Hyperthyroidism and hypothyroidism Notes
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NOTES NOTES HYPERTHYROIDISM & HYPOTHYROIDISM GENERALLY, WHAT ARE THEY? PATHOLOGY & CAUSES ▪ Imbalance in thyroid hormones triiodothyronine (T3), thyroxine (T4) → alterations in metabolism CAUSES Hyperthyroidism ▪ Thyroid gland hyperfunction → overproduction of thyroid hormones ▫ Primary: dysfunction of thyroid gland ▫ Secondary: ↑ thyroid-stimulating hormone (TSH) secretion by pituitary gland Hypothyroidism ▪ Thyroid hormone deﬁciency ▫ Primary: dysfunction of thyroid gland ▫ Central (secondary): pituitary/ hypothalamic gland dysfunction → ↓ thyrotropin-releasing hormone (TRH)/ TSH COMPLICATIONS ▪ Hyperthyroidism: thyroid storm ▪ Hypothyroidism: myxedema, cretinism (infants, young children) SIGNS & SYMPTOMS ▪ Hyperthyroidism: hypermetabolic state, related to sympathetic nervous system stimulation ▪ Hypothyroidism: hypometabolic state 120 OSMOSIS.ORG DIAGNOSIS DIAGNOSTIC IMAGING Radioiodine uptake scan (RAIU) ▪ Measures thyroid function ▫ Ability to absorb radioactive iodine (123I) Ultrasound ▪ Size of thyroid; characteristics of nodules/ cysts Color ﬂow Doppler sonography (CFDS) ▪ Thyroid blood ﬂow velocity, vascularity LAB RESULTS ▪ Serum levels of TSH, total T4, free (unbound) T4, total T3, thyroid-stimulating immunoglobulins (TSI), TSH-receptor antibodies (TRAb) TREATMENT MEDICATIONS Hyperthyroidism ▪ Antithyroid medication ▪ Beta blockers for symptomatic thyrotoxicosis Hypothyroidism ▪ Exogenous thyroid hormone replacement SURGERY ▪ Hyperthyroidism ▫ Radioactive thyroid ablation ▫ Thyroidectomy
Chapter 19 Hyperthyroidism & Hypothyroidism EUTHYROID SICK SYNDROME osms.it/euthyroid-sick-syndrome PATHOLOGY & CAUSES ▪ Older term; describes acquired, transient central hypothyroidism in severely sick ▫ Thought to be euthyroid despite ↓ T3 +/T4 concentrations ▫ Transient central hypothyroidism coincident with peripheral T3 metabolism/production abnormalities ▪ ↓ 5’-monodeiodinase activity → ↓ peripheral (skeletal muscle, liver, kidney) T4 → T3 conversion → ↓ T3 serum concentration ▪ ↑ 5’-monodeiodinase (D3) activity → ↑ conversion of T3 → rT3 → ↓ T3 serum concentration (↑ rT3, T2 breakdown products) CAUSES ▪ Poor caloric intake ▪ High endogenous serum cortisol in setting of exogenous glucocorticoid therapy ▪ Circulating inhibitors of deiodinase activity (e.g. free/nonesteriﬁed fatty acids) ▪ Medications (e.g. amiodarone; propranolol, in high doses) ▫ Inhibit 5’-monodeiodinase activity ▪ Cytokines ▫ Tumor necrosis factor (TNF), interferonalpha (IFN-α), nuclear factor kappa-beta (NF-kB), interleukin 6 (IL-6) ▪ Impaired peripheral T4 uptake → ↓ T3 production SIGNS & SYMPTOMS ▪ Similar to hypothyroidism, not attributable to critical illness ▫ Fatigue, cold intolerance, weight loss/ gain, constipation, muscle cramps, headache, hair loss/brittleness, menstrual irregularities DIAGNOSIS LAB RESULTS ▪ Serum TSH (required for diagnosis) ▫ Detects TSH suppression TREATMENT OTHER INTERVENTIONS ▪ Standard replacement therapy (e.g. levothyroxine) ▫ No beneﬁt, unless diagnosis of preceding hypothyroidism/progression to myxedema coma RISK FACTORS ▪ Severe illness, intensive care unit (ICU) hospitalization COMPLICATIONS ▪ Myxedema coma OSMOSIS.ORG 121
GRAVES' DISEASE osms.it/graves-disease PATHOLOGY & CAUSES ▪ Autoimmune disease; production of antibodies against TSH receptor ▪ Most common cause of hyperthyroidism (80%) ▪ Thyroid-stimulating immunoglobulin (TSI) antibody binds to TSH receptors, acts as analog ▫ Exophthalmos dries eyes → corneal ulcers; weakens muscles controlling eye, upper lid ▪ Inﬁltrative dermopathy ▫ Glycosaminoglycan builds up → pretibial myxedema → non-pitting edema ▪ Pretibial myxedema RISK FACTORS ▪ Genetic; polymorphisms in CTLA4, PTPN22, HLA-DR3 allele ▪ Peak incidence occurs at 20–40 years old ▪ Individuals who are biologically female affected 10 times more often COMPLICATIONS ▪ Congestive heart failure, osteoporosis ▪ Thyroid storm ▪ Autoimmune conditions ▫ Rheumatoid arthritis, systemic lupus erythematosus, pernicious anemia, diabetes mellitus Type I ▪ Radioiodine treatment → hypothyroidism SIGNS & SYMPTOMS ▪ Effects of TSI ▫ Thyroid hypertrophy, hyperplasia → diffuse goiter ▫ Increased synthesis, release of T3, T4 ▫ Follicular cells express molecules on surface, attract nearby T cells → T cells bind to follicular cells, inﬁltrate interstitium of thyroid tissue ▫ TSI stimulation of ﬁbroblasts in eye orbit → increased production of glycosaminoglycans → local inﬂammation, swelling → exophthalmos, lid retraction 122 OSMOSIS.ORG Figure 19.1 The clinical appearance of Graves’ disease. There is proptosis and lid retraction bilaterally. DIAGNOSIS DIAGNOSTIC IMAGING ▪ Radioiodine scans, measurements of iodine uptake ▫ Diffusely increased LAB RESULTS ▪ ↓ TSH, ↑ T3, ↑ T4, ↑ TSI TREATMENT MEDICATION ▪ Antithyroid medication ▫ Thioamides ▪ Beta-blockers
Chapter 19 Hyperthyroidism & Hypothyroidism SURGERY ▪ Thyroidectomy ▪ Radioiodine radioisotope surgery ▫ Partially/completely destroy thyroid gland with radiation OTHER INTERVENTIONS ▪ Ophthalmopathy ▫ Steroids, radiation and surgery Figure 19.2 The histological appearance of scalloped colloid within a hyperplastic thyroid follicle; a classic sign of Graves’ disease. Figure 19.3 The histological appearance of the thyroid gland in Graves’ disease. There are enlarged thyroid follicles lined by hyperplastic follicular epithelium. The epithelium demonstrates papillary infolding. HYPERTHYROIDISM osms.it/hyperthyroidism PATHOLOGY & CAUSES ▪ Disorder caused by excessive amount of thyroid hormone produced by overactive thyroid gland ▪ ↑ thyroid hormone synthesis, secretion → thyrotoxicosis (↑ circulating thyroid hormones) CAUSES ▪ Autoimmune ▫ Graves’ disease (most common cause) ▪ TSH-related disease ▫ TSH-secreting pituitary adenoma; stimulation of TSH receptors due to excess hCG (e.g. trophoblastic tumors, hyperemesis gravidarum) ▪ Solitary autonomous adenoma ▪ Excessive iodine ingestion RISK FACTORS ▪ More common in individuals who are biologically female ▪ Smoking, genetic inheritance (Graves’ disease) COMPLICATIONS ▪ Thyroid storm OSMOSIS.ORG 123
DIAGNOSIS SIGNS & SYMPTOMS ▪ Thyroid ▫ Normal/enlarged, with/without palpable nodules (may be diffusely ﬁrm, tender) ▪ Cardiovascular ▫ Bounding, rapid pulse; hypertension; palpitations ▪ Respiratory ▫ Tachypnea, dyspnea on exertion ▪ Gastrointestinal (GI) ▫ ↑ appetite/↓ weight; hyperdefecation ▪ Integumentary ▫ Warm, ﬂushed, moist skin; patchy hair loss; thyroid acropachy (digital clubbing); inﬁltrative dermopathy (pretibial myxedema) ▪ Musculoskeletal ▫ Osteoporosis (↑ bone resorption); skeletal muscle atrophy ▪ Neurological ▫ Heat intolerance, ﬁne tremor, agitation, insomnia ▪ Reproductive ▫ Menstrual irregularities, ↓ libido, infertility ▪ Ocular changes (Graves’ disease) ▫ Wide, staring gaze; lid lag, exophthalmos DIAGNOSTIC IMAGING RAIU ▪ ↑ 123I uptake conﬁrms hyperthyroidism CFDS ▪ ↑ blood ﬂow due to thyroid hyperactivity Ultrasound ▪ Benign/malignant nodules (e.g. microcalciﬁcations, hypoechogenicity in malignant nodules) LAB RESULTS ▪ ↓ TSH, ↑ free T4, total/free T3 ▫ Conﬁrms hyperthyroidism with suppressed TSH ▪ ↑ TSH, free T4, total/free T3 ▫ Conﬁrms TSH-induced hyperthyroidism ▪ ↑ TRAb/TSI TREATMENT MEDICATIONS ▪ Antithyroid drugs SURGERY ▪ Thyroidectomy OTHER INTERVENTIONS ▪ Radioactive thyroid ablation 124 OSMOSIS.ORG
Chapter 19 Hyperthyroidism & Hypothyroidism HYPOTHYROIDISM osms.it/hypothyroidism PATHOLOGY & CAUSES ▪ Hypometabolic state caused by underproduction of thyroid hormones T3, T4 ▪ ↓ availability of thyroid hormone → general slowing of thyroid hormone-induced cell metabolism ▪ Accumulation of matrix glycosaminoglycans in interstitial space → myxedema TYPES Primary hypothyroidism (thyroid gland dysfunction) ▪ Iodine deﬁciency ▪ Autoimmune: Hashimoto’s thyroiditis ▫ Autoantibodies against thyroglobulin (Tg), thyroid peroxidase (TPO), TSH receptor → bound antibodies facilitate T-cell, complement-mediated immune destruction of thyroid cells; steric hindrance at TSH receptor ▪ Congenital ▫ Inborn errors of thyroid hormone metabolism ▫ Thyroid agenesis/hypoplasia ▪ Iatrogenic ▫ Treatment of hyperthyroidism, thyroid neoplasm (radiation, surgical) ▪ Medication-induced ▫ Overdose of antithyroid drugs (propylthiouracil, methimazole) ▫ Agents ↓ T4 absorption (cholestyramine, iron salts) ▫ Agents ↓ T4 → T3 conversion (amiodarone) ▫ Agents ↓ clearance of T4 (phenytoin, carbamazepine) ▫ Others: lithium carbonate, interferon alpha, IL-2, tyrosine kinase inhibitors (esp. sunitinib), P-aminosalicylic acid Secondary, tertiary hypothyroidism (central hypothyroidism) ▪ Disorder of pituitary/hypothalamus/ hypothalamic-pituitary communication → ↓ TSH/TRH ▫ Hypopituitarism: surgical resection/ radiation for adenoma, trauma, postpartum pituitary necrosis (Sheehan’s syndrome), inﬁltrative disease ▫ Hypothalamic damage: radiation, granulomas, neoplasms RISK FACTORS ▪ ↑ age ▪ More common in individuals who are biologically female COMPLICATIONS ▪ Myxedema coma ▫ Common in older individuals who are biologically female with longstanding hypothyroidism; precipitated by acute event (e.g. trauma, infection, myocardial infarction) ▪ Dyslipoproteinemias ▪ Dilated cardiomyopathy; ↓ thyroid hormone → dysregulation of myocardial enzymes → ↓ myocardial contractility ▪ Anemia ▫ Hypoproliferative (normochromic, normocytic)/pernicious anemia (most common in chronic autoimmune thyroiditis) ▪ Hyperprolactinemia → galactorrhea ▪ ↓ clearance of drugs (e.g. antiepileptic, anticoagulant, opioids) in setting of hypothyroidism → ↑ accumulation of drugs → potential drug toxicity ▪ Congenital hypothyroidism ▫ Failure to thrive, intellectual disability OSMOSIS.ORG 125
SIGNS & SYMPTOMS ▪ Fatigue, cold intolerance, constipation, muscle weakness, headache, weight gain, brittle hair/loss of eyebrow hair, menstrual irregularities, goiter (primary hypothyroidism) ▪ Neurologic manifestations ▫ Difﬁculty concentrating, poor memory, peripheral neuropathy, carpal tunnel syndrome, ↓ deep tendon reﬂexes ▪ Myxedema (nonpitting edema) ▫ Periorbital edema, tongue enlargement, puffy facies ▪ Myxedema coma ▫ Altered mental status, hypothermia, multi-organ failure, hypotension, bradycardia, hyponatremia, hypoglycemia, hypoventilation Figure 19.4 Myxedema of the hands in an individual with hypothyroidism. DIAGNOSIS LAB RESULTS ▪ Primary hypothyroidism ▫ ↑ TSH, ↓ free T4 ▪ Central hypothyroidism ▫ ↓ free T4, ↓/↔/↑ TSH ▪ Autoimmune autoantibody detection (Hashimoto’s thyroiditis) ▫ ↑ ↑ anti-TPO/Tg/TSH receptor antibodies OTHER DIAGNOSTICS ▪ History, physical examination TREATMENT MEDICATIONS ▪ Synthetic T4 (levothyroxine) replacement therapy 126 OSMOSIS.ORG Figure 19.5 Pretibial myxedema in an individual with hypothyroidism.
Chapter 19 Hyperthyroidism & Hypothyroidism THYROID STORM osms.it/thyroid-storm PATHOLOGY & CAUSES DIAGNOSIS ▪ Severe, acute, life-threatening complication of hyperthyroidism LAB RESULTS CAUSES OTHER DIAGNOSTICS ▪ Abrupt termination of hyperthyroidism therapy ▪ Complication of hypothyroid treatment ▪ Diabetic ketoacidosis ▪ Stressors (surgery, infection, trauma, childbirth) ▪ Increased sensitivity of tissues to thyroid hormone, catecholamines COMPLICATIONS ▪ Myocardial infarction (MI), heart failure; coma, death SIGNS & SYMPTOMS ▪ ↓ TSH, ↑ T3, ↑ T4 ECG ▪ Conﬁrmation TREATMENT MEDICATION ▪ Beta blockers ▪ Thyroid hormones reduction ▫ Thioamides, iodine preparations, glucocorticoids, bile acid sequestrants OTHER INTERVENTIONS ▪ Plasmapheresis ▪ Exaggerated hyperthyroidism symptoms ▫ Heat intolerance → fever ▫ Hyperactivity, anxiety → agitation, confusion, seizures, coma ▫ Tachycardia → cardiac arrhythmias, high-output heart failure OSMOSIS.ORG 127
TOXIC MULTINODULAR GOITER osms.it/toxic-multinodular-goiter PATHOLOGY & CAUSES ▪ Excess thyroid hormone production from multiple autonomous thyroid nodules, without stimulation of TSH ▪ Second most common cause of hyperthyroidism; AKA Plummer’s disease ▪ Starts as non-toxic multinodular goiter caused by chronic lack of dietary iodine ▫ Lack of iodine → low levels of thyroid hormones→ anterior pituitary releases TSH → thyroid hypertrophy, hyperplasia → some parts of thyroid gland more responsive to TSH than others → uneven growth → most responsive follicular cells grow quickly, develop into nodule → multiple nodules appear ▫ More follicular cells compensate for low thyroid hormone production → euthyroid state ▪ Non-toxic multinodular goiter becomes toxic when genetic mutation for TSH receptor occurs in one of dividing follicular cells → cell becomes constitutively active without TSH → overstimulation of thyroid to divide, produce thyroid hormone → toxic multinodular goiter COMPLICATIONS ▪ Malignancy (rare) SIGNS & SYMPTOMS ▪ Increased synthesis, release of T3, T4 → hyperthyroidism ▫ Increased basal metabolic rate, catabolism of proteins, carbohydrates, bone resorption ▫ Exacerbation of sympathetic nervous system ▫ Impairment of reproductive system 128 OSMOSIS.ORG ▪ Thyroid hypertrophy, hyperplasia → goiter ▫ Difﬁculty swallowing, airway obstruction ▫ Compression of recurrent laryngeal nerve → hoarse voice ▫ Superior vena cava syndrome → facial, arm swelling Figure 19.6 The clinical appearance of a goiter. DIAGNOSIS DIAGNOSTIC IMAGING ▪ Radioiodine scans, measurements of iodine uptake ▫ Uneven (“hot” autonomous nodules) LAB RESULTS ▪ ↓ TSH, ↑ T3, ↑ T4 TREATMENT MEDICATION ▪ Beta blockers ▪ Antithyroid medication ▫ Thioamides ▫ If radioiodine therapy, surgery not appropriate
Chapter 19 Hyperthyroidism & Hypothyroidism SURGERY ▪ Thyroidectomy ▪ Radioiodine radioisotope surgery ▫ Partially/completely destroy thyroid nodules with radiation OTHER INTERVENTIONS ▪ Inject ethanol into nodules Figure 19.7 A CT scan of the head and neck in the sagittal plane demonstrating a massive goiter extending from the mandible to the suprasternal notch. OSMOSIS.ORG 129
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