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Subclinical hypothyroidism- serum TSH above upper limit, ... 12 Grebe, SKG et al. Treatment of hypothyroidism with once weekly thyroxine. JCEM 1997; 82: 870. ... – PowerPoint PPT presentation

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Title: Hypothyroidism

  • Katherine Stanley, MD
  • January 14, 2008

  • Overt hypothyroidism serum TSH above upper limit
    of normal, free T4 below lower limit
  • Subclinical hypothyroidism- serum TSH above upper
    limit, free T4 in normal range

  • Subclinical 5 of adults
  • Overt 0.1-2 of adults
  • 2 of adolescents (subclinical and overt)
  • 5-8x more common in women
  • Congenital HT in 14000 newborns

Clinical Manifestations
  • Constitutional
  • Fatigue, weight gain, cold intolerance
  • Skin
  • Coarse hair and skin, brittle nails, puffy
    facies, nonpitting edema
  • Enlargement of tongue, periorbital edema,

Clinical Manifestations
  • Cardiovascular
  • Bradycardia, decreased contractility, increased
    SVR-gtincr diastolic BP, increased cholesterol (2x
    the general population)2, increased homocysteine,
    pericardial effusions
  • Respiratory
  • DOE, rhinitis, decreased exercise capacity, OSA
    (macroglossia), pleural effusions

Clinical Manifestations
  • GI
  • Constipation
  • Heme
  • Normocytic anemia, macrocytic anemia
    (pernicious), hypocoagulable state, incr LDH
  • Renal
  • Hyponatremia, increased creatinine

Clinical Manifestations
  • Reproductive
  • Menstrual irregularities, decreased fertility,
    incr prolactin, decr libido, ED, delayed
  • Musculoskeletal
  • Delayed DTRs, myalgias, arthralgias, incr CK,
    carpal tunnel
  • Neurologic
  • Depression, dementia, Hashimotos encephalopathy,
    myxedema coma

A few words about myxedema coma
  • Presents w/ altered consciousness, hypothermia,
    hypoglycemia, hyponatremia, hypoventilation,
    bradycardia, hypotension
  • Mortality 30-40
  • Treatment
  • IV T4- load 200-400 mcg, f/b 50-100 mcg/day
  • Use of T3 controversial
  • Glucorticoids until adrenal insufficiency ruled

Clinical Manifestations in Children
  • Most common manifestation is declining growth
    velocity, short stature
  • Generally insidious
  • May be only symptom
  • Altered school performance
  • May actually improve in some children
  • Delayed pubertal development
  • Enlarged sell turcica 2/2 hyperplasia of
    thyrotroph cells
  • Rarely symptomatic
  • Reversible with therapy

Other reasons to check the TSH
  • Goiter
  • Surgery around the thyroid
  • Irradiation
  • Drugs that affect thyroid
  • Lithium, amiodarone
  • Autoimmune diseases
  • DM 1, pernicious anemia, vitiligo, primary
    adrenal insufficiency, PBC
  • Chromosomal disorders, eg Downs, Turners,

Causes of Hypothyroidism
  • Chronic autoimmune thyroiditis (Hashimotos)
  • Most common cause in both children and adults
  • Thyroidectomy
  • 2-4 weeks with total, variable with subtotal
  • Neck irradiation
  • Radioiodine therapy
  • Iodine- deficiency or excess
  • Drugs
  • Lithium, amiodarone, kelp, IFN-a, IL-2, contrast
  • Infiltrative disease

Hypothyroidism in Childhood Cancer Survivors
  • One study found that 36 of childhood cancer
    survivors had developed primary HT, 32
  • Major risk is from radiation to head and neck
  • Current guidelines recommend yearly TSH and T4 in
    such patients4
  • May be some risk from chemo alone
  • 30 of the patients in above study had not
    received any radiation

  • Check the TSH
  • 98 sensitive, 92 specific
  • Why is TSH the best test?
  • T4 has wide range of normal
  • Everyone has endogenous optimum set point
  • TSH will increase when fall below set point
  • If TSH increased, check free T4

Tricky Thyroid- when TSH doesnt work
  • Secondary/Tertiary Hypothyroidism
  • TSH can be low, inappropriately nl, or slightly
    high (biologically inactive)
  • Check FT4 if suspect
  • Suspect if known hypothalamic or pituitary dz,
    prior cranial irradiation, mass lesion in
    pituitary, s/sx of other hormonal deficiencies
  • Drugs that affect Thyroid Testing
  • See next slide
  • Dont forget about sick euthyroid

Drugs and Thyroid Testing
  • Decreased TSH secretion
  • Glucocorticoids, dopamine
  • Decreased TBG
  • Glucocorticoids, androgens, niacin
  • Increased TBG
  • Estrogens, tamoxifen, methadone, heroin,
  • Increased T4 clearance
  • Phenytoin, carbamazepine, rifampin, phenobarbital
  • Decreased T4 binding to TBG
  • Furosemide, heparin, salicylates, NSAIDs

To screen or not to screen?
  • American Thyroid Association recommends universal
    screening q5yrs beginning at 355
  • High prevalence
  • Known clinical consequences
  • Accurate, available, safe, inexpensive assay
  • Effective treatment
  • Cost effectiveness analysis published in JAMA6
    found 9223 per quality adjusted life year (QALY)
    in women, 22595 per QALY in men, mostly based on
    relieving sxs associated with thyroid failure

To screen or not to screen?
  • U.S. Preventive Task Force Guidelines declares
    evidence insufficient to recommend routine
  • Poor evidence that treatment improves clinically
    important outcomes
  • Low PPV in primary care population

  • Average required dose is 1.6 mcg/kg
  • Required dose more closely w/lean body mass than
    fat mass8
  • May want to consider dosing closer to ideal body
    weight in obese pts

Treatment in children
  • Children clear T4 more rapidly than adults
  • Age 1-3 4-6 mcg/kg
  • Age 3-10 3-5 mcg/kg
  • Age 10-16 2-4 mcg/kg
  • Avoid overtreatment
  • Maintain TSH in lower nl range, T4 in upper
  • Can cause craniosynostosis in infants,
    deleterious effects on behavior, school
    performance, growth
  • May spontaneously remit, but should continue
    treatment until complete growth and puberty

Start low, go slow?
  • Some physicians adhere to this principal in all
  • RCT comparing full dose vs. low starting dose of
    25 mcg9
  • Excluded pts with known cardiac disease
  • Everyone remaining screened with dobutamine
    stress echos
  • Full dose group reached euthyroidism more quickly
  • No cardiac events in either group
  • No difference in rate of QOL improvement or
    cholesterol improvement

  • Pts older than 65, known cardiac disease should
    start at 25 mcg
  • Young, healthy patients should start at full dose
    (1.6 mcg/kg)
  • Check TSH 3-6 wks after starting and after any

What brand should I use?
  • Bioequivalence studies of Synthroid, Levoxyl, and
    2 generic preps showed no significant differences
    for area under curve, time to peak, peak conc of
    T3, T4, and FTI10
  • However, FDA recommends remaining on same
    preparation, checking TSH after 6 wks if pt must

What if my patient wont take their Synthroid?
  • T4 has very long half life
  • Can give total weekly dose qwk12
  • Caveat- above recommendation based on small,
    relatively short study

What if my pt wants more Synthroid?
  • Pts often say they feel better on higher doses
    which put their TSH in lower range of normal,
    even a bit hyperthyroid
  • Double blind crossover study comparing low,
    middle, and high doses113
  • No difference in quality of life, cognitive
    measurements when compared both based on dose and
    TSH level

Special Cases- Cardiac Disease14
  • Treatment should improve cholesterol, DBP,
  • Improves angina in some (38), 46 have no
    change, 16 have increased sxs
  • No evidence of decr CV MM with tx of
  • Some evidence of increased CV MM when initiating
  • Generally, start very slowly (25 mcg), consider
    extensive cardiac assessment, eg stress or angio,
    and possible medical tx and/or stenting or CABG

Special Cases-Elderly
  • Another population to start slowly with, perhaps
    consider not treating
  • Cohort study addressing disability and survival
    in old age in relation to thyroid status15
  • No difference in mortality rate, decline in
    cognitive fxn, decline in ability to carry out
    ADLs and IADLs, depression with increased TSH
  • May even have decr mortality w/incr TSH
  • ?Survival benefit

Special Cases- Subclinical16
  • TSH 4.5-10, no treatment
  • Rate of progression 2.6 Ab-, 4.3 Ab
  • Monitor TSH q6-12 mos
  • TSH gt10, consider tx given 5 rate of progression
    to overt but inconclusive evidence of benefit
  • Pregnancy, treat given evidence of worsened fetal
  • Treated overt, adjust dosage

What if I have SHT and ?
  • Depression17,19
  • No difference in cognitive and emotional fxn
    between those with SHT (TSH 3.5-10) and without
  • No difference in above in those with SHT after tx
    w/T4 vs. placebo
  • Obesity18,19
  • No diff in BMI or body weight after tx of SHT
  • High cholesterol20,2
  • While pts w/SHT may have worse lipid profiles, no
    beneficial effect of tx has been conclusively
  • Fatigue19
  • No difference in impr btw treatment and placebo

Subclinical hypothyroidism in children21
  • Baseline TSH less predictive of rate of
    progression than in adults
  • Higher baseline thyroglobulin Ab and thyroid
    volume may be predictive
  • Increasing TPO Ab over time may be indicative of
    declining thyroid fxn
  • No growth retardation in children w/SHT followed
    over 5 years
  • Treatment is controversial22,23

Special Cases-Pregnancy
  • Increased TBG, T4 clearance, and transfer of T4
    to fetus
  • Increased requirement begins _at_ 8 wks, plateaus _at_
    wk 16
  • Consider increasing dose when pregnancy
    confirmed, then check TSH q4wks until TSH nl

Special Cases-Congenital hypothyroidism
  • Most common treatable cause of mental retardation
  • Etiologies
  • Most common is thyroid dysgenesis
  • Defects in thyroid hormone synthesis, secretion,
    and transport
  • Central- congenital syndromes, birth injury,
    insufficient tx of maternal hyperthyroidism
  • Transient-iodine deficiency or exposure,
    antithyroid drugs, maternal transfer of blocking

Congenital HT24
  • Clinical Manifestations
  • Lethargy, slow movement, hoarse cry, feeding
    difficulties, constipation, macroglossia,
    umbilical hernia, large fontanels, hypotonia, dry
    skin, hypothermia, prolonged jaundice
  • But most infants have few if any s/sx
  • Hence part of newborn screen
  • Some screens check T4, some check TSH
  • Advantages and disadvantages of both
  • Treatment
  • Oral T4 (crushed pills)
  • 10-15 mcg/day
  • Avoid soy formula

Congenital HT
  • Prognosis
  • Normal growth, development, and intelligence if
    treated early (lt2 wks)
  • Improved outcomes with higher initial T4 dose and
    shortened time to target T4 and TSH25

Special Cases-Drugs affecting Treatment
  • Drugs that affect TBG or binding of T4 to TBG
  • I already told you
  • Drugs that decrease absorption of T4
  • Cholestyramine, CaCO3, FeSO4, sucralfate, PPIs,
    and others

Special Cases- Surgery
  • Higher incidence of ileus, hypotension,
    hyponatremia, CNS dysfunction
  • Consider postponing elective surgeries
  • Not urgent surgeries, just be aware of slightly
    increased complications

  • 1 Hollowell, JG et al. Serum TSH, T4, and
    thyroid antibodies in the US population
    (1988-1994) National Health and Nutrition
    Examination Survey (NHANES III). JCEM 2002 489.
  • 2 Diekman, T et al. Prevalence and correction of
    hypothyroidism in a large cohort of patients
    referred for dyslipidemia. Arch Intern Med 1995
    155 1490.
  • 3 Rose, SB et al. Diagnosis of hidden central
    hypothyroidism in survivors of childhood cancer.
    JCEM 1999 4472.
  • 4 Childrens Oncology Group. Long-term follow-up
    guidelines for survivors of childhood,
    adolescent, and young adult cancers. National
    Guidelines Clearinghouse 2006 www.guideline.gov.
  • 5 Ladenson, P et al. American Thyroid
    Association Guidelines for Detection of Thyroid
    Dysfunction. Arch Intern Med 2000 160 1573.
  • 6 Danesee, MD et al. Screening for mild thyroid
    failure at the periodic health examination a
    decision and cost-effectiveness analysis. JAMA
    1996 276 285.
  • 7 US Preventive Services Task Force. Screening
    for thyroid disease recommendation statement.
    National Guidelines Clearinghouse 2004
  • 8 Santini, F et al. Lean body mass is a major
    determinant of levothyroxine dosage in the
    treatment of thyroid diseases. JCEM 2005 90-
    124. 9 Roos, A et al. The starting dose of
    levothyroxine in primary hypothyroidism
    treatment a prospective, randomized,
    double-blind trial. Arch Intern Med 2005 165
  • 10 Dong, BJ et al. Bioequivalence of generic and
    brand-name levothyroxine products in the
    treatment of hypothyroidism. JAMA 1997 277
  • 11 Joint statement on the U.S Food and Drug
    Administrations decision regarding
    bioequivalence of levothyroxine sodium. Thyroid
    2004 14486.
  • 12 Grebe, SKG et al. Treatment of hypothyroidism
    with once weekly thyroxine. JCEM 1997 82 870.
  • 13 Walsh, JP et al. Small changes in thyroxine
    dosage do not produce measurable changes in
    hypothyroid symptoms, well-being, or quality of
    life results of a double-blind, randomized
    clinical trial

  • 14 Feldt-Rasmussen, U. Treatment of
    hypothyroidism in elderly patients and in
    patients with cardiac disease. Thyroid 2007 16
  • 15 Gussekloo J. Thyroid Status, disability and
    cognitive function, and survival in old age.
    JAMA 2004 292 2591.
  • 16 Subclinical thyroid disease scientific review
    and guidelines for diagnosis and management.
    National Guidelines Clearinghouse 2004.
  • 17 Jorde, et al. Neuropsychological function and
    symptoms in subjects with subclinical
    hypothyroidism and the effect of thyroxine
    treatment. JCEM 2006 91 145.
  • 18 Portmann L. Obesity and hypothyroidism myth
    or reality? Revue Medicale Suisse 2007 105 859.
  • 19 Kong, WK, et al. A 6-month randomized trial
    of thyroxine treatment in women with mild
    subclinical hypothyroidism. Am J Med. 2002 112
  • 20 Pearce, EN. Hypothyroidism and dyslipidemia
    modern concepts and approaches. Current
    Cardiology Reports 2004 6 451.
  • 21 Radetti G. et al. The natural history of
    euthyroid Hashimotos thyroiditis in children. J
    Pediatr. 2006 149 827.
  • 22 Fatourechi, Vahab. Subclinical
    hypothryoidism how should it be managed?
    Treatments in Endocrinology 2002 1 211.
  • 23 Moore, DC. Natural course of subclinical
    hypothyroidism in childhood and adolescence.
    Arch Pediatr Adolesc Med 1996 150 293.
  • 24 Rose, SR et al. Update of newborn screening
    and therapy for congenital hypothyroidism.
    Pediatrics 2006 1172290.

  • 25 Selva, KA et al. Neurodevelopmental outcomes
    in congenital hypothyroidism comparison of
    initial T4 dose and time to reach target T4 and
    TSH. J Pediatr 2005 147 775.
  • 26 Surks, M. Clinical manifestations of
    hypothyroidism. www.utdol.com.
  • 27 Ross, DS. Diagnosis of and screening for
    hypothyroidism. www.utdol.com.
  • 28 Ross, DS. Treatment of hypothyroidism.
  • 29 Green, GB. Hypothyroidism. Washington
    Manual of Medical Therapeutics. Lippincott
    Williams Wilkins, Philadelphia, 2004 489-492.
  • 30 Ross, DS. Myxedema coma. www.utdol.com
  • 31 LaFranchi, S. Acquired hypothyroidism in
    childhood and adolescence. www.utdol.com
  • 32 LaFranchi, S. Clnical features and detection
    of congenital hypothyroidism. www.utdol.com
  • 33 LaFranchi, S. Treatment and prognosis of
    congenital hypothyroidism. www.utdol.com

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