Alvin C. Powers, M.D. 1/27/06

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Thyroid Histology Follicular Cells ECF side

1 Thyroid Histology Follicular Cells ECF side Apical lumen Thyroid Follicles um Parafollicular or C-cells Colloid Photos from University of Manchester and tutorial created by Dr. James Crimando, GateWay Community College Clinical Management Course 1

Thyroid Peroxidase I +* Iodotyrosine Thyroglobulin ECF

2 Thyroid Follicular Cell Iodine TSH T 4, T 3 + I _ TSH Receptor Thyroglobulin H 2 O 2 Thyroid Peroxidase Thyroid Peroxidase I +* Iodotyrosine Thyroglobulin ECF (Plasma) Apical Lumen (Colloid) Clinical Management Course 2

3 Clinical Management Course 3

21 year old female is referred from her cardiologist for treatment of hyperthyroidism. She is followed for asymptomatic aortic insufficiency. Total T4 = 15.

4 21 year old female is referred from her cardiologist for treatment of hyperthyroidism. She is followed for asymptomatic aortic insufficiency. Total T4 = 15.6 (nl( = 4-12) Free T4 = 1.35 (nl( = ) TSH = 1.2 (nl( = ) Thyroid Function Tests Total T 4 Total T 3 Free T 4 TSH Clinical Management Course 4

Thyroxine Metabolism Transport and Metabolism of Thyroid Hormones

Metabolism, Felig,, Baxter, Frohman, 1995 Total T 4 Major

serum Unbound T 4 is converted to T 3 and should be considered a

5 Thyroxine Metabolism Transport and Metabolism of Thyroid Hormones T4 T3 Adapted by UptoDate from Utiger, Endocrinology and Metabolism, Felig,, Baxter, Frohman, 1995 Total T 4 Major circulating thyroid hormone hormone Over 99% bound to proteins in serum Unbound T 4 is converted to T 3 and should be considered a prohormone Levels affected by drugs and non-thyroidal illnesses Clinical Management Course 5

6 Free T4 Reflection of bioactive hormone Either measured directly or calculated Calculated Free T4 (using Total T4 and an estimate of thyroid hormone binding capacity, the resin T3 uptake) is called a Free T4 index Should order a Free T4 and not a total T4. Total T 3 Results from peripheral conversion from T 4 and thyroid production of T 3 Bioactive hormone and is the major ligand for the thyroid hormone receptor Always elevated in hyperthyroidism Often normal in hypothyroidism Thyroid Stimulating Hormone Gold standard-best overall indicator of thyroid disease Capable of separating hyperthyroid, euthyroid, and hypothyroid states Clinical Management Course 6

7 TSH Levels in <0.01 Normal 1 o 2 o Hyperthyroidism Hypothyroidism Misleading TSH Values Patients with hypothalamic or pituitary disease Patients hospitalized Psychiatric Intensive care units During transition phase of hyperthyroidism Summary of TFT s TT4 FT4 T3 TSH Hyperthyroidism Primary Hypothyroidism Secondary Hypothyroidism Non-thyroid disease nl nl Clinical Management Course 7

Suggested Use of Thyroid Function Tests Suspect thyroid disease -Free T4 and TSH Monitor T4 replacement -TSH If pituitary disease is present -Free T4 48 year old man from Shelbyville is referred by

8 Suggested Use of Thyroid Function Tests Suspect thyroid disease -Free T4 and TSH Monitor T4 replacement -TSH If pituitary disease is present -Free T4 48 year old man from Shelbyville is referred by his primary care physician for weight loss, tachycardia, and tremor. Free T4 = 4.2 (nl( = ) TSH < (nl( = ) How would you evaluate him? Normal Thyroid Scan Clinical Management Course 8

9 Thyroid Scan in Graves Disease Graves Disease Hyperthyroidism Ophthalmopathy Dermopathy (pre-tibial myxedema) Thyroid Follicular Cell TSH TSI Iodine TSH Receptor Thyroglobulin T 4 + Iodine Iodotyrosine Thyroid Peroxidase Clinical Management Course 9

A 34 year old woman, who is 4 months post- partum (twin boys), reports a month long history of trouble sleeping, emotional lability, fatigue, and neck swelling.

10 A 34 year old woman, who is 4 months post- partum (twin boys), reports a month long history of trouble sleeping, emotional lability, fatigue, and neck swelling. On examination, she is mildly tachycardiac and has a diffusely enlarged thyroid. She has no eye findings to suggest Graves Disease. Free T4 = 2.8 (normal ) TSH = <0.05 (normal ) HOW WOULD YOU EVALUTE HER? Low Uptake on Thyroid Scan Causes of Thyrotoxicosis Normal or Increased Activity on Thyroid Scan Graves Disease Multinodular Goiter or Hot Nodule Decreased Activity on Thyroid Scan Thyroiditis Iodine-induced thyrotoxicosis (amiodarone( amiodarone) Exogenous thyroid hormone use Clinical Management Course 10

Multinodular Goiter A 71 year old man comes for the evaluation of weight loss, poor appetite, and new-onset congestive heart failure (mild). His thyroid function tests show: Free T4 = 1.9 (normal 0.

11 Multinodular Goiter A 71 year old man comes for the evaluation of weight loss, poor appetite, and new-onset congestive heart failure (mild). His thyroid function tests show: Free T4 = 1.9 (normal ) TSH = <0.05 (normal ) IS HE HYPERTHYROID? Individualized Set Point for T 4 Normal A = Develops hyperthyroidism TSH B A B A B = Develops hypothyroidism Normal T 4 Clinical Management Course 11

12 Treatment of Hyperthyroidism Antithyroid Drugs Radioactive Iodine Surgery 74 year old woman is brought by her son who has noticed: Decreased memory Fatigue Constipation She has the heat on in her house in the summer. Clinical Management Course 12

or ultrasound is not necessary Autoimmune or

13 Patient with Hypothyroidism Hypothyroidism TSH is best indicator May or may not have a goiter Thyroid scanning or ultrasound is not necessary Autoimmune or post-surgical are the most common causes Clinical Management Course 13

14 Clinical Management Course 14

15 Treatment of Hypothyroidism You know the thyroid gland in your throat-the one that stokes the engine and keeps the old brain working. In some people the thing doesn t t work properly and they turn out to be cretinous imbeciles.., but feed em the stuff and they come out absolutely all right.... Lord Peter Wimsey in Dorothy Sayers Hangman s s Holiday,, 1933 Thyroid Hormone Supplements Well-tolerated; well-absorbed from GI tract One of most commonly prescribed medications Current preparations consist of synthetic T 4 (Euthyrox, Levothyroid, Levoxyl,, Synthroid, Unithroid) ) and/or T 3 New evidence does not support replacement with T 4 and T 3 T 3 results from T 4 metabolism and is not routinely prescribed. Clinical Management Course 15

16 Thyroid Hormone Supplements Dose should be titrated to achieve a normal TSH level. Recheck TSH 4-6 weeks after a dose change because of the long half-life of T4 (7 days). Excessive levels (as evidenced by a suppressed TSH) cause iatrogenic hyperthyroidism and accelerated bone loss. Drugs that Affect Thyroid Function Drugs that cause hypothyroidism Inhibit T4 synthesis/release (lithium, perchlorate, iodine-containing drugs) Amiodarone Decrease T4 absorption Drugs that cause hyperthyroidism Amiodarone/interferon-alpha Iodides Inhibit thyroid hormone synthesis (autoregulation) Adjunctive therapy for severe hyperthyroidism Clinical Management Course 16

Iodides Saturated Solutions of Potassium Iodide (SSKI) is most common preparation; some countries have emergency stores of this in case of a nuclear accident.

17 Iodides Saturated Solutions of Potassium Iodide (SSKI) is most common preparation; some countries have emergency stores of this in case of a nuclear accident. 19 year old Vanderbilt undergraduate is referred for a left sided thyroid nodule that was found in Student Health when she was seen for a sore throat. TFT s normal Thyroid Nodules Most are benign. Hot nodules are benign; thyroid cancer is cold on scanning. Most are cold on thyroid scanning Ultrasound cannot confirm or exclude malignancy. FNA is required for all cold nodules. Clinical Management Course 17

18 Clinical Management Course 18

Diseases of thyroid & parathyroid glands (1 of 2)

Diseases of thyroid & parathyroid glands (1 of 2) Thyroid diseases Thyrotoxicosis Hypothyroidism Thyroiditis Graves disease Goiters Neoplasms Chronic Lymphocytic (Hashimoto) Thyroiditis Subacute Granulomatous