Hyperthyroidism and Graves' Disease Overview

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Questions and Answers

What condition is indicated by low TSH and high T3 and T4 levels?

Toxic Multinodular Goiter (correct)

Subclinical Hypothyroidism

Primary Hyperthyroidism (correct)

Secondary Hypothyroidism

Which treatment is typically considered for Toxic Multinodular Goiter in appropriate patients?

Levothyroxine

Thyroid hormone replacement

Sodium iodide

Radioiodine therapy (correct)

What is a common symptom of a toxic multinodular goiter?

Weight gain

Cold intolerance

Insomnia

Heart failure (correct)

Amiodarone-induced thyrotoxicosis Type 1 is primarily caused by which mechanism?

Iodine excess Signup and view all the answers

In amiodarone-induced thyrotoxicosis Type 2, which treatment is indicated?

Prednisone Signup and view all the answers

Which laboratory finding is associated with subclinical hypothyroidism?

Increased TSH Signup and view all the answers

What imaging result is typically seen with a toxic multinodular goiter during a RAIU scan?

Irregular patchy distribution with high uptake Signup and view all the answers

What could happen in older patients with longstanding diseases regarding goiters?

Goiters become toxic Signup and view all the answers

What is the prognosis for a patient with Graves' disease when treated with anti-thyroid drugs?

A course of remissions and exacerbations with a chance of becoming hypothyroid Signup and view all the answers

How does a toxic adenoma affect the secretion of thyroid hormones?

It autonomously hypersecretes T3 and T4 independent of TSH stimulation Signup and view all the answers

What is a common laboratory finding in patients with toxic adenoma?

Low TSH and high T3 levels Signup and view all the answers

Which treatment option is generally effective for managing toxic adenoma?

Radioactive iodine which spares the contralateral lobe Signup and view all the answers

What differentiates toxic adenoma from Graves' disease in terms of physical examination findings?

A large nodule on one side with minimal thyroid tissue on the other Signup and view all the answers

What is a characteristic symptom of toxic adenoma that is absent in Graves' disease?

Ophthalmopathy Signup and view all the answers

What can happen to the contralateral lobe of the thyroid due to a toxic adenoma?

It can experience atrophy and reduced function Signup and view all the answers

Which statement is true regarding the management of toxic multinodular goiter?

Radioactive iodine treatment is often indicated for larger nodules Signup and view all the answers

What is the expected outcome for the majority of patients after receiving radioactive iodine treatment for Graves’ disease?

They will become hypothyroid within 6—12 months. Signup and view all the answers

In which situation is a thyroidectomy considered the first choice of treatment?

For patients who are non-compliant with medication. Signup and view all the answers

Which of the following is true regarding the monitoring of patients after thyroid surgery?

Levothyroxine is required for patients who become hypothyroid post-surgery. Signup and view all the answers

What is the role of β-adrenergic-blocking agents in the treatment of thyrotoxicosis?

They are used to control adrenergic symptoms during the acute phase. Signup and view all the answers

Which of the following is a contraindication for using radioactive iodine?

Severe eye disease. Signup and view all the answers

Which food items should be avoided due to their goitrogenic properties in a naturopathic approach to treating Graves’ disease?

Raw Brassicas such as cabbage and turnips. Signup and view all the answers

What is the purpose of administering potassium iodide before thyroid surgery?

To diminish vascularity and decrease intraoperative blood loss. Signup and view all the answers

Which of the following statements about iodine in the treatment of thyrotoxicosis is correct?

It can cause hyperthyroidism in euthyroid patients due to Jod-Basedow phenomenon. Signup and view all the answers

What is a common side effect of thyroidectomy?

Hypoparathyroidism in approximately 1% of cases. Signup and view all the answers

Which of the following is typically prescribed to patients who develop hypothyroidism following radioactive iodine treatment?

Levothyroxine. Signup and view all the answers

What is the initial dose of Methimazole recommended for treatment in young patients?

10-20 mg/d Signup and view all the answers

Which of the following is an advantage of Methimazole over Propylthiouracil (PTU)?

Longer duration of action Signup and view all the answers

For which condition is Propylthiouracil (PTU) preferred over Methimazole?

In pregnant women during the first trimester Signup and view all the answers

What is a common adverse reaction that can occur in patients treated with antithyroid drugs?

Severe sore throat and fever due to agranulocytosis Signup and view all the answers

What should be monitored in patients undergoing treatment for Graves' disease to assess their response to antithyroid drugs?

Serum fT4 and T3 levels Signup and view all the answers

Why is TSH not a reliable indicator of thyroid function in the early stages of treatment?

It can remain suppressed for weeks or months Signup and view all the answers

What is the potential severe side effect of Propylthiouracil (PTU)?

Severe or fatal hepatotoxicity Signup and view all the answers

What is the treatment of choice for most patients over 21 years old with Graves' disease in the US?

Radioactive Iodine Signup and view all the answers

What is the expected outcome in 20-50% of patients after 1-2 years of treatment with Methimazole?

Sustained remission Signup and view all the answers

What is an uncommon adverse reaction associated with antithyroid drugs?

Cholestatic jaundice Signup and view all the answers

What is the most common cause of thyrotoxicosis?

Graves’ disease Signup and view all the answers

Which of the following symptoms is NOT commonly associated with Graves' disease?

Hypoglycemia Signup and view all the answers

In which age group is Graves' disease most commonly diagnosed?

20-40 years old Signup and view all the answers

What is the typical laboratory finding in Graves' disease?

Low TSH, high fT4 and fT3 Signup and view all the answers

Which factor is NOT considered an environmental trigger for Graves' disease?

Physical activity Signup and view all the answers

Which of the following describes thyroid dermopathy associated with Graves' disease?

Accumulation of glycosaminoglycans on the lower tibia Signup and view all the answers

What is a hallmark sign of a thyrotoxic crisis?

Severe agitation and delirium Signup and view all the answers

What is the role of autoantibodies in Graves' disease?

Mimic the action of TSH leading to excessive hormone production Signup and view all the answers

Which imaging technique is commonly used to assess Graves’ disease?

Radioactive iodine uptake Signup and view all the answers

Which of the following is a common consequence of thyrotoxicosis?

Fatigue Signup and view all the answers

Which of the following is a common characteristic of the thyroid in Graves' disease upon physical exam?

Symmetrically enlarged and smooth Signup and view all the answers

What symptom indicates the presence of thyroid-related ophthalmopathy in Graves' disease?

Lid lag Signup and view all the answers

What finding on laboratory tests can be specifically associated with Graves' disease?

Elevated Thyroid Stimulating Antibodies (TSAb) Signup and view all the answers

Which mechanism contributes to increased catecholamine response in hyperthyroidism?

Increased β-adrenergic receptors Signup and view all the answers

Study Notes

Hyperthyroidism

A clinical syndrome that occurs when tissues are exposed to high thyroid hormone levels.
Accelerates metabolism.
Caused by several conditions, including Graves' disease, toxic thyroid adenoma, Plummer's disease, TSH-secreting pituitary tumors, and exogenous thyroid hormone.

Graves' Disease

Also known as Diffuse Toxic Goiter.
Most common cause of thyrotoxicosis/hyperthyroidism.
Five times more prevalent in women.
Peak incidence is between 20-40 years old.
It is a familial disease affecting 15% of family members.
Environmental factors include stress, tobacco, infection, iodine exposure, and postpartum state.

Graves' Disease: Signs and Symptoms

Thyrotoxicosis: high serum levels of T3 and T4.
Diffuse goiter: bilateral and non-nodular thyroid enlargement.
Ophthalmopathy: bulged eyes, proptosis.
Thyroid Dermopathy/Pre-tibial Myxedema: pretibial skin thickening due to glycosaminoglycans accumulation.
Other signs and symptoms: rapid growth, accelerated bone maturation, palpitations, nervousness, fatigue, hyperkinesia, diarrhea, excessive sweating, intolerance to heat, weight loss, muscle weakness, and loss of muscle mass.

Graves' Disease: Pathogenesis

Autoantibodies: T-lymphocytes are sensitized to thyroid gland antigens, activating B-lymphocytes to produce antibodies (Abs) against these antigens.
Thyroid stimulating antibodies (TSAb) or Thyroid Stimulating Immunoglobulin (TSI): bind to TSH receptors, mimicking TSH and constantly stimulating the thyroid.
Other contributing factors: interferon alfa, viral or bacterial infections, and psychological stress.

Graves' Disease: Ophthalmopathy

A shared antigen exists in the TSH receptor, thyroid tissue, orbital fibroblasts, and extraocular muscles.
Cytokines from T-lymphocytes and cytotoxic antibodies activate and proliferate orbital fibroblasts and pre-adipocytes.
This results in increased retro-orbital fat, glycosaminoglycans, and swollen extraocular muscles.
This leads to proptosis, diplopia, redness, congestion, conjunctival and periorbital edema.
Smoking increases the risk of developing ophthalmopathy.

Graves' Disease: Pretibial Myxedema

Thickening of the skin, primarily around the lower tibia.
Accumulation of glycosaminoglycans.
Appearance resembles peau d’orange.

Graves' Disease: Labs

Free T4 (fT4): elevated.
Free T3 (fT3): elevated.
TSH: low.
TSAb/TSI: elevated.
Anti-TPO: can be elevated (also observed in Hashimoto's disease).
Anti-TG: can be elevated (also observed in Hashimoto's disease).
CBC: anemia, low or slightly depressed WBCs, lymphocytosis, and monocytosis.
SHBG: can be elevated, leading to low free testosterone levels.
Diabetic patients may exhibit increased HbA1c.
Lipid panel: low cholesterol and triglyceride levels.

Graves' Disease: Differential Diagnoses

T3 Thyrotoxicosis: 5% of Graves' disease patients present with normal fT4 and elevated T3.
Subclinical hyperthyroidism: TSH is low, but fT4 and T3 levels are within the normal range.
Secondary hyperthyroidism: TSH-secreting pituitary tumor. Patients exhibit elevated TSH, T3, fT4, and RAIU.
Sick Euthyroid Syndrome: severely ill patients experience decreased TRH and TSH production due to cytokines impacting the hypothalamus and pituitary.

Graves' Disease: Imaging

CT or MRI: extraocular muscle enlargement is seen in most patients.
Radioactive Iodine Uptake (RAIU): increased and diffuse uptake.

Graves' Disease: Complications

Thyrotoxic Crisis/ Thyroid Storm: commonly occurs after surgery, radioactive iodine therapy, delivery, or during severe illness such as uncontrolled diabetes, trauma, infections, severe drug reactions, or myocardial infarction.
Thyroid storm characteristics: marked hypermetabolism, excessive adrenergic responses, and significant adrenergic binding sites, leading to exaggerated stress response.

Graves' Disease: Thyrotoxic Crisis

Signs and symptoms: fever, flushing, sweating, tachycardia, atrial fibrillation, high pulse pressure, agitation, restlessness, delirium, coma, nausea, vomiting, diarrhea, jaundice.
Treatment: supportive measures, antiadrenergic drugs, thionamides, iodine preparations, glucocorticoids, cholestyramine, treatment of underlying condition, and plasmapheresis.

Graves' Disease: Treatment: Conventional

Anti-thyroid drugs (immunosuppressive effects): methimazole (Tapazole) and propylthiouracil (PTU).
Methimazole: inhibits TPO-mediated iodination of TG to form T4 and T3.
Methimazole preferred over PTU: fewer adverse effects, longer duration of action.
PTU: potential for severe or fatal hepatotoxicity and vasculitis.
Treatment duration: 1-2 years with subsequent tapering or discontinuation.

Graves' Disease: Medications: Methimazole

Initial dose: 10-20 mg/day.
Maintenance dose: 5-10 mg/day.
20-50% of patients experience remission.
Teratogenic: PTU is preferred in pregnancy and breastfeeding.

Graves' Disease: Medications: Propylthiouracil (PTU)

Initial dose: 100 mg every 8 hours.
Maintenance dose: 50-200 mg daily.
Treatment duration: 1-2 years followed by tapering or discontinuation.
Teratogenicity of methimazole makes PTU a preferred option in the first trimester of pregnancy.

###Graves' Disease: Monitoring Thyroid Hormone Levels

Serum fT4 and T3: used to monitor patient response and adjust medication dosages.
TSH: remains suppressed for weeks or months after treatment initiation and is not a reliable indicator of thyroid function during the initial phase of therapy.
Ideally, TSAbs should be undetectable at the end of therapy.
Thyroid gland should return to normal size.
Lifelong monitoring of all patients is crucial.

Graves' Disease: Treatment: Radioactive Iodine

Preferred treatment in the US for patients over 21.
Single oral dose.
Results in thyroid gland shrinkage and euthyroidism within 2-6 months.
80% of patients develop hypothyroidism within 6-12 months.
Hypothyroidism management: levothyroxine (or DTE) for life.
Long-term studies: no evidence of infertility, birth defects, or cancer caused by radioactive iodine.

Graves' Disease: Radioactive Iodine: Contraindications

Severe eye disease.
Patients with mild to moderate eye disease: prednisone (0.4 mg/kg/d) for 1-2 months is administered after radioactive iodine to prevent worsening eye symptoms.

Graves' Disease: Treatment: Conventional: Surgical Treatment

Thyroidectomy: total or near-total surgical removal of the thyroid gland.
First choice for patients with very large glands, non-compliance with other therapies, pregnancy, allergies to iodine or drug therapy, multinodular goiters, or malignant nodules.
Results in hypothyroidism, requiring levothyroxine (or DTE) for life.
Potential complications: hypoparathyroidism, damage to the recurrent laryngeal nerve leading to hoarseness.

Graves' Disease: Pre-surgical Thyroidectomy Management

Patients are treated with anti-thyroid drugs until euthyroid (approximately 6 weeks) to prevent thyroid storm.
Potassium iodide (5 drops bid) is administered for two weeks before surgery to reduce gland vascularity and minimize intraoperative blood loss.

Graves' Disease: Treatment: Other Medical Measures

β-adrenergic-blocking agents: Propranolol, Inderal LA, nadolol, atenolol, metoprolol.
Used to control acute phase adrenergic symptoms such as tachycardia, hypertension, and atrial fibrillation.
Gradually withdrawn as other therapies restore normal thyroid hormone levels.
Cholestyramine: binds to T4 in the gut and may be used in severe cases.

Graves' Disease: Treatment: Naturopathic

Reduce risk factors like stress and smoking.
Increase rest.
High-calorie and high-protein diet with frequent meals.
Anti-thyroid foods: raw Brassicas (turnips, cabbage, rutabagas, mustard, rapeseeds, cassava root, peanuts, pine nuts, millet, and soy) - restrict iodine intake.
Indole-3-carbinol: 200-600 mg/day.
L-Carnitine: 2-4 g/day.

Graves' Disease: Treatment: Naturopathic: Botanicals

Lycopus spp.: blocks TSH receptors, inhibits peripheral T4 conversion to T3, 5 mL tid (100 mL max/week).
Leonurus cardiaca: inhibits TSH, reduces thyroid hormone production, cardiac tonic, hypotensive, nervine.
Lithospermum officinale: blocks TSH receptors.
Lemon balm (Melissa officinalis): blocks TSH receptors, 2-6 mL tid.
Nervines: Valariana officinalis, Scutellaria lateriflora.
Cactus grandiflorus: heart tonic for rapid pulse.
Iris versicolor: reduces goiter swelling.
Eleutherococcus senticosus: 5 mL/day.
Vitex agnus-castus: 3 mL/day.

Graves' Disease: Treatment: Iodine

High doses temporarily reduce thyrotoxicosis symptoms by suppressing hormone synthesis (Wolff-Chaikoff effect).
Effects are unpredictable, and the thyroid may resume hormone synthesis at a reduced or increased rate.
Can induce hyperthyroidism (Jod-Basedow phenomenon) in euthyroid patients.
Fucus spp. (high in iodine): use with caution.

Graves' Disease: Prognosis

Anti-thyroid drugs: likely lead to remissions and exacerbations.
"Burned-out Graves' disease": 25% transition to hypothyroidism due to autoimmune thyroid destruction.
Hypothyroidism: persists for life after surgical removal or radioactive iodine therapy.
Lifelong monitoring of TSH and thyroid hormones is essential.

Non-Graves' Hyperthyroidism

Toxic Adenoma
Toxic Multinodular Goiter (Plummer's Disease)
Amiodarone-Induced Thyrotoxicosis.

Toxic Adenoma

A functioning thyroid adenoma that secretes excess T3 and T4.
Typically benign follicular adenomas.
Does not require TSH stimulation to function.
Suppresses TSH, leading to reduced function and atrophy in the contralateral lobe.

Toxic Adenoma: Signs and Symptoms

Similar to Graves' disease, but without ophthalmopathy.

Toxic Adenoma: Physical Exam

A large nodule on one side with minimal thyroid tissue on the other side.

Toxic Adenoma: Labs and Imaging

TSH: low.
T3: high.
fT4: borderline elevation.
RAIU Scan: hot nodule on one side, diminished or absent function of the other side.

Toxic Adenoma: Treatment

Radioactive iodine: typically effective, spares the contralateral lobe.
Surgery: if the nodule is large and causes obstructive symptoms such as dysphagia or breathing problems.
Medications are only used before surgery or radiotherapy.

Toxic Multinodular Goiter/ Plummer's Disease

Initiates with euthyroid multinodular goiter.
Multiple nodules function autonomously, resulting in hyperthyroidism.
The nodules are typically benign.
Can cause compression and lead to dysphagia or dyspnea.

Toxic Multinodular Goiter/ Plummer's Disease: Treatment

Radioactive iodine: the preferred treatment.
Surgery: if the goiter is large or causes compression symptoms.
Thyroid hormone suppression (L-T4): used for symptomatic relief.

Toxic Multinodular Goiter (Plummer’s Disease)

Toxic multinodular goiter is a condition where the thyroid gland overproduces thyroid hormones
It is common in older patients with a history of thyroid disease
Nodules in the thyroid gland may become active following treatment with iodine or iodine-containing drugs (Jod-Basedow phenomenon)
Symptoms include tachycardia, arrhythmia, heart failure, weight loss, nervousness, weakness, tremors, and excessive sweating
Physical examination may reveal a multinodular goiter, which may be small or large and can extend substernally

Labs/Imaging

Thyroid stimulating hormone (TSH) is low
Triiodothyronine (T3) is high
Thyroxine (T4) is moderately high
Radioactive iodine uptake (RAIU) scan shows high uptake in nodules and an irregular, patchy distribution

Treatment

Treatment for toxic multinodular goiter includes anti-thyroid drugs and/or radioiodine therapy
Surgery may be considered for suitable patients

Amiodarone-Induced Thyrotoxicosis

Amiodarone is an antiarrhythmic drug that contains iodine
It can be stored in fatty tissues, the heart, liver, and lungs
Amiodarone-induced thyrotoxicosis occurs in 2% of patients treated with the drug
Two types of amiodarone-induced thyrotoxicosis:
- Type 1: Due to excess iodine, usually occurring within 6-12 months after starting the drug. Blood flow is increased on Doppler ultrasound and treated with methimazole and beta-blockers
- Type 2: Result of thyroiditis, typically after taking the drug for 2-3 years. Blood flow is decreased on Doppler ultrasound and treated with prednisone

Thyroid Labs

Subclinical Hypothyroidism: TSH elevated, T4 normal, T3 normal
Primary Hyperthyroidism: TSH decreased, T4 elevated, T3 elevated
Primary Hypothyroidism: TSH elevated, T4 decreased, T3 decreased

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This quiz explores hyperthyroidism, its causes, and the specific case of Graves' disease. You'll learn about the signs, symptoms, and key factors contributing to these conditions. Test your knowledge on thyroid health and its impact on metabolism.