5/5/11. Overview. THYROID Diagnosis and Treatment. The Endocrine System. Thyroid

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1 The Endocrine System Thyroid THYROID Diagnosis and Treatment Robert Ferraro, MD Medical Director Southwest Endocrinology Assoc. Albuquerque, NM Physiology Diagnostic Testing Pathology Hypothyroidism Hyperthyroidism Thyroid nodules Thyroid cancer Medical therapy Overview 1

2 Thyroid - Anatomy Thyroid - Physiology Thyroid - Physiology 1 - thyroid follicle 2 - cavity of the thyroid follicle, filled with colloid 3 - blood vessel 4 - parafollicular cells forming interfollicular clumps 2

3 Thyroid - Physiology Thyroid - Physiology Thyroid - Physiology 3

4 Thyroid - Physiology Functions of thyroid homone: important in regulating body energy, the body's use of other hormones and vitamins, and the growth and maturation of body tissues. Thyroid Symptoms Symptoms of Hypothyroidism fatigue, exhaustion feeling run down and sluggish depression difficulty concentrating, brain fog unexplained or excessive weight gain dry, coarse and/or itchy skin dry, coarse and/or thinning hair feeling cold, especially in the extremities constipation muscle cramps increased menstrual flow more frequent periods infertility/miscarriage Thyroid - Symptoms Symptoms of Hyperthryoidisim nervousness irritability increased perspiration thinning of your skin fine brittle hair muscular weakness especially involving the upper arms and thighs shaky hands panic disorder insomnia racing heart more frequent bowel movements weight loss despite a good appetite lighter flow, less frequent menstrual periods 4

5 Thyroid Diagnostic studies Physical exam Thyroid function tests Imaging studies Ultrasound Nuclear Medicine Radio-iodine uptake Thyroid scan Thyroid thyroid function tests Thyroid Diagnostic imaging Thyroid Ultrasound 5

6 Thyroid - Ultrasound Thyroid Nuclear medicine Thyroid scan Thyroid Physical exam 6

7 Thyroid Physical exam Thyroid Physical exam Thyroid - Cases 7

8 Thyroid - Pathophysiology Hypothyroidism Primary Autoimmune thyroid disease (Hashimoto s thyroiditis) Post-surgical Post-radioiodine treatment Secondary Pituitary tumor Pituitary surgery/radiation 8

9 Thyroid - Hypothyroidism Diagnosis Clinical symptoms: Physical findings: Laboratory findings: Thyroid Hyperthyroidism Causes Autoimmune (Grave s disease) Toxic thyroid nodule/toxic mutinodular thyroid Iatrogenic Factitious Iodine induced Medication side effects Thyroid - Hyperthyroidism Diagnosis Clinical symptoms: Physical findings: Laboratory findings: 9

10 Thyroid Case stories - #1 24 y/o female referred for evaluation of abnormal thyroid functions and possible hyperthyroidism. Asymptomatic - Med Hx - neg PE normal - Meds: Vitamins, OCP s Thyroid functions: Total T4 elevated What next steps for diagnosis? Labs Imaging Diagnostic differential Treatment Thyroid Case stories - #2 52 y/o female referred for management of thyroid hormone replacement therapy. Her dosage has fluctuated between mg and mg daily over the past 3 years. Her TSH has fluctuated between 0.04 uiu/ml and 8 uiu/ml. In past 6 months, her dosage has remained constant, mg daily, but her TSH has varied, with each measurement, every 2 months: 8/ uiu/ml 10/ uiu/ml 12/ uiu/ml What additional history do you need? Thyroid Case stories - #2 Factors which can affect thyroid hormone absorbtion Food Drugs Calcium, vitamins Cholestyramine Ferrous sulfate Sulcrafate Antacids with aluminum hydroxide Factors which accelerate levothyroine metabolism Drugs Anticonvulsants Rifampine Sertraline (Zoloft) 10

11 Thyroid Case stories - #3 76 y/o male with Type II diabetes, insulin requiring, whose TSH has been consistently below normal, although the free T4 and free T3 are normal, for the past 4 months: 12/ uiu/ml 3/ uiu/ml He is asymptomatic and his physical exam is normal. What additional clinical or physical data do you need? What is the operative diagnosis? What is the next diagnostic study? Thyroid Nuclear medicine Thyroid scan Thyroid Case stories - #4 32 y/o female referred for evaluation and management of nodular thyroid disease and hyperthyroidism. She has the following symptoms: -15 lb unintentional weight loss over the past 3 yrs. - anxiety - insomnia - diffuse muscle pain - intermittent palpitations Previous nuclear medicine studies (1 year earlier) reveal normal uptake at 24 hours, but the scan revealed various hot nodules and several large cold defects. PE: normal pulse, neg goiter, mildly hyperreflexic 11

12 Thyroid Case stories - #4 What are your impressions? What is the next diagnostic study? What are the treatment options? Thyroid Case stories - #5 34 y/o female self-referred because she is convinced she has a metabolic disorder. Her complaints: - hair falling out by the handful lb unintentional weight gain over past year, with no significant change in lifestyle. - can t focus or concentrate, this is affecting performance at work. - mild dysthymia - hands and feet are always cold. She has no labs to review. PE: normal What is the next diagnostic study? Thyroid Case stories - #5 Labs: CBC, CMP were normal. TSH = 4.9 uiu/ml (nl range: uiu/ml) Free T4 = 0.8 ng/dl (nl range: ng/dl) Impressions? Additional diagnostic studies? Treatment options? 12

13 Thyroid Subclinical Thyroid Disease Consensus Development Conference* (AACE, ATA and Endocrine Society) Proper diagnosis and treatment of subclinical throid disease Subclinical Hypothyroisim Paucity of evidence-based data TSH limit should remain 4.5 uiu/ml rather then as some other organizations have suggested Since the available data do not show clear-cut benefit from early thyroxine therapy, routine treatment for patients with TSH between 4.5 and 10 uiu/ml is not warranted. * JAMA 2004; 291: Thyroid Subclinical Thyroid Disease Subclinical Hyperthyroidism The report concluded that it is reasonable to treat patients with TSH <0.1. Those with TSH between 0.1 and 0.45 uiu/ml should be monitored but not treated. Thyroid Case stories - #5 Labs: CBC, CMP were normal. TSH = 4.9 uiu/ml (nl range: uiu/ml) Free T4 = 0.8 ng/dl (nl range: ng/dl) Impressions? Additional diagnostic studies? Treatment options? 13

14 Thyroid AACE* guidelines AACE guidelines differs in several areas with the Consensus statement: The upper limit of normal for TSH should be 3.0 uiu/ml Anti-thyroid antibodies should be measured in patients with subclinical hypothroidism AACE recommends treatment of patients with TSH >5.0 uiu/ ml if: Goiter present Anti-thyroid antibodies present Patient is symptomatic Pregnancy or imminent pregnance The provider who has performed an exam and history should decide on the treatment of each individual patient * American Association of Clinical Endocrinolology Thyroid Case stories - #6 45 y/o male with 3 month history of palpitations, 20 lb unintentional weight loss, heat intolerance and insomnia. PCP referred after getting thyroid functions. The TSH was suppressed, the free T4 was elevated and the free T3 was markedly elevated. PE: pulse was 110 at rest, he had a prominent diffuse goiter, there was a bruit over the thyroid, he was tremulous and hyperreflexic. He had a wide eyed stare with upper lid restraction but no proposis. Impression? What additional diagnostic studies would be helpful to confirm your diagnostic impression? Thyroid Case stories - #6 What treatment options do you have? Should you wait for any confirmatory studies or can you treat now? What medications would you prescribe? What is the risk of sending this patient to nuclear medicine for definitive therapy now? 14

15 Thyroid Case stories - #7 42 y/o female with longstanding history of hypothyroidism, currently treated with Synthroid mg daily. She takes her medication religiously on an empty stomach, 1 hour before any food or vitamins/minerals. Her TSH is consistenly normal, uiu/ml. In the past 6 months she has been feeling more fatigued, particularly in the afternoons, is having more trouble concentrating and often feels that she has foggy brain. Her weight is up 5 pounds and she can t seem to exercise like she used to. Her metabolic workup is completely normal. Impressions? Thyroid Case stories - #7 Patient was referred to endocrinology for further evaluation and management. Plan: trial with combination T3/T4 therapy. Start liothyronine 5 ug tabs, 1 tab daily for 1 week and if tolerated, increase to 2 tabs (10 ug) daily, in the AM. Decrease Synthroid to ug daily. Repeat TSH in 4 weeks with follow-up. Response: Patient feels 100% better; TSH was 1.5 uiu/ml. Plan: continue combination therapy and recheck TSH in 2 months then annually Thyroid Controversies Treatment with combination T3 plus T4 AACE and ATA guidelines both state that there is a paucity of large scale, randomized prospective studies of combination therapy. Therefore, there is insufficient evidence to know which patient with hypothyroidism would be better treated with a combination of T4 plus T3 rather than with T4 alone. Generic vs Branded levothyroxine AACE recommends the use of high-quality brand preparations of levothyroxine 15

16 Thyroid Controversies Brand vs generic cont d AACE, ATA and TES issued a joint statement regarding the use and interchangeability of Thyroxine products in 2004.* The FDA acknowledged concerns about its method for determining bioequivalence The FDA has not changed its methodology and has proceeded to grant generic status to a a variety of levothyroxine preparations. Patients and many physicians are unaware of these concerns * AACE website home page Quick Links AACE Position statements #6 Thyroid Controversies BEST MEDICAL PRACTICE Patient should be maintained on the same brand name levothyroxine product. If the brand is changed, from a brand to another brand or to a generic or from a generic to another generic, then TSH needs to be remeasurred 6 weeks later and the drug should be retitrated as needed. Thyroid Controversies Levothyroxine vs Armour thyroid Biological (Armour thyroid) and synthetic thyroid hormone preparations containing both T4 and T3 (Thyrolar) are also not currently recommended for therapy since they produce fluctuating and often elevated T3 concentrations, although their use is not necessarily contraindicated 16

17 Thyroid in Pregnancy Hypothyroidism Thyroid hormone requirements are higher in pregnancy and dosages need to be titrated to maintain a normal level Hyperthyroidism Treatment with anti-thyroid medications PTU most commonly used, although methimzole can be used and is more convenient 17

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