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What is the initial change in thyroid function observed in neonates after delivery?
What is the initial change in thyroid function observed in neonates after delivery?
What factor is essential to consider when interpreting thyroid hormone tests during pregnancy?
What factor is essential to consider when interpreting thyroid hormone tests during pregnancy?
What is a distinguishing characteristic of thyroid hormone resistance syndromes?
What is a distinguishing characteristic of thyroid hormone resistance syndromes?
Which test is used to distinguish secondary hyperthyroidism from thyroid hormone resistance?
Which test is used to distinguish secondary hyperthyroidism from thyroid hormone resistance?
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What happens when TRAbs are strongly positive in treated hyperthyroid patients about to have their medication withdrawn?
What happens when TRAbs are strongly positive in treated hyperthyroid patients about to have their medication withdrawn?
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What is the function of Thyroxine binding globulin (TBG) in relation to thyroid hormones?
What is the function of Thyroxine binding globulin (TBG) in relation to thyroid hormones?
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What is the percentage of free T4 and T3 that circulates in plasma?
What is the percentage of free T4 and T3 that circulates in plasma?
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Which hormone is primarily involved in negative feedback regulation of the hypothalamic–pituitary–thyroid axis?
Which hormone is primarily involved in negative feedback regulation of the hypothalamic–pituitary–thyroid axis?
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What characterizes subclinical thyroid disease?
What characterizes subclinical thyroid disease?
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How do nonthyroidal illnesses affect thyroid function tests?
How do nonthyroidal illnesses affect thyroid function tests?
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Which of the following is a common cause of thyroid dysfunction?
Which of the following is a common cause of thyroid dysfunction?
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What is the main purpose of performing thyroid function tests?
What is the main purpose of performing thyroid function tests?
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Which of the following correctly identifies the conversion process involving T4 and T3?
Which of the following correctly identifies the conversion process involving T4 and T3?
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What is the primary function of the sodium iodine symporter in the thyroid?
What is the primary function of the sodium iodine symporter in the thyroid?
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Which hormone is predominantly produced by the thyroid and is a biologically active form?
Which hormone is predominantly produced by the thyroid and is a biologically active form?
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What is the consequence of an abnormal TSH in clinically euthyroid patients?
What is the consequence of an abnormal TSH in clinically euthyroid patients?
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In which situation is thyroid function testing likely to be unreliable?
In which situation is thyroid function testing likely to be unreliable?
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What approach is recommended in managing subclinical hypothyroidism when TSH is between 4.5 and 10 mU/L?
What approach is recommended in managing subclinical hypothyroidism when TSH is between 4.5 and 10 mU/L?
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What is the recommended action following a change in the T4 replacement dose for hypothyroidism?
What is the recommended action following a change in the T4 replacement dose for hypothyroidism?
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What is a common treatment option for patients with hyperthyroidism?
What is a common treatment option for patients with hyperthyroidism?
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What happens to TSH concentrations in hospitalized patients recovering from nonthyroidal illness?
What happens to TSH concentrations in hospitalized patients recovering from nonthyroidal illness?
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Which of the following factors could lead to abnormal thyroid function test results in euthyroid patients?
Which of the following factors could lead to abnormal thyroid function test results in euthyroid patients?
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What is a unique feature of thyroid hormone resistance syndromes?
What is a unique feature of thyroid hormone resistance syndromes?
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Which test is essential for predicting relapse in treated hyperthyroid patients when discontinuing anti-thyroid medication?
Which test is essential for predicting relapse in treated hyperthyroid patients when discontinuing anti-thyroid medication?
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Which statement is true regarding hormonal changes during pregnancy?
Which statement is true regarding hormonal changes during pregnancy?
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Which condition is indicated by the presence of antiTPO antibodies?
Which condition is indicated by the presence of antiTPO antibodies?
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What is the primary site of production for thyroxine?
What is the primary site of production for thyroxine?
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What is a common management strategy for treating hyperthyroidism?
What is a common management strategy for treating hyperthyroidism?
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What is the primary paradoxical effect observed in the hypothalamic–pituitary–thyroid axis when T4 and T3 levels are elevated?
What is the primary paradoxical effect observed in the hypothalamic–pituitary–thyroid axis when T4 and T3 levels are elevated?
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Which thyroid hormone is involved in the negative feedback regulation of the hypothalamic-pituitary-thyroid axis?
Which thyroid hormone is involved in the negative feedback regulation of the hypothalamic-pituitary-thyroid axis?
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Which biochemical pattern is most indicative of primary hypothyroidism?
Which biochemical pattern is most indicative of primary hypothyroidism?
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What happens to the proportion of free thyroid hormones in cases of thyroid dysfunction?
What happens to the proportion of free thyroid hormones in cases of thyroid dysfunction?
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In what condition is T4 therapy typically deemed necessary?
In what condition is T4 therapy typically deemed necessary?
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Which condition is commonly associated with abnormal thyroid function tests in the absence of primary thyroid disease?
Which condition is commonly associated with abnormal thyroid function tests in the absence of primary thyroid disease?
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When should thyroid function tests be interpreted with caution due to illness?
When should thyroid function tests be interpreted with caution due to illness?
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When managing subclinical thyroid disease, what parameter is most critical for deciding on treatment?
When managing subclinical thyroid disease, what parameter is most critical for deciding on treatment?
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What is the role of the sodium iodine symporter in thyroid physiology?
What is the role of the sodium iodine symporter in thyroid physiology?
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Which protein is primarily responsible for binding the majority of circulating thyroid hormones?
Which protein is primarily responsible for binding the majority of circulating thyroid hormones?
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What should be done if the T4 replacement dose is changed in a patient with hypothyroidism?
What should be done if the T4 replacement dose is changed in a patient with hypothyroidism?
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What should be evaluated when interpreting thyroid function tests during treatment with certain medications?
What should be evaluated when interpreting thyroid function tests during treatment with certain medications?
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Which thyroid-related condition is characterized by abnormal TSH levels regardless of thyroid hormone status?
Which thyroid-related condition is characterized by abnormal TSH levels regardless of thyroid hormone status?
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Which is a characteristic feature of thyroid hormone action?
Which is a characteristic feature of thyroid hormone action?
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Study Notes
Pathophysiology of Thyroid Dysfunction
- Thyroid dysfunction encompasses hyperthyroidism (excess thyroid hormone) and hypothyroidism (deficient thyroid hormone).
- The presentation and associated biochemical abnormalities are crucial for diagnosis.
- Thyroid dysfunctions are characterized by excessive or deficient production of thyroid hormones, leading to various clinical presentations.
Outcomes and Assessment Criteria
- Outcomes: Identifying the clinical presentation of thyroid disorders (excess and deficient function). Interpreting thyroid function tests. Recognizing common thyroid disease states and patterns in biochemical abnormalities.
- Assessment Criteria: Listing thyroid disease features. Applying clinical knowledge to clinical cases. Analyzing biochemical thyroid function tests. Stating diagnoses. Listing common disease states (hyper/hypothyroidism). Applying clinical thyroid disease knowledge to patient cases.
Learning Objectives
- Understanding the biosynthetic pathways involved in thyroid hormone synthesis and how they function.
- The mechanisms regulating the hypothalamic-pituitary-thyroid axis.
- Recognizing the causes, features of thyroid dysfunction, and appropriate diagnostic investigations.
- Interpreting thyroid function tests for diagnosis and monitoring treatment.
- Understanding the concept of subclinical thyroid disease and when to treat.
- Identifying the mechanisms responsible for changes in thyroid function test results due to non-thyroidal illnesses and interpreting the results.
- Understanding the drugs that commonly cause abnormal thyroid function tests, including their mechanisms of action.
- Recognizing situations where thyroid function testing may not be the most appropriate initial approach.
Clinical Features of Thyroid Disease
- Hypothyroidism: Hair loss, impaired cognitive function, enlarged thyroid gland (goiter), reduced heart rate, fatigue, cold intolerance, dry skin, weight gain, puffiness, memory problems, constipation, irregular menstrual periods, severe PMS, depression, mood swings, joint/muscle pain, high cholesterol.
- Hyperthyroidism: Hair loss, bulging eyes, enlarged thyroid (goiter), heart palpitations, tremors, heat intolerance, sleep disturbances, weight loss, shortness of breath, diarrhea, increased appetite, irregular menstrual periods, muscle weakness, sweating, anxiety, nervousness, depression, mood swings.
Investigations of Thyroid Function
- TSH: The single most useful test for thyroid function. Increased in hypothyroidism, decreased in hyperthyroidism.
- Total T4 and Total T3: >99% of T4 and T3 circulate bound to protein (mainly TBG). Changes in protein levels affect these values.
Regulation of Synthesis and Metabolism
- Negative feedback: T4 and T3 exert negative feedback on the hypothalamus and pituitary gland, regulating TSH release.
- Conversion of T4 to T3: T4 is converted to the active form T3 in peripheral tissues.
- Thyroxine-binding Globulin (TBG): The major thyroid hormone binding protein in the blood. Other binding proteins, including Transthyretin and Albumin significantly impact hormone levels.
- Iodine trapping: Active transport of iodine into thyroid follicular cells.
- Iodine oxidation: Iodine oxidation by thyroid peroxidase.
- Iodine organification: Incorporation of iodine into tyrosyl residues of thyroglobulin.
- Thyroglobulin synthesis and cleavage: Production of thyroid hormones (T4 and T3) by coupling iodotyrosyl residues in thyroglobulin.
- Release of hormones: Secretion of T4 and T3 into the circulation.
Thyroid Hormones-Mechanism of Action
- T4 and T3 enter cells via diffusion or carrier-mediated transport.
- T4 is converted to T3 with the help of 5' and 3' monodeiodinases enzymes, which increases activity of active thyroid hormone (T3).
- Thyroid hormone receptors are found throughout the body's cells, which then bind to specific regions on the DNA in the nucleus and enhance transcription of various genes.
Who Should Have Thyroid Function Tests Done?
- Symptomatic patients (features or history of a thyroid disorder or being elderly with non-specific symptoms).
- Patients at higher risk of developing thyroid disease (diabetes, autoimmune disorders, treatment with medications possibly affecting thyroid function).
- Women experiencing menopause.
Thyroid Hormones
- Thyroxine (T4): The primary hormone produced by the thyroid gland.
- Triiodothyronine (T3): The active form of thyroid hormone.
- Reverse T3 (rT3): An inactive form of thyroid hormone.
Synthesis of Thyroid hormones
- Trapping of iodide from plasma: iodide is actively transported into the thyroid follicle.
- Oxidation of iodide to iodine: thyroid peroxidase oxidises iodide to iodine.
- Incorporation of iodine into thyroglobulin: iodide is incorporated into tyrosyl residues of thyroglobulin.
- Production of T4 and T3: the coupled iodotyrosyl residues from thyroglobulin are cleaved to produce T4 and T3.
- Release of T4 and T3: T3 and T4 are released into the circulation.
Hyperthyroidism Management
- Radioiodine: Used for treatment of hyperthyroidism by destroying thyroid tissue.
- Carbimazole: Medication used to inhibit the production of thyroid hormones.
- Thyroidectomy: Surgical removal of all or part of the thyroid gland.
- Measurement of TSH is not reliable in first 4-6 months post-treatment.
Hypothyroidism Causes
- Inflammation (e.g., Hashimoto's, atrophic thyroiditis, Post-partum thyroiditis)
- Congenital issues (e.g., Thyroid aplasia, dyshormonogenesis)
- Latrogenic causes (e.g., Thyroidectomy, radioactive iodine)
- Other medications (e.g., amiodarone)
- Iodine deficiency
Hypothyroidism Management
- T4 replacement therapy
- Make the patient feel well and restore TSH and T4 within reference range
- Once stabilised, annual check
- If dose is changed, wait 6–8 weeks before doing lab tests.
Other Situations
- Subclinical hypothyroidism: Treatment only required if TSH > 10 mU/L.
- Treatment in central hypothyroidism: T4 therapy; TSH may not be of clinical value.
- Thyroid function tests are not reliable in situations like non-thyroidal illness (NTI), recovery from illness, pregnancy, or neonates.
Interpretation of Thyroid Function Tests (TFTs) in suspected Hypothyroidism
- If TSH is normal, consider other causes of symptoms.
- If TSH is elevated, and FT4 is normal, consider subclinical hypothyroidism.
- If TSH is elevated, and FT4 is low, consider overt hypothyroidism.
- If TSH is low, and FT4 is normal or slightly raised, consider subclinical hyperthyroidism or other non-thyroidal cause.
- Follow-up testing is frequently required to confirm suspected disorders and to monitor treatment responses.
Tests Affected by Thyroid Status
- Hyperthyroidism: Hyperglycemia, impaired glucose tolerance, hypocholesterolemia, abnormal liver function tests, hypercalcemia, elevated SHBG.
- Hypothyroidism: Hyponatremia, hypercholesterolemia, hyperprolactinemia, increased CK, decreased SHBG.
Drugs Affecting Thyroid Status
- Drugs that can alter thyroid function include: Dopamine, glucocorticoids, Lithium, Amiodarone, Iodine, Carbimazole, methimazole, propylthiouracil, Lithium, Oestrogens, tamoxifen, heroin, methadone, Androgens, glucocorticoids, etc.
Causes of Abnormal Results in Euthyroid Patients
- Abnormal TBG
- Genetic variants of albumin and pre-albumin (familial dysalbuminemic hyperthyroxinaemia)
- Assay interference (patients with endogenous antibodies that interfere in assays).
- Medications.
Thyroid Hormone Resistance Syndromes
- Rare
- Mutations in beta nuclear T3 receptor
- Elevated FT4 & FT3 with normal or slightly raised TSH.
- Generalized/Pituitary/Peripheral thyroid hormone resistance
Other Miscellaneous Tests
- TRH test (distinguishes secondary hyperthyroidism from TSH-resistance)
- Anti-TPO (Hashimoto's Thyroiditis, Grave's disease)
- TRAbs (predicting relapse in treated hyperthyroid patients and indicating a high risk of immediate relapse.)
Unreliable Thyroid Function Tests
- Non-thyroidal illness (NTI)/Sick euthyroid syndrome
- Recovery from illness
- Neonates
- Pregnancy
- Use of medications
Effects of Illness on Thyroid Hormones
- Thyroid hormone and thyrotropin (TSH) concentrations can change in response to illness severity, with lower concentrations observed in more severe cases.
Thyroid Function Testing in Patients with Nonthyroidal Illness (NTI)
- Abnormal TFTs are common in patients with non-thyroidal illnesses.
- Low T3 is a frequent finding.
- TSH being low is more likely due to NTI than hyperthyroidism.
- Elevated TSH more likely due to recovery from illness than primary hypothyroidism.
- In general, thyroid function tests would not be needed unless thyroid dysfunction was suspected as a contributor to the non-thyroidal illness.
Recovery from Illness
- When a patient recovers from illness, abnormalities in TSH, T4 and T3 eventually resolve.
- In some patients, TSH concentrations may rise transiently above the reference range in the recovery phase. In hospitalized patients, an elevated TSH is as likely to be due to recovery from non-thyroidal illness as primary hypothyroidism.
Neonate
- Plasma TSH is widely used to screen for congenital hypothyroidism in the neonate.
- Marked changes in thyroid function occur in the early days of life, with an initial surge in TSH and thyroid hormone after delivery, followed by a marked decline in hormone levels over the next few days.
Pregnancy
- Marked changes in thyroid hormone concentration and TSH occur throughout pregnancy, and it is essential to use trimester-related reference ranges.
Tests Affected by Thyroid Status
- Hyperthyroidism: Hyperglycemia, impaired glucose tolerance, hypocholesterolemia, abnormal liver function tests, hypercalcemia, elevated SHBG.
- Hypothyroidism: Hyponatremia, hypercholesterolemia, hyperprolactinemia, increased CK, decreased SHBG.
Drugs Affecting Thyroid Status
- Drugs that can alter thyroid function include: Dopamine, glucocorticoids, Lithium, Amiodarone, Iodine, Carbimazole, methimazole, propylthiouracil, Lithium, Oestrogens, tamoxifen, heroin, methadone, Androgens, glucocorticoids, and other medications.
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Description
Test your knowledge on thyroid function and hormone regulation, particularly in relation to neonates and pregnancy. This quiz covers key concepts like thyroid hormone resistance syndromes and the role of Thyroxine binding globulin. Perfect for students studying endocrinology and related fields.
