Thyroid Charts

Calcitonin opposes PTH by lowering serum calcium, preventing bone resorption and calcium mobilization by osteoclasts.

Thyrotropin-releasing hormone (TRH).

It is part of non-thyroidal illness syndrome, which is adaptive to reduce metabolic rate.

T3 and T4 inhibit TRH secretion from the hypothalamus and TSH secretion from the pituitary.

Circadian rhythms, stress, cold exposure, somatostatin, and dopamine.

Early Graves' disease, toxic goiter/adenoma, or overtreatment of hypothyroidism with levothyroxine.

Graves Disease

20-40 years

Female (7 times more common than men)

Autoantibody mediated involving TSH receptor autoantibodies leading to thyroid hormone release.

Total Thyroidectomy (surgery)

1. Hyperthyroidism with diffuse goiter. 2. Exophthalmos (ophthalmopathy). 3. Pretibial myxedema (dermopathy).

Tall, columnar, crowded follicular epithelium with papillary infoldings and pale scalloped colloid.

Decreased TSH and increased T4 and T3 levels.

They are indicative of the autoimmune nature of the disease and help in diagnosis.

Abnormal protrusion of the eyeball with a wide, staring gaze and lid lag, which may persist or worsen despite treatment.

Corneal injury due to exposure keratitis and weakness of extraocular muscles leading to diplopia.

An autoimmune manifestation affecting the skin over the shins, presenting as scaly thickening and induration with mucin deposition.

Dietary iodine deficiency.

Indications include a 1cm indeterminate mass, a solid mass greater than 5mm, or a simple cyst greater than 1cm.

FNA cannot always distinguish between adenoma and carcinoma; capsular or vascular invasion is required for diagnosis.

A family history of first-degree relatives with thyroid cancer is a risk factor.

A 'cold' nodule does not take up dye, which may indicate a higher risk of malignancy.

Immune-mediated inflammation and fibroblast activation in retroorbital tissues, with TSH receptors expressed on orbital fibroblasts and adipocytes.

Exophthalmos (proptosis), diplopia, and eye irritation; severe cases may risk optic nerve compression.

1. Diffuse thyroid enlargement; 2. Ophthalmopathy (exophthalmos); 3. Dermopathy (pretibial myxedema).

Symmetric, non-tender goiter due to diffuse hyperplasia with increased blood flow possibly producing an audible bruit.

Irregular borders, hypervascularity, hypoechogenicity, and microcalcifications are concerning ultrasound findings.

It is most likely benign and can be followed without FNA.

Microcalcifications are more likely to be benign in the thyroid compared to breast nodules.

Follicular epithelium, hence termed follicular adenomas.

The vast majority are nonfunctional.

Local compressive symptoms such as dysphagia and airway compression.

A painless thyroid nodule, often found incidentally.

Surgical removal to exclude malignancy.

Excellent; they are benign and do not recur once excised.

Nonfunctional follicular adenomas lack invasion, despite genetic overlap.

They take up less iodine than normal thyroid and appear as 'cold nodules'.

RAS mutations and PTEN mutations.

Somatic mutations leading to constitutive activation of the TSH receptor signaling pathway.

TSHR gene mutations (most common) and GNAS (Gsa subunit) mutations (less common).

Continuous stimulation leading to autonomous growth and hormone secretion, resulting in hyperthyroidism independent of TSH.

Heat intolerance, palpitations, and weight loss.

They take up more iodine and appear as 'warm' or 'hot nodules'.

Female predominates over male.

Most are indolent with excellent survival rates.

Anaplastic thyroid carcinoma, with a prognosis of about 6 months.

Many may never have caused harm, raising concerns of overdiagnosis.

Papillary Thyroid Carcinoma

Excellent overall, with a 10-year survival rate greater than 95%.

MAP kinase (MAPK) activation.

BRAF mutations, RET/PTC or NTRK gene fusions, and RAS mutations.

Ionizing radiation, especially in childhood.

Surgery, specifically lobectomy or total thyroidectomy depending on the size and features of the tumor.

Painless neck mass, often discovered incidentally, and nonfunctional tumors that do not cause hyperthyroidism.

Rapidly enlarging neck mass, compressive symptoms like dysphagia, hoarseness, dyspnea, and distant metastases.

External beam radiation with chemotherapy is the mainstay of treatment; surgery is often palliative.

Highly anaplastic cells, pleomorphic giant cells, spindle-shaped cells, frequent mitoses, and necrosis with no evidence of thyroid differentiation.

It shares mutations with well-differentiated carcinomas (RAS, PIK3CA) and has unique aggressive mutations like TP53 loss-of-function.

Older age, rapid growth, compressive symptoms, and uniformly poor prognosis.

Adenomas are encapsulated with no capsular/vascular invasion, while carcinomas show capsular and/or vascular invasion.

A hot nodule (toxic adenoma) is usually benign.

Cold nodules have a higher risk for malignancy and require fine needle aspiration (FNA).

Papillary architecture, ground-glass nuclei, nuclear grooves, pseudo-inclusions, and psammoma bodies.

Toxic adenomas are associated with TSHR or GNAS gain of function mutations.

Nuclear features alone are diagnostic of Papillary Thyroid Carcinoma.

Solitary nodule or multiple lesions in both lobes, often with necrosis and hemorrhage in larger tumors.

Lymph node mapping is very important for preoperative evaluation.

It may arise de novo or more often from progression of papillary or follicular carcinoma.

The mean age is approximately 65 years.

It is one of the most aggressive human malignancies with near 100% mortality and an average survival of 6 months.

T3 is the biologically active form.

Pheochromocytoma.

T4 acts as a prohormone and is converted to T3 by deiodinase in peripheral tissues.

By inhibiting bone resorption by osteoclasts and promoting calcium storage in bone.

Activates T4 to T3 in all tissues, with a focus on the liver and kidney.

The gland is lobulated, asymmetrically enlarged, and can reach massive size with multiple irregular nodules and variable amounts of brown, gelatinous colloid.

Colloid-rich follicles lined by flattened, inactive epithelium, areas of follicular hyperplasia intermixed with degenerative changes, and marked heterogeneity in follicle size and activity.

Plummer Syndrome.

They produce thyroid hormone independent of TSH, resulting in Thyrotoxicosis.

Low overall risk (<5%).

Thyrotoxicosis without Graves disease features, such as lack of ophthalmopathy and dermopathy.

Weight gain, cold intolerance, bradycardia, fatigue, constipation.

Non-pitting edema of skin, most common around face and eyes.

A rare, life-threatening form of severe hypothyroidism.

Low Free T3/T4 and High TSH (compensatory).

Low Free T3/T4 and Low or inappropriately normal TSH.

Congenital vs adult-onset disease.

Hypothalamus

Free T3/T4: Low; TSH: Low or inappropriately normal

Thyroid

Free T3/T4: Normal; TSH: Mild Increase

Cretinism or Congenital Iodine Deficiency

Lymphatic invasion, especially to cervical lymph nodes.

Follicular Thyroid Carcinoma

40-60 years

Iodine deficiency

95%

PI3K/AKT activation

By blood to the lungs, bone, and liver

PAX8–PPARG fusion gene

Capsular and vascular invasion

Total Thyroidectomy

Invasion into capsule and/or vessels

Hurthle Cell Carcinoma has a slightly worse prognosis at 85%.

Total thyroidectomy and central lymph node dissection as needed.

Calcitonin.

RET proto-oncogene activation.

Isolated thyroid mass in middle-aged adults, may cause compression symptoms like dysphagia and hoarseness.

Calcitonin levels in serum are used for screening and monitoring after surgery.

Amyloid deposits in the stroma due to misfolded calcitonin.

Thyroid hormones work with growth hormone to regulate growth and metabolism.

20 times more T4 than T3 is produced.

Thyroxine-binding globulin (TBG).

Regulation of metabolic rate, growth and development, and body temperature.

Thyroxine (T4) and triiodothyronine (T3).

They produce calcitonin, which helps lower blood calcium levels.

Superior thyroid artery, inferior thyroid artery, and thyroid ima artery (not standard anatomy).

Superior and middle thyroid veins drain to the internal jugular vein; inferior thyroid veins drain to the brachiocephalic vein.

Damage to the nerve can cause hoarseness and dysphagia.

C5-T1 levels, just below the larynx.

Pyramidal lobe.

PTH is the primary regulator of calcium and phosphate homeostasis, acting on bone, kidney, and indirectly on intestines.

TRH stimulates thyrotrophs in the anterior pituitary to secrete TSH.

T4 (thyroxine) and T3 (triiodothyronine).

T3 and T4 inhibit the release of TSH from the pituitary and TRH from the hypothalamus.

Estrogen promotes axis activity by increasing the synthesis of TSH and its receptors, as well as thyroglobulin and thyroid peroxidase synthesis.

A condition where patients with severe illness show low T3, normal or increased T4, and normal or decreased TSH, often due to suppression of TRH and TSH secretion.

Thyroid follicles combine iodine with tyrosine to make mono and diiodotyrosine, which are coupled to make T3 and T4.

TSH (Thyroid Stimulating Hormone).

They are stored in the follicles bound to thyroglobulin.

20 times more T4 than T3 is produced.

T4 is converted to T3 by deiodinase, which is present throughout the body.

The Gs-protein pathway, leading to thyroid hormone synthesis and release.

Iodide uptake, iodide oxidation, thyroglobulin production, thyroglobulin iodination, MIT/DIT coupling, and thyroglobulin proteolysis.

It indicates endogenous thyroid activity.

TSH (Thyroid Stimulating Hormone).

It allows sodium and iodide to enter the follicular cells using the sodium gradient generated by the Na/K-ATPase.

Iodide enters the colloid via a transporter called Pendrin.

Thyroid peroxidase (TPO).

Thyroglobulin is a large glycoprotein that serves as a scaffold for the production of thyroid hormones T3 and T4.

MIT (Monoiodotyrosine) and DIT (Diiodotyrosine).

DIT + DIT forms T4 (thyroxine) and DIT + MIT forms T3 (triiodothyronine).

TSH (Thyroid Stimulating Hormone).

Free T3 and T4 cross the basolateral membrane of the follicular cell and enter the bloodstream.

Low T3/T4 levels lead to increased TSH, follicular cell hypertrophy, and goiter formation.

Thyroid hormone (TH).

1. Serum Total T3 (TT3) and T4 (TT4), 2. Resin Uptake Test (RT3U, RT4U), 3. Free Thyroxine Indices (FT3I, usually FT41), 4. Dialyzable T3 and T4.

It measures the number of unoccupied binding sites on TBG.

More than a trace of TG in the blood is abnormal; it should be inside the follicle.

They include antithyroid microsomal (TPO Ab), antibodies to the TSH receptor (TSH-R Ab), thyroid stimulating immunoglobulins, and thyroid inhibiting immunoglobulins (rarely).

T3 increases BMR and overall energy turnover.

T3 increases protein synthesis in target cells.

T3 increases carbohydrate catabolism, enhancing glucose utilization.

T3 increases lipolysis in adipose tissue.

T3 increases ventilation and maintains hypoxic and hypercapnic drive in respiratory centers.

T3 increases heart rate and performance.

T3 generally stimulates growth, especially in younger individuals, and enhances bone turnover.

T3 is synergistic with GHRH, increasing the release of growth hormone.

T3 participates in axis crosstalk by influencing the activity of other endocrine systems through receptor upregulation or increased hormone synthesis.

Follicles.

Cuboidal to low columnar epithelium.

Thyroglobulin.

Primary hyperthyroidism (even in subclinical disease).

Serum TSH.

Graves disease.

Toxic adenoma.

Thyroiditis (hormone leak), not new synthesis.

Hyperthyroidism, Hypothyroidism, Mass lesions (nodules, goiter, malignancy).

Graves disease, which accounts for approximately 85% of cases.

Thyroid storm is an abrupt, severe thyrotoxicosis often triggered by infection, surgery, or stress, and can be fatal due to cardiac arrhythmias if untreated.

Symptoms include soft, warm, flushed skin, heat intolerance, weight loss despite increased appetite, hypermotility diarrhea, palpitations, anxiety, and ocular signs like wide staring gaze.

High Free T3/T4 and low TSH (suppressed).

In secondary hyperthyroidism, the problem is located in the pituitary, with high Free T3/T4 and high or inappropriately normal TSH levels.

In subclinical hyperthyroidism, Free T3/T4 levels are normal while TSH is low (suppressed).

Iodine deficiency impairs thyroid hormone synthesis, leading to decreased T3/T4, loss of negative feedback, increased TSH secretion, and thyroid hypertrophy and hyperplasia.

Compensatory enlargement leads to adequate hormone production, maintaining a euthyroid state (clinically 'nontoxic goiter').

Compensation fails, leading to goitrous hypothyroidism or rarely, hyperfunctioning nodules resulting in toxic multinodular goiter (Plummer syndrome).

Cosmetic neck mass, airway obstruction, esophageal compression, vascular compression, and hoarseness due to recurrent laryngeal nerve compression.

Occurs in regions where more than 10% of the population is affected, primarily due to dietary iodine deficiency.

Widespread iodine supplementation (iodized salt) has greatly reduced the prevalence and severity of endemic goiter.

Puberty and young adulthood.

Substances that interfere with thyroid hormone synthesis, such as calcium excess and cruciferous vegetables.

It is a late stage, irregular/nodular gland due to repeated hyperplasia-involution cycles.

Impaired skeletal growth, impaired CNS development, coarse facial features, broad nose, protruding tongue, umbilical hernia.

Usually iodine deficiency or rare enzyme defects; maternal thyroid hormone transfer is also a factor.

Severe neurodevelopmental impairment in the fetus.

Hypothyroidism in older children and adults.

Fatigue, apathy, mental sluggishness, constipation, and decreased sweating.

Cool, pale skin and decreased cardiac output leading to dyspnea and decreased exercise capacity.

It leads to impaired contractility and bradycardia, with increased total cholesterol and LDL, accelerating atherosclerosis and CAD risk.

Accumulation of glycosaminoglycans (GAGs) and hyaluronic acid in interstitial spaces, leading to non-pitting edema.

Broad, coarse facial features and macroglossia (enlarged tongue).

Hoarseness or a deep voice due to laryngeal tissue infiltration.

Chronic Lymphocytic Thyroiditis or Autoimmune Thyroiditis.

Ages 45-65.

10:1 to 20:1.

Antiperoxidase antibody (anti-TPO).

Diffuse, symmetric enlargement of the thyroid with a pale, fleshy, and firm surface due to fibrosis.

Lymphocytic infiltrates with germinal centers, atrophic follicles, and Hürthle cells.

Primary Hypothyroidism with increased TSH and decreased T4 and T3.

Levothyroxine, though the dose may need to be increased.

Lymphocytes attack thyroid antigens leading to progressive thyroid epithelial cell loss.

1. Hashitoxicosis (Early Phase) - Caused by destruction of thyroid follicles leading to leakage of preformed hormones. 2. Progressive Hypothyroidism (Later Phase) - As the gland is destroyed, T₄ and T₃ gradually decline, leading to increased TSH and overt clinical hypothyroidism.

In Hashitoxicosis, RAIU shows decreased uptake, while in Graves disease, there is increased uptake.

It typically follows an upper respiratory tract infection, presenting with painful thyroid enlargement, fever, malaise, sore throat, and neck pain, with a classic vignette clue of painful goiter and transient hyperthyroidism.

It is caused by a post-viral or virus-triggered inflammatory response, typically following an upper respiratory tract infection.

Rapid growth (50% increase in size) even if the original FNA was colloid.

The thyroid shows disrupted follicles with neutrophils and lymphocytes early, and later granulomatous inflammation with multinucleated giant cells and colloid inside.

The thyroid gland is firm with an intact capsule, may be enlarged (unilateral or bilateral), and has a cut surface that is yellow-white with focal areas of inflammation.

Lymphocytic or Silent thyroiditis; postpartum variant is called postpartum thyroiditis.

Mainly middle-aged women.

Considered a variant of Hashimoto thyroiditis with autoimmune etiology and circulating antithyroid antibodies.

Painless neck mass, thyrotoxicosis, transient hyperthyroidism followed by hypothyroidism.

It is a rare manifestation of IgG4-related disease marked by lymphoplasmacytic infiltrates and extensive fibrosis.

Hard, fixed, stone-like thyroid gland, may simulate invasive thyroid carcinoma, and about 1/3 of patients develop hypothyroidism.

Fibrous tissue with chronic inflammatory infiltrate including lymphocytes and plasma cells.

Painless Thyroiditis is transient and self-limited with antibodies present, while Riedel Thyroiditis involves progressive fibrosis beyond the thyroid and mimics malignancy.

Antiperoxidase antibodies (anti-TPO).

It is a fibrosing thyroiditis that mimics malignancy due to a hard, fixed mass and involves systemic IgG4.

A post-URI history with painful goiter and transient hyperthyroidism.

It is a silent variant of Hashimoto's, autoimmune, transient, and often postpartum.

Any thyroid nodule raises suspicion for carcinoma.

Less than 1%.

Multinodular goiter, Hashimoto's thyroiditis, simple cysts, follicular adenomas, or hemorrhagic cysts.

Papillary carcinoma, follicular carcinoma, Hurthle cell carcinoma, medullary carcinoma, anaplastic carcinoma, lymphomas, and metastatic disease.

Solitary nodules, young age (<30 years), male sex, history of radiation exposure, and cold nodules on radioactive iodine scan.

Fine-needle aspiration (FNA) cytology is the first-line diagnostic test.

It is a red flag for malignancy.

It revolutionized thyroid cancer diagnosis and avoids unnecessary surgeries in benign cases.

Most solitary nodules are benign, but evaluation must be thorough.

Fine Needle Aspirate (FNA) is the gold standard, as it is safe and inexpensive.

The sensitivity of FNA is 90%.

It has an excellent prognosis, and treatment involves lobectomy if <4cm and no suspicious features, or total thyroidectomy if >4cm or with positive lymph nodes or invasion.

It is associated with RAS mutations, spreads hematogenously, has a variable prognosis, and requires total thyroidectomy for treatment.

It originates from parafollicular (C) cells, produces calcitonin, and is treated with total thyroidectomy and central lymph node dissection.

It is an undifferentiated cancer with rapid growth, compressive symptoms, and uniformly poor prognosis, often requiring palliative surgery.