Hypothyroidism Nursing 870

Hypothyroidism Hypothyroidism is a common endocrine disorder resulting from deficiency of thyroid hormone Usually a primary process, thyroid gland is unable to produce sufficient amounts of thyroid hormone Can be secondary, the thyroid gland is normal, but it receives insufficient stimulation because of low secretion of thyrotropin (ie, thyroid-stimulating hormone [TSH]) from the pituitary gland May be iatrogenic, drug induced May be congenital

Hypothyroidism: Causes Lack of iodine: most common in the world Autoimmune: most common in the US Hashimoto’s thyroiditis

Thyroid Screening No universal recommendation The American Thyroid Association Screening at age 35 years and every 5 years More frequent if at high risk Pregnant women Women older than 60 years Patients with type 1 diabetes or other autoimmune disease Patients with a history of neck irradiation

Thyroid Screening The American College: screening women older than 50, with 1 or more clinical features of disease The American Academy of Family Physicians: screening asymptomatic patients older than 60 years The American Association of Clinical Endocrinologists: recommends TSH measurements in all women of childbearing age before pregnancy or during the first trimester The US Preventive Task Force concludes that the evidence is insufficient to recommend for or against routine screening for thyroid disease in adults

PollEv: A TSH of 40 is consistent with Hyper - Or Hypo – thyroidism?

Hypothyroidism: Patho The hypothalamic-pituitary-thyroid axis. Levels of circulating thyroid hormones are regulated by a complex feedback system involving the hypothalamus and pituitary gland. Although hypothalamic or pituitary disorders can affect thyroid function, localized disease of the thyroid gland that results in decreased thyroid hormone production is the most common cause of hypothyroidism. Under normal circumstances, the thyroid releases 100-125 nmol of T4 daily and only small amounts of T3. The half-life of T4 is approximately 7-10 days. T4, a prohormone, is converted to T3, the active form of thyroid hormone, in the peripheral tissues by 5’-deiodination.

Hypothyroidism: Patho Early in the disease process, compensatory mechanisms maintain T3 levels Decreased production of T4 causes an increase in the secretion of TSH by the pituitary gland TSH stimulates hypertrophy and hyperplasia of the thyroid gland and 5’-deiodinase activity, thereby increasing T3 production.

Hypothyroidism: Patho CV Decreased contractility Cardiac enlargement Pericardial effusion Decreased pulse, Decreased cardiac output GI tract changes Achlorhydria Prolonged intestinal transit time Gastric stasis GYN Delayed puberty Anovulation Menstrual irregularities, Infertility are common. TSH screening should be a routine part of any investigation into menstrual irregularities or infertility. TSH screening should be a routine part of any investigation into menstrual irregularities or infertility.

Hypothyroidism: Patho Can cause Increased levels of total cholesterol Increased LDL Decreased HDL because of a change in metabolic clearance. In addition Increase in insulin resistance.

Hypothyroidism: Etiology Primary hypothyroidism Chronic lymphocytic (autoimmune) thyroiditis Postpartum thyroiditis Subacute (granulomatous) thyroiditis Drug-induced hypothyroidism Iatrogenic hypothyroidism Genetic Iodine deficiency or excess Postpartum thyroiditis Up to 10% of postpartum women may develop lymphocytic thyroiditis (postpartum thyroiditis) in the 2-12 months after delivery. The frequency may be as high as 25% in women with type 1 diabetes mellitus. Although a short course of treatment with levothyroxine (LT4) may be necessary, the condition is usually transient (2-4 months). However, patients with postpartum thyroiditis (anti-TPO–positive) are at increased risk of permanent hypothyroidism or recurrence of postpartum thyroiditis with future pregnancies. The hypothyroid state can be preceded by a short thyrotoxic state. High titers of anti-TPO antibodies during pregnancy have been reported to have high sensitive and specificity for postpartum autoimmune thyroid disease. The following medications reportedly have the potential to cause hypothyroidism: Amiodarone Interferon alfa Thalidomide Lithium Stavudine Oral tyrosine kinase inhibitors – Sunitinib, imatinib[8] Bexarotene[9] Perchlorate Interleukin (IL)-2 Ethionamide Rifampin Phenytoin Carbamazepine Phenobarbital Aminoglutethimide Sulfisoxazole p -Aminosalicylic acid Ipilimumab Treatment with radioactive iodine: usually within 3-6 mo. Post treatment External neck irradiation (for head and neck neoplasms, breast cancer, or Hodgkin disease) may result in hypothyroidism. Iodine deficiency or excess Worldwide, iodine deficiency is the most common cause of hypothyroidism. Excess iodine, as in radiocontrast dyes, amiodarone, health tonics (herbal and dietary supplements), and seaweed, can transiently inhibit iodide organification and thyroid hormone synthesis (the Wolff-Chiakoff effect). Most healthy individuals have a physiologic escape from this effect. In patients with iodine overload, the sodium-iodide symporter shuts down, and this allows intracellular iodine levels to drop and hormone secretion to resume. The Wolff-Chiakoff effect is short-lived because the sodium-iodide symporter is capable of rapidly downregulation. However, exposure to excess iodine can produce more profound and sustained hypothyroidism in individuals with abnormal thyroid glands (eg, from autoimmune thyroiditis, subtotal thyroidectomy, or prior radioiodine therapy).

Hypothyroidism: Etiology Central hypothyroidism (secondary or tertiary) Results when the hypothalamic-pituitary axis is damaged Pituitary adenoma Tumors impinging on the hypothalamus Lymphocytic hypophysitis Sheehan syndrome History of brain or pituitary irradiation Drugs (eg, dopamine, prednisone, or opioids) Congenital nongoiterous hypothyroidism type 4 TRH resistance TRH deficiency

Hypothyroidism: Epidemiology The National Health and Nutrition Examination Survey (NHANES 1999-2002) of 4392 individuals reflecting the US population reported hypothyroidism (defined as TSH levels exceeding 4.5 mIU/L) in 3.7% of the population The WHO data from 130 countries found inadequate iodine nutrition in 30.6% of the population.

Hypothyroidism: Epidemiology Age Frequency of hypothyroidism, goiters, and thyroid nodules increases with age Most prevalent in elderly populations, with 2-20% of older age groups having some form of hypothyroidism The Framingham study found hypothyroidism (TSH > 10 mIU/L) in 5.9% of women and 2.4% of men older than 60 years

Hypothyroidism: Epidemiology Gender More common in females (2-8 times higher) Race Higher in whites (5.1%) and Mexican Americans than in African Americans (1.7%) African Americans tend to have lower median TSH values.

PollEv: Name a symptom of hypothyroidism:

Hypothyroidism: Symptoms Fatigue, loss of energy, lethargy Weight gain Decreased appetite Cold intolerance Dry skin Hair loss Sleepiness Muscle pain, joint pain, weakness in the extremities Depression Emotional lability, mental impairment Forgetfulness, impaired memory, inability to concentrate Constipation Menstrual disturbances, impaired fertility Decreased perspiration Paresthesias, nerve entrapment syndromes Blurred vision Decreased hearing Fullness in the throat, hoarseness Commonly manifests as a slowing in physical and mental activity but may be asymptomatic. Classic symptoms (cold intolerance, puffiness, decreased sweating, and coarse skin) may not be present as commonly as was once believed. Many of the more common symptoms are nonspecific and difficult to attribute to a particular cause. Individuals can also present with obstructive sleep apnea (secondary to macroglossia) or carpal tunnel syndrome. Women can present with galactorrhea and menstrual disturbances. Consequently, the diagnosis of hypothyroidism is based on clinical suspicion and confirmed by laboratory testing.

Myxedema Coma A severe form of hypothyroidism that results in An altered mental status Hypothermia Bradycardia Hypercarbia Hyponatremia Cardiomegaly, pericardial effusion, cardiogenic shock, and ascites may be present Myxedema coma most commonly occurs in individuals with undiagnosed or untreated hypothyroidism who are subjected to an external stress, such as low temperature, infection, myocardial infarction, stroke, or medical intervention (eg, surgery or hypnotic drugs).

Hypothyroidism: PE Weight gain Slowed speech and movements Dry skin Jaundice Pallor Coarse, brittle, straw-like hair Loss of scalp hair, axillary hair, pubic hair, or a combination Dull facial expression Coarse facial features Periorbital puffiness Macroglossia Goiter (simple or nodular)

Hypothyroidism: PE Hoarseness Decreased systolic blood pressure and increased diastolic blood pressure Bradycardia Pericardial effusion Abdominal distention, ascites (uncommon) Hypothermia (only in severe hypothyroid states) Nonpitting edema (myxedema) Pitting edema of lower extremities Hyporeflexia with delayed relaxation, ataxia, or both Additional signs specific to different causes of hypothyroidism, such as diffuse or nodular goiter and pituitary enlargement or tumor, can occur.

Hypothyroidism: Differential Anemia Autoimmune thyroid disease Goiter Myxedema Subacute Thyroid lymphoma Iodine deficiency Addison’s disease Anovulation Sleep apnea

Hypothyroidism: Differential Cardiac tamponade Chronic fatigue syndrome Constipation Depression Dysmenorrhea Many other considerations related to symptoms

Hypothyroidism: Diagnostics TSH Normal accepted as 0.40-4.2 mIU/L Generally the most sensitive screening tool for primary hypothyroidism Less expensive than other tests Rapid turn around time T4 Generally obtained if TSH is above normal More expensive than TSH Takes longer for results If TSH levels are above the reference range, the next step is measure free thyroxine (T4). Another option is to measure total T4 and binding proteins. T4 is highly protein-bound (99.97%), with approximately 85% bound to thyroid-binding globulin (TBG), approximately 10% bound to transthyretin or thyroid-binding prealbumin, and the remainder bound loosely to albumin. The levels of these binding proteins can vary by hormonal status, inheritance, and in various disease states. Hence, free T4 assays, which measure unbound (ie, free) hormone, are becoming popular. Free T4 assays can be unreliable in the setting of severe illness or pregnancy.

Hypothyroidism: Diagnostics Primary hypothyroidism Elevated TSH levels and decreased T4 If elevated TSH levels (usually 4.5-10.0 mIU/L) but normal T4, considered to have mild or subclinical hypothyroidism

Hypothyroidism: Diagnostics Assays for anti–thyroid peroxidase (anti-TPO) and antithyroglobulin (anti-Tg) antibodies May be helpful in determining the etiology of hypothyroidism or in predicting future hypothyroidism Once antibody positive, repeated antibody testing is not recommended. Anti-TPO antibodies have been associated with increased risk of infertility and miscarriage; levothyroxine (LT4) treatment may lower this risk

Hypothyroidism Overt hypothyroidism Subclinical hypothyroidism Diagnosis when TSH >10 with a subnormal free T4 Subclinical hypothyroidism TSH above normal limit, with a normal free T4 Only if no severe illness and if normal hypothalamic, pituitary axis

Hypothyroidism: Diagnostics CBC: may show anemia Electrolytes: may show dilutional hyponatremia Lipid levels may be elevated Creatinine may be elevated (reversible) Liver function and creatinine kinase elevations have been found

Hypothyroidism: Diagnostics US: used to detect nodules and infiltrative disease Fine needle aspiration: Procedure of choice for evaluating suspicious nodules 5-15% of solitary nodules are cancerous

Hypothyroidism: Treatment Treat any underlying disorder Thyroid replacement (levothyroxine) For most cases of mild to moderate hypothyroidism, a starting levothyroxine dosage of 50-75 µg/day For elderly or if known ischemic heart disease Start at 1/4th to ½ of the expected dosage Adjust in small increments after no less than 4-6 weeks Clinical benefits begin in 3-5 days and level off after 4-6 weeks After dosage stabilization, monitored q 6 months or annually The treatment goals for hypothyroidism are to reverse clinical progression and correct metabolic derangements, as evidenced by normal blood levels of TSH and T4 Achieving a TSH level within the reference range may take several months because of delayed readaptation of the hypothalamic-pituitary axis. When taking levothyroxine dosing changes should be made every 6-8 weeks until the patient’s TSH is in target range.

Hypothyroidism: Treatment If central (ie, pituitary or hypothalamic) hypothyroidism Use T4 levels, not TSH levels to guide treatment In most cases, the free T4 level should be kept in the upper third of the reference range

Hypothyroidism: Treatment Monitor the patients clinical status Look for evidence of overtreatment If symptoms continue after normalization of TSH Investigate other possible causes

Sub-clinical Hypothyroidism Controversy re treatment Treatment has been shown to reduce total cholesterol, non-HDL cholesterol, to decrease arterial stiffness and systolic blood pressure. In patients with concomitant subclinical hypothyroidism and iron deficiency anemia, iron supplementation may be ineffective if levothyroxine not given Arguments include: treatment of these patients improves symptoms, prevents progression to overt hypothyroidism, and may have cardioprotective benefits. Reviews by the US Preventive Services Task Force and an independent expert panel found inconclusive evidence to recommend aggressive treatment of patients with TSH levels of 4.5-10 mIU/L. The Endocrine Society recommends T4 replacement in pregnant women with subclinical hypothyroidism. The American College of Obstetricians and Gynecologists does not recommend replacement as a routine measure. Ultrasonography may have prognostic value in subclinical hypothyroidism. In an Italian study, progression to overt hypothyroidism occurred more often in patients whose ultrasonographic thyroid scan showed diffuse hypoechogenicity (an indication of chronic thyroiditis).

Sub-clinical Hypothyroidism Treat for TSH > 10 mIU/L Treat for TSH 5-10 mIU/L in conjunction with goiter or positive anti-TPO antibodies (Guidelines from the American Association of Clinical Endocrinologists) These patients have the highest rates of progression to overt hypothyroidism. An initial LT4 dosage of 50-75 µg/day can be used, titrated every 6-8 weeks to achieve a target TSH of between 0.3 and 3 mIU/L

References Garber, J., Cobin, R., Gharib, H., Hennessey, J., Klein, I., et al. (2012). Clinical practice guidelines for hypothyroidism in adults: Cosponsored by the American Association of Endocrinologist and the American Thyroid Association. Endocrine Practice, 18, 6, 988-1028, Available at: https://www.aace.com/files/final-file-hypo-guidelines.pdf