Thyrotoxicosis and Myxedema-Preoperative preparation and

Intraoperative complications and Management

R.Srihari

Topics for Discussion

• Thyrotoxicosis: – Etiology– Signs and Symptoms– Diagnosis– Treatment– Management of

Anesthesia– Thyroid Storm

• Myxedema:– Etiology– Signs and Symptoms– Diagnosis– Treatment– Management of

Anesthesia– Myxedema Coma

Thyrotoxicosis

• Introduction– Thyrotoxicosis:

• State of thyroid hormone excess

– Hyperthyroidism:• State of excessive thyroid function

• Major etiologies of thyrotoxicosis are hyperthyroidism caused by primary and secondary causes

Etiology

• Thyotoxicosis caused by hyperthyroidism:– Graves Disease– Toxic MNG– Toxic adenoma– Struma ovari– TSH secreting pituitary

adenoma– Chorionic gonadotropin

secreting tumours– Iodine overdose

• Thyrotoxicosis caused by hypothyroidism:– Drug induced thyroiditis– Subacute thyroiditis

Clinical Manifestations

• Symptoms:– Hyperactivtity and

Irritability– Palpitations– Fatigue and Weakness– Weight loss with

increased appetite– Diarrhoea– Polyuria– Oligomenorrhoea with

loss of libido

• Signs:– Tachycardia– Atrial Fibrillation– Tremors– Goitre– Warm, moist skin– Muscle weakness– Proximal myopathy– Lid retraction– Cardiomyopathy (severe)

• Graves’ Disease:– Associated with Graves’ ophthalmopathy and

dermopathy

– Graves’ Ophthalmopathy:• Dalrymple sign• Von Grafe sign• Joffroy sign• Moebius sign

• NO SPECS scheme – acronym derived from following eye changes:– N – no changes– O – only signs, no symptoms (lid retraction/lag)– S – Soft tissue involvement (Periorbital edema)– P – Proptosis (>22m)– E – Extraocular muscle involvement (diplopia)– C – Corneal involvement– S – Slight loss

– Thyroid dermopathy:• Almost always seen with Graves ophthalmopathy• Overall incidence < 5%

• Although most frequent over anterior and lateral aspects of lower leg( aka pretibial myxedema)

Skin changes can occur at any site esp. after trauma

• Typical lesion – non inflamed, indurated plaque with deep purple/pink color and orange skin appearance

– Thyroid acropachy:• Clubbing seen in Thyrotoxicosis pt (<1%) – strongly a/w Thyroid dermopathy

• Investigations:– CBC Microcytic anemia with thrombocytopenia– ECHO/Ecg if cardiac symptoms +– S. Creatinine (if patient more 60 yrs)– IDL to r/o pre-existing vocal cord palsy– CT scan of neck– Flow volume loop– Thyroid function tests

Treatment

• Hyperthyroidism of Graves’ Disease is treated by decreasing thyroid hormone synthesis – Using antithyroid drugs

OR– Reducing the amount of thyroid tissue

OR– Thyroidectomy

• Antithyroid drugs:– Main drugs Thionamides

PTU/Carbimazole/MethimazoleAct by inhibiting TPO decreasing oxidation and

organification Decreasing Antithyroid antibody levelsPTU also inhibits T4T3

• Carbimazole/ Methimazole :– 10-20 mg Q8h-Q12h initially once euthyroid 10-20mg OD Duration of action- 6 hours

• PTU:– 100-200mg Q6h-Q8h dose decreased as thyrotoxicosis improves

• TFTs and clinical manifestation are reviewed 3-4 weeks after starting treatment

• Euthyroid state seen 6-8 weeks following therapy

• Remission rates seen after 18-24 months following therapy

• Common side effects of anti-thyroid drugs:– Rash – Urtacaria May resolve spontaneously– Fever or substituting with alternatives– Arthralgia

• Rare but major side effects:– Hepatitis– SLE like vasculitis– Agranulocytosis confirmed with complete blood count

• Propanolol:– 20-40 mg Q6h– Helps to control adrenergic symptoms especially in early stages

brfore antithyroid drugs take effect– Alternatives: atenolol

• Sodium ipodate/ iopanoic acid:– 500mg- 3g OD– Mainly used in adequate response to treatment/relapse– Progressive destruction of thyroid cells and can be used as

initial treatment or for relapses after a trial of antithyroid drugs– Pregnancy: Contraindicated

– Iodine in high concentration inhibit release of hormones from hyperfunctioning gland effect occurs immediately but lasts only for several weeks

Hence preserved for preserved for • preparing hyperthyroid patients for surgery • Management of patients with thyrocardiac disease

– High concentrations of iodide reduce all phases of thyroid synthesis and release result in decreased gland size and vascularity

– Admininistered orally as SSKI 3 drops Q8h 10-14 days

• Surgery:– Indicated only after patient returns to euthyroid

state Anithyroid drugs should be continued

– Anticoagulants/ Coumarins:• Used if Atrial fibrillation present

Management of Anesthesia

• Preparation :– Extremely important– For elective surgery all patients should be made

euthyroid with course of antithyroid drugs for 6-8 weeks preoperatively • Low TSH levels should not be a contraindication to surgery

– TSH levels remain suppressed from prolonged hyperthyroidism in patients who have normalised T3 and T4 levels

• SSKI – given 7-14 days prior to Sx• Beta blockers to control heart rate perioperatively

– For emergency surgery:• Antithyroid drug should be administered even though it

has limited effect if taken less than 2 weeks• Antithyroid drugs should preceed iodide by 2-3 hours• IV beta blockers (Esmolol -0.5mg/kg infusion 0.03-

0.3mg/kg/min)• Sodium ipodate 500mg BD• Dexamethasone – 2mg q6h

• Euthyroid state usually achieved in 5-7 days

• Preoperative Preparation:– Premedication: Barbiturates/BZDs/Narcotics

NO ATROPINE

– Monitoring: • SpO2, BP, HR,eTCO2 and temperature• IBP in patients with uncontrolled thyroid condition• Central line if large amounts of blood loss anticipated

• Induction:– Thiopentone –preferred– Ketamine –avoided– Propofol- large doses to be given

• Muscle relaxants: the following can be used safely– SCh– Rocuronium– Vecuronium

• Maintenance of anesthesia:– Should be kept in deeper plane of anesthesia– MAC not affected – Isoflurane and Sevoflurane- ideal with N20 + O2

• Agents to correct hypotension:– IVF– Phenylephrine

• Eye protection- very important

• Reversal of anesthesia:– Glyco + Neostigmine

• Removal of thyrotoxic gland does not mean immediate resolution of thyrotoxicosis– T1/2 of T4 7-8 days

– Hence beta blocker therapy may be need to be continued post-operative period

– Antithyroid drug therapy can be discontinued

Thyroid Storm

• Introduction :– Most serious compication of hyperthyroidism with

mortality ranging from 10-75% of hospitalised patients

– Most common in patients with poorly controlled Graves’ Disease

– Clinical diagnosis acute disruption of the normal steady state of circulating hormones

• Precipitating Factors:– Infection/Sepsis– Withdrawal of anti-thyroid drugs– Surgery/Trauma– Parturition– DKA– Iodinated contrast dyes– Hypoglycemia– Excessive manipulation of thyroid gland– Burns

• Clinical features:– Fever + Tachycardia Most common

– Fever: Most characteristic >41 C

– CVS:• Tachycardia• Atrial fibrillation, Ventricular arrhytmias• Heart failure• Hypertension with wide pulse pressure(early), Hypotension (late)

• Neuromuscular:– Tremors– Encepalopathy– WeaknessCan progress to CVA/ Status epilepticus/Thyrotoxic

myopathy/Rhabdomyolysis

• GI:– Nausea/ Vomiting/ Diarhoea– Jaundice (indicated hepatocellular injury- poor prognosis)

• Respiratory– Dyspnea– Increased eTCO2 and O2 consumption Aggravated with pulmonary oedema/ respiratory muscle weakness and

tracheal obstruction from goitre

• Lab testing:– Increased FT3/FT4– Hyperglycemia– Leucocytosis– Abnormal LFT– Reduced K/Mg ; Increased Ca inc bone

resorption

• Management:– Treatment aimed at:• Control and relief of adrenergic symptoms• Control of thyroid function abnormality• Stopping Precipitating factor• Investigation and treatment of underlying thyroid

disease• Supportive measures

• Beta blockers:– Mainstay of controlling adrenergic symptoms– IV propanolol – 0.5-1mg increments over 10 minutes while

monitoring CV response decreases sympathetic hyperactivity+Inhibits conversion of T4 T3 +Concurrent administration of enteral propanolol with doses of 60-120mg Q4h to Q6h to enhance elimination during thyroid crisis

– Esmolol loading dose -250-500 mcg/kg infusion 50-100mcg/kg/min allows titration with minimal side effects

– Thionamides:• These drugs block de novo synthesis of thyroid hormones within

1-2 hours of administration But no effect on release of preformed Glandular store of Thyroid Hormone

• PTU- Drug of choice – 200mg Q4h• Methimazole -100mg stat foll by 20mg Q8h

– Iodine:• Release of glandular store of thyroid hormone inhibited by

administering Iodine/Lithium• Should be given only after Thionamides given after 1 hour or it

will exacerbate Storm• SSKI -10 drops Q8h (8mg iodide/iodine per drop)

– Amidarone:• Blocks peripheral conversion of T4 T3

+Decreased concentration of T3 induced adrenoceptors in cardiac

myocytes

– Bile acid sequesterants:• Thyroid hormone are metabolised in the liver where they are

conjugated with glucoronide and sulfate excreted in bile which are reabsorbed in intestine

• Cholestyramine(4g Q6h) interferes the thyroid hormone reabsorption in enterohepatic circulation

• Steroids:– Decrease T4 T3 conversion– Modulate auto-immune process during Thyroid crises– Inj. Hydrocortisone 100mg Q8h or Inj. Dexa 4mg iv Q6h

– Supportive therapy:• Fluid management• Nutrition• Drug therapy salicylates and Frusemide AVOIDED • Precipitating factors• Plasmapheresis LAST RESORT

Myxedema

• Etiology:– Primary:

• Iodine Deficiency• Hasimoto’s• Iatrogenic- !odine 131 deficiency/ Total thyroidectomy• Drugs: Iodine excess/ Amiodarone/ Antothyroid drugs• Infiltrative disorders: Amyloidosis/ Sarcoidosis

– Secondary:• Hypopituitarism• Isolated TSH deficiency

Clinical Manifestations • Symptoms:

– Tiredness, weakness– Dry skin– Feeling cold– Difficulty concentrating/poor

memory– Constipation– Weight gain with poor appetite– Dypnea– Hoarseness of voice– Menorrhagia– Hearing Loss

• Signs:– Dry coarse skin– Cool peripheral extremities– Puffy face,palms– Diffuse alopecia– Peripheral edema– Carpal tunnel syndrome– Delayed tendon reflexes– Myocardial contractility +

decreased PR decreased Stroke volume and bradycardia with increased peripheral vascular resistance

– Non-pitting edema: seen due to accumulation of hydrophilic mucopolysaccharides in dermis and other areas :• Tongue• Vocal cords – hoarseness of voice

Investigations

– Findings in Hypothyroidism:• Thyroid function test• Increased CPK• Elevated cholesterol and triglycerides• Macrocytic anemia• Adynamic ileus• ECG: low amplitude P wave and QRS complexes +

flattened/ inverted T waves + Sinus bradycardia

Treatment– L-thyroxine- given for treatment of hypothyroidism

consistent potency, reliably restores levels of T4 and T3 to normal and has prolonged duration of action

– Gradual onset with half life of 7-8 days

– If no residual thyroid function, daily replacement dose 1.6mcg/kg (~100-150mcg/day)

– In patients who develop hypothyroidism after treatment of Graves’ Disease necessary to replace with 75-125mcg/day

• Adults <60 years without evidence of heart disease may be started on 50-100 mcg/day daily

Dose is adjusted on basis of TSH levels goal of treatment being normal TSH / less than normal

TSH responses are gradual and should be measured at 2 months after instituting therapy or after any subsequent change in levothyroxine dosage

• Clinical effects after initiation of therapy are slow to appear Pts may not experience full relief from symptoms 3-6 months after TSH is normal

• Adjustments is made in 12.5 to 25 mcg increments if TSH is high

• Once full replacement is obtained and TSH stable- follow up – yearly

• Important component of therapy Compliance to Rx

• For elderly or those with CAD starting dose of 25 mcg/kg increasing monthly by 25 mcg till euthyroidism is achieved

• Patients with hypothyroid cardiomyopathy improvement in cardiac function in 2-4 months on 100mcg /day of L-thyroxine

• Subclinical hypothyroidism treatment started only if– TSH increased persistently for 3 months– TSH>10 mU/l– If TPO Ab+ve

Management of Anesthesia

• Preoperative Issues:– Patients with overt hypothyoidism should be treated prior to

elective surgery

– In emergency , if Surgery can be delayed for 24-48 hours iv T3 can be given (peak action-24-38 hours)

– Because of increased adrenocortical insufficiency + decreased hormone response to stress hypothyroid patients should receive hydrocortisone cover during periods of increased surgical stress

– Hypothyroid patients may be at increased risk when receiving either general or regional anesthesia:• Airway compromise secondary to swollen oral cavity

with large tongue• Edematous vocal cords• Goitrous enlargement• Decreased gastric emptying increasing risk of

regurgitation and aspiration

• Hypodynamic cardiovascular system:– Low cardiac output/ Stroke volume/ heart rate/

baroreceptor reflexes and intravascular volumeCompromised by surgical stress and cardiac

depressant anesthetic agents

– Hypothermia occurs quickly and is difficult to prevent and treat

– Hematological and Metabolic abnormalities:• Anemia• Platelet and coagulation factor abnormalities• Hypoglycemia• Hyponatremia

– Increased sensitivity to volatiles dec CO

– PATIENTS WITH SUBCLINICAL HYPOTHYROIDISM DO NOT PRESENT ANY ANESTHETIC PROBLEM

• If pt is planned for emergency surgery– Increased risk of cardiovascular instability

intraoperatively– Myxedema coma postoperatively

• Preoperative Sedation:– Contraindicated in hypothyroid patients for elective

surgery increased sensitivity to sedative drugs

• REGIONAL ANESTHESIA IS RECOMMENDED WHERE THERE ARE NO CONTRAINDICATIONS

• Monitoring:– Routine– Swan-Ganz if severe hemodynamic impairment with

TEE -> to assess intravascular volume

• IVF of choice DNS

– Induction agents:• Ketamine• Barbiturates and BZDs – in titrated doses

– Muscle relaxants:• Sch• Intermediate NDMR: Vecuronium and Rocuronium

– Opioids:• Short acting fentanyl and its derivatives

– Maintenance:• N20:O2 + Volatiles carefully used esp. in hypovolemia

blunted barorecptor response

– Intraop monitoring:• Temperature• Electrolyte and Fluid status• Invasive monitors in patients undergoing major surgery• Peripheral nerve stimulator

– Warming: very important

– Exaggerated hypotension:• Common and should be treated with judicious fluid and

inotropes and vasopressors – Ephredrine– Dopamine– Epinephrine

• NO PURE ALPHA 1 AGONIST

• IF unresponsive steroids should be given

• Ventilation:– Should be controlled – not spontaneous As hypoventilation seen due to increased

sensitivity to anesthetic drugs

Delayed recovery is common and postoperative ventilation may be required

Myxedema Coma• Introduction:

– Myxedema coma extreme manifestation of hypothyroidism although rare

Mortality 30-50%

– Term misnomer

– Condition considered in patients presenting with reduced level of consciousness with hypothermia

– Most common in elderly women with long standing undiagnosed or undertreated hypothyroidism, in whom an additional significant stress is experienced

– Precipitating Factors:• Infections• Cold environment• Burns• Stroke• Surgery• Trauma• CHF• Co2 retension

– Clinical manifestation:• Decreased mental status• Hypothermia• Clinical features of hypothyroidism

– CVS– RS– Airway– GI– Metabolic

– Though TBW is increased intravascular volume decreased

• Treatment:– Mainstay of Rx:• Thyroid replacement therapy• Steroid replacement• Supportive measures

– Thyroid Replacement Therapy:• All patients with suspected myxedema coma should

receive presumptive treatment with thyroid hormones

• Severity of clinical presentation does not correlate with doses of replacement hormone required– Rapid replacement: a/w life threatening myocardial ischemia

and arrhythmias– Delayed replacement: exposes prolonged risk of complication

from crises

– Loading doses 200-400 mcg iv saturates binding proteins

Followed by 50-100 mcg daily till conversion

– Steroid replacement:• Corticosteroids important part of treatment as

relative/ absolute hypoadrenalism may occur concurrent with hypothyroid disease• Inj. Hydrocortisone 100mg iv Q8h (or) Inj. Dexa 4mg iv

Q6h S.Cortisol level should be collected prior to starting

therapy (Inj. Hydrocortisone) if normal ..Rx stopped

– Supportive Treatment:• Hypothermia warming where possible

• Cardiac output monitoring guide fluid therapy

• Hyponatremia reversible with thyroxine treatment If severe - fluid restriction + Hypertonic saline

• Hypoglycemia 25% Dextrose via central venous line

• Precipitating factor should be corrected

• DVT prophyllaxis

• Ulcer prophyllaxis

• Mechanical ventilation

Thank you