Hyperthyroidism and Thyroid StormTintinalli Chapter 21512/15/05

Prepared by Trent W. SmithLecture by Dr. Klien MD

Normal Thyroid StateSynthesis and release of thyroid hormone is controlled by TSH relaesed form the anterior pituitaryTSH is controlled by the release of thyroid releasing hormone (TRH) from the hypothalmus and a negative feedback loop to the pituitaryThyroid hormone production s dependent on adequate adequate iodine intake

Normal Thyroid StateThyroid hormone is reversible bound to various proteins including thyronine-binding globulin (TBG)Free unbound portions are biologically activeT4 is the predominant circulating hormoneT4 is deiodinated to t3T3 is biologically more active than T4 but has a shorter half-life

HyperthyroidismOccurs in in all ages Uncommon under the age of 1510 xs more common in women (1/10,000)Graves disease is the most common etiology80% of cases in the U.S.Common in the 3rd and 4th decadesCaused by autoimmune thyroid-stimulating antibodiesAssociated with diffuse goiter, opthalmopathy, and local dermopathy

HyperthyroidismToxic multinodular and toxic nodular goiters are the next most common etiologiesUsually occurs in older populationsCommonly with previous history of goiter Often with milder symptoms of thyrotoxicosis

HyperthyroidismAmiodarone-induced thyrotoxicosis (AIT)Amiodarone is iodine rich and may cause both hyper and hypothyroidismDifficult to treat because of incomplete understanding of mechanismTwo major forms exists Type 1 occurs with a normal thyroidType 2 occurs with a abnormal thyroidTx. Varies based on the the type

HyperthyroidismHyperthyroidism resembles a state of increased adrenergic activity despite a normal or low serum cortisol levelClassic complaints include heat intolerance, palpitations, weight loss, sweating, nervousness, and fatigue

Hyperthyroidism

HyperthyroidismConfirmed by thyroid function testElevated free T4 and Low TSHIn some cases of graves disease T4 may be normal and TSH decreased but the patient appears thyrotoxicT3 level should be done to rule out T3 toxicosisHypothyroidism secondary to pituitary adenoma will have elevated TSH levels

HyperthyroidismTreatmentPalliative treatment of mild hyperthyroidism is accomplished using B-blockersMost commonly used is propanololTreatment of Graves diseases include long-term use of antithyroid medications, radioactive iodine, or subtotal thyroidectomyType I AIT is treated with methimazole and potassium perchlorateType II AIT is treated with glucocorticoids

HyperthyroidismTreatment cont.Toxic multinodular goiter and solitary adenomas may be treated with radioiodine therapyThryoiditis is usually self limited and therapy is rarely needed

Thyroid StormA life threatening hypremetabolic state due to hyperthyroidismMortality rate is high (10-75%) despite treatmentUsually occurs as a result of previously unrecognized or poorly treated hyperthyroidismThyroid hormone levels do not help to differentiate between uncomplicated hyperthyroidism and thyroid storm

Thyroid StormPreciptatnts of Thyroid Storm (tabel 215-4)

InfectionTraumaDKAMICVAPESurgeryWithdrawal of thyroid medIodine administrationPalpation of thyroid glandIngestion of thyroid hormoneUnknown etiology (20-25%)

Thyroid StormClinical featuresThe most common signs are fever, tachycardia out of proportion to the fever, altered mental status, and diaphoresisClues include a history of hyperthyroidism, exophthalmoses, widened pulse pressure and a palpable goiterPatients may present with signs of CHF

Thyroid StormClinical features cont.Common GI symptoms include diarrhea and hyperdeficationApathetic thyrotoxicosis is a distinct presentation seen in the elderlyCharacteristic symptoms include lethargy, slowed mentation, and apathetic faciesGoiter, weight loss , and proximal muscle weakness also present

Thyroid StormDiagnosisThyroid storm is a clinical diagnosis based upon suspicion and treated empiricallyLab work is non specific and may include Leukocytosis, hyperglycemia, elevated transaminase and elevated bilirubin

Thyroid StormTreatmentInitial stabilization includes airway protection, oxygenation, fluids and cardiac monitoringTreatment can then be divided into 5 areas: General supportive careInhibition of thyroid hormone synthesisRetardation of thyroid hormone releaseBlockade of peripheral thyroid hormone effectsIdentification and treatment of precipitating events

Thyroid StormDrug Treatment of Thyroid Storm (table 216-6)Decrease de novo synthesis:Porpythiouracil600-1000mg PO initially, followed by 200-250 mg q 4 hrsMethimazole40 mg PO initial dose, then 25 mg PO q6hPrevent relases of hormone (after synthesis blockade intiated)IodineIaponoric acid (Telepaque) 1 gm IV q8h for the first 24 h, then 500 mg bid or Potassium iodide (SSKI) 5 drops PO q6h or Lugol solution 8-10 drops PO q6hLithuim 800-1200 mg PO every dayPrevent peripheral effects:B-BlockerPropanolol (IV) titrate 1-2 mg q 5min prn (may need 240-480mg PO q day) or Esmolol (IV) 500 mcg/kg IV bolus, then 50-200 mcg/kg per min maintenanceGuanethidine30-40 mg PO q 6 hReserpine 2.5-5 mg IM q4-6hOther consideration:CorticosteroidsHydrocortisone 100 mg IV q 8 h or dexamethosone 2 mg IV q 6 hrAntipyreticsCooling blanket acteaminophen 650 mg PO q 4-6h

Thyroid StormTreatment contPropranolol has the additional effects or blocking perpheral conversion of T4-T3Avoid Salicylates because it may displace T4 from TBGIf the patient continues to deteriorate despite appropriate therapy circulating thyroid hormone may be removed by plasma transfusion, plasmapheresis, charchoal plasmaperfusionRemember you must not administer iodine until the synthetic pathway has been blocked

Thyroid StormDispositionAdmit to the ICU

Hypothyroidism and Myxedeam ComaTintinalli Chapter 21512/15/05

Prepared by Trent W. SmithLecture by Dr. Klien MD

HypothyroidismOccurs when there is insufficient hormone production or secretionOccurs more frequently in women (0.6 to 5.9 %)The most common etiologies arePrimary thyroid failure due to autoimmune diseases (Hashimoto thyroiditis is the most common)Idiopathic causesAblative therapyIodine deficiencyMay be transientPathophysiology is unclear but may be viral in nature

HypothyroidismEtiologies of Hypothyroidism PrimaryAutoimmune etiologies Hashimotos is the most commonIdopathicPost ablation (surgical, radioiodine)Post external radiationThryoiditis (subacute, silent, postpartum) Postpartum thyroiditis occurs within 3-6 months and occurs in 2- 16 % of womenSelf limited etiologies, often prededed by hyperthroid phaseInfiltrative disease (lymphoma, sarcoid, amyloidosis, TuberculosisCongenital

HypothyroidismEtiologies of HypothyroidismPost PartumOccurs 3-6 months post partum and occurs in 2-16% of womenSecondary (pituitary)NeoplasmInfiltrative Dz.HemorrhageTertiary (hypothalamic)NeoplasmInfiltrative Dz.

HypothyroidismEtiologies of Hypothyroidism DrugsAmiodaroneOccurs in 1-32% of patientsMost likely due to the large amount of iodine released in the metabolism of the drug which inhibits thyroid hormone synthesis, release, and conversion of T4 to T3LithiumActs similarly to iodine and inhibit thyroid hormone releaseIodine (in patients with pre-existing autoimmune disease)Antithyroid medication

HypothyroidismClinical FeaturesThe typical symptoms of hypothyroidism include fatigue, weakness, cold intolerance, constipation, weight gain, and deepening of voice.Cautaneous signs include dry, scaly, yellow skin, non-pitting, waxy edema of the face and extremities (myxedema): and thinning eyebrows

HypothyroidismClinical Features cont.Cardiac findings include bradycardia, enlarged heart, and low-voltage electrocardiogramParesthesia, ataxia, and prolongation or DTRs are characteristic neurologic findingsSee table below for more complete list

HypothyroidismSymptoms and Signs or Hypothyroidism (table 216-2)

SymptomsSignsFatigueHoarsenessWeight GainHypothermiaCold intolerancePeriobital puffinessDepressionDelayed relaxation of ankle jerksMenstrual irregularitiesLoss of outer third of eyebrowConstipationCool, rough, dry skinJoint PainNonpitting edemaMuscle crampsBracycardiaInfertilityPeripheral Neuropathy

HypothyroidismTreatmentMost patient with uncomplicated symptomatic Hypothyroidism may be referred to the primary physician for further evaluation and initiation of treatmentIf hypothyroidism is due to a secondary etiology initiation of thyroid hormone therapy may exacerbate preexisting adrenal insufficiency

MyxedemaMyxedema is a rare life threatening decompensation of hypothyroidismUsually in individuals with long-standing hypothyroidismMost often seen in the winter monthsMore common in elderly women with underdiagnosed or undertreated hypothyroidism

MyxedemaPrecipitating events includeInfectionCHFTraumaCVAExposure to coldDrugsSedativesLithiumAmiodarone

MyxedemaIn addition to the clinical features of hypothyroidism patients may present withHypothermiaAltered metal statusComa, delusions, and psychosis (myxedema maddness) HyponatremiaDilutional secondary to decreased free-water clearanceHypoglycemiaSecondary to impaired gluconeogenesisHypotensionBradycardiaRespiratory FailureSecondary to decreased strength of respiratory muscleHypercapnia and hypoxia is common

MyxedemaDiagnosisMust have high clinical suspicionCommonly has Hx. Of hypothyroidismDelcine in function is usually insidious in onset

MyxedemaDiagnosis contLaboratory evaluation may revealAnemiaHyponatremiaHypoglycemia Transaminases CPK LDHPo2 and PCo2 on ABGs

MyxedemaDiagnosis cont.EKG may revealSinus BradycardiaProlonged QT intervalLow voltageFlattened or inverted T waves

MyxedemaTreatment (see table 216-5 below)No prospective studies on optimal therapy have been done thus treatment recommendations are not uniformAirway stabilization with adequate oxygenation and ventilation or vitalCardiovascular status must be monitored closelyHypothermic patients should be gradually rewarmed with gentle passive external rewarmingHypotension from reversal of hypothermic vasoconstriction should be avoided

MyxedemaTreatment cont.Hyponatremia typically responds to fluid restrictions. Severe cases may require hypertonic saline with lasixsVasopressors are usually ineffective and should only be used in severe hypotensionLovothyroxine 300-500 mcg slow IVP followed by 50-100 mcg daily

MyxedemaTreatment cont.L-triiodothyronine 25 mcg IV or orally q 8 h is a alternativeThis dose should be halved in patients with cardiovascular diseaseHydrocortisone 100 mg IV q 8 hours should be givenSend baseline cortisol level to lab if possiblePrecipitating causes should be sought and treated

MyxedemaTreatment of Myxedema Coma (table 216-5)RecognitionSupportive therapy including ventilatory supportThyroid replacementLovothyroxine 300-500 mcg slow IVP followed by 50-100 mcg daily orT3 25 mcg IV or PO q 8 hrsGlucocorticoidHydrocortisone: 100 mg IV q8hHypothermiaPrevent additional lossPassive external rewarmingElectrolyte correctionGentle fluid restriction for dilutional hyponatremiaHypertonic saline for severe hyponatremiaHypoglycemiaDextrose-containing IV fluidsMonitoringAggressive treatment of presipitating causesAdmit patient to a monitored setting

MyxedemaDispositionAdmit to appropiately monitored bed

Questions1. Hyperthyroidism is Characterized by which of the followingA. FatigueB. PalpitationsC. Weight LossD. Heat intoleranceE. All the above

2. The most common etiology of hyperthyroidism isA. Toxic MultinodularB. Graves C. Toxic NodularD. Amiodarone induces

3. Typical Feature of Hyperthyroidism includeA. FatigueB. Weakness C. ConstipationE. Cold IntoleranceF. All the above

4. T or F Hyperthyroidism is more common in women5. T or F Hypothyroidism is more common in women6. T or F Mild hyperthyroidism may be treated with B-blockers

Answers 1. E 2. B 3. F 4.T 5.T 6.T