Hyperthyroidism and Thyroid Storm Tintinalli Chapter 215 12/15/05 Prepared by Trent W. Smith Lecture by Dr. Klien MD

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

Normal Thyroid State Thyroid hormone is reversible bound to various proteins including thyronine-binding globulin (TBG) Free unbound portions are biologically active T4 is the predominant circulating hormone T4 is deiodinated to t3 T3 is biologically more active than T4 but has a shorter half-life

Hyperthyroidism Occurs in in all ages Uncommon under the age of 15 10 x’s more common in women (1/10,000) Graves disease is the most common etiology 80% of cases in the U.S. Common in the 3rd and 4th decades Caused by autoimmune thyroid-stimulating antibodies Associated with diffuse goiter, opthalmopathy, and local dermopathy

Hyperthyroidism Toxic multinodular and toxic nodular goiters are the next most common etiologies Usually occurs in older populations Commonly with previous history of goiter Often with milder symptoms of thyrotoxicosis

Hyperthyroidism Amiodarone-induced thyrotoxicosis (AIT) Amiodarone is iodine rich and may cause both hyper and hypothyroidism Difficult to treat because of incomplete understanding of mechanism Two major forms exists Type 1 occurs with a normal thyroid Type 2 occurs with a abnormal thyroid Tx. Varies based on the the type

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

Hyperthyroidism Symptoms Signs Weaknes Goiter/thyroid burit Fatigue Hyperkinesis Heat intolerance Opthalmopathy Nervousness Lid retraction/stare Increased sweating Lid lag Tremors Tremor Palpitations Warm moist skin Weight loss Hyperreflexia Hyperdefication Tachycardia/arrhythmia Dyspnea Systolic hypertension Menstrual abnormalities Widened pulse pressure

Hyperthyroidism Confirmed by thyroid function test Elevated free T4 and Low TSH In some cases of graves disease T4 may be normal and TSH decreased but the patient appears thyrotoxic T3 level should be done to rule out T3 toxicosis Hypothyroidism secondary to pituitary adenoma will have elevated TSH levels

Hyperthyroidism Treatment Palliative treatment of mild hyperthyroidism is accomplished using B-blockers Most commonly used is propanolol Treatment of Graves diseases include long-term use of antithyroid medications, radioactive iodine, or subtotal thyroidectomy Type I AIT is treated with methimazole and potassium perchlorate Type II AIT is treated with glucocorticoids

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

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

Thyroid Storm Preciptatnts of Thyroid Storm (tabel 215-4) Infection Trauma DKA MI CVA PE Surgery Withdrawal of thyroid med Iodine administration Palpation of thyroid gland Ingestion of thyroid hormone Unknown etiology (20-25%)

Thyroid Storm Clinical features The most common signs are fever, tachycardia out of proportion to the fever, altered mental status, and diaphoresis Clues include a history of hyperthyroidism, exophthalmoses, widened pulse pressure and a palpable goiter Patients may present with signs of CHF

Thyroid Storm Clinical features cont. Common GI symptoms include diarrhea and hyperdefication Apathetic thyrotoxicosis is a distinct presentation seen in the elderly Characteristic symptoms include lethargy, slowed mentation, and apathetic facies Goiter, weight loss , and proximal muscle weakness also present

Thyroid Storm Diagnosis Thyroid storm is a clinical diagnosis based upon suspicion and treated empirically Lab work is non specific and may include Leukocytosis, hyperglycemia, elevated transaminase and elevated bilirubin

Thyroid Storm Treatment Initial stabilization includes airway protection, oxygenation, fluids and cardiac monitoring Treatment can then be divided into 5 areas: General supportive care Inhibition of thyroid hormone synthesis Retardation of thyroid hormone release Blockade of peripheral thyroid hormone effects Identification and treatment of precipitating events

Thyroid Storm Drug Treatment of Thyroid Storm (table 216-6) Decrease de novo synthesis: Porpythiouracil 600-1000mg PO initially, followed by 200-250 mg q 4 hrs Methimazole 40 mg PO initial dose, then 25 mg PO q6h Prevent relases of hormone (after synthesis blockade intiated) Iodine Iaponoric 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 q6h Lithuim 800-1200 mg PO every day Prevent peripheral effects: B-Blocker Propanolol (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 maintenance Guanethidine 30-40 mg PO q 6 h Reserpine 2.5-5 mg IM q4-6h Other consideration: Corticosteroids Hydrocortisone 100 mg IV q 8 h or dexamethosone 2 mg IV q 6 hr Antipyretics Cooling blanket acteaminophen 650 mg PO q 4-6h

Thyroid Storm Treatment cont Propranolol has the additional effects or blocking perpheral conversion of T4-T3 Avoid Salicylates because it may displace T4 from TBG If the patient continues to deteriorate despite appropriate therapy circulating thyroid hormone may be removed by plasma transfusion, plasmapheresis, charchoal plasmaperfusion Remember you must not administer iodine until the synthetic pathway has been blocked

Thyroid Storm Disposition Admit to the ICU

Hypothyroidism and Myxedeam Coma Tintinalli Chapter 215 12/15/05 Prepared by Trent W. Smith Lecture by Dr. Klien MD

Hypothyroidism Occurs when there is insufficient hormone production or secretion Occurs more frequently in women (0.6 to 5.9 %) The most common etiologies are Primary thyroid failure due to autoimmune diseases (Hashimoto thyroiditis is the most common) Idiopathic causes Ablative therapy Iodine deficiency May be transient Pathophysiology is unclear but may be viral in nature

Hypothyroidism Etiologies of Hypothyroidism Primary Autoimmune etiologies Hashimotos is the most common Idopathic Post ablation (surgical, radioiodine) Post external radiation Thryoiditis (subacute, silent, postpartum) Postpartum thyroiditis occurs within 3-6 months and occurs in 2- 16 % of women Self limited etiologies, often prededed by hyperthroid phase Infiltrative disease (lymphoma, sarcoid, amyloidosis, Tuberculosis Congenital

Hypothyroidism Etiologies of Hypothyroidism Post Partum Occurs 3-6 months post partum and occurs in 2-16% of women Secondary (pituitary) Neoplasm Infiltrative Dz. Hemorrhage Tertiary (hypothalamic)

Hypothyroidism Etiologies of Hypothyroidism Drugs Amiodarone Lithium Occurs in 1-32% of patients Most 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 T3 Lithium Acts similarly to iodine and inhibit thyroid hormone release Iodine (in patients with pre-existing autoimmune disease) Antithyroid medication

Hypothyroidism Clinical Features The 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

Hypothyroidism Clinical Features cont. Cardiac findings include bradycardia, enlarged heart, and low-voltage electrocardiogram Paresthesia, ataxia, and prolongation or DTR’s are characteristic neurologic findings See table below for more complete list

Hypothyroidism Symptoms and Signs or Hypothyroidism (table 216-2) Fatigue Hoarseness Weight Gain Hypothermia Cold intolerance Periobital puffiness Depression Delayed relaxation of ankle jerks Menstrual irregularities Loss of outer third of eyebrow Constipation Cool, rough, dry skin Joint Pain Nonpitting edema Muscle cramps Bracycardia Infertility Peripheral Neuropathy

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

Myxedema Myxedema is a rare life threatening decompensation of hypothyroidism Usually in individuals with long-standing hypothyroidism Most often seen in the winter months More common in elderly women with underdiagnosed or undertreated hypothyroidism

Myxedema Precipitating events include Infection CHF Trauma CVA Exposure to cold Drugs Sedatives Lithium Amiodarone

Myxedema In addition to the clinical features of hypothyroidism patients may present with Hypothermia Altered metal status Coma, delusions, and psychosis (myxedema maddness) Hyponatremia Dilutional secondary to decreased free-water clearance Hypoglycemia Secondary to impaired gluconeogenesis Hypotension Bradycardia Respiratory Failure Secondary to decreased strength of respiratory muscle Hypercapnia and hypoxia is common

Myxedema Diagnosis Must have high clinical suspicion Commonly has Hx. Of hypothyroidism Delcine in function is usually insidious in onset

Myxedema Diagnosis cont Laboratory evaluation may reveal Anemia Hyponatremia Hypoglycemia ↑ Transaminases ↑ CPK ↑ LDH ↓Po2 and ↑PCo2 on ABG’s

Myxedema Diagnosis cont. EKG may reveal Sinus Bradycardia Prolonged QT interval Low voltage Flattened or inverted T waves

Myxedema Treatment (see table 216-5 below) No prospective studies on optimal therapy have been done thus treatment recommendations are not uniform Airway stabilization with adequate oxygenation and ventilation or vital Cardiovascular status must be monitored closely Hypothermic patients should be gradually rewarmed with gentle passive external rewarming Hypotension from reversal of hypothermic vasoconstriction should be avoided

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

Myxedema Treatment cont. L-triiodothyronine 25 mcg IV or orally q 8 h is a alternative This dose should be halved in patients with cardiovascular disease Hydrocortisone 100 mg IV q 8 hours should be given Send baseline cortisol level to lab if possible Precipitating causes should be sought and treated

Myxedema Treatment of Myxedema Coma (table 216-5) Recognition Supportive therapy including ventilatory support Thyroid replacement Lovothyroxine 300-500 mcg slow IVP followed by 50-100 mcg daily or T3 25 mcg IV or PO q 8 hrs Glucocorticoid Hydrocortisone: 100 mg IV q8h Hypothermia Prevent additional loss Passive external rewarming Electrolyte correction Gentle fluid restriction for dilutional hyponatremia Hypertonic saline for severe hyponatremia Hypoglycemia Dextrose-containing IV fluids Monitoring Aggressive treatment of presipitating causes Admit patient to a monitored setting

Myxedema Disposition Admit to appropiately monitored bed

Questions 1. Hyperthyroidism is Characterized by which of the following A. Fatigue B. Palpitations C. Weight Loss D. Heat intolerance E. All the above

2. The most common etiology of hyperthyroidism is A. Toxic Multinodular B. Graves C. Toxic Nodular D. Amiodarone induces

3. Typical Feature of Hyperthyroidism include A. Fatigue B. Weakness C. Constipation E. Cold Intolerance F. All the above

4. T or F Hyperthyroidism is more common in women 5. T or F Hypothyroidism is more common in women 6. T or F Mild hyperthyroidism may be treated with B-blockers Answers 1. E 2. B 3. F 4.T 5.T 6.T