A 50 year old male came to the OPDwith the chief complaint of havinglump in front of the neck whichmoves with swallowing. He also haddifficulty in breathing & change inhis voice for the past 4 months. Inaddition to this physician elicit peri-orbital oedema and his ENT report &RFT was also normal…….what’s the condition??????
One of the largest endocrine, butterflyshaped organ Profoundly influence normal growth &development. Essential for mental & psychologicaldevelopment in infancy & childhood.
Bilobed structure lobus dexter (right lobe)and lobus sinister (left lobe) connected viathe isthmus. Anterior side of the neck, lying against thelarynx and trachea. Extra thyroidal tissue from thymus-pyramidallobe. Weight- 15-20 gms.
Develops from the floor of the primitivepharynx- 3rd week of gestation. With thyroglossal duct migrates from floor oftongue to the neck. Thyroid hormone synthesis – 11th week.
Thyroxine(T4)Triiodothyronine(T3)Reverse triiodothyronine(RT3) All thyroid hormones are iodine containigaminoacids. T3 is the active form. RT3 is the inactive form. Calcitonin-calcium lowering hormone.
500µg of iodine500 120Intestine4060 80bile20µg-stoolECFIˉTHYROIDLIVERKIDNEY480 µg
Iodide trapping Conversion of iodide to iodine-organification Thyroglobulin synthesis Coupling Proteolysis of thyroglobulin Secretion of thyroid hormones
Available through certain foods(eg, seafood, bread, dairy products), iodizedsalt, or dietary supplements, as a tracemineral The recommended minimum intake is 150g/day Iodized salt & iodate-preservatives in flour &bread. Soln of iodized poppy seed oil –i.m.
Other tissues accumulate iodide salivarygland,placenta,choroid plexus,gastricmucosa,ciliary body. Disease states in synthesis:congenital hypothyroidismNIS deficiency: mutation of NISgene, AR, decreased iodide uptake.
Pendred syndrome:Pendrin – apical surface of the thyroid cellsregulation of iodide inflowalso present in cochlea of middle earMutation leads to pendred syndrome.Characterized by defective organification,goiter, sensory neural deafness.
Released hormones 99.9% - T499.6% - T3binds to plasma proteins. TBG(70%T4 , 45%T3) TBPA-Transthyretin –(20%T4 ,<1%T3) TBA(10%T4,55%T3)
Physiological effects depend on free formlevel in plasma. Normal values: Total T4:4.8-10.4mg/dl(62-134nmol/L) Total T3:79-149ng/dl(1.2-2.3nmol/L) Free T4:0.7-1.86ng/dl(9-24pmol/L) Free T3:145-348pg/dl(2.2-5.4pmol/L) TSH :0.4-4µIu/L
TSH also increases blood supplyincreases the size & number of follicle-goiter. 45% of T4 is converted to T3 by 5’ deiodinaseby peripheral metabolism. Ideal to measure total & free levels ofhormone in blood for diagnosing thyroiddysfunction.
Hypothyroidism is a disorder withmultiple causes in which the thyroid failsto secrete an adequate amount ofhormone.◦ The most common thyroid disorder.◦ Usually caused by primary thyroid gland failure.◦ Also may result from diminished stimulation ofthe thyroid gland by TSH.
TSH T4 T3Hypothyroidism High Low LowHyperthyroidism Low High High
• Primary hypothyroidism– From thyroid destruction• Central or secondary hypothyroidism– From deficient TSH secretion, generally due to sellar lesionssuch as pituitary tumor or craniopharyngioma– Infrequently is congenital• Central or tertiary hypothyroidism– From deficient TSH stimulation above level of pituitary—ie, lesions of pituitary stalk or hypothalamus– Is much less common than secondary hypothyroidism
Congenital hypothyroidism◦ Agenesis of thyroid◦ Defective thyroid hormone biosynthesis due to enzymaticdefect Thyroid tissue destruction as a result of◦ Chronic autoimmune (Hashimoto) thyroiditis◦ Radiation (usually radioactive iodine treatment forthyrotoxicosis)◦ Thyroidectomy◦ Other infiltrative diseases of thyroid (eg, hemochromatosis) Drugs with antithyroid actions(eg, lithium, iodine, iodine-containingdrugs, radiographic contrast agents, interferonalpha)
Thyroxine is absorbed best in the duodenumand ileum. absorption is modified by intraluminal factorssuch as food, drugs, gastric acidity, andintestinal flora. Oral bioavailability of current preparations ofL-thyroxine averages 80%
T3 is almost completely absorbed (95%). T4 and T3 absorption appears not to beaffected by mild hypothyroidism but may beimpaired in severe myxedema. These factors are important in switchingfrom oral to parenteral therapy. Forparenteral use, the intravenous route ispreferred for both hormones.
synthetic (levothyroxine, liothyronine, liotrix animal origin (desiccated thyroid). Synthetic levothyroxine is the preparation ofchoice for replacement because,-stability,-content uniformity,-low cost,-lack of allergenic foreign protein,-easy laboratory measurement ofserum levels, and long half-life (7 days), whichpermits once-daily administration.
T3 is 4 times potent than T4 Shorter half life(24 hours) Greater risk of cardiotoxicity Best used for short term suppression of TSH. The shelf life of synthetic hormones is about2 years.
DRUG EFFECT DRUGSInhibition of TRH or TSH secretionwithout induction ofhypothyroidism orhyperthyroidism.Dopamine, levodopa,corticosteroids, somatostatin,metformin, bexarotene.Inhibition of thyroid hormonesynthesis or release with theinduction of hypothyroidism (oroccasionally hyperthyroidism).Iodides (including amiodarone),lithium, aminoglutethimide,thioamides, ethionamide.Change in thyroid hormone synthesis
Alteration of thyroid hormone transport and serumtotal T 3 and T4 levels, but usually no modification ofFT 4 or TSH.DRUG EFFECT DRUGSIncreased TBG Estrogens, tamoxifen, heroin,methadone, mitotane, fluorouracilDecreased TBG Androgens, glucocorticoidsDisplacement of T3 and T4 fromTBG with transienthyperthyroxinemiaSalicylates, fenclofenac,mefenamic acid, furosemide
DRUG EFFECTS DRUGSInduction of increased hepaticenzyme activity.Nicardipine, imatinib, proteaseinhibitors, phenytoin,carbamazepine, phenobarbital,rifampin, rifabutin.Inhibition of 5-deiodinase withdecreased T3, increased rT3.Iopanoic acid, ipodate,amiodarone, blockers,corticosteroids,propylthiouracil, flavonoids.Alteration of T 4 and T 3 metabolism with modified serum T 3and T 4 levels but not FT 4 or TSH levels
Drug effects drugsInterference with T4 absorption. Cholestyramine, chromiumpicolinate, colestipol,ciprofloxacin, proton pumpinhibitors, sucralfate, sodiumpolystyrene sulfonate, raloxifene,sevelamer hydrochloride,aluminum hydroxide, ferroussulfate, calcium carbonate, bran,soy, coffee.Induction of autoimmune thyroiddisease with hypothyroidism orhyperthyroidism.Interferon- , interleukin-2,interferon- , lithium, amiodarone.Other interactions
DRUG EFFECTS DRUGSAnticoagulation Lower doses of warfarin requiredin hyperthyroidism, higher dosesin hypothyroidism.Glucose control Increased hepatic glucoseproduction and glucoseintolerance in hyperthyroidism;impaired insulin action andglucose disposal inhypothyroidism.Cardiac drugs Higher doses of digoxin requiredin hyperthyroidism; lower doses inhypothyroidism.Effect of thyroid function on drug effects
The average dosage for an infant 1–6 months ofage is 10–15 mcg/kg/d. whereas for an adult is about 1.7 mcg/kg/d.Older adults (> 65 years of age) may require lessthyroxine for replacement. should be administered on an empty stomach. Serum TSH and free thyroxine should bemeasured.
takes 6–8 weeks after starting a given doseof thyroxine to reach steady-state levels inthe bloodstream. dosage changes should be made slowly.Reduced dosages in-Older patients,-patients with cardiac disease,For such patients 12.5-25mcg/d for 2 weeks.daily dose by 25mcg for every 2 weeks.Untilleuthyroid or drug toxicity.
In children: restlessness, insomnia, andaccelerated bone maturation and growth may besigns of thyroxine toxicity. In adults: increased nervousness, heatintolerance, episodes of palpitation andtachycardia, or unexplained weight loss may bethe presenting symptoms. Chronic overtreatment with T4 , particularly inelderly patients, can increase the risk of atrialfibrillation and accelerated osteoporosis.
MYXOEDEMA COMA:◦ Myxedema coma is an end state of untreatedhypothyroidism.◦ It is associated with progressive weakness, stupor,hypothermia, hypoventilation, hypoglycemia,hyponatremia, water intoxication, shock, anddeath.◦ Medical emergency. treat with tracheal intubationand mechanical ventilation.Associated illnessessuch as infection or heart failure must be treatedby appropriate therapy.◦ It is important to give all preparationsintravenously, because patients with myxedemacoma absorb drugs poorly from other routes.
Rx: loading dose of levothyroxineintravenously— 300–400 mcg initially,followed by 50–100 mcg daily. Intravenous hydrocortisone is indicated if thepatient has associated adrenal or pituitaryinsufficiency. Opioids and sedatives must beused with extreme caution.
Hypothyroidism & pregnancy:The daily dose of thyroxine be adequate becauseearly development of the fetal brain depends onmaternal thyroxine.In many hypothyroid patients, an increase in thethyroxine dose (about 30–50%) is required tonormalize the serum TSH level during pregnancybecause of the elevated maternal TBG.
Sub clinical hypothyroidism:
DRUG INDUCED HYPOTHYROIDISM:◦ Managed with L thyroxine if offending agent cannotbe stopped.◦ For amiodarone induced,T4 is necessary even afterthe cessation because of long half life.NON TOXIC GOITER:Enlarge thyroid due to TSH stimulation due toinadequate T4Iodide def-managed by iodide intake about 150-200 mcg
THYROID NODULE: Benign functioning nodules regress when TSH issuppressed by T4 therapy Therapy should be stopped if the nodule doesn’tdecrease in size within 6 mths and when it startsregressing.Papillary carcinoma of thyroid :responsive to TSHfull doses to T4 suppress TSH secretion