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THYROID FUNCTION
THE THYROID
● Responsible for the production of thyroid hormone and calcitonin ● Calcitonin is secreted by the parafollicular cells (C cells) and is involved in the calcium homeostasis ● Thyroid hormone is critical in regulating body metabolism, neurologic development, and numerous other body functions THYROID ANATOMY ● The thyroid gland is positioned in the lower anterior neck and is shaped like a butterfly ● Made up of two lobes resting on each side of the trachea, bridged by the isthmus , with a band of thyroid tissue running anterior to trachea ● Regulated by: ○ Hypothalamus ○ Pituitary Gland ● Posterior to the thyroid gland is the parathyroid gland, which regulates: ○ Serum calcium levels ○ Recurrent laryngeal nerves innervating the vocal cords ● Follicle, tiny bags or sacs, is the fundamental structural unit of the thyroid gland ● Microscopically, the thyroid gland is composed of thyroid follicles ○ Each follicle contains an outer layer of follicular endothelial cells that surround the lumen willed with colloid ○ Colloid is predominantly thyroglobulin , a protein used to produce thyroid hormone ○ Parafollicular cells (C cells) are located between the follicular endothelial cells and secretes calcitonin ○ Follicular cells = T3 and T ○ Parafollicular cells = Calcitonin ○ Iodine + tyrosine ● Medullary Carcinoma (Parafollicular) = Increased calcitonin Practice Question: Thyroid hormones are derived from which amino acid? A. Phenylalanine B. Methionine C. Tyrosine D. Histidine Correct answer: C THYROID DEVELOPMENT ● The fetal thyroid develops from an outpoaching of the foregut at the base of the tongue that migrates to its final location over the thyroid cartilage in the first 4 to 8 weeks of gestation ● By week 11 of gestation, thyroid glands begin to produce measurable amounts of thyroid hormone ● Iodine is an essential component of the thyroid hormone ○ Without iodine, neither the mother nor the fetus can produce thyroid hormone leading to hypothyroidism ○ Neonatal hypothyroidism can lead to mental impairment and cretinism ● If the mother has normal thyroid function, small amounts of maternal thyroid hormone crossing the placenta can protect the fetus during development
THYROID HORMONE SYNTHESIS
● Thyroid hormone is made primarily of trace element iodine , a key determinant in thyroid function ○ Iodine is found in seafoods, dairy products, and vitamins ○ The recommended daily intake of iodine in adults: 150 ug ○ Average daily intake of iodine is at an estimated: 190-300 ug ○ If iodine intake drops below 50 ug, the thyroid gland is unable to produce adequate amounts of thyroid hormone, resulting to hypothyroidism ● Thyroid cells (thyrocytes) are organized into spheres surrounding a central core of fluid called colloid (these structures are called follicles ) ● Thyroglobulin, the major component of colloid, is a glycoprotein produced exclusively by thyroid follicular cells and rich in tyrosine ○ Some of these tyrosyl residues will be iodinated to produce building blocks of thyroid hormone ● On the outer side of the follicle, iodine is actively transported into the follicular cells by sodium/iodide (Na+/I-) symporter located on the basement membrane ● Inside the thyroid cell, iodide diffuses across the cell to the apical side of the follicle, which abuts the core of colloid ○ Here, iodide is oxidized and bound with tyrosyl residues, catalyzed by the enzyme thyroid peroxidase (TPO) resulting in the production of monoiodothyronine (MIT) and diiodothyronine (DIT) ● TPO also aids in the coupling of two tyrosyl residues to form triiodothyronine (T3) and thyroxine (T4) ○ T3 = 1 MIT residue + 1 DIT residue ○ T4 = 2 DIT residues ○ These are the two predominant thyroid hormones ● The thyroglobulin matrix, bound to T4 and T3, is stored in the thyroid lumen filled with colloid ● Thyroid-stimulating hormone (TSH) from the APG signals the follicular cells to ingest a droplet of colloid by endocytosis ○ Inside the follicular cell, these droplets are digested by intracellular lysosomes into T4, T3, and other products. ○ T4 and T3 are then secreted by the follicular cells into circulation ● Activity of the thyroid hormone depends on the location and number of iodide molecules T4 80% is metabolized into either T3 (35%) or rT3 (45%) Outer ring deiodination leads to production of 3,3’,5-triiodothyronine (T3) Inner ring deiodination leads to production of metabolically inactive rT T3 3-8x more metabolically active than T Often considered to be the biologically active form of thyroid hormone T4 = Prehormone Thyroglobulin = Prohormone Prohormone: a precursor with minimal hormonal effect
This negative feedback loop requires a normally functioning hypothalamus, pituitary, and thyroid gland, as well as an absence of interfering agents or agents that mimic TSH action ACTION OF THYROID HORMONES ● Once released from the thyroid gland, TH circulate in the bloodstream either bound to protein or as free, active hormone ● Free T4 and T3 are able to bind to cellular membrane transporters are then moved across the cell membrane ● In the cytoplasm , T4 is deiodinated into T3 (more biologically active) ● T3 combines with its nuclear receptor on thyroid hormone-responsive genes resulting to production of mRNA that, in turn, leads to production of proteins that influence metabolism and development ● Effects of thyroid hormone include: ○ Tissue growth ○ Brain maturation/CNS development ○ Sexual maturation ○ Increased energy production/conservation ○ Elevated heat production; energy expenditure ○ Influence carbohydrate and protein metabolism ○ Stimulation of heart rate and contraction ○ Synthesis of degradation of cholesterol and triglycerides ○ Increased oxygen consumption ○ Enhanced sensitivity of ꞵ-adrenergic receptors to catecholamines ○ Specific effects to each organ (heart, liver, kidneys, skeletal muscle, and skin) ● Hyperthyroidism/thyrotoxicosis = increased metabolic activity such as tachycardia and tremor ● Hypothyroidism = decreased metabolic activity such as edema and constipation
TEST FOR THYROID FUNCTION
THYROID-STIMULATING HORMONE
● The most useful test for assessing thyroid function is the TSH , currently in its third generation ● All TSH immunoassays are capable of screening for thyroid dysfunction, including: ○ Primary hyperthyroidism with elevated levels of TSH Second-generation TSH Immunometric Assays Has a limit of detection (LOD) of 0.1 mU/L Effectively screen for hyperthyroidism Third-generation TSH Chemiluminometric Assays Has an increased sensitivity to detection limits of 0.01 mU/L Gives fewer false-negative results More accurately distinguish between euthyroidism and hyperthyroidism Third-generation Ultrasenstitive (s-TSH) Assays Preferred method for monitoring and adjusting thyroid hormone replacement therapy and screening for abnormal TH production Ref. range: 0.3-4.2 mIU/L Fourth-generation Assays Provides a 10-fold increase in sensitivity compared to third-generation assays Although it exists, it is used primarily for research purposes ● The sensitivity of third-generation TSH assays led to the detection of what is termed as subclinical disease, ○ A mild degree of thyroid dysfunction due to the large, reciprocal change in TSH levels seen for even small changes in free T
SUBCLINICAL
HYPOTHYROIDISM
TSH = minimally increased FT4 = normal SUBCLINICAL HYPERTHYROIDISM TSH = low FT4 = normal Table 14.1 Interpretation of Thyroid Tests Low Free T4 Normal Free T4 High Free T Low TSH Secondary hypothyroidism Subclinical hyperthyroidism Primary hyperthyroidism Severe nonthyroidal illness Nonthyroidal illness Normal TSH Severe hypothyroidism Normal Test artifact Severe nonthyroidal illness Secondary hyperthyroidism Preanalytical error caused by blood drawn within 6-9h of thyroxine dose High TSH Primary hypothyroidism Subclinical hypothyroidism Test artifact Secondary hyperthyroidism Thyroid hormone resistance THYROXINE (T4) GENERAL INFORMATION ● Principal secretory product ● Major function of organic iodine in the circulation ● A prohormone for T3 production ● All circulating T4 originates in the thyroid gland ● The amount of serum T4 is a good indicator of the thyroid secretory rate ● Elevated thyroxine causes inhibition of TSH secretion, vice versa
● PREDOMINANT FORM OF THYROID HORMONE
FUNCTION &
REGULATION
● Major carrier of organic iodine in blood ○ Negative feedback: ■ ↑ T₄ → ↓ TSH ■ ↓ T₄ → ↑ TSH BINDING & MEASUREMENT ● >99.9% protein-bound (to TBG, albumin, etc.) ● Because of this: ○ Total T₄ can be misleading ○ Changes in binding proteins ≠ true thyroid dysfunction FREE VS TOTAL T₄ ● Free T₄ (FT₄) = biologically active form : Preferred test clinically (more accurate reflection of thyroid function) ● Total T₄: Can be affected by pregnancy, drugs, liver disease, etc. ASSAYS ● Measured using immunometric/chemiluminescent assays ● FT₄ assays are not perfect → still affected by abnormal binding proteins ● If results are suspicious → use equilibrium dialysis (gold standard) CLINICAL SIGNIFICANCE ● Serum T₄ level reflects thyroid secretory rate ● FT₄ + TSH = best initial evaluation of thyroid function REFERENCE RANGE 0.4 – 4.0 mIU/L
THYROTROPIN-RELEASING HORMONE (TRH)
● Regulate their own production by feedback inhibition to synthesis of TRH and TSH in the hypothalamus and pituitary ● TRH also stimulated Growth Hormone and Prolactin Question: TRH Test is performed when: A. Borderline cases of Hyperthyroidism B. Classifying hyperthyroidism C. Evaluating I-thyroxine suppression D. Evaluation euthyroid grave’s disease Practice Question: Which assay is used to confirm difficult cases of hypothyroidism? E. Free T3 Assay F. Free Thyroxine index G. Thyrotropin-releasing hormone (TRH) stimulation test H. TBG Assay Correct answer: C THYROTROPIN STIMULATING HORMONE (TSH) ● Best for screening thyroid problem ● It is regulated by the hypothalamus through TRH as well as negative feedback from the thyroid hormones ● Most important test in determining thyroid dysfunction ● Synthesized in the anterior pituitary gland that controls the biosynthesis and release of thyroid hormones from thyroglobulin REVERSE TRIIODOTHYRONINE (rT3) ● Major metabolite of thyronine and produced by 5-deiodination of T4. ● Majority of rT3 results in the peripheral deiodination of T4. ● Inactive ● Increased levels associated with Nonthyroidal Illness but decreased total T Practice Question: Which of the following statements is true regarding reverse T3 (rT3)? A. Formed in the blood by degradation of T B. Physiologically active, but less than T C. Decreased in euthyroid sick syndrome D. Interferes with the measurement of serum T Correct answer: A FREE TRIIODOTHYRONINE (FT3) GENERAL INFORMATION ● Unbound T₃ (~0.3%) ● Biologically active form ● ~99.7% bound (TBG, albumin) CLINICAL SIGNIFICANCE ● Not routinely measured ● 3rd-line test (after TSH, FT₄, T₃) ● Used to confirm hyperthyroidism ● T₃ toxicosis ● Abnormal binding proteins (pregnancy, dysalbuminemia) ● ↑ FT₃ → Hyperthyroidism / excess hormone REFERENCE RANGE 2.8–4.4 pg/mL THYROGLOBULIN GENERAL INFORMATION ● From thyroid follicular cells only ● Prohormone in circulation → indicates presence of thyroid tissue CLINICAL SIGNIFICANCE ● Tumor marker for well-differentiated thyroid cancer ● Used for post-treatment surveillance ● After surgery + radioactive iodine → Tg should be undetectable ASSAYS ● Immunoenzymatic (sandwich), ELISA, IRMA, ICMA
● Accuracy depends on antibody specificity and absence of interference LIMITATIONS AND OTHER INFO ● Anti-thyroglobulin antibodies (TgAb) interfere → unreliable results ● Always screen TgAb when measuring Tg ● If TgAb present → Tg value has limited value ~25% of patients have TgAb ● After successful treatment → TgAb should disappear over time THYROID AUTOIMMUNITY GENERAL INFORMATION ● Many thyroid diseases are autoimmune ● Antibodies target thyroid tissue → variable effects GRAVE’S DISEASE (HYPERTHYROIDISM) ● Most common cause of hyperthyroidism ● Autoantibodies target TSH receptor (TSHR ) → stimulation ● Leads to ↑ thyroid hormone + goiter GRAVE’S TESTING ● Detect TSHR antibodies ● Methods: ○ Competition assays (binding inhibition) ○ TSI assays → measure cAMP production ● TSHR Ab positive in 70–100% Hashimoto’s Thyroiditis (Hypothyroidism) ● Chronic lymphocytic thyroiditis ● Autoimmune destruction → ↓ thyroid hormone ● Most common cause of hypothyroidism Hashimoto’s Testing ● Best test: TPO antibodies ● Present in: ○ 10–15% general population ○ 80–99% autoimmune hypothyroidism THYROGLOBULIN ANTIBODY Table 14.2 Presence of Thyroid Autoantibodies Antibody General Population Grave’s Disease Hashimoto’s thyroiditis Thyroglobulin antibody (anti-Tg)
Thyroperoxidase antibody (anti-TPO)
Thyrotropin receptor antibody (anti-TSHR/TRAb)
DEFINITION ● Antibodies against thyroglobulin (Tg) ● Tg is important for thyroid hormone synthesis, storage, and release PATHOPHYSIOLOGY ● Tg is normally not in bloodstream ● Thyroid destruction/inflammation (thyroiditis) → Tg leaks into blood ● → Triggers formation of anti-Tg antibodies ● Same process can also form anti-TPO antibodies CLINICAL SIGNIFICANCE ● Most common in Hashimoto’s thyroiditis ● Present in: ○ 35–60% of autoimmune hypothyroidism ○ 12–30% of Graves’ disease ● Marker of autoimmune thyroid disease ● Often seen with other thyroid antibodies (e.g., anti-TPO) REFERENCE RANGE < 4.0 IU/mL
thyroid cancer ● Cancer tissue takes up iodine → detected on whole-body imaging ● Higher doses used for ablation/treatment Thyroid Ultrasound ● Uses high-frequency sound waves to image thyroid ● Noninvasive (gel + probe on neck) ● Evaluates thyroid anatomy & palpable abnormalities ● Detects non-palpable nodules ● Detects small nodules (<1.5 cm) ● Small nodules seen in ~50% of clinically normal thyroid glands Fine-Needle Aspiration ● First step & most accurate test for thyroid nodules (if no hyperthyroidism) ● Enables prompt identification of malignancy ● Helps avoid unnecessary surgery in benign lesions ● Procedure: small-gauge needle → aspirate cells → cytology ● Increasingly ultrasound-guided ● Results reported via Bethesda System ( categories): ○ Nondiagnostic/unsatisfactory ○ Benign ○ Atypia / FLUS ○ Follicular neoplasm / suspicious for follicular neoplasm ○ Suspicious for malignancy ○ Malignant ● Categories guide management → monitoring vs surgical excision
DISORDERS OF THE THYROID
CLASSIFICATIONS (AS PER SIR KR):
- Hyperthyroidism
- Hypothyroidism
- Euthyroidism HYPOTHYROIDISM DEFINITION ● Develops whenever insufficient amounts of thyroid hormone are available to tissue LAB PATTERN/FINDINGS ● Low FT4 levels ○ Total T4: decreased ○ Free T4: Decreased ● Normal or high TSH ● Thyroid Peroxidase Antibody: Positive EPIDEMIOLOGY ● Most common thyroid gland disorder ● Occurs in 20% of women over the age of 65 FACTORS AFFECTING THE SYMPTOMS OF HYPOTHYROIDISM ● Depends on the: ○ Degree of hypothyroidism ○ Rapidity of its onset TREATMENT Thyroid Hormone Replacement therapy
SIGNS AND SYMPTOMS OF HYPOTHYROIDISM
SIGNS ● Delayed relaxation phase of deep tendon reflex testing ● Bradycardia ● Diastolic hypertension ● Coarsened skin ● Yellowing of skin (hypercarotenemia/carotenemia) ● Edema in the face and hands ● Thinning of eyebrowsloss if lateral aspect of brows ● Pleural/pericardial effusion ● Ascites SYMPTOMS ● Cold intolerance ● Fatigue ● Weight gain ● Depression ● Intellectual disability ● Menorrhagia (menstrual irregularities) ● Growth failure (children) ● Pubertal delay ● Dry skin ● Edema ● Constipation ● Hoarseness ● Dyspnea of exertion
OTHER ABNORMALITIES CAUSED BY HYPOTHYROIDISM
In the presence of these clinical abnormalities, evaluation of hypothyroidism as a potential secondary cause can be considered HYPONATREMIA ● Occur from the combination of increased urinary sodium excretion and an inability to maximally dilute urine due to inappropriate release of antidiuretic hormone. MYOPATHY ● Result of severe and prolonged hypothyroidism; often presents with elevated Creatine Kinase (CK). ANEMIA ● Seen either as a result of a decreased demand for oxygen carrying capacity or through an associated autoimmune pernicious anemia, menorrhagia, or malabsorption of iron and folic acid. HYPPERLIPIDEMIA ● Found in 50% or more of uncorrected cases; typically improves with thyroid hormone replacement. TYPES OF HYPOTHYROIDISM TYPE AFFECTED ORGAN Primary Thyroid gland dysfunction Secondary Pituitary dysfunction Tertiary Hypothalamic dysfunction
SCREENING
According to the American Thyroid Association and American Association of Clinical Endocrinologists guidelines for hypothyroidism screening CATEGORY GUIDELINES Routine Screening Start at age 35 Frequency Every 5 years High-Risk Groups - Symptoms present - Risk factors - Other autoimmune disease - First-degree relative with autoimmune thyroid disease Special Monitoring Lithium use, amiodarone use → monitor TSH more closely + physical exam TREATMENT CATEGORY DETAILS Main Therapy Thyroid hormone replacement Treatment of Choice Levothyroxine (T₄) Primary goal (Primary) Achieve normal TSH level ● TSH used as primary marker Primary Goal (Secondary/Tertiary) Achieve a mid-normal $FT_4$ level (TSH is not useful here) Levixythyroxine half-life Half-life ≈ 7 days Dose Adjustment Wait ≥5 half-lives (~35 days) before rechecking thyroid function tests
EUTHYROIDISM
DEFINITION Indicative of Hypothyroidism LAB PATTERN/FINDINGS ● Increased rT ● Normal FT4I ● Normal TSH TEST Abnormal function test but illness in non thyroidal (critically - illness, elderly, hospitalized indiivduals) THYROTOXICOSIS DEFINITION ● A constellation of findings resulting from peripheral tissues responding to an excess of thyroid hormone PRIMARY SOURCES ● Excessive thyroid hormone ingestion ● Leakage of stored thyroid hormone from storage in the thyroid follicles ● Excessive thyroid gland production of thyroid hormone ○ Hyperthyroidism ○ Low TSH ○ Normal FT ○ Increased FT3-T
SIGNS AND SYMPTOMS OF THYROTOXICOSIS
SIGNS ● TachycardiaTremor ● Warm, moist, flushed, smooth skin ● Lid lag, widened palpebral fissures ● Ophthalmopathy (Graves’ disease) ● Goiter ● Brisk deep tendon reflexes ● Muscle wasting and weakness ● Dermopathy/pretibial myxedema (Grave’s disease) ● Osteopenia, osteoporosis SYMPTOMS ● Nervousness ● Irritability ● Anxiety ● Tremor ● Palpitations ● Fatigue ● Weakness ● Decreased exercise tolerance ● Weight loss ● Heat intolerance ● Hyperdefacation ● Menstrual changes (oligomenorrhea) ● Prominence of eyes DISORDERS ASSOCIATED WITH THYROTOXICOSIS CONDITION PATHOGENIC MECHANISM TSH LEVEL RAIU OTHER TESTS Hyperthyroidism Graves’ disease
Anti-TSHR ↓ ↑ Anti-TSHR
positive TSI positive Toxic adenoma Benign nodule
↓ ↑ Seen on
Thyroid scans Toxic multinodula r goiter Foci of functional autonomy
↓ ↑ Seen on
Thyroid scans TSH-secretin g tumor Benign pituitary tumor Normal
↑ Pituitary
MRI Non- hyperthyroidism Painful Thyroiditis Leakage of thyroid hormone
↓ ↓ ↑ Tg
Postpartum thyroiditis Leakage of thyroid hormone
↓ ↓ ↑TPO Ab
Exogenous hormone Excess medication
Ectopic thyroid tissue Metastatic thyroid cancer Struma ovarii
↓ ↓ Distant
metastasis seen on radioactive iodine scans HYPERTHYROIDISM DEFINITION ● Refers to excess of circulating thyroid hormone ● Most common cause of Graves’ disease PRIMARY HYPERTHYROIDISM ● Elevated T3 and T ● Decreased TSH SECONDARY HYPOERTHYROIDISM ● Increased TSH and T ○ Due to primary lesion in the pituitary gland
TREATMENT MODALITIES AND RISK
Treatment Mechanism / Usage Risks / Side Effects β-blockers Used initially to control adrenergic excess (tremor, tachycardia). N/A (per text) Thyroperoxid ase inhibitors Propylthiourac il (PTU) Methimazole (MMI)) Inhibit thyroid hormone biosynthesis/s ecretion preferred in pregnancy/ breastfeeding . Rash, hepatotoxicity, agranulocytosis, and aplastic anemia. Radioactive Iodine The goal is to destroy enough tissue to make the patient May cause an acute flaring of eye problems. hypothyroid preferred treatment modality in the US. Surgery Preferred if cancer is suspected, if ophthalmopa thy is severe, or in 2nd trimester of pregnancy. Recurrent laryngeal nerve injury (hoarseness), parathyroid injury (hypocalcemia).
TOXIC ADENOMA AND MULTINODULAR GOITER
DEFINITION AND
PATHOPHYSIOLOGY
● Most relatively common causes of hyperthyroidism ● Caused by autonomously functioning thyroid tissue ● Does not require TSH nor TSHR-stimulating immunoglobulin to stimulate thyroid hormone production MECHANISM Receptor mutations can occur, mimicking chronic TSH receptor stimulation SIGNS AND SYMPTOMS ● Hyperthyroidism ● Palpable nodules LAB/SCAN FINDINGS ● Nodules appear “hot” on thyroid scan – that is if they take up radioactive iodine ● RAIU is inappropriately high within the nodule despite suppressed TSH TREATMENT RADIOACTIVE IODINE ● Tends to destroy only the hyperactive nodules ● Normal (suppressed) tissue is often left undamaged SURGERY Effective for removing autonomous tissue THYROPEROXIDASE INHIBITORS Can block hormone production but not expected to lead to remission in these conditions LONG-TERM OUTLOOK Patients may be left with normal function after treatment, potentially avoiding lifelong hormone replacement DRUG-INDUCED THYROID DYSFUNCTION AMIODARONE-INDUCED THYROID DISEASE AMIODARONE ● A drug used to treat cardiac arrhythmias ● Fat-soluble drug with a long half-life (50 days) that interferes with normal thyroid function ● 37% of molecular weight is iodine ● Blocks T4 to T4 conversion IODINE ● When given in large doses, acutely leads to inhibition of thyroid hormone production ○ This is termed as WOLFF-CHAIKOFF EFFECT COMBINATION OF THE TWO Leads to hypothyroidism in 8% of patients with chronic amiodarone therapy AMIODARONE IN HYPERTHYROIDISM Can lead in hyperthyroidism in 3% of patients treated chronically with this medication
THYROID NODULES
EPIDEMIOLOGY Common and clinically apparent thyroid nodules are present in: ● 6.4% of adult women ● 1.5% of adult men AUTOPSY FINDINGS Find nodules in 50% of normal thyroid glands MALIGNANCY RISK Only 6% to 9% of non-palpable nodules prove to be thyroid cancer. STANDARD PRACTICE FNA (Fine Needle Aspiration) with cytologic examination. GOAL OF TESTING Distinguish nodules requiring surgical removal from those that do not. SUMMARY TABLES NI SIR KR HYPOTHYROIDISM HYPERTHYROIDISM Increased serum cholesterol, triglycerides Increased skin temperature, pulse rate, pulse pressure Increased serum carotene (yellow skin discolorization) Decreased serum cholesterol, triglycerides Increased serum levels of muscle enzymes: CPK, AST, LDH INcreased serum levels of ALT/AST and ALP Increased serum prolactin Increased retention of BSP Normochromic anemia, hemoglobin around 10 g/dl Altered glucose insulin relationship Increased capillary fragility Increased proportion of lymphocytes in differential white count Increased spinal fluid protein INcreased urinary calcium retention Decreased urinary excretion of 17-KS, 17OHCS TSH T3 TOTA L T rT3 T3RU Serum Chol.
CK
Hyperthyroidism ↓ ↑ ↑ N / ↑ ↑ ↓ N / ↑ Hypothyroidism ↑ ↓ ↓ N / ↑ ↓ ↑ N / ↑ Euthyroid sick syndrome
N ↓ N / ↓ ↑ N N N
Excess TBG N ↑ ↑ N ↓ N N CLINICAL CONDITION TT4 TT3 FT4 TSH PRIMARY HYPOTHYROIDISM (^) ↓ ↓ ↓ ↑ SECONDARY HYPOTHYROIDISM (^) ↓ ↓ ↓ ↓ PRIMARY HYPERTHYROIDISM (^) ↑ ↑ ↑ ↓ SECONDARY HYPERTHYROIDISM (^) ↑ ↑ ↑ ↑ PRIMARY INCREASE TBG (^) ↑ ↑ N N PRIMARY DECREASE TBG (^) ↓ ↓ N N
Practice Questions:
- A 32-year-old female presents with palpitations, weight loss, heat intolerance, diffuse goiter, and exophthalmos. Labs: TSH ↓, FT4 ↑, RAIU ↑. What is the underlying mechanism? A. Destruction of thyroid follicles releasing preformed hormone B. Autoantibodies stimulating TSH receptors C. Excess iodine intake inhibiting hormone synthesis D. Pituitary adenoma secreting TSH
- A patient with neck pain and recent viral infection has thyrotoxicosis. Labs: TSH ↓, FT4 ↑, RAIU ↓. What is the cause? A. Graves disease B. Toxic adenoma C. Subacute thyroiditis D. TSH-secreting tumor
- Which enzyme catalyzes iodination and coupling reactions in thyroid hormone synthesis? A. Deiodinase B. Thyroid peroxidase C. Thyroglobulin D. Na+/K+ ATPase
- T3 is more biologically active than T4 because: A. It is more protein bound B. It has longer half-life C. It binds nuclear receptors more effectively D. It is produced only in thyroid
- Which protein carries most circulating T4? A. Albumin B. Prealbumin C. Thyroxine-binding globulin D. Hemoglobin
- A patient has TSH ↑ and FT4 ↓. Diagnosis? A. Primary hypothyroidism B. Secondary hypothyroidism C. Hyperthyroidism D. Euthyroid sick syndrome
- Which is the most sensitive test for thyroid function screening? A. Total T B. T C. TSH D. Thyroglobulin
- T3 thyrotoxicosis is characterized by: A. ↑ T3 only B. ↑ T4 only C. ↓ T3 and ↓ T D. Normal T3 and ↑ T
- Which antibody is most sensitive for Hashimoto thyroiditis? A. Anti-Tg B. Anti-TPO C. Anti-TSHR D. ANA
- A patient with nonthyroidal illness typically shows: A. ↑ T B. ↓ rT C. ↑ rT D. ↑ TSH
- Which condition shows high RAIU despite low TSH? A. Thyroiditis B. Graves disease C. Exogenous hormone intake D. Iodine excess
- Which hormone is considered a prohormone? A. T
