Thyroid Disease Facts

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Thyroid Disease Facts

• Jeffrey Medland
• Lt Col, USAF, MC, SFS
• Chief, Endocrinology
• MGMC, Andrews AFB, MD
• Capital Conference-June 2007

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Outline

• Thyroid Testing
• Hypothyroidism
• Causes
• Signs/symptoms
• Treatment
• Hyperthyroidism
• Causes
• Signs/symptoms
• Treatment
• Thyroid Nodules/ Cancer
• Thyroid Disease and Pregnancy
• Hypothyroidism
• Hyperthyroidism (Hyperemesis Gravidarum, Graves)
• Thyroiditis
• Factors affecting Thyroid function, LT4

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Thyroid
Apical Membrane
Colloid
Basal Membrane
4
Thyroid Peroxidase (TPO)
Coupling Reaction
Iodination Reaction
5
Thyroid Testing

• TSH
• Best test for screening for thyroid dysfunction!
• Log/linear response w/ FT4
• A 2-fold change in FT4 produces a 100-fold change
  in TSH
• Not specific for a particular thyroid disease.
• Dont use TSH alone for diagnosis!
• Also useful in
• Assessing LT4 tx in 1 hypothyroidism
• Monitoring TSH-suppressive tx in thyroid Ca

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Thyroid Testing

• FT4
• Testing methods
• Equilibrium dialysis
• Analog assays
• Abnormal TSH check this next
• Indications
• In conjunction w/ TSH for diagnosing
  hyperthyroidism or hypothyroidism.
• Monitoring LT4 replacement in central
  hypothyroidism (TSH not helpful)
• Assessing response to tx following 131-RAIA
  (Graves, toxic nodules)
• Monitoring ATD tx in pregnant females
• FT3
• Abnormal TSH normal FT4, then check this (T3
  Thyrotoxicosis)

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Overview of Thyroid Function Tests
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Thyroid Testing

• Thyroid Antibodies (TPO, Tg, TSI, TRAb)
• TPO
• TPO Tg Abs assoc w/ Hashimotos. TPO more
  sensitive.
• Helpful in predicting those w/ subclinical
  hypothyroidism who are at ? risk for
  progression to overt hypothyroidism.
• TSI
• When dx of Graves in question
• Note a negative test does not r/o Graves
• Pregnant women w/ Graves
• to determine fetal risk of thyroid dysfunction
  (due to transplacental passage of stimulating or
  blocking Abs).
• Suspected euthyroid ophthalmopathy.
• In pts w/ alternating hyper- and hypothyroidism
  (due to fluctuations in TSH receptor stimulating
  and blocking and stimulating Abs)
• Thyroglobulin (Tg)
• Indications
• Thyroid cancer recurrence
• Factitious (exogenous) vs. endogenous
  hyperthyroidism
• Note Most assays are not reliable in pts ()
  for anti-Tg Ab
• Interferes w/ method of Tg measurement (causing
  factitious low Tg)

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Thyroid Testing

• Radioactive Iodine Uptake and Scan (RAIU/Scan)
• 123-RAIU/Scan or 131-RAIU/Scan
• Indications
• biochemically hyperthyroid pt
• No role in euthyroid or hypothyroid pts
• RAIU produces a number.
• 4-hr (normal 10-15)
• 24-hr (normal 20-30)
• The scan produces a picture
• Tc99m-Pertechnetate Scan
• Picture only, no number

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Thyroid Testing

• Fine Needle Aspiration (FNA)
• provides the most direct information about a
  thyroid nodule
• 95 sensitivity
• Ultrasound
• to assess thyroid nodule size and characteristics
  (cystic vs. solid)
• often used to guide FNAs
• Calcitonin
• h/o MTC
• Thyroid nodule and () FHx of MTC (Familial,
  MEN2A, MEN2B)
• MEN2A MTC, HyperPTH, Pheo
• MEN2B MTC, Pheo, Mucosal neuromas

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F-15D
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Hypothyroidism

• More common than hyperthyroidism
• 99 is primary (
• Hashimotos
• most common thyroid problem (4 of population)
• most common cause in iodine-replete areas
• aka chronic lymphocytic thyroiditis
• Assoc w/ TPO Abs (90), less commonly Tg Abs.
• Iatrogenic Hypothyroidism from 131-RAIA
  (following tx for Graves)
• Postpartum (silent) thyroiditis
• Silent/painless
• Occurs within 6 weeks?6 months postpartum
• Incidence 10-15 of all women, 25 women w/
  Type 1 DM
• Up to 50 are TPO Ab ()
• 70 chance of recurrence w/ subsequent pregnancies

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Hypothyroidism

• Subacute thyroiditis
• aka de Quervains, Granulomatous
• Painful, often radiates to the ear
• c/o malaise, pharyngitis, fatigue, fever, neck
  pain/swelling
• Viral etiology (URI/ pharyngitis)
• self-limited. Can tx inflammation w/ ASA,
  NSAIDs or steroids
• Suppurative/ Acute Infectious Thyroiditis
• Infections of the thyroid are rare
• normally protected from infection by its thick
  capsule
• Bacterial fungal, mycobacterial or parasitic
• Pts are acutely ill w/ a painful thyroid gland
• assoc w/ fever/chills, anterior neck
  pain/swelling, dysphagia and dysphonia

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Thyroiditis
Stage 1
Stage 2
Stage 4
Stage 3

• Clinical Course of Painful Subacute Thyroiditis,
  Painless Postpartum Thyroiditis,
• and Painless Sporadic Thyroiditis.
• Measurements of serum thyrotropin (TSH),
  Thyroxine(T4) and iodine-123 (123I)
• uptake show thyrotoxicosis during the first
  three months, followed by
• hypothyroidism for three months and then by
  euthyroidism.

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Hypothyroidism

• Reidels Struma/Thyroiditis (rare)
• Pts present w/ a painless, hard, fixed goiter
• hypothyroidism occurs when entire gland becomes
  fibrosed
• can see fibrosis of other tissues (fibrosing
  retroperitonitis, orbital fibrosis, or sclerosing
  cholangitis)
• Drug-induced
• Amiodarone
• Lithium
• Interferon-alpha
• Interleukin-2
• Iodine deficiency
• Most common cause of hypothyroidism worldwide!!

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Hypothyroidism

• Symptoms
• General Slowing Down
• Lethargy/somnolence
• Depression
• Modest Weight Gain
• Cold Intolerance
• Hoarseness
• Dry skin
• Constipation (? peristaltic activity)
• General Aches/Pains
• Arthralgias or myalgias (worsened by
  cold temps)
• Brittle Hair
• Menstrual irregularities
• Excessive bleeding
• Failure of ovulation
• ? Libido

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Hypothyroidism

• Exam
• Dry, pale, course skin w/ yellowish tinge
• Periorbital edema
• Puffy face and extremities
• Sinus Bradycardia
• Diastolic HTN
• ? Body Temperature
• Delayed relaxation of DTRs
• Megacolon (? peristaltic activity)
• Pericardial/ pleural effusions
• CHF
• Myxedema (nonpitting edema)
• Bradycardia and hypothermia- think
  hypothyroidism!

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Hypothyroidism

• Laboratory Findings
• Elevated TSH
• Low FT4
• TPO Ab ()
• Pregnant women w/ TPO Ab ()
• Miscarriage rate doubles
• ? risk post partum thyroiditis (35)
• mild anemia
• ? CPK-MB
• ? LDL,? Chol (? lipid clearance)
• Hyponatremia

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Hypothyroidism (Treatment)

• Synthroid (LT4)
• Initial starting dosage 1.6 mg/kg/day.
  
• Dose correlates better w/ lean body wt
• 80 of PO dose of LT4 is absorbed
• vs. Cytomel which is 95 absorbed
• The main absorptive sites proximal and
  mid-jejunum.
• Food can ? LT4 absorption up to 40-50.
  
• Serum LT4 levels rise 10-15 after ingestion,
  peaking at 2-4 hrs.
• Serum LT3 levels dont change due to the slow
  peripheral conversion of T4 ? T3.
• T-1/2 LT4 is 7 days
• can be given weekly in non compliant pts.
• Goal LT4 replacement TSH 1.0-2.5 mU/L

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Hypothyroidism (treatment in general)

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

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Hypothyroidism (treatment in general)

• Hypothyroidism surgery
• Postpone elective surgery in any hypothyroid pt
  until the euthyroid state is restored, however
• Urgent surgery should not be postponed in
  hypothyroid pts,
• though potential complications should be watched
  for.
• Hypothyroidism elderly
• It is prudent to begin treatment with low dose
  LT4, starting at 12.5 or 25 mcg/day
• Titrate to goal or less than goal if cardiac
  symptoms develop despite max anti-anginal tx.

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Hypothyroidism (treatment in general)

• Combined LT4/LT3 tx
• Bottom Line
• most studies show combination T4/T3 therapy does
  not appear to be superior to LT4 alone, for the
  management of hypothyroid symptoms.
• If you decide to try combined T4/T3 therapy
• ? LT4 by 50 mcg and add 12.5 mcg LT3 (cytomel) in
  the a.m.
• ? LT4 by 12.5-25 mcg, and add 5 mcg LT3 in the
  a.m.
• Check TSH before LT3 dose
• T-1/2 Cytomel is 1 day

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Hyperthyroidism

• Thyrotoxicosis any condition that results in
  thyroid hormone excess
• Includes Graves Disease, Toxic Goiter,
  Thyroiditis, and Excessive Thyroxine Ingestion
• Hyperthyroidism Specifically hyperfunctioning
  of the thyroid gland
• Most Commonly caused by Graves Disease in the
  young
• Toxic Nodular Goiter in the elderly

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Hyperthyroidism

• Graves Disease
• Due to autoAbs directed against the TSH
  receptor, resulting in continuous stimulation of
  the thyroid gland to secrete hormone.
• Abs to TSH receptor () in 80 of Graves pts
  
• Abs to TPO or Tg are () in 80 of Graves
  pts
• FemaleMale (5-101)
• Caucasian Asian Black
• Toxic MNG
• Generally arises in the setting of a
  long-standing MNG
• More common in the elderly, areas of iodine
  deficiency
• Toxic Adenoma (Plummers Disease)
• More common in women, areas of iodine deficiency
• adenomas 3 cm are more prone to overt
  hyperthyroidism

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Hyperthyroidism

• Iodine-induced Hyperthyroidism (jod-basedow
  phenomenom)
• Amiodarone-induced (AIT Type 1)
• IV Contrast
• Diets high in iodine
• Thyroiditis
• Subacute (de Quervains)
• painful
• Postpartum
• painless
• Suppurative
• painful
• Amiodarone-induced (AIT Type 2)

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Hyperthyroidism

• Symptoms
• Jittery, shaky, nervous
• Difficulty concentrating
• Emotional lability
• Insomnia
• Rapid HR, palpitations, DOE
• Feeling Hot
• Weight Loss (can see weight gain)
• Freq BMs (hyperdefecation, not diarrhea)
• Fatigue
• Menses w/ lighter flow, shorter duration

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Hyperthyroidism

• Exam
• Eye findings (20)
• Goiter
• Thyroid bruit or thrill
• Tachycardia Sinus Tach, A-Fib
• Flow murmur
• Systolic Hypertension
• Hyperreflexia
• Tremors
• UE, tongue
• Proximal muscle weakness
• Thenar/ hypothenar atrophy
• Acropachy
• Onycholysis (
• separation of nail from the nailbed
• Dermopathy (1)

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Hyperthyroid Eye Disease

• Hyperthyroidism (any cause)
• Lid lag, lid retraction and stare
• Due to increased adrenergic tone stimulating the
  levator palpebral muscles.
• True Graves Ophthalmopathy
• Proptosis
• Diplopia
• Inflammatory changes
• Conjunctival injection
• Periorbital edema
• Chemosis
• Due to thyroid autoAbs that cross-react w/ Ags
  in fibroblasts, adipo-cytes, myocytes behind
  the eyes.

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Hyperthyroid Eye Disease

• Causes of Worsening Ophthalmopathy
• Pre-existing eye disease
• Smoking
• marked ? T3
• marked ? TSI titers
• Not letting pt get to hypothyroid state following
  131-RAIA.
• Does131-RAIA worse ophthalmopathy?
• Majority of cases arise in the 18 mos before to
  18 mos after the onset of thyrotoxicosis.
• Thus a fair number of cases can be ex-pected to
  coincide w/ timing of 131-RAIA.
• Two prospective randomized trials have shown that
  131-RAIA more likely (vs. other tx modalities) to
  worsen ophthalmopathy.

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Graves Dermopathy

• Thyroid Dermopathy
• Thickening and redness of the dermis
• Due to lymphocytic infiltration
• Distribution
• Pretibial (93.3),
• Pretibial feet (4.3),
• Pretibial UE (1.1).

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Graves Dermopathy
Localized plaque on the outer aspect of the skin.
Horny form over shin and dorsum of the foot
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Thyroid Acropachy

• Thyroid acropachy. This is most marked in the
  index fingers and thumbs.

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Hyperthyroidism

• Laboratory Findings
• TSH nearly undetectable
• Elevated FT4 or FT3
• mild leukopenia,
• N/N anemia,
• ? LFTs and alk phos,
• mild ? Ca,
• ? albumin
• ? chol

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RAIU/Scan

• Increased RAIU
• Graves Disease
• Toxic Nodules
• MNG
• Adenoma
• hCG secreting tumors
• Hydatidiform mole
• Choriocarcinoma
• TSH mediated thyrotoxicosis
• Pituitary tumor
• Pituitary resistance to thyroid hormone
• Iodine Deficiency

• RAIU produces a number.
• 4-hr (normal 10-15)
• 24-hr (normal 20-30)
• The scan produces a picture.

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RAIU/Scan

• Decreased RAIU
• Thyroiditis
• Chronic painless
• Postpartum
• Subacute
• Amiodarone-induced
• Thyroiditis Factitia
• Iodine Excess
• Contrast dye
• Diet
• Amiodarone
• Struma ovarii
  (ectopic thyroid hormone production from thyroid
  tissue in an ovarian teratoma)

• RAIU produces a number.
• 4-hr (normal 10-15)
• 24-hr (normal 20-30)
• The scan produces a picture.

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Hyperthyroidism (Treatment)

• 1) ß-blockers (symptom control)
• Propranolol (Inderal ) LA 60-320 mg daily
• Atenolol (Tenormin ) 50-100 mg daily
• Metoprolol (Lopressor ) 50-100 mg bid
• If ß-blocker contraindicated then Verapamil
  (Calan ) 40-80 mg tid
• 2) 131-RAIA (70 thyroidologists prefer)
• Dosing
• Graves 10-15 mCi
• Toxic MNG/Adenoma 20-30 mCi
• Absolute contraindications
• Pregnancy and nursing moms (excreted in breast
  milk)!
• Pregnancy should be deferred for at least 6
  months following tx w/ 131-RAIA.
• Prudent to avoid 131-RAIA in pts w/ active
  moderate? severe Graves ophthalmopathy.

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Hyperthyroidism (Treatment)

• 3) Antithyroid Drugs (30 thyroidologists prefer)
• Propylthiouracil (PTU)
• 100 mg bid-tid to start
• Tapazole (Methimazole)
• 10X more potent the PTU
• 10 mg bid-tid to start
• Complications of ATDs
• Dose dependent w/ Tapazole, Idiosyncratic w/ PTU.
• Agranulocytosis (1/200-500)
• usually presents w/ acute pharyngitis/ tonsilitis
  or pneumonia.
• Rash
• Hepatic necrosis w/ PTU, Cholestatic jaundice w/
  Tapazole.
• Arthralgias

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Hyperthyroidism (Treatment)

• 3) Antithyroid Drugs (30 thyroidologists prefer)
• Candidates for ATDs
• Children and adolescents
• Pts w/ moderate? severe ophthalmopathy
• Thyroid Storm
• Pts w/ mild disease small goiter, low titers of
  TSI (TSH-R Ab), low maintenance dose
• Pts w/ severe disease prior to 131-RAIA
• stop ATDs 5-7 days prior to 131-RAIA
• Labs
• Follow TSH/FT4, CBC, LFTs

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Hyperthyroidism (Treatment)

• 4) Surgery (sub-total thyroidectomy)
• Indications
• Pt preference
• Pregnant women w/ failed ATDs
• Large or symptomatic goiters
• When there is question of malignancy
• Need to be euthyroid prior to surgery
• To ? the risk of arrhythmias during induction of
  anesthesia
• To ? the risk of thyroid storm post operatively
• ATDs ß-blockers
• Risks
• Permanent hypoparathyroidism
• Recurrent laryngeal nerve problems
• Permanent hypothyroidism

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Hyperthyroidism

• Apathetic Hyperthyroidism
• Elderly pts w/ Graves' disease may present w/
  apathy, weight loss, muscular weakness,
  arrhythmias (esp A-fib), CHF, constipation.
• A goiter may not be palpable in as many as 70 of
  pts
• There symptoms may suggest PMR or depression
• The usual hyperkinetic signs and symptoms seen in
  Graves are not typically present in the elderly.
• Check all elderly w/ new-onset atrial arrhythmias
  or CHF for hyperthyroidism

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Hyperthyroidism

• Thyroid Storm
• A life-threatening condition characterized by an
  exaggeration of the manifestations of
  thyrotoxicosis
• Diagnostic Criteria (based on point system)
• Thermoregulatory Dysfunction ? Temp (99?104)
• CNS /-, mild (Agitation)/mod (delirium)/severe
  (seizures, coma)
• Tachycardia (99?140 bpm)
• CHF /-, mild (edema)/mod (rales)/severe (pulm
  edema)
• Atrial Fibrillation /-
• Precipitant History
• Treatment
• ATDs (PTU, Tapazole)
• Iodide (Lugols solution)
• ß-blockers
• Corticosteroids
• Avoid ASA
• Definitive Tx when euthyroid 131-RAIA or surgery

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Subclinical Hyperthyroidism

• Refers to an elevation in T4 and/or T3 within the
  normal range, leading to suppression of the
  pituitary secretion of TSH in the subnormal range
  (i.e. normal T4 and T3, low TSH).
• Clinical symptoms and signs are frequently absent
  or nonspecific.
• Usually found in the elderly
• Often due to an autonomously functioning MNG or
  adenoma.
• Studies have linked subclinical thyrotoxicosis to
• Accelerated bone loss in postmenopausal women
• A higher incidence of atrial dysrhythmias (esp
  atrial fibrillation)
• Recent studies suggest an increase in cognitive
  impairment and all-cause mortality (esp CV
  disease).
• A TSH below the lower limit of normal, but above
  0.1 mIU/mL are less likely to result in such
  complications.
• If pts are not treated, then careful f/u.

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Thyroid Nodules

• Structural disorders of the thyroid (i.e.
  nodules- simple or multiple) are more common than
  functional disorders.
• Prevalence
• Palpable 5
• Non-Palpable 40-50
• Cancer in nodules 5
• Risks
• Women Men
• Smoking
• h/o XRT to head/neck (esp children)
• Iodine deficiency
• Most are Euthyroid and Asymptomatic
• Less than 1 with thyrotoxicosis

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Thyroid Nodules

• Red Flags concerning for Cancer
• Male
• Extremes of age (60)
• Rapid Growth
• 4 cm
• Symptoms of local invasion
• hoarseness, dysphagia
• h/o XRT to the head/neck (esp children)
• Family history of Thyroid Ca
• (PTC or MTC)
• Hard, fixed lesion
• () LN
• h/o familial adenomatous polyposis

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Thyroid Nodules

• FNA Results
• Benign (69)
• f/u 6-12 months
• Surgery if
• MNG w/ compressive Symptoms
• Growth of Nodule
• Recurrence of cystic nodule after aspiration
• Insufficient (17)
• Repeat FNA 3-4 months
• Indeterminate/ Suspicious (10)
• follicular neoplasm
• 85 benign adenomas
• 123-RAIU/Scan
• Surgery
• Malignant (5)
• Surgery
• 131-RAIA if PTC or FTC

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Thyroid Nodules Mimickers

• Thyroid Hemiagenesis
• Agenesis of one lobe of the thyroid, w/
  hypertrophy of the other presenting as a mass in
  the neck mimicking a nodule.
• Occurs in 1/2500 people
• Usually the left lobe that fails to develop w/
  hypertrophy in the right lobe.
• 95 of the time
• Parathyroid gland
• Thyroglossal duct remnants

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Thyroid Cancer

• Papillary Thyroid Ca (PTC) 75
• Follicular Thyroid Ca (FTC) 15-20
• Medullary Thyroid Ca (MTC)
• Anaplastic
• Lymphoma rare
• Hashimotos is a risk factor
• Metastatic to thyroid rare
• Breast, Renal cell, melanoma and lung Ca
• MTC
• FMTC
• MEN2A
• MTC, HyperPTH, Pheo
• MEN2B
• MTC, Pheo, Mucosal neuromas

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Thyroid Disease in Pregnancy

• Four 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.
• 3) Alterations in immune function leading to
  onset, exacerbation, or amelioration of an
  underlying autoimmune thyroid disease.
• 4) ? urinary iodide excretion, which can cause
  impaired thyroid hormone production in areas of
  marginal iodine deficiency (
• - ? risk of goiter and hypothyroidism

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Thyroid Disease in Pregnancy

• Women need more LT4 during pregnancy
  
• ? in TBG (2- to 3-fold) due to E2
• resulting in a 30-100 increase in total T4 and
  total T3, but
• and ? in FT4 and FT3
  
• ? renal LT4 clearance
  
• Transfer of LT4 to the fetus
• Known Hypothyroidism already on LT4
• ? dose by 30 (25-50 µg) taking an extra pill 2
  days a week as soon as pregnancy is confirmed.
• Make further dose changes based on serum FT4
  TSH levels measured every 4 weeks until it is
  normal, and then measure the TSH once per
  trimester.

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Thyroid Disease in Pregnancy
Stage 1
Stage 2
Stage 4
Stage 3

• Frequency of various clinical presentations of
  postpartum thyroid dysfunction
• Hypothyroid (postpartum exacerbation of
  Hashimotos) 40
• Hyper-/Hypothyroid (postpartum thyroiditis) 25
• Hyperthyroid Thyroiditis (postpartum
  thyroiditis) 24
• Hyperthyroid Graves 20

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Thyroid Disease in Pregnancy
hCG Peak 10-12 wks

• Glycoprotein hormones
• LH, FSH, TSH hCG
• Share a similar alpha subunit (a-SU)
• Beta subunit (ß-SU) are immunologically
  biologically unique.
• There is considerable homology between ß-SUs of
  hCG and TSH.
• Distinct 1st trimester increase in hCG
• 10-20 of normal pregnant women have low TSH
  concentrations at peak hCG.

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Thyroid Disease in Pregnancy

• Hyperemesis Gravidarum (HG)
• Hyperthyroidism is assoc w/ severe vomiting
  (toxic vomiting) 5 wt loss
• Hyperemesis is assoc w/ elevated T4 low TSH in
  50 of affected woman.
• Usu transient w/ normal TFTs by 2nd trimester
• In transient cases, no goiter, (-) Thyroid Abs,
  few manifestations of hyperthyroidism
• Due to elevated hCG levels
• 75,000-100,000 IU/L
• Treatment is controversial
• ATDs do not reduce vomiting despite
  normalization of TFTs
• Consider ATDs if hyperthyroxinemia extends into
  the 2nd trimester.

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Thyroid Disease in Pregnancy

• Hyperemesis Gravidarum vs. Graves
• Can be a difficult distinction if pt actively
  vomiting
• Clues pointing to Graves Disease
• Goiter
• Thyroid bruit
• Ophthalmopathy
• Onycholysis
• Pre-existing thyroid c/o prior to pregnancy
• () TSI
• Elevated FT3 levels
• See ? T4?T3 conversion w/ HG (assoc w/ ? in
  nutrition)
• Diagnostic123-RAI or 131-RAI scanning
  contraindicated!!!
• At 12 weeks gestation the fetal thyroid has
  20-50x the avidity for iodine than does the
  maternal thyroid.

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Thyroid Disease in Pregnancy

• Graves (Treatment)
• PTU, Tapazole and ß-blockers all cross the
  placenta.
• ATDs still mainstay of tx
• PTU preferred (crosses placenta
• Tapazole may be assoc w/ aplasia cutis
• The lowest possible dose should be given
• Goal of tx w/ ATD maintain the mothers FT4 or
  FT3 in the high-normal range.
• TSH levels often remain suppressed w/ FT4 or FT3
  in these ranges cant be accurately used for
  titrating ATD.
• If unable to use ATD- surgery (subtotal
  thyroidectomy) can be done during 2nd trimester.
  
• 1st trimester ? risk of miscarriage
• 3rd trimester ? risk of preterm labor

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Causes of Increased LT4 requirement

• Post menopausal therapy
  
• Estrogen
• Drugs known to interfere with absorption
  
• FeSO4
• Calcium carbonate
• Cholestyramine (and probably colestipol)
• Sodium polystryene sulfonate (Kayexalate)
• sulcrafate (Carafate)
  
• Aluminum hydroxide (Amphogel)
  
• soy-based feeding formulas (infants,
  post-menopausal women)
  
• Raloxifene (Evista)
• Separate LT4 and other medications or supplements
  at least 2-4 hrs apart!

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Causes of Increased LT4 requirement

• Drugs that increase LT4 metabolism in the liver
  by inducing microsomal enzymes
  
• Rifampin
  
• Carbamazepine (Tegretol)
  
• Phenytoin (Dilantin)
  
• Phenobarbitol
• Increased clearance
  
• Nephrotic syndrome
  
• Pregnancy
• Drugs with unknown mechanism
  
• Sertraline (Zoloft)
  
• Lovastatin (Mevacor)- 1 case report

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Causes of Increased LT4 requirement

• Malabsorptive States
  
• High fiber diets
  
• Intestinal diseases celiac disease,
  inflammatory bowel disease, short bowel
  syndromes, protein losing enteropathy
• Pancreatic exocrine insufficiency
  
• Hepatic cirrhosis
• Weight gain
• Progression of the hypothyroid disease process
  itself!

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Drugs Affecting Thyroid Function
Somatostatin, Glucocorticoids
-
-
Dopamine
-
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Amiodarone Effect on Thyroid Function
TSH
P
T
T Tyrosyl ring (aka Inner ring) P Phenolic
ring (aka Outer ring)
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The End!
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Amiodarone and the Thyroid

• Iodine Effect
• Inability to Escape from the Wolff-Chaikoff
  effect results in an increased goiter or
  Hypothyroidism.
• Jod-Basedow phenom could occur in someone with
  occult MNG (AIT type 1)
• Direct Toxic Effect
• Thyroiditis (AIT type 2)
• Innocent Changes
• Innocent changes in TFTs can occur in 50 of
  pts
• Due to a Decreased conversion of T4 ?T3
  (Inhibition of Types I II 5- deiodinase)
  
• T4 levels Increase 20-40 during the 1st month,
  then gradually fall towards baseline
  
  
• T3 levels Decrease by up to 30 within the 1st
  few weeks of tx and remain at this level
  
  
• rT3 levels Increase by 20 soon after initiation
  of tx and remain at this level
  
  
• TSH levels initially Increase, then return to NL
  in 2-3 mos

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Jod-Basedow phenomenon (Historical)

• Definition- Hyperthyroidism induced by excess
  Iodine.
• Coindet (French physician) in 1821 published his
  cases about Hyperthyroidism.
• In the English speaking world this became known
  as Graves disease (1835), and in the German
  speaking world as von Basedows disease (1840).
• Coindets cases of hyperthyroidism were actually
  Iodine-induced, hence it came to be known as the
  Iodine-Basedow phenom.
• Jod is German for Iodine, hence the Jod-Basedow
  phenom!
• Coindet was deprived of credit for not only
  describing Hyper- thyroidism, but also the
  variant of hyperthyroidism caused by excess
  Iodine
• The credit was given to Dr Jod who never
  existed!

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Conditions affecting Thyroid Function
Block peripheral T4 ? T3 Conversion Proparanolol G
lucocorticoids PTU (Propylthiouracil) Amiodarone N
a ipodate (iopanic acid)
Somatostatin, Glucocorticoids
-

-
Dopamine
-
-

Block Synthesis of new T4 T3 Lithium Iodine PTU
Methimazole Amiodarone
-
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Thyroid Disease in Pregnancy

• Euthyroid women, () TPO Abs
• Euthyroid pregnant women w/ () TPO Abs develop
  impaired thyroid function
• Tx w/ LT4 reduces the risk of miscarriage and
  prematurity in TPO Ab () women
• LT4 doses
• 0.5 mcg/kg/d for TSH
• 0.75 mcg/kg/d for TSH 1-2 mU/L
• 1 mcg/kg/d for TSH 2 mU/L or TPO Ab titers
  11500
• Is it reasonable to screen all pregnant women for
  TPO Abs and TSH?
• Negro R, et al. JCEM 2006

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Autoimmune Polyglandular Syndromes 2

• Classic Triad
  
• Adrenal Insufficiency
  
• Autoimmune thyroid disease (hypo or
  hyperthyroidism)
• Type 1 DM
• Only 2 of the 3 are required for diagnosis
• FM 31
• Age of onset tends to be between 20 and 30 years
• Other components of APS-2
  
• Primary Hypogonadism
  
• Myasthenia Gravis
  
• Celiac disease
  
• Pernicious Anemia
  
• Alopecia
  
• Vitiligo
  
• Serositis
  
• Stiffman Syndrome
  
• ITP
  
• IgA deficiency/ Goodpastures syndrome

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Hyperthyroidism

• Hypokalemic Periodic Paralysis
• Reported in conjunction w/ thyrotoxicosis
• More common in Asian men
• Symptoms sudden
• Muscle stiffness/cramps
• Flaccid paralysis
• Due to shift of K intracellularly
• Treatment
• K for hypokalemia
• ?-blockers
• Rapid reduction in thyroid hormone

75
Hyperthyroid Eye Disease

• Does 131-RAIA worsen ophthalmopathy?
• The natural course of Graves disease is such
  that 15-20 have significant ophthalmopathy.
• The majority of cases arise in the 18 mos before
  to 18 mos after the onset of thyrotoxicosis.
• Thus a fair number of cases can be expected to
  coincide w/ the timing of 131-RAIA.
• Two prospective randomized trials have shown that
  131 RAIA is more likely than other tx modalities
  to worsen ophthalmopathy.
• Prudent to avoid 131-RAIA in pts w/ active
  moderate? severe Graves ophthalmopathy.
• Tx others at ? risk (esp smokers) w/ course of
  oral corticosteroids.

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Cutis Aplasia
Cutis Aplasia Keloid
Cutis Aplasia
Congenital absence of the skin, particularly on
the scalp, larger defects may extend to the dura
or meninges. Generally isolated lesions, but can
also be associated with a variety of other
genetic disorders. Heals as a flat scar or keloid
lump.
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Thyroid Binding Globulin (TBG)
Increased TBG
Decreased TBG

• Hepatitis/ Biliary Cirrhosis
• OCPs
• Pregnancy
• Estrogens (also Tamoxifen
  Raloxifene)
• Drugs
  (Narcotics/Heroin, Methadone, Clofibrate, Major
  Tranquilizers, 5-FU)

• Steroids/Glucocorticoids
• Hypoalbuminemia
• Androgens (Testosterone,
  Danazol)
• Nephrotic syndrome
• Acromegaly
• Drugs (Niacin,
  L-asparginase)

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Thyroid Regulation
Somatostatin, Glucocorticoids
-
-
Dopamine
-
80
TSH
T Tyrosyl ring (aka Inner ring) P Phenolic
ring (aka Outer ring)
P
T
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Myxedema
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Hyperthyroid Eye Disease
92
Lid Lag
93
T4 binds tightly to TBG, but weakly to albumin T3
also binds to these proteins but not as strongly
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Thyroid Disease in Pregnancy

• 1st trimester increase in hCG
• Glycoproteins
• LH/FSH, TSH hCG
• Share a similar alpha subunit (a-SU)
• Beta subunit (ß-SU) are immunologically
  biologically distinct

97
T Tyrosyl ring (aka Inner ring) P Phenolic
ring (aka Outer ring)
P
T
98
T Tyrosyl ring (aka Inner ring) P Phenolic
ring (aka Outer ring)
P
T
99
T Tyrosyl ring (aka Inner ring) P Phenolic
ring (aka Outer ring)
P
T
100
T Tyrosyl ring (aka Inner ring) P Phenolic
ring (aka Outer ring)
P
T
101
T Tyrosyl ring (aka Inner ring) P Phenolic
ring (aka Outer ring)
P
T
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Amiodarone the Thyroid

• Innocent changes in TFTs can occur in 50 of
  pts
• Due to a Decreased conversion of T4 ?T3
  (Inhibition of Types I II 5- deiodinase)
  
• T4 levels Increase 20-40 during the 1st month,
  then gradually fall towards baseline
  
  
• T3 levels Decrease by up to 30 within the 1st
  few weeks of tx and remain at this level
  
  
• rT3 levels Increase by 20 soon after initiation
  of tx and remain at this level
  
  
• TSH levels initially Increase, then return to NL
  in 2-3 mos

103
Amiodarone Effects on Thyroid

• 37 of Amiodarones mass is Iodine (contains 2
  iodine molecules).
• Dietary Recommendations for Daily Iodide (World
  Health Organization) for Adults 150 mcg.
• Avg US intake 240- 700 mcg
• Each 200mg tab contains 75 mg Iodine
• 10 (7mg) as free is released iodine, almost
  50xs the daily recommended allowance!
• Accumulates in the Liver and Adipose Tissue
• T-1/2 100 days. Total body Iodine stores can
  remain elevated for up to 9 months after stopping
  the drug

104
Amiodarone Effects on Thyroid

• Pts with underlying thyroid disease often have
  defects in the autoregulation of Iodine.
• National Health Nutrition Examination Study
  11.3 positive for Anti-TPO Abs
• Iodine Effect
• Inability to Escape from the Wolff-Chaikoff
  effect results in an increased goiter or
  Hypothyroidism.
• Jod-Basedow phenom could occur in someone with
  occult MNG (AIT type 1)
• Direct Toxic Effect
• Thyroiditis (AIT type 2)

105
Thyroid Hormone

• There is no absorption from the stomach.
  Absorption occurs in the small bowel.
• The main absorptive sites appear to be the
  proximal and mid-jejunum.
• Progressively decreasing degrees of absorption
  occur along the distal bowel and proximal colon.
• Hypothyroidism can lead to a slight increase in
  absorption.

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Images obtained from technetium-99m-pertechnetate
(TcO4) thyroid scintigraphy show abnormally
increased homogeneous radiotracer uptake
throughout the thyroid, which is normal in size.
The intensity of thyroid gland uptake exceeds the
uptake in both salivary glands (arrows),
background activity is markedly decreased, and
the pyramidal lobe is clearly visible. All of
these findings indicate a hyperfunctioning gland.
There is no focal photopenic or focal hot area to
suggest a nodule.