内分泌与代谢疾病nontoxic goiterPhysiological function; Synthesis of thyroid hormonesTests of thyroid function : Measurement of total serum thyroid hormone concentrationsSerum free T4 and T3 concentrationsRadioactive iodine uptakeTests of thyroid regulation: Serum thyrotropinAnatomic evaluation of the thyroid gland :The thyroid scan ,Thyroid ultrasound ,Needle biopsy Anti-thyroid antibodies : thyroid microsomal antibody (TMAb)thyroglobulin antibodies (TgAb)thyroid TSH receptor (TRAb’sThe roles of thyroid hormonesregulate tissue metabolismcentral nervous system developmentgrowth and bone maturationEtiology and pathogenesisendemic goiter：iodine deficiencySporadic goiter: diet ,drugs , heredity , immunityClinical manifestations: Simple thyroid gland intumescence，usually asymptomatic，severintumescence can cause press symptomeI: diameter<3cm II: diameter 3-5 cm III: diameter 5-7 cmIV: diameter 7-9 cm V: diameter >9cmLaboratory findingsT3、T4 、TSH normalRadioactive iodine uptake increase, but the time of peak dose not move forewardThyroid globulin increaseAntibodies to thyroid are negativePrevention and treatmentEndemic goiter prevention: iodine saltTreatment : levothyroxine; SurgeryHyperthyroidismDefinition: Syndrome that reflects the hypermetabolism resulting from excessive quantities of circulating thyroid hormonesGD: The most common form of thyrotoxicosisclinical syndrome: hypermetabolism,diffuse enlargement of the thyroid gland exophthalmos,pretibial myxedemaEtiology and pathogenesisAutoimmune disorder: TRAbGenetic inheritanceOthers factorsSymptoms and signsHypermetabolic signs : moist warm skin; tachycardia or atrial fibrillation , even (rarely) heartfailure; fine resting finger tremors, hyperreflexia.Goiter: most common, but on occasion absent, Symmetric diffusive enlargement, Move with swallow, Soft to moderate in consistency, Not pain, Commonly bruit or murmurs can be heard and/or thrill can be feltEyes: 25%-50% with exophthalmos (eye forward protruding) Mostly Simple–proptosis<18mm–Stare (Stellwag sign), “pop-eye”–Upper lid retraction leads to widening of the palpebralfissure–Lid lag (von Graefe sign), globe lag–No wrinkle when look upward (Joffroy sign)–Inward gaze or convergence is impaired (Mobius sign)Infiltrative or malignant or graves’: Proptosis>18mmSpecial manifestation: Thyrocardiac disorders(Arrhythmia,Cardiomegaly, dilation of thechambers, Cardiac insufficiency/failureThyrotoxic CrisisPretibial MyxedemaApathetic Graves’s diseaseUsually in senile personWithout/mild goiterSlight or insidious thyrotoxicosis & often go unnoticed, therefore, prone to develop crisis ?Most often present with anorexia, vomiting, diarrheaSometimes to see the cardiologist for tachycardia or arrhythmiaEasy to be suspected with malignancy because of weight loss Isolated T3 or T4 HyperthyroidismT3 hyperthyroidism–Early stage of goiter, under antithyroid therapy or simple iodine deficient goiter –Mild thyrotoxicosis–FT3 & T3↑, FT4 & T4→, TSH → /↓, RAIU →/ ↑T4 Hyperthyroidism–GD with severe systemic disorders–FT4 & T4 ↑, FT3 & T3 →/slight ↓ TSH → /↓, RAIU →/ ↑Subclinical HyperthyroidismT3 & T4 →, TSH↓Under TH treatment or during antithyroid treatmentMay lead to heart impairment or present with periodical paralysis or opthalmopathy. ?Generally need not to be treated Euthyroid Graves exophthalmos<5% Graves’ exophthalmosUnilateral or bilateralMostly infiltrativeThyrotoxicosis develops usually in several months or years Most often have thyroid dysfunction, TSH↓ or suppressed TRH stimulation Thyrotoxic Periodic ParalysisMost often occurs among oriental malesIncidence was estimated as high as 13% of men and 0.4% of women in thyrotoxicosis. ?Severity is not related to thyroid state, but the PP may be accentuated by hyperthyroidism ?Potassium intake is very effective to alleviate the symptomAntithyroid therapy is prudent in reducing the recurrenceLaboratory Examination1. Thyroid hormones: Total T4 (T T4 ) and T3（T T3 ）, Free T4（FT4 ）and Free T3 （FT3）Thyrotropin (Thyroid-Stimulating Hormone, TSH ) decrease2.3.TSH receptor antibodies (TRAb): Untreated 80%-100% positive, Early diagnosis,Activity, RelapseTPOAb and TGAb: 50%~90% positive4.Anatomic evaluation of the thyroid gland5. BiopsyDiagnosis: Typical s/s and lab test—easy to makeNotice atypical, transient and tumor—biopsy and imaging is helpful DifferentialPsychosis diseaseanxiety neurosis or mania : the thyroid is not enlarged and thyroid functiontests are usually normal.acute psychiatric disorders : about 30% of whom have hyperthyroxinemiawithout thyrotoxicosis. The TSH is notsuppressed, distinguishing psychiatric disorderfrom true hyperthyroidism. T4 levels return tonormal gradually.Simple goiterPheochromocytoma: this is an adrenal coma,often associated with hypermeta-bolitism, the function of thyroid is normalOthers: weight loss—malignancy, diarrhea—inflammatory bowel disease,arrhythmia—CHD, ophthalmopathy—orbital tumor, etc.Treatment1.General MeasuresEnough rest, sufficient nutrition, esp. calories, protein, lipid and sugarNo need replenish iodine, use salt withoutSedatives maybe helpful for psychosis, sleepless2.Antithyroid agents or ThionamidesCLASSES: Thiouracils, Mazols3. PharmacologyInhibit the synthesis of TH by inhibiting the organification of iodinemethimazole and propylthiouracil PTUβ-Adrenergic blocking agents Iodinated contrast agentsFactors favoring long term remission after antithyroid therapySymptoms and signs of hyperthyroidism disappearDecrease in goiter size during therapyNormal thyroid functionNormal TRH stimulation testNormal or positive to negative TRAbrelapse within 3 months, ? in 6months4.Radioactive iodine (131I)Indications Most patients may receive radioiodineContraindications pregnant women, Thyrotoxic Crisis, Ophthalmopathy,Leucocyte <3×109/LDrawbacks hypothyroidism , ophthalmopathy5. Surgerypregnant woman whose thyrotoxicosis is not controlled with low doses of thioureaspatients with particularly large goitersPatients with a significant chance of malignancyContraindicationsSevere or progressive infiltrative ophthalmopathy–Patients with severe heart, hepatic, lunch or kidney disease –Pregnant（<3months）and（>6 months）preparationThiourea drug and Propranolol are givenHeart rate <80/minTH normalIpodate sodium or iopanoic acid or iodine is used 7-10 days before operation ?Drawback–damage to the recurrent laryngeal nerve–Hypoparathyroidism–Infection–Thyroid strom–Hypothyroidism–Aggravation of exophthalmosChoice of TherapyMedical treatment: Effective and safe, but need long term therapy and monitoringof thyroid function and hematology. Sometime leads to hepaticnecrosis or toxic hepatitis and many othersSurgery–Fast control and effective, but mortality rate 1.3%–30% relapse–Many complicationsRadioiodine–effective and generally safe Generally no relapse–High rate of hypothyroidism, Radiothyroiditis, aggravation ofexophthalmosManagement of Thyroid CrisisInhibition of TH synthesis: PTUInhibition of TH release: Iodine, 1-2hrs post PTUI of conversion of T4 to T3 and binding of T3 to its receptor: prednisoneand -adrenergic antagonist ?Increase the response to stressing: HydrocortisoneDecrease the TH in circulation: dialysisSupportive: fluid volume and electrolytesPalliative: fever and oxygenResume of standardized antithyroid therapyManagement of infiltrative exophthalmosPalliative therapyAntithyroid therapy when hyperfunction existsLT4 replacement may be effective by suppressionof TSH elevation ?Immunosuppression and/or modulationRetro-orbital steroid injection or radiationOrbital depressionRadiotherapy with linear accelerator (59% in 624 patients during 1973-2000) Treatment of hyperthyroidism during pregnancyNo need to stop pregnancyMedical therapy is preferredLower dose and PTU is of choicePropanolol is not recommendedSubtotal thyroidectomy is unsuitable during pregnancy,if must,chose midterm (4th-6th m)Hypothyroidism and MyxedemaDefinition:refers to any state in which thyroid hormone production , secretion or activity is below normalThree types: 呆小型，幼年型，成年型CretinismPathology; Hashimoto thyroiditis, Hypo-pituitarismClinical manifestationsEarly symptoms: weakness, fatigue, cold intolerance, constipation, joint ormuscle pain. Features may include thin, brittle finger-nails, thin and brittle hair, and paleness.Late stage: slow speech, dry flaky skin, absence of sweating, thickening of theskin, puffy face, feet, peripheral edema, decreased taste and smell,thinning of eyebrows, hoarseness, the heart rate is slow,hypothermia may be present. and abnormal menstrual periods mayoccur.The condition may progress into hypothermic, stuporous state (myxedema coma)with respiratory depressionSubclinical hypothyroidism is state of normal thyroid hormone levels and mildelevation of TSH, despite the name, some patients may have minor symptoms.Laboratory findings1. T3、T4 、TSH2. TRH excited test3. Others４. Imagine studiesDiagnosis and differential dignosisClinical manifestations: symptoms and signsLaboratory test: T4 TSH antibodies against TPO and TGTreatmentLevothyroxine ( thyroxine; T4)Routine initiation of treatmentMaintenanceTreatment myxedema coma1. Levothyroxine sodium 100-300ug is given intravenously asa loading dose,followed by 50 ug intravenously daily.2.Keep warmed only with blankets3.Anti-infection4.Hydrocortisone must be used intravenously in patients suspected of havingconcomitant adrenal insufficiency.Special hypothyroidism1.Subclinical hypothyroidism2.Over dosage of anti-thyroid drugs3.Hypothyroidism with pregnancyCushing syndromeDefine: manifestations of excessive corticosteroidsdue to supraphysiologic doses of glucocorticoid drugs and spontaneous production of excessive corticosteroids by the adrenal cortexClinical presentationsLipid Metabolism :Central obesity ( protuberant abdomen, thin extremitie)moon face buffalo hump supraclavicular fat padsProtein metabolism: Purple striae Petechia Muscular weaknessOsteoporosis Growth delayGlucose metabolism: Impaired glucose tolerance even to diabetesElectrolyte metabolism: HypokalemiaCardiovascular system: hypertension 、heart failureSport system: OsteoporosisImmunologic system: inhibitated immuneNerve system: From diminished ability to concentrate to increased lability of mood to frank psyc procreation system: female：Oligomenorrhea or amenorrheamale：impotence in the maledigestive system: polyphagiaHematic systempossible causeAdrenal gland:hypothalamus-pituitary:Non-pituitary neoplasms:Cushing diseaseEctopic ACTH syndromeLaboratory Findings一. The serum and urine cortisol and its rhythm二.hypothalamus-pituitary-adrenal axis functionThe small-dose dexamethasone inhibitory testThe large-dose dexamethasone inhibitory test三.Serum ACTH四. Ultrasound, MRI and CT scan, isotopic scanDiagnosis1.function diagnosis —— yes or not Cushing syndrome2. position diagnosis——pituitary、adrenal3.Etiologic diagnosis—adenoma hyperplasia cancer附诊断流程图临床和实验室检查：低血钾性碱中毒，女性男性化表现，皮肤色素沉着24h尿17-KS(17-ketosteroid)增多异位ACTH综合征，肾上腺皮质癌Differential DiagnosisObesity&Type 2 diabetes：皮质醇节律正常，小剂量地塞米松可抑制Artificial Cushing Syndrome：见于酗酒兼有肝损害者，血、尿皮质醇增高，不能被小剂量地塞米松抑制，戒酒一周后，血尿皮质醇恢复正常Depressed patients：实验室检查有异常，如24小时尿游离皮质醇、17-羟、17酮可增高无Cushing综合征临床表现。