Thyroid Disorders and Treatments Quiz

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Questions and Answers

What is the primary use of hydrocortisone in the context of hypotension?

To directly manage abdominal pain

To inhibit conversion of thyroxine to triiodothyronine (correct)

As a diuretic for fluid retention

As a thyroid hormone replacement

Which treatment option for Plummer's Disease is noted for its low morbidity and no mortality?

Propranolol therapy

Methimazole medication

Surgical treatment (correct)

Radioactive iodine therapy

What is the reason PTU is not recommended for use in the pediatric population?

It is associated with liver injury (correct)

It causes severe skin reactions

It has a higher risk of cardiac complications

It can lead to rapid weight gain

In which trimester is methimazole preferred over PTU for pregnant patients?

Both second and third trimesters Signup and view all the answers

What is a significant concern regarding the use of PTU during pregnancy?

It may result in fetal cretinism and goiter Signup and view all the answers

What is the preferred treatment for thyrotoxicosis during the first trimester of pregnancy?

Propylthiouracil (PTU) Signup and view all the answers

What is a critical intervention to reduce operative risks before subtotal thyroidectomy?

Achieve a euthyroid state Signup and view all the answers

Which of the following symptoms is NOT typically associated with thyroid storm?

Bradycardia Signup and view all the answers

Why is propylthiouracil preferred over methimazole during thyroid storm management?

It impairs the conversion of T4 to T3 Signup and view all the answers

What adjunct treatment is used prior to surgery for hyperthyroidism to decrease gland vascularity?

Iodide for 7-10 days Signup and view all the answers

What is the primary therapeutic use of 131I?

Destruction of an overactive thyroid Signup and view all the answers

Which of the following statements about the action of 131I is correct?

Destructive β-particles act on parenchymal cells of the thyroid. Signup and view all the answers

What common condition may arise as a disadvantage of 131I treatment?

Hypothyroidism Signup and view all the answers

Which of the following is a contraindication for the use of 131I therapy?

Pregnancy Signup and view all the answers

What effect can radioactive iodine treatment have on salivary glands?

Decreased salivary output Signup and view all the answers

What is the relative potency ratio of T4 to T3?

1:4 Signup and view all the answers

Which transporter is primarily responsible for thyroid hormone transport into cells in humans?

Monocarboxylic acid transporter 8 (MCT8) Signup and view all the answers

Which of the following is a major physiological effect of T3 compared to T4?

Enhanced brain development Signup and view all the answers

Levothyroxine is best described as which of the following?

A synthetic hormone used to treat hypothyroidism Signup and view all the answers

Which dietary component can decrease T4 absorption?

Soybeans Signup and view all the answers

What is one of the cardiovascular effects of thyroid hormones?

Cardiac hypertrophy Signup and view all the answers

How does fasting affect T4 absorption?

Increases absorption Signup and view all the answers

What should levothyroxine be separated from to prevent formation of insoluble chelates?

Calcium and aluminum supplements Signup and view all the answers

What is the primary site of degradation for T4 and T3?

Liver Signup and view all the answers

In what percentage of cases is T4 eliminated in the stool?

20% Signup and view all the answers

What is the recommended initial daily dose range of levothyroxine sodium for adults?

12.5-50 µg Signup and view all the answers

Why may levothyroxine dosage need to be increased in pregnant hypothyroid patients?

Due to increased serum concentration of TBG Signup and view all the answers

What percentage of thyroid nodules decrease in volume by more than 50% with levothyroxine treatment?

22% Signup and view all the answers

What condition can cause an indistinguishable hypermetabolic state from thyrotoxicosis?

Levothyroxine overdose Signup and view all the answers

What is the recommended frequency of dosing for levothyroxine sodium?

Once daily Signup and view all the answers

Which symptom is NOT typically associated with thyrotoxicosis?

Weight gain Signup and view all the answers

Which thyroid hormone is primarily produced by the parafollicular cells of the thyroid gland?

Calcitonin Signup and view all the answers

What is the effect of decreased stores of thyroid iodine on iodide uptake?

Decreases NIS protein expression Signup and view all the answers

What role does thyroid peroxidase play in the synthesis of thyroid hormones?

Facilitates the oxidation of iodide and iodination of tyrosine Signup and view all the answers

Which of the following processes is NOT stimulated by thyroid-stimulating hormone (TSH)?

Thyroid hormone degradation Signup and view all the answers

What percentage of circulating triiodothyronine (T3) is attributed to the conversion of thyroxine (T4) in the peripheral tissues?

80% Signup and view all the answers

Which protein primarily carries thyroid hormones in the bloodstream?

Thyroxine-binding globulin (TBG) Signup and view all the answers

How does TSH affect the vascularity of the thyroid gland?

Increases vascularity Signup and view all the answers

Which enzyme is responsible for the conversion of mono- and diiodotyrosines during thyroid hormone synthesis?

Iodotyrosine Deiodinase Signup and view all the answers

What is the primary site of non-deiodinative degradation of thyroid hormones?

Liver Signup and view all the answers

What is the relationship between TSH and the release of thyroid hormones?

TSH stimulates the release of preformed thyroid hormones Signup and view all the answers

Which statement about the sodium iodide symporter (NIS) is true?

It facilitates iodide uptake into the thyroid gland Signup and view all the answers

Which of the following is synthesized in the hypothalamus and stimulates TSH release from the anterior pituitary gland?

Thyrotropin-Releasing Hormone (TRH) Signup and view all the answers

Which of the following correctly describes the metabolic activity of thyroid hormones in the blood?

Only unbound hormone is metabolically active Signup and view all the answers

What triggers the iodination of tyrosine residues during thyroid hormone synthesis?

Oxidation of iodide Signup and view all the answers

Study Notes

Thyroid and Anti-Thyroid Drugs

Thyroid gland produces two types of hormones:
- Iodothyronines from thyroid follicles (thyroxine (T4) and 3,5,3'-triiodothyronine (T3))
- Calcitonin from parafollicular cells (C-cells)
Thyroid hormones are synthesized and stored as amino acid residues of thyroglobulin, a glycoprotein.
T3 is 3-4 times more potent than T4.
T3 has a half-life of 1 day, while T4 has a half-life of 7 days.
T4 is secreted by the gland solely, whereas T3 is produced via thyroid and peripheral conversion.
The thyroid gland produces 80% of T4 and 20% of T3.
The major carrier of thyroid hormones is thyroxine-binding globulin (TBG), a glycoprotein.

Major Steps in Synthesis, Storage, Release, and Interconversion of Thyroid Hormones

Uptake of iodide ion (I−) by the gland.
Oxidation of iodide and iodination of tyrosyl groups of thyroglobulin.
Coupling of iodotyrosine residues to generate iodothyronines.
Resorption of thyroglobulin colloid from the lumen into the cell.
Proteolysis of thyroglobulin, releasing thyroxine and triiodothyronine into the blood.
Recycling of iodine within the thyroid cell via deiodination of mono- and diiodotyrosines, and reuse of the I−.
Conversion of thyroxine (T4) to triiodothyronine (T3) in peripheral tissues and in the thyroid.

Uptake of Iodide

Dairy products and fish are relatively high in iodine.
Iodine in the diet reaches circulation as iodide ion (I−).
The thyroid actively transports I− via sodium iodide symporter (NIS).
NIS is inhibited by thiocyanate and perchlorate.

Oxidation and Iodination

Iodination of tyrosine requires iodinating species to be in a higher state of oxidation.
Thyroid peroxidase accomplishes the oxidation of iodide to its active form.
Iodination leads to the formation of monoiodotyrosyl and diiodotyrosyl residues in thyroglobulin.
Thyroglobulin is stored in the thyroid follicle lumen.

Formation of Thyroxine and Triiodothyronine from lodotyrosines

Coupling of two diiodotyrosyl residues forms thyroxine (T4).
Coupling of monoiodotyrosyl and diiodotyrosyl residues forms triiodothyronine (T3).
The same thyroid peroxidase catalyzes these couplings.
The rates of synthesis depend on TSH concentration and iodide availability.

Resorption, Proteolysis, and Secretion

Endocytosis of colloid from the thyroid follicle lumen.
Within the cell, thyroglobulin appears as intracellular colloid droplets, fusing with lysosomes containing proteolytic enzymes.
TSH increases the degradation of thyroglobulin.
Liberated hormones (T3 and T4) exit the cell.
Monoiodotyrosine and diiodotyrosine are selectively metabolized, and iodine is reincorporated into protein.

Thyroid Hormone Metabolism and Conversion (T4 to T3)

Normal daily thyroxine production is ~ 80-100 μg.
Normal daily triiodothyronine production is ~ 30-40 μg.
Peripheral deiodination of T4 in tissues accounts for ~ 80% of circulating triiodothyronine.

Transport of Thyroid Hormones in the Blood

Thyroid hormones are transported in the blood in strong but non-covalent association with plasma proteins (TBG).
TBG is the major carrier of thyroid hormones.
T4, but not T3, is also bound by transthyretin (thyroid-binding prealbumin).
Albumin can bind T4 when carrier proteins are saturated.
Only unbound hormone has metabolic activity.

Factors that Alter Binding to TBG

Drugs that increase binding include estrogens, methadone, and clofibrate.
Drugs that decrease binding include glucocorticoids, androgens, L-asparaginase, salicylates, and mefenamic acid.
Systemic factors, like liver disease and acute/chronic illness might influence binding.

Degradation and Excretion

The liver is the major site of non-deiodinative degradation of thyroid hormones.
T4 and T3 are conjugated with glucuronic and sulfuric acids via their phenolic hydroxyl groups.
The conjugated hormones are excreted in bile.

Regulation of Thyroid Function

Thyrotropin-releasing hormone (TRH) is synthesized by the hypothalamus.
TRH stimulates the release of preformed TSH from the anterior pituitary.
TSH secretion is controlled by TRH and thyroid hormone concentration via feedback mechanisms.

Actions of Thyroid-Stimulating Hormone (TSH)

TSH stimulates all the phases of hormone synthesis & release (hormone synthesis, iodide uptake, organification, endocytosis, proteolysis of colloid).
TSH results in increased vascularity of the gland and hypertrophy and hyperplasia of thyroid cells.
In response to TSH, the thyroid produces and secretes T4, which is then converted to T3.

Actions of Thyroid Hormones

Thyroid hormones act primarily through binding to nuclear thyroid hormone receptors (TRs) and modulating specific genes.
Thyroid hormones have diverse effects; for instance, the body's development, thermoregulation, and cardiovascular function.

Major Clinical Effects of Thyroid Hormones

Effects on growth and development, including brain development.
Effects on thermogenesis
Cardiovascular effects, including positive chronotropic/inotropic effects, cardiac hypertrophy, and decreased peripheral vascular resistance.
Metabolic effects, including increased glucose absorption from the gut, metabolism of cholesterol to bile acids, and insulin resistance.

Levothyroxine

A synthetic T4 hormone used to treat hypothyroidism.
Levothyroxine can be used with surgery or radioiodine therapy to manage thyrotropin-dependent well-differentiated thyroid cancer.

Absorption of Oral T4

Absorption from the gastrointestinal tract is 40-80% primarily in the jejunum and upper ileum.
Absorption increases with fasting and decreases with malabsorption syndromes and some foods (soybeans, milk, etc.).
Many drugs affect absorption (bile acid sequestrants, sucralfate, proton pump inhibitors, various minerals).
For optimal absorption, levothyroxine should be taken on an empty stomach, 2-4 hours before meals and any interacting drugs.

Liver Degradation and Excretion

The liver is the major site of non-deiodinative degradation of thyroid hormones.
Thyroid hormones are conjugated with glucuronic and sulfuric acids.
Conjugated hormones are excreted in the bile.

TSH Suppression Therapy

TSH suppression therapy in patients with thyroid nodules or thyroid cancer involves administering levothyroxine to suppress TSH.
It decreases nodule volume.
TSH suppression should not be routinely recommended as a general practice but may be appropriate in cases of elevated TSH.

Anti-Thyroid Drugs and Other Thyroid Inhibitors

Anti-thyroid drugs interfere directly with thyroid hormone synthesis.
Ionic inhibitors block iodide transport.
High iodide concentrations decrease thyroid hormone release and synthesis.
Radioactive iodine damages the gland with ionizing radiation.

Adjuvant Therapy

Adjuvant therapy with drugs that have no specific effects on thyroid hormone synthesis but useful for controlling peripheral manifestations of thyrotoxicosis.
These include inhibitors of peripheral thyroxine deiodination (e.g., dexamethasone).
Also, beta-adrenergic receptor antagonists (e.g., propranolol, atenolol).

Three General Categories of Antithyroid Drugs

Thioureylenes (e.g., propylthiouracil, methimazole, carbimazole)
Aniline derivatives (e.g., sulfonamides)
Polyhydric phenols (e.g., resorcinol).

Propylthiouracil (PTU)

A thiourea antithyroid agent.
PTU binds to thyroid peroxidase and inhibits iodide to iodine conversion.
PTU interferes with iodine incorporation into tyrosyl residues of thyroglobulin and inhibits coupling of iodotyrosyl residues to form iodothyronines.
In addition to blocking hormone synthesis, PTU partially inhibits the peripheral deiodination of T4 to T3.

Propylthiouracil (PTU) Administration and Dosage

PTU is administered orally, initially in three divided doses (300 mg/day).
After the initial treatment, the dosage is adjusted to 100-150 mg/day.

Propylthiouracil (PTU) Absorption, Distribution, and Duration

Absorption: ~75%
Distribution: 80-85% bound to plasma proteins (lipoproteins, albumin).
Duration: ~12-24 hours.

Propylthiouracil (PTU) Adverse Reactions

Acute liver injury (common in pregnancy, adults, and children).
Hypothyroidism.
Vasculitis (symptoms include fever, weight loss, myalgia, arthralgia, and paresthesia; onset within weeks to years).
Hypersensitivity reactions (Steven Johnson syndrome, toxic epidermal necrolysis, urticaria).
Agranulocytosis (rare, potentially life-threatening, fever, sore throat, and granulocyte count less than 500/µL).

Methimazole

A thionamide antithyroid agent, active metabolic product of carbimazole.
10 times more potent than PTU.
Inhibits thyroid peroxidase actions—leading to reduced thyroid hormone synthesis.
Does not affect the existing thyroxine (T4) and triiodothyronine (T3) in the circulation.

Methimazole Administration and Absorption

Rapid and extensive absorption after oral administration.
Little-to-no protein binding.
Rapidly and extensively metabolized by the liver.
Excreted mainly via the urine; fecal elimination is minimal.

Methimazole Adverse Effects

Side effects are mostly dose-related (hives, itching).
Serious adverse effects (most commonly):
- Agranulocytosis
- Hepatotoxicity
Teratogenicity

Teratogenicity

Methimazole may cross the placental membrane readily & causes immense fetal adverse effects, especially during the first trimester of pregnancy. This includes possible congenital disabilities such as goiter, cretinism, etc.
Propylthiouracil (PTU) is generally preferred over methimazole for use during pregnancy, especially during the first trimester.

Ionic Inhibitors (thiocyanate, perchlorate, and fluoroborate)

Substances that interfere with iodide concentration by the thyroid gland.
Thiocyanate is produced by plant glycoside hydrolysis (e.g., cabbage and cigarette smoking; significantly increased concentration in blood and urine).
Perchlorate is a strong inhibitor of iodide transport, and is associated with many effects such as GI irritation and skin rash.

Radioactive Iodine (Iodine-131)

A radioactive isotope primarily used for thyroid diagnosis and treatment.
Radioactive iodine (I-131) emits both gamma rays and beta particles, degrading within 56 days.
Used to treat overactive or enlarged thyroids, as well as thyroid cancer.
Treatment can cause hypothyroidism.
Pregnancy is a major contraindication.

Iodine-Basedow Phenomenon

Hyperthyroidism arising from iodine supplementation.
May occur in those with pre-existing iodine deficiency.

Thyroid Storm

Life-threatening complication of thyrotoxicosis.
Symptoms: Fever, tachycardia, agitation, nausea, vomiting, diarrhea, and confusion; coma or death is possible.
Treatment: supportive measures like intravenous fluids, cooling blankets, antipyretics; high doses of anti-thyroid drugs are important.

Plummer's Disease (Toxic Nodular Goiter)

A form of hyperthyroidism due to abnormal nodules in the thyroid gland.
Medical therapy less effective for Plummer's Disease compared to Graves' Disease.
RAI is also effective, though results are delayed and it usually fails to resolve a goiter.
Surgical treatment is preferred for Plummer's Disease.

Other Information

Pediatric population: PTU is associated with liver injury in both adults and children.
Renal impairment: dose adjustment is not required.
Hepatobiliary disease: PTU should not be used in cases of liver impairment.
Pregnancy: PTU can cross placenta and cause fetal cretinism and goiter; methimazole is preferred over PTU in pregnancy to lower the risk of adverse effects for the developing fetus.
Breastfeeding: PTU is present in breast milk, but generally no clear-cut recommendations.
Thyroid storm: life-threatening complication of thyrotoxicosis, characterized by severe hyperthyroidism.

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Test your knowledge on the management of thyroid disorders, including treatment options for conditions such as Plummer's Disease and thyrotoxicosis. This quiz covers important considerations for medication use during pregnancy, operative risks, and symptom recognition in thyroid storms.