Hypothyroidism (1 of 7) 1 Patient presents w/ signs & symptoms suggestive of hypothyroidism 2 DIAGNOSIS Evaluate thyroid stimulating hormone (TSH) & thyroxine (FT4) levels High TSH & High TSH Low/normal normal FT4 & low FT4 TSH & low FT4 3 4 5 SUBCLINICAL/MILD PRIMARY CENTRAL HYPOTHYROIDISM HYPOTHYROIDISM HYPOTHYROIDISM A Pharmacological 5 therapy THERAPY • EVALUATION DECISION Levothyroxine See next page A FOLLOWUP Pharmacological therapy Follow-up exams • Levothyroxine • Every 6-8 weeks initially to monitor patient’s response to MIMSthe dose of Levothyroxine until TSH is normalized • en every FOLLOWUP 6-12 months Follow-up exams • Every 6-8 weeks initially to monitor patient’s response to the dose of Levothyroxine to maintain FT4 above the median value of © normal range • en every 12 months Not all products are available or approved for above use in all countries. Specifi c prescribing information may be found in the latest MIMS. B1 © MIMS 2020 Hypothyroidism (2 of 7) THERAPY DECISION FOR SUBCLINICAL/MILD HYPOTHYROIDISM HYPOTHYROIDISM yroid antibody present? Yes No DETERMINE TSH LEVEL TSH TSH ≥10 mU/L <10 mU/L 3 A Pharmacological therapy Presence of goiter, Yes • Low-dose Levothyroxine high total or LDL-C level, other symptoms? No FOLLOWUP Follow-up exams • Every 4-8 weeks initially to monitor patient’s response to the dose of Levothyroxine ANNUAL until TSH is normalized THYROID • en every 12 months MIMSEXAM © Not all products are available or approved for above use in all countries. Specifi c prescribing information may be found in the latest MIMS. B2 © MIMS 2020 Hypothyroidism (3 of 7) 1 HYPOTHYROIDISM • yroid hormone defi ciency due to underactive thyroid that may be secondary to hypothalamic-pituitary disease or primary thyroid disease Signs & Symptoms • Variable signs & symptoms but typical symptoms are fatigue, weight gain, cold intolerance, constipation & dry skin • HYPOTHYROIDISM Neurological - Weakness - Depression - Poor memory - Delayed relaxation of deep tendon refl exes • Head & neck - Periorbital puffi ness - Hair loss/alopecia - Voice change; hoarseness - Slow speech • Gastrointestinal - Constipation • Cardiovascular - Bradycardia - Hyperlipidemia - Pericardial eff usion • Others - Menorrhagia - Myxedema (non-pitting edema) - Pallor - Goiter - Myalgia - Anemia - Galactorrhea Special Population w/ Higher Risk of Developing Hypothyroidism • Postpartum women • Infertile individuals • Individuals w/ a family history of autoimmune thyroid disorders • Patients w/ previous head & neck or thyroid irradiation • Other autoimmune endocrine conditions - Type 1 diabetes mellitus (DM), adrenal insuffi ciency (AI), ovarian failure • Other non-endocrine autoimmune disorders - Celiac disease, vitiligo, pernicious anemia, Sjogren’s syndrome, multiple sclerosis • Down’s & Turner’s syndrome 2 DIAGNOSIS Lab Tests MIMS Confi rmation & Types of Hypothyroidism • Measure serum thyroid stimulating hormone (TSH): Most sensitive test for detecting hypothyroidism • Confi rm w/ measurement of serum thyroxine (FT4) • Primary hypothyroidism: High TSH & low FT4 • Central hypothyroidism: Low/normal TSH & low FT4 • Subclinical hypothyroidism: High TSH & normal FT4 Other Tests • Lipid profi le • yroid autoantibodies - Antithyroid© peroxidase, antithyroglobulin autoantibodies • yroid scan, ultrasonography (may do both) • Neuroradiologic studies [magnetic resonance imaging (MRI) or computed tomography (CT)] - Recommended in patients w/ biochemical evidence of central hypothyroidism to assess the hypothalamic- pituitary region B3 © MIMS 2020 Hypothyroidism (4 of 7) 3 SUBCLINICAL/MILD HYPOTHYROIDISM • Refers to the state of slightly increased serum TSH w/ normal serum FT4 in patients who are usually asymptomatic Other Causes of Elevated TSH that Should be Excluded • Recent Levothyroxine dose adjustment wherein a steady state is not achieved • Transient increase in TSH during recovery from severe illness or destructive thyroiditis • Untreated primary adrenal insuffi ciency HYPOTHYROIDISM • Administration of recombinant human TSH • Presence of heterophilic antibodies against mouse proteins • Temporary increase in TSH due to calorie intake restriction Determination of Treatment for Subclinical Hypothyroidism: Further Evaluation • yroid antibodies detection (if positive, for treatment); if negative (TSH >10 mU/L, for treatment) • Physical exam • Lipid profi le • yroid ultrasound Risk Assessment • Higher risk of progression to overt hypothyroidism if TSH >10 mU/L, presence of thyroid antibodies, goiter, hyperlipidemia, pregnancy, ovulatory dysfunction w/ infertility - Treatment is recommended in higher risk patients - If patient is not at high risk, perform annual thyroid exam 4 PRIMARY HYPOTHYROIDISM Etiologies Autoimmune yroiditis (Hashimoto’s Disease) • Most common cause • Diagnosis - yroid antibodies [anti-thyroid peroxidase (TPO)- in 95% or antithyroglobulin (TG) detection in 60%] - Careful history of radiation exposure, radioactive iodine therapy, neck surgery, recent viral infection, medi- cations, pregnancy, change in diet - Presence of thyroid antibodies & absence of any of the above history confi rms diagnosis of Hashimoto’s thyroiditis Other Causes • Congenital: Endemic iodine defi ciency (Athyreosis, dyshormonogenesis), thyroid hormone resistance, TSH-receptor defect • Acquired: Iodine defi ciency, iatrogenic (post-thyroidectomy, thyroid irradiation, medications, radioactive iodine therapy) • Transient: Subacute thyroiditis (de Quervain’s), lymphocytic thyroiditis (silent, postpartum & painless thyroid- itis), neonatal hypothyroidism 5 CENTRAL HYPOTHYROIDISM Evaluation MIMS • orough exam of the function of the hypothalamic-pituitary axis • Determine adrenal status, if adrenal insuffi cient: - yroxine administration may increase metabolism & precipitate an adrenal crisis - Glucocorticoid should be replaced prior to thyroxine administration to avoid adrenal crisis Etiologies • Divided into secondary hypothyroidism (defect is in the pituitary gland) & tertiary hypothyroidism (defect is in the hypothalamus) • Occurs due to failure of the hypothalamic-pituitary axis causing decreased TSH secretion or reduced TSH biological activity • Pituitary: ©Tumor, vascular insuffi ciency, empty sella syndrome, infi ltrating disease, infection, iatrogenic (surgery & radiotherapy) • Hypothalamic: Tumor, infection, vascular insuffi ciency, thyrotropin-releasing hormone (TRH) defi ciency, iatrogenic Not all products are available or approved for above use in all countries. Specifi c prescribing information may be found in the latest MIMS. B4 © MIMS 2020 Hypothyroidism (5 of 7) LIFETHREATENING COMPLICATION MYXEDEMA COMA 1 Patient presents w/ signs & symptoms suggestive of myxedema coma HYPOTHYROIDISM ADMIT TO ICU CONFIRM DIAGNOSIS Non-pharmacological therapy • Close monitoring & supportive care - IV fl uids, gradual warming - Monitor CV function & for syndrome of inappropriate secretion of antidiuretic hormone (SIADH) - Ensure adequate ventilation - Treat underlying cause A Pharmacological therapy • Glucocorticoids - If central hypothyroidism cannot be ruled out • Levothyroxine IV or oral via NGT &/or Liothyronine IV 1 MYXEDEMA COMA • Correct diagnosis is imperative because critical illnesses are clinically similar to myxedema coma & can also present w/ altered thyroid function - If diagnosis is wrong, high doses of thyroid hormone is dangerous to the patient • A high suspicion of myxedema coma can be made in a poorly responsive patient w/ a thyroidectomy scar or history of radioiodine therapy or hypothyroidism - ere may also be antecedent symptoms of thyroid dysfunction followed by progressive lethargy, stupor & coma Signs & Symptoms • Severe hypothermia (<27°C) • Bradycardia • Respiratory failure & loss of consciousness • Hypercapnia • Hyponatremia • Long-standing hypothyroidism MIMS Precipitating Factors • Infection • CV event • History of thyroidectomy or radioiodine therapy • Exposure to cold Diagnostic Tests • Very low serum T4 concentration • High serum TSH concentration • Diagnostic scoring system for myxedema coma gives points for the degree of hypothermia, neurological eff ects, gastrointestinal© fi ndings, precipitating event, cardiovascular dysfunction, & metabolic disturbances - Score of ≥60 is highly suggestive of myxedema coma, while scores between 45 & 59 classify the patient at risk for myxedema coma Not all products are available or approved for above use in all countries. Specifi c prescribing information may be found in the latest MIMS. B5 © MIMS 2020 Hypothyroidism (6 of 7) A PHARMACOLOGICAL THERAPY1 Levothyroxine • 1st-line agent for treatment of hypothyroidism • May be used to manage myxedema coma • Safe for use in pregnancy • Actions: HYPOTHYROIDISM - Used as a replacement therapy in hypothyroidism to substitute thyroid hormone - Long half-life (T½), slow onset, regular bioconversion which is appropriately regulated by the tissues to the biologically active compound T3 • Eff ects: Safe & predictable eff ects - Requires several weeks to achieve peak therapeutic eff ects w/ regular oral dosing • Due to diff erent bioavailability of the various preparations of Levothyroxine, patients are encouraged to use the same brand of Levothyroxine - If a change in brand is needed, the patient’s serum TSH should be retested every 6 weeks & dosage of Levothyroxine be re-titrated Liothyronine • Actions: - Short T½, rapid onset - Biologically active compound (no conversion is necessary) - Used as a replacement therapy in hypothyroidism to substitute thyroid hormone • Generally