Reading...
Play button
Play button
Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
86 Cards in this Set
- Front
- Back
|
The Hypothalamic-Pituitary-Thyroid Axis :
|
|
|
|
Hormonal Assessment of the HPT Axis:
|
*Best initial test for assessment of thyroid function: TSH
*PITFALLS: -Inaccurate with hypothalamic or pituitary dysfunction -Confusing when thyroid function is changing -May need T4 or T3 estimate to assess SEVERITY of dysfunction |
|
|
THYROID HORMONE ASSAYS:
|
*Total T4, total T3, free T4, free T3
*The unbound or free fraction is responsible for biologic activity *But the choice of lab assay depends not only on accuracy but on turnaround time, availability, and cost *The most practical choices usually include: free T4 with or without total T3 or, less often, free T3 |
|
|
Hypothyroidism: Definitions--
|
*Hypothyroidism: deficient thyroidal production of thyroid hormone OR thyroid hormone deficiency in target tissues (rare)
*Anatomic site of dysfunction Primary: defect is in the thyroid gland Secondary (central): defect is in the hypothalamic-pituitary area *Time of onset Congenital Acquired |
|
|
Hypothyroidism: Discuss severity--
|
Severity:
*Clinical (overt) hypothyroidism Free T4 is low, symptoms often present *Subclinical (compensated) hypothyroidism -Refers to the state of early or pre- hypothyroidism (primary) -By current definition, free T4 concentration is normal but TSH is elevated |
|
|
Hypothyroidism: History--
|
*Goiter (Latin, struma): enlarged thyroid
*Cretinism (1500’s): the constellation of clinical features including large goiter, short stature, and MR that was eventually attributed to untreated, congenital hypothyroidism *Myxedema (1879 – Gull, Ord): original term for the hypothyroid syndrome in previously normal adults; now refers to cases of severe and/or complicated hypothyroidism or more specifically, the skin manifestations of severe hypothyroidism |
|
|
DIAGNOSIS OF HYPOTHYROIDISM:
|
*TSH
The most sensitive test for dx of primary hypothyroidism of any severity *Free thyroxine (FT4) Decreased in overt hypothyroidism *TSH and FT4 Need both tests for dx of secondary hypothyroidism *Total and free T3 tests are RARELY USEFUL in the diagnosis of hypothyroidism |
|
|
Diagnosis of Hypothyroidism-- describe 1˚, subclinical, and 2˚ hypothyroidism:
|
*Primary Hypothyroidism
FT4 low TSH high *Subclinical Hypothyroidism FT4 nl TSH high *Secondary Hypothyroidism FT4 low TSH low (occas normal) |
|
|
Are Other Tests Useful to Identify the Cause of Primary Hypothyroidism?
|
*Thyroid Peroxidase (TPO) antibodies – Marker of thyroid autoimmunity
*Thyroid radioisotope scan and uptake – Not useful for diagnosis of hypothyroidism *Thyroid ultrasound and/or thyroid biopsy -- Not useful for diagnosis of hypothyroidism (useful for evaluation of accompanying nodule or goiter) |
|
|
Hypothyroidism: Prevalance--
|
*Prevalence in adults (NHANES, 2002):
Subclinical hypothyroidism: 4.3% Overt hypothyroidism: 0.3% *Prevalence, primary/secondary >500:1 *Prevalence, women/men ~ 10:1 *Prevalence increases with age; ~15% in women > 60 years of age (subclinical + overt) *Higher prevalence with other autoimmune conditions |
|
|
HYPOTHYROIDISM: CLASSIC SYMPTOMS--
|
Lethargy, Fatigue
Dry Skin, Cold intolerance Brittle nails, Coarse hair, Hair loss (scalp)) Poor Memory & Concentration, Depression Constipation, - Appetite, + Weight Hoarse Voice, Impaired hearing Menorrhagia, Oligo- or amenorrhea, Infertility |
|
|
HYPOTHYROIDISM: CLINICAL FEATURES based on appearance--
|
*Thyroid: size range -- very large to atrophic
*Dry coarse skin -Diminished sweating -Thinned epidermis *Puffy face, hands, feet + Dermal gycosaminoglycan leads to: + H2O content --> skin thickening -“Non-pitting edema” (myxedema) *Weight gain (usually modest) *Pallor -Yellow tinge ( +carotene content) *Nail growth retarded *Hair dry and brittle -Hard to manage -loss of scalp hair --> diffuse alopecia -Lateral eye-brow thinning |
|
|
HYPOTHYROID FACIES
-PUFFY FACE |
|
|
HYPOTHYROIDISM: CLINICAL FEATURES--cardio and fluid accumulation sx:
|
*Cardiovascular dysfunction
-Myocardial contractility goes down -Pulse rate goes down -Peripheral resistance increases -leads to DIASTOLIC hypertension *Fluid accumulation -Pericardial & other effusions -Middle ear --> hearing loss |
|
|
HYPOTHYROIDISM: CLINICAL FEATURES--reproductive sx:
|
*Reproductive dysfunction
-Menorrhagia, oligo- or amenorrhea (low fertility) -increased Prolactin, sometimes with galactorrhea -Increased frequency of miscarriage -Diminished I.Q. of children born of hypothyroid (and ? subclinically hypothyroid) mothers |
|
|
HYPOTHYROIDISM: CLINICAL FEATURES--pulm sx:
|
*Pulmonary function tests generally normal
*Dyspnea *Pleural effusions -decreased Respiratory muscle function *Sleep apnea *Decreased respiratory drive *HE SKIPPED THIS SLIDE* |
|
|
HYPOTHYROIDISM: CLINICAL FEATURES--MS and neuro sx:
|
*Musculoskeletal dysfunction
-Carpal tunnel & other nerve entrapment syndromes -Myopathy -Stiffness, cramps, pain -Slow deep tendon reflex relaxation time *Neurologic dysfunction -decreased Memory & concentration; reversible dementia -Psychosis, cerebellar ataxia, coma |
|
|
PRIMARY HYPOTHYROIDISM: MAJOR CAUSES--
|
*Iodine deficiency
*Congenital *Autoimmune (Hashimoto’s) thyroiditis *Surgical or radioiodine ablation *Drugs: Lithium, TNF-alpha, amiodarone, sunitinib, *PTU/MMI *Infiltrative Diseases -Amyloidosis, sarcoidosis, hemachromatosis |
|
|
SECONDARY HYPOTHYROIDISM: CAUSES--
|
*Hypopituitarism
-Tumors, Surgery, Irradiation, Trauma, Genetic, Infiltrative diseases, Sheehan’s syndrome (things damaging the pituitary) *Isolated TSH deficiency or bioinactivity *Hypothalamic Disease -Tumors, Trauma, Infiltrative disease *Drugs -Dopamine, bexarotene therapy |
|
|
Discuss IODINE DEFICIENCY:
|
*The #1 cause of hypothyroidism worldwide
*Tends to occur in inland, mountainous geographic regions such as the Alps, Andes, and Himalayas *The thyroid compensates by enlarging and increasing ratio of T3/T4 production *A minority of patients develop overt hypothyroidism *Use of iodized foods (salt) has reduced the prevalence of iodine deficiency, but 200 million people may still be affected |
|
|
CONGENITAL HYPOTHYROIDISM--
|
*Prevalence: 1/4,000 births in areas of iodine sufficiency
*Etiology: sporadic or inherited gene mutations causing -Thyroid gland agenesis or dysgenesis (85%) -Defective thyroid hormone biosynthesis (15%) *Because clinical features are often subtle, all newborns in U.S. undergo routine screening *Less than 10% have classic clinical features such as prolonged jaundice, hypothermia, bradycardia, enlarged posterior fontanelle *Permanent neurologic damage results if treatment is not immediate (mother’s T4 is protective in utero) *CNS malfunction is due to decreased myelination |
|
|
AUTOIMMUNE THYROID DISEASE:
|
*Thyroid autoimmunity is involved in the pathogenesis of many thyroid diseases
-Autoimmune (Hashimoto’s, lymphocytic) thyroiditis -Silent thyroiditis -Post-partum thyroiditis -Graves Disease -Neonatal thyroid dysfunction (rare) *About 10% of women have circulating thyroid antibodies with normal thyroid function, +/- goiter *Strong genetic predisposition *Causal defect uncertain: ? Antigen-specific defect in suppressor T-lymphocytes *Major thyroidal antigens: TPO, thyroglobulin, and the TSH-receptor *Clinical manifestations depend on genetic background, the specific antibodies involved, strength of the immune response, and iodine intake |
|
|
AUTOIMMUNE (Hashimoto) THYROIDITIS
-Thyroid follicle that looks like a lymph node -The #1 cause of hypothyroidism in iodine-sufficient areas |
|
|
Discuss AUTOIMMUNE THYROIDITIS--
|
*Most common in women over age 35; increases with age
*Hypothyroidism (overt or subclinical) may or may not be present; often progresses slowly over a period of years *Goiter may or may not be present *Serum TPO abs are present in 90%, TG abs in 60% *TPO abs are associated with ~4X increased risk of hypothyroidism *Associated with other autoimmune abnormalities both endocrine (polyglandular failure type 1 and 2) and non-endocrine (vitiligo, pernicious anemia) |
|
|
TRANSIENT THYROIDITIS & TRANSIENT HYPO- HYPERTHYROIDISM:
|
*Silent and post-partum thyroiditis
*Subacute (granulomatous, giant cell, deQuervain’s) *Drug-induced (amiodarone, interferon, interleukin-2) *Acute Thyroiditis is rare, origin usually a bacterial or fungal infection, and does not generally cause hyper- or hypothyroidism (not a big focus for us) |
|
|
SILENT THYROIDITIS:
|
*A subgroup of autoimmune thyroiditis
*Classic findings: Painless, transient thyrotoxicosis followed by transient hypothyroidism *~70% return to euthyroid state *Overall course often lasts 4-12 months *Diagnosis -Typical pattern of thyroid function results, clinical setting, elevated TPO abs (usually) -Thyroidal radioiodine uptake is low during hyperthyroid phase |
|
|
SILENT THYROIDITIS: TYPICAL COURSE
hyper--eu--hypo--eu |
|
|
POST-PARTUM THYROIDITIS:
|
*Silent thyroiditis in post-partum women
*Reflects the post-partum rebound in autoimmunity that occurs after pregnancy *Occurs in ~5% of all women, ~25% of women with TPO abs *At risk up to 12 months after delivery *NO radioiodine tests in nursing mothers!!! |
|
|
SUBACUTE THYROIDITIS:
|
*Hallmark feature is neck pain related to thyroid inflammation
*Etiology probably post-viral, not immune *Pathology: infiltration of neutrophils and multinucleated giant cells, occasional granulomas *Diagnosis -Thyroid function pattern similar to silent thyroiditis but neck pain is prominent & other inflammatory features are often present -Radioiodine uptake is low during hyperthyroid phase (distinguishes from silent thyroiditis) |
|
|
When is Thyroid Hormone Therapy Indicated?
|
*For Thyroid Replacement
-Hypothyroidism -Subclinical Hypothyroidism (some cases) *Other -Goiter (+/-); may reduce gland size -Thyroid carcinoma (+/-); higher dose for anti-neoplastic effect |
|
|
What is the consensus treatment of choice for hypothyroidism? Why?
|
L-T4 (levo T4)
It’s physiologic, free of side-effects, and inexpensive |
|
|
Thyroid Hormone Pharmacology:
|
L-T4 L-T3
Half-life, days 7 <1 GI absorption,% 75 85 Production/24h, ug 80 30 Thyroid content, ug/g 200 15 Affinity for TBG 30 1 Protein-bound, % 99.97 99.70 Free Hormone, ng/dl 2 0.2 Biologic potency 1 4 |
|
|
Why Not L-T3 Replacement?
|
*Is there a role for L-T3 therapy in treating primary hypothyroidism?
-Physiological arguments: “active” hormone, heterogeneity of deiodinases -Clinical arguments: several studies suggest that L-T3 +/- L-T4 improve symptoms more than L-T4 alone; most studies disagree *Exogenous L-T4 alone almost always results in normal and stable FT4, FT3, and TSH levels *The shorter half-life of L-T3 often leads to T3 peaks and valleys, low T4, and variable TSH |
|
|
Is L-T3 Replacement Ever Useful?
|
*Often used to prepare patients with thyroid cancer for radioiodine treatment or testing
*A possible (unproven) treatment option for persons with severe, acute hypothyroidism (“myxedema coma”) |
|
|
What Are the Risks of L-T4 Therapy?
|
*Hyperthyroidism
*Hypothyroidism *Rare: -Angina, MI, arrhythmias (if significant coronary heart disease present) -Precipitation of adrenal insufficiency (in patients at risk) -Allergy to dye in tablets |
|
|
How is L-T4 treatment titrated and monitored?
|
*If patient is elderly or has heart disease, start low and titrate slow
*In young/healthy, start with estimated L-T4 replacement dose (~1.5 mcg/kg) *Aging: L-T4 requirement tends to decrease *Weight gain: L-T4 requirement tends to increase *Pregnancy: L-T4 requirement usually increases 30-50% |
|
|
L-T4 Treatment Goals:
|
*Primary hypothyroidism: Normal TSH
*Secondary hypothyroidism: Normal FT4; TSH of no value |
|
|
Treatment of Hypothyroid Emergencies, eg, Myxedema Coma:
|
*Treatment is empirical; no clinical studies available to support specific treatment(s)
*L-T4 i.v. in large doses, eg, 3-5 times the usual replacement dose *L-T3 i.v. has also been used; faster onset may be beneficial -- or perhaps harmful? *Other therapeutic measures |
|
|
Do any drugs interact with L-T4 Rx?
|
Estrogen (increased TBG), Androgens (decreased TBG)
*Iron, calcium, cholestyramine, sucralfate (can interfere with L-T4 absorption) *Phenytoin, carbamazepine, rifampin (increased T4 clearance) |
|
|
Hormonal Assessment of the HPT Axis:
|
*Best initial test for assessment of thyroid function: TSH
*PITFALLS: -Inaccurate with hypothalamic or pituitary dysfunction -Confusing when thyroid function is changing -May need T4 or T3 estimate to assess severity of dysfunction |
|
|
DIAGNOSIS OF HYPERTHYROIDISM :
|
*TSH
*Free T4 Increased in 95% of pts with thyrotoxicosis *Total or free T3 Increased in 95% of pts with thyrotoxicosis T3 toxicosis: FT3 increased but not FT4 (5% of patients) |
|
|
THYROTOXICOSIS & HYPERTHYROIDISM: DEFINITIONS--
|
*Thyrotoxicosis= Thyroid hormone excess
*Hyperthyroidism= Thyroid hormone excess resulting from increased synthesis & release of thyroid hormone *Practically, “hyperthyroidism” is often used in place of “thyrotoxicosis” |
|
|
THYROTOXICOSIS & HYPERTHYROIDISM: anatomic site--
|
*Anatomic site of dysfunction
Primary: thyroid Secondary: pituitary or hypothalamus *Congenital hyperthyroidism is rare |
|
|
THYROTOXICOSIS & HYPERTHYROIDISM: different severities--
|
*Clinical or overt hyperthyroidism
Usually refers to presence of elevated free T4 and/or T3 with low (very low) TSH *Subclinical hyperthyroidism Early or borderline hyperthyroidism Refers to lab values of low TSH with normal free T3 and free T4 |
|
|
Diagnosis of Hyperthyroidism:
|
*Hyperthyroidism (Primary)
FT4 high* FT3 high* TSH low *Subclinical Hyperthyroidism FT4 nl FT3 nl TSH low *Hyperthyroidism (Secondary) FT4 high FT3 high TSH high *FT4 or FT3 are occasionally normal; only one needs to be high for diagnosis |
|
|
Adjunctive Tests for Identifying the Cause of Hyperthyroidism (Primary):
|
*Thyroid radioioisotope scan and uptake: particularly useful when clinical or lab features are not diagnostic
*Autoimmune markers: Thyroid-receptor antibodies are specific for Graves Disease; TPO (and TG) antibodies are non-specific markers of autoimmune thyroid disease *Other tests are cause-specific, such as blood hCG level for thyrotoxicosis caused by an hCG-producing tumor |
|
|
THYROTOXICOSIS: CAUSES of 1˚ hyperthyroidism:
|
Graves’ Disease
Solitary Toxic Nodule Toxic Multinodular Goiter Iodine Excess (Jod-Basedow) Struma Ovarii (thyroid tissue found in ovary) Functional Thyroid Cancer Metastases |
|
|
THYROTOXICOSIS: CAUSES of non-hyperthyroid thyrotoxicosis:
|
*Subacute Thyroiditis (Painful)
*Silent and post-partumThyroiditis *Inflammatory processes Medications, eg, amiodarone Radiation *Exogenous hormone ingestion |
|
|
THYROTOXICOSIS: CAUSES of 2˚ hyperthyroidism and non-TSH stimulation of TSH receptor:
|
*Secondary Hyperthyroidism (rare)
TSH Secreting Pituitary Adenoma Thyroid Hormone Resistance *Non-TSH stimulation of TSH receptor hCG-Producing Tumor Gestational Thyrotoxicosis |
|
|
Epidemiology of GRAVES’ DISEASE:
|
*60-75% of all cases of thyrotoxicosis
*F/M ~ 10/1 *Occurs in < 0.5% of the population *Peak onset 20-50 years of age *Correlates with higher iodine intake |
|
|
Pathogenesis of GRAVES’ DISEASE:
|
*Pathogenesis: Immunoglobulins (Thyroid-receptor antibodies, TRAbs) that bind to the TSH-Receptor
-Thyroid: most TRAbs activate the TSH-receptor but some block it -Extra-thyroidal (orbitopathy, dermopathy): -Cytokines --> Fibroblast activation, inflammation -Glycosaminoglycans --> H20 & edema (also seen in hypothyroidism) |
|
|
THYROTOXIC SYMPTOMS:
|
Hyperactivity, Irritability, Dysphoria, Insomnia
Heat Intolerance, Sweating Palpitations Fatigue, Weakness Weight Loss, Hyperphagia, Frequent bowel movements Oligo- or amenorrhea Tremor, Insomnia |
|
|
THYROTOXIC SIGNS: weight and neuro--
|
*Weight Loss & increased Appetite
Enhanced Metabolic Rate 5% have Weight increase due to higher food intake *Neurologic Manifestations Fine Tremor, Hyperreflexia Muscle Wasting, Chorea (Rare) Proximal Myopathy Hypokalemic Periodic Paralysis (Especially Asian Males) |
|
|
THYROTOXIC SIGNS: cardio--
|
*Sinus Tachycardia, Supraventricular tachycardia
-Palpitations *Atrial Fibrillation -Usually in those > 60 years *High cardiac output -Bounding pulse, increased pulse pressure, aortic systolic murmur -Worsening of angina or CHF |
|
|
THYROTOXIC SIGNS: skin--
|
*Warm, Moist, Diapharesis, Heat intolerance
*Palmar Erythema, Onycholysis *Pruritus, Urticaria (less common) *Hair texture fine Diffuse Alopecia in 40% of patients *Thyroid Dermopathy <5% Pre-tibial Myxedema <1% Acropachy |
|
|
Dermopathy of Graves’ Disease
51 year old woman with Graves’ hyperthyroidism. Dermopathy extends bilaterally from knees to feet. Edema as well. |
|
|
THYROTOXIC SIGNS: defecation and menstrual--
|
*Hyperdefecation
-Gastrointestinal Transit Time Decreased -Occasional Mild Steatorrhea *Oligo- Amenorrhea -Anovulatory Cycles - decreased Fertility But Not Absolute |
|
|
THYROTOXIC SIGNS: bone and thyroid ∆s--
|
*Enhanced Bone Resorption
-Direct Effect of Thyroid hormone on Osteoclast -increased bone Turnover, (-) Calcium Balance -Osteopenia and Osteoporosis (esp. older pts) -higher Future Fracture Risk *Typically: Diffuse thyroid enlargement -2-3 X Normal size, Mildly Firm -Thrill, Bruit (increased gland vascularity) |
|
|
THE GRAVES’ THYROID:
|
*Diffuse Goiter
-Firm/ “Rubbery” -Pyramidal Lobe -Thrill/ Bruit *Scan -Homogeneous pattern -Radioiodine Uptake: high, > 30% @ 24 h |
|
|
Thyroid Scan
|
|
|
THYROTOXIC SIGNS: eyes--
|
*Lid retraction (Stare)
-Any Thyrotoxicosis --> increased sympathetic activity *Graves’ Orbitopathy -80% bilateral, 20% unilateral -65% -- onset is within 1 year of diagnosed thyrotoxicosis (25% before or after 1 year) -10% of cases never develop thyrotoxicosis |
|
|
GRAVES ORBITOPATHY:
|
*Symptoms may occur without signs; grittiness, dryness, tearing
*Scleral Injection / Chemosis *Periorbital Edema *Impaired ocular movement *Proptosis (Exophthalmos) -Measure with exophthalmometer *Corneal exposure/damage *Optic nerve damage, blindness |
|
|
GRAVES ORBITOPATHY
|
|
|
SOLITARY TOXIC NODULE:
|
*Pathogenesis:
Most are due to acquired, somatic, activating mutations of the TSH-receptor *Clinical Hyperthyroidism is often mild Nodule may be palpable, often large “Hot” area on radioisotope scan with suppression of remaining gland |
|
|
TOXIC MULTINODULAR GOITER:
|
*Pathogenesis:
-Autonomously functioning tissue -Mono- and polyclonal nodules: -Suggests hyperplasia 2° to growth factors and cytokines -Activating TSH-receptor mutations are rare *Most common in the ELDERLY. *Hyperthyroidism may be precipitated by an iodine load (Jod-Basedow Syndrome), as in testing. |
|
|
hCG & TSH -- INDUCED THYROTOXICOSIS :
|
*High hCG Levels (tumors, some pregnancies)
-hCG binds weakly to the TSH-receptor *TSH- Secreting Pituitary Tumor -TSH usually high or high-normal -T4 & T3 high with diffuse goiter -Pituitary mass on MRI |
|
|
APATHETIC (often elderly) THYROTOXICOSIS:
|
*In elderly persons with thyrotoxicosis; tend to have a different set of symptoms than younger persons
-More common: apathy, lethargy, weight loss, depression, altered mentation -Less common: hyperphagia, sweating, warm skin, palpable goiter, tremor *Often misdiagnosed as depression, dementia, cancer *May be accompanied by atrial fibrillation |
|
|
Treatment of Thyrotoxicosis:
|
*Varies depending on the cause
*Subclinical Hyperthyroidism -Decision regarding treatment depends on estimated risk -Risks are generally greatest in adults over 60 yo & include progression of disease, symptoms, atrial fibrillation, and osteoporosis |
|
|
What Are the Standard Treatment Options for Hyperthyroidism (Graves Disease and Toxic Nodules)?
|
Thionamides
I-131 Surgical excision Beta-blockers (adjunctive therapy) |
|
|
THIONAMIDES
|
|
|
How do THIONAMIDES work?
|
-Decrease T3/T4 synthesis by inhibiting TPO.
|
|
|
THIONAMIDES:
|
*Currently available in U.S:
Methimazole (MMI): generally preferred Propylthiouracil (PTU) is backup *Mechanisms Reduce thyoxine synthesis by inhibiting thyroid peroxidase activity Inhibit T4 to T3 conversion (PTU) Inhibit immune system function (?) |
|
|
THIONAMIDES: PHARMACOLOGY--
|
PTU MMI
POTENCY/mg 1 10+ SERUM t1/2, HRS 1-2 6-22 CLINICAL ACTION, HRS 6-8 12-24 PROTEIN BINDING, % 75 0 PLACENTAL PASSAGE Low Mod BREAST MILK LEVELS Low Mod VOL OF DISTRIB, L 20 40 |
|
|
What are the Potential Adverse Effects of Thionamides?
|
*Minor
Skin rash, GI symptoms, taste disturbances *Major -Hepatitis (PTU) ; cholestatic jaundice (MMI) -MMI may be associated with birth defects: aplasia cutis & methimazole GI embryopathy--use PTU in pregnancy. -Agranulocytosis (0.2%) – fever, pharyngitis, etc -Lupus-like syndrome or vasculitis – vasculitis, renal disease *Patient education is critical! For new symptoms, patient must stop drug and call M.D. |
|
|
Thionamides: Clinical Strategy in Graves Disease--
|
*Complete remission occurs in ~30% of patients treated effectively with thionamides for 12-18 months
*No highly accurate predictors of remission *Lifelong follow-up is necessary due to possibility of late hypo- or hyperthyroidism |
|
|
Thionamides during Pregnancy--
|
*Class D (High-risk) – primarily because of potential for fetal hypothyroidism – but usually safe & effective when used appropriately
*Consider PTU for first trimester *Important to use lowest effective dose; maternal-fetal health is usually achievable with “borderline high” free T4 as treatment target |
|
|
Radioisotopes and the Thyroid: Radioactive Iodine--
|
*Stable (non-radioactive) iodine = I-127
(53 protons, 74 neutrons) *In small doses, radioactive iodine and other isotopes make useful diagnostic tracers for imaging and iodine uptake measurement *In higher doses, therapeutic I-131 causes tissue damage: cellular inflammation and necrosis, then atrophy and fibrosis |
|
|
Range of I-131 Doses:
|
Diagnostic testing 0.1 mCi
Treatment (Graves Disease) 10 mCi Treatment (Toxic Nodule) 30 mCi Treatment (Thyroid Cancer) 100+ mCi |
|
|
Isotopes Used for Thyroid Diagnosis and Treatment:
|
*Iodine-123: short half-life (13 hours) and predominant gamma ray emission make it very useful for diagnostic imaging
*Technetium-99: similar to I-123 *Iodine-131 Long half-life (8 days) Somewhat useful for diagnosis; has some gamma ray emission Very useful for treatment b/o high energy beta particle emission *he skipped most of this slide |
|
|
Radioiodine: Potential Adverse Effects--
|
*Hypothyroidism (especially with Graves Disease)
*Lack of clinical effect (hyperthyroidism persists) *Radiation thyroiditis *Potential radiation concerns **Adverse effects during pregnancy & lactation** Infertility* Increased risk of cancer* Genetic effect on offspring* *NOT observed in adults at doses used for HYPERTHYROIDISM |
|
|
Other (Non-thionamide) Medications for Hyperthyroidism:
|
Beta-blockers
Iodine Corticosteroids Lithium carbonate |
|
|
Beta-adrenergic Blockers:
|
*Used for symptom relief and/or heart rate control (no direct effect on thyroid gland)
*Mechanisms: Inhibit peripheral T4 to T3 conversion & reduce adrenergic activity *The BETA-1 effect is important *Improve: Nitrogen balance, tremor, diapharesis, nervousness, eyelid retraction, and pulse rate *Adverse effects: Bronchospasm, other |
|
|
Iodine in treating hyperthyroid:
|
*Acutely reduces release of stored T4 and T3 -- decreases iodine uptake AND synthesis of T4, T3 (Wolff-Chaikoff Effect)
*Often used for hyperthyroid emergencies and prior to therapeutic thyroidectomy; but can’t give therapeutic I-131 for weeks after *Onset of action within hours but escape occurs after several weeks (Escape from Wolff-Chaikoff Effect) *Usually administered by mouth *Adverse effects: skin eruption, sialoadenitis, vasculitis (all rare) |
|
|
Corticosteroids and Lithium carbonate in treating hyperthyroid:
|
*Corticosteroids
Reduce T4 to T3 conversion & reduce inflammation Used in severe thyrotoxicosis, subacute thyroidits *Lithium carbonate Some iodine-like effects; beware of adverse CNS & cardiac effects An option for iodine-allergic patients *he glossed over this one* |
|
|
Treatment for Inflammatory Thyrotoxicosis:
|
*Primarily supportive therapy
Beta-blockers Anti-inflammatory agents or analgesics (ASA, NSAIDs) Corticosteroids |
|
|
Drugs that affect thyroid function or are affected by changes in thyroid function:
|
*Amiodarone: High iodine content, inhibits T4-T3 conversion; can cause thyroiditis, hypo- and hyperthyroidism
*Interferon, IL-2: May cause thyroiditis, hypo- and hyperthyroidism *Dopamine: Inhibits TSH secretion *Digoxin: Dose requirement increased by hyperthyroidism (increased excretion, decreased absorption) *Warfarin: Dose requirement decreased by hyperthyroidism ( catabolism of Vit K-dependent clotting factors) *Calcium, iron: Reduce L-T4 absorption from GI tract *he glossed over this one* |
