Thyroid Disease

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Thyroid Disease

• Womens Health Symposium
• August 1, 2009

Michael Gardner, MD University of Missouri
Columbia Departments of Internal Medicine and
Child Health Division of Endocrinology
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A 24 Year Old Woman With Fatigue

• A 24 year old woman complains of fatigue weight
  gain and trouble sleeping at night
• PMH and PE unremarkable
• TSH is drawn and comes back at 7 mU/L (0.3-5)
• What is the diagnosis?
• What other test should be ordered?
• What is any therapy should be started?

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Progression of Hypothyroidism
TSH
Normal Range
T3
T4
Subclinical Hypothyroid
Primary Hypothyroid
Euthyroid
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Hypothyroidism

• Primary hypothyroidism
• TSH generally gt10, low free T4
• Treat with levothyroxine
• Adjust dose to keep TSH in normal range
• Subclinical hypothyroidism
• TSH gt5 and normal T4
• Check for anti-TPO antibodies

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Progression of Subclinical to Overt
Hypothyroidism

• Progression to overt hypothyroidism estimated is
  4 to 18 per year
• Increased likelihood with
• Higher TSH
• Positive antibodies
• () antibodies doubles likelihood
• History of RAI therapy
• Lithium therapy
• Age lt55yrs

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A 24 Year Old Woman With Fatigue

• A free T4 is 1.54 (0.71-1.8) Anti TPO Antibodies
  are strongly positive
• She is diagnosed with Subclinical Hypothyroidism
  and started on L-thyroxine 0.075 mg/day
• Four months later her TSH is 0.7 mU/L
• She is still complaining of fatigue and trouble
  sleeping and has not lost any weight.
• Says she has been reading on the Internet that
  she might need treatment bioequivalent hormone
  found in Armour thyroid.

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A 24 Year Old Woman With Fatigue

• What do you do?
• Increase her L-thyroxine dose to treat her
  symptoms
• Change to Armour 1 grain daily
• Screen for other causes of her symptoms

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A 24 Year Old Woman With Fatigue

• Excessive doses of thyroid hormone will not fix
• Depression
• Metabolic syndrome / increased adiposity
• Sleep apnea / Sleep deprivation
• Etc.
• No evidence for increased efficacy with the
  addition of Liothyronine (T3) to Levothyroxine
• Most T3 in humans is produced by peripheral
  conversion of T4
• Dessicated thyroid is desiccated porcine thyroid
  gland.
• Dose based on organic iodine not thyroid hormone
  content

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Other Causes of Increased TSH

• Recovery from serous non thyroidal disease
• Random pulses of TSH (particularly in evening)
• Assay variability (Lab error)
• Adrenal insufficiency
• Treatment with metoclopramide
• TSH producing tumor and thyroid hormone resistant
  states
• Extremely Rare
• Free T4 should be increased

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Reasons to Treat Subclinical Hypothyroidism

• Very Little Evidence of Benefit
• Possible benefits
• Stabilize Goiter
• Widely accepted, conflicting evidence
• Prevent Progression to Overt Hypothyroid
• Good association
• Improved lipids
• Decrease CAD
• Only in younger patients
• May increase risk gt70 yo
• Improved non-specific symptoms
• Generally patients symptoms unrelated

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Potential Disadvantages to Treating Subclinical
Hypothyroidism

• Relatively safe in young patients
• Cost of life long therapy and monitoring
• Generic is 4 at national chains
• Over treatment
• Atrial fibrillation
• Bone loss
• Having an asymptomatic patient taking medication
  for the rest of life

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High TSH in Patients Taking L-Thyroxine

• May indicate need for more hormone
• Other causes need to be considered
• TSH takes longer to come down than the T4 takes
  to come up
• Missed doses
• Generally TSH high with high normal or elevated
  T4
• Medications interfering with absorption
• Iron/Calcium supplements
• Bile binders
• Proton pump inhibitors

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32 Year Old Woman With Fatigue and
Cold Intolerance

• A 32 y/old woman is seen by her PCP complaining
  of fatigue and cold intolerance
• ROS otherwise negative
• PE Normal except for dry doughy skin
• Lab
• TSH is 0.9 mU/L (0.3-5.0)
• Is this patient hyper, hypo or euthyroid?
• What should be done next in the work up of this
  patients?

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Secondary Hypothyroidism

• TSH can only be used to screen for primary
  hypothyroidism
• When the TSH is discordant with the symptoms or
  physical exam, check the free T4 and occasionally
  free T3
• Cases were the history or physical exam suggests
  hypopituitarism you must also check Free T4
• Amenorrhea / Hypogonadism
• Growth Failure (children)
• Postpartum hemorrhage
• Past head trauma etc.

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A 48 Year Old Man With Nervousness

• A 48 year old man complains of increased
  nervousness.
• He denies heat or cold intolerance
• His weight is stable
• There is no hair or skin changes
• Lab TSH 0.1 mU/l
• Is this patient
• Hyperthyroid?
• Euthyroid?

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Progression of Graves Hyperthyroidism
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Subclinical Hyperthyroidism

• Low TSH with normal free T4 and T3
• Log linear relationship between thyroid hormone
  and TSH
• Very small changes in thyroid hormone result in
  dramatic changes in TSH

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Subclinical Hyperthyroidism Importance

• Clinical importance
• Bone
• Thyroid hormone stimulates bone resorption
• Studies are conflicting
• Atrial fibrillation
• More common in patients with low TSH
• Lower the TSH, high the risk
• Other areas
• Sleep
• Exercise

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Treatment of Subclinical Hyperthyroidism

• Few long term studies
• Depends on degree and clinical setting
• TSH 0.1-0.3 and no symptoms or atrial
  arrhythmias follow
• TSH lt0.1
• Repeat and if still low consider course of
  antithyroid medications
• Many patients will be normal after 1-2 years

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Exogenous Subclinical Hyperthyroidism

• Treatment with thyroid hormone
• Treat hypothyroidism
• Goal is normal TSH
• If TSH is low on one visit, wait 6-12 weeks and
  repeat
• Suppress growth of thyroid tissue
• Goal is suppressed TSH
• Thyroid cancer 0.1-0.3

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A 48 Year Old Man With Nervousness

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

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Hyperthyroidism due to an Autonomous Nodule
T3
Normal Range
Or
T4
TSH
Subclinical Hyperthyroid
Overt Hyperthyroid
T3 Toxicosis
Euthyroid
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Indication for I123 Uptake and Scan

• Suppressed TSH with elevated T4 and/or T3
• Distinguish Hyperthyroidism from acute
  thyroiditis
• Distinguish Graves from autonomous nodules
• Some autonomous nodules produce both T3 and T4
• Role in diagnosis of nodules diminishing
• Unable to distinguish cyst from cold solid
  nodule
• Ultrasound in skilled hands combined with FNA
  better for cancer determination

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Thank You

• Questions?

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(No Transcript)
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56 Year Old Man In ICU

• 66 year old post MVA with multiple fractures,
  pneumonia, respiratory failure on respiratory
  failure on respirator
• The patients develops atrial fibrillation and a
  TSH is 0.08 mU/l (0.3-5)
• Is this patient hyperthyroid?

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Severe Illness and Thyroid Testing

• Several changes are seen in thyroid function test
  in patients with acute illnesses
• Low T3 levels (decrease T4 to T3 conversion)
• Increased Reverse T3 levels
• Total T4 is often low
• More severe illness
• Pituitary TSH secretion is diminished

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T4 Peripheral Conversion
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Severe Illness and Low T4

• Seen in more severely ill patients
• Appears to be do to abnormalities in binding
• Low TBG, TBPA, and Albumin may be low
• Circulating substance the impair binding
• High free fatty acids are one possibility
• Measurement of free T4 are effected differently
• Free thyroid index is usually low
• Free T4 by equilibrium is usually elevated
• Measurement of free T4 by direct assay may be
  low, normal or high

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Severe Illness and Thyroid Testing

• The lower the T4 in severely ill patients, the
  higher the mortality
• Thyroid hormone replacement does not help this

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TSH In Severely Ill Patients

• In severe illness patients may have transient
  central hypothyroidism
• TSH may be low
• In primary hypothyroidism, TSH may be normal
• Always use ultra sensitive TSH assay
• Values 0.01-0.05 suggest hyperthyroidism,
  0.05-0.3 will usually be normal later
• During recovery from acute illness, TSH levels
  may be transiently elevated

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In Severely Ill Patients

• Testing may make euthyroid patient look
  hypothyroid or hyperthyroid
• Primary hypothyroidism may be masked
• Hyperthyroidism may be masked

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Effects of Drugs on Thyroid Tests

• The following drugs suppress TSH values in normal
  and hypothyroid individuals
• Dopamine
• Dobutamine
• Glucocorticoid
• T4 may be displaced from binding sites by
• Furosemide
• Salsalate
• Heparin
• Phenytoin
• Carbamazepine

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Thyroid Testing In Severely Ill Patients

• Thyroid function should not be assessed in
  severely ill patients unless there is strong
  suspicion of underling thyroidal illness
• NO SCREENING!
• When there is a strong suspicion, TSH (ultra
  sensitive), Free T4, Free T3 and Reverse T3 need
  to be assessed
• Physical exam look for clinical findings and
  goiter
• History ask about past history of thyroid
  disease and hormone use
• FHx Thyroid problems often run in families

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Thyroid Function in Elderly Patients

• TSH levels tend to drop with age
• Several older patients have low Free T4 with
  normal or minimally elevated TSH levels
• Several older patients have low TSH and normal
  free T4 and free T3 and no evidence of thyroid
  disfunction

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TSH Cascade
2nd or 3rd Generation TSH Assay Patient without
pituitary or severe illness
Low
Normal
Elevated
Check FT4
No further testing
Taking thyroid Reduce dose
Check FT4
Normal Subclinical Hypothyroid
Low Primary Hypothyroid
Normal Check T3
High Hyperthyroid
Taking thyroid Low/Low normal Increase dose
Normal Follow
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notes

• Elderly
• decreased t4 but normal tsh
• normal t4 but low tsh
• treat thyroid cancer, nodules or hx rt
• creast subclincal hyperthyroid
• benefit exceds the risk
• causes of endougeous sublcin hyper
• module high precentage of automas
• do euthyroid graves dises 60 have supressed tsh

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Prevalence of Subclinical Hypothyroidism
Increased Risk in Whites vs Blacks, Women
vs. Men, and elderly subjects. Sawin CT et
al., Arch Int Med 1451386, 1985 Bagchi N
et al., Arch Int Med 150785, 1990
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32 Year Old Woman With Fatigue and
Cold Intolerance

• When seen by endocrinology, the patient recalled
  she had required blood transfusions after the
  birth of her last child
• Free T4 was 0.4
• ACTH stimulation test showed pre value of 2 and
  30 min value of 4
• Prolactin was undetectable
• After 10 mg of Provera for 10 days there was no
  menstrual bleeding and FSH and LH levels were
  undetectable
• Growth hormone did not stimulate

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32 Year Old Woman With Fatigue and
Cold Intolerance

• The patient was started on predinsone 2.5 mg TID
• The next day, she was started on L-Thyroxine
• Cyclical estrogen and progesterone were begun
• She was begun on human growth hormone therapy

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Euthyroid Graves Disease