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Thyroid Disorders

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    • 1. Thyroid Disorders Tapan A. Patel Cuong Nguyen Mona Jamaldinian
    • 2. Thyroid Gland
      • Second largest endocrine gland in body
      • Small butterfly shaped gland located at base of neck below the sternocleidomastoid muscles
      • Thyroid is controlled
      • by the hypothalmus
      • and pituitary
    • 3. Functions
      • Stimulates & maintains metabolic processes
        • Produces thyroid hormones T3-triiodothyronine and T4-thyroxine
        • These hormones regulate metabolism & affect the growth and function of other systems in the body
      • Secretes calcitonin to lower serum calcium levels
      • Parathyroid gland secretes PTH to raise serum calcium levels
    • 4. Functions
      • Metabolic stimulants of:
        • Neural and skeletal development
        • Oxygen consumption at rest
        • Stimulating bone turnover by increasing formation and resorption
        • Promoting chronitropic and ionotropic effects
        • Increasing number of catecholamine receptors in heart
        • Increasing production of RBC
        • Altering the metabolism of carbs, fats, and protein
    • 5. Hormones: T3 & T4
      • T3 (Triiodothyronine) & T4 (Tetraiodothyronine
        • Stored in Follicles (round sacs) in the thyroid filled with thyroglobulin, a thyroid protein.
          • Dietary iodine enters follicles where they are stored as T3 and T4
        • T4 is converted to T3 by peripheral organs such as kidney, liver, and spleen
        • T3 is 10x more active than T 4
    • 6. Hormones: T4 to T3
        • Only 20% of total T3 is secreted by thyroid
          • Majority is formed from catalysis of T4 by 5’-iodthryonine deiodinase (highest activity in liver and kidney)
    • 7. Hormones: T4
      • T4-thyroxine contains 4 iodine atoms
      • It is a slow-acting pre-hormone
      • T4 takes 4 days to peak in blood
        • Half-life 7 days
      • Overall effects take 6 weeks
      • T3 is the active and faster-acting hormone
      • The immediate effects of T3 last 1-2 days
        • Half-life 1.5 days
    • 8. Iodine
      • Dietary Iodide is removed from the bloodstream by means of an active pump
      • The pump can concentrate iodide in the follicular sacs at 350x greater than the blood concentration
      • Oxidation of iodide by thyroid peroxidase converts iodide  iodine
      • Peripheral de-iodination of T4 to T3 is regulated by many factors including health, nutritional status, and other hormones
    • 9. Hormones- TSH
      • TSH
        • TSH is a pituitary hormone
        • Controlled by TRH-thyrotropin releasing hormone from hypothalamus
        • Functions to stimulate thyroid hormone production
          • May enlarge thyroid (goiter) when under producing
        • Labs:
          • High TSH indicates low thyroid hormone= hypo
          • Low TSH indicates high thyroid hormone = hyper
    • 10. Hormones-Calcitonin & PTH
      • Produced by thyroid to regulate serum calcium levels
      • Calcitonin stimulates movement of calcium into bone
      • Parathyroid hormone (PTH) opposite effect of calcitonin
    • 11. Negative Feedback System The disruption of any of these mechanisms can cause abnormal levels of T3 and T4 leading to thyroid disease TRH T3 & T4 Thyroid TSH
    • 12. Diseases
      • Hypothyroidism-Under Activity
      • Prevalence
        • Affects 5-17% of population
        • Females> Males
        • Higher in >60 years old
      • Types
        • Hashimoto’s thyroiditis
        • Ord’s thyroiditis
        • Postoperative hypothyroidism
        • Postpartum hypothyroidism
        • Iatrogenic hypothyroidism
    • 13. Diseases
      • Hyperthyroidism- Over activity
      • Prevalence
        • Affect 5-17% of population
        • Females> Males
        • More common in younger persons
      • Types
        • Thyroid storm
        • Graves disease
        • Toxic thyroid nodule
        • Plummers disease
        • Hashitoxicosis
        • De Quervain thryoiditis
        • Iatrogenic hyperthyroidism
    • 14. Labs 80-220ng/dL Bound & Free T 3 Total(T 3 ) 0.25-6.7U/mL Thyroid stimulating hormone TSH 22-34% Binding capacity of TBG T 3 Resin Uptake 80-220ng/dL Bound & Free T 3 Total T 3 (TT 3 ) 0.8-1.5 ng/dL Free T 4 Free T 4 (FT 4 ) 4.5-12.5mg/dL Bound & Free T 4 Total T 4 (TT 4 ) Normal Range Measurement Thyroid Function Test
    • 15. Labs
      • Hyperthyroidism
        •  FT4
        •  TSH
      • Hypothyroidism
        •  FT4
        •  TSH
    • 16. Hyperthyroidism-Types
      • Graves disease
        • Most common form (70-80%)
          • Autoimmune disorder in which thyroid-stimulating antibodies are circulating in blood. These bind to thyroid cells and activate cells in the same manner as TSH.
        • 7 times greater in women
        • Peak onset is 20-30’s
    • 17. Hyperthyroidism-Types
      • Can be caused by:
        • Toxic multinodular goiter
        • Solitary toxic nodule
        • Thyroiditis
        • Drug-induced thryotoxicosis
        • Pituitary or trophoblastic tumors
    • 18. Hyperthyroidism-Symptoms
      • Weight loss
      • Tachycardia
      • Bulging eyes
      • Nervous/Anxious
      • Insomnia
      • Intolerant of heat
      • Goiter
    • 19. Goiter
      • A diet deficient in iodine
      • Increase in thyroid stimulating hormone (TSH) in response to a defect in normal hormone synthesis within the thyroid gland.
    • 20. Thyroid Storm
      • Life threatening syndrome
      • Decompensated hyperthyroidism
      • Symptoms
        • Hyperthyroid symptoms with agitation, confusion, delirium, psychosis
        • Gastrointestinal: Nausea/Vomiting, Abdominal pain
        • Tachycardia associated with CHF
    • 21. Thyroid Storm Treatment
      • Antithyroids
        • PTU 200-400mg po/NG q4-8h
        • Methimazole 60-120mg/d PO/NG divided q6-8h
      • Potassium Iodide 2-5 drops PO/NG q6h
      • Lugol Solution-Strong Iodine10 drops po TID
      • Glucorticoids: block conversion of T4 to T3
        • Hydrocortisone succinate 100-200mg IV q6-8
        • Dexamethasone 2mg Po/IV q6-8h
      • BB
        • Esmolol: 500mcg/kg/min
        • Propranolol 20-80mg/dose PO/NG q4-6h
    • 22. Hyperthyroidism-Treatment
      • Drug Therapy
        • Beta blocker
          • Atenolol 50mg-100mg po daily
          • Propranolol 20-40mg po TID
        • Antithyroids
          • Methimazole 15-30mg po daily
          • Propylthiouracil (PTU) 300mg TID
    • 23. Hyperthyroid-Treatment
      • Procedural Therapy
        • Radionuclide albation of thyroid gland
        • Total thyroidectomy
    • 24. Methimazole
      • Methimazole prevents peroxidase enzyme from coupling and iodinating the tyrosine residues on thyroglubulin. Reduces T3 & T4 production.
      • Dosage
        • 15-30mg PO daily
    • 25. Methimazole
      • Adverse Effects
        • Skin rash
        • Loss of taste
        • GI upset
        • Drowsiness
        • Decreased Platelets
      • antagonistic properties of Methimazole
    • 26. Methimazole
      • Drug Interactions:
        • Discontinue before treatment with radioiodine; affects uptake
        • Amiodarone: Increases T3 and T4 serum levels
        • Warfarin: enhanced due to vitamin K
    • 27. Propylthiouracil -PTU
      • Thio-urea derivative
      • Preferred agent in pregnant women
      • DOC for severe thyrotoxicosis
      • Dosage
        • Adults: 300-450mg/day divided q8h
        • Severe cases: 600-1200mg/day
        • Maintenance dose 100-150mg/day divided q 8-12 hours
      • Drug Interactions
        • Similar to Methimazole
    • 28. PTU
      • Adverse reactions
        • Rash
        • Itching
        • Hives
        • Agranulocytosis
        • Vasculitis
    • 29. Carbimazole-UK
      • Pro-drug converted to active form -methimazole
      • Dosage
        • 15-40mg PO daily until normal function
        • Reduce to 5-15mg po daily maintenance dose
      • Adverse Effects
        • Bone marrow suppression
        • Neutropenia
        • Agranulocytosis
    • 30. Sodium Iodide I-131 (Iodotope)
      • Quickly absorbed and taken up by thyroid
      • No other tissue capable of retaining radioactive iodine therefore low adverse effects
      • Dose
        • Adult 75-150mCi/g of thyroid x estimated thyroid gland size
        • 24hour radioiodine uptake
        • Discontinue antithyroid therapy 3-4days before
    • 31. Hypothyroidism
      • Types:
        • Primary hypothyroidism
          • Most common cause
          • Failure of thyroid gland
          • Occurs primarily in women aged 30-50 years old
            • Chronic autoimmune thyroiditis or Hashimotos disease is the most common primary hypothyroidism AND hypothyroidism overall
        • Secondary Hypothyroidism
        • Tertiary Hypothyroidism
        • Other causes
    • 32. Hypothyroidism-Symptoms
      • Fatigue
      • Weight Gain
      • Depression
      • Dry skin
      • Bradycardia
      • Constipation
      • Intolerant to cold
    • 33. Hashimoto’s Disease
      • Autoimmune disorder in which antibodies are directed against a thyroid sites to :
        • Inhibit thyroid peroxidase
        • Inhibit effects of TSH
        • Stimulate thyroid growth
    • 34. Hypothyroidism-Primary
      • Drug induced
        • Amiodarone, lithium, thiocyanates, phenylbutazone, sulfonylureas, PTU & methimazole
      • Iatrogenic
        • Surgical removal of the thyroid gland and radiation treatment
    • 35. Primary Hypothyroidism
      • Thyroid gland failure
        • Decrease T3 & T4
        • Increase TRH due to negative feedback
        • Increased TSH due to decreased TRH
    • 36. Secondary Hypothyroid
      • Pituitary failure
        • Insufficient TSH release as a result of:
          • Pituitary tumors
          • Surgery
          • Pituitary radiation
          • Pituitary necrosis
          • Autoimmune mechanisms
    • 37. Tertiary Hypothyroidism
      • Hypothalamic Failure- very rare
      • Insufficient TRH release as a result of:
        • Trauma
        • Irradiation
        • Tumors
    • 38. Hypothyroidism-Treatment
      • Drug Therapy
        • Levothyroxine Sodium-DOC synthetic T4
          • Adults 1-1.5mgc/kg/day orally initially, adjust as needed. Average dose 1.6-1.8mcg/kg/day
          • Pediatrics 1-1.5mgc/kg/day. Average 4 mcg/kg/day
        • Thyroid (Armour)
          • 30mg PO daily, increase 15mg q 2-3 week
        • Liotrix (Thyrolar) synthetic combo T3 & T4
          • Thyrolar 1/2 (6.25/25mcg) start1 tab daily , increase PRN q 2-3 weeks.
        • L-triiodothyronine (Cytomel) synthetic T3
          • 25mcg PO daily/ increase 12.5-25mcg daily every 1-2 weeks
    • 39. Hypothyroidism-Treatment
      • Adverse Effects
        • MI
        • Osteopenia
        • HA
      • Contraindicated
        • Acute MI
        • Treatment of obesity
        • Uncontrolled HTN
    • 40. Monitoring
      • Obtain baseline FT4, TSH, LFT, CBCs before initiation of therapy
      • Repeat FT4 and TSH after 4-6 weeks on therapy and 4-6 weeks after adjustments
      • Once euthyroid state obtain thyroid function test after 3-6 months
    • 41.