hypothyroidism final draft

Hypothyroidism

Dr.HASSAN EL MEEDANI UNDERSUPERVISION OF DR.AMAL AL ALI CONSULTANT FM,ASSOCIATE DIRECTOR OF FM PROGRAM

Objectives

• Case discussion• Epidemiology• Classification • Causes• Clinical approach• Screening• Diagnosis• Hypothyroidism with pregnancy• Treatment and dose adjustment• Referral and consultation

Case 1

A 27 years old, female, presents to the office with a chief complaint of chronic fatigue for about 4 months. She reports 17 pounds weight gain over the last 3 months, despite a decreased appetite . She became more sleepy lately.

What is your approach for the case above ? How can the diagnosis best be confirmed?What is the MOST likely cause of this patient’s disease ?

LABORATORY RESULTS for the patient are

WBC: 4,500 cells/mm3Hb: 11 g/dLHct: 32% MCV 91TSH: 22.3 IU/mL (0.4 to 4.8)Free T4: 0.56 ng/dL (0.93 to 1.70)

List the expected laboratory finding for this patient How should this patient be managed ?

Your patient is started on 25 mcg levothyroxine (Synthroid) and is scheduled to return in 2 months.

At follow-up, she reports a general improvement in symptoms but is not “back to normal.” She reports continues constipation, lack of energy, and feeling depressed. She has not lost any further weight . Laboratory results are as follows: TSH: 11.8 IU/mL Free T4: 0.75 ng/dL (0.93 to 1.70)

What adjustments, if any, should be made to her regimen ? How you follow up your patient ?

Case 2

A 25-year-old woman complains of fatigue and cold intolerance increasing over the past 3 months.

On examination, she manifests dry skin, which she says is a change from her usual. She admits to be puzzled and saddened over the situation.

heart rate is 65 b/m with regular rhythm. Bp123\80 ..TSH level is 0.3 IU/mL (0.4 to 4.8).

She gives a further history of difficult labor with sever bleeding required ICU admission.

What is the most likely cause of her condition ?What is the most important consideration in the management of this patient ?

Case 3

A 38-year-old woman is seen in your office for a complete baseline health assessment. She feels well and tells you that she is “wonderfully healthy except for lack of energy she have lately .

You perform thyroid function test that show her TSH to be elevated 10mu/l and her free T4 to be normal.

What is your diagnosis ? What is your management approach for this patient ?

Types:• Subclinical hypothyroidism is characterized by a serum TSH above the upper

reference limit in combination with a normal free thyroxine (T4). This designation is only applicable when thyroid function has been stable for weeks or more, the hypothalamic-pituitary-thyroid axis is normal, and there is no recent or ongoing severe illness.

• Overt Hypothyroidism elevated TSH, usually above 10 mIU/L, in combination with a subnormal free T4.

Epidemiology

• Data blow derived from the National Health and Nutrition Examination Survey (NHANES III) in USA.

• The prevalence of subclinical disease was 4.3% and overt disease 0.3%.

• The prevalence increases with age, and is higher in females than in males. Ratio 2:1

• It is estimated that nearly 13 million Americans have undiagnosed hypothyroidism.

Causes

• Hypothyroidism may occur as a result of gland failure (Primary), or insufficient thyroid gland stimulation by the hypothalamus or pituitary gland (Secondary).

• Primary Hypothyroidism result from congenital abnormalities, autoimmune destruction (Hashimoto disease), iodine deficiency, and infiltrative diseases.

• Autoimmune thyroid disease is the most common etiology of hypothyroidism in the United States.

• The Most common cause worldwide is iodine deficiency.

Cont’d

• Iatrogenic.

• Disorders generally associated with transient hypothyroidism include postpartum thyroiditis, subacute thyroiditis, silent thyroiditis, and thyroiditis associated with thyroid-stimulating hormone (TSH) receptor-blocking antibodies.

• Drugs classically associated with thyroid dysfunction include lithium, amiodarone, interferon alfa, interleukin-2, and tyrosine kinase inhibitors .

Cont’d

Central hypothyroidism occurs when there is insufficient production of bioactive TSH due to :

a) Pituitary or hypothalamic tumors (including craniopharyngiomas), inflammatory (lymphocytic or granulomatous hypophysitis) or infiltrative diseases. b)Hemorrhagic necrosisc)Surgical and radiation treatment for pituitary or hypothalamic disease.

Cont’d

• Consumptive hypothyroidism is a rare condition that may occur in patients with hemangiomata and other tumors in which type 3 iodothyronine deiodinase is expressed, resulting in accelerated degradation of T4 and triiodothyronine (T3).

Clinical Presentation

• Symptoms of hypothyroidism may vary with age and sex.

• Infants and children may present more often with lethargy and failure to thrive.

• Women who have hypothyroidism may present with menstrual irregularities and infertility.

• In older patients, cognitive decline may be the sole manifestation.

Common Symptoms

ArthralgiaCold intoleranceConstipationDepressionDifficulty concentratingDry skinFatigueHair thinning/hair lossMemory impairmentMenorrhagiaMyalgiaWeaknessWeight gain

Clinical SignsBradycardia

Coarse facies

Cognitive impairment

Delayed relaxation phase of deep tendon reflexes

Diastolic hypertension

Edema

Goiter

Lateral eyebrow thinning

Low-voltage electrocardiography

Macroglossia

Periorbital edema

Pleural and pericardial effusion

Laboratory results

Elevated C-reactive protein

Hyperprolactinemia

Hyponatremia

Increased creatine kinase

Increased low-density lipoprotein cholesterol

Increased triglycerides

Normocytic, Macrocytic anemia

Proteinuria

screening

American Thyroid Association Women and men >35 years of age should be screened every 5 years.

American Association of Clinical Endocrinologists Older patients, especially women, should be screened.

American Academy of Family Physicians Patients ≥60 years of age should be screened.

American College of Physicians Women ≥50 years of age with an incidental finding suggestive of symptomatic thyroid disease should be evaluated.

U.S. Preventive Services Task Force Insufficient evidence for or against screening.

Royal College of Physicians of London Screening of the healthy adult population unjustified.

Screening

• While there is no consensus about population screening for hypothyroidism, there is compelling evidence to support case finding for hypothyroidism in those with:

• Autoimmune disease, such as type 1 diabetes • Pernicious anemia • First-degree relative with autoimmune thyroid disease • history of neck radiation to the thyroid gland including radioactive iodine therapy for hyperthyroidism and external beam radiotherapy for head and neck malignancies • Prior history of thyroid surgery or dysfunction • Abnormal thyroid examination • Psychiatric disorders • Taking amiodarone or lithium

Diagnosis

• The best laboratory assessment of thyroid function, and the preferred test for diagnosing primary hypothyroidism, is a serum TSH test.

• If the serum TSH level is elevated, testing should be repeated with a serum free thyroxine (T4) measurement.

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• Overt primary hypothyroidism is indicated with an elevated serum TSH level and a low serum free T4 level.

• An elevated serum TSH level with a normal range serum free T4 level is consistent with subclinical hypothyroidism.

• A low serum free T4 level with a low, or inappropriately normal, serum TSH level is consistent with secondary hypothyroidism and will usually be associated with further evidence of hypothalamic-pituitary insufficiency.

Treatment

• Most patients will require lifelong thyroid hormone therapy.

• The normal thyroid gland makes two hormones: T4 and T3. Although T4 is produced in greater amounts, T3 is the biologically active form.

• Approximately 80%of T3 is derived from the peripheral conversion of T4. Because T3 preparations have short biologic half-lives, hypothyroidism is treated almost exclusively with once-daily synthetic thyroxine preparations. Once absorbed, synthetic thyroxine, like endogenous thyroxine, undergoes deiodination to the more biologically active T3.

• The starting dosage of levothyroxine in young, healthy adults for complete replacement is 1.6 mcg per kg per day.

• Levothyroxine dosing for infants and children is weight-based and varies by age.

• Thyroid hormone is generally taken in the morning, 30 minutes before eating.

• Patients who have difficulty with morning levothyroxine dosing may find bedtime dosing an effective alternative.

• In a well-designed study conducted in the Netherlands, bedtime dosing of levothyroxine resulted in lower TSH and higher free T4 levels, but no difference in quality of life.

• Alternatively, patients with marked difficulty in adhering to a once-daily levothyroxine regimen can safely take their entire week's dosage of levothyroxine once weekly.

Special Populations

• Six populations deserve special consideration:

(1) older patients(2) patients with known or suspected ischemic heart disease (3) pregnant women (4) patients with persistent symptoms of hypothyroidism despite taking adequate doses of levothyroxine(5) patients with subclinical hypothyroidism(6) patients suspected of having myxedema coma

OLDER PATIENTS AND PATIENTS WITH ISCHEMIC HEART DISEASE

• Initial dosage is generally 25 mcg or 50 mcg daily, with the dosage increased by 25 mcg every three to four weeks until the estimated full replacement dose is reached.

• Thyroid hormone increases heart rate and contractility, therefore increases myocardial oxygen demand. Starting at higher doses may precipitate acute coronary syndrome or an arrhythmia.

• However, there are no high-quality studies that show that lower starting doses and slow titration result in fewer adverse effects than full-dose levothyroxine replacement in these patients.

PREGNANCY

• Thyroid hormone requirements increase during pregnancy.

• In one prospective study, 85% of pregnant patients required a median increase of 47% in their thyroid hormone requirements.

• These increases in levothyroxine dosing were required as early as the fifth week of pregnancy in some patients, which is before the first scheduled prenatal care visit.

• It is recommended that women on fixed doses of levothyroxine take nine doses each week (one extra dose on two days of the week), instead of the usual seven, as soon as pregnancy is confirmed.

• Serum TSH should be measured at four to six weeks' gestation, then every four to six weeks until 20 weeks' gestation, then again at 24 to 28 weeks' and 32 to 34 weeks' gestation (Grade C).

• The increase in thyroid hormone requirement lasts throughout pregnancy.

• Hypothyroidism during pregnancy should be treated with levothyroxine, with a serum TSH goal of less than 2.5 mIU per L (Grade A).

• Screening for hypothyroidism in pregnancy apply only for high risk pregnant ladies for hypothyroidism(Grade C).

Effects of Hypothyroidism on Pregnancy Outcomes

Anemia

Hypertension

Preeclampsia

Abruptio placenta

Postpartum hemorrhage

Maternal Fetal

Miscarriage

Preterm delivery

Low birth weight

Stillbirth

Psychoneurologic impairment

PATIENTS WITH PERSISTENT SYMPTOMS

• A small number of patients with hypothyroidism, mostly women, treated with an adequate dose of levothyroxine will report persistent symptoms such as fatigue, depressed mood, and weight gain despite having a TSH level in the normal range.

• Some patients may have an alternative cause for their symptoms; so a limited laboratory and clinical investigation is reasonable.

• Combination T3/T4 therapy, in the form of desiccated thyroid hormone preparations (thyroid USP, Armour thyroid) or levothyroxine plus liothyronine (Cytomel), is sometimes prescribed for those patients.

• Desiccated thyroid hormone preparations are not recommended by the AACE for the treatment of hypothyroidism, and a meta-analysis of 11 randomized controlled trials of combination T3/T4 therapy versus T4 monotherapy showed no improvements in bodily pain, depression, or quality of life.

• A subsequent study showed that a small subset of patients who have a specific type 2 deiodinase polymorphism may benefit from combination therapy.

• However, there is insufficient evidence to recommend the use of combination T3/T4 in treatment of primary hypothyroidism. Furthermore, genetic testing for a type 2 deiodinase polymorphism is not practical.

Alternative Causes of Persistent Symptoms in Patients with Normal-Range TSH Levels

Adrenal insufficiency (rare)

Anemia

B12 deficiency

Iron deficiency

Chronic kidney disease

Depression, anxiety disorder, and/or somatoform disorders

Liver disease

Obstructive sleep apnea

Viral infection (e.g., mononucleosis, Lyme disease, human immunodeficiency virus/AIDS)

Vitamin D deficiency

Common Reasons for Abnormal TSH Levels on a Previously Stable Dosage of Thyroid Hormone• Decreased absorption of thyroid hormone:

a) Patient is now taking thyroid hormone with food. b)Patient takes thyroid hormone within four hours of calcium, iron, soy products, or aluminum-containing antacids. c) Patient is prescribed medication that decreases absorption of thyroid hormone, such as cholestyramine (Questran), colestipol (Colestid), orlistat (Xenical), or sucralfate (Carafate).

• Patient nonadherent to thyroid hormone regimen (missing doses).

• Patient is now pregnant or recently started or stopped estrogen-containing oral contraceptive or hormone therapy.

• Generic substitution for brand name or vice versa, or substitution of one generic formulation for another.

• Patient started on sertraline (Zoloft), another selective serotonin reuptake inhibitor, or a tricyclic antidepressant.

• Patient started on carbamazepine (Tegretol) or phenytoin (Dilantin).

SUBCLINICAL HYPOTHYROIDISM

• Subclinical hypothyroidism is a biochemical diagnosis defined by a normal-range free T4 level and an elevated TSH level.

• Patients may or may not have symptoms attributable to hypothyroidism. On repeat testing, TSH levels may spontaneously normalize in many patients.

• However, in a prospective study of 107 patients older than 55 years, an initial TSH level greater than 10 to 15 mIU per L was the variable most strongly associated with progression to overt hypothyroidism.

• Elevated thyroid peroxidase antibody titers also increase the risk of progressing to frank thyroid gland failure, even when the TSH level is less than 10 mIU per L.

• Treatment with levothyroxine should be considered for patients with: 1 Initial TSH levels greater than 10 mIU per L. 2 Elevated thyroid peroxidase antibody titers. 3 Symptoms suggestive of hypothyroidism and TSH levels between 5 and 10 mIU per L. 4 Pregnancy or are attempting to conceive.

Myxedema coma

• Myxedema coma is a rare but extremely severe manifestation of hypothyroidism that most commonly occurs in older women who have a history of primary hypothyroidism.

• Mental status changes including lethargy, cognitive dysfunction, and even psychosis, and hypothermia are the hallmark features of myxedema coma.

• Hyponatremia, hypoventilation, and bradycardia can also occur.

• Because myxedema coma is a medical emergency with a high mortality rate, even with appropriate treatment, patients should be managed in the ICU where proper ventilatory, electrolyte, and hemodynamic support can be given. Corticosteroids may also be needed.

• A search for precipitating causes such as infection, cardiac disease, metabolic disturbances, or drug use is critical.

Treatment Summary

Levothyroxine Dosing Guidelines for Hypothyroidism in AdultsNonpatientspregnant1.6 mcg per kg per day initial dosage.

Older patients; patients with known or suspected cardiac disease25 or 50 mcg daily starting dosage; increase by 25 mcg every three to four weeks until full replacement dosage reached.

Pregnant patients Increase to nine doses weekly (one extra dose on two days of the week) at earliest knowledge of pregnancy; refer to endocrinologist.

Patient with subclinical hypothyroidism - TSH < 10 mIU per L: 50 mcg daily, increase by 25 mcg daily every six weeks until TSH = 0.35 to 5.5 mIU per L.- TSH ≥ 10 mIU per L: 1.6 mcg per kg per day.

When to refer patients with hypothyroidism:

• Age??.• Cardiac disease.• Coexisting endocrine diseases.• Myxedema coma suspected.• Pregnancy.• Presence of goiter, nodule, or other structural thyroid gland

abnormality.• Unresponsive to therapy.

• References :• American academy of endocrinologists…• American thyroid assosciation…• American academy of family physicians…• Uptodate .com

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hypothyroidism final draft

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