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)