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Home , Thyroiditis

1:55 – 2:25 PM Disorders of Function 2019

Cases in : • SubClinical Hypo and Thyroid Disorders • Graves Disease and Hasimoto’s Thyroiditis • SPEAKER • Coma John A. Tayek, MS, MD, FACN, FACP

• email: [email protected] • @DrMetabolism

Learning Objectives Biotin Supplement • 1) Identify risk factors associated with hyperthyroidism and new onset atrial fibrillation, • Many hospital and outpatient labs use the rapid Biotin anxiety disorder, psychosis and osteoporosis. dependent assay.

• 2) Measure both FT4 and TSH in hospitalized • Oral Biotin can displace assay readings to provide a falsely patients high Ft4, total T3. • Case reports of hyperthyroidism has been tx in patients with Biotin supplements. • 3) Identify long term risk of mildly elevated or reduced TSH concentration. Case 1: GOITER (Basaria NEJM 2004) GOITER and Shortness of Breath

(Basaria NEJM 2004)

“Thyroid cork” or Case 2: Progressive Weakness for 3 Months Pemberton’s Sign (Basaria NEJM 2004) • 82 y/o male with normal CBC, Chemistry, ANA, B12, Folate, Heavy Metal, S-PEP, U-PEP, RPR, CXR, nerve conduction: reduced amplitude; nerve biopsy: axonal degeneration; LP: CSF: no cell, elevated protein 254 mg/dl (15-45). • Dx: CIDP: Chronic Inflammatory Demyelinating Polyneuropathy; 5 iv IGG Txs without help • TSH 144, free T4 0.4; 3-months of Tx: TSH 33 mild improvement; 12 months Tx: TSH normal, patient walks (Razavi M, Lancet 355:38, 2000) Case 3: 40 y/o Mail Carrier with Case 3: 40 y/o Mail Carrier with Fatigue and Muscle Pain Fatigue and Muscle Pain

• TSH of 10 • Muscle pain as caused by is very rare but it does exist; CPK can be elevated • Can’t do her usual 3 mile walking mail delivery route. • Biopsy shows loss of fast twitch muscle fibers (type • Seen by rheumatologist with no diagnosis and sent to II). Only 10 cases have been identified in 16 years. the endocrinologist for evaluation of TSH of 10. • Treatment is simple, treat with thyroid hormone even • I told her that her pain and weakness was not likely due if the TSH is only slightly elevated (TSH of 10-15). to TSH of 10 • 1 year later I was proven wrong.

Genetic T4 Set-Point HYPOTHYROID MYOPATHY (<1%) 1000 From: Spencer et al JCEM 70: 453, 1990

• CASE TSH(4-4.4) CPK (30-200) / ALDOLASE (0-8.1) NOTES: 100 • F 10 300* / -- • F 21 1138* / -- 10 TSH • F 16 3000* / -- mIU/L 1.0 A • F 158 816* / 4.8 LDH 317* (nl 109-230) B • M -- 484* / -- AUTOPSY: pituitary increased TSH 0.1 • F 207 1536* / 6.1 CPK decreased to 62 at 6 weeks Tx • M 15 39 / 4.8 LDH 353*/380* 0.01 • F 377 1125* / 5.4 CK decreased to 183 at 6 months Tx undetectable • F 107 382* / -- Hypothyroid NORMALEuthyroid Hyperthyroid • M 47 139 / 12.7 * T4 (Free T4) • average: 106+41 896+295 / 6.8+3.3 (mean+sem) HYPOTHYROIDISM WITH AGE AND Screen for > 60 • USPSTF: The USPSTF (2013) concludes the evidence is insufficient to SEX recommend for or against routine screening for thyroid disease in adults. • AGE MEN WOMEN • Thyroid Society: American Thyroid Association (ATA), which recommends • 0-10 0.025% 0.025% thyroid screening in all adults beginning at age 35 years, and every 5 years • 20-50 0.1 % 0.2 % thereafter. • 60-70 0.5 % 1.0 % • The ATA/AACE Clinical Practice Guidelines for Hypothyroidism in Adults • 70-80 1.0 % 4.0 % recommend screening for hypothyroidism be considered in patients over the • 80-90 2.0 % 10.0 % age of 60.

• The American Academy of Family Physicians (AAFP) recommends routine screening only in asymptomatic patients older than 60.

CASE 4: Muscle Pain and Weakness SITE OF HYPOTHYROIDISM • UNSURE: Repeated the T4 level on the day of consult: • 99% of hypothyroidism originates at the thyroid which was 3.3 and is now 1.1 * today. (Dangerously low) gland. •TSH 3.3 yesterday

• 1% of the time the pituitary or hypothalamus is •Cortisol 3.4 today (normal random cortisol for hospitalized responsible for the hypothyroidism. patients is between 10 and 30 (without liver disease)

• ACTH stimulation test cortisol was 3.4, 9.0 at 30 min and • Don’t forget about the secondary causes since 10 at 60 min: confirming the dx of secondary adrenal they are usually associated with other pituitary insufficiency) diseases (tumor, autoimmune, etc) • Diagnosis Pan-Hypo Pit with Mild MYXEDEMA COMA • This is Medical Emergency:

• She was tx with 100 of hydrocortisone and 200 mcg of oral L-thyroxine. Serum T4 increased to 4.4 the next day. Patient woke up the next day and was discharged on day 4.

• She had loss of menstrual period 30 years prior just after the birth of her child at ate 35. She had no axillary or pubic hair.

11 Cases of Myxedema Coma (91% Sodium <135) Myxedema Coma 3/11 had normal TSHs; 36% mortality) Sodium is low in 9 of 11 patients with myxedema coma

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* TSH Specificity Loss in Patients with Pituitary Disease 1000 Inpatient Confused Female Normal Reference 100 • Always get at the minimum of free T4, TSH and cortisol. 10

Normal • Free T4 TSH 1.0 Reference mIU/L •TSH Central 0.1 Hypothyroidism • Cortisol 0.01

• (Do not forget my case of r with TSH 3)

0 7.5 1 5 3 0 4 5 • T4 =3; TSH = 3 and Cortisol 3 . This is Pan- TT4 ug/dlol hypopituitary until proven otherwise.

MYXEDEMA COMA Top 7 Causes of Hyponatremia • This is a Clinical Diagnosis; overt hypothyroidism • Diuretics with progressive stupor and coma; look for triad: • The Three Failures: CHF hypothermia, hypotension and hypoventilation Cirrhosis • Patients may also have seizures, hyponatremia, hypoglycemia, and respiratory acidosis. Nephrosis • SIADH • Give T4 (0.3 mg) by IV push into vein. Do not give • Exercise-associated hyponatremia it piggy back; it is not soluble and will stick to the • Pan-hypopituitarism (usually women) plastic tubing. Also give hydrocortisone 50mg Q 8hrs; and T4 0.1 mg daily by IV push. THYROID STORM CASE 5 continued: • Medical Emergency- treat in ER • Dx: Graves Disease • Tx of hyperthyroidism can double your heart’s • Clinical Diagnosis; look for signs of Ejection Fraction (28% to 55%; Umpierrez, AJMS hyperthyroidism(a goiter is common) 1995) • Fever (>38.5) and Tachycardia, (but the patients may have anorexia, nausea, vomiting, abdominal • Two of the 3 (FreeT4 (or Free T4 index), T3 Total and pain and CHF). TSH) should be consistent to make the diagnosis. • She had a three abnormal TFTs so she has Graves • Tx: Methimizole 30 mg @8 hrs po, ng or pr. Dx or Hasimoto’s thyroiditis or excessive L-thyroxine Propranolol 40mg Q 6 hr, & hydrocortisone 50mg Q 8hrs; One hour after Methimizole give SSKI 5 gtts Q6 hrs ()

Atrial Fibrillation Relative Risk of Developing Atrial Fibrillation in > 60-Year Old Individuals Sawin NEJM 331:1249, 1994 * • 6% of men and 3% of women over the age of 65 4 p< 0.05 have Afib. 3 • 16% of men and 12% of women over age of 75 * have Afib. REL. p< 0.05 * p< 0.05 • While the most common cause is idiopathic, the RISK 2 second most common cause of thyroid disorder with approximately 75% due to hyperthyroidism 1 and 25% due to hypothyroidism. 0 < 0.1 0.1 - 0.4 0.4 - 5.0 > 5.0 • Always check both TSH and FT4. TSH mU/L Adults have a 13% risk of New Onset Afib Grave’s Eye Disease over 8 years with a “Low-Normal” TSH • New onset AFib occurred in 13% (105/1426) of patients with “normal” TSH • The authors set at a odds ratio of 1 (TSH 2.2-4.0), • OR was 1.3 for a TSH 1.05-2.2 (not significant) • But: TSH of 0.1-1.04 had a 1.97 Odds Ratio (p<0.05) for New Onset A-Fib (Rotterdam Study, Heeringa J, 2008) • • (Keep TSH 1.1 to 4.0 in 60+ year old patients)

Teprotumumab (IGF-1 receptor antibody) Thyroid- ETIOLOGY OF Associated Ophthalmopathy (NEJM Smith, T, 2017) HYPERTHYROIDISM Intention to Treat Analysis: 20% vs 69% response rate at 24-week, p < 0.001 Proptosis 23.4 mm decreased to 20.9 mm at 24 weeks, p < 0.001 • Graves Disease (most common) • Early Hashimoto’s Thyroiditis (anti-TPO Diagnostic) • (occurs in 1-6% of women postpartum @ 2-6months p birth; lasts 2-8 weeks • (post viral syndrome) • Toxic Nodule(s) • Thyroid CA; Pituitary Tumor; Trophoblastic tumor (HCG cross reacts with TSH receptor) Thyroid Dermopathy (Pretibial Myxedema) METHOD TO DIAGNOSIS SOURCE OF HYPERTHYROIDISM • Graves Disease : 24hr 123I uptake >40%, +TSI, proptosis >24mm, or pretibial plaquing(myxedema)

• Hashimoto’s Thyroiditis: 123I uptake patchy; TPO + Abs

• Postpartum & Subacute Thyroiditis: 123I uptake <5%

• Toxic Nodule(s): 123I uptake only in nodule(s)

Case 7 TSH Specificity Loss in Patients with Pituitary Disease SICK EUTHYROID IN CRITICAL ILLNESS 1000 TSH-Secreting Normal Pituitary Tumor Reference • Diagnosis: very low T3, normal cT4 and normal TSH. 100 • No need to treat “low T3 syndrome”. 10 • Beneficial Response to Conserve Energy. Normal TSH 1.0 Reference • TSH increases during recovery but usually does not mIU/L

exceed 16 IU/ml. 0.1 Central Hypothyroidism

TSH is not 0.01 • Only consider treating if patient has TSH >16 and has 100% an increased PaCO2, decreased body temperature specific in

(hypothermia) or an altered mental status; Or a Hospitalized 0 7.5 1 5 3 0 4 5 reduced “corrected T4” <3.0. patients TT4 ug/dlol Treatment of SubClinical Hypothyroidism Treating Hypothyroidism

 737 pts (>65yo) with Subclinical Hypothyroidism were  Most generic L-thyroxine have a variable rate of randomized to receive levothyroxine or placebo for 1 yr. absorption. TSH>4.6 to 19.9 (Average 6.4) [few had TSH >10]  Follow TSH every year while on the same generic Treatment reduced TSH to 3.5 vs 5.5 placebo medication.  Remember that L-thyroxine taken on an empty  No Benefits in hypothyroid symptom score, tiredness score, CV stomach will increase absorption by 20 to 30% events, A-fib, heart failure, hand grip strength, blood pressure,  Likewise, PPI (and likely H2) therapy (raising stomach BMI, waist circumference. pH from 2 to 5-6) will reduce absorption by 20-30%. Stott, et al NEJM 2017:376:2534-44.

All patients seeking pregnancy or newly pregnant should undergo TSH testing if any of the below risk factors exist: Subclinical Hypothyroidism in  1. A history of or signs/symptoms of thyroid dysfunction Pregnancy  2. Known thyroid antibody positive or goiter  3. History of head/neck radiation or thyroid surgery  TPO + and TSH above normal (Tx with Levothyroxine  4. Age > 30 therapy)  5. Autoimmune disorder  TPO- and TSH > 10 (Tx with Levothyroxine therapy)  6. History of pregnancy loss, preterm delivery, or infertility  7. > 2 prior pregnancies  8. Family history of thyroid dysfunction  TPO + and TSH > 2.5 consider to treat (moderate  9. Morbid Obesity (BMI > 40) evidence)  10 Use of amiodarone, lithium, or recent iodinated radiologic contrast  TPO - and 4.5 to 10.0 consider to treat (weak  11. Residing in area of moderate to severe iodine insufficiency evidence) Alexander et al. Thyroid 2017 Rec 97 (Alexander et al Thyroid 27, 315, 2017) Summary (Inpatient Evaluations) Summary (Out-Patient) • TSH may be inaccurate in a Hospital also get a free T4 or T4 • TSH accounts for approximately 95% in the accuracy of the • Pituitary disease and other illnesses can alter the accuracy outpatient diagnosis. • of the meaning of a “Normal” TSH. • Subclinical hypothyroidism should be treated in patients with TSH • A low T3 is not useful in critical illness due to euthyroid sick over 10; or if they have a TSH between 4.5-10 and a postiveTPO syndrome. antibody (since approximately 42-58% will progress to overt • Get additional FT4 Index or Free T4 and repeat them as needed in hypothyroidism). someone who has an altered mental status. Don’t forget to sent an • Keep TSH between 2-4 in the elderly to prevent new onset Afib. AM Cortisol and Dx if < 10 mg/dl • Worry about TSH < 1.0 as it may contribute to new onset Afib in I suggest a Total T4 and T3 uptake to calculate a Free T4 Index the elderly. FT4 index = total T4 x T3 uptake / normal hospital T3 uptake