Thyrotoxicosis - bowenstaff.bowen.edu.ng
Transcript of Thyrotoxicosis - bowenstaff.bowen.edu.ng
Thyrotoxicosis
IntroductionCauses of thyrotoxicosisInvestigationsTreatmentSpecial situations in hyperthyroidismconclusion
The term thyrotoxicosis refers to the biochemicaland physiologic manifestations of excessivequantities of the thyroid hormones.The term hyperthyroidism is reserved for disordersthat result from overproduction of hormone by thethyroid gland itself, of which Graves' disease is themost common.
The manifestations depend on the severity of thedisease, the age of the patient, the presence orabsence of extrathyroidal manifestations, and thespecific disorder producing the thyrotoxicosis
Epidemiology
Thyrotoxicosis is common, affecting perhaps 2-5% ofall females at some time and with a sex ratio of 5 :1,most often between ages 20 and 40 years.Nearly all cases (> 99%) are caused by intrinsicthyroid disease; a pituitary cause is extremely rare
CommonGraves' disease (autoimmune)Toxic multinodular goitreSolitary toxic nodule/adenoma
UncommonSubcute thyroiditisSubacute granulomatous thyroiditis (de Quervain's)postpartumGestational thyrotoxicosis (HCG stimulated)Exogenous iodine Drugs – amiodaroneThyrotoxicosis factitia (secret T4 consumption)
RareTSH-secreting pituitary tumoursMetastatic differentiated thyroid
carcinomaHCG-producing tumoursHyperfunctioning ovarian
teratoma (struma ovarii)
Graves‘ disease
This is the most common cause ofthyrotoxicosis
It is due to an autoimmune process.Serum IgG antibodies bind to the
thyroid TSH receptor stimulatingthyroid hormone production, behavinglike TSH. These TSH receptorantibodies can be measured in serum.
Epidemiology
Account for 60-80% of thyrotoxicosisPrevalence varies among populationdepending on iodine intakeHigh I-intake is associated with anincrease prevalence of GDOccur in 2% of women but one-tenthas frequent in menOccur between 20-50 years of age
Pathogenesis
A combination of genetic factors,including HLA-DR and CTLA-4polymorphism and environmentalfactors contribute to GDsusceptibilityConcordance in monozygotictwin is 20-30% compared to 5% indizygotic twins
Environment
Stress (operating via the neuroendocrineeffects on the immune system)SmokingSudden increase in iodine intake mayppt Graves’Post partumDrugsIrradiationInfection
Pathogenesis
1. A basic defect in antigen-specific suppressor Tcells allows an imbalance in helper cell action versussuppressor cell function, resulting in the excessivegeneration or unregulated synthesis of TSH receptorantibodies.
2. A defect may exist in the mechanism by whichthyrocytes and T cells initiate helper T-cell activation.
3. The third hypothesis relates to molecular mimicry
Clinical manifestations of GD
Clinical manifestation depends onSeverity of thyrotoxicosisDuration of the diseaseIndividual susceptibility to thyroidhormonePatient’s age – apathetichyperthyroidism in the elderly px
Usually, the thyroid is palpable,diffusely enlarged, and smooth.May be soft initially but becomesprogressively firmer. There maybe a systolic bruit heard
Clinical features
SymptomsWeight loss IncreasedappetiteIrritability/behaviourchangeRestlessnessMalaiseStiffnessMuscle weaknessTremorChoreoathetosisBreathlessnessPalpitation
SIGNSHeat intoleranceItchingThirstVomitingDiarrhoeaEye complaints*GoitreOligomenorrhoeaLoss of libidoGynaecomastiaOnycholysisTall stature (in children)SweatingProximal myopathy Proximal
muscle wastingOnycholysis Palmar erythema Graves' dermopathy*Thyroid acropachyPretibial myxoedema
Features of Graves’ diseaseThyroid eye disease Graves' dermopathy, are very rare. Rarely lymphadenopathy and splenomegaly mayoccur. Graves' disease is also associated with otherautoimmune disorders such as pernicious anaemia,vitiligo and myasthenia gravis.
CVS
Sinus tachycardia (associated withpalpitation, (±SVT, Atrial fibrillation iscommon in > 50years)Bounding pulseWide pulse pressureAortic regulationAnginaHeart failure
Thyrotoxicosis with periodic paralysis(rare) - characterized by sporadic
attacks, most commonly causingflaccidity and paralysis of the legs,arms, and trunk, although any muscle(e.g., facial) can be involved
Eye involvement
10% of Graves’ diseaseBilateral or unilateral (10%)Sensation of grittiness or eyes discomfort and excesstearingLid retractionLid lag
Proptosis (⅓)Perirobital oedemaScleral injection and chemosisDiplopiaCompression of the optic nerve →papilloedema, peripheral field defects →permanent loss of vision
Assessing severity of eye involvement
N = No sign and symptomO = Only sign (lid retraction or lag) no symptomS = Soft tissue involvement (periorbital oedema)P = ProptosisE = Extra ocular muscle involvement (diplopia)C = Corneal involvementS = Sight loss
Thyroid dermopathy
Pretibial myxoedema affects anterior/ lateralaspects of the leg.Typically
Non inflamedIndurated plague(Pink or Purple colour)
Orange skin appearance Thyroid acropachy (<10%)--Clubbing
Investigation
BiochemicalThyroid function testSerum Thyroid stimulating Hormone (TSH) issuppressedAssay free T4 and T3 are also elevated
X-Ray of the neck antero-posterior and lateralincluding thoracic inlet.C X ROrbital & thyroid UltrasoundComputed tomography scan/Magnetic ResonanceImaging. Demonstrate swelling of extraocular muscles inGraves’ disease even if no clinical evidence ofophthalmopathy
Treatment modalities
The use of antithyroid drugsRadioactive iodineSurgery: thyroidectomy
Choice of therapy
Indications for radioiodine are:patient choicepersistent drug side-effectspoor compliance with drug therapyrecurrent hyperthyroidism after drugs.
Indications for drug therapy
ChildrenAdolescentFemale patient with graves’ diseaseDrug thyrotoxicosisImpalpable thyroid + thyrotoxicosisThyrotoxicosis +Heart failureThyrotoxic crisisRecurrence after subtotal thyroidectomy
Antithyroid drugs
Carbimazole 10-15mg 8hrly ormethimazole 30mg-40mg BD or dailyPrevent conversion of iodide to
iodinePrevent binding of iodine to tyrosinePrevent coupling of
monoiodotyrosine (MIT) andDiiodothyroxine to T3 and T4
PropylthiouracilActs like carbimazoleAlso impair conversion of T4 to T3 inperipheral tissue and thyroid Β blockers - PropanololRelieve sympathetic effects & inhibitperipheral conversion of T4 to T3
Iodine and iodine - containingagents
Mechanism -large doses acutelyinhibit organic binding (Wolffchaikoff effect)
-inhibit hormone release-Acutely retards the rate of
secretion of T4 in Graves’ disease
Indications for iodine use
Preparation for thyroid surgeryActual or impending thyrotoxic crisisSevere thyrocardiac diseaseActual surgical emergencies
SURGERY
Surgery and radioiodine are ablative therapyused in Graves’ diseaseThyroidectomy - make patient euthyroid first.Advantages
1. Given prompt control of the disease 2. Lower incidence of myxedema 3. Prevent thyroid failure (except total
thyroidectomy)
Indications for surgery
Toxic multinodular goitre Toxic solitary nodule Presence of pressure symptoms Large goitre Male patient – since relapse is most
likely Failure of patient to take the drugsComplications during drug therapyRelapses after previous drug therapyExophthalmosPossibility of malignancyCosmetic
RADIOIODINE (131I) THERAPY
I.II.III.IV.V.VI.
It produces thyroid ablationComplications
hypothyroidism (late)Time needed to gain control of diseaseRadiation thyroiditisTherapeutic dosing dilemmaWorsening eye diseases ( orbitopathy)Hypoparathyroidism, (though rare)
Radioiodine therapy - Contraindications
Pregnancy, Nursing mothers.Make patient euthyroid withcarbimazole and thiouracil before 131Iadministration but no evidence ofbetter outcome with pretreatmentwith antithyroid drugs..
Thyroid Storm
Causes
SurgeryRadioactive Iodine TherapySevere Infectiondiabetic ketoacidosis,Traumapulmonary thromboembolismSalicylates
DiagnosisClinical – tachycardia, hyperpyrexia, thyrotoxicosis symptomsLabs (Low TSH, High T4, FT4)
TreatmentPropranolol IV / esmolol vs. Verapamil IVPropylthiouracil, MethimazoleSodium IodideAcetamenophen, cooling blanketsPlasmapheresis (rare)