Thyroid Disorders

Cheatsheet Content

### Thyroid Gland Overview The thyroid gland is a butterfly-shaped endocrine gland located in the neck, anterior to the trachea. It produces hormones, primarily T3 (triiodothyronine) and T4 (thyroxine), which regulate metabolism, growth, and development. #### Anatomy and Physiology - **Location:** Anterior neck, below the larynx. - **Hormones:** - **Thyroxine (T4):** Prohormone, converted to T3 in peripheral tissues. - **Triiodothyronine (T3):** More potent, metabolically active hormone. - **Calcitonin:** Produced by parafollicular C cells, regulates calcium metabolism (less significant in thyroid disorders). - **Regulation:** Hypothalamic-Pituitary-Thyroid (HPT) axis. - **TRH (Thyrotropin-Releasing Hormone):** From hypothalamus, stimulates TSH release. - **TSH (Thyroid-Stimulating Hormone):** From anterior pituitary, stimulates thyroid to produce T3/T4. - **Negative Feedback:** High T3/T4 levels inhibit TRH and TSH release. ### Hypothyroidism A condition characterized by insufficient production of thyroid hormones. #### Causes - **Primary Hypothyroidism (most common):** - **Hashimoto's Thyroiditis:** Autoimmune destruction of thyroid gland (most common cause). - **Iodine Deficiency:** Lack of iodine, essential for hormone synthesis. - **Post-ablative:** After radioactive iodine therapy or thyroidectomy. - **Drug-induced:** Lithium, amiodarone, interferon-alpha. - **Congenital Hypothyroidism:** Thyroid dysgenesis or dyshormonogenesis. - **Secondary Hypothyroidism:** - Pituitary disease (TSH deficiency). - **Tertiary Hypothyroidism:** - Hypothalamic disease (TRH deficiency). #### Clinical Features - **General:** Fatigue, weight gain, cold intolerance, bradycardia, hyporeflexia. - **Skin & Hair:** Dry skin, coarse hair, hair loss, brittle nails. - **Neuromuscular:** Muscle weakness, cramps, carpal tunnel syndrome. - **Gastrointestinal:** Constipation. - **Reproductive:** Menstrual irregularities, infertility. - **Neuropsychiatric:** Depression, impaired memory, slowed mentation. - **Severe:** Myxedema coma (life-threatening, severe hypothermia, altered mental status). #### Investigations and Significance - **TSH (Thyroid-Stimulating Hormone):** - **Significance:** Most sensitive marker for primary hypothyroidism. - **Results:** **High TSH** (primary), Normal/Low TSH (secondary/tertiary). - **Free T4 (FT4):** - **Significance:** Measures unbound, biologically active T4. - **Results:** **Low FT4** (primary, secondary, tertiary). - **Total T4 (TT4):** - **Significance:** Measures total T4, influenced by protein binding. Less reliable than FT4. - **Results:** Low TT4. - **Free T3 (FT3):** - **Significance:** Measures unbound, biologically active T3. Often normal in mild hypothyroidism. - **Results:** Low FT3 (in severe cases). - **Thyroid Peroxidase Antibodies (TPOAb):** - **Significance:** Marker for autoimmune thyroid disease (Hashimoto's). - **Results:** **Positive** in 90-95% of Hashimoto's. - **Thyroglobulin Antibodies (TgAb):** - **Significance:** Also indicates autoimmune thyroid disease. Less specific than TPOAb. - **Results:** Positive in 60-80% of Hashimoto's. - **Complete Blood Count (CBC):** - **Significance:** May show anemia (normocytic, normochromic). - **Results:** Anemia. - **Lipid Profile:** - **Significance:** Hypothyroidism can cause dyslipidemia. - **Results:** Elevated total cholesterol, LDL-C, triglycerides. - **ECG:** - **Significance:** Bradycardia, low voltage, prolonged PR/QT intervals. - **Results:** Bradycardia, generalized low voltage. - **Imaging (Thyroid Ultrasound):** - **Significance:** Evaluate thyroid size, texture, and nodules. - **Results:** Enlarged, heterogeneous gland in Hashimoto's; atrophy in late-stage disease. ### Hyperthyroidism A condition characterized by excessive production and secretion of thyroid hormones. #### Causes - **Graves' Disease (most common):** Autoimmune disorder, antibodies stimulate TSH receptors. - **Toxic Multinodular Goiter (TMNG):** Multiple autonomous nodules producing excess hormone. - **Toxic Adenoma:** Single autonomous nodule. - **Thyroiditis:** - **Subacute Thyroiditis (De Quervain's):** Viral infection, transient hyperthyroidism followed by hypo- and euthyroidism. - **Postpartum Thyroiditis:** Autoimmune, transient. - **Silent (Painless) Thyroiditis:** Autoimmune, transient. - **Exogenous Thyroid Hormone Intake:** Over-treatment with levothyroxine. - **Iodine-induced Hyperthyroidism (Jod-Basedow phenomenon):** In susceptible individuals with pre-existing thyroid disease. - **TSH-secreting Pituitary Adenoma (rare).** #### Clinical Features - **General:** Weight loss (despite increased appetite), heat intolerance, sweating, palpitations, tremors, anxiety, irritability, hyperreflexia. - **Cardiovascular:** Tachycardia, atrial fibrillation, high output cardiac failure. - **Skin & Hair:** Warm, moist skin; fine, thin hair. - **Neuromuscular:** Muscle weakness (proximal), fine tremor. - **Gastrointestinal:** Increased bowel movements, diarrhea. - **Reproductive:** Oligomenorrhea, amenorrhea. - **Ocular (Graves' disease specific):** Exophthalmos (proptosis), diplopia, gritty sensation. - **Dermopathy (Graves' disease specific):** Pretibial myxedema (rare). - **Severe:** Thyroid storm (life-threatening, severe fever, tachycardia, delirium, coma). #### Investigations and Significance - **TSH (Thyroid-Stimulating Hormone):** - **Significance:** Most sensitive marker for primary hyperthyroidism. - **Results:** **Low/Undetectable TSH** (primary), High TSH (secondary, rare). - **Free T4 (FT4):** - **Significance:** Measures unbound, biologically active T4. - **Results:** **High FT4** (primary, secondary). - **Total T4 (TT4):** - **Significance:** Measures total T4, influenced by protein binding. Less reliable than FT4. - **Results:** High TT4. - **Free T3 (FT3):** - **Significance:** Measures unbound, biologically active T3. Can be elevated even with normal FT4 ("T3 toxicosis"). - **Results:** High FT3. - **TSH Receptor Antibodies (TRAb) / Thyroid-Stimulating Immunoglobulins (TSI):** - **Significance:** Diagnostic for Graves' disease. - **Results:** **Positive** in Graves' disease. - **Thyroid Peroxidase Antibodies (TPOAb):** - **Significance:** Can be positive in Graves' disease, but not diagnostic. - **Results:** Positive in 70-80% of Graves' disease. - **Thyroglobulin Antibodies (TgAb):** - **Significance:** Can be positive in Graves' disease. - **Results:** Positive in 30-50% of Graves' disease. - **Radioactive Iodine Uptake (RAIU) Scan:** - **Significance:** Differentiates causes of hyperthyroidism. - **Results:** - **High Uptake:** Graves' disease, toxic nodular goiter. - **Low Uptake:** Thyroiditis (hormone leak, not overproduction), exogenous hormone intake. - **Thyroid Ultrasound:** - **Significance:** Evaluate thyroid size, nodules, and blood flow. - **Results:** Diffusely enlarged gland with increased vascularity in Graves'; nodules in TMNG/toxic adenoma. - **ECG:** - **Significance:** Assess cardiac effects. - **Results:** Sinus tachycardia, atrial fibrillation, other arrhythmias. ### Thyroid Nodules and Cancer Thyroid nodules are common, but only a small percentage are malignant. #### Thyroid Nodules - **Definition:** Discrete lumps within the thyroid gland. - **Prevalence:** Palpable in 5% of adults, detected by ultrasound in 20-76%. - **Risk Factors for Malignancy:** - **History:** Radiation exposure, family history of thyroid cancer, MEN2 syndrome. - **Nodule Characteristics:** Rapid growth, firm/hard consistency, fixation to surrounding structures, vocal cord paralysis, regional lymphadenopathy. - **Ultrasound Features:** Microcalcifications, irregular margins, taller-than-wide shape, hypoechogenicity, increased internal vascularity. #### Thyroid Cancer Types 1. **Papillary Thyroid Carcinoma (PTC):** Most common (80-85%), excellent prognosis, often multifocal, spreads via lymphatics. 2. **Follicular Thyroid Carcinoma (FTC):** Second most common (10-15%), typically solitary, spreads hematogenously (to bone, lung), worse prognosis than PTC. 3. **Medullary Thyroid Carcinoma (MTC):** Rare (1-2%), arises from parafollicular C cells, secretes calcitonin, often familial (MEN2 syndrome), spreads via lymphatics and hematogenously. 4. **Anaplastic Thyroid Carcinoma (ATC):** Very rare ( ### Thyroiditis Inflammation of the thyroid gland, often causing transient thyroid dysfunction. #### Types of Thyroiditis 1. **Hashimoto's Thyroiditis (Chronic Lymphocytic Thyroiditis):** - **Cause:** Autoimmune destruction of thyroid follicles. - **Clinical Course:** Initially euthyroid, often progresses to hypothyroidism. May have transient hyperthyroidism (Hashitoxicosis). - **Key Feature:** High TPOAb and TgAb. Goiter (enlarged gland) is common. 2. **Subacute Thyroiditis (De Quervain's Thyroiditis):** - **Cause:** Viral infection (post-viral illness). - **Clinical Course:** Painful thyroid gland. Triphasic course: hyperthyroidism (due to hormone leak) -> transient hypothyroidism -> euthyroidism. - **Key Feature:** Elevated ESR/CRP, low radioiodine uptake. 3. **Silent (Painless) Thyroiditis:** - **Cause:** Autoimmune, similar to Hashimoto's but without pain or prominent goiter. - **Clinical Course:** Triphasic course: hyperthyroidism -> transient hypothyroidism -> euthyroidism. - **Key Feature:** Low radioiodine uptake. 4. **Postpartum Thyroiditis:** - **Cause:** Autoimmune, occurs within 1 year after childbirth. - **Clinical Course:** Similar to silent thyroiditis, triphasic course. - **Key Feature:** High TPOAb often present. 5. **Suppurative (Acute) Thyroiditis:** - **Cause:** Bacterial or fungal infection. - **Clinical Course:** Painful, tender, red, swollen gland; fever, chills. - **Key Feature:** Leukocytosis, abscess formation, often associated with pre-existing thyroid lesion (e.g., thyroglossal duct cyst). 6. **Riedel's Thyroiditis (Fibrous Thyroiditis):** - **Cause:** Rare, idiopathic, fibrous replacement of thyroid tissue. - **Clinical Course:** Hard, "woody" thyroid gland, often mistaken for cancer. Can cause compressive symptoms (dysphagia, dyspnea). - **Key Feature:** Associated with other fibrosclerotic conditions. #### Investigations and Significance - **TSH, FT4, FT3:** - **Significance:** To assess the current thyroid functional status. - **Results:** Varies by phase (hyper, hypo, eu). - **ESR (Erythrocyte Sedimentation Rate) and CRP (C-Reactive Protein):** - **Significance:** Inflammatory markers, particularly elevated in subacute thyroiditis. - **Results:** Markedly elevated in subacute thyroiditis. - **Thyroid Antibodies (TPOAb, TgAb):** - **Significance:** To identify autoimmune causes. - **Results:** Positive in Hashimoto's, silent, and postpartum thyroiditis. Usually negative in subacute and suppurative. - **Radioactive Iodine Uptake (RAIU) Scan:** - **Significance:** Differentiates destructive thyroiditis (low uptake) from Graves' disease (high uptake). - **Results:** **Low uptake** in subacute, silent, and postpartum thyroiditis (due to hormone leak, not overproduction). - **Thyroid Ultrasound:** - **Significance:** Evaluate gland size, echogenicity, and rule out abscess/nodules. - **Results:** Heterogeneous, hypoechoic gland in Hashimoto's. Diffuse hypoechogenicity in subacute. Abscess in suppurative. - **FNA Biopsy:** - **Significance:** Rarely needed, but can confirm diagnosis in atypical cases or rule out malignancy. Essential for Riedel's. - **Results:** Histology characteristic of each type (e.g., giant cells in subacute, fibrosis in Riedel's). - **Bacterial Culture (for Suppurative Thyroiditis):** - **Significance:** To identify the causative organism for targeted antibiotic therapy. - **Results:** Positive bacterial growth. ### Special Considerations #### Pregnancy and Thyroid Disorders - **Hypothyroidism in Pregnancy:** Requires careful monitoring and increased levothyroxine dose (often 25-50% increase). Untreated hypothyroidism can lead to adverse maternal and fetal outcomes (pre-eclampsia, preterm birth, impaired fetal neurodevelopment). - **Hyperthyroidism in Pregnancy:** Graves' disease is the most common cause. Propylthiouracil (PTU) is preferred in the first trimester, then methimazole (MMI) in the second and third trimesters. Untreated hyperthyroidism can lead to pre-eclampsia, preterm birth, and fetal hyperthyroidism. TRAb can cross the placenta and cause fetal or neonatal Graves' disease. #### Thyroid Emergencies - **Myxedema Coma:** Severe, life-threatening hypothyroidism. Characterized by hypothermia, altered mental status, bradycardia, hypoventilation, and hyponatremia. Treatment involves IV levothyroxine, glucocorticoids, and supportive care. - **Thyroid Storm:** Severe, life-threatening hyperthyroidism. Characterized by fever, severe tachycardia, arrhythmias, altered mental status, and gastrointestinal symptoms. Treatment involves anti-thyroid drugs (PTU preferred), iodine, beta-blockers, glucocorticoids, and supportive care. #### Drug Effects on Thyroid Function - **Amiodarone:** Can cause both hypothyroidism (common, due to iodine content and direct toxicity) and hyperthyroidism (Type 1: iodine-induced, Type 2: destructive thyroiditis). - **Lithium:** Can inhibit thyroid hormone release, leading to hypothyroidism. - **Interferon-alpha, Interleukin-2:** Can induce thyroiditis and thyroid dysfunction. - **Tyrosine Kinase Inhibitors:** Can cause thyroid dysfunction. - **Iodinated Contrast Media:** Can induce hyperthyroidism (Jod-Basedow) or hypothyroidism in susceptible individuals. #### Thyroid Function Tests Interpretation Summary | Condition | TSH | FT4 | FT3 (if measured) | Antibodies | RAIU Scan | |-----------------------|-----------------------|-----------------------|-----------------------|-----------------------|-----------------------| | **Primary Hypothyroid** | High | Low | Low (severe) | TPOAb/TgAb (+) in Hashimoto's | N/A | | **Subclinical Hypothyroid** | High | Normal | Normal | TPOAb/TgAb (+) in Hashimoto's | N/A | | **Primary Hyperthyroid** | Low/Undetectable | High | High | TRAb (+) in Graves' | High (Graves', TMNG) | | **Subclinical Hyperthyroid** | Low/Undetectable | Normal | Normal | TRAb (+) in Graves' | High (Graves', TMNG) | | **Thyroiditis (Hyper phase)** | Low/Undetectable | High | High | TPOAb (+) (Hashi, Silent, Postpartum) | Low | | **Secondary Hypothyroid** | Low/Normal | Low | Low | Negative | N/A | | **Euthyroid Sick Syndrome** | Variable (often low/normal) | Low (or normal) | Low | Negative | N/A |