Thyroid

Diagnosis is based on a combination of clinical features, thyroid antibodies, and thyroid function tests. Additional studies like ultrasound and fine-needle aspiration may be obtained to rule out alternative conditions and support the diagnosis.

Management consists of lifelong monitoring and, in most cases, hormone replacement therapy with levothyroxine.

The prevalence of Hashimoto thyroiditis is approximately 5% in the US, making it the most common form of thyroiditis and the most frequent cause of hypothyroidism in the country.

• Primarily asymptomatic
• Goiter: nontender or painless, rubbery thyroid with moderate and symmetrical enlargement
• Possible Hashitoxicosis: transient thyrotoxicosis due to follicular rupture of hormone-containing thyroid tissue, manifesting with signs of hyperthyroidism (e.g., irritability, heat intolerance, diarrhea)

• Thyroid may be normal-sized or small if extensive fibrosis has occurred.
• Signs of hypothyroidism include cold intolerance, constipation, and fatigue.

• A rare neurological syndrome associated with high TPOAb or TgAb titers.
• Clinical features are widely variable and may include:
  • Impairment of cognitive function and vigilance
  • Ataxia
  • Myoclonus
  • Seizures
  • Psychosis
• Treatment involves glucocorticoids.

• Consider Hashimoto thyroiditis in patients with signs of hypothyroidism, thyrotoxicosis (less common), and/or painless goiter.
• Obtain the following for all patients:
  1. Thyroid function tests
  2. Thyroid antibodies to confirm the diagnosis
  3. In patients with goiter or suspected thyroid nodules: Obtain a thyroid ultrasound.
• Consider additional studies to rule out differential diagnoses.

Destructive thyroiditis shows no or minimal activity throughout the gland, indicated by a decrease in activity (↓).

Exogenous thyrotoxicosis is characterized by overall decreased activity on the thyroid scan (↓).

A thyrotropic adenoma presents as an enlarged gland with increased activity (↑) on the thyroid scan.

Indications for thyroid ultrasound with Doppler include:

1. Palpable abnormality, e.g., goiter or nodules
2. Additional study following nuclear medicine thyroid scan or as a second-line initial imaging study
3. Preferred imaging technique in pregnant or breastfeeding women

Typical findings in a thyroid ultrasound with Doppler include:

• Changes to morphology: diffuse enlargement or nodules
• Increased perfusion: either diffuse (Graves disease, toxic adenoma) or nodular (toxic MNG)
• Decreased perfusion: destructive thyroiditis

Hypoechoic areas appear darker than the surrounding tissue on ultrasound, indicating possible inflammation or malignancy in the thyroid gland.

An autonomous thyroid adenoma is characterized by a well-defined nodule within the thyroid gland that has a different texture compared to the surrounding tissue.

Peripheral calcification in a thyroid nodule is indicated by bright, dense areas around the edges of the nodule, suggesting the presence of calcium deposits.

Increased vascularity in Graves' disease is shown by red and blue colors indicating blood flow, with additional colors like green and yellow highlighting excessive blood flow within the thyroid gland.

Hypervascularity in Graves' disease is represented by a web of red and blue lines, indicating significant blood flow within the thyroid tissue, which suggests increased metabolic activity and inflammation.

In Graves' disease, variations in the thyroid gland can include changes in texture and blood flow, with color Doppler images highlighting increased vascularity and a network of blood vessels within the thyroid tissue.

Ultrasound-guided FNAC is performed to evaluate suspicious nodules and can help confirm the etiology if the diagnosis remains uncertain.

Thyroid peroxidase antibodies (TPOAb) are indicated for suspected subacute lymphocytic thyroiditis, including postpartum thyroiditis.

The recommended diagnostic workup for postpartum thyroiditis in patients with thyrotoxicosis includes:

1. Total T3 and total T4 tests
2. TRAB testing
3. Consideration of thyroid imaging

RAIU measurement is contraindicated in pregnancy and lactation, but if necessary during lactation, iodine-123 or technetium-99m should be used, with advice to pump and discard breast milk for 3–5 days afterward.

Postpartum thyroiditis is the most common cause of hyperthyroidism in the postpartum period; however, the incidence of Graves disease is 3–4 times higher postpartum than in the nonpostpartum period.

Common risk factors for postpartum thyroiditis include:

• Personal or family history of autoimmune thyroid disease
• Type 1 diabetes
• History of postpartum thyroiditis

In postpartum thyroiditis, symptoms of hypothyroidism are more common than those of hyperthyroidism, which are typically mild or absent in affected individuals.

Symptoms usually appear less than 3 months or commonly more than 6 months after delivery.

TSH receptor antibodies are typically positive in Graves disease.

A T3:T4 ratio greater than 20 may indicate hyperthyroidism, while a ratio less than 20 is typically seen in other conditions.

A thyroid ultrasound with Doppler typically shows increased blood flow in Graves disease.

Use propranolol or metoprolol at the lowest effective dose and monitor TSH every 4–8 weeks.

Consider levothyroxine replacement for patients with overt hypothyroidism who are breastfeeding, trying to conceive, or have a TSH level > 10 mU/L.

Goiter is an abnormal enlargement of the thyroid gland. The most common cause worldwide is iodine deficiency, while in the US, Hashimoto's disease and Graves' disease are more prevalent.

Goiters can be classified based on:

1. Morphology
2. Function
3. Dignity (benign or malignant)

Symptoms of goiter depend on the underlying etiology and may often be absent. However, patients may present with:

• Hyperthyroidism
• Hypothyroidism
• Large goiters may cause obstructive symptoms due to compression of the trachea and/or esophagus.

Diagnosis of goiter is established through:

• Clinical examination
• Laboratory tests
• Imaging techniques

Management of goiter depends on the underlying condition and may include:

• Administering iodine for nontoxic euthyroid goiter
• Performing surgery for local compression or thyroid cancers

Rhabdomyosarcoma is the most common soft tissue sarcoma and malignant orbital tumor in children, primarily occurring in the first decade of life.

Clinical features include:

• Growing orbital mass that may be painful and have potential hemorrhage
• Proptosis or dysconjugate gaze
• Minimally painful, rapidly increasing, gross swelling

Diagnostics include:

1. Open or core needle biopsy for light microscopy to look for rhabdomyoblasts
2. X-ray of the primary site and chest to determine bone and lung involvement for staging
3. CT of the primary site and chest to search for lung metastases and bone destruction
4. MRI to determine specific location of mass and any soft tissue invasion

Treatment options include:

• Surgery (complete excision) if a functional and cosmetic result is possible
• Combination of radiation and chemotherapy following a diagnostic biopsy if complete excision is not feasible

The prognosis is more favorable for localized tumors of the orbit and less favorable for metastatic disease.

Hypothyroidism is a condition characterized by an underactive thyroid gland, leading to a deficiency of thyroid hormones (T3 and T4). The main causes include:

• Congenital hypothyroidism: Often due to thyroid dysplasia or aplasia.
• Acquired hypothyroidism: Typically caused by autoimmune conditions like Hashimoto thyroiditis or iatrogenic factors (e.g., radiation therapy).

Typical clinical features of hypothyroidism include:

• Fatigue
• Cold intolerance
• Dry skin
• Constipation

More severe manifestations can include myxedematous heart disease and myxedema coma, which can be fatal if untreated.

In adults, hypothyroidism is diagnosed based on serum levels of:

• Thyroid-stimulating hormone (TSH)
• Free T4 (FT4)

The treatment for both congenital and acquired hypothyroidism consists of:

• Lifelong treatment with levothyroxine
• Regular checkups to monitor disease activity

Common etiologies of goiter include:

• Iodine deficiency
• Hashimoto thyroiditis
• Graves disease
• Thyroid cysts
• Thyroid adenomas
• Thyroid carcinomas
• Ingestion of goitrogens (e.g., lithium carbonate)
• Elevated TSH production due to conditions like pituitary adenoma or paraneoplastic syndrome
• Congenital goiter

A normal thyroid gland weighs approximately 20-30 g and has a volume of about 7-10 mL, located caudal to the larynx surrounding the trachea. A goiter is characterized by an enlarged volume of the thyroid gland, which can be differentiated based on morphology, thyroid function, and benignity/malignancy.

Nontoxic goiter is characterized by normal TSH, fT3, and fT4 levels.

Toxic goiter is distinguished by increased thyroid hormone production, while nontoxic goiter has normal hormone levels.

Conditions associated with hypothyroid goiter include Hashimoto's disease and congenital hypothyroid goiter.

Patients with goiter are commonly asymptomatic, but may experience:

• Altered hormone metabolism
• Symptoms of hyperthyroidism or hypothyroidism
• Obstructive symptoms such as:
  • Compression of the trachea leading to exertional dyspnea, stridor, or wheezing
  • Compression of the esophagus causing dysphagia
• Potential lymph node enlargement in malignant cases
• Pemberton sign indicating obstructed thoracic inlet.

The best initial step in the diagnosis of goiter is palpation of the thyroid gland.

The initial workup for goiter diagnosis includes:

1. TSH levels
2. Possible screening for thyroid antibodies
3. If medullary carcinoma is suspected, check calcitonin levels.

Surgery is preferred to avoid complications such as obstructive symptoms.

Further evaluation may include:

1. CT (Computed Tomography)
2. MRI (Magnetic Resonance Imaging)

Treatment is not needed if the patient is asymptomatic. Schedule follow-ups for possible dysfunctional thyroid and/or obstructive symptoms.

Iodine supplementation is the treatment for iodine deficiency related to goiter.

In cases other than iodine deficiency, goiter treatment varies depending on the exact etiology of the condition.

• Cold intolerance
• Fatigue, decreased physical activity
• Weight gain (despite decreased appetite)
• Bradycardia
• Myxedematous heart disease (dilated cardiomyopathy, bradycardia, dyspnea)
• Decreased cardiac output
• Hypothyroid myopathy (proximal muscle weakness with elevated creatine kinase levels)
• Entrapment syndromes (e.g., carpal tunnel syndrome)
• Myoedema
• Constipation

• Abnormal menstrual cycle (secondary amenorrhea or menorrhagia)
• Galactorrhea
• Decreased libido, erectile dysfunction, delayed ejaculation, and infertility in men

• Impaired cognition (concentration, memory)
• Somnolence
• Depression

• Diffuse, smooth, nontender goiter, often with audible bruit
• Heat intolerance
• Weakness, fatigue
• Weight loss (despite increased appetite)
• Tachycardia
• Palpitations, irregular pulse
• Hypertension with widened pulse pressure
• Increased systolic pressure
• Decreased diastolic pressure
• Abnormal heart rhythms (e.g., atrial fibrillation)
• Chest pain
• Hyperthyroid myopathy (proximal muscle weakness with normal creatinine kinase levels)
• Osteopathy (osteoporosis)
• Frequent bowel movements (due to intestinal hypermotility)

• Oligo/amenorrhea
• Anovulatory infertility
• Dysfunctional uterine bleeding
• In men: gynecomastia, decreased libido, infertility, erectile dysfunction

• Anxiety
• Restlessness
• Insomnia

Hyporeflexia is a condition characterized by reduced reflexes. It can be associated with hypothyroidism, where decreased thyroid hormone levels lead to diminished neurological function, affecting reflex responses.

The Woltman sign is a clinical sign where there is a delayed response in muscle contraction after a reflex is elicited. It is often seen in hypothyroidism, indicating impaired neuromuscular function due to low thyroid hormone levels.

Tendulousness refers to a fine tremor observed in the outstretched fingers. This symptom can be associated with hyperthyroidism, where increased thyroid hormone levels lead to heightened neuromuscular excitability and tremors.

Hyperreflexia is characterized by exaggerated reflexes. It can occur in hyperthyroidism, where elevated thyroid hormone levels enhance neuromuscular excitability, leading to increased reflex responses.

Hashimoto thyroiditis is the most common cause of overt primary hypothyroidism, as indicated by thyroid function tests showing elevated TSH levels and decreased Free T4 and Free T3 levels.

In overt primary hypothyroidism, thyroid function tests typically show:

• TSH: Increased
• Free T4: Decreased
• Free T3: Decreased

Causes of transient hypothyroidism include:

• Silent thyroiditis
• Subacute granulomatous thyroiditis These conditions can lead to temporary changes in thyroid hormone levels, affecting test results.

Secondary hypothyroidism can be caused by:

1. Pituitary disorders (e.g., pituitary adenoma)
2. Infiltrative diseases
3. Iatrogenic causes (e.g., following pituitary surgery)

Subclinical hypothyroidism is characterized by:

• Asymptomatic
• Mildly elevated TSH levels
• Normal T3 and T4 levels
  It shares the same etiology as primary hypothyroidism.

Low T3 syndrome occurs in the context of:

• Severe illness or
• Severe physical stress
  It is characterized by low T3 levels while TSH and T4 levels remain normal.

The causes of primary hyperthyroidism include:

• Graves disease
• Toxic multinodular goiter (MNG)
• Toxic adenoma
• Postpartum thyroiditis
• Subacute granulomatous thyroiditis (de Quervain thyroiditis)
• Thyrotropic adenoma

Primary hyperthyroidism has various causes such as Graves disease and toxic adenoma, while secondary hyperthyroidism shares the same etiology as primary but typically involves an issue with the pituitary gland. In secondary hyperthyroidism, the thyroid hormone levels are usually normal or increased.

Subclinical hyperthyroidism is a condition where thyroid hormone levels are normal, but thyroid-stimulating hormone (TSH) levels are low, indicating an early stage of hyperthyroidism without overt symptoms.

Thyrotoxicosis refers to the symptoms caused by excessive circulation of thyroid hormones, typically due to hyperthyroidism. Common causes include:

1. Graves disease (most common)
2. Toxic multinodular goiter (MNG)
3. Toxic adenoma
4. Thyroiditis (inappropriate release from a damaged thyroid)
5. Rarely, TSH-producing pituitary tumors, excessive hCG production, or oral intake of thyroid hormones.

Common symptoms of thyrotoxicosis include:

• Fatigue
• Anxiety
• Heat intolerance
• Increased perspiration
• Palpitations
• Significant weight loss despite increased appetite

Thyrotoxicosis is diagnosed through:

• Thyroid function tests (TFTs) to confirm thyrotoxicosis
• TSH receptor antibodies to identify the etiology
• Thyroid ultrasonography
• Radioactive iodine uptake tests

Thyroid storm is a life-threatening hypermetabolic state caused by an acute exacerbation of thyrotoxicosis. Management includes:

1. Urgent stabilization in critical care settings
2. Fluids
3. Beta blockers
4. Antithyroid medications (e.g., propylthiouracil, potassium iodide)
5. Parenteral glucocorticoids
6. Active cooling
7. Management of tachyarrhythmias

Definitive therapy with radioactive iodine ablation or surgery is considered once the patient is stable.

Initial management of thyrotoxicosis involves:

• Control of symptoms with:
  • Beta blockers
  • Antithyroid drugs

This is often followed by definitive therapy with either radioactive iodine ablation (RAIA) or thyroid surgery.

Thyrotoxicosis is a hypermetabolic condition caused by high levels of circulating thyroid hormones, regardless of the source. Hyperthyroidism specifically refers to the overproduction of thyroid hormones by the thyroid gland, which can lead to thyrotoxicosis.

• Decreased serum TSH levels
• Increased serum free T4 and/or T3 levels
• Patients typically experience symptoms of thyrotoxicosis.

• Decreased serum TSH levels
• Normal serum free T4 and T3 levels
• Patients are usually asymptomatic or mildly symptomatic and may progress to overt hyperthyroidism.

The most common cause of hyperthyroidism in the US is autoimmune due to TSH receptor autoantibodies, with a peak incidence occurring between 20-30 years of age.

For hyperthyroidism, the gender ratio is ♀:♂ (8:1) in the 20-30 years age group. For hypothyroidism, the peak incidence is >50 years of age with a gender ratio of ♀:♂ (3:1).

Causes of hyperthyroidism related to iodine include chronic iodine deficiency and iodine excess from diet, contrast, or amiodarone.

Goiter consistency can be:

1. Diffuse and smooth
2. Multinodular
3. Diffuse and firm The consistency depends on the underlying thyroid disorder.

Other findings associated with thyroid disorders include:

• Painless goiter
• Graves ophthalmopathy
• Painful goiter with increased ESR, fever, and malaise
• Nonspecific pain.

During the thyrotoxic phase, thyroid function tests show:

• Decreased TSH
• Increased T3/T4
• Increased thyroglobulin

Histopathological findings in subacute thyroiditis include:

• Diffuse hyperplasia and hypertrophy of follicular cells
• Patches of enlarged follicular cells distended with colloid
• Flattened epithelium
• Granulomatous inflammation with multinucleated giant cells
• Absence of germinal follicles and lymphocytic infiltration

During the hypothyroid phase, thyroid function tests show:

• Increased TSH
• Decreased T3/T4

In subacute thyroiditis, antibody findings typically include:

• Increased TRAbs
• Absent anti-TPO antibody
• Anti-TPO antibody may be present
• Possible increased TRAb in patients with Graves disease

Iodine uptake patterns in subacute thyroiditis are characterized by:

• Diffuse and multiple areas of reduced uptake
• Focal areas of increased uptake on scintigraphy

The prevalence of overt hyperthyroidism is approximately 1%.

Graves disease typically presents in individuals aged 20 to 30 years.

The peak incidence for toxic multinodular goiter (MNG) is over 50 years of age.

The hypothalamic-pituitary-thyroid axis is a self-regulating circuit that involves the hypothalamus, anterior pituitary gland, and thyroid gland. It regulates thyroid hormone production through a feedback mechanism:

• The hypothalamus releases thyrotropin-releasing hormone (TRH), stimulating the anterior pituitary to secrete thyroid-stimulating hormone (TSH).
• TSH then stimulates the thyroid gland to produce T3 and T4 hormones.
• Increased levels of T3/T4 lead to a compensatory decrease in TSH production, maintaining hormonal balance.

Thyrotoxicosis leads to several physiological changes:

• Generalized hypermetabolism: Increased substrate consumption and energy expenditure.
• Increased Na+/K+-ATPase: Elevation of basal metabolism and promotion of thermogenesis.
• Upregulation of β-adrenergic receptors: Hyperstimulation of the sympathetic nervous system.
• Cardiac effects:
  • Increased cardiac output due to enhanced myocardial contractility.
  • Decreased peripheral vascular resistance, leading to improved blood flow.

Common skin manifestations include:

• Infiltrative dermopathy (pretibial myxedema)
• Onycholysis (thickened nails with distal white discoloration and separation of the nail plate)
• Thyroid acropachy (nail clubbing in late stages of Graves disease)

Cardiovascular symptoms include:

• Tachycardia
• Palpitations and irregular pulse (due to atrial fibrillation/ectopic beats)
• Hypertension with widened pulse pressure
• Thyrotoxicosis-induced cardiac failure in elderly patients, presenting with pedal edema and exertional dyspnea

Gastrointestinal symptoms include:

• Weight loss despite increased appetite
• Frequent bowel movements due to intestinal hypermotility

Ocular manifestations include:

• Lid lag due to adrenergic overactivity
• Lid retraction, giving a 'staring look'
• Graves ophthalmopathy (exophthalmos and edema of the periorbital tissue)

Musculoskeletal symptoms include:

• Fine tremor of the outstretched fingers
• Hyperthyroid myopathy, characterized by muscle weakness, pain, and atrophy, predominantly affecting proximal muscles (e.g., hip flexors, quadriceps)

T3 has a direct effect on osteoclastic bone resorption, which can lead to osteoporosis and an increased risk of fractures, particularly in the elderly.

Common reproductive symptoms in females include oligomenorrhea, amenorrhea, anovulatory infertility, and dysfunctional uterine bleeding.

In males, hyperthyroidism can lead to gynecomastia, decreased libido, infertility, and erectile dysfunction.

Hyperthyroidism is associated with glucose intolerance, which includes impaired insulin secretion and decreased insulin sensitivity of peripheral tissues.

Neuropsychiatric symptoms of hyperthyroidism can include anxiety, emotional instability, depression, restlessness, insomnia, tremulousness, and hyperreflexia.

Exogenous thyrotoxicosis is caused by excessive intake of thyroid hormone, which can be intentional or unintentional.

Intentional causes include:

• Therapeutic: suppressive doses for thyroid cancer treatment
• Related to psychiatric illness (e.g., eating disorders, body dysmorphia, factitious disorders)
• Attempting weight loss

Unintentional causes include:

• Iatrogenic
• Accidental ingestion (primarily in children)
• Dietary supplements

The clinical features of exogenous thyrotoxicosis include:

• Symptoms of thyrotoxicosis
• Goiter is absent.

The diagnostic criteria for exogenous thyrotoxicosis include:

• Low/undetectable TSH
• High levels of T4 and/or T3; T3:T4 ratio < 20 ng/mcg
• Low Tg levels
• Low RAI uptake on scintigraphy

The treatment approach for exogenous thyrotoxicosis includes:

1. Taper and stop the exogenous thyroid hormone.
2. Consider symptomatic therapy for thyrotoxicosis with beta blockers if symptoms are severe.

• Clinical assessment
• Screen thyroid function tests (TFTs)
• Routine laboratory studies

Consider alternate diagnoses if TFTs are normal.

Thyroid scintigraphy is the first-line imaging technique for most patients with uncertain diagnoses, such as suspected thyroid adenoma or toxic multinodular goiter (MNG).

If characteristic features of Graves disease are present, investigations can be stopped and management of Graves disease can begin.

TSH receptor antibody (TRAb) is used for suspected Graves disease without characteristic features.

Consider serum thyroglobulin to identify exogenous thyrotoxicosis.

Refer for fine-needle aspiration cytology (FNAC) if suspicious nodules are visible on imaging.

Typically low or undetectable (↓).

Free T4 and Total T3 levels are both normal.

It is indicated if Graves disease is suspected but classic clinical features are absent.

A nuclear medicine thyroid scan visualizes the distribution of thyroid function using a radiotracer, helping to assess thyroid conditions.

The RAIU test quantifies the percentage of the administered amount of radioactive iodine taken up by the thyroid gland.

Indications include:

1. First-line test for uncertain etiology of thyrotoxicosis
2. Assessment of functional status of thyroid nodules
3. Thyroid malignancy
4. Identification of ectopic thyroid tissue
5. Evaluation of retrosternal goiters
6. Evaluation of thyroglossal cysts

In Graves disease, the thyroid gland appears diffusely enlarged with increased activity.

A 'hot nodule' indicates hyperfunctioning tissue that takes up large amounts of radioactive iodine, suggesting increased thyroid activity.

A 'cold nodule' indicates non-functioning nodules that do not take up radioactive iodine, while surrounding normal tissue appears 'warm'.

The contraindications include pregnant or breastfeeding women.

Common adverse effects of thionamides include:

• Allergy/hypersensitivity: Pruritic rash (especially with methimazole).
• Hematologic side effects:
  • Agranulocytosis (affects ~0.5% of patients, more common in elderly and high doses).
  • Aplastic anemia.
  • Thrombocytopenia.
• Hepatotoxicity: Seen with propylthiouracil use, including hepatitis, cholestatic jaundice, and liver failure.
• Teratogenicity: Increased risk of congenital malformations with carbimazole and methimazole.
• Other effects: Diffuse goiter and impaired sense of taste (dysgeusia).

During the first trimester of pregnancy, propylthiouracil is recommended due to the teratogenic effects of methimazole and carbimazole. After the first trimester, it is advised to switch back to carbimazole or methimazole because of the hepatotoxic effects associated with propylthiouracil.

Serum thyroglobulin (Tg) is indicated for suspected exogenous hyperthyroidism with unclear history, and its levels can indicate whether hyperthyroidism is exogenous (↓ Tg) or endogenous (normal or ↑ Tg).

Differential diagnoses for thyrotoxicosis symptoms include:

1. Neuropsychiatric symptoms: anxiety/panic disorders
2. Hyperadrenergic symptoms: intoxication with anticholinergics; cocaine/amphetamine misuse; withdrawal syndromes
3. Weight loss: diabetes mellitus, malignancy
4. Cardiac symptoms: congestive cardiac failure

Immediate treatment of thyroid storm should be started if present, including screening with BWPS.

The first-line treatment for hyperadrenergic symptoms is beta blockers, such as propranolol.

Effective management options for Graves disease include antithyroid drugs, radioactive iodine ablation (RAIA), and thyroid surgery.

The preferred definitive therapy for toxic MNG and toxic adenoma is radioactive iodine ablation (RAIA) or thyroid surgery, rather than antithyroid drugs.

For asymptomatic younger adults without risk factors, either observation or treatment should be considered.

Beta blockers are used to provide immediate control of hyperadrenergic symptoms and decrease the risk of cardiac complications in thyrotoxicosis.

Amiodarone should be avoided in the treatment of atrial fibrillation in patients with thyrotoxicosis.

20–75% of patients with Graves disease may achieve permanent remission after 1–2 years of antithyroid drug treatment.

Initial management of thyroid storm includes:

1. Beta-blockers to control symptoms.
2. Antithyroid medications such as methimazole or propylthiouracil.
3. Supportive care including hydration and cooling measures.
4. Prevention in at-risk patients involves optimizing thyroid function prior to surgery or radioactive iodine ablation (RAIA).

The choice of medication for hyperthyroidism depends on:

• Severity of symptoms: More severe symptoms may require more aggressive treatment.
• Patient factors: Considerations include age, pregnancy status, and comorbidities.
• Specific medications: Methimazole is typically used for most patients, while propylthiouracil is preferred during thyroid storm or in the first trimester of pregnancy.

The typical duration of therapy for primary treatment of Graves disease is 12–18 months. This duration may vary based on individual patient response and clinical judgment.

Monitoring for patients on antithyroid drugs includes:

1. Complete Blood Count (CBC) and liver chemistries: Obtain baseline prior to therapy and repeat if febrile illness or symptoms of liver injury occur.
2. Thyroid Function Tests (TFTs): Measure free T4 and T3 levels 2–6 weeks after initiation of therapy and adjust dosage accordingly.

Contraindications for the use of antithyroid drugs include:

• Destructive thyroiditis: ATDs are ineffective in managing thyrotoxicosis caused by this condition.
• Hyperthyroidism in pregnancy: Special considerations may apply.
• Limited life expectancy and patient preference may also influence treatment decisions.

RAIA is the destruction of thyroid tissue via radioactive iodine (iodine-131) through a sodium/iodine symporter.

Indications for RAIA include:

• Toxic multinodular goiter (MNG) and toxic adenoma with high nodular radioactive iodine uptake
• Failure to achieve euthyroidism with antithyroid drugs in Graves disease due to refractory disease, contraindications to ATDs, major adverse reactions to ATDs, high surgical risk, limited life-expectancy, thyrotoxic periodic paralysis, post-surgical treatment of certain thyroid cancers, and large/compressive nontoxic goiters.

Contraindications for RAIA include:

• Pregnant or breastfeeding women
• Children under 5 years of age
• Initial treatment for confirmed or suspected thyroid malignancy
• Moderate to severe Graves ophthalmopathy
• Inability to follow radiation safety regulations.

Preparations for RAIA include:

1. Prophylactic treatment to reduce complications in high-risk patients.
2. Consider beta blockers even in asymptomatic patients.
3. Administer methimazole to achieve a euthyroid state, discontinued 2-3 days before RAIA.
4. Avoid excess iodine for 7 days prior to RAIA.
5. Confirm a negative pregnancy test in women of childbearing potential within 48 hours before RAIA.

Early complications of RAIA include:

• Most patients with Graves disease becoming hypothyroid and requiring lifelong thyroid hormone replacement with L-thyroxine.
• Gastritis, which may present as nausea and vomiting.

Radiation-induced thyroiditis is a form of acute thyroiditis that occurs a few days after the thyroid gland is exposed to radiation. It is most commonly seen following radioiodine therapy in patients with Graves disease or after external beam radiotherapy for head and neck cancers.

Patients with radiation-induced thyroiditis typically present with:

• Pain in the thyroid region
• Thyrotoxicosis due to the release of T3 and T4 following rapid destruction of thyroid tissue

Indications for thyroid surgery include:

1. Large goiters (≥ 80 g) or obstructive symptoms
2. Confirmed or suspected thyroid malignancy
3. Graves disease with:
   • Concomitant primary hyperparathyroidism or periodic paralysis
   • Moderate to severe active Graves ophthalmopathy
4. Toxic multinodular goiter (MNG) or toxic adenoma with:
   • Concomitant primary hyperparathyroidism
   • Insufficient radioiodine ablation (RAIA)
   • Retrosternal extension
5. Other factors such as large thyroid nodules, refractory amiodarone-induced thyrotoxicosis, planned pregnancy within the next 6 months, or patient preference.

Contraindications for thyroid surgery include:

1. Severe comorbidities that influence surgical risk
2. Pregnancy

Preparation for thyroid surgery includes:

• Achieving euthyroidism prior to surgery by using antithyroid drugs (and beta blockers if necessary) for at least 4-8 weeks if possible.

Potassium iodide solution should be administered for 10 days preoperatively to harness the Wolff-Chaikoff effect.

Assess for hypocalcemia and replete calcium dosage and 25-hydroxy vitamin D as needed.

Consider adding corticosteroids and cholestyramine in consultation with a specialist.

The recommended surgical procedure is near-total or total thyroidectomy.

Measure serum calcium and PTH levels at 6 and 12 hours post-operatively and start calcium and calcitriol.

Ongoing management is usually provided by endocrinology and/or surgery, with thyroid function measured at set intervals depending on the treatment given.

Management of hyperthyroidism differs slightly in select patient groups, such as individuals who are pregnant or planning pregnancy, and newborns.

Thyroid storm is an acute exacerbation of hyperthyroidism that results in a life-threatening hypermetabolic state, also known as thyrotoxic crisis.

• Hyperpyrexia with profuse sweating
• Tachycardia (> 140/minute) and possibly severe arrhythmia (e.g., atrial fibrillation)
• Hypertension with wide pulse pressure, congestive cardiac failure
• Hypotension/shock secondary to high output heart failure or hypovolemia
• Symptoms of thyrotoxicosis
• Abdominal pain, severe nausea, vomiting, diarrhea, possibly jaundice
• Severe agitation, anxiety, delirium, psychoses, seizures, coma

A thyroid storm is diagnosed based on:

• Classic clinical features
• Supporting thyroid function test (TFT) abnormalities:
  • Low/undetectable TSH
  • Elevated free T3/T4

Further tests may include:

• ECG to assess for atrial fibrillation
• Liver chemistries to check for jaundice

The Burch-Wartofsky Point Scale (BWPS) can be used to assess disease severity and guide treatment.

A temperature of ≥ 40°C (≥ 104°F) indicates a thyroid storm.

A heart rate of ≥ 140 beats per minute is associated with severe tachycardia in the context of thyroid storm.

The presence of atrial fibrillation is scored as 10 points in the assessment of thyroid storm.

A score of 25–44 points indicates an impending thyroid storm.

A score of 20 corresponds to severe gastrointestinal-hepatic dysfunction symptoms such as jaundice.

1. Consult critical care for ICU admission and monitoring.

2. Start symptomatic treatment to manage hypotension, hyperpyrexia, and tachycardia.

3. Administer medication to reduce thyroid hormone synthesis and release, and inhibit their peripheral action.

4. Identify and treat any precipitating cause.

5. Once stable, initiate definitive therapy for hyperthyroidism and thyrotoxicosis.

6. Consider plasmapheresis or emergency surgery for rare refractory cases.

• Beta blockers are first-line for hyperadrenergic symptoms.
• Preferred: Propranolol due to combined beta-blockade and antithyroid effects.
• Alternatives:
  • Esmolol for patients with preexisting heart failure.
  • Atenolol or Metoprolol for mild obstructive airway disease/stable asthma.
• If beta blockers are contraindicated, consider CCBs like Diltiazem.

• External cooling techniques: Ice packs, cooling blankets, alcohol washes.
• Antipyretics: IV acetaminophen is recommended.
• Avoid aspirin.

• Fluid resuscitation to treat insensible and gastrointestinal losses.
• Preferred fluids: 5-10% dextrose to meet high metabolic demand.
• Fluid requirement: Often high, around 3-5 L/day.

• Benzodiazepines, such as Lorazepam, are recommended for agitation.

Propylthiouracil (PTU) is the first-line antithyroid drug used in the treatment of thyroid storm.

The acute management checklist for thyroid storm includes:

1. Conduct ABCDE survey and initial laboratory studies (e.g., TFTs, BMP, liver chemistries).
2. Begin IV fluid resuscitation.
3. Identify and treat tachyarrhythmias or acute heart failure.
4. Treat hyperadrenergic symptoms with beta blockers (first-line: propranolol).
5. Treat hyperthermia with external cooling and acetaminophen.

Iodine solutions are used to inhibit thyroid hormone release through the Wolff-Chaikoff effect. They should be given at least 1 hour after administering antithyroid drugs. Potassium iodide and Lugol solution are examples of iodine solutions used in this context.

Beta blockers, specifically propranolol, are used to treat hyperadrenergic symptoms in thyroid storm.

Consider BWPS (Burch-Wartofsky Point Scale) if there is uncertainty in the diagnosis or for assessing severity and need for aggressive therapy.

Benzodiazepines are administered as needed to manage agitation associated with hyperthyroidism and thyrotoxicosis.

Plasmapheresis should be considered for life-threatening refractory cases of hyperthyroidism and thyrotoxicosis.

Electrolyte repletion is important to correct any electrolyte imbalances that may occur due to the condition or its treatment, ensuring better overall patient stability.

After stabilization, it is essential to ensure definitive therapy for hyperthyroidism and thyrotoxicosis to prevent recurrence and manage the underlying condition effectively.

Graves disease (GD) is an autoimmune condition where TSH receptor autoantibodies stimulate the thyroid gland, leading to increased thyroid hormone production. It is the most common cause of hyperthyroidism.

Clinical features of Graves disease include:

• Symptoms of hyperthyroidism
• Diffuse goiter
• Graves ophthalmopathy
• Thyroid dermatopathy (e.g., pretibial myxedema) Presentation may vary with patient age.

Diagnosis of Graves disease is confirmed through:

• Clinical presentation
• Thyrotoxicosis on thyroid function testing
• In cases of diagnostic uncertainty, elevated TSH receptor antibody (TRAb) levels or characteristic findings on thyroid imaging can confirm the diagnosis.

Treatment options for Graves disease include:

1. Symptomatic therapy for thyrotoxicosis (e.g., beta blockers)
2. Antithyroid drugs for GD
3. Radioactive iodine ablation (RAIA)
4. Thyroid surgery Treatment choice depends on factors such as patient characteristics (age, pregnancy, preference) and clinical presentation (size of goiter, TRAb levels).

Graves disease is the most common cause of hyperthyroidism in the United States with an incidence of approximately 30 cases per 100,000 people per year. It predominantly affects females with a ratio of about 10:1 and typically occurs in individuals aged 20-50 years.

Genetic predisposition plays a role in Graves disease, with about 50% of individuals having a family history of autoimmune disorders such as:

• Type 1 diabetes mellitus
• Hashimoto disease
• Pernicious anemia
• Myasthenia gravis

HLA-DR3 and HLA-B8 alleles are associated with the autoimmune disorder.

Triggers include:

1. Infectious agents (e.g., Yersinia enterocolitica, Borrelia burgdorferi)
2. Stress (physical and psychological)
3. Pregnancy
4. Environmental factors (smoke, irradiation, drugs, endocrine disruptors)

The general mechanism involves:

1. B and T cell-mediated autoimmunity
2. Production of stimulating immunoglobulin G (IgG) against TSH-receptor (TRAb)
3. Increased thyroid function and growth
4. Resulting in hyperthyroidism and diffuse goiter

Clinical features include:

1. Symptoms of hyperthyroidism
2. Diffuse goiter (smooth, uniformly enlarged)
3. Bruit at the thyroid gland poles
4. Pemberton sign
5. Ophthalmopathy (Graves ophthalmopathy)
6. Exophthalmos
7. Ocular motility disturbances

Thyroid-associated ophthalmopathy involves:

1. Activated B and T cells infiltrating the retro-orbital space
2. Targeting orbital fibroblasts leading to cytokine release (e.g., TNF-α, IFN-γ)
3. Local inflammatory response causing fibroblast proliferation and differentiation to adipocytes
4. Increased volume of intraorbital fat and muscle tissues, resulting in exophthalmos and ocular motility disturbances.

Common skin manifestations include:

1. Pretibial myxedema: Bilateral pretibial nonpitting edema and skin thickening.
2. Plaques and/or nodules: May be observed on the skin.
3. Patchy vitiligo: Loss of skin pigmentation.
4. Thyroid acropachy: Rare condition characterized by clubbing of fingers and toes.

These conditions typically occur in patients with Graves ophthalmopathy.

Pretibial myxedema is a rare manifestation of Graves disease that presents as:

• Bilateral pretibial nonpitting edema
• Skin thickening in the pretibial area
• Possible plaques and/or nodules
• May also occur in other skin areas, especially after trauma.

A severe condition that can occur in patients with Graves disease is thyroid storm, which is a life-threatening exacerbation of hyperthyroidism characterized by:

• High fever
• Rapid heart rate
• Severe agitation
• Confusion or delirium
• Potentially leading to multi-organ failure if not treated promptly.

Graves ophthalmopathy, also known as thyroid-associated orbitopathy (TAO), is an autoimmune condition that is generally associated with Graves disease. It is characterized by inflammation and swelling of the eye muscles and surrounding tissues.

Graves ophthalmopathy is primarily caused by an autoimmune antibody reaction. It can be associated with various thyroid states including:

1. Hyperthyroidism (most common)
2. Euthyroidism
3. Hypothyroidism (such as Hashimoto's thyroiditis)
4. Other autoimmune disorders
5. Thyroid cancer
6. Neck irradiation

Localized myxedema in Graves dermopathy is characterized by swelling and discoloration of the skin, particularly in the hands. It is a manifestation of the underlying autoimmune process associated with Graves disease.

Common risk factors include:

• Family history of Graves disease
• Tobacco smoking
• Age: More common in older adults

The pathophysiology involves:

1. Presence of TSH autoantibodies in the orbital cavity.
2. Binding to TSH receptor antigen on cells, leading to an autoimmune reaction.
3. Lymphocytic infiltration into orbital tissues causing inflammation.
4. Release of cytokines from CD4+ T cells stimulating fibroblasts.
5. Fibroblasts secrete glycosaminoglycans (hyaluronic acid), pulling water into the interstitial space, causing expansion of retro-orbital tissue due to increased fluid, lymphocytic infiltration, and adipogenesis.

Clinical features include:

• Exophthalmos (unilateral or bilateral, often asymmetric)
• Ocular motility disturbances
• Binocular diplopia
• Poor convergence (Moebius sign)
• Restriction of extraocular muscles (Ballet sign)
• Lid retraction (thyroid stare)
• Dalrymple sign: retraction of the upper eyelid with visible sclera
• Von Graefe sign: lagging of the upper eyelid on downgaze
• Stellwag sign: infrequent and incomplete blinking
• Vigouroux sign: eyelid fullness
• Lagophthalmos leading to keratitis
• Joffroy sign: absent forehead creases during superior gaze
• Conjunctival injection and chemosis
• Ocular discomfort (pain or pressure)
• Photopsia on upward gaze
• Possible features of hyperthyroidism or hypothyroidism.

Laboratory findings indicative of hyperthyroidism include:

• Decreased TSH
• Increased free T3/T4
• Increased TSH receptor antibodies (specific and sensitive to Graves disease)

Imaging techniques used include:

• CT scan: Confirmatory test showing exophthalmos, increased fat density, inflammation, and enlargement of extraocular muscles.
• MRI: Alternative to CT, showing similar findings and potential compression of the optic nerve.

Pseudoproptosis refers to the appearance of protrusion or bulging of the eye(s) that is not due to anterior displacement of the eye. It differs from true proptosis, which involves actual displacement of the eye forward due to conditions such as thyroid eye disease or tumors.

Conservative management strategies for mild thyroid eye disease include:

1. Eye protection (e.g., artificial tears, sunglasses)
2. Sleeping with the head of the bed elevated
3. Treating hyperthyroidism, if present
4. Smoking cessation
5. Selenium supplementation, if deficient

Treatment options for moderate to severe thyroid eye disease include:

1. High-dose IV steroids
2. Orbital decompression surgery (following steroid administration)
3. Strabismus correction
4. Lid-lengthening surgery
5. Blepharoplasty
6. For refractory cases: teprotumumab, rituximab, cyclosporine, octreotide, intravenous immunoglobulin, and tarsorrhaphy

The goals of therapy for thyroid eye disease include:

• Treatment of hyperthyroidism
• Smoking cessation
• Eye protection
• Decreasing inflammation

1. Obtain thyroid function tests.
2. Confirm hyperthyroidism and assess for clinical features of Graves disease (GD) to determine if diagnostic criteria have been met.
3. If criteria are not met, order confirmatory studies for GD.
4. Consider additional studies based on clinical findings, such as:
   • Thyroid nodules: Initiate workup for thyroid nodules.
   • Graves ophthalmopathy: Conduct a comprehensive eye examination with imaging consideration.
5. Stabilize individuals with life-threatening conditions before diagnostic testing.

GD can be diagnosed without further testing if the patient meets all of the following criteria:

1. Overt hyperthyroidism.
2. TSH: Decreased or undetectable.
3. Free T4 and total T3: Increased.
4. New onset of features of Graves ophthalmopathy.
5. Symmetric enlargement of the thyroid gland (goiter).

Options for confirmatory studies for GD include:

• TSH receptor antibodies (TRAbs).
• Thyroid imaging studies.
  The choice of test depends on availability, cost, and treatment preference.

Elevated levels of stimulating TSH receptor antibodies (TRAbs) are specific to Graves disease (GD). However, TRAbs can be negative in very mild cases of GD.

Indications for a nuclear medicine thyroid scan include:

1. Nonpregnant adults with thyrotoxicosis of unknown cause.
2. Evaluation of diffuse thyroid enlargement and radioactive iodine uptake.

Typical findings in a nuclear medicine thyroid scan for Graves disease include:

• Diffuse thyroid enlargement.
• Diffuse uptake of radioactive iodine (123I).

Thyroid ultrasound with color Doppler is the preferred imaging modality for pregnant or lactating individuals with thyrotoxicosis of unknown cause.

Radioactive iodine uptake scans are contraindicated during pregnancy and lactation.

On ultrasound, the thyroid gland in Graves disease typically shows:

• Enlarged, hypervascular, hypoechoic thyroid gland.
• Increased vascularity indicated by color Doppler imaging.

The macroscopic features include:

• Diffuse, uniform gland enlargement
• Beefy red appearance on cut surfaces

The microscopic features include:

• Diffuse hyperplasia of thyroid follicles
• Tall, hyperplastic and hypertrophic follicular cells
• Colloid reabsorption with peripheral scalloping
• Irregular stromal lymphocytic infiltration

A Color Doppler ultrasound in Graves disease shows:

• Enlarged thyroid gland
• Increased blood flow, indicating hypervascularity

• Initiate symptomatic therapy for thyrotoxicosis, including treatment for thyroid storm if necessary.
• Refer all patients to endocrinology for treatment of Graves disease (GD).
• Consider further referrals based on clinical features, such as:
  • Graves ophthalmopathy: refer to ophthalmology.
  • Significant cardiac features: refer to cardiology.
• Provide ongoing management for GD.

Indications for antithyroid drugs (ATDs) include:

• Individuals with a high likelihood of remission:
  • Mild disease
  • Small goiter
  • Low TRAb titers
• Pregnant individuals
• Poor surgical candidates
• Individuals with moderate to severe Graves ophthalmopathy
• As an adjunctive treatment to achieve euthyroidism before and/or after radioactive iodine ablation (RAIA) or thyroid surgery.

Patients with Graves ophthalmopathy should be immediately referred to ophthalmology if they exhibit:

• Orbital pain
• Impaired vision or diplopia
• Impaired eye movement
• Afferent pupillary defect

Definitive treatment options for Graves disease include:

• Radioactive iodine ablation
• Thyroid surgery

Shared decision-making should be used to determine the most appropriate choice for the patient.

The preferred thionides for treating hyperthyroidism are methimazole (MMI) and carbimazole (not available in the US).

The recommended treatment for pregnant patients with hyperthyroidism is propylthiouracil.

If ATD therapy is unsuccessful, radioactive iodine ablation (RAIA) or thyroid surgery may be required.

The potential complications of antithyroid drug therapy include agranulocytosis and hepatotoxicity. A CBC should be obtained in patients with fever and/or pharyngitis, and liver chemistries should be obtained in patients with symptoms of liver failure.

Indications for RAIA include:

1. Desire for definitive treatment and either wishes to avoid or is at increased risk from surgery.
2. Planned pregnancy in > 6 months.
3. Presence of conditions such as thyrotoxic periodic paralysis, pulmonary hypertension, or heart failure.
4. Contraindications to antithyroid drugs (ATDs).

Contraindications for RAIA include:

1. Pregnant and/or lactating patients.
2. Patients unable to follow radiation safety regulations.
3. Patients with confirmed or suspected thyroid cancer.
4. Other treatment modalities are preferred in patients with Graves ophthalmopathy or age < 5 years.

Prior to the RAIA procedure, it can transiently worsen symptoms, so consider prophylactic use of ATDs for Graves disease and symptomatic therapy for thyrotoxicosis for patients at increased risk. After the procedure, iatrogenic hypothyroidism can occur, requiring lifelong levothyroxine replacement.

RAIA is contraindicated during pregnancy. It is important to test for pregnancy no more than 48 hours prior to RAIA in all patients of reproductive age.

Indications for thyroid surgery include:

1. Desire for definitive treatment when radioiodine therapy is unlikely to be successful (low uptake on RAIU testing).
2. Anticipated pregnancy within 6 months.
3. Presence of specific conditions such as:
   • Suspected thyroid cancer
   • Hyperparathyroidism or thyrotoxic periodic paralysis
   • Moderate to severe Graves ophthalmopathy
   • Large and/or symptomatic goiter

Options for surgery include near-total thyroidectomy or total thyroidectomy.

Complications of thyroid surgery can be serious and may include:

• Iatrogenic hypothyroidism, requiring lifelong thyroid hormone replacement.
• Permanent hypoparathyroidism may develop.

To reduce the risk of complications:

• An experienced thyroid surgeon is highly recommended.
• Optimize medical management as part of preparation for surgery.
• Follow postprocedural care guidelines.

Ongoing management strategies for patients with Graves disease include:

• Encouraging smoking cessation.
• Regular follow-up with endocrinology, surgery, and ophthalmology as indicated.
• For patients on antithyroid drugs (ATDs), medication may be stopped after 12–18 months if TSH and TRAb levels are normal.
• Discuss options for patients wishing to conceive, particularly in relation to Graves disease management during pregnancy.

• Optimize management of Graves disease before conception.
• Advise avoiding pregnancy until:
  • TFTs have been in the normal range for at least 1 month.
  • At least 6 months have passed after receiving RAIA (if performed).
• Discuss management options for patients taking ATDs for Graves disease, such as:
  • Definitive treatment for hyperthyroidism before conception.
  • Switching from methimazole to propylthiouracil before conception or as soon as pregnancy is confirmed.
  • An ATD discontinuation trial as soon as pregnancy is confirmed.

Hyperthyroidism occurs in less than 1% of pregnancies, with approximately 95% of cases caused by Graves disease.

The clinical features of Graves disease are similar between pregnant and nonpregnant adults. However, some symptoms of hyperthyroidism, such as heat intolerance, palpitations, and mild thyroid enlargement, may overlap with symptoms of pregnancy, potentially delaying recognition of hyperthyroidism.

Diagnosis of hyperthyroidism in pregnancy relies on interpreting elevated thyroid hormones using trimester-specific reference ranges. TSH reference ranges are lower during pregnancy.

Total T4 and total T3 reference ranges are higher during pregnancy.

In pregnancy, all patients with suspected or confirmed GD should have a TRAb measurement. The imaging study of choice is thyroid ultrasound. In cases of diagnostic uncertainty, serum hCG should be measured to differentiate GD from hCG-mediated hyperthyroidism.

The treatment goals for managing GD in pregnancy are to keep the free T4 level at or just above the upper limit of normal using the lowest possible dose of antithyroid drugs (ATDs).

For symptomatic patients with Graves disease during pregnancy, consider a low-dose beta-blocker (such as propranolol or metoprolol) for 2-6 weeks. Antithyroid drugs (ATDs) are preferred for treatment.

The differential diagnoses of hyperthyroidism in pregnancy include:

1. Graves disease
2. hCG-mediated hyperthyroidism (rare)
3. Toxic adenoma

Fetal Complications:

• Death: spontaneous abortion, stillbirth
• Poor growth: IUGR, small for gestational age, low birth weight
• Prematurity
• Congenital conditions: malformations, thyroid disease

Maternal Complications:

• Hypertension
• Premature labor
• Heart failure
• Thyroid storm

Neonatal hyperthyroidism occurs in approximately 5% of babies born to mothers with Graves disease (GD).

Clinical Features of Neonatal Hyperthyroidism:

• Hyperthyroidism: irritability, restlessness, tachycardia, diaphoresis, hyperphagia, poor weight gain
• Diffuse goiter (can cause tracheal compression)
• Microcephaly (due to craniosynostosis)
• May present directly after birth or be delayed for up to 10 days due to transplacental antithyroid medication.

Screening for Neonatal Hyperthyroidism: Maternal TRAbs (thyroid receptor antibodies) should be performed for all women with a history of Graves disease to assess the risk of neonatal hyperthyroidism.

All infants born to women with positive or unknown TRAbs should be screened. Cord blood should be measured at delivery for TRAbs; if negative, no further screening is required. Additionally, TSH and free T4 should be measured at day 3-5 and again at day 10-14, with clinical follow-up until 2-3 months of age.

Infants with symptomatic hyperthyroidism are usually treated with methimazole and propranolol. This condition typically resolves within 1-3 months.

Untreated symptomatic hyperthyroidism in infants can lead to cardiac failure and intellectual disability.

The classic clinical features of Graves disease (GD) in children are often less marked or variable compared to adults. Common features include:

• Goiter that can vary in size
• Milder Graves ophthalmopathy
• Rare dermopathy
• Additional symptoms such as behavioral problems, poor performance in school, emotional instability, and growth spurts with advanced bone age.

The initial confirmatory test for diagnosing Graves disease (GD) in children is TRAb titers. If TRAb titers are normal, a thyroid ultrasound may be performed.

TRAb titers and thyroid ultrasound are preferred for diagnosis in children with suspected GD due to the radiation exposure associated with radioactive iodine uptake (RAIU) tests.

The preferred first-line treatment for Graves disease in children is a trial of methimazole (MMI).

If there is no improvement in TFTs with methimazole, or if the medication is not tolerated, definitive treatment such as radioactive iodine ablation (RAIA) or thyroid surgery should be considered.

Patient factors, including contraindications to methimazole, low chance of remission with methimazole, and indications for thyroid surgery, determine the preferred modality of definitive treatment.

Propylthiouracil is not recommended in children and adolescents due to an increased risk of liver injury.

Clinical features of Graves disease in older adults include weight loss, shortness of breath, atrial fibrillation, and nonspecific symptoms such as depression and lethargy (apathetic hyperthyroidism).

The common diagnostic tools include:

1. ECG (Electrocardiogram)
2. Echocardiogram
3. Holter monitor
4. Myocardial perfusion imaging

The recommended management includes:

• Symptomatic therapy for thyrotoxicosis is strongly recommended.
• Manage associated cardiovascular complications, including anticoagulation for atrial fibrillation.
• ATD therapy with MMI or RAIA is generally preferred over surgery.
• Definitive therapy is recommended for individuals with cardiovascular complications due to hyperthyroidism.
• For patients undergoing RAIA, prophylactic use of ATDs for Graves disease and symptomatic therapy for thyrotoxicosis is recommended.

Typical symptoms include exophthalmos (protrusion of the eye) and diplopia (double vision).

The primary treatment for both preseptal and orbital cellulitis is the prompt initiation of antibiotics.

Preseptal cellulitis is confined to soft tissues anterior to the orbital septum, while orbital cellulitis involves soft tissues posterior to the orbital septum.

The most common etiology for orbital cellulitis is bacterial sinusitis.

The emergency treatment for orbital compartment syndrome (OCS) is immediate lateral canthotomy and cantholysis to prevent significant vision loss.

The initial treatment for a confirmed case of orbital cellulitis includes:

1. Empiric IV antibiotics: Administered to address potential systemic infections.
2. Hospital admission: Required for monitoring and management of complications.

Potential complications associated with orbital cellulitis include:

• Visual loss: Can occur due to pressure on the optic nerve.
• Orbital compartment syndrome: Increased pressure within the orbit can lead to severe consequences.
• Systemic or CNS infections: Such as brain abscesses.
• Cavernous sinus thrombosis: A serious condition that can arise from orbital infections.

For a patient with red flags of orbital cellulitis, the recommended management includes:

1. Clinical diagnosis confirmed on CT orbits and sinuses with contrast.
2. Empiric IV antibiotics: To treat potential infections.
3. Hospital admission: For close monitoring and treatment of complications.

Preseptal cellulitis is an infection confined to the orbital soft tissues anterior to the orbital septum, primarily involving the skin of the eyelid and/or the orbicularis oculi muscle. In contrast, orbital cellulitis affects the tissues behind the orbital septum, potentially impacting eye movement and vision.

Preseptal cellulitis shows inflammation in front of the orbital septum, while orbital cellulitis shows inflammation behind the septum, affecting the eye muscles and optic nerve.

Common clinical features include unilateral pain, swelling, and redness of the eyelid and periorbital tissues, along with systemic signs of infection such as fever.

Red flags for orbital cellulitis include reduced visual acuity, RAPD (relative afferent pupillary defect), diplopia, ophthalmoplegia, and/or proptosis. Further investigation is required if these symptoms are present.

Common causes include:

1. Direct inoculation (most common), e.g., scratch, insect bite, animal bite
2. Local spread from adjacent infections, e.g., sinusitis, dacryocystitis
3. Hematogenous spread from distant infections, e.g., acute otitis media, pneumonia

Preseptal cellulitis is more common in children, particularly in the age group of less than 5 years old.

Preseptal cellulitis is primarily diagnosed clinically. However, laboratory studies such as CBC and cultures, as well as imaging like CT scans of the orbits and sinuses with contrast, may be performed if there is diagnostic uncertainty.

Red flags for orbital cellulitis include findings such as soft tissue thickening anterior to the orbital septum and an inability to perform a comprehensive eye examination due to eyelid edema.

Differential diagnoses for preseptal cellulitis include orbital cellulitis, conjunctivitis, and blepharitis.

Empiric oral antibiotics are indicated for all patients. In severe cases, IV antibiotics and ophthalmology consultation may be required, especially if there is concern for orbital cellulitis.

Options include:

1. Amoxicillin/clavulanic acid
2. Cefpodoxime
3. Cefdinir
4. Moxifloxacin (off-label, adults only)

Options include:

1. Trimethoprim/sulfamethoxazole (off-label)
2. Clindamycin
3. Doxycycline (off-label, adults only)

Patients should be admitted if they are:

1. Age < 5 years
2. Toxic appearance
3. Unable to attend follow-up
4. No improvement within 24–48 hours

Potential complications include:

1. Progression to orbital cellulitis
2. Spread to CNS, such as meningitis or encephalitis (uncommon)

Orbital cellulitis is a medical emergency characterized by infection primarily involving the orbital soft tissues posterior to the orbital septum. It affects the orbital fat, extraocular muscles, and/or neurovascular tissues.

Common causes of orbital cellulitis include:

1. Local spread from adjacent infections such as:

   • Bacterial rhinosinusitis (most common)
   • Odontogenic infection
   • Preseptal cellulitis
   • Dacryocystitis

2. Direct inoculation from:

   • Orbital trauma
   • Surgery

3. Hematogenous spread from:

   • Bacteremia
   • Septic emboli

Orbital cellulitis is more common in children than adults, with the highest incidence occurring in winter.

Localized features include unilateral pain, swelling, and redness of the eyelid and periorbital tissues.

Systemic features of infection may include fever and malaise.

Red flags for orbital cellulitis include proptosis, chemosis, decreased visual acuity, ophthalmoplegia, and signs of optic neuropathy (e.g., dyschromatopsia, RAPD).

Orbital cellulitis is diagnosed clinically and confirmed with CT imaging. Laboratory studies may include CBC, inflammatory markers, and cultures (e.g., conjunctival, blood).

Imaging studies include CT of the orbits and sinuses with contrast to confirm the diagnosis and evaluate for orbital abscess or retained foreign bodies.

IVIRT (Intravenous Imaging of the Retro-orbital Tissue) is used to rule out suspected cavernous sinus thrombosis and other intracranial complications by providing detailed imaging of the orbital and sinus structures.

The initial management steps include:

1. Consult ophthalmology urgently.
2. Initiate empiric IV antibiotics, such as:
   • Vancomycin
   • Plus one of the following:
     • Ampicillin/sulbactam
     • Piperacillin/tazobactam
     • Ceftriaxone and metronidazole
3. Consider management of systemic fungal infections in at-risk patients.
4. Manage any present orbital abscess.

Supportive therapies include:

1. Nasal decongestant spray for concomitant sinusitis (e.g., oxymetazoline).
2. Ophthalmic lubricants if proptosis interferes with eye closure.
3. Systemic corticosteroids to reduce local inflammation, only with expert guidance.

Potential complications include:

• Orbital abscess: a purulent collection in the orbital compartment, usually diagnosed on CT.
• Reduced visual acuity or vision loss.
• Intracranial abscess.
• Cavernous sinus thrombosis.
• Endophthalmitis.

Urgent surgical drainage is often required to prevent intracranial extension, cavernous sinus thrombosis, and/or vision loss.

Orbital compartment syndrome (OCS) is an ophthalmic emergency where orbital compartment pressure exceeds the perfusion pressure of the optic nerve and retina, potentially causing compressive optic neuropathy. OCS can lead to irreversible loss of vision within 1-2 hours if not treated promptly.

The most common cause of orbital compartment syndrome is retrobulbar hemorrhage.

All patients should be admitted for IV antibiotics and assessment by an ophthalmologist. Consult additional specialists as needed, such as:

• Otolaryngology: for evidence of sinusitis.
• Neurosurgery: for evidence of intracranial extension or meningitis.
• Oral maxillofacial surgery: for evidence of odontogenic infection.
• Infectious diseases: for suspected fungal infection.

The common clinical features of OCS include:

1. Proptosis
2. Relative Afferent Pupillary Defect (RAPD)
3. Firm globe resistant to digital retropulsion
4. Eyelid opening resistant to digital pressure
5. Eye pain
6. Periorbital swelling
7. Reduced visual acuity (late finding)
8. Dyschromatopsia
9. Ophthalmoplegia and/or diplopia

The diagnostic methods for OCS include:

• Tonometry: Elevated intraocular pressure (IOP) is a key indicator.
  • IOP > 30 mm Hg: Urgent ophthalmology consult is indicated.
  • IOP > 40 mm Hg: Urgent lateral canthotomy and cantholysis is indicated.
• Fundoscopy: To check for papilledema, venous congestion, retinal artery pulsation, and retinal artery occlusion.
• Laboratory studies: CBC, BMP, coagulation panel.
• CT orbits: Indicated if there is diagnostic uncertainty and/or to evaluate the etiology of OCS.
• Point-of-care ocular ultrasound: May show signs of retrobulbar hemorrhage.

Note: OCS is primarily a clinical diagnosis; do not delay emergent orbital decompression for confirmatory imaging.

The recommended treatment approach for OCS includes:

• Consult ophthalmology as soon as OCS is suspected to ensure timely intervention.
• Urgent interventions may be required based on the level of intraocular pressure (IOP) and clinical findings.

Lateral canthotomy and cantholysis are emergency surgical procedures used to treat orbital compartment syndrome (OCS) by decompressing the orbit.

Indication: Clinical diagnosis of orbital compartment syndrome (OCS).
Contraindication: Open globe injury.

Supportive care includes:

• Head of the bed at 45°
• Pain management
• Antiemetics
• Cough suppressants

• Treatment within 2 hours of symptom onset: Most patients have final visual acuity > 20/40.
• Treatment after 2 hours of symptom onset: Poor visual acuity outcomes are common.

1. Obtain informed consent.
2. Perform skin preparation and create a sterile field.
3. Administer single-point local anesthesia at the lateral canthus.
4. Apply a clamp horizontally from the lateral canthus to the orbital wall for 1 minute.
5. Remove the clamp and incise the lateral canthus with blunt-tipped scissors.
6. Grasp the lower lid with the forceps and lift anteriorly, away from the globe.
7. Identify the inferior lateral canthal tendon located inferoposterior to the lateral canthal fold.

Rhabdomyosarcoma is a malignant mesenchymal tumor of primitive skeletal muscle cells (rhabdomyoblasts) that have failed to fully differentiate.

Medullary thyroid carcinoma can be associated with multiple endocrine neoplasia type 2 (MEN2), which accounts for about 25% of cases.

Common symptoms include diarrhea and facial flushing. Medullary thyroid carcinoma also produces calcitonin.

Approximately 75% of Medullary thyroid carcinoma cases are sporadic.

A characteristic feature is the presence of psammoma bodies, which are round, laminated calcifications commonly found in this type of carcinoma.

Papillary carcinoma is the most prevalent type of thyroid cancer. It features palpable lymph nodes and has the best prognosis compared to all other types of thyroid cancer.

Hurthle cell carcinoma is characterized by hypercellularity with a predominance of Hurthle cells, which are large, polygonal epithelial cells with eosinophilic granular cytoplasm due to numerous altered mitochondria.

Hurthle cells are nonspecific and can also be observed in Hashimoto thyroiditis, Graves disease, previously-irradiated thyroid glands, and in Hurthle cell adenoma.

Risk factors for hypothyroidism include:

• Genetic predisposition (family history)
• Autoimmune diseases
• Radiation exposure

Hashimoto thyroiditis is the most common cause of primary hypothyroidism in iodine-sufficient regions.

Hashimoto thyroiditis is associated with HLA-DR3 and other autoimmune diseases such as vitiligo, pernicious anemia, type 1 diabetes mellitus, and systemic lupus erythematosus.

Postpartum thyroiditis occurs within 1 year of delivery and has an incidence of approximately 1:100 women.

The incidence of subacute granulomatous thyroiditis (De Quervain) is approximately 12:100,000 per year.

Riedel thyroiditis has an incidence of approximately 1.6:100,000 per year.

Secondary hypothyroidism is caused by pituitary disorders leading to TSH deficiency, while tertiary hypothyroidism is due to hypothalamic disorders resulting in TRH deficiency.

• Autoimmune thyroiditis is associated with HLA-DR3.
• It occurs more frequently in females with a ratio of 7:1.
• It can also be a variant of subacute lymphocytic thyroiditis affecting 5% of women.
• Viral infections can damage follicular cells, with a male to female ratio of 3:1.
• Thyroid dysgenesis is the most common cause in iodine-sufficient regions, while iodine deficiency is the most common cause worldwide, with a male to female ratio of 2:1.

• The clinical course can be asymptomatic or present with transient hyperthyroidism followed by hypothyroidism.
• The classic triphasic course is:
  1. Hyperthyroid
  2. Hypothyroid
  3. Recovery
• Hashitoxicosis occurs in the early phase, where thyroid hormones are released from damaged cells, causing transient hyperthyroidism, followed by hypothyroidism in the late phase.
• Approximately 30% of patients may develop hypothyroidism, while most remain euthyroid.

• In the early stage, goiter is described as rubber-like.
• It can be diffuse and firm or nodular.
• The growth of the goiter is typically slow.

In late-stage thyroid disorders, the thyroid gland may be normal-sized or small if extensive fibrosis has occurred, resulting in a stone-hard texture.

The hypothalamic-pituitary-thyroid axis is a self-regulatory circuit involving the hypothalamus, anterior pituitary gland, and thyroid gland. In hypothyroidism:

• Primary hypothyroidism: Peripheral thyroid disorders lead to decreased T3/T4 production and compensatory increase in TSH.
• Secondary hypothyroidism: Pituitary disorders result in decreased TSH levels, leading to decreased T3/T4 levels.
• Tertiary hypothyroidism: Hypothalamic disorders cause decreased TRH levels, resulting in decreased TSH and T3/T4 levels.

Hypothyroidism leads to apathy and slowed cognition in the CNS.

Hypothyroidism causes skin dryness and alopecia (hair loss).

Hypothyroidism results in an increase in low-density lipoproteins and triglycerides in the lipid profile.

Hypothyroidism leads to bradycardia and decreased cardiac output due to decreased transcription of sarcolemmal genes, such as calcium ATPases, resulting in myopathy.

Myxedema is characterized by the accumulation of glycosaminoglycans and hyaluronic acid in the dermis, leading to nonpitting edema. Initially, the edema is pretibial but can generalize as the condition progresses.

Hypothyroidism causes hyperprolactinemia, where increased prolactin production is stimulated by TRH, leading to suppression of LH, FSH, GnRH, and testosterone, as well as stimulation of breast tissue growth.

• Fatigue and decreased physical activity
• Cold intolerance
• Decreased sweating
• Hair loss (Queen Anne sign)
• Brittle nails and cold, dry skin
• Weight gain despite poor appetite
• Constipation
• Bradycardia
• Hypothyroid myopathy, myalgia, stiffness, cramps

Woltman sign is a delayed relaxation of the deep tendon reflexes, commonly seen in patients with hypothyroidism. It may also be associated with advanced age, pregnancy, and diabetes mellitus.

• Doughy skin texture and puffy appearance
• Myxedematous heart disease (dilated cardiomyopathy, bradycardia, dyspnea)
• Hoarse voice and difficulty articulating words
• Pretibial and periorbital edema
• Myxedema coma

• Abnormal menstrual cycle (especially secondary amenorrhea or menorrhagia)
• Galactorrhea
• Decreased libido, erectile dysfunction, delayed ejaculation, and infertility in men

Older patients may not exhibit typical symptoms of hypothyroidism. Instead, they may appear to have dementia or depression.

The initial evaluation method for diagnosing hypothyroidism is thyroid function tests (TFTs), specifically measuring the TSH level.

An elevated TSH level with classic clinical features is typically diagnostic for primary hypothyroidism.

If the TSH level is abnormal, Free T4 (FT4) should be ordered for further evaluation.

Thyroid antibody testing should be considered if autoimmune thyroiditis is suspected, although it is not routinely indicated.

Imaging studies may be indicated if there is suspicion of structural pathology such as thyroid nodules, goiters, or malignancy.

Normal TSH levels generally rule out both primary hypothyroidism and hyperthyroidism, making it a decisive parameter in screening for these conditions.

TSH is the best initial screening test for primary hypothyroidism; it is also used to diagnose and monitor the condition.

FT4 is the confirmatory test for primary hypothyroidism if TSH is elevated.

Serum thyroid antibody testing can confirm suspected autoimmune thyroid disease and may include measurements of thyroid peroxidase antibodies in patients with subclinical hypothyroidism or recurring miscarriages.

Thyroglobulin antibodies (TgAb) and thyroid peroxidase antibodies (TPOAb) are detectable in the majority of patients with autoimmune hypothyroidism, while TSH receptor antibodies (TRAbs) can be found in up to 20% of cases.

• CBC: Mild anemia
• BMP: Hyponatremia (in acute hypothyroidism), hypoglycemia (rare)
• Lipid profile: Hypercholesterolemia (increased LDL), hyperlipidemia
• Creatine kinase: Increased in hypothyroid myopathy

Imaging has no role in the primary evaluation of hypothyroidism but may be indicated if structural abnormalities are present or suspected. Common imaging methods include:

• Thyroid ultrasound: Assesses thyroid vascularity, goiters, and thyroid nodules; possible findings include signs of thyroiditis.
• Nuclear medicine thyroid scan: May be indicated in the workup of thyroid nodules and goiters; in hypothyroidism, radiotracer activity is decreased.

Nonthyroidal illness syndrome (NTIS), also known as euthyroid sick syndrome (ESS), is characterized by:

• A change in thyroid hormone levels (typically decreased) occurring in severe illness or physical stress.
• Common in intensive care patients and associated with morbidity and mortality.
• Thyroid gland function typically remains normal despite altered hormone levels due to factors like cytokines affecting TSH and thyroid hormones.
• Altered deiodinase enzyme activity leads to decreased conversion of T4 to T3 and increased conversion of T4 to reverse T3 (rT3).

In NTIS, the typical diagnostic findings include:

• Decreased FT3 levels
• Normal or decreased FT4 levels
• Normal or decreased TSH levels
• Absent typical clinical features of hypothyroidism

The recommended treatment approach for NTIS includes:

1. Continued treatment of the underlying illness
2. Thyroid hormone replacement is usually not recommended.

Conditions that can mimic hypothyroidism include:

• Adrenal insufficiency
• Hypopituitarism
• Congestive heart failure (CHF)
• Other causes of pulmonary edema
• Sepsis and systemic infections
• Depression
• Major neurocognitive disorders
• Encephalopathy
• Environmental hypothermia

In both low T3 syndrome and low T3 low T4 syndrome, TSH levels are typically normal. In low T3 low T4 syndrome, FT4 levels may be low in prolonged illness, indicating a poor prognosis.

Levothyroxine, a synthetic form of T4, is the first-line choice for the treatment of hypothyroidism.

Treatment should be initiated in cases of overt hypothyroidism.

Starting dose and monitoring requirements vary depending on factors such as age and comorbidities.

Subclinical hypothyroidism should be treated in select cases, particularly if TSH is ≥ 10 mIU/L or TSH is < 10 mIU/L with positive TPOAb, cardiac risk factors, or during planned/current pregnancy.

In primary hypothyroidism, levothyroxine is gradually titrated according to serial TSH measurements, increasing the dose for ↑ TSH and decreasing for ↓ TSH.

Liothyronine, a synthetic form of T3, is part of the treatment for myxedema coma but is not recommended as monotherapy or in combination with levothyroxine for long-term treatment of hypothyroidism.

Repeat TSH measurement after 1-3 months to confirm the diagnosis of subclinical hypothyroidism.

Ensure follow-up is in place for patients with subclinical hypothyroidism if treatment is not initiated.

Check TSH levels 4-6 weeks after starting treatment or dosage change, then review TSH 4-6 months after achieving normal levels, and annually thereafter.

If TSH is above the reference range, increase the levothyroxine dose. If TSH is below the reference range, reduce the levothyroxine dosage.

Patients should increase their levothyroxine dose by two extra doses per week as soon as pregnancy is suspected, with TSH and FT4 monitored monthly during the first half of pregnancy and once around 30 weeks.

Levothyroxine should be taken 30–60 minutes before breakfast and separately from interfering drugs.

Dosing in consultation with endocrinology is recommended for infants and children, pregnant patients, patients with cardiac disease, other endocrine conditions, and those with structural thyroid pathology.

Overtreatment can lead to symptoms of thyrotoxicosis, which may include:

• Sweating
• Heat intolerance
• Tremors
• Tachycardia
• Palpitations
• Arrhythmias
• Weight loss
• Osteoporosis

In patients with hypothyroidism who are pregnant, the levothyroxine dose must be increased to meet the increased demand, as hypothyroidism adversely affects the development of the fetal nervous system.

Reasons for treatment failure may include:

1. Nonadherence to the treatment regimen.
2. Malabsorption due to gastrointestinal conditions such as gastritis or celiac disease.

Triggers for myxedema coma include:

• Infections
• Severe illness or trauma
• Certain drugs

Drugs that can reduce levothyroxine absorption include:

• PPIs (Proton Pump Inhibitors)
• Calcium salts
• Ferrous sulfate
• Bile acid sequestrants

Additionally, treatment with estrogens may necessitate a dose increase, while treatment with androgens may require a dose reduction. Glucocorticoids can interfere with thyroid hormone metabolism, potentially necessitating a dose reduction of levothyroxine.

The cardinal symptoms include:

• Impaired mental status
• Hypothermia
• Myxedema

Laboratory findings typically include:

• ↑ TSH
• ↓ T4 and T3
• Possible hypoglycemia and hyponatremia
• ↓ Cortisol in patients with concomitant adrenal insufficiency

Immediate measures include:

1. Airway management
2. Fluid resuscitation
3. Intravenous hormone substitution with levothyroxine, liothyronine, and hydrocortisone
4. Supportive treatment such as passive rewarming and ventilatory support as needed

The prognosis is poor, with mortality rates of up to 60% reported even with treatment.

In patients suspected of having myxedema coma, it is important to evaluate precipitating factors, such as:

• Screening for infectious causes
• Obtaining cardiac enzymes
• Performing an ECG to exclude myocardial infarction

The most common cause of hypothyroidism is Hashimoto thyroiditis, which is also the only known risk factor for primary thyroid lymphoma. Almost all primary thyroid lymphomas are non-Hodgkin large B-cell lymphomas.

Perform the ABCDE survey to assess the patient's condition.

Secure the airway and begin ventilatory support if there is respiratory failure.

Send blood samples for thyroid function tests, cortisol, BMP, CK, LDH, and coagulation panel.

Administer IV hydrocortisone together with or prior to thyroid hormone replacement until concomitant adrenal insufficiency is ruled out.

Begin continuous cardiac and respiratory monitoring and consider invasive BP monitoring.

Identify and treat hypoglycemia as part of the acute management.

Urgently consult endocrinology and critical care for admission to ensure appropriate management of the condition.

Admit the patient to the ICU for close monitoring and management.

• Abdominal distention
• Delayed passage of meconium
• Umbilical hernia
• Prolonged neonatal jaundice (most commonly unconjugated hyperbilirubinemia)
• Hypotonia
• Decreased activity, poor feeding, and adipsia
• Hoarse cry, macroglossia
• Hypothermia
• Failure to thrive (length affected more than weight)

Neonatal screening is vital because most children with congenital hypothyroidism do not exhibit symptoms at birth due to maternal thyroid hormone supply. Early detection through screening can prevent irreversible intellectual disabilities and allow for timely management.

The 7 P's are:

1. Pot-bellied
2. Pale
3. Puffy-faced
4. Protruding umbilicus
5. Protuberant tongue
6. Poor brain development
7. Prolonged neonatal jaundice

Cretinism is a complication of severe, untreated congenital hypothyroidism that leads to impaired development of the brain and skeleton, resulting in skeletal abnormalities (e.g., short stature, delayed fontanelle closure) and permanent intellectual disabilities.

To detect congenital hypothyroidism, as increased TSH levels indicate this condition.

Lifelong hormone replacement is necessary to manage the condition.

Normalization is vital to prevent brain damage and developmental disorders.

Hashimoto thyroiditis is the most common type of autoimmune thyroiditis and the leading cause of hypothyroidism in the United States.

Patients may initially be asymptomatic or show signs of thyrotoxicosis, progressing to hypothyroidism as the organ parenchyma is destroyed.

TPOAbs are significant in the diagnosis of thyroid disorders as they are positive in:

• 70–80% of patients with Graves disease
• ~15% of individuals without thyroid disease

This indicates that while TPOAbs are a strong marker for autoimmune thyroid disease, they can also be present in individuals without thyroid conditions, highlighting the need for comprehensive evaluation.

The differential diagnoses for Hashimoto's thyroiditis include:

1. Subacute thyroiditis (de Quervain thyroiditis)
2. Diffuse toxic goiter/Graves disease
3. Nontoxic/multinodular goiter
4. Riedel thyroiditis (Riedel struma) - characterized by inflammatory infiltration and fibrosclerotic changes of thyroid tissue.
5. Rare forms of autoimmune thyroiditis - part of the IgG4-related disease spectrum, which includes conditions like sclerosing sialadenitis, retroperitoneal fibrosis, autoimmune pancreatitis, and aortitis.
6. Goiter - typically painless, hard (stone-like), and fixed.

Symptoms include anterior neck pressure, dysphagia, hoarseness, stridor, and dyspnea.

Acute suppurative thyroiditis is an extremely rare bacterial infection of the thyroid gland characterized by an acute febrile course with tenderness. It is diagnosed using ultrasound.

Treatment includes administration of broad-spectrum antibiotics (e.g., clindamycin or amoxicillin with clavulanate). If abscess formation occurs, the abscess should be opened, and culture and antibiotic sensitivity testing of the contents should be performed.

Management typically requires lifelong oral levothyroxine replacement. The dosage may vary based on the patient's age and comorbidities, with full-dose levothyroxine for young, healthy patients and low-dose for others. In cases of subclinical hypothyroidism, low-dose levothyroxine may be considered.

Thyroidectomy may be considered in patients with obstructive symptoms or for cosmetic reasons.

• Lifelong annual TSH measurements
• Clinical assessment for lymphoma and associated autoimmune diseases
• Monitor TSH level after 4-6 weeks following levothyroxine initiation or dosage change

• Myxedema coma
• Primary thyroid lymphoma

Epidemiology: 40- to 80-fold increase in risk in patients with Hashimoto thyroiditis

Pathophysiology: Usually originating from B cells

Patients with Hashimoto thyroiditis are at increased risk of having or developing:

• Type 1 diabetes
• Systemic lupus erythematosus (SLE)
• Graves disease
• Addison disease
• Non-Hodgkin lymphoma

Approximately 95% of thyroid nodules are benign. The most common causes include colloid cysts, follicular adenomas, and Hashimoto thyroiditis.

The initial evaluation of all thyroid nodules includes a TSH assay and thyroid ultrasound.

Identification of a follicular neoplasm on FNAC necessitates further diagnostic evaluation with either molecular testing or surgical excision and histopathology because cytology cannot reliably distinguish between a follicular adenoma and a follicular carcinoma.

Treatment for thyroid nodules depends on the underlying etiology and may include:

1. Surgery (thyroidectomy) for malignant and autonomous nodules
2. Aspiration for thyroid cysts
3. Observation for small, benign nodules

• Thyroid adenomas
• Follicular adenoma (most common)
• Hürthle cell adenoma
• Toxic adenoma
• Papillary adenoma (least common)
• Thyroid cysts
• Dominant nodules of multinodular goiters
• Hashimoto thyroiditis

• Patient characteristics:

  • Male sex
  • Age: < 14 years or > 70 years
  • History of radiation to the head or neck
  • Family history of:
    • MEN2 syndrome
    • Differentiated thyroid cancer (e.g., papillary, follicular, or medullary thyroid cancer)
    • Gardner syndrome

• Symptoms:

  • Rapid growth of thyroid nodule
  • Recent onset of persistent hoarseness, dysphagia, or dyspnea

• Palpatory findings:

  • Firm or hard nodule
  • Fixed nodule
  • Cervical lymphadenopathy

A solid nodule on thyroid ultrasound or a cold nodule on thyroid scintigraphy should raise suspicion for thyroid cancer.

The initial tests for all patients with thyroid nodules include:

1. TSH levels
2. Thyroid ultrasound

Elevated TSH levels are associated with a higher risk of malignancy in thyroid nodules.

For low-risk thyroid nodules, the recommended follow-up actions are:

• Routine Follow Up
• Discharge

For patients with low TSH levels, thyroid scintigraphy is indicated.

High-risk thyroid nodules may present with:

• Solid hypoechoic nodule
• Solid hypoechoic component with at least one additional suspicious feature.

• Irregular margins
• Taller-than-wide shape
• Microcalcifications
• Rim calcifications with extruding tissue
• Extrathyroidal extension

A solid hypoechoic nodule without high-risk features is classified as having intermediate risk for malignancy.

• Isoechoic or hyperechoic solid nodule
• Cystic nodule with eccentric solid component

• Partially cystic nodule
• Spongiform nodule

Cystic nodules (anechoic) without solid component are classified as benign.

Thyroid ultrasound is indicated as an initial test for patients with palpable thyroid nodules or clinical suspicion for thyroid malignancy.

Solid, hypoechoic nodules with irregular margins, microcalcifications, taller-than-wide shape, extrathyroidal growth, and/or cervical lymphadenopathy should raise suspicion for malignancy and require further evaluation with FNAC.

Thyroid scintigraphy is indicated for thyroid nodule(s) in a patient with low TSH levels.

The contraindications for thyroid scintigraphy include pregnant and breastfeeding women.

A cold nodule (hypofunctioning nodule) indicates the need to evaluate for indications for FNAC (fine-needle aspiration cytology) of thyroid nodules with ultrasound.

A hot nodule (hyperfunctioning nodule) is rarely malignant, and FNAC is not recommended. A solitary hot nodule may indicate a toxic adenoma, while multiple hot nodules suggest a toxic multinodular goiter.

Indications for FNAC include:

1. Solid hypoechoic nodules ≥ 1 cm with/without additional sonographic signs of thyroid cancer.
2. Solid hypoechoic nodules < 1 cm if:
   • Extrathyroidal growth is present.
   • Cervical lymphadenopathy is present.
   • Symptoms suggestive of distant metastases are present.
   • Patient prefers FNAC over observation.
3. Partly cystic, isoechoic, and hyperechoic nodules ≥ 1.5 cm (low-risk pattern).
4. Spongiform or partly cystic nodules ≥ 2 cm (very low-risk pattern).

The procedure for FNAC involves:

1. Obtaining thyroid cells using a fine needle (e.g., 25-gauge).
2. Observing the collected cells under a microscope.
3. Multiple nodules may require FNAC based on their sonographic appearance.

The Bethesda system categorizes thyroid cytopathology findings. For category I (Nondiagnostic or unsatisfactory), the management steps are:

1. Repeat FNAC under ultrasound guidance.
2. Consider surgery if:
   • High risk category on ultrasound.
   • Red flags for thyroid cancer are present.
   • There is an increased size of the nodule on follow-up scan.