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The Thyroid: Too Much, Too Little and Under the Weather Bonnie is a 52 year old woman with a 25 year history of MS. She has been quadriplegic for the past 20 years, living in a group home until 8 months ago when she became ventilator dependent. She has become drowsier in the past few days, Temp 34, HR 58 and BP 138/65. Her WBC has increased to 22. Cultures reveal pseudomonas in her PICC blood. Brenda Lynn Morgan RN BScN MSc CNCC(C) Clinical Nurse Specialist, Critical Care Trauma Centre Victoria Hospital, London Health Sciences Centre Cases What treatment is indicated? TSH: 105 Euthyroid: 0.27-4.20 mIU/L Suppressed: < 0.10 mIU/L Elevated: > 15.00 mIU/L FT4: 3.2 (10-24 pmol/L) FT3: 1.5 (3.0-6.5 pmol/L) David was involved in an MVC and has been declared neurologically dead. What medications are indicated in preparation for organ donation. Mrs. Beems is admitted with hypertension, hypoglycemia and decreased LOC. She is in rapid atrial fib with warm, moist skin. Thyroid function reveals: 1 Cases TSH: 0.01 Euthyroid: 0.27-4.20 mIU/L Suppressed: < 0.10 mIU/L Elevated: > 15.00 mIU/L Cases Mrs. Kilbert has been in the ICU for the past 3 months, with failure to wean following recovery from urosepsis. Screening thyroid function reveals the following. Thyroid Hormone TSH: .22 Euthyroid: 0.27-4.20 mIU/L Suppressed: < 0.10 mIU/L Elevated: > 15.00 mIU/L FT4:7.8 (10-24 pmol/L) FT3: 1.9 (3.0-6.5 pmol/L) Thyroid Hormone Thyroid hormone requires iodine; iodine is essential to diet Thyroid traps and stores iodine If dietary iodine is low, thyroid works overtime to try to make more thyroid hormone, producing goiter Seafood and seaweed highest food source growth and development beta stimulation metabolism temperature regulation energy production Thyroid Hormone Increased dietary iodine initially decreases thyroid production Prolonged high intake can cause hyperthyroid Low iodine levels or high thyroid production can cause goiter 2 Thyroid Releasing Hormone (TRH) Thyrotopin Releasing Hormone (TRH) From hypothalamus Stimulates anterior pituitary to release thyrotropin (TSH) Increased TRH triggered by decreased thyroid hormone output Decreased TRH triggered by increased thyroid hormone output Thyrotropin (TSH) From anterior pituitary Transports iodide from serum into the cells Stimulates oxidation of iodide and iodination of tyrosine residues Stimulates synthesis of T4 and T3 Thyroid Hormones (T4, T3) Thyroxine (T4) and Triiodothyronine (T3) Both composed of a phenyl ring attached to tyrosine with two idodine atoms on the inner tyrosine ring T4 has two additional iodine atoms on its outer tyrosine; T3 has only one Thyroid gland has large storage of thyroglobulin; the protein within which T4 and T3 are synthesized and stored Storage in thyroglobulin enables rapid secretion Thyroid Hormones (T4, T3) Thyroxine (T4) made soley in thyroid gland T3 is made in thyroid gland AND in peripheral tissues and liver by deiodination of T4 rT3 (reverse T3) is formed in liver if an iodine atom is removed from inner ring of T4; rT3 has no biological activity 3 Drug Interaction T4, T3 I Colloid: rich bath of thyroglobulin Many drugs interact Heparin can raise T4 Salicylates and furosemide can lower T4, T3 Calcium carbonate reduces absorption of levothyroxine Dose adjustment needed with many anticonvulsants Beta blockers inhibit T4 conversion to T3 Drug Interaction IV contrast administration can cause hyperthyroidism (within several weeks of administration) Amiodarone (contains iodine): can cause hyperthyroidism after ~21 months of therapy; can be treated with prednisone Amiodarone and lithium can both cause hyper or hypothyroidism; depends on underlying thyroid function Dopamine and somatostatin inhibit TSH secretion Thyroid Hormone Disorders Thyroid Hormone Disorders • Hyperthyroidism • Hypothyroidism • Non-thyroidal Hormone Disorders Hyperthyroidism 4 Graves Disease • Most common cause of hyperthyrodism • Autoimmune disease • Autoantibodies that stimulate TSH recepter • Stimulates T4, T3 production • Unusual activity for antibody (most block) Graves Disease Graves Disease • Woman > men (3% vs 0.3% US) • Family history of autoimmune disease • Pregnancy • Goiter; bruit • Puffy eyes Graves Ophthlmopathy Graves Ophthlmopathy • Swollen, red and/or bulging eyes • Believed to be due to autoimmune interactions on TSH receptor within orbit • May appear before, during or after hormone secretion increases Three Phases: • Active period of inflammation • Regression • Inactive “burnt out” period 5 Graves Ophthlmopathy • Increased production of gycosaminoglycans that attract large amounts of water to orbit • Increased pressure causes bulging (proptosis) • Can put pressure of blood supply and threaten vision • Extra-orbital lid retraction does not threaten vision Clinical Findings: Hyperthyroidism • • • • • • Anxiety, Emotional lability Weakness Tremor Palpitations Heat intolerance, sweating Weight loss despite normal or increased appetite (some may have increased weight) Clinical Findings: Hyperthyroidism • • • • • Hyperdefecation (not diarrhea) Urinary frequency Oligomenorrhea/amenorrhea Gynecomastia/erectile dysfunction Heart failure, shortness of breath, arrhythmias, hyperclacemia • Beta stimulation (cardiac with vasodilation) 6 Clinical Findings: Hyperthyroidism • • • • • • • • “Stare” (lid retraction) and lid lag Rapid speach, hyperactivity Skin warm and moist Hair thin and brittle Tachycardia/atrial fibrillation Exophthalmos only in graves Enlarged thyroid Single palpable nodule Treatment; Hyperthyroidism Treat peripheral effects of hormone beta blockers blocks CVS effects mildly blocks conversion of T4 to T3 corticosteroids replace cortisol deficit triggered by thyroid hormone blocks conversion of T4 to T3 augments PTU Clinical Findings: Hyperthyroidism • • • • Low TSH High T4 High T3 Overt hyperthyroidism due to graves or nodular disease, T3 increase > T4 (increased production and peripheral conversion of T3) • Amiodarone toxicity inhibits T3 conversion; T4 > T3 Treatment; Hyperthyroidism Block thyroid gland propylthioruracil (PTU) inhibits T3 conversion from T4 inhibits new hormone synthesis methimazole (MMI) more potent inhibits new hormone synthesis potassium iodide (SSKI) May be used preop or for the most severe hyperthyroid crisis Short term administration decreases thyroid hormone release Temporarily blocks iodine uptake by thyroid gland (maximum effect ~10 days) Lithium carbonate has similar effect Treatment; Hyperthyroidism Removal of circulating hormone plasmapheresis, charcoal perfusion Supportive Hypothyroidism fluid and electrolyte replacement correct hypoglycemia fever management cardiovascular support Corrective Removal Radioactive iodine 7 Primary (thyroid gland), Secondary (pituitary) and Tertiary (hypothalamus) Hashimoto’s Disease • Similar risk (female, history of autoimmune) to Graves • Autoimmune is most common cause • Instead of stimulation, antibodies cause thyroid destruction • Congenital or childhood hypothyroidism can lead to stunted growth/impaired mental development Hashimoto’s Disease (chronic lymphocytic thyroiditis) Hashimoto’s Disease • Goiter (despite thyroid cell destruction) due to lymphocyte infiltration • Increased TSH (due to low T4, T3) stimulates hyperplasia • Diffuse goiter, with rubbery feel • Goiter rarely causes problems or requires surgery Diagnosis: Primary Hypothyroidism • • • • Goiter High TSH Low T4, T3 Thyroid antibodies (if Hashimoto) 8 Iodine Deficiency • Goiter • Rare in Canada, more common in mountanous regions • Replace iodine deficiency Central (secondary) Hypothyroid: • Infrequent • Inappropriately low TSH despite low T4 and T3 • Pituitary disease: adenoma most common (may be associated with other endocrine deficiencies) • Similar presentation to primary hypothyroidism • Treatment of hypothryoidism same as other causes Central (tertiary) Hypothyroid: • Inappropriately low TRH (testing not readily available) • Low TRH causes inappropriately low TSH andT4 and T3 • Most common reason is acute intracranial hypertension/lesion • Treatment of hypothryoidism same as other causes 9 Clinical Findings: Hypothyroidism Common: • • • • • • • • • Fatigue Cold intolerance Depression, poor concentration Anemia Brittle hair/hair loss, dry skin Bradycardia Aches and pains Carpal tunnel Puffy eyes Treatment • Levothyroxine (T4) • T4 to T3 conversion at periphery is physiologically regulated • Dose adjusted to TSH Myxedema Coma • Mortality 30-40% • Acts like beta blockade: bradycardia, heart failure, mild hypertension • Hypothermia (aggressive peripheral warming may cause hypotension) • Hyponatremia • Hypercapnea • Anemia Clinical Findings: Hypothyroidism • • • • • • • Constipation Hoarse voice Menorrhagia Edema Cerebellar signs Deafness Psychiatric Myxedema • Severe form of hypothyroid with coma • Non-goitrous myxedma may be the result of total destruction of thyroid cells • Often triggered by stressor such as infection Treatment of Myxedema Coma: • IV levothyroxine (T3 not available in Canada) • Steroids (due to risk of simultaneous adrenal insufficiency known as Schmidt’s syndrome) 10 Treatment; Myxedema Supportive respiratory cardiovascular fluids correct anemia prevent further heat loss Non-Thyroidal Thyroid Hormone Dysfunction avoid aggressive rewarming treat cause Critical Illness Non-thyroidal Disorders • Critical illness commonly associated with thyroid hormone disorders that are not due to thyroid gland disease • Normal or low TSH, low or normal T4 and/or T3 • rT3 elevation (produced by breakdown of T4 in liver; no biological activity) • rT3 binds to T3 receptor sites impacting activity • May be bodies attempt to reduce metabolism • Failure to wean associated with abnormal thyroid hormones • Kidney contributes to clearance of iodide (by glomerular filtration) • Cortisione and renal failure decrease T4 conversion to T3 11