thyroid disease women’s health symposium august 1, 2009 michael gardner, md university of missouri...

Thyroid DiseaseThyroid Disease

Women’s Health SymposiumWomen’s Health SymposiumAugust 1, 2009August 1, 2009

Michael Gardner, MDMichael Gardner, MD

University of Missouri ColumbiaUniversity of Missouri Columbia

Departments of Internal Medicine and Child HealthDepartments of Internal Medicine and Child Health

Division of EndocrinologyDivision of Endocrinology

A 24 Year Old Woman With FatigueA 24 Year Old Woman With Fatigue

A 24 year old woman complains of fatigue A 24 year old woman complains of fatigue weight gain and trouble sleeping at nightweight gain and trouble sleeping at nightPMH and PE: unremarkable PMH and PE: unremarkable

TSH is drawn and comes back at 7 mU/L (0.3-5)TSH is drawn and comes back at 7 mU/L (0.3-5)What is the diagnosis?What is the diagnosis?What other test should be ordered?What other test should be ordered?What is any therapy should be started?What is any therapy should be started?

Progression of HypothyroidismProgression of Hypothyroidism

NormalNormalRangeRange

TSHTSH

TT44EuthyroidEuthyroid SubclinicalSubclinical

HypothyroidHypothyroidPrimaryPrimary

HypothyroidHypothyroid

TT33

HypothyroidismHypothyroidism

Primary hypothyroidismPrimary hypothyroidismTSH generally >10, low free T4TSH generally >10, low free T4Treat with levothyroxine Treat with levothyroxine Adjust dose to keep TSH in normal rangeAdjust dose to keep TSH in normal rangeSubclinical hypothyroidismSubclinical hypothyroidismTSH >5 and normal T4TSH >5 and normal T4Check for anti-TPO antibodiesCheck for anti-TPO antibodies

Progression of Subclinical to Progression of Subclinical to Overt HypothyroidismOvert Hypothyroidism

Progression to overt hypothyroidism Progression to overt hypothyroidism estimated is 4 to 18% per yearestimated is 4 to 18% per year

Increased likelihood withIncreased likelihood withHigher TSHHigher TSHPositive antibodiesPositive antibodies(+) antibodies doubles likelihood(+) antibodies doubles likelihood

History of RAI therapyHistory of RAI therapyLithium therapyLithium therapyAge <55yrsAge <55yrs


A free T4 is 1.54 (0.71-1.8) Anti TPO Antibodies A free T4 is 1.54 (0.71-1.8) Anti TPO Antibodies are strongly positiveare strongly positiveShe is diagnosed with Subclinical She is diagnosed with Subclinical

Hypothyroidism and started on L-thyroxine Hypothyroidism and started on L-thyroxine 0.075 mg/day0.075 mg/day

Four months later her TSH is 0.7 mU/LFour months later her TSH is 0.7 mU/LShe is still complaining of fatigue and She is still complaining of fatigue and

trouble sleeping and has not lost any weight. trouble sleeping and has not lost any weight.

Says she has been reading on the Internet Says she has been reading on the Internet that she might need treatment bioequivalent that she might need treatment bioequivalent hormone found in Armour thyroid.hormone found in Armour thyroid.


What do you do?What do you do?Increase her L-thyroxine dose to treat her Increase her L-thyroxine dose to treat her

symptomssymptomsChange to Armour 1 grain dailyChange to Armour 1 grain dailyScreen for other causes of her symptomsScreen for other causes of her symptoms


Excessive doses of thyroid hormone will not fix:Excessive doses of thyroid hormone will not fix:DepressionDepressionMetabolic syndrome / increased adiposity Metabolic syndrome / increased adiposity Sleep apnea / Sleep deprivationSleep apnea / Sleep deprivationEtc.Etc.

No evidence for increased efficacy with the No evidence for increased efficacy with the addition of Liothyronine (T3) to Levothyroxineaddition of Liothyronine (T3) to LevothyroxineMost T3 in humans is produced by peripheral Most T3 in humans is produced by peripheral

conversion of T4conversion of T4Dessicated thyroid is desiccated porcine Dessicated thyroid is desiccated porcine

thyroid gland. thyroid gland. Dose based on organic iodine not thyroid Dose based on organic iodine not thyroid

hormone contenthormone content

Other Causes of Increased TSH Other Causes of Increased TSH

Recovery from serous non thyroidal diseaseRecovery from serous non thyroidal diseaseRandom pulses of TSH (particularly in evening)Random pulses of TSH (particularly in evening)Assay variability (Lab error)Assay variability (Lab error)Adrenal insufficiencyAdrenal insufficiencyTreatment with metoclopramide Treatment with metoclopramide TSH producing tumor and thyroid hormone TSH producing tumor and thyroid hormone

resistant statesresistant statesExtremely RareExtremely RareFree T4 should be increasedFree T4 should be increased

Reasons to Treat Subclinical Reasons to Treat Subclinical HypothyroidismHypothyroidism

Very Little Evidence of BenefitVery Little Evidence of Benefit Possible benefitsPossible benefits

Stabilize GoiterStabilize GoiterWidely accepted, conflicting evidenceWidely accepted, conflicting evidence

Prevent Progression to Overt HypothyroidPrevent Progression to Overt HypothyroidGood associationGood association

Improved lipidsImproved lipidsDecrease CADDecrease CAD

Only in younger patientsOnly in younger patientsMay increase risk >70 yoMay increase risk >70 yo

Improved non-specific symptomsImproved non-specific symptomsGenerally patients symptoms unrelated Generally patients symptoms unrelated

Potential Disadvantages to Treating Potential Disadvantages to Treating Subclinical HypothyroidismSubclinical Hypothyroidism

Relatively safe in young patientsRelatively safe in young patientsCost of life long therapy and monitoringCost of life long therapy and monitoringGeneric is $4 at national chainsGeneric is $4 at national chains

Over treatmentOver treatmentAtrial fibrillationAtrial fibrillationBone lossBone loss

Having an asymptomatic patient taking Having an asymptomatic patient taking medication for the rest of lifemedication for the rest of life

High TSH in Patients Taking L-Thyroxine High TSH in Patients Taking L-Thyroxine

May indicate need for more hormoneMay indicate need for more hormoneOther causes need to be considered Other causes need to be considered TSH takes longer to come down than the T4 TSH takes longer to come down than the T4

takes to come uptakes to come upMissed dosesMissed dosesGenerally TSH high with high normal or Generally TSH high with high normal or

elevated T4elevated T4Medications interfering with absorptionMedications interfering with absorptionIron/Calcium supplementsIron/Calcium supplementsBile bindersBile bindersProton pump inhibitorsProton pump inhibitors

32 Year Old Woman With Fatigue 32 Year Old Woman With Fatigue and Cold Intoleranceand Cold Intolerance

A 32 y/old woman is seen by her PCP A 32 y/old woman is seen by her PCP complaining of fatigue and cold intolerancecomplaining of fatigue and cold intoleranceROS: otherwise negativeROS: otherwise negativePE: Normal except for dry doughy skin PE: Normal except for dry doughy skin

Lab: Lab: TSH is 0.9 mU/L (0.3-5.0)TSH is 0.9 mU/L (0.3-5.0)

Is this patient hyper, hypo or euthyroid?Is this patient hyper, hypo or euthyroid?What should be done next in the work up of What should be done next in the work up of

this patients?this patients?

Secondary HypothyroidismSecondary Hypothyroidism

TSH can only be used to screen for TSH can only be used to screen for primaryprimary hypothyroidismhypothyroidismWhen the TSH is discordant with the symptoms When the TSH is discordant with the symptoms

or physical exam, check the free T4 and or physical exam, check the free T4 and occasionally free T3 occasionally free T3

Cases were the history or physical exam Cases were the history or physical exam suggests hypopituitarism you must also check suggests hypopituitarism you must also check Free T4Free T4Amenorrhea / HypogonadismAmenorrhea / HypogonadismGrowth Failure (children)Growth Failure (children)Postpartum hemorrhagePostpartum hemorrhagePast head trauma etc.Past head trauma etc.

A 48 Year Old Man With “Nervousness”A 48 Year Old Man With “Nervousness”

A 48 year old man complains of increased A 48 year old man complains of increased nervousness. nervousness. He denies heat or cold intolerance He denies heat or cold intolerance His weight is stableHis weight is stableThere is no hair or skin changesThere is no hair or skin changes

Lab: TSH 0.1 mU/lLab: TSH 0.1 mU/l Is this patientIs this patientHyperthyroid?Hyperthyroid?Euthyroid?Euthyroid?

Progression of Graves HyperthyroidismProgression of Graves Hyperthyroidism


TSHTSH

TT44

EuthyroidEuthyroid SubclinicalSubclinicalHyperthyroidHyperthyroid

OvertOvertHyperthyroidHyperthyroid

TT33

T3T3ToxicosisToxicosis

Subclinical HyperthyroidismSubclinical Hyperthyroidism

Low TSH with normal free T4 and T3Low TSH with normal free T4 and T3Log linear relationship between thyroid Log linear relationship between thyroid

hormone and TSHhormone and TSHVery small changes in thyroid hormone Very small changes in thyroid hormone

result in dramatic changes in TSHresult in dramatic changes in TSH

Subclinical Hyperthyroidism: ImportanceSubclinical Hyperthyroidism: Importance

Clinical importanceClinical importanceBoneBoneThyroid hormone stimulates bone resorptionThyroid hormone stimulates bone resorptionStudies are conflictingStudies are conflicting

Atrial fibrillation Atrial fibrillation More common in patients with low TSHMore common in patients with low TSHLower the TSH, high the riskLower the TSH, high the risk

Other areasOther areasSleepSleepExerciseExercise

Treatment of Subclinical HyperthyroidismTreatment of Subclinical Hyperthyroidism

Few long term studiesFew long term studiesDepends on degree and clinical settingDepends on degree and clinical settingTSH 0.1-0.3 and no symptoms or atrial TSH 0.1-0.3 and no symptoms or atrial

arrhythmias: followarrhythmias: followTSH <0.1TSH <0.1Repeat and if still low consider course of Repeat and if still low consider course of

antithyroid medicationsantithyroid medicationsMany patients will be normal after 1-2 yearsMany patients will be normal after 1-2 years

A 48 Year Old Man With “Nervousness”A 48 Year Old Man With “Nervousness”

Total T4 is 5.9 mcg/dL (5-12)Total T4 is 5.9 mcg/dL (5-12)Free T4 is 0.62 ng/dL (0.58-1.64) Free T4 is 0.62 ng/dL (0.58-1.64) Total T3 is 300 ng/dL (87-178)Total T3 is 300 ng/dL (87-178) Is this patientIs this patientHyperthyroid?Hyperthyroid?Euthyroid?Euthyroid?

Hyperthyroidism due to an Autonomous Hyperthyroidism due to an Autonomous NoduleNodule


TSHTSH

TT44

EuthyroidEuthyroid SubclinicalSubclinicalHyperthyroidHyperthyroid

OvertOvertHyperthyroidHyperthyroid

TT33

T3T3ToxicosisToxicosis

OrOr

Indication for I123 Uptake and ScanIndication for I123 Uptake and Scan

Suppressed TSH with elevated T4 and/or T3Suppressed TSH with elevated T4 and/or T3Distinguish Hyperthyroidism from acute Distinguish Hyperthyroidism from acute

thyroiditis thyroiditis Distinguish Graves from autonomous Distinguish Graves from autonomous

nodulesnodulesSome autonomous nodules produce both Some autonomous nodules produce both

T3 and T4 T3 and T4 Role in diagnosis of nodules diminishingRole in diagnosis of nodules diminishingUnable to distinguish cyst from “cold” solid Unable to distinguish cyst from “cold” solid

nodulenoduleUltrasound in skilled hands combined with Ultrasound in skilled hands combined with

FNA better for cancer determinationFNA better for cancer determination

Thank YouThank You

Questions?Questions?

56 Year Old Man In ICU56 Year Old Man In ICU

66 year old post MVA with multiple fractures, 66 year old post MVA with multiple fractures, pneumonia, respiratory failure on respiratory pneumonia, respiratory failure on respiratory failure on respirator failure on respirator The patients develops atrial fibrillation and a The patients develops atrial fibrillation and a

TSH is 0.08 mU/l (0.3-5)TSH is 0.08 mU/l (0.3-5) Is this patient hyperthyroid?Is this patient hyperthyroid?

Severe Illness and Thyroid TestingSevere Illness and Thyroid Testing

Several changes are seen in thyroid function Several changes are seen in thyroid function test in patients with acute illnessestest in patients with acute illnessesLow T3 levels (decrease T4 to T3 Low T3 levels (decrease T4 to T3

conversion)conversion)Increased Reverse T3 levelsIncreased Reverse T3 levelsTotal T4 is often lowTotal T4 is often low

More severe illnessMore severe illnessPituitary TSH secretion is diminishedPituitary TSH secretion is diminished

TT44 Peripheral Conversion Peripheral Conversion

T4

Reverse T3

T35’ Deiodinase5’ Deiodinase

5 Deiodinase5 Deiodinase

T2

5 Deiodinase5 Deiodinase

5’ Deiodinase5’ Deiodinase

Severe Illness and Low T4Severe Illness and Low T4

Seen in more severely ill patientsSeen in more severely ill patientsAppears to be do to abnormalities in bindingAppears to be do to abnormalities in bindingLow TBG, TBPA, and Albumin may be lowLow TBG, TBPA, and Albumin may be lowCirculating substance the impair bindingCirculating substance the impair bindingHigh free fatty acids are one possibilityHigh free fatty acids are one possibility

Measurement of free T4 are effected differentlyMeasurement of free T4 are effected differentlyFree thyroid index is usually lowFree thyroid index is usually lowFree T4 by equilibrium is usually elevatedFree T4 by equilibrium is usually elevatedMeasurement of free T4 by direct assay may be low, Measurement of free T4 by direct assay may be low,

normal or highnormal or high

Severe Illness and Thyroid TestingSevere Illness and Thyroid Testing

The lower the T4 in severely ill patients, the The lower the T4 in severely ill patients, the higher the mortalityhigher the mortality

Thyroid hormone replacement does not help Thyroid hormone replacement does not help thisthis

TSH In Severely Ill PatientsTSH In Severely Ill Patients

In severe illness patients may have transient In severe illness patients may have transient central hypothyroidismcentral hypothyroidismTSH may be lowTSH may be lowIn primary hypothyroidism, TSH may be normalIn primary hypothyroidism, TSH may be normalAlways use ultra sensitive TSH assayAlways use ultra sensitive TSH assayValues 0.01-0.05 suggest hyperthyroidism, Values 0.01-0.05 suggest hyperthyroidism,

0.05-0.3 will usually be normal later0.05-0.3 will usually be normal laterDuring recovery from acute illness, TSH levels During recovery from acute illness, TSH levels

may be transiently elevatedmay be transiently elevated

In Severely Ill PatientsIn Severely Ill Patients

Testing may make euthyroid patient look Testing may make euthyroid patient look hypothyroid or hyperthyroidhypothyroid or hyperthyroid

Primary hypothyroidism may be maskedPrimary hypothyroidism may be maskedHyperthyroidism may be maskedHyperthyroidism may be masked

Effects of Drugs on Thyroid TestsEffects of Drugs on Thyroid Tests

The following drugs suppress TSH values in normal and The following drugs suppress TSH values in normal and hypothyroid individualshypothyroid individualsDopamine Dopamine Dobutamine Dobutamine GlucocorticoidGlucocorticoid

T4 may be displaced from binding sites byT4 may be displaced from binding sites byFurosemideFurosemideSalsalate Salsalate HeparinHeparinPhenytoinPhenytoinCarbamazepine Carbamazepine

Thyroid Testing In Severely Ill PatientsThyroid Testing In Severely Ill Patients

Thyroid function should not be assessed in severely ill Thyroid function should not be assessed in severely ill patients unless there is strong suspicion of underling patients unless there is strong suspicion of underling thyroidal illnessthyroidal illnessNO SCREENING!NO SCREENING!

When there is a strong suspicion, TSH (ultra sensitive), When there is a strong suspicion, TSH (ultra sensitive), Free T4, Free T3 and Reverse T3 need to be assessed Free T4, Free T3 and Reverse T3 need to be assessed Physical exam: look for clinical findings and goiterPhysical exam: look for clinical findings and goiterHistory: ask about past history of thyroid disease History: ask about past history of thyroid disease

and hormone useand hormone useFHx: Thyroid problems often run in families FHx: Thyroid problems often run in families

Thyroid Function in Elderly PatientsThyroid Function in Elderly Patients

TSH levels tend to drop with ageTSH levels tend to drop with ageSeveral older patients have low Free T4 with Several older patients have low Free T4 with

normal or minimally elevated TSH levelsnormal or minimally elevated TSH levelsSeveral older patients have low TSH and Several older patients have low TSH and

normal free T4 and free T3 and no evidence of normal free T4 and free T3 and no evidence of thyroid disfunctionthyroid disfunction

TSH CascadeTSH Cascade

2nd or 3rd Generation TSH Assay 2nd or 3rd Generation TSH Assay Patient without pituitary or severe illnessPatient without pituitary or severe illness

2nd or 3rd Generation TSH Assay 2nd or 3rd Generation TSH Assay Patient without pituitary or severe illnessPatient without pituitary or severe illness

LowLowLowLow NormalNormalNormalNormal ElevatedElevatedElevatedElevated

Check FT4Check FT4Check FT4Check FT4 No further No further testingtesting

No further No further testingtesting

Taking Taking thyroidthyroidReduce Reduce

dosedose

Taking Taking thyroidthyroidReduce Reduce

dosedose

NormalNormalCheck T3Check T3

NormalNormalCheck T3Check T3

HighHighHyperthyroidHyperthyroid

HighHighHyperthyroidHyperthyroid

Check FT4Check FT4Check FT4Check FT4

NormalNormalSubclinicalSubclinical


NormalNormalSubclinicalSubclinical


LowLowPrimaryPrimary


LowLowPrimaryPrimary


Taking thyroidTaking thyroidLow/Low normalLow/Low normalIncrease doseIncrease dose

Taking thyroidTaking thyroidLow/Low normalLow/Low normalIncrease doseIncrease doseNormal FollowNormal FollowNormal FollowNormal Follow

Prevalence of Subclinical HypothyroidismPrevalence of Subclinical Hypothyroidism

Age SubjectsHi TSHLow T4

Hi TSHnormal T4

Framingham* >60 2,139 3% 8%

Detroit* >55 968 1% 7%

*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


When seen by endocrinology, the patient recalled she had When seen by endocrinology, the patient recalled she had required blood transfusions after the birth of her last childrequired blood transfusions after the birth of her last child

Free T4 was 0.4Free T4 was 0.4ACTH stimulation test showed pre value of 2 and 30 min ACTH stimulation test showed pre value of 2 and 30 min

value of 4value of 4Prolactin was undetectableProlactin was undetectableAfter 10 mg of Provera for 10 days there was no menstrual After 10 mg of Provera for 10 days there was no menstrual

bleeding and FSH and LH levels were undetectable bleeding and FSH and LH levels were undetectable Growth hormone did not stimulate Growth hormone did not stimulate


The patient was started on predinsone 2.5 mg The patient was started on predinsone 2.5 mg TIDTID

The next day, she was started on L-ThyroxineThe next day, she was started on L-ThyroxineCyclical estrogen and progesterone were Cyclical estrogen and progesterone were

begun begun She was begun on human growth hormone She was begun on human growth hormone

therapytherapy

Euthyroid Graves DiseaseEuthyroid Graves Disease

thyroid disease women’s health symposium august 1, 2009 michael gardner, md university of missouri...

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