Interpretation of laboratory thyroid function tests

Dr. Hussam El-Mouzi Clinical Pathologist Al Borg Laboratory

The “Hidden” Health Problem

Who do you know with thyroid disease?

5 % of world population suffers from thyroid diseases

Khan A, Muzaffar M, Khan A et al. Thyroid Disorders, Etiology and Prevalence. J Med Sci. 2002;2:89-94

Hypothalamic-Pituitary-Thyroid Axis

Thyroid Hormones AffectsMany Organs and General Health

UterusUterus

HeartHeart

LiverLiverKidneyKidney

BrainBrain

SkinSkin GI TractGI Tract

LungsLungsEyesEyes

• All newborns (neonatal screening)• personal history of thyroid disease• strong family history of thyroid disease • Have an autoimmune disease, such as Type 1

Diabetes • Some genetic conditions (e.g. Down,

Turner syndromes)• past history of neck irradiation • drug therapies such as lithium and amiodarone • women over age 35 • elderly patients• Pregnant women during the first trimester• women 6 weeks to 6 months post-partum• Have elevated lipid levels

Thyroid Disease – Who Is At Risk ?

Investigation and Management of Primary Thyroid Dysfunction. Toward Optimized Practice Program, Edmonton: AB, 2008 Update.

• American Association of Clinical Endocrinologist (AACE), American Academy of Family Physicians (AAFP), The American College of Physician (ACP) and the American Thyroid Association (ATA) vary greatly in their recommendations.

• ATA recommending routine screening at age 35 then every five years

To screen or not to screen for thyroid dysfunction

When the Thyroid Doesn’t Work

• Hyperthyroidism • Hypothyroidism

Hypothyroidism• More common than hyperthyroidism• 99% is primary (< 1% due to TSH deficiency) Hashimoto’s: • Most common cause of hypothyroidism

• Goiter• Anti TPO antibodies (90%)

• Anti Thyroglobulin antibodies (20-50%)

Postpartum (silent):

• Silent/painless

• Occurs within 6 weeks6 months postpartum

Subacute thyroiditis:• Most common cause of painful thyroiditis

2001; Intenzo CM, et al. Scintigraphic features of autoimmune thyroiditis. 21: 957-964

Common Signs and Symptomsof Hypothyroidism

Dry skin

Brittle and lustreless hair

Weight gain

Tiredness

Constipation

Muscle aches

Bradycardia

Cold intolerance

Depression

Memory Loss

Heavy periods

Laboratory findings in Hypothyroidism

• Elevated TSH

• Low FT4

• TPO Ab (+)

• Macrocytic anemia due to VIT B12 deficiency

• ↑ CPK-MB

• ↑ LDL,↑ Chol (↓ lipid clearance)

• Hyponatremia

Hypothyroid Algorithm

SuppressedHypothyroid

ElevatedAutoimmune

Disease

Thyroid AntibodiesAnti-TPO

Within Normal Limits

Order FT4

Mildly Elevated4 - 10 mIU/ml

Within Normal LimitsType Title Here

Hypothyroid

FT4Suppressed

Elevated> 10 mIU/ml

TSH

Reference: Modified from Mayo Medical Laboratories Communique’ March 2009.

Hyperthyroidism• less common than hypothyroidism• 99% is primary (< 1% due to TSH deficiency)• Graves’ Disease

• Goiter• Most common cause of hyperthyroidism• Anti-TSHr antibodies (80%)

• Toxic Nodular Disease• Single or multiple nodules• Occurs mostly in older age than graves

• T3 Thyrotoxicosis: Approximately 5% of clinically hyperthyroid

patients with normal FT4

Common Signs and Symptomsof Hypothyroidism

Worm moist skin

Hair loss

Weight loss

Nervousness

Increased bowel movements

Muscle weakness

Tachycardia

Heat intolerance

Insomnia

Difficulty in concentrating

Light or Absent periods

Laboratory findings in Hyperthyroidism

• TSH nearly undetectable

• Elevated FT4 or FT3

• Mild leukopenia

• N/N anemia

• ESR elevated

• ↑ LFT’s and alk phosph

• Mild ↑ Ca++

• ↓ Albumin

• ↓ Cholesterol

Hyperthyroid Algorithm

Sensitive TSH

0.3- 4.8 mIU/L

Within normal Limits no further testing indicated

0.1- 0-3 mIU/L

Borderline Low TSH

< 0.1 mIU/L

Low TSH

FT4

Hyperthyroid

If normal FT4

Order FT4

Order FT3 Reference: Modified from Mayo Medical Laboratories Communique’ March 2009.

Spectrum of Thyroid Disease

Sever

mild

Subclinical

Subclinical Thyroid Disease

• Asymptomatic• Among the group with subclinical thyroid

disease, 73.8% are hypothyroid and 26.2% are hyperthyroid.

• TSH outside the reference interval but normal serum levels of T3 and T4

• The prevalence of SCH is about 4% to 10% in the general population and may be as high as 20 percent in women older than 60 years

• Antithyroid antibodies can be detected in 80% of patients with SCH.

• 80% of patients with SCH have a serum TSH of less than 10 mIU/L.

• To treat or not to treat

Case Study

A 30-year-old woman presents to gastroenterology clinic with constipation in last 3 months

Also she developed fatigue and a weight gain of 9.1 kg in the past 6 months in spite of her tight trials for diet control.

She say she become to much depressed , asked psychiatric advices and started antidepressant therapy which claimed as a cause for her weight gain. She was planning for pregnancy before but she also loss her desire for sex.

She has a sister who is receiving levothyroxine therapy for hypothyroidism.

On examination, she looked slightly pale, pulse 72/min regular,bl pr 110/80,chest ,heart and abdomen :clinically free, thyroid is not palpable.

All Laboratory tests are unremarkable except a serum TSH level of 7 mIU/L. Thyroperoxidase (TPO) antibodies are detected.

Subclinical hypothyroidism• The TSH level may be borderline elevated in the

presence of normal levels of fT4.• Treatment for subclinical hypothyroidism is

recommended when: TSH greater than 10mU/L; TSH is above the upper reference interval limit,

but ≤10 mU/L and any of the following are present: • elevated thyroid peroxidase (TPO) antibodies• goitre• strong family history of autoimmune disease• Pregnancy• Dyslipidemia

Thyroid function test: a clinical lab perspective. Medical Laboratory Observer, February, 2007:10-19.

Subclinical hyperthyroidism

TSH level may be borderline suppressed in the presence of normal levels of fT4

Subclinical hyperthyroidism is much less common than Subclinical hypothyroidism

Treatment for subclinical hyperthyroidism is recommended when:

• Any cardiac disease• Age > 60• Osteoporosis

Subclinical Hyperthyroidism: to treat or not to treat? Postgrad Med J. 2004;80:394-398.

Case Study

• 67 year old man admitted to the hospital with severe decompensated CHF. Responds to initial therapy in terms of oxygenation, but does not regain normal mental status as quickly.

• Lab work was done to rule out reversible causes of altered mental status. TSH is elevated at 13. On further testing, free T4 is normal, but T3 is low.

• Is this patient hypothyroid?

Sick Euthyroid Syndrome• Thyroid related changes that occur during

systemic illness in the absence of intrinsic thyroid disease

• The syndrome is acute, reversible, and occurs commonly after surgery, starvation and in many acute febrile illnesses, These changes may be observed in up to 75% of hospitalized patients

• Any abnormality in hormone level is possible, usually low fT3 and tT3

Thyroid Disorders in Elderly Patients, S Med J 2005;98(5):543-549

Drugs that can lead to alterations inthyroid function

• Lithium: decreased TH release

• Amiodarone: iodine-rich drug widely used for the management of arrhythmiaswhich may cause hypo or hyperthyrodism

• SSRI anti-depressants (example Prozac): increased TSH

• Estrogens: Increase TBG, decrease FT4 level

• Androgens/corticosteroids : Decrease TBG, increase FT4 level

Misleading TSH Results

• TSH in normally released in a pulsatile fashion, peaking during the night it generally takes 4-6 weeks for TSH levels to reflect the status of thyroid hormone in the blood

• Acutely ill patients: “sick euthyroid syndrome”• Following thyroid hormone replacement:

“pituitary reset”, wait 6-8 weeks before measuring TSH

• During treatment phase of hyperthyroid patients: “pituitary reset”, wait 3 months before measuring TSH

• Patients with severe hypo- or hyperthyroidism may display an abnormal TSH for several months after clinical euthyroidism is achieved.

What the American Association of Clinical Endocrinologists Said...

TSH Reference range ?

AACE believes the new range will result in proper diagnosis for millions of Americans who suffer from a mild thyroid disorder, but have gone untreated until now."

Three factors alter thyroid function in pregnancy

1) Transient ↑ in hCG, during the 1st trimester can stimulate the TSH-R

- Gestational Transient Thyrotoxicosis (GTT)

- Hyperemesis gravidarum

2) E2-induced ↑ in TBG during the 1st trimester, which is sustained during pregnancy affecting TT4 and TT3

3) Alterations in immune function leading to onset, exacerbation, or improvement of an underlying autoimmune thyroid disease.

Thyroid Disease in Pregnancy

Thyroid Disease in Pregnancy• Pre-pregnancy and early pregnancy: TSH screening for hypothyroidism is indicated in women

who are planning pregnancy or are in early pregnancy if they have a goiter or strong family history of thyroid disease.

• Pregnancy: TSH may be suppressed as a normal finding within the

first trimester of pregnancy. A normal fT4 generally excludes hyperthyroidism.

US Endocrine Society recommends thyroid function screening for all pregnant women

• Post pregnancy: Post-partum thyroiditis (PPT) may occur in 5-10% of

women

Subclinical hypothyroidism with pregnancy

• Undetected SCH during pregnancy may adversely affect the neuropsychological development ,survival of the fetus

• Associated with hypertension and toxaemia

• Subclinical hypothyroidism is associated with ovulatory dysfunction and infertility..

Congenital Hypothyroidism

Because newborns are asymptomatic at birth, screening programs developed worldwide

Incidence 1 in 3,000

One of the commonest treatable causes of mental retardation

Treating Thyroid Disorders

Indications for LT4 replacement Asymptomatic: TSH > 10 Asymptomatic and TPO Ab (+): TSH > 5 Symptomatic: TSH > 5 Pregnant female: TSH > 5 Goitrous: TSH > 5

• Annual Monitoring only with TSH every 6 to 8 weeks until the TSH level reaches 0.5mIU/L to 2.0 mIU/L

• After the TSH level has normalized, maintenance dosage is continued and the TSH test repeated annually or whenever the patient becomes symptomatic

HypothyroidismHypothyroidism

Treating Thyroid Disorders

• Radioiodine Therapy• Stop Thyroid Hormone Production• Anti-thyroid Drugs Often Helpful

• Surgery Maybe Necessary• Once treatment begins, FT4 is recommended to

monitor therapy during early transition phase ( usually not more than 3 months )

• TSH is not recommended for following treatment of hyperthyroidism unless FT4 drops to low-normal levels, the thyroid gland enlarges and symptoms of hypothyroidism present

HyperthyroidismHyperthyroidism

Possible explanations for various result combinations

High T4 Normal T4 Low T4

High TSH

Irregular use of thyroxine

AmiodaronePituitary

hyperthyroidism (TSH-producing pituitary tumour - rare)

Thyroid hormone resistance (very rare)

Subclinical hypothyroidism

T4 under replacement

Primary hypothyroidism

Normal

TSH

As aboveSome drugs (steroids,

beta-blockers, NSAIDS)

Non-thyroidal illnessT4 replacement

(sometimes stablises with normal TSH and FT4)

Normal Some drugs (anticonvulsants,anti-T3, anti-T4)

Pituitary or hypothalamic hypothyroidism,

Severe non-thyroidal illness

Low TSH

Primary hyperthyroidism

Subclinical hyperthyroidism

Subtle T4 over replacement

Non-thyroidal illness

Pituitary or hypothalamic hypothyroidism,

Severe non-thyroidal illness

Thyroid Scale Diagram

Test Lab Low Optimal Range Lab High

TSH 0.5 1.3-1.8 5.0

Free T4 0.8 1.2-1.3 1.8

Free T3 2.3 3.2-3.3 4.2

Optimal zone is an approximation and that it is meant to be used as a rough guide.

Cancer thyroid• Thyroid carcinoma occurs relatively infrequently compared

to the common occurrence of benign thyroid disease

• Thyroglobulin Assays: Determines the amount of thyroid tissue after a thyroidectomy ie

there should be no thyroglobulin after complete thyroid gland removal.

Used to monitor the recurrence of the common thyroid cancers (follicular cell–derived tumors)

Tg measurements should always be interpreted in the context of simultaneous measurement of Tg autoantibodies (TgAB). TgAB occur in about 20% of thyroid cancer patients and can lead to falsely low Tg measurements

• Calcitonin Assay: Used to detect and monitor the recurrence of medullary thyroid

cancer

Patients Responsibilities

• Tell Your Doctor if You Have Symptoms

• Ask Your Doctor for a TSH Test and Free T4 -- Make These

Tests as Part of Your Medical Routine if You Are a Woman

Over 35 or a man over 60 years

• Take Your Medication as Directed

• Take Your Thyroid Medication Separately from

Iron, Calcium and Multivitamins

• Do Not Change Brand or Dose of Your Thyroid Medication Without Consulting Your Doctor

• If Symptoms Persist or Return, Tell Your Doctor

Conclusion • TSH is a good screening test to assess

thyroid function in an outpatient setting. If TSH is abnormal, the diagnosis is confirmed with thyroid hormone levels.

• Screening for thyroid diseases especially those at high risk is cost effective as up to 20% of those with subclinical thyroid disease may turn to clinical thyroid disease

• Timing and choosing the right thyroid test is the best approach in understanding the meaning of the results.

THANK YOU