Thyroid Emergencies

Robina Rana28th August, 2013

Objectives

• Discuss common thyroid problems: • Thyroid Emergencies:– Thyroid Storm– Myxedema Coma– Thyrotoxic Periodic Paralysis

• Epidemiology• Presentation• Diagnosis• Management

Relationship between serum-free thyroxine by dialysis (FT4) ng/dL and log10 TSH in euthyroid, hyperthyroid, hypothyroid, and T4-suppressed euthyroid individuals.

Spectrum of autoimmune disease of the thyroid gland.

The clinical manifestations of autoimmune disease of the thyroid gland range from idiopathic myxedema, through nontoxic goiter, to diffuse toxic goiter, or Graves

disease. Progression of autoimmune disease from one form to another in the same patient

can occasionally occur.

Spectrum of autoimmune disease of the thyroid gland.

The clinical manifestations of autoimmune disease of the thyroid gland range from idiopathic myxedema, through nontoxic goiter, to diffuse toxic goiter, or Graves

disease. Progression of autoimmune disease from one form to another in the same patient

can occasionally occur.

Hypothryoidism:

MYXEDEMA COMA:

“End stage of untreated or inadequately treated hypothyroidism”

Myxedema Coma

• The clinical picture is often that of – an elderly obese female– who has become increasingly

withdrawn, – lethargic, sleepy, and confused.

• The history from the patient may be inadequate, but the family may report that – the patient has had thyroid surgery or– radioiodine treatment in the past or– that the patient has previously been

receiving thyroid hormone therapy.

The presentation is one of severe hypothyroidism, with or without coma (the term myxedema coma may, therefore, be a misnomer). Myxedema coma may be precipitated by an – illness such as a cerebrovascular accident, myocardial

infarction, or – an infection such as a urinary tract infection or pneumonia. – gastrointestinal hemorrhage; – acute trauma; – excessive dehydration; or – administration of a sedative, narcotic, or potent diuretic drug.

A schematic representation of the changes in serum thyroid hormone values with increasing severity of non thyroidal illness.

A rapidly rising mortality rate accompanies the fall in serum total T4 (TT4) and free T4 (FT4) values.

Pathogenesis of myxedema coma

• The physical findings are not specific. The patient may be – semi comatose or comatose – with dry, coarse skin, – hoarse voice, – thin scalp and eyebrow hair, – possibly a scar on the neck, and– slow reflex relaxation time. – Marked hypothermia, with body temperature sometimes falling to as low as

24°C (75°F), particularly in the winter months. – Precipitating factors such as pneumonia, urinary tract infection, ileus,

anemia, hypoglycemia, or seizures.

– Fever may be masked by coexistent hypothermia. – Often there are pericardial, pleural, or peritoneal effusions.

Remember the Basics;• High index of suspicion – clinical features

• Adherence to ABCs – LOC, Vitals (temp, arrhythmia ), IV access, IV fluids,

• Order confirmatory tests – Thyroid function tests– Other pituitary function tests

• Institute early treatment– Cortisol– Levothyroxine

• Identify and manage precipitant

Management of Myxedema Coma.(1) Admit to ICU for

• ventilatory support and• for intravenous medications.{Oral medications may be poorly absorbed (due to gastric atony or

ileus), and medications should be given intravenously if possible}.

(2) Parenteral thyroxine: Give a loading dose of 300-400 mcg IV, then maintainance 50-100 mcg IV daily. (May also give small doses of T3 (liothyronine) , 10 mcg IV every 8 h for the first 48 h if necessary. but this is usually not necessary, and it may contribute to untoward cardiovascular events.)

(3) Electrolytes: Water restriction for hyponatremia. Avoid fluid overload.

(4) Limit sedation. Appropriate reduction in drug dosage.

(5) Glucocorticoids: Controversial but necessary in hypopituitarism or polyglandular failure. Dosage: Hydrocortisone, 50-100 mg every 6 h initially and tapered downward over 1 wk. (If initial serum cortisol was >30 mcg/dL (827.7 nmol/L) corticosteroids are unnecessary.)

(6) Hypothermia: Do not externally rewarm. (Once myxedema coma is suspected in a hypothermic patient, external rewarming should be avoided, because this may cause redistribution of blood flow to subcutaneous tissues and cardiovascular collapse.)

(7) Treat the precipitating illness (eg, pneumonia or urinary tract infection).

Mortality from myxedema coma was about 80%.Prior to the recognition of the need for intravenous T4 and for respiratory support, Currently, the mortality is about 20% Predictors of acute mortality include

– level of consciousness, – lower Glasgow scores, and– higher APACHE II (acute physiology and chronic health evaluation) scores

• Higher mortality is also associated with – increased age,– cardiac complications, – and high-dose thyroid hormone replacement (500 g/d of L-T4 or–75 g/d of L-

T3). The latter presumably reflects the increased metabolic demand attendant to high dose replacement in the setting of limited physiologic reserve.

• Persistent hypothermia and bradycardia, despite therapy, are associated with a poor prognosis.

Laboratory tests useful in the differential diagnosis of hyperthyroidism

THYROID STORM / THYROID CRISIS:

An acute life-threatening exacerbation of thyrotoxicosis.

Thyroid Storm:

• It accounts for 1% to 2% of hospital admissions for thyrotoxicosis.

• It occurs in a patient with– Predisposition to hyperthyroidism • a history of Graves disease who has discontinued anti

thyroid medication or • in a patient with previously undiagnosed

hyperthyroidism.

– Precipitants• Non thyroid related

Thyroid Storm—Precipitating Factors.

Withdrawal of antithyroid drugs Severe infection Diabetic ketoacidosis Myocardial infarction Cerebrovascular accident Cardiac failure Surgery Parturition Trauma (eg, hip fracture) Radioiodine (rare) Drug reaction Iodinated contrast medium

• The clinical picture is that of ;– an acute onset of hyperpyrexia (with temperature >40°C [104°F]),– sweating, – marked tachycardia often with atrial fibrillation, – nausea, – vomiting, – diarrhea, – agitation, – tremulousness, and – delirium.– The presence of jaundice is considered a poor prognostic sign.

• Occasionally, the presentation is “apathetic without the restlessness and agitation”,

but with symptoms of weakness, confusion, cardiovascular and gastrointestinal dysfunction, and hyperpyrexia.

Diagnosis is largely based on the clinical findings;• Serum T4, free T4, T3, and free T3 are all elevated, and TSH is

suppressed. These findings are not different from what is seen in other patients with hyperthyroidism, but the difference is in the setting.

• It is thought that thyroid storm represents an exacerbation of thyrotoxicosis associated with – a shift of T4 from the bound to the free compartment with an

increase in free T3 and T4, as well as – an exaggerated response to a surge of catecholamines that results

from the stress of the precipitating event.• The cause of death is usually cardiac arrhythmia and failure.• Liver function abnormalities are often seen, as is

leukocytosis, even in the absence of infection.

Remember the Basics;• High index of suspicion – clinical features

• Adherence to ABCs – LOC, Vitals (temp, arrhythmia ), IV access, IV fluids,

• Order confirmatory tests – Thyroid function tests– Other pituitary function tests

• Institute early treatment

• Identify and manage precipitant

The therapeutic regimen typically consists of multiple medications, each of which has a different mechanism of action:• A beta-blocker

– to control the symptoms and signs induced by increased adrenergic tone

• A thionamide – to block new hormone synthesis

• An iodine solution – to block the release of thyroid hormone

• An iodinated radiocontrast agent (if available)– to inhibit the peripheral conversion of T4 to T3

• Glucocorticoids – to reduce T4-to-T3 conversion, – promote vasomotor stability, and – possibly treat an associated relative adrenal insufficiency

Effects of Antithyroid Drugs.(THIONAMIDES)

1. Propylthiouracil(PTU)2. Methimazole(Tapazole)

Inhibition of thyroid hormone synthesis

a reduction in intrathyroidal immune dysregulation

Reduction of the peripheral conversion of thyroxine to triiodothyronine. (in the case of propylthiouracil)

*Tyrosine-Tg denotes tyrosine residues in thyroglobulin, I+ the iodinating intermediate, and TPO thyroid peroxidase.

Cooper DS. N Engl J Med 2005;352:905-917.

Management of Thyroid Storm.

Supportive care

• Fluids• Oxygen• Cooling blanket• Acetaminophen (Aspirin should be avoided, because it will displace T4 from thyroid

hormone—binding globulin, resulting in an increase in FT4

• Multivitamins• If indicated, antibiotics, digoxin to treat a-fib and heart failure

Specific measures

• Propranolol, 40-80 mg orally every 6 h ( adrenergic blockade)• Propylthiouracil, 150 mg every 6 h, or methimazole, 20 mg every 8 h; may be administered

per rectum if oral route is unavailable• INORGANIC IODINE: inhibit thyroid hormone synthesis but also block the conversion of T4 to T3,.

• Saturated solution of potassium iodide, 5 drops (250 mg) orally twice daily; or • iopanoic acid, 0.5 g IV or orally twice daily; or• iohexol, 0.6 g (2 mL of Omnipaque 300) IV twice daily

• Dexamethasone, 2 mg every 6 h ( for adrenal support and decrease FT4 FT3 )• Cholestyramine or colestipol, 20-30 g/d ( interferes with enterohepatic circulation of T4)

THYROTOXIC PERIODIC PARALYSIS:

Thyrotoxic periodic paralysis (TPP) is a rare but frightening thyroid emergency.

Thyrotoxic Periodic ParalysisThe usual clinical presentation is of an• Asian male (male:female ratio approximately 17:1) • with symptoms of untreated hyperthyroidism • who awakens at night or in the morning with flaccid ascending paralysis. • Typically, there is a history of vigorous exercise and/or a large high-

carbohydrate meal before retiring. • There is usually no family history of periodic paralysis, but there may be a

family history of autoimmune thyroid disease.

The acute episode may be complicated by cardiac arrhythmias due to the concomitant presence of hypokalemia.

The illness has also been reported to occur in Native Americans, African Americans, and in individuals of Mexican or South American descent, but these ethnic groups are affected rarely.

The paralysis initially – involves the lower extremities but – progresses to the girdle muscles, – followed by the upper extremities.

• Proximal muscle groups are affected to a greater extent than distal.

• Facial and respiratory muscles are usually spared.• Sensory function, bowel and bladder function

are not affected. • Deep tendon reflexes are depressed or absent.

Pathogenesis of thyrotoxic periodic paralysis;

The differential diagnosis of TPP includes • familial periodic paralysis, • Guillain-Barré syndrome, and• acute intermittent porphyria.The diagnosis is based on the • absence of a family history, • the characteristic presentation, • the presence of hyperthyroidism due either to Graves disease or toxic nodular goiter (other

types of hyperthyroidism have been implicated as well), and• usually a low serum potassium level.• The electromyogram, performed while the patient is experiencing weakness,

– shows myopathic changes with reduced amplitude of compound muscle action potentials. These do not change in amplitude after administration of intra-arterial low-dose epinephrine (distinguishes from familial periodic paralysis).

• Electrocardiograms show changes associated with– hypokalemia, – tachycardia, – increased QRS voltage, – first-degree heart block, and, – on occasion, serious ventricular arrhythmias.

Management of Thyrotoxic Periodic Paralysis.With appropriate treatment, recovery is rapid, and once the thyrotoxicosis is controlled, the paralysis will not recur

(1) Oral potassium supplement cautiously (if needed); monitor serum K+

(2) Oral propranolol (60 mg every 6 h) blocks the -adrenergic stimulation of Na+-K+ ATPase. (3) Antithyroid drug therapy should be started immediately, even though it takes time to bring the patient into a euthyroid state.

Avoid:

• IV potassium (important to be cautious if administering intravenous potassium, which may raise total body potassium to toxic levels as the episode resolves.

• IV glucose which stimulates insulin secretion and worsens hypokalemia, (ie, crystalloid fluid replacement only)

• Adrenergic agonists (eg, isoproterenol) which promote movement of potassium into the intracellular compartment and exacerbate the problem

• Acetazolamide, which has been shown to reduce frequency of attacks in familial periodic paralysis, may worsen attacks of thyrotoxic periodic paralysis and should be avoided.

Conclusion

• Myxedema coma:– Passive warming– Load Synthroid

• Daily IV– Start Hydrocortisone– Look for inciting event

• Thyroid storm:– Control heart rate

• B-blockade• Calcium channel

blockade– Thionamide therapy– Look for inciting event

• Thyrotoxic Periodic Paralysis:

• With appropriate treatment, recovery is rapid, and once the thyrotoxicosis is controlled, the paralysis will not recur

Thank You