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  2. Evaluating Hoarseness: Keeping Your Patient's Voice Healthy - June 1998 - American Academy of Family Physicians;
  3. Age group • Infants (0 -11mth) • Children (12 mnth - 59 mnth) • School age child (6-12 year) • Adults (above 12 year) • Pregnant & lactating women Iodine requirement(μg) 50 90 120 150 200 WHO/UNICEF Recommended daily iodine
  4. • Iodine essential for thyroid hormone • Adult hypothyroidism and cretinism occurs in severe iodine deficiency • Daily adult require 1 to 2 μg / Kg / day. • Iodine used for iodine-deficiency goiter • Iodine or iodate added to salt (iodized salt) 100 μg of iodine per gram Relation of Iodine to Thyroid Function
  5. Growth and development • Normal growth and development of organism • DNA transcription, critical control of protein synthesis and translation of genetic code • Brain development • Irreversible mental retardation (cretinism) in absence of thyroid hormones during active neurogenesis (upto 6 month postpartum) - Severe morphological alteration in brain -Supplementation during first 2 weeks of life prevent development of brain changes Functions of Tyhroid Hormones
  6. Metabolism: • Lipid: Induce lipolysis (catecholamines), ↑ free plasma fatty acid and all phases of cholesterol metabolism enhanced (bile acid more) - Hyperthyroidism – hypercholesterolemia • Carbohydrate: Stimulation of carbohydrate metabolism, glycogenolysis, gluconeogenesis - Hyperthyroidism – diabetes-like state • Protein: Certain protein synthesis increased but overall catabolic action – negative nitrogen balance - Hyperthyroidism – Weight loss and wasting Functions of Tyhroid Hormones
  7. Calorigenic & CVS(Cardio Vascular System) Effects • T3 and T4 increases basal metabolic rate (BMR) by stimulation of cellular metabolism – maintenance of body temperature • Hyperdynamic state of circulation - due to direct CVS action and ↑ peripheral demand o Hyperthyroidism: tachycardia, ↑ Total Periferic Resistance(TPR) o Hypothyrodism: bradycardia, ↓ cardic index, ↓ TPR Others: • Nervous system – mental retardation • GIT – Increased gut motility Functions of Tyhroid Hormones
  8. 16 Mechanism of actions of thyroid hormones T3, via its nuclear receptor, induces new proteins generation
  9. Differences between T3 and T4 T3 T4 Four time more potent thanT4 Less potent Peak effect reaches with in 24-48hrs. Peak effect reaches in 6-8 hrs Plasma protein binding capacity isless It bind more tightly to plasmaproteins It is active in vitro It is inactive invitro Thyroid gland produce 20%of T3 Thyroid gland produces 80%of T4 T3is the active form T4 is less active than T3 18
  10. • Normal range: • T4: 77- 155nmol/l • T3 : 1.2- 2.8nmol/l • TSH: 0.3- 4mU/L • The levels of hormones above or below indicate hyperthyroidism or hypothyroidism.
  11. Definition andEpidemiology • Hypothyroidism is traditionally defined as deficient thyroidal production of thyroid hormone • Prevalence of overt hypothyroidism varies from 0.1 to 2 percent. • Hypothyroidism is five to eight times more common in women than men. © AACE. All Rights Reserved.
  12. Manifestations ofHypothyroidism © AACE. All Rights • Common symptoms: fatigue,cold intolerance,weightgain, constipation, dry skin,myalgia,andmenstrualirregularities • Physical examination: goiter ,bradycardia, diastolic hypertension, andadelayed relaxation phaseof thedeep tendon reflexes • Metabolic abnormalities: hypercholesterolemia, macrocytic anemia,elevatedcreatine kinase,andhyponatremia
  13. TSH (2)  T4 & T3 are feed-back regulators of TSH  TSH is stimulated by a-adrenergic agonists  TSH secretion is inhibited by: Dopamine Bromocreptine Somatostatin Corticosteroids
  14. THYROID HORMONES (3)  Conversion of T4 to T3 is decreased by: Acute & chronic illnesses b-adrenergic receptor blockers Starvation & severe PEM Corticosteroids Propylthiouracil High iodine intake (Wolff-Chaikoff effect)
  15. THYROXINE (2)  Total T4 is decreased when the following drugs are used: Steroids Phenytoin Salicylates Sulfonamides Testosterone Maternal TBII
  16. THYROXINE (3)  Total T4 is increased with: Acute thyroiditis Acute hepatitis Estrogen therapy Clofibrate iodides Pregnancy Maternal TSI
  17. GOITROGENS •DRUGS Anti-thyroid Cough medicines Sulfonamides Lithium Phenylbutazone PAS Oral hypoglycemic agents
  18. GOITROGENS  FOOD Soybeans Millet Cassava Cabbage
  19. Hypothyroidism definition: Thyroid gland does not produce enough hormones ● affect People who are most at risk include those over age 50 & mainly in females ● Diagnosed by low plasma levels of T3 & T4 and TSH causes: congenit al in children, hypothyroidism leads to delay in growth (dwarfism),and intellectual development (cretinism) Primar y Iodine deficiency is the most common cause of primary hypothyroidism and endemic goiter worldwide Autoimmune; Hashimoto’s thyroiditis Radioactive iodine treatment of hyperthyroidism Post thyroidectomy Anti-thyroid drugs (CMZ , PTU) Other drugs(lithium, amioderone) Sub-acute thyroiditis Thyroid carcinoma Inadequat e function of the gland itself seconda ry Hupothalamic and pitutary diseases
  20. mind map before starting, please check our endocrine block correction
  21. 23 Thyroid drugs • Levothyroxine sodium: The synthetic Na salt of levo (L) isomer of thyroxine (T4) • Liothyronine (T3) • Liotrix (T4 plus T3) Pharmacokinetics Orally easily absorbed; the bioavalibility of T4 is 80%, and T3 is 95%. Drugs that induce hepatic microsomal enzymes (e.g., rifampin, phenbarbital, phenytoin, and etc) improve their metabolism.
  22. treatment of hypothyroidism: Thyroid preparation Levothyroxine (T4) Liothyronine (T3) Liotex (mix T4 and T3) Pharmacokinatic s ● A synthetic form of the thyroxine (T4) , is the drug of choice for replacement therapy. ● Stable and has a long half life ( 7 days). ● Administered once daily. ● Restores normal thyroid levels within 2-3 weeks. ● Absorption is increased when hormone is given on empty stomac h.● Oral preparations available from 0.025 to 0.3 mg tablets. ● Parnteral preparation 200- 500μ. ★ in old patient and patient with any cardiac problems, start with reduced (12.5 – 25 μg/day) for two weeks and then increased every ● More potent (3-4 times) and rapid action than levothyroxine . ● has a short half life, not recommended for routine replacement therapy (because it’s given multiple daily doses). ● oral preparation available. ● parenteral use. (used in life threatening cases) ● Combination of synthetic T4 & T3 in a ratio 4:1 that attempt to mimic the natural hormonal secretion . ● The major limitations of this product are high cost and lack of therapeutic rationale because 35% of T4 is peripherally converted to T3, so the drug is under the study yet.
  23. Levothyroxine (T4) Liothyronine (T3) Liotex (mix T4 and T3) Clinical use Any Hypothyroidism case ,regardless of etiology ( including Congenital ,Hashimoto thyroiditis , Pregnancy and Thyroid carcinoma ) . - - ADR Overdose in children:- restlessness , insomnia and accelerated bone maturation Over dose in adult :- -cardiac arrhythmias (Tachycardia, atrial fib.) - tremor , restlessness ,headache -heat intolerance -muscle pain -change in appetite, weight loss Should be avoided in cardiac patient -
  24. Levothyroxine sodium (T4) Use: thyroid replacement and suppression therapy. Advantages: -high stability -uniform -low cost -lack of allergenic foreign protein -easy laboratory measurement of serum levels -long half-life -7 days (once-daily administration) -In addition, T4 is converted to T3 intracellularly; thus, administration of T4 produces both hormones.
  25. LEVOTHYROXINE : • Individualize the dosage and adjust based upon the factors including patient age, body weight, cardiovascular status, concomitant medical conditions (including pregnancy ). • Primary hypothyroidism in adults who have been hypothyroid for a short time – initially , give full thyroid replacement dose – 1.6mcg/kg PO/ OD • Adjust dose by 12.5 – 25mcg increments every 4 – 8 weeks until patient is clinically euthyroid and TSH is normal. • Doses >200 and 300mcg/day are rarely needed. • Severe longlasting Hypothyroidism : • initial dose – 12.5 – 25mcg PO/OD ; adjust in 11.5- 25mcg increments every 2-4 weeks. • Hospitalized , not critically ill when enteral administration is not feasible, 75%of the oral dose given IV.
  26. Liothyronine (T3) is 3 to 4 times more potentthan levothyroxine. • Use: short-term suppression of TSH. • Disadv: - Shorter half-life -24 hours (not recommended for routine replacement therapy which requires multiple daily doses) - Higher cost - Difficulty of monitoring. - Its greater hormone activity and consequent greater risk of cardiotoxicity- avoided in patients with cardiac disease.
  27. Liotrix - Mixture of thyroxine and liothyronine - Expensive Clinical use • Hypothyroidism: cretinism & myxedema • Cretinism: Decrease in the levels of thyroid hormone in infants or during foetal stage is known as cretinism • Myxedema: a condition in which hypothyroidism results in accumulation of mucopolysaccharide in the intercellular spaces of muscle and skin Adverse reactions • Overmuch leads to thyrotoxicosis • Angina or myocardial infarction usually appears in aged
  28. Conditions RequiringDoseAdjustment © AACE. All Rights Increased doserequirement 1 . Decreased intestinal absorption of T4 • Dietary fibersupplements •Reducedgastric acid secretion:H.pylori infection, atrophic gastritis,proton-pump inhibitors •Malabsorption: coeliac disease, short bowel syndrome,lactose intolerance, bariatricsurgery • Bile-acid sequestrants •Agentsthatbind L -T4:sucralfate, aluminumhydroxide, ferrous sulfate, calcium carbonate,sevelamer
  29. Conditions RequiringDoseAdjustment © AACE. All Rights Increased doserequirement 2.Increased need for T4 • Weightgain • Estrogens • Pregnancy 3.Increased metabolic clearance of T4 •Antiepileptic drugs(phenobarbital, phenytoin,carbamazepine) • Tuberculostatic drugs(rifampicin)
  30. Conditions RequiringDoseAdjustment © AACE. All Rights Decreased doserequirement 1 .Decreased need for T4 • Weightloss • Androgens 2.Decreased metabolic clearance of T4 • Old age
  31. CentralHypothyroidism © AACE. All Rights • Decreased thyroidal secretion of hormonecaused by insufficient stimulationof thyroid glandby TSH. • Pituitary TSHrelease (secondary hypothyroidism) • Hypothalamic TRHrelease (tertiaryhypothyroidism) • Characterizedby Low T4concentration/TSHnot appropriately elevated • Central hypothyroidism less common than primary hypothyroidism
  32. CentralHypothyroidism © AACE. All Rights • Shouldbe suspected inthefollowing circumstances: • Thereis knownhypothalamic orpituitary disease • A masslesion is present inthepituitary • When symptoms/signsof hypothyroidism associated withpituitary hormonaldeficiencies • Goal of replacement therapyis to Titrate FT4/FT3to mid-upper normal. • TSHnotmonitored asit is unreliable.
  33. MyxedemaComa © AACE. All Rights • Myxedema comarepresentsdecompensated stateof severeuntreated hypothyroidism. • The prognosis is poor withareported mortality between 20%and50%. • Triad of hypothermia, hyponatremia, and hypercapnia. • Commonprecipitating factors include cold exposure,infection, trauma, oranesthesia.
  34. MyxedemaComa © AACE. All Rights • Physical manifestations include hypotension, bradycardia, macroglossia,delayed deep-tendon reflexes. cold, clammy,anddryskin, nonpitting edema,andperiorbital edema. • Laboratory examination mayreveal anemia, hyponatremia, hypoglycemia, hypercholesterolemia, andhighserumcreatine kinase concentrations. • Most patients havelow serumFT4andhighserumTSH.
  35. MANAGEMENT OF MYXEDEMA COMA Hypothyroidism Largeinitialivdose of 300-500μgT4,if noresponse add T3 Alternative-initialIVdose of 200-300μg T4plus10-25μg T3 Hypocortisolemia IV hydrocortisone200-400 mgdaily Hypoventilation Don’tdelayintubation andmechanical ventilationtoo long Hypothermia Blankets,noactiverewarming Hyponatremia Mild fluidrestriction Hypotension Cautiousvolumeexpansionwithcrystalloid orwholeblood Hypoglycemia Glucoseadministration Precipitatingevent Identificationandeliminationby specific treatment,liberal useof antibiotics © AACE. All Rights MyxedemaComa
  36. MyxedemaComa © AACE. All Rights Therapeutic endpoints inMyxedemacomashould be: • Improved mentalstatus • Improved cardiacfunction • Improved pulmonaryfunction Measurement of thyroid hormonesevery1-2daysto ensureafavorable trajectory inthebiochemical parameters.
  37. • MYXEDEMA COMA: • Initial dose – 300 – 500mcg IV once ;F/B maintenance dose of 50 -100mcg IV/OD until patient can tolerate oral therapy. • Liothyronine – loading dose of 5- 20mcg IV f/b maintenance dose 2.5 – 10mcg IV every 8 hrs. • Thyroid stimulating hormone suppression therapy , pituitary- doses > 2mcg/kg/day /PO are usually required to suppress TSH below 0.1milli international units/L. • PEDIATRIC DOSING: • 0-3 months : 10 – 15mcg /kg/day po ( solution, tab) • 3- 6 months : 8- 10mcg/kg/day po. • 6- 12 months:6- 8 mcg /kg/day po • 1 – 5 yrs : 5-6 mcg /kg/day po • 6 – 12 yrs : 4 – 5mcg/kg/day po ( capsule, solution, tab) • Older than 12 yrs : 1.6mcg/kg/day po
  38. • As soon as pregnancy is confirmed add 2 additional doses per week of the current dose given as 1 extra dose twice weekly with several days increase. • If TSH is above normal range increase the dose by 12.5 to 25mcg daily and measure TSH every 4 weeks until stable. • Pregnant women with new onset of hypothyroidism- • Normalize thyroid function as rapidly possible intiate 1mcg/kg ( mild hypothyroidism TSH less than 10milli international units/L) to 1.6mcg/kg ( moderate to severe) if greater than 10MIU/L. .
  39. • GERIATRIC: • Initial dose( <1.6mcg/kg/day), consider 12.5 – 25mcg PO/OD, adjust dose every 6-8 weeks.( normal TSH ranges are higher in older populations ) • Underlying cardiac disease or at risk for atrial fibrillation : initiate orally at a lower starting dose ( <1.6mcg/kg/day) , consider 12.5- 25mcg PO/OD adjust dose to every 6-8 weeks. • Large body weight change: adjust dosage based on thyrotropin, and assess thyrotropin 4-6 weeks after dosage change.
  40. LIOTHYRONINE: • Initial dose – 25mcg PO/ OD, increase by 25mcg /day every 1- 2 weeks; maintenance dose : 25- 75mcg od. • Myxedema coma : 25- 50mcg IV . • Patients with h/o of coronary artery disease or arrythmias – loading dose , 5 -20mcg IV f/b 2.5- 10mcg IV every 8 hrs. • Pediatrics: • Initial dose- 5mcg po od ; infants to few months older may require 20mcg/day; pts 1 yr or older may require 50mcg/day , children older than 3 yrs to adult dose 25-75mcg/day. • Geriatrics: • Initiate 5mcg OD and increase by 5mcg increments every 1- 2 weeks if neded.
  41. PROPYLTHIOURACIL • ADULTS: • Initial dose 50- 150mg PO TID , based on severity or 300mg PO daily in 3 evenly divided doses at 8 hr intervals. • May increase to 400mg/day for severe hyperthyroidism, very large goiters, or both; 600- 800mg/day (occasionally). • Maintenance dose- 50mg PO 2-3 times daily or 100-150 mg PO TID every 8 hrs. • Preganacy- Thyrotoxicosis due to graves disease: • Use lowest dose to keep mothers total T3 and T4 levels slightly above normal range for pregnancy, keep TSH suppressed , assess monthly and adjust dose as required. • Switch to methimazole for 2nd and 3rd trimesters. • THYROID STORM: • 500-1000MG –loading dose PO F/B 250mg PO every 4 hours. • Pediatric dosing: • Initial (6yr or older) : 50mg PO daily carefully uptitrated.
  42. METHIMAZOLE: • Initial dose: mild- 15mg/day PO TID at 8hr intervals. • Moderately severe condition: initial dose 30- 40mg/day PO TID -8hr intervals. • Severe : initial dose 60mg/day PO TID -8hr intervals. • Maintenance 5-15mg/day TID – 8hr intervals. • Radioactive iodine therapy: discontinue methimazole 2-3 days prior to RAI and consider resuming 3-7 days after RAI administration in patients who are at increased risk of complications a/w worsening of hyperthyroidism. • Thyroidectomy: treat until euthyroid and discontinue at the time of surgery. • Thyroid storm: 60-80mg/kg PO • Thyrotoxicosis, drug induced: • Amiodarone induced- initially 40mg PO OD until the pt is euthyroid, generally 3-6 months. • Iodine induced- 20-40mg PO as a single or divided doses.
  43. • Pediatric dosing: • Initial- 0.4mg/kg/day PO TID – 8 hrs intervals; maintenance dose approx. 50% of initial dosage. • infants: 1.25mg/day; 1-5yrs : 2.5- 5mg/day; 5-10yrs: 5-10mg/day;10- 18yrs : 10-20mg/day.
  44. RADIOACTIVE IODINE ( RAI ) MOA Accumulates in the thyroid gland and destroys parenchymal cells, producing a long- term decrease in thyroid hormone levels. Pharmacokinetic • Clinical improvement may take 2-3 months • Half -life 5 days • Cross placenta & excreted in breast milk • Easy to administer ,effective , painless and less expensive • Available as a solution or in capsules clinical uses • Hyperthyroidism mainly in old patients (above 40) • Graves, disease • Patients with toxic nodular goiter • As a diagnostic Disadvantages • High incidence of delayed hypothyroidism • Large doses have cytotoxic actions ( necrosis of the follicular cells followed by fibrosis ) • May cause genetic damage
  45. IODINE (Lugol's solution, potassium iodide) Eamples •Organic iodides as : iopanoic acid or ipodate •Potassium iodide Mechanism of action •Inhibit thyroid hormone synthesis and release •Block the peripheral conversion of T4 to T3 •The effect is not sustained ( produce a temporary remission of symptoms ) Therapeutic uses & size of the gland • Prior to thyroid surgery to decrease vascularity •Following radio-active iodine therapy •Thyrotoxicosis Precautions / toxicity - Iodism Symptoms: skin rash , hypersalivation •Should not be used as a single therapy •Should not be used in pregnancy •May produce iodism ( Rare, as iodine is not much used now) oral ulcers bad breath.
  46. ADRENOCEPTOR BLOCKING AGENTS Mechanism ofaction Adjunctive therapy to relief the adrenergic symptoms of hyperthyroidism such as tremor, palpitation, heat intolerance and nervousness. Examples Propranolol, Atenolol , Metoprolol contraindication Propranolol is contraindicated in asthmatic patients Thyrotoxicosis during pregnancy: Better to start therapy before pregnancy with 131I or subtotal thyroidectomy to avoid acute exacerbation during pregnancy During pregnancy radioiodine is contraindicated, Propylthiouracil is the drug of choice during pregnancy. pregnanc y
  47. ★ Thyroid storm: ● A sudden acute exacerbation of all of the symptoms of thyrotoxicosis, presenting as a life threatening syndrome. ● There is hyper metabolism, and excessive adrenergic activity, death may occur due to heart failure and shock. ● It is a medical emergency . ★ management ofthyroid storm: ● should be treated in an ICU for close monitoring of vital signs and for access to invasive monitoring and inotropic support ● Correct electrolyte abnormalities, Treat cardiac arrhythmia ( if present ) & Aggressively control hyperthermia by applying ice packs ● Promptly administer antiadrenergic drugs (e.g. propranolol) 1-2mg to minimize sympathomimetic symptoms and if not controlled tachycardia add diltiazem 60-120mg twice a day orally. ● High-dose Propylthiouracil 200-300mg 6th hourly (PTU) is preferred because of its early onset of action ( risk of severe liver injury and acute liver failure ) ● Administer iodine compounds (Lugol's iodine or potassium iodide) 6-10 dropsorally or via a nasogastric tube ● Hydrocortisone 50 mg IV every 6 hours to prevent shock. ● Rarely, plasmapheresis has been used to treat thyroid storm
  48. Management of Hyperthyroidism due to Graves’ disease Severe Hyperthyroidism [ markedly elevated serum T4 or T3 very large goiter, > 4 times normal ] Definitive therapy with radioiodine preferred in adults Normalization of thyroid function with anti-thyroid drugs before surgery in elderly patients and those with heart disease Mild/moderate hyperthyroidism [ small or moderately enlarged thyroid; children or pregnant or lactating women ] Primary anti-thyroid drug therapy should be considered Start methimazole, 5–30 mg/day, (PTU preferred in pregnant women) Monitor thyroid function every 4–6 wk until euthyroid state achieved Discontinue drug therapy after 12–18 mo Monitor thyroid function every 2 mo for 6 mo then less frequently Relapse Remission Monitor thyroid function every 12 mo indefinitely Definitive radioiodine therapy in adults (Second course of anti-thyroid drug therapy in children)