Thyroid Disease. Women’s Health Symposium August 1, 2009. Michael Gardner, MD University of Missouri Columbia Departments of Internal Medicine and Child Health Division of Endocrinology. A 24 Year Old Woman With Fatigue.
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Thyroid Disease Women’s Health Symposium August 1, 2009 Michael Gardner, MD University of Missouri Columbia Departments of Internal Medicine and Child Health Division of Endocrinology
A 24 Year Old Woman With Fatigue • A 24 year old woman complains of fatigue weight gain and trouble sleeping at night • PMH and PE: unremarkable • TSH is drawn and comes back at 7 mU/L (0.3-5) • What is the diagnosis? • What other test should be ordered? • What is any therapy should be started?
Progression of Hypothyroidism TSH Normal Range T3 T4 Subclinical Hypothyroid Primary Hypothyroid Euthyroid
Hypothyroidism • Primary hypothyroidism • TSH generally >10, low free T4 • Treat with levothyroxine • Adjust dose to keep TSH in normal range • Subclinical hypothyroidism • TSH >5 and normal T4 • Check for anti-TPO antibodies
Progression of Subclinical to Overt Hypothyroidism • Progression to overt hypothyroidism estimated is 4 to 18% per year • Increased likelihood with • Higher TSH • Positive antibodies • (+) antibodies doubles likelihood • History of RAI therapy • Lithium therapy • Age <55yrs
A 24 Year Old Woman With Fatigue • A free T4 is 1.54 (0.71-1.8) Anti TPO Antibodies are strongly positive • She is diagnosed with Subclinical Hypothyroidism and started on L-thyroxine 0.075 mg/day • Four months later her TSH is 0.7 mU/L • She is still complaining of fatigue and trouble sleeping and has not lost any weight. • Says she has been reading on the Internet that she might need treatment bioequivalent hormone found in Armour thyroid.
A 24 Year Old Woman With Fatigue • What do you do? • Increase her L-thyroxine dose to treat her symptoms • Change to Armour 1 grain daily • Screen for other causes of her symptoms
A 24 Year Old Woman With Fatigue • Excessive doses of thyroid hormone will not fix: • Depression • Metabolic syndrome / increased adiposity • Sleep apnea / Sleep deprivation • Etc. • No evidence for increased efficacy with the addition of Liothyronine (T3) to Levothyroxine • Most T3 in humans is produced by peripheral conversion of T4 • Dessicated thyroid is desiccated porcine thyroid gland. • Dose based on organic iodine not thyroid hormone content
Other Causes of Increased TSH • Recovery from serous non thyroidal disease • Random pulses of TSH (particularly in evening) • Assay variability (Lab error) • Adrenal insufficiency • Treatment with metoclopramide • TSH producing tumor and thyroid hormone resistant states • Extremely Rare • Free T4 should be increased
Reasons to Treat Subclinical Hypothyroidism • Very Little Evidence of Benefit • Possible benefits • Stabilize Goiter • Widely accepted, conflicting evidence • Prevent Progression to Overt Hypothyroid • Good association • Improved lipids • Decrease CAD • Only in younger patients • May increase risk >70 yo • Improved non-specific symptoms • Generally patients symptoms unrelated
Potential Disadvantages to Treating Subclinical Hypothyroidism • Relatively safe in young patients • Cost of life long therapy and monitoring • Generic is $4 at national chains • Over treatment • Atrial fibrillation • Bone loss • Having an asymptomatic patient taking medication for the rest of life
High TSH in Patients Taking L-Thyroxine • May indicate need for more hormone • Other causes need to be considered • TSH takes longer to come down than the T4 takes to come up • Missed doses • Generally TSH high with high normal or elevated T4 • Medications interfering with absorption • Iron/Calcium supplements • Bile binders • Proton pump inhibitors
32 Year Old Woman With Fatigue and Cold Intolerance • A 32 y/old woman is seen by her PCP complaining of fatigue and cold intolerance • ROS: otherwise negative • PE: Normal except for dry doughy skin • Lab: • TSH is 0.9 mU/L (0.3-5.0) • Is this patient hyper, hypo or euthyroid? • What should be done next in the work up of this patients?
Secondary Hypothyroidism • TSH can only be used to screen for primary hypothyroidism • When the TSH is discordant with the symptoms or physical exam, check the free T4 and occasionally free T3 • Cases were the history or physical exam suggests hypopituitarism you must also check Free T4 • Amenorrhea / Hypogonadism • Growth Failure (children) • Postpartum hemorrhage • Past head trauma etc.
A 48 Year Old Man With “Nervousness” • A 48 year old man complains of increased nervousness. • He denies heat or cold intolerance • His weight is stable • There is no hair or skin changes • Lab: TSH 0.1 mU/l • Is this patient • Hyperthyroid? • Euthyroid?
Progression of Graves Hyperthyroidism T3 T4 Normal Range TSH Subclinical Hyperthyroid T3 Toxicosis Overt Hyperthyroid Euthyroid
Subclinical Hyperthyroidism • Low TSH with normal free T4 and T3 • Log linear relationship between thyroid hormone and TSH • Very small changes in thyroid hormone result in dramatic changes in TSH
Subclinical Hyperthyroidism: Importance • Clinical importance • Bone • Thyroid hormone stimulates bone resorption • Studies are conflicting • Atrial fibrillation • More common in patients with low TSH • Lower the TSH, high the risk • Other areas • Sleep • Exercise
Treatment of Subclinical Hyperthyroidism • Few long term studies • Depends on degree and clinical setting • TSH 0.1-0.3 and no symptoms or atrial arrhythmias: follow • TSH <0.1 • Repeat and if still low consider course of antithyroid medications • Many patients will be normal after 1-2 years
A 48 Year Old Man With “Nervousness” • Total T4 is 5.9 mcg/dL (5-12) • Free T4 is 0.62 ng/dL (0.58-1.64) • Total T3 is 300 ng/dL (87-178) • Is this patient • Hyperthyroid? • Euthyroid?
Hyperthyroidism due to an Autonomous Nodule T3 Normal Range Or T4 TSH Subclinical Hyperthyroid T3 Toxicosis Overt Hyperthyroid Euthyroid
Indication for I123 Uptake and Scan • Suppressed TSH with elevated T4 and/or T3 • Distinguish Hyperthyroidism from acute thyroiditis • Distinguish Graves from autonomous nodules • Some autonomous nodules produce both T3 and T4 • Role in diagnosis of nodules diminishing • Unable to distinguish cyst from “cold” solid nodule • Ultrasound in skilled hands combined with FNA better for cancer determination
Thank You Questions?
56 Year Old Man In ICU • 66 year old post MVA with multiple fractures, pneumonia, respiratory failure on respiratory failure on respirator • The patients develops atrial fibrillation and a TSH is 0.08 mU/l (0.3-5) • Is this patient hyperthyroid?
Severe Illness and Thyroid Testing • Several changes are seen in thyroid function test in patients with acute illnesses • Low T3 levels (decrease T4 to T3 conversion) • Increased Reverse T3 levels • Total T4 is often low • More severe illness • Pituitary TSH secretion is diminished
5’ Deiodinase 5 Deiodinase T3 T4 T2 Reverse T3 5 Deiodinase 5’ Deiodinase T4 Peripheral Conversion
Severe Illness and Low T4 • Seen in more severely ill patients • Appears to be do to abnormalities in binding • Low TBG, TBPA, and Albumin may be low • Circulating substance the impair binding • High free fatty acids are one possibility • Measurement of free T4 are effected differently • Free thyroid index is usually low • Free T4 by equilibrium is usually elevated • Measurement of free T4 by direct assay may be low, normal or high
Severe Illness and Thyroid Testing • The lower the T4 in severely ill patients, the higher the mortality • Thyroid hormone replacement does not help this
TSH In Severely Ill Patients • In severe illness patients may have transient central hypothyroidism • TSH may be low • In primary hypothyroidism, TSH may be normal • Always use ultra sensitive TSH assay • Values 0.01-0.05 suggest hyperthyroidism, 0.05-0.3 will usually be normal later • During recovery from acute illness, TSH levels may be transiently elevated
In Severely Ill Patients • Testing may make euthyroid patient look hypothyroid or hyperthyroid • Primary hypothyroidism may be masked • Hyperthyroidism may be masked
Effects of Drugs on Thyroid Tests • The following drugs suppress TSH values in normal and hypothyroid individuals • Dopamine • Dobutamine • Glucocorticoid • T4 may be displaced from binding sites by • Furosemide • Salsalate • Heparin • Phenytoin • Carbamazepine
Thyroid Testing In Severely Ill Patients • Thyroid function should not be assessed in severely ill patients unless there is strong suspicion of underling thyroidal illness • NO SCREENING! • When there is a strong suspicion, TSH (ultra sensitive), Free T4, Free T3 and Reverse T3 need to be assessed • Physical exam: look for clinical findings and goiter • History: ask about past history of thyroid disease and hormone use • FHx: Thyroid problems often run in families
Thyroid Function in Elderly Patients • TSH levels tend to drop with age • Several older patients have low Free T4 with normal or minimally elevated TSH levels • Several older patients have low TSH and normal free T4 and free T3 and no evidence of thyroid disfunction
TSH Cascade 2nd or 3rd Generation TSH Assay Patient without pituitary or severe illness Low Normal Elevated Taking thyroid Reduce dose Check FT4 No further testing Check FT4 Normal Subclinical Hypothyroid Low Primary Hypothyroid Normal Check T3 High Hyperthyroid Taking thyroid Low/Low normal Increase dose Normal Follow
Prevalence of Subclinical Hypothyroidism *Increased Risk in Whites vs Blacks, Women vs. Men, and elderly subjects. Sawin CT et al., Arch Int Med 145:1386, 1985 Bagchi N et al., Arch Int Med 150::785, 1990
32 Year Old Woman With Fatigue and Cold Intolerance • When seen by endocrinology, the patient recalled she had required blood transfusions after the birth of her last child • Free T4 was 0.4 • ACTH stimulation test showed pre value of 2 and 30 min value of 4 • Prolactin was undetectable • After 10 mg of Provera for 10 days there was no menstrual bleeding and FSH and LH levels were undetectable • Growth hormone did not stimulate
32 Year Old Woman With Fatigue and Cold Intolerance • The patient was started on predinsone 2.5 mg TID • The next day, she was started on L-Thyroxine • Cyclical estrogen and progesterone were begun • She was begun on human growth hormone therapy