endocrinology primary care update - mce conferences … 1011/5_hypothyroidism_tricks_of… · lynn...

Lynn Kohlmeier, MDEndocrine Associates

509-777-5000Endocrine Associates of Spokanewww.SpokaneOsteoporosis.com

EndocrinologyPrimary Care Update

MCE ConferencesLas Vegas, NV

May 27-29, 2011

THYROID DISEASEHypothyroidism: The Tricks of TSH Levels

Hyperthyroidism: A Real AnxietyThyroid Nodules & Goiters

http://www.SpokaneOsteoporosis.com


Outline

• Normal Physiology• Evalua5on of a low TSH -‐ Thyrotoxicosis

Treatment )psMild ‘subclinical’ hyperthyroidism Thyroidi)s

• Evalua5on of a high TSH -‐ HypothyroidismTreatment )psOvert vs. Mild ‘subclinical’ hypothyroidism

• Interpre5ng Thyroid levels in Pregnancy• Thyroid Nodules

Subclinical Hypothyroid

n A 38 y.o. female sees you for a routine check. She mentions a FHx of hypothyroidism so you screen her. TSH is 5.6 (0.5-4.5), fT4 1.0. Would you treat her? If so, what dose?n Would thyroid antibodies sway your decision?n What if her TSH was 8.0 instead?n What if she were contemplating getting

pregnant?n What if she was 70 instead? n What if she were your colleague?

slide compliments of Linda A. Barbour, MD, MSPH, FACP

Adapted slides compliments of Peter Capell, MD

Screening for Thyroid DiseaseSuspect or Screen for Thyroid Disease

TSH High Normal Low (hypothyroidism) (hyperthyroidism)

Free T4 +/-‐ An)-‐TPO Ab?

*Key Assump3ons:• Intact Pituitary Axis• Stable• Ambulatory (not in ICU)• Not pregnant


Hypothyroidism: Incidence and Associa5ons

• 10-‐15% of women >50• Higher incidence in presence of other autoimmune disorders, e.g.: Type 1 DM • May be subclinical early but almost invariably progresses• Symptoms are oKen non-‐specific; need high suspicion in pa3ents at risk or rou3ne screen


Elevated TSH with Normal or Low Normal T4

• This combina,on usually means– mild primary (subclinical) hypothyroidism (TSH 5-‐10) – overt hypothyroidism (TSH > 10)– An,-‐TPO Abs are useful to establish e,ology/likelihood of progression


Symptoms and Signs of Hypothyroidism

Common• *Cold Intolerance• Cons)pa)on• Fa)gue• Weight gain• Dry skin• Hair loss• Depression* Only sx. significantly different from general clinic popula3on

Less Common• Galactorrhea• Hyperlipidemia• Infer)lity• Precocious Puberty• Muscle Cramps • Periorbital puffiness


Progression to Overt Hypothyroidism

TSH Level 4.5-‐9.5• 2.5-‐5%/year conversion to overt hypothyroidism• 5-‐10%/ year conversion if TPO Ab +

Diez,et al J Clin Endocrinol Metab 2005;4124-‐27Huber, et al J Clin Endocrinol Metab 2002;3221-‐26Vanderpump, et al Clin Endocrinol 1995;55-‐68


Transient Eleva,ons of TSH Levels

• Expected: § Recovery from subacute thyroidi3s§ T4 treatment for prolonged hypothyroidism

• Unexplained: § Acute severe illness§ Random fluctua3ons: 62% of TSH levels 5.5-‐10 in pts with no known thyroid disease (N=12,500) were in the normal range on repeat tes3ng

(Meyerovitch, J. et al. Arch. Int. Med. 167:1533,2007)


Mild and Overt Hypothyroidism

TSHFT4

Euthyroidism(Normal Thyroid)

Overt

Hypothyroidism

Start Mild

5% per year

Do 50% improve ?

Prevalence of Thyroid Disease by Age

Elevated TSH, %(Age in Years)

18 25 35 45 55 65 75

Male 3 4.5 3.5 5 6 10.5 16

Female 4 5 6.5 9 13.5 15 21

The Colorado Study: Canaris GJ, et al. Arch Intern Med. 2000;160:523-534.

Slide compliments of Ken Cathcart, MD

Cost-‐Effec,veness of TSH Screening q. 5 yrs vs Other Preven,ve Medical Prac,ces

0Most cost-effective

20 40 60 80 100Least cost-

effectiveDollars

(1994 $ thousands)

Cholesterol screening of asymptomatic population

Breast cancer screening: women aged 65 to 74 y

Hypertension screening: women aged 40 y

Hypertension screening: men aged 40 y

Hypothyroidism: men aged 35 y

Exercise for CHD prevention

Smoking cessation

Hypothyroidism: women aged 35 y

Flu vaccine: adults aged 45 to 65 y

Breast cancer screening: women aged 40 to 74 y

Adapted from Danese MD et al. JAMA. 1996;276:285. Slide compliments of Ken Cathcart, MD

• TSH cost-effectiveness ratio is comparable to that of other preventive measures such as screening for breast cancer in

women 40 - 74 y/o or screening for HTN in men 40 y/o

Screening: RecommendaAonsVarious socie)es and authors disagree about

popula)on-‐based screening

Surks. JAMA. 2004 Jan 14;291(2):228-38.American Academy of Family Physicians. Subclinical Thyroid Disease. Available at: http://www.aafp.org/afp/20051015/1517.pdf Accessed February 16, 2006. The American Thyroid Association Web site. American Thyroid Association Guidelines for Detection of Thyroid Dysfunction. Available at: http://thyroid.org/professionals/publications/documents/GuidelinesdetectionThyDysfunc_2000.pdf. Accessed February 16, 2006.

• The AAFP recommends screening high-‐risk popula3ons:– women with a family hx of thyroid disease– women >35 yo– pregnant women– abnormal physical exam– diabe3c pa3ents– Hx of autoimmune disorder

• The American Thyroid Associa3on indicates that screening is jus3fiable in men > 35 yo as well (q 5 years)


Who Needs Treatment?

• All with TSH > 10 assuming not cri5cally ill• Symptoma5c pa5ents with TSH > 5 (at least a trial)• Symptoma5c pa5ents with TSH > 4-‐4.5 & TPO +

Hypothyroidism: Treatment

• Otherwise healthy, < 60 yrs, no cardiac Hx:• ~1.6 µg/kg/day, 6 - 8 week F/U TSH, 25 µg dose

increments• Older patients, > 60: require 20-30% less

• 50 µg/day, increase by 12-25 µg dose increments• Congenital hypothyroidism

• Initiate Rx with 10-15 µg/kg/d, Usually 50 µg/d X 1 wk, then 37 µg/d

• Pediatric hypothyroidism• Initial dose: 25-50 µg/d X 2-4 wks; Titration: 25 µg

increments Q 4- 8 wks


• Best to take thyroid everyday, 4 hrs away from iron, calcium, PPIs or antacids (on an empty stomach)

• Absorption of thyroid hormone decreased ~15% if taken with calcium supplements

• Free and total T4 concentrations fell significantly during co-administration of calcium carbonate by 8%

• Mean TSH increased by 69% (1.6 mU/L to 2.7 mU/L, p = 0.008), and 20% of patients had serum TSH above the normal range (highest 7.8 mU/L)

• T4 should not be taken until several hours after administration of the bile acid-binding resin. Normal gastric acid secretion appears to be necessary for normal thyroid hormone absorption

• PPIs: Omeprazole, lansoprazole, and presumably other medications that reduce gastric acid secretion may interfere with thyroid hormone absorption as well and should be taken away from T4

• Do not over treat...excess thyroid (suppressed TSH) is associated with bone loss and atrial fibrillation


• Timing of levothyroxine administration affects serum thyrotropin concentration. Bach-Huynh TG, Nayak B, Loh J, Soldin S, Jonklaas J. JCEM 2009;94(10):3905-12

• Patients treated with levothyroxine typically ingest it in a fasting state to prevent food impairing its absorption

• Participants were randomized to 1 of 6 sequences, each consisting of three 8-wk regimens in a 3-period crossover design: Fasting state, at bedtime, and with breakfast. The concentrations of TSH, free T(4), and total T(3) during each of the three timing regimens were documented

• Primary outcome was difference between TSH under fasting conditions compared with concentrations during the other 8-wk regimens


• Study participants were receiving levothyroxine for treatment of hypothyroidism or thyroid cancer.

• RESULTS: 65 patients completed the study

• Mean TSH was 1.06 +/- 1.23 mIU/liter when T4 was administered in the fasting state. When T4 was taken with breakfast, the serum thyrotropin concentration was significantly higher (2.93 +/- 3.29 mIU/liter), as it also was when taken at bedtime (2.19 +/- 2.66 mIU/liter).

• CONCLUSION: Nonfasting regimens of T4 are associated with higher and more variable serum TSH concentrations. If a specific serum TSH goal is desired, thereby avoiding iatrogenic subclinical thyroid disease, then fasting ingestion of levothyroxine ensures that TSH remain within the narrowest target range. Division of Endocrinology, Georgetown University Medical Center, Washington, DC 20007


• Altered intestinal absorption of L-thyroxine caused by coffee. Benvenga S, Bartolone L, Pappalardo MA, Russo A, Lapa D, Giorgianni G, Saraceno G, Trimarchi F Thyroid. 2008;18(3):293-301.

• 8 case histories, and in vivo and in vitro studies showing coffee's potential to impair thyroxine (T4) intestinal absorption.

• In vivo test was also administered to 6 women on T4 and 9 control volunteers.

• In 3 separate tests, two 100 microg T4 tablets were swallowed with coffee, water, or water followed, 60 minutes later, by coffee. Serum T4 was assayed over the 4-hour period of the test.

• 2 patients and 2 volunteers also agreed on having tested the intestinal absorption of T4 swallowed with solubilized dietary fibers.


• Altered intestinal absorption of L-thyroxine caused by coffee. Benvenga S, Bartolone L, Pappalardo MA, Russo A, Lapa D, Giorgianni G, Saraceno G, Trimarchi F Thyroid. 2008;18(3):293-301.

• Coffee lowered AIRST4 (average incremental rise of serum T4) by 36% and 29%), PIRST4 (peak incremental rise of serum T4) by 30% and 19%), and AUC (average area under the curve) by 36% and 27% and delayed TMIRST4 (time to maximum...) by 38 and 43 minutes.)

• Bran was a superior interferer. In the in vitro studies, coffee was weaker than known T4 sequestrants

• CONCLUSION: Coffee should be added to list of interferers of T4 intestinal absorption

Sezione di Endocrinologia del Dipartimento Clinico Sperimentale di Medicina e Farmacologia, Universit? di Messina, Messina, Italy

Mild Hypothyroidism• Low Rx dose• Poor compliance• Drug interac)on• Dietary interference w absorp)on

• Pregnancy• ↓ Residual gland func)on• Formula)on switch

Mild Thyrotoxicosis• High Rx dose• Factitious ingestion• Aging with ↓

requirement for LT4

• Nonsuppressed endogenous gland function

• Stopping estrogen therapy

• Formulation switch

SubopAmal Thyroxine TherapyWhat Causes It?

Excessive Thyroxine Therapy

Inadequate Thyroxine Therapy

30%

20%

10%

Ross, 1990

Parle,1993

Canaris, 2000 Hollowell, 2002

27%

21%

14%

18% 18%

22%

15%

18%

10%

20%

30%

Ross DS, et al. JCEM.1990;71:764-769. Parle JV, et al. Br J Gen Pract. 1993;43:107-109. Canaris GJ, et al. Arch Intern Med. 2000;160:526-534. Hollowell J, et al. JCEM. 2002;87:489-499.

How Common Is Subop,mal Thyroxine Therapy?

Carr D, et al. Clin Endocrinol. 1988;28:325-333.

Suboptimal Thyroxine Therapy Impact of Small Thyroxine Dose Changes

10

8

6

4

2

0.2.1

-50 -25 +25 +50

TSHmU/L

T4 (µg/day) Dose

• 21 hypothyroid adults with normal TSH on thyroxine

• Dose changed by only 25 µg q 6 weeks

+75Optimum

10

8

6

4

2

0.2.1

-50 -25 +25 +50

TSHmU/L

T4 (µg/day) Dose+75

Normal TSH rangeAbove-normal TSH

Below-normal TSH

Optimum

Carr D, et al. Clin Endocrinol. 1988;28:325-333.

Suboptimal Thyroxine Therapy Impact of Small Thyroxine Dose Changes

Clinical Consequences of Mild Hypothyroidism

• ↑ Cholesterol• ↑ AtheroscleroPc cardiovascular disease • ↑ MI risk• ↑ Miscarriage risk• Impaired fetal development• Inadequate TSH suppression in thyroid cancer paPents

Consequences of Overt Hypothyroidism Effect of Thyroid Replacement on Lipids

T4 Therapy

↓

↓

±

↓

Hypothyroid State

↑

↑

±

↑

Total cholesterol

LDL-cholesterol

HDL-cholesterol

Triglycerides

Modified from Frankyn JA. In: Braverman LE, Utiger RD, eds. Werner & Ingbar's The Thyroid: A Fundamental and Clinical Text. 8th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2000:833-836.


Physiologic Influences of Pregnancy on Maternal Thyroid Func,on

• In pregnancy, 2 factors increase T4 produc)on:– E2 raising TGB levels– HCG which s3mulates T4 produc3on

• TSH levels are lower due to HCG ac)on on the thyroid• Total T4 levels are important to monitor, fT4 not accurate in pregnancy

• TSH levels are lower for the upper and lower limits of normal compared to non-‐pregnant state. There are trimester specific normal ranges.

Management of Thyroid Dysfunction during Pregnancy and Postpartum J. Clin Endocr.Metab 92: Number 8 Supplement, 2007

77

Thyroid Func,on During Pregnancy

78

Hypothyroidism in PregnancyIncreased LT4 Requirements

Mandel KaplanPatients whose TSH 75% 50-75%rose above normal Mean increase in 45% 40-100%required LT4 dose

Mandel S, N Engl J Med 1990; 323:91-6Kaplan M, Thyroid 1992;2:147-52


Summary in Pregnancy

• Levels below 0.4 may well be normal• TSH levels need to be interpreted with the aid of recently published normograms• TSH levels > 3.5 indicate subclinical hypothyroidism and a risk to the fetus

Low thyroxine levels during late pregnancy associated with risk of assisted

delivery

BBC News (12/23/10) JCEM reports a study of nearly 1,000 healthy pregnant women, where Dutch researchers found that "lower levels of thyroxine at 36 weeks of pregnancy was strongly linked to abnormal positioning of the baby's head and risk of assisted delivery."

http://mailview.custombriefings.com/mailview.aspx?m=2009122301endo&r=3665244-3f5f&l=015-fb2&t=c

http://mailview.custombriefings.com/mailview.aspx?m=2009122301endo&r=3665244-3f5f&l=015-fb2&t=c

Subclinical Hypothyroid

n A 38 y.o. female sees you for a routine check. TSH returns at 5.6 (0.5-4.5), fT4 1.0. Would you treat her? If so, what dose?n Would thyroid antibodies sway your decision?

n Possibly if TSH 3-4.5 and TPO Ab +... Still Rx!?n If her TSH was 8.0 instead? Rx!n If she were contemplating getting pregnant? Wait

until TSH normal and <2.5 to conceiven If she was 70y/o... Consider pros and cons of Rxn If she were your colleague.... Rx! Especially if you

work with her!

slide compliments of Linda A. Barbour, MD, MSPH, FACP

Thank You For Your AYen5on!Lynn Kohlmeier, MD

Endocrine Associates509-777-5000

Endocrine Associates of Spokanewww.SpokaneOsteoporosis.com

EndocrinologyPrimary Care Update

MCE ConferencesLas Vegas, NV

May 27-29, 2011

THYROID DISEASEHypothyroidism: The Tricks of TSH Levels

Hyperthyroidism: A Real AnxietyThyroid Nodules & Goiters



endocrinology primary care update - mce conferences … 1011/5_hypothyroidism_tricks_of… · lynn...

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