adult hypothyroidism -finalised

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Adult Hypothyroidism and its Management Presented by Dr. ASHA PATHAK Assistant professor Pharmacology department Up rimS & r saifaI etawah

INTRODUCTION: 

INTRODUCTION The thyroid gland produces two related hormones, thyroixine (T 4 ) and triiodothyronine (T 3 ). Acting through nuclear receptors, these hormones play a critical role in cell differentiation during development and help maintain thermogenic and metabolic homeostasis in the adult. Autoimmune disorders of the thyroid gland can either stimulate the overproduction of thyroid hormones (thyrotoxicosis) or cause glandular destruction and hormone deficiency (hypothyroidism). Because thyroxine (T 4 ) regulates such essential functions as heart rate, digestion, physical growth, and mental development, an insufficient supply of this hormone can slow life-sustaining processes, damage organs and tissues in every part of the body, and lead to life-threatening complications.

Hypothyroidism: definition : 

Hypothyroidism: definition Hypothyroidism is a syndrome characterized by clinical and biochemical manifestations of thyroid hormone deficiency in the target tissues of thyroid hormone.

History: 

History Hypothyroidism as a clinical syndrome was described in 1874 by Gull under the name myxedema in veiw of the swollen skin (oedema) and it’s excess content of mucin (Myx-). In 1883 Semon noted striking similarities between patients with myxedema and patients who had under gone total thyroidectomy. In 1888 a committee nominated by The Clinical Society of London reported that in critenism, myxedema and postthyroidectomy changes, all were due to loss of thyroid function. 1891, Murray reported cure of myxedema by hypodermic injections of sheep thyroid extract. The active principle of thyroid extract was isolated by Kendall in 1914, and named thyroxine. Harrington elucidated the precise constitution of thyroixine in 1926 and was able to synthesized it. As of the 1960s leothyroxine sodium surplanted gradually desicated thyroid as the preferred treatment modalities

Epidemiology: 

Epidemiology Primary hypothyrodism is a common disease worldwide, especially in iodine deficient areas. It also is a prevalent disease in iodine replete regions. The prevalence of primary hypothyroidism is 1:100, but increases to 5:100 if patients with subclinical hypothyroidism (normal T 4 , raised TSH) are included. Female: male ratio is approximately 6:1

Thyroid Disease Spectrum: 

Thyroid Disease Spectrum 0  10 5 TSH,  IU/mL Mild Thyroid Failure TSH >4.0  IU/mL , Free T 4 Normal Overt Hypothyroidism TSH >4.0  IU/mL, Free T 4 Low Euthyroid TSH 0.4-4.0  IU/mL , Free T 4 Normal Thyrotoxicosis TSH <0.4  IU/mL , Free T 3 /T 4 Normal or Elevated

Aetiology of Hypothyroidism: 

Aetiology of Hypothyroidism Primary: Resulting from an intrinsic disorder of thyroid gland. Serum T 4 is low and TSH elevated . Autoimmune hypothyroiditis: Hashimoto’s thyroiditis Atrophic thyroiditis Iatrogenic: I 131 treatment Subtotal /total thyroidectory External radiation of neck for lymphoma or cancer Drugs: Iodine excess-Iodine containing contrast media, amiodarone Lithium, antithyroid drugs, paraaminosalicylic acid, interferon and other cytokines, aminoglutethemide Sunitinib (protein tyrosine kinase inhibitor) used to treat GI stromal malignancy Congenital hypothyroidism: Absent or ectopic thyroid gland Dyshormongencies, TSH-R mutation Iodine deficiency Infilterative disorders Amyloidoisis, Sarcoidosis, Haemochromatosis, Scleroderma, Ridel’s thyroiditis,

Aetiology of Hypothyroidism continued……: 

Aetiology of Hypothyroidism continued…… Central/Secondary. It occurs much less often and result from diminished stimulation of thyroid by TSH because of pituitary failure (secondary hypothyroidism) or hypothalamic failure (tertiary hypothyroidism Hypopituitarism: Tumor Pituitary surgery or irritation Infiltrative disorders Sheehan Syndrome Trauma Genetic forms of combined pituitary hormone deficiencies Hypothalamic disease Tumors Trauma Infiltrative disorder Idiopathic

Aetiology of Hypothyroidism continued……: 

Aetiology of Hypothyroidism continued…… Transient Silent thyroiditis including post partum thyroiditis Sub acute thyroiditis Withdrawal of thyroxine treatment in individuals with an intact thyroid After I 131 or treatment subtotal thyroidectomy for Grave’s disease

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Systemic manifestations Of hypothyroidism

Neurologic and psychiatric manifestations : 

Neurologic and psychiatric manifestations Headache, Numbness, tingling, painful paresthesias Slow movement & thought, less alert Decreased concentration and memory Slow speech and auditory impairment Almost treatable dementia Carpal tunnel syndrome (30%) Delayed relaxation of deep tendon reflexes Cognitive deficits Sleep apnea Myxedema coma Depression, psychoses, bipolar disorders .

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Peripheral vascular resistance: 50-60% Cardiac output: 30-50% Systolic blood pressure: Diastolic blood pressure: Heart rate and stroke volume: Pre-ejection time and isovolumic contraction time prolong and ventricular relaxation rate during diastole is slower. Occasionally cardiac enlargement and peripheral non-pitting oedema Cardiovascular system

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The severity of hypothyroidism parallels the incidence of impaired ventilatory drive. Weakness of the respiratory muscles has also been implicated as a cause of alveolar hypoventilation. Patients with myxedema may develop carbon dioxide retention. Myxedematous patients are more subject to respiratory infections. Obstructive sleep apnea has been documented in hypothyroidism in about 7% and is reversible with therapy. RESPIRATORY SYSTEM

G.I manifestations: 

G.I manifestations Symptoms Anorexia Gaseous distention Signs Prolonged gastric emptying leads to constipation Prolonged intestinal transit time Slowed intestinal absorption Rarely ileus or ascites Slight abnormal reversible liver function test Gallbladder hypotonia Malabsroption Myxeodema ascitis rare

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ENERGY AND NUTRIENT METABOLISM Decreased Increased BMR (upto 50%) Appetite, food intake Synthesis and degradation of protein Body wt (10%), Total serum cholesterol and LDL Ratio: total Cholesterol/HDL; LDL/HDL Atherogenic lipid profile Reduced thermogenesis is related to the characteristic cold intolerance of hypothyroid patients

RENAL FUNCTION, WATER AND ELECTROLYTES: 

Diminished urinary output. Serum creatinine is raised by 10-20% Occasionally, minimal proteinuria is seen, may be due to CHF or increased capillary transudation of protein. The total body sodium content is increased. The serum uric acid level is elevated as a consequence of a decrease in renal blood flow, characteristic of the disease RENAL FUNCTION, WATER AND ELECTROLYTES

musculoskeletal system.: 

Myalgia, Muscle weakness, Stiffness, Cramps, Fatigue Arthralgias Joint stiffness Joint effusions Pseudogout Carpal tunnel syndrome musculoskeletal system.

REPRODUCTIVE FUNCTION: 

REPRODUCTIVE FUNCTION In both sexes libido is usually, but not invariably decreased Abortion is frequent Pregnancy-induced hypertension is 2 to 3 times more common Low birth weight is secondary to premature delivery for gestational hypertension. Oligomenoerhoea and menorrahgia are the most Amenorrhea and galactorrhea are occasionally found in adult hypothyroidism due to hyperprolactinemia and are reversible with treatment Concentrations of both testosterone and estradiol in serum are decreased, predominantly due to a diminution in the concentration of the carrier sex hormone-binding globulin (SHBG) The metabolic clearance rate of testosterone increases in hypothyroidism .

ENDOCRINE SYSTEM: 

ENDOCRINE SYSTEM The serum prolactin concentration is elevated in approximately one-third of patients. The growth hormone response to insulin-induced hypoglycemia is blunted Adrenal steroid metabolism and production decrease. The decreased production is accomplished automatically by the pituitary through decreased ACTH secretion.

Hematopoietic SYSTEM: 

Hematopoietic SYSTEM Plasma volume and RBC mass are both diminished, and blood volume is decreased. Anemia of mild degree is commonly present Megaloblastic anemia due to folic acid deficiency which occures due to reduced intestinal absorption Leukopenia might indicate associated vitamin B12 or folic acid deficiency. Mean platelet volume can be decreased. prolonged bleeding time, decreased platelet adhesiveness, and low plasma concentrations of factor VIII and Von Willebrand factor

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Face is expression less at rest Voice is husky, low-pitched, and coarse. Enlargement of the tongue The hair, both of the head and elsewhere, is dry, brittle, and sparse, and lacks shine . Disappearance of eye bows begins at the lateral margin, Retardation in the rate of healing of surgical wounds and of ulcerations FACIES AND INTEGUMENT

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Poor capillary refilling, reflective of weak inotropy in the heart, leads to poor circulation at the extremities and patient experience cold hands and feet and this also facilitates fungal overgrowth in the nails. These signs are typical of longstanding hypothyroidism. FACIES AND INTEGUMENT continued………….

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Fluid leakage into extracellular spaces, a result of reduced glycoaminoglycan production also results in a characteristic swollen, scalloped tongue, which is very common in hypothyroid people. Thyroid deficiency will manifest as a yellowish buildup of carotene in the skin of the palms and soles. FACIES AND INTEGUMENT continued………….

Co-morbidity: 

Co-morbidity Hypercholesterolemia Depression Infertility Diabetes mellitus

Hypothyroidism and Hypercholesterolemia: 

Hypothyroidism and Hypercholesterolemia 14% of patients with elevated cholesterol have hypothyroidism Approximately 90% of patients with overt hypothyroidism have increased cholesterol and / or triglycerides

Hypothyroidism and Depression: 

Hypothyroidism and Depression Depressive symptoms are common in hypothyroidism Depressed patients may be more likely than normal individuals to be hypothyroid

Hypothyroidism and Depression Have Many Common Features: 

Hypothyroidism and Depression Have Many Common Features Depression Hypothyroidism Sleep decrease Suicidal ideation Weight change Delusions Constipation Decreased Concentration Decreased libido Depressed mood Diminished interest Fatigue Weight increase Bradycardia Cardiac and lipid Abnormalities Cold intolerance Delayed reflexes Goitre Hair and skin changes All depressed patients should be evaluated for thyroid dysfunction

The Role of Thyroxine in Depression: 

The Role of Thyroxine in Depression Antidepressants may be less effective if thyroid function not normalized Thyroxine therapy is recommended for patients with depression who have persistently elevated serum TSH

Hypothyroidism and Infertility: 

Hypothyroidism and Infertility Infertility : Evaluate thyroid function, treat hypothyroidism Hypothyroidism associated with Infertility (anovulatory), Miscarriage (spontaneous abortion) Preterm labor Stillbirth

Hypothyroidism and Diabetes Mellitus: 

Hypothyroidism and Diabetes Mellitus Approximately 10% at patients with type 1 diabetes mellitus may develop subclinical hypothyroidism Diabetes patients to examine for goitre TSH measurement at regular intervals

DIAGNOSIS OF HYPOTHYROIDISM: 

DIAGNOSIS OF HYPOTHYROIDISM Evaluation of a patient suspected of hypothyroidism starts with obtaining conclusive evidence that thyroid hormone deficiency is absent or present. Clinical examination suffices to provide a definitive answer in very severe cases of thyroid hormone deficiency, but is less accurate in mild cases. Biochemical proof of thyroid hormone deficiency is thus required in the vast majority of patients.

PowerPoint Presentation: 

www.drsarma.in 32 Algorithm for Hypothyroidism Measure TSH Elevated TSH Normal /lowTSH Measure FT4 Considering Pituitary Normal Low No Yes Sub-clinical hypo TPO + TPO - T4 repl Annual FU Primary hypothyroid TPO + TPO - No tests Measure FT4 Low Normal No tests Evaluate Pituitary Sick Euthyroid Drugs effect Hashimoto Others

Patient history : 

Patient history Personal history or family history of thyroid disease? Recent delivery (women 6 weeks to 6 months post-partum) Previous thyroid surgery or I131 therapy (neck irradiation) Use of antithyroid drugs or drug therapies such as lithium and amiodarone? Exposure to iodine excess? Symptoms and signs of a pituitary mass or of hypopituitarism suggest the presence of central hypothyroidism Physical examination may reveal a goiter (like the characteristic firm rubbery’ goiter in goitrous Hashimoto’s hypothyroidism), but many if not most hypothyroid patients have no palpable thyroid gland. Diagnosis of autoimmune disease• Women over age 50 Elderly patients

Clinical presentations: 

Clinical presentations Symptoms Signs Common Wt gain Fatigue Lethargy Depression Weakness Dysponea on exertion Arthrelgia/ Myalgias Muscle cramps Paresthesia Cold intolerance Dry skin Carpal tunnel syndrome Menorrhagia Bradycardia Diastolic Hypertension Thin brittle nails Thinning of hair Peripheral Oedema Puffy face and eyelid Skin pallor Delayed relaxation of deep tendon reflexes Goiter Less common Diminished appetite Wt. loss Hoarseness of voice Decreased sense of taste and smell Diminished auditory activity Dysphasia or Neck discomfort Menorrhagia Scant menses or amenorrhea Thinning of lateral ½ of eye brow Thickening of the tongue Hard pitting of oedema and effusion into pleural, peritoneal and joints Galoactorhoea presented as cardiac enlargement and pericardial effusion Hypothermia and stupor or myxedema coma which often associated with infection (especially pneumonia) may develop.

Thyroid Function Tests: 

Thyroid Function Tests Total T 4 (thyroxine), Total T 3 (triiodothyronine) Free T 4 , Free T 3 TSH T 3 -Uptake Free T 4 Index, Free T 3 Index Anti-Thyroid Antibodies Anti-Thyroid Antibodies Anti Microsomal (TM ) Antibodies Anti Thyroglobulin (TG) Antibodies Anti Thyroxine Per Oxidase (TPO) Ab. Anti Thyroxine antibodies Thyroid Stimulating (TSA) Antibodies High titres TPO Ab in Hashimotos & Reidle’s thyroiditis Anti thyroxine Ab in peripheral resistance to Thyroxine TSA (TSI) in Graves’ Hyperthyroidism High titers of TPO antibodies indicate chronic autoimmune thyroiditis, the most prevalent cause of hypothyroidism

Tests of Thyroid Function: 

Tests of Thyroid Function Test Reference Ranges TT 4 (total thyroxine) 64-142 mmol/L (5-11 µg/ dL ) FT4 (Free thyroxine) 9-24 pmol /L (0.7-1.9 ng /dl) F T4 I (free thyroxine index ) 16-50mmol –calculated by RT3U and TT4 107-118 mmol/L –calculated by TT4 and T4 uptake RT3 U (resin T 3 uptake ) 0.25-0.37 (25-37%) T4 U (T4 uptake) 0.6-1.2 TT3 (total T3) 1.1 -2.0nmol/L (70-132ng/dl) F T3 I (free T3 index) 0.28-0.75 nmol /L (18-49ng/dl) RAIU (I131 radioactive iodine uptake) 5%-15% at 5 hours 10-35% at 24 hours

Hypothyroidism Many Causes, One Treatment: 

Hypothyroidism Many Causes, One Treatment Goal : normalize TSH level regardless of cause of hypothyroidism 1 Treatment : once daily dosing with thyroxine - sodium (1.6µg/kg/day) 2 Monitor TSH levels at 6 to 8 weeks, after initiation of therapy or dosage change 3

thyroid hormone replacement preparations: 

thyroid hormone replacement preparations Levothyroxine: L-thyroxine (T4)-Synthroid Liothyronine: T3 –Cytomel, Triostat Desiccated thyroid Liotrix: (T3 +T4)-Thyrolar

thyroxine: 

thyroxine Thyroxine is presently recommended as the drug of choice in view of its long half-life ready quantitation in the blood, ease of absorption, and the availability of multiple tablet strengths. L-thyroxine is prescribed as the sodium salt in order to enhance its absorption, which occurs along the entire small intestine. Intestinal absorption of oral T4 is on average 80% , and is greater in the fasting than in the fed state. Altered bioavailability has been reported due to changes in the formulation of preparations. Serum T4 concentrations peak 2 to 4 hours after an oral dose and remain above normal for approximately 6 hours in patients receiving daily replacement therapy The gradual conversion of T4 into T3 in various tissues increases serum T3 concentrations so slowly after thyroxine absorption that with daily levothyroxine administration, no significant changes in circulating free T3 are detectable. are higher than those for adults .

Thyroxine continued …….: 

Institution of therapy: The rapidity with which normal thyroid hormone levels should be restored depends on a number of factors, including the age of patient, the duration and severity of the hypothyroidism, and the presence or absence of other disorders, particularly those of the cardiovascular system. Most patients under the age of 60 can immediately begin a complete replacement dose of 1.6 to 1.8 μg levothyroxine/kg ideal body weight (about 0.7 to 0.8 μg/1b). Requirements for children and infants Thyroxine continued …….

Thyroxine continued …….: 

The cause of hypothyroidism also influences replacement in that patients with total thyroidectomy or severe primary hypothyroidism have slightly higher requirements than do patients who become hypothyroid after radioiodine or surgical treatment for Graves’ disease . The latter group may have some residual thyroid function that is autonomous, and thus a complete replacement dose is excessive. For most women, a complete replacement dose will be between 100 and 150 μg per day and, for most men, between 125 and 200 μg per day. Individual l-T(4) requirements are dependent on lean body mass. Age- and genderrelated differences in l-T(4) needs reflect different proportions of lean mass over the total body wt . Thyroxine continued …….

Thyroxine continued …….: 

Thyroxine continued ……. Full replacement doses should not be administered initially to patients over the age of 60, to patients who have a history of coronary artery disease, or to patients with long-standing severe hypothyroidism. While levothyroxine improves cardiac function in patients with hypothyroidism and increases cardiac output and decreases systemic vascular resistance and end-diastolic volume, it also increases myocardial oxygen consumption. To avoid precipitating acute myocardial ischemia, the dose should be titrated, starting with 25μg a day and increased by increments of 25 μg at 8-week-intervals until serum TSH falls to normal or symptoms of angina worsen or appear. A similar slow approach is prudent in patients with long-standing, severe hypothyroidism, also because occasionally psychosis or agitation occurs during the initial phase of replacement in such cases.

Thyroxine continued …….: 

In the patient given what is thought to be a complete replacement dose of levothyroxine (SYNTHROID), a TSH and free T4 index should be measured about 2 months after therapy begins to establish that the estimated dose is appropriate for the patient. At that time, serum TSH may be still elevated, indicating the need for a modest increase in dose, or TSH may be suppressed, indicating that a reduction is in order. This is usually done in 12- to 25-μg increments, depending on the patient 10. These studies should be repeated again in 2 months to titrate proper dosage. After proper dosage has been achieved, the test should be repeated yet again after the patient has been euthyroid for approximately 6 months. Thyroxine continued …….

Thyroxine continued …….: 

Thyroxine continued ……. In patients with severe primary hypothyroidism, few adjustments will be required after the initial titration until the eight decade. However, patients with Graves’ disease who have had radioactive iodine may require dosage adjustments up to as long as 5 to 10 years after treatment is begun. A similar course may be followed by patients who have had subtotal thyroidectomy for Graves’ disease due to the slow deterioration of residual thyroid function

PowerPoint Presentation: 

Therapy should be monitored with TSH measurements and estimates of free T4. As the goal of levothyroxine therapy is to normalize the thyroid status of the patient, and as serum TSH provides the most sensitive and readily quantification of thyroid status in the patient with primary hypothyroidism, one aims at TSH values in the low normal range. Serum FT4 concentrations will generally be above the middle of the normal range or slightly elevated if serum TSH concentrations are normalized, but serum T3 concentrations (predominantly derived from T4-5’-monodeiodination) will be in the midnormal range . In patients with central hypothyroidism one should rely primarily on serum FT4 and T3; the required replacement dose will frequently suppress serum TSH values to below 0.1 mU/l

Clinical Response: 

Clinical Response In general, serum thyroxine normalizes before serum TSH, and both may normalize before the disappearance of all of the symptoms of hypothyroidism. In the severely hypothyroid patient with long-standing disease, a number of profound alterations may occur as the hypothyroid state is corrected. Thus, loss of weight, primarily due to mobilization of interstitial fluid as the glycosaminoglycans are degraded, is prominent. The moon facies, coarse nasal voice, puffy fingers, deafness, and sleep apnea will all diminish. Many of nonspecific symptoms, such as fatigue or cold intolerance, will eventually reverse as well. Hair and skin abnormalities take longer to improve. Despite weight loss due to fluid loss, the obese patient should not expect more than a 10-pound weight change, particularly if serum TSH values are only modestly elevated. Virtually all of the weight loss in hypothyroidism is associated with mobilization of fluid, and significant decreases in body fat rarely occur. While metabolic rate increases, in general, appetite increases as well, and a new equilibrium is established.

Treatment failures: 

Treatment failures In patients whose symptoms do not improve with levothyroxine therapy, one should establish that they are taking and absorbing the medication and that it is effective in reducing TSH. The most common cause of treatment failure is poor compliance with ingestion of thyroxine tablets. Compliance might be enhanced by the (supervised) administration of thyroxine once weekly. A slightly larger dose than 7 times the normal daily dose may be required a singly weekly gift of 1000 μg T4 orally seems to be effective and well tolerated.

Adverse effects of treatment: 

Adverse effects of treatment Life-long treatment with thyroxine when properly monitored, seems to be free of complications. Long-term morbidity and mortality are normal. Thyroxine treatment in TSH-suppressive doses, however, might give reason for some concern as it has been associated with detrimental effects on the heart and the bones. A TSH value of =0.1 mU/l has been identified as a risk factor for the development of atrial fibrillation . Long-term levothyroxine therapy in TSH suppressive doses may cause left ventricular hypertrophy , and increases the risk of ischemic heart disease in patients under the age of 65 years . TSH-suppressive doses of levothyroxine have been associated with bone loss in some but not all studies.

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CIRCUSTANCES REQUIRING DOSE ADUSTMENT Increased dose requirement Decreased intestinal absorption of T4 Malabsorption (e.g. celiac disease) and short bowel syndrome Dietary fiber supplements Drugs: Bile-acid sequestering agents ( colestipol,cholestyramine ) Sucralfate , aluminium hydroxide , Ferrous sulfate 2. increased need for T4 Weight gain Pregnancy 3. increased clearance of T4 Phenobarbital , Phenytoin , Carbamazepine , Rifampicin 4. precise mechanism unknown Amiodarone Sertraline Chloroquine Decreased dose requirement 1. Decreased need for T4 Wight loss Androgens 2. Decreased clearance of T4 Old age

Liothyronine -(LT3): 

Liothyronine -(LT3) Content: Synthetic pure T3 Advantage: Oral administration of L-tri-iodothyronine sodium (which is more readily absorbed than T4) peak levels of serum T3 are observed within 2 to 4 hours because of uniform absorption Disadvantage: Expensive Supraphysiologic T3 level can produce toxicity Requires bid daily dosing Even 25 μg, sometimes associated with cardiac symptoms like palpitations because of fast onset of action. The half-life of T3 is approximately one day.

Liothyronine -(LT3) continued………: 

Liothyronine -(LT3) continued……… Effect on thyroid function test: Low FT4 Normal or increased TT3 Normal TSH Liothyronine : not drug of choice for hormone replacement, monitor T3 and TSH levels Preparations of L-T3 are useful in the management of patients with thyroid cancer to shorten the period of hypothyroidism required for diagnosis and treatment of remaining tumor tissue with I 131 .

Desiccated thyroid: 

Desiccated thyroid Desiccated thyroid is prepared from porcine or bovine thyroid glands Content: Defatted dried pig thyroid containing 0.17-0.23% iodine Advantage: Inexpensive Disadvantage: Poor standardization with variable hormonal content T4/T3 ratios Deterioration with storage Effect on thyroid tests: Normal FT4 / FT4 I Normal TSH Increased TT3 Current guidelines stipulate that one grain (65 mg) of desiccated thyroid contains about 44 μg T4 and 9 μg of T3; the hormones are in the form of thyroglobulin Obsolete product

Liotrix--Combinations of T3 and T4 : 

Liotrix--Combinations of T3 and T4 Liotrix is the only combination preparation T3 and T4 Content: 50 μg T4 and 12.5 μg T3 grain equivalent (4:1 ratio) and mimic natural secretion of hormone It is biologically equivalent to a 65 mg (1 grain) tablet of desiccated thyroid. Advantage: both short and long acting effect Disadvantage: Expensive Effect on thyroid function test: Normal thyroid function values No real need for liotrix since T4 is peripherally converted to T3

Treatment of Overt Hypothyroidism: 

Treatment of Overt Hypothyroidism Goal : normalize TSH level Thyroid hormone replacement therapy with levothyroxine sodium is the treatment of choice for the routine management of primary hypothyroidism Starting dose for healthy patients <50 years should be at 1.6 µg/kg/day Starting dose for healthy patients > 50 years should be < 50 µg/day. Dose should be increased by 25 µg/day, if needed, at 6 to 8 weeks intervals. 1 Start low and go slow Starting dose for patients with heart disease should be 12.5 to 25 µg/day and increase by 12.5 to 25 µg/day, if needed, at 6 to 8 weeks intervals 2

Primary Hypothyroidism Treatment Algorithm: 

Primary Hypothyroidism Treatment Algorithm TSH >4 IU/mL TSH <0.5 IU/mL Initial Levothyroxine Dose Increase Levothyroxine Dose by 12.5 to 25  g/d Repeat TSH Test 6-8 Weeks TSH 0.5- 2.0 IU/mL Symptoms Resolved Measure TSH at 6 Months, Then Annually or When Symptomatic Continue Dose Decrease Levothyroxine Dose by 12.5 to 25  g/d Singer PA, et al. JAMA . 1995;273:808-812. Demers LM, Spencer CA, eds. The National Academy of Clinical Biochemistry Web site. Available at: http://www.nacb.org/lmpg/thyroid_lmpg.stm. Accessed July 1, 2003.

Over - and Under-Replacement Risks: 

Over - and Under-Replacement Risks Over-replacement Risks Reduced bone density/osteoporosis 1 Tachycardia, arrhythmia. atrial fibrillation In elderly or patients with heart disease, angina, arrhythmia, or myocardial infarction Under-replacement Risks Continued hypothyroid state Long-term end-organ effects of hypothyroidism Increased risk of hyperlipidemia

PowerPoint Presentation: 

INTERFERENCE WITH CO-EXISTENT CONDITIONS Hypocortisolemia: Primary hypothyroidism due to chronic autoimmune thyroiditis is associated with primary adrenocortical insufficiency due to autoimmune adrenalitis. The very cause of central hypothyroidism in many instances will also result in ACTH deficiency and secondary adrenocortical insufficiency. If the two entities co-exist, it is important to replace glucocorticoid before starting thyroxine. Ischemic heart disease. Treatment of hypothyroidism with levothyroxine will improve myocardial function and reduce peripheral vascular resistance, it will increase the need for oxygen in the myocardium . In patients with an already compromised myocardial blood supply due to coronary atherosclerosis, thyroxine treatment may provoke anginal symptoms. Drugs. The metabolism of many drugs is slowed in hypothyroidism, resulting in higher sensitivity to a loading dose and a lower maintenance dose. Marked respiratory depression can occur after a single small dose of morphine. An increase in the dose of digoxin or insulin is sometimes noticed once euthyroidism has been stored.

Special cases of hypothyroidism: 

Special cases of hypothyroidism In pregnancy Post partum thyroiditis Myxedema coma Subclincal Hypothyroidism

Thyroid & Pregnancy: Normal Physiology: 

Thyroid & Pregnancy: Normal Physiology Increased estrogen  increased TBG Higher total T4, T3 (normal FT4, FT3 if thyroid gland working properly) hCG peak end of 1 st trimester, weak TSH agonist so may cause slight goitre Fetal thyroid starts working at 11 wks T4 & T3 do NOT cross placenta (or do so minimally)

Hypothyroidism in Pregnancy May Be Difficult to Diagnose: 

Hypothyroidism in Pregnancy May Be Difficult to Diagnose Signs and symptoms (weight gain, fatigue) can overlap with common pregnancy complaints 1 among pregnant hypothyroid patient 2,3 one third have few or no symptoms one third have moderate symptoms one third have classical presentation of hypothyroidism

HYPOTHYROIDISM DURING PREGNANCY : 

HYPOTHYROIDISM DURING PREGNANCY General issues Overt hypothyroidism complicating pregnancy is unusual. Two factors contribute to this finding: some hypothyroid women are anovulatory; and hypothyroidism (new or inadequately treated) complicating pregnancy is associated with a high rate of first trimester spontaneous abortion. Increased rates of fetal loss have also been reported in euthyroid women with high serum anti-thyroid peroxidase antibody concentrations. Often associated with infertility because of ovulatory disturbance Associated with increased risk of obstetrical complications

In continuing pregnancies, hypothyroidism has been associated with an increased risk of several complications, including: : 

In continuing pregnancies, hypothyroidism has been associated with an increased risk of several complications, including: Preeclampsia and gestational hypertension Placental abruption Non reassuring fetal heart rate tracing Preterm delivery, including very preterm delivery (before 32 weeks) Low birth weight (which was likely due to preterm delivery for preeclampsia in one study, but not in a second study where the rate of preeclampsia was negligible. Increased rate of caesarean section Perinatal morbidity and mortality Neuropsychological and cognitive impairment Postpartum hemorrhage The risk of these complications is greater in women with overt, rather than subclinical, hypothyroidism.

PowerPoint Presentation: 

Screening for Thyroid Dysfunction during Pregnancy recommend case finding among the following groups of women at high risk for thyroid disease by measurement of TSH: Women with a history of hyperthyroid or hypothyroid disease, PPT, or thyroid lobectomy. Women with a family history of thyroid disease. Women with a goiter. Women with thyroid antibodies (when known). Women with symptoms or clinical signs suggestive of thyroid underfunction or overfunction, including anemia, elevated cholesterol, and hyponatremia. Women with type I diabetes. Women with other autoimmune disorders. Women with infertility who should have screening with TSH as part of their infertility work-up. Women with previous therapeutic head or neck irradiation. Women with a history of miscarriage or preterm delivery

Treatment of Hypothyroidism in Pregnancy: 

Treatment of Hypothyroidism in Pregnancy Goal : normalize TSH level Women with established hypothyroidism often require thyroxine dose increase Thyroxine dose adjustment should occur in early pregnancy Regular clinical and laboratory follow-up is essential

PowerPoint Presentation: 

Both maternal and fetal hypothyroidism are known to have serious adverse effects on the fetus. Therefore maternal hypothyroidism should be avoided. Targeted case finding is recommended at the first prenatal visit or at diagnosis of pregnancy If hypothyroidism has been diagnosed before pregnancy, adjustment of the preconception thyroxine dose to reach a TSH level not higher than 2.5 μU/mL prior to pregnancy. The T4 dose usually needs to be incremented by 4-6 wk gestation and may require a 30-50% increase in dosage. Hypothyroidism and Pregnancy: Maternal and Fetal Aspects RECOMMENDATIONS Of USPSTF (U.S Preventive Services Task Force )

PowerPoint Presentation: 

If overt hypothyroidism is diagnosed during pregnancy Thyroxine dosage should be titrated to rapidly reach and thereafter maintain serum TSH concentrations of less than 2.5 μU/mL in the first trimester (or 3 μU/mL in the second and third trimester) or to trimester-specific normal TSH ranges. Thyroid function tests should be remeasured within 30-40 days. Women with thyroid autoimmunity who are euthyroid in the early stages of pregnancy are at risk of developing hypothyroidism and should be monitored for elevation of TSH above the normal range. In Subclinical hypothyroidism, T4 treatment has been shown to improve obstetrical outcome but has not been proved to modify long-term neurological development in the offspring After delivery, most hypothyroid women need a decrease in the thyroxine dosage they received during pregnancy )

Postpartum Thyroid dysfunction (PPTd) (silent thyroditis): 

Postpartum Thyroid dysfunction ( PPTd) (silent thyroditis) Definition PPTD is a painless lymphocytic thyroditis characterized by transient thyrotoxicosis alone, transient hypothyroidism alone, thyrotoxicosis followed by hypothyroidism during the postpartum period in women who were euthryroid during pregnancy. It occurs in 3-16% of women biochemically and less clinically Thyrotoxicosis occurs 2-4 months postpartum and lasts 2-6 weeks Hypothyroidism occurs 3-8 months postpartum and lasts 2-6 weeks Thyroid function returns to normal 3-9 month after delivery. Recurrence in subsequent pregnancies Tendency to permanent hypothyroidism

Postpartum Thyroid dysfunction continued………: 

Postpartum Thyroid dysfunction continued……… Patients at high risk Antithyroid peroxidase antibody Type 1 diabetes, Previous history of PPT Other autoimmune disease such as Hashimoto’s disease and Graves’ disease. Clinical features: In case of hypothyroidism complaining of fatigue, poor memory, dry skin and cold intolerance. In case of hyperthyroidism complaining irritability and fatigue Laboratory finding Hypothyroidism characterised by increased TSH and decreased Free T 4 For hyperthyroidism, TSH is suppressed and elevated Free T 4

Treatment of Postpartum Thyroid dysfunction : 

Treatment of Postpartum Thyroid dysfunction Goal : Normalize TSH level Symptomatic hypothyroidism women require treatment with low dose of thyroxine (50-75 microg/day) In case of thyrotoxicosis Atenolol 50-100mg/day Antithyroid drugs are not useful Annually follow up of TSH recommended after return to normal functions

Myxedema coma: 

Myxedema coma Diagnostic criteria Altered mental status. From disorientation and lethargy to psychosis and coma Defective thermoregulation: hypothermia, or the absence of fever despite infectious disease. Precipitating event: cold exposure, infection, drugs (diuretics, tranquillizers, sedatives, analgesics'), trauma, stroke, heart failure, gastrointestinal bleeding. Myxedema coma is a rare, life-threatening clinical condition in patients with long-standing, severe untreated hypothyroidism in whom adaptive mechanisms fail to maintain homeostasis.

Myxedema coma CONTIUED……..: 

Myxedema coma CONTIUED…….. Most cases occur in elderly women and winter. The presence of cool pale skin and absence of mild diastolic hypertension are warning signs. Serum free T4 is low, serum TSH is usually high but sometimes only slightly elevated. Serum creatine phosphokinase mostly extremely elevated.

treatment of myxedema coma: 

treatment of myxedema coma Hypothyroidism large initial intravenous dose of 300-500 μg T4; if no response within 48 hours, add T3 hypocortisolemia intravenous hydrocortisone 200-400 mg daily hypoventilation don’t delay intubation and mechanical ventilation too long hypothermia blankets, no active rewarming hyponatremia mild fluid restriction hypotension cautious volume expansion with crystalloid or whole blood hypoglycemia glucose administration precipitating event identification and elimination by specific treatment (liberal use of antibiotics)

PowerPoint Presentation: 

Subclinical hypothyroidism is defined as an increased serum TSH in the presence of a normal serum F T4 and T3 concentration. Prevalent in women and elderly person SUBCLINICAL HYPOTHYROIDISM (Mild thyroid failure) Subclinical hypothyroidism may have Endogenous causes Chronic autoimmune thyroiditis, Subacute thyroiditis, Postpartum thyroiditis Exogenous causes thyroidectomy, 131I therapy, antithyroid drugs, inadequate thyroid hormone replacement therapy

Progression of Mild Thyroid Failure : 

Progression of Mild Thyroid Failure Years NORMAL RANGE TSH Overt Hypothyroidism Mild Thyroid Failure Euthyroid T 3 T 4 Nature course of subclinical hypothyroidism secondary to chronic autoimmune thyroiditis and spontaneous return to normal TSH values (5-6%) Progression to overt hypothyroidism is common, specially if thyroid antiboies are present

subclinical hypothyroidism : 

subclinical hypothyroidism Symptoms Biochemistry Fatigue and weight gain Depression, Impaired cognitive functions high serum LDL cholesterol low serum HDL cholesterol high serum procollagen II peptide high serum myoglobulin 10 high serum creatine kinase Peripheral tissue function tests frequently indicate a limited degree of thyroid hormone deficiency; example Prolonged Achilles tendon reflex time Prolonged systolic time intervals Decreased myocardial contractility Impaired muscle energy

PowerPoint Presentation: 

Treatment still debated. Nevertheless, a panel of experts found insufficient evidence to recommend routine treatment of patients with subclinical hypothyroidism and took a conservative stand. Thyroxine therapy is recomended in the case of TSH 1o mlU/L or greater or TPO antibodies or both. If TSH <1o mlU/L and TPO antibodies are absent, thyroxine therapy still might be warrented by the presence of symptom, goitor, elevated total or LDL cholesterol, pregnancy, or ovulatory dysfucntion with infertility When in doubt because of non specific complain, a trial of T4 treatment for atleast 3 month can be considered. Such therapy seems specially worthwhile in the case of mood disturbances or cognitive impairment MANAGEMENT OF SCH

FOLLOW UP : 

FOLLOW UP Serum TSH should be checked after 8 weeks, and the dose should be adjusted. Once a normal serum TSH level has been achieved, TSH should be measured again after 6 months and then annually. In younger persons, a reasonable goal for serum TSH is 0.3 to 3.0 mIU/L. For older age groups, the therapeutic goal can be higher. The benefits of fine-tuning levothyroxine therapy to achieve lower levels of serum TSH should be weighed against the possibility of adverse effects of large dose levothyroxine therapy resulting in suppressed TSH.

Summary: 

Summary Mild thyroid failure often underdiagnosed TSH is the Primary diagnostic test TSH screening should be part of routine examination in high-risk patient groups Hypothyroidism is linked to other disease states Early diagnosis ad treatment relieves symptoms, improves co-morbidities and quality of life Careful dose titration and follow-up are essential

PowerPoint Presentation: 

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