labs:
      • T4:
      • TSH:
      • Thyroid Scan:

    Multinodular Goiter - Clinical

    • Usually euthyroid,
      • may have subclinical hypothyroidism
      • May have hyperthyroidism
    • Symptoms:
      • Cosmetic
      • Mass effect and compression
        • Vascular
        • Airway
        • SVC syndrome

    Goiter - Terminology

    • Diffuse Nontoxic Goiter
    • Multinodular Goiter
    • Toxic Multinodular Goiter
    • “hot” nodule
    • “cold” nodule

    Thyroid Tumors

    • Benign:
      • Hyperplastic Nodule/Multinodular Goiter
      • Follicular Adenoma
    • Malignant:
      • Papillary Thyroid Carcinoma
      • Follicular Carcinoma
      • Medullary Carcinoma
      • Insular Carcinoma
      • Anaplastic Carcinoma

    Thyroid Nodules

    • Up to 8% of US population has a thyroid nodule
    • Found more in men
    • Age Peak: 40-50yrs
    • Mostly incidental findings on physical or imaging

    Follicular Adenoma - Clinical

    • Most are non-functioning, “cold” nodules:
      • Non-functioning, cold nodules
      • Incidental findings
    • Minority show constitutive activation of TSH:
      • Toxic and hot
      • TSH receptor mutations
      • G-protein α subunit mutations

    Follicular Adenoma - Morphology

    • Encapsulated
    • Well circumscribed
    • NO capsular penetration
    • NO vascular invasion
    • Small caliber follicles, “microfollicles”
    • Must be removed for diagnosis
    • Surgery is curative

    Follicular Adenoma - Fine Needle Aspirate Findings

    • Fine Needle Aspirate findings

    Thyroid Cancer

    • Incidence 50,000/yr in US
    • 98% 5 yr survival
    • Types:
      • Papillary Carcinoma 80%
        • Very low grade
      • Follicular Carcinoma 10%
      • Poorly differentiated or Anaplastic 5%
      • Medullary Carcinoma 5%
    • Risk factors:
      • Ionizing radiation as youth: especially for Papillary and Follicular
      • Family history, especially for Medullary

    Thyroid Cancer - Genetics

    • Papillary
      • Translocation: RET-PTC or NTRK gene fusions
      • Activating Point mutations: BRAFv600e- - ->worse prognosis
    • Follicular
      • RAS or PIK3 gain of function
      • PTEN loss of function
      • PPARG-Pax8 fusion gene
    • Poorly Differentiation/Anaplastic
      • Arise from PTC, FTC
      • Same mutations with addition of p53, β-catenin, and/or TERT
    • Medullary
      • RET oncogenes

    Papillary Carcinoma

    • Malignant neoplasm of follicular epithelial cells with papillary morphology (cytologic or architectural)
    • 80+% of thyroid cancers
    • 25-50 years
    • Tend to be cold nodules
    • Associated with radiation exposure
    • Dissemination is through lymphatic route
    • Prognosis: >95% 10 year survival

    Papillary Carcinoma - Morphology

    • Nuclear features:
      • Longitudinal grooves
      • INCI’s
      • Ground glass nuclei
    • Architecture:
      • Papillae with fibrovascular cores
      • Psammoma bodies

    Non-invasive Follicular Thyroid Neoplasm with Papillary-like Nuclear Features (NIFT-P)

    • Putative benign precursor to Follicular
    • Total may be increased/decreased even though euthyroid

    Free T4 and Free T3

    • Unbound hormone which is physiologically active form
    • Most will start with free T4/T3

    I-123 Uptake Scan

    • Nuclear medicine scan to assess thyroid metabolic activity
    • Thyroid avidly takes iodine out of circulation
    • Radioactive label allows visualization:
      • Gland contour
      • Relative metabolic activity: Hot and Cold

    TSH and T4/T3

    • TSH is very sensitive to levels of T4/T3
    • Small changes in hormone cause large changes in TSH
    • TSH alone is sometimes used as screening test:
      • TSH interpreted in light of T4/T3
      • If TSH abnormal, then get T4/T3
      • TSH is initial test of choice for hypo/hyperfunction

    TSH, T4, T3 and I-Uptake

    • If a patient has hyperthyroidism due to a primary thyroid disorder:
      • TSH - Low
      • T4 - High
      • T3 - High
      • I-uptake - High/Increased

    Fine Needle Aspiration

    • Low morbidity procedure to assess thyroid nodule/mass
    • DDx: Cancer or Not cancer. 1-5% are cancer.
    • FNA allows triage to two different buckets:
      • This might be malignant; High sensitivity; low predictive value
      • This is not malignant; safe to leave in place
    • Remove all “might be malignant” cases

    Fine Needle Aspiration - Aspiration Findings

    • Cells:
      • Follicular cells:
        • Papillary features
        • Microfollicular features
      • C-cells:
        • Normally too few to recognize
      • Lymphocytes:
        • Benign or Malignant
      • Others
    • Colloid:
      • More colloid=more likely to be benign

    Thyroid Developmental Disorders

    • Thyroglossal duct path lies between foramen cecum to the pyramidal lobe of thyroid

    Ectopic Thyroid

    • May lie anywhere along thyroglossal duct path
    • Ectopic thyroid is in DDx of:
      • mediastinal
      • lingual
      • anterior neck masses
    • DO NOT EXCISE lingual mass without knowing what it is!

    Thyroglossal Duct Cyst

    • Failure of duct involution
    • Cystic remnants may persist anywhere along this path
    • Sinus tracts to tongue may also be present
    • Cysts are lined by squamous to follicular epithelium; filled with mucus and/or thyroid hormone
    • Most 1-3 cm
    • Classic location: Midline, above thyroid cartilage, below hyoid bone
    • Prone to infection with URI
    • Rarely develop malignancy

    Hyperthyroidism

    • Excess T4/T3 activity
    • Increase basal metabolic rate
      • ↑ O2 consumption; ↑Heat production
      • ↑ Heart Rate; ↑ Cardiac Output
      • ↑ gut motility
      • ↑bone turnover
      • ↑gluconeogenesis and glycogenolysis
      • ↑sensitivity to catecholamines- - ->alertness, sweating, heart rate

    Hyperthyroidism - Clinical Features

    • Increased basal metabolic rate:
      • Heat intolerance
      • Weight loss
    • Cardiac dysfunction:
      • Tachycardia and palpitations
      • Arrhythmias, especially atrial fibrillation
      • Congestive Heart Failure
        • May be high output
        • May be low output d/t LV dysfunction, especially elderly
    • Sympathetic hyperfunction:
      • Hyperactivity, anxiety, tremor, insomnia
      • Hyperhydrosis
      • Hyperdefecation d/t increased gut motility
      • Peripheral vasodilation
    • Other:
      • Ocular-wide staring gaze with lid lag
      • Skin: Warm and moist
      • Skeletal-osteoporosis and increased fractures
      • Fatty liver
      • Muscle weakness/atrophy (Graves)

    Hypothyroidism - Clinical Features

    • Common, especially in woman (10x rate of men)
    • Cool, dry skin, decreased sweating
    • Thin, hyperkeratotic skin
    • Thick, puffy appearance of eyes, hands/feet, shoulders
      • Dermal glycosaminoglycans→non-pitting edema (AKA myxedema)
    • Constipation
    • Weight gain (modest, mostly due to myxedema)
    • Cold intolerance
    • Decreased cardiac contractility
    • Decreased libido and fertility (remember TRH:Prl connection)

    Hypothyroidism

    • Common, easily treatable disorder
    • DDx: the user is tired, bored with life, overweight, and pale.
    • Lab features:
      • Central hypothyroidism: 1% of cases, low TSH, low T4, T3 falls later in the disease process.
      • Primary hypothyroidism: 99% of cases, high TSH, low T4.
    • Causes of hypothyroidism:
      • Hashimoto's/autoimmune thyroiditis (most common cause)
      • Radiation injury
      • Surgical removal
      • Iodine deficiency
      • Hypopituitarism
      • Subclinical hypothyroidism (6-10% of population, especially elderly)
    • Neonatal hypothyroidism: 1/4000 worldwide, greatly reduced in wealthy areas due to iodine supplementation and neonatal screening.
      • Causes:
        • Maternal thyroid disease --> cretinism (supplies baby up to about 3-4 months gestation, prenatal screening if personal or family history, transplacental passage of autoantibodies)
        • Neonatal thyroid disease --> neonatal hypothyroidism (iodine deficiency, thyroid gland dysgenesis/agenesis, dyshormonogenesis, TSH-R antibody mediated)

    Neonatal Hypothyroidism

    • Effects: relatively normal at birth due to maternal hormone, large head and wide fontanels due to brain myxedema, prolonged jaundice, sluggish feeding, crying, and general activity, umbilical hernia is common, developmental, growth and cognitive delays, and features of adult hypothyroidism.

    Cretinism

    • Intellectual disability due to intrauterine hypothyroidism (maternal)
    • Cognitive delay and impairment (irreversible)
    • Growth impairment
    • Umbilical hernia
    • Protruding tongue
    • Largely eradicated with universal newborn screening

    Euthyroid Sick Syndrome

    • Misleading laboratory results due to release of inflammatory mediators by systemically sick patients
    • Decreased/altered binding proteins
    • Decreased deiodination
    • Altered TSH response: spuriously high or low
    • May have: low total T3, normal T4, normal TSH, low TSH, high TSH, low T4 and T3
    • Best solution is to test at recovery

    Grave's Disease

    • Autoimmune disease caused by thyroid stimulating anti-TSH receptor antibodies
    • Most common cause of hyperthyroidism
    • Affects 1-2% of US women

    Papillary Carcinoma

    • Mutations: V600E, may have BRAF, but not BRAF
    • Benign prognosis criteria: complete encapsulation, no vascular or capsular invasion, no necrosis, rare mitoses (90% 10 year survival)
    • Minimally Invasive: 50% 10 year survival.

    Follicular Carcinoma

    • Morphology: malignant neoplasm of follicular epithelial cell, often surrounded by a fibrous capsule, cells and architecture same as follicular adenoma, defined by capsular and/or vascular invasion.
      • Minimally invasive: if 4 vessels or extensive invasion of thyroid and soft tissues.

    Poorly/Undifferentiated Carcinoma

    • High-grade neoplasms of follicular epithelium
    • Most likely arise from pre-existing papillary or follicular carcinoma
    • Same demographics, but older
    • Addition of p53 inactivation or β-catenin activation
    • Approaching 100% 1-year mortality
      • PD carcinoma slightly better
    • Clinical: rapidly enlarging, bulky masses, elderly patients, often with long-term goiter, tend to be locally invasive and unresectable, symptoms from invasion, compression of local structures (hoarseness, stridor, dysphagia, nerve dysfunction)
    • Morphology: highly variable (spindled/sarcomatoid, spindled and giant cells, sheets of malignant epithelial cells, some with recognizable areas of residual Papillary or Follicular Carcinoma)

    Medullary Carcinoma

    • Malignant neoplasm of thyroid C-cells (neuroendocrine cells which secrete calcitonin)
    • Arise in two settings: sporadic, familial (MEN-2a and MEN-2b syndromes)
    • Malignant neuroendocrine neoplasm of C-cells: ~5% of thyroid malignancies
      • Sporadic: 70%, 40-50 year old, single mass, no surrounding C-cell hyperplasia
      • Familial: teens and 20's, often multiple, C-cell hyperplasia
    • Clinical: secrete calcitonin (normal calcium levels usually, used diagnostically and for follow-up), symptoms from mass effect, sometimes secrete VIP and/or ACTH (diarrhea, Cushing's syndrome), prognosis highly stage dependent (100% survival if limited to thyroid, overall 50% 5 year survival), treatment includes surgery, prophylactic surgery if syndromic
    • Morphology: spindled and epithelioid cells, calcitonin positive, produce amyloid frequently.

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