Содержание
-
Thyroid Disease and Cancer
Amy E. Baker, PA-C Clinical Medicine
-
Review: Thyroid
Gland comprised of two lobes spanning the trachea Produces thyroxine (T4) and triiodothyronine (T3) T4 is produced only in the thyroid 20-25% of T3 is secreted by the thyroid, the rest is formed by deiodination of T4
-
Role of Thyroid Hormones
Stimulate neural and skeletal development during fetal life Stimulate oxygen consumption at rest and bone turnover Increase GI motility Increase heart rate and contractility Maintain basal body temperature Increase production of RBC’s Control respiratory drive Increase metabolism
-
Thyroid Hormone Secretion
-
Regulated by a feedback system involving the hypothalamus, pituitary gland, and thyroid gland TRH (thyrotropin-releasing hormone) is secreted by the hypothalamus This stimulates the synthesis and release of TSH from the anterior pituitary
-
TSH stimulates the thyroid gland to produce T3 and T4 T3 and T4 directly inhibit the pituitary TSH secretion Negative feedback will increase free thyroid hormones that cause a decrease in TSH secretion and vice versa Becomes very useful in evaluating signs and symptoms of thyroid disease
-
Hypothyroidism aka Myxedema
Deficiency of thyroid hormone secretion causing a generalized slowing of metabolism Primary disease of the thyroid, secondary disease of lack of pituitary TSH, or tertiary disease resulting in failure of hypothalamus to secrete TRH
-
Hypothyroidism
Most common cause- Hashimoto’s Thyroiditis (aka Chronic Lymphocytic Thyroiditis) Also caused by iodine deficiency, thyroid ablation, radiation, medications, adenomas, pituitary destruction, sarcoidosis Amiodarone (due to high concentration of iodine in the drug) Hepatitis C patients (due to administration of interferon during treatment)
-
Hypothyroidism: Signs and Symptoms
Early S/S Lethargy Weakness Cold intolerance Constipation Dry Skin Menorrhagia Depression Mild weight gain Late S/S Slowed speech Lack of sweating Peripheral edema Hoarseness Decreased sense of taste and smell Increased weight gain
-
Hypothyroidism: Physical Exam Findings
Early PE Thin brittle nails Thinning of hair Pallor Delayed deep tendon reflexes Bradycardia Late PE Goiter Puffiness of face and eyelids Carotenemic skin color Hard pitting edema Pleural, peritoneal, and pericardial effusions
-
Goiter
Diffuse enlargement of the thyroid Associated with hypothyroidism caused by Hashimoto’s, iodine deficiency, genetic thyroid enzyme defects, or drugs Hypothyroid phase that occurs in subacute viral thyroiditis
-
Hashimoto’s Thyroiditis
Presents with enlarged tender thyroid gland Positive thyroid antibodies Increased TSH Can resolve on its own, but mostly treated with synthetic thyroxine
-
Hypothyroidism: Differential Diagnosis
Any other condition causing unexplained menstrual abnormalities, myalgias, constipation, weight changes, hyperlipidemia, or anemia Myxedema added into DDX of unexplained CHF without relief from traditional medical therapy Unexplained ascites Depression and psychosis Pituitary adenomas
-
Primary Hypothyroidism: Labs
Increased TSH (normal 0.4-5.5) Overt: TSH increased, free T4 low: treat Subclinical: TSH increased: free T4 normal: subclinical, treat if symptomatic or TSH over 10, controversial Antibody titers of thyroperoxidase and thyroglobulin increased in Hashimoto’s May also see increased cholesterol Nonspecific findings such as increased LFT’s, anemia, hyponatremia, hypoglycemia, increased creatinekinase
-
Hypothyroidism: Treatment
Treatment of choice is levothyroxine Dosing is typically calculated at 1.6mcg/kg/day Starting doses vary depending on age, pregnancy, and other comorbidities, usually start with 50-100 mcg Start low, go slow with elderly (25 mcg) Early treatment has a very good outcome Overt: TSH increased, free T4 low: treat Subclinical: TSH increased: free T4 normal: subclinical, treat if symptomatic or TSH over 10, controversial Patients taking same daily dose demonstrate a significant increase in serum T4 levels within 1-2 weeks and near peak in 3-4 weeks
-
Monitor labs after 1 month, then 3 months, then every 6 months to evaluate efficacy of maintenance dose and need for dose adjustment Relapse can occur if treatment is interrupted Maintenance dose varies between 75-250mcg
-
Hypothyroidism: Complications
Mostly cardiac in nature secondary to overzealous thyroid replacement Increased susceptibility to infection Psychosis Miscarriage in pregnancy TSH secreting tumors Myxedema Coma
-
Myxedema Coma
Associated with severe hypothyroidism Induced by underlying infection (cardiac, pulmonary, or CNS), cold exposure, or drug use Caused by interstitial accumulation of mucopolysaccharides and inappropriate secretion of ADH leading to lymphedema Hyponatremia results from impaired renal tubular sodium reabsorption
-
Sx- hypothermia, hypoventilation, hyponatremia, hypoxia, hypercapnia, hypotension, convulsions, and CNS signs Mostly seen in elderly women High mortality rate, medical emergency
-
Myxedema Coma: Treatment
Levothyroxine sodium 400 mcg IV as loading dose, then 100 mcg IV daily Treat hypothermia with warming blankets Treat hypercapnia with intubation and ventilation Treat any underlying infection Assess for and treat patients with adrenal insufficiency with hydrocortisone
-
Hypothyroidism and Pregnancy
Critical to treat mother early on as fetus depends on T4 from mother for CNS development Maternal hypothyroidism in 1st Trimester has shown to cause some developmental delays Follow mother with TSH levels every 4-6 weeks Tight control with narrower window in pregnancy
-
Dosing of levothyroxine is variable Women who are already hypothyroid before pregnancy typically need a dose increase of 30% once pregnancy is confirmed Typically return to their original dose post-partum
-
Congenital Hypothyroidism: Cretinism
Common cause of preventable mental retardation Affects 1:5000 infants Evident in 1st several months Can be due to congenital lack of thyroid or abnormal biosynthesis TH is essential for normal brain development and growth Neonatal screenings have been implemented to detect early If treated properly, risk of mental retardation in nonexistent Treatment of choice: levothyroxine lifelong
-
Cretinism
Parents will report: Feeding problems Somnolence Jaundice Flaccidity Constipation Developmental delays Child will present with: Broad flat nose Protruding tongue Protruding abdomen Development of goiter Umbilical hernia Delayed growth, short stature Developmental delays
-
Children with cretinism
-
Hyperthyroidism
-
Hyperthyroidism aka Thyrotoxicosis
Involves an increase of thyroid hormone Increased rate of metabolism Most common cause is Grave’s Disease Autoimmune Gland is usually enlarged Mostly women (8:1 ratio to men) Onset between 20-40 years of age Familial tendency
-
Hyperthyroidism
Commonly associated with DM, myasthenia gravis, and pernicious anemia Grave’s patients are at an increased risk of developing Addison’s disease, alopecia areata, celiac disease, DM I, myasthenia gravis, cardiomyopathy, and hypokalemic periodic paralysis
-
Hyperthyroidism Grave’s disease
Accompanied by infiltrative ophthalmopathy (exophthalmus) and pretibial myxedema Grave’s demonstrates positive antibodies on thyroid panel
-
Other Causes of Hyperthyroidism
Most common cause-Grave’s Disease Toxic adenomas Subacute thyroiditis Thyrotoxicosis factitia Medications, especially amiodarone Also pituitary tumor, pregnancy, thyroid cancer
-
Hyperthyroidism: Signs and Symptoms
Symptoms Nervousness Restlessness Heat intolerance Muscle cramps Frequent bowel movements Weight changes (mostly loss) Palpitations Angina Menstrual irregularities Physical Exam Findings Stare Lid lag Fine resting tremor Moist warm skin Hyperreflexia Fine hair A-fib Ophthalmopathy
-
Hyperthyroidism: Differential Diagnosis
Anxiety or mania Anemia, leukemia, polycythemia Pheochromocytoma Acromegaly True cardiac arrythmias Myasthenia gravis
-
Primary Hyperthyroidism: Labs
Decreased TSH, usually less than 0.1 Increased T3, T4, thyroid resin uptake, Free T4 Increased RAI uptake in Grave’s
-
Hyperthyroidism: Treatment
Often treated by endocrinology upon initial diagnosis Varies according to age and severity Propanolol Symptomatic relief of tremor, tachycardia, diaphoresis, and anxiety Used until hyperthyroidism definitively treated Also treatment of choice for thyroid storm
-
Thiourea Drugs Methimazole or Propylthiouracil (PTU) Used for young adults or patients with mild hyperthyroidism, small goiters, or those who do not want isotope therapy Can be administered long term Lower occurrence of post-treatment hypothyroid than with surgery or RAI PTU is drug of choice during lactation and pregnancy
-
Iodinated contrast agents Effective for temporary relief Iopanoic acid or ipodate sodium Effective with severely symptomatic patients
-
Radioactive Iodine Excellent method of destroying overactive thyroid tissue by damaging the cells that concentrate it No increased risk of malignancy following treatment Contraindicated during pregnancy Usually given with propanolol Higher failure rate if given to Grave’s patients also on methimazole or PTU
-
Radioactive Iodine complications Exophthalmus/Grave’s ophthalmopathy can worsen afterwards in 15% of patients (incidence is higher in smokers) Lifelong follow-up with labs Higher incidence of rebound hypothyroidism
-
Thyroid Surgery Surgical removal of all or part of gland Good option for women who are pregnant or have small children Risk of hypoparathyroidism and laryngeal nerve palsy
-
Hyperthyroidism: Complications
Grave’s Ophthalmopathy Subacute Thyroiditis Cardiac Complications A-fib Sinus tach Heart failure
-
Thyroid Crisis or Storm Occurs with stressful illness, thyroid surgery, or RAI administration S/S: marked delerium, severe tachycardia, n/v/d, dehydration, very high fever Very high mortality rate Propanolol is the drug of choice
-
Pretibial myxedema Thyrotoxic hypokalemia Periodic paralysis Suspect in Asian/Native American men with sudden symmetric flaccid paralysis, hypokalemia, and hypophosphatemia
-
Hyperthyroidism and Pregnancy
Very rare Diagnosis may be delayed because many s/s are similar to what is considered “normal pregnancy” Increased risk of thyroid storm Fetal retardation of growth Premature delivery
-
Subclinical Hyperthyroidism
Asymptomatic individuals with decreased TSH and normal T3 and Free T4 Usually does not progress to overt thyrotoxicosis Can be at increased risk of bone loss Chance of developing complications is low
-
Prognosis of Hyperthyroidism
Rarely subsides spontaneously Variety of options for treatment Complications can persist after treatment Recurrence even after treatment is common Post-treatment hypothyroidism is common Women are at an increased risk of death from thyroid disease
-
Thyroid Nodules and Multinodular Goiter
-
General Information
Diffuse or nodular palpable enlargement 4% of North American adults Incidence greater in iodine deficient areas Most patients are euthyroid, but still have an increased incidence of hyper/hypothyroidism Most nodules are benign (70%)
-
Diffuse Multinodular Goiter
Usually benign Causes Benign multinodular goiter Iodine deficiency Pregnancy Grave’s disease Hashimoto’s thyroiditis Subacute thyroiditis Infection
-
Solitary Thyroid Nodule
Mostly benign adenoma Colloid nodule Cysts Sometimes primary thyroid malignancy or metastatic neoplasm
-
Incidence of malignancy increases in patients with a history of head/neck radiation, family history of thyroid cancer, or history of other malignancies Increased risk of malignancy in nodules that are large, adherent to the trachea or strap muscles, or those associated with lymphadenopathy
-
Nodules or goiter can be large enough to be cosmetically embarrassing, cause discomfort, hoarseness, or dysphagia Retrosternal large multinodular goiters can cause dyspnea or SVC syndrome
-
Evaluation and Treatment of Nodules
Ultrasound first- can also aid with biopsy or aspiration Biopsy indicated if nodules are growing as being monitored, appear malignant, or if over 1 cm Follow-up ultrasound in 3 months to 1 year if findings are non-invasive for stability
-
Radioactive Iodine (RAI) uptake scan-radioactive iodine (I131 or I123 injection to evaluated hot (hyperfunctioning) vs. cold (hypofunctioning) has limited use Oncology referral and radiation if indicated Toxic Solitary Nodules treated with surgery or RAI Toxic Multinodular Goiter treated with propanolol, RAI more so than surgery, and methimazole
-
Thyroid Cancer
-
Female:Male ratio 3:1 26,000 people in U.S. are diagnosed with thyroid cancer yearly and 1/250 people eventually receive this diagnosis About 13% of people at time of autopsy are found to have thyroid cancer
-
Types of Thyroid Cancer
Papillary Follicular Medullary Anaplastic
-
Thyroid Cancer: Papillary
Most common, least aggressive 81% of all thyroid cancers Usually presents as a single thyroid nodule Caused by genetic mutations or translocations Radiation exposure can cause it to be more aggressive
-
Tumor spreads via lymphatics becoming multifocal in 60% of patients, and involving both lobes in 30% 80% have microscopic mets in cervical lymph nodes Even with palpable mets, mortality rate does not increase, but risk of local occurrence increases Chronic low grade papillary cancer can sometimes undergo late anaplastic transformation into aggressive cancer
-
Thyroid Cancer: Follicular
Results from gene mutations or translocations 14% of all thyroid cancers, more aggressive than papillary Some secrete enough T4 to cause thyrotoxicosis if tumor load becomes significant
-
Mets- neck, bone, lung Most absorb iodine to make diagnostic imaging possible Poorly differentiated and oncocytic cell variants are associated with high risk of mets and recurrence
-
Thyroid Cancer: Medullary
Caused by germline mutations 3% of all thyroid cancers (1/3 familial, 1/3 sporadic, 1/3 MEN Type 2) Genetic analysis needed for diagnosis Arises from parafollicular thyroid cells that can secrete calcitonin, prostaglandins, serotonin, ACTH, and other peptides Can cause symptoms and be used as tumor markers
-
Early mets usually present adjacent to muscle and trachea and mediastinal lymph nodes Late mets to bone, lung, adrenals, liver Does not concentrate iodine Symptoms are flushing and diarrhea
-
Thyroid Cancer: Anaplastic
Least common, most aggressive Caused by gene mutations 2% of thyroid cancers Older patients present as a rapidly enlarging goiter or mass Mets early to surrounding nodes and distant sites Local pressure symptoms of dysphagia, hoarseness, vocal cord paralysis Does not concentrate iodine
-
Other Thyroid Malignancies
3% of all thyroid cancers Lymphomas Older women Rapidly forming enlarged painful mass arising out of multinodular goiter and affected by autoimmune thyroiditis Mostly B-cell or MALT Metastatic cancer from bronchogenic, breast, or renal cancers, or malignant melanoma
-
Thyroid Cancer: Labs and Studies
Labs usually normal with the exception of hormone secreting tumors RAI entire body scan- used after thyroidectomy for surveillance and to look for mets U/S-evaluate nodule or goiter/aid in guidance for biopsy CT/MRI-search for mets PET Scan-search for bone mets
-
Thyroid Cancer: Treatment
Surgery (treatment of choice) Need for thyroid hormone replacement for life s/p surgery Monitor TSH Thyroid cancer is resistant to chemo RAI therapy Radiation
-
Thyroid Cancer: Prognosis
Papillary Very good especially in adults
-
Medullary 10 year survival rate 90% confined to thyroid 70% in cervical nodes 20% in distant mets Women
-
Questions?
Нет комментариев для данной презентации
Помогите другим пользователям — будьте первым, кто поделится своим мнением об этой презентации.