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Hypothyroidism Diagnosis and Management

Hypothyroidism Diagnosis and Management. dr Pandji M,SpPD, KEMD ,FINASIM. Definition :. Hypothyroidism is a clinical syndrome resulting from a deficiency of thyroid hormone which in turn results in generalized slowing down of metabolic processes. Etiology of Hypothyroidism. Primary :

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Hypothyroidism Diagnosis and Management

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  1. HypothyroidismDiagnosis and Management dr Pandji M,SpPD, KEMD ,FINASIM

  2. Definition : Hypothyroidism is a clinical syndrome resulting from a deficiency of thyroid hormone which in turn results in generalized slowing down of metabolic processes.

  3. Etiology of Hypothyroidism Primary : 1. Hashimoto’s thyroiditis : a.With goiter b.“Idiopathic” thyroid atrophy, presumably end-stage auto-immune thyroid disease, following either Hashimoto’s thyroiditis or Graves’ disease c.Neonatal hypothyroidism due to placental transmision of TSH-R blocking antibodies. 2. Radioactive iodine therapy for Graves’ disease 3. Subtotal thyroidectomy for Graves’ disease or nodular goiter 4. Excessive iodide intake (kelp, radiocontrast dyes) 5. Subacute thyroiditis 6. Rare causes in the USA a.Iodide deficiency b.Other goitrogens (Adapted : Greenspan FS, 2001)

  4. Secondary: Hypopituitarism due to Pituitary Adenoma Pituitary Ablative Therapy or Pituitary Destruction Tertiary : Hypothalamic Dysfunction ( rare ) Peripheral resistance to the action of thyroid hormone

  5. Pharmacologic Hypothyroidism I. Thyroid Hormone Synthesis Inhibitor • Tionamide : MTU, PTU, Carbimazol • Perchlorat, Sulfonamid • Yodide (Expectoran, Amiodaron) • Lithium II. Thyroid Hormone Destruction • Phenitoin & Phenobarbital • Enterohepatic pathway inhibitor of thyroid hormone  Colestipol, Colestyramin

  6. The Hypothalamic-Hypophysial-Thyroid Axis Hypothalamus TRH T3 Portal system Anterior pituitary + T4 TSH “Free” T3 T3 T4 Tissue + Thyroid T4

  7. Grades of Hypothyroidism 200 100 40 10 4.0 Individual and median values of thyroid function tests in patients with various grades of hypothyroidism. Discontinuous horizontal lines represent upper limit (TSH) and lower limit (FT4, T3) of the normal reference ranges. TSH mU/L 15 12 9 6 3 0 FT4 pmol/L 2.5 2.0 1.5 1.0 0.5 0 T3nmol/L Subclinical Hypothyroldism Mild Hypothyroldism Overt Hypothyroldism (Adapted : Greenspan FS, 2001)

  8. Pathogenesis Thyroid Hormones Synthesis of hyaluronate fibronectin and collagen by fibroblast Accumulation of glucosaminoglycans mostly hyaluronic acid in interstitial tissues Hydrophilic substance increase capillary permeability to albumin Interstitial edema Skin Many organs (heart muscle, striated muscle) (Wiersinga, 2004: The thyroid and its disease)

  9. Hypothyroidism in adult (myxedema)

  10. Physiologic Effect of Thyroid Hormone Endocrine Tissue growth Lipid & carbohydrate metabolism Brain maturity Heat production & Oxygen consumption Skeletal neuromuscular THYROID Cardiovascular Gastrointestinal Sympathetic Hematopoitic Pulmonary

  11. DIAGNOSIS HYPOTHYROIDISM

  12. Clinical Hypothyroidism FT4 TSH FT4  TSH  FT4 N TSH  FT4  TSH N/ FT4 N TSH N Primary Hypothyroidism Subclinical Hypothyroidism Secondary Hypothyroidism Normal TRH Test FT4  TSH  FT4  TSH  No Response Primary Hypothyroidism Tertiary Hypothyroidism Secondary Hypothyroidism

  13. Management of Hypothyroidism Pay attention to : 1. Initial dosage of thyroxin 2. The way to increase thyroxin dosage

  14. The Purpose of Hypothyroidism Treatment 1. To relief symptom and sign 2. To normalize metabolism 3. To normalizeTSH, level but not supressed 4. To normalize T3 & T4 levels 5. Avoid risk and complications

  15. Principles to conduct thyroxine replacement therapy 1. The more severe the disease, the lower the initial and the slower the increase dosage of thyroxine 2. The older the patients should more pay attention especially in cases of angina pectoris, congestive heart failure, cardiac arythmia

  16. Thyroid Hormone available on the market: • L-Thyroxin (T4)  Euthyrox L-Triiodothyronine (T3) Thyroid Extract The best is L-Thyroxin • Should be taken before meals • Dosage Recommendation : • L-T4 : 112 ug/d or 1,6 ug/kgB.W • L-T3 : 25-50 ug (RRJ : Djoko Moeljanto, 2002)

  17. Starting dose of thyroxin • There is no evidence base for determining how thyroxine therapy should be initiated, but it is customary to prescribe 50 ug daily, increasing to 100 ug daily after 3-4 weeks. • Measurement of serum T4 and TSH at two months after starting will dictate any further adjustment of dosage. • In the elderly, symptomatic ischemic heart disease, starting dose of 25 ug/d is advisable with increments of 25 ug/3-4 weeks. • A full replacement dose of 100-150 ug/d. (Toff AD, 2001; Thyroid International)

  18. The TSH level can be used as a guideline to establish the substitution dosage of thyroxin TSH level Thyroxin 20 uU/ml 50-75 ug/d 44-75 uU/ml 100-150 ug/d 90% Hypothyroidism cases used LT4 100-200ug (RRJ : Djoko Moeljanto, 2002)

  19. Variation in dosage of thyroxin Once thyroxin therapy is established it is good practice to review patients annually and measure serum TSH not only to ensure compliance but also to determine whether and adjustment of dose is required.

  20. Situation in which an adjustment of the dose of thyroxine may be necessary Increased dose required Use of other medication Phenobarbitone Phenytoin Carbamazepine increased thyroxine clearance Rifampicin *Sertraline *Chloroquine Cholestyramine Sucralfate Aluminium hydroxide interference with intestinal Ferrous sulphate absorption Dietary fibre supplements Pregnancy increased concentration of serum Oestrogen therapy thyroxine-binding globulin After surgical or iodine-131 reduced thyroidal secretion ablation of Graves’ disease with time Malabsorption e.g. coelic disease Decreased dose required Aging decreased thyroxine clearance Graves’ disease developing switch from production of blocking in patient with long-standing to stimulating TSH-receptor anti- primary hypothyroidish bodies * mechanism not fully established (Adapted : Toff AD, 2001)

  21. Suggested management of patients taking thyroxine replacement therapy, depending upon pattern of thyroid function test results and clinical symptoms TSH T4 T3 Symptoms Action normal normal or normal none none raised normal normal or normal present increase thyroxine by 25-50 g daily raised until serum TSH is suppressed but ensure T3 unequivocally normal < 0.05 mU/l normal or normal none none raised < 0.05 mU/l normal or normal yes* reduce thyroxine by 25-50 g daily raised to restore normal TSH < 0.05 mU/l normal or high normal yes* or no reduce thyroxine by 25-50 g daily raised or raised to restore unequivocally normal T3  Symptoms of possible undertreatment might include tiredness and weight gain * Symptoms of possible overtreatment might include unexplained atrial fibrillation and reduced bone mineral density (Adapted : Toff AD, 2001)

  22. Summary • Some basic principles to remember that active hormone is free hormone. • Cells metabolism are based on FT3 not FT4 • Diagnosis established by symptom, sign, FT4 and TSH • Should be careful to start and increase the dosage of thyroxine especially in case of angina pectoris,CHF,arythmia • Drug of choice is L-thyroxine • Target of treatment is normal TSH level

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