Hypothyroidism

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HYPOTHYROIDISM
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INTRODUCTION

• Hypothyroidism is defined as a deficiency in
  thyroid hormone secretion and action
  that produces a variety of clinical signs and
  symptoms of Hypometabolism.
• Overt Hypothyroidism is defined as an elevated
  serum TSH concentration (usually above 10 mIU/L)
  and reduced free Thyroxine concentration (fT4)
• Subclinical Hypothyroidism is defined as serum
  TSH above the upper reference limit
  in combination with a normal free Thyroxine (fT4)

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Prevalence

• According to a projection from various studies on
  Thyroid disease, it has been estimated that about
  42 million people in India suffer from Thyroid
  diseases. The prevalence of Hypothyroidism was
  3.9. The prevalence of subclinical
  Hypothyroidism was 9.4. In women, the
  prevalence was higher, at 11.4, when compared
  with men, in whom the prevalence was 6.2.
  The prevalence of subclinical Hypothyroidism
  increased with age. About 53 of subjects
  with subclinical hypothyroidism were positive for
  anti-TPO antibodies.

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CLINICAL PRESENTATION

• Hypothyroidism can affect all organ systems
  these manifestations are largely independent of
  the underlying disorder but are a function of the
  degree of hormone deficiency.

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CAUSES OF HYPOTHYROIDISM
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HASHIMOTOS THYROIDITIS

• Hashimotos Thyroiditis is an autoimmune disease
  in which the thyroid gland is attacked by
  a variety of cell and antibody-mediated immune
  processes, causing primary Hypothyroidism.
  The resulting inflammation from Hashimotos
  disease, also known as Chronic Lymphocytic
  Thyroiditis, often leads to an underactive
  Thyroid gland (Hypothyroidism).
• The diagnosis of Hashimotos Thyroiditis is
  supported by recognition of autoantibodies
  against TPO or Thyroglobulin. 90 of patients
  with Hashimotos Thyroiditis have anti-TPO
  antibodies and anti-Thyroglobulin antibodies,
  making these antibodies excellent markers for
  Hashimotos Thyroiditis. Anti-TPO antibody
  positivity is more common at the time of
  diagnosis than anti-Thyroglobulin antibody.

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Hypothyroidism in Pregnancy

• Convincing data suggest that pregnant women who
  are positive for Thyroid autoantibodies (especiall
  y anti-TPO antibodies) leads to higher frequency
  of miscarriage (13.8) than is seen in pregnant
  women who lack anti-TPO antibodies (2.4), and
  that T4 treatment of the anti-TPO antibody
  positive group reduces the risk of miscarriage to
  approximately 3.5.
• Over Hypothyroidism (OH) in pregnancy is defined
  as an elevated TSH (gt2.5 mIU/L) in conjunction
  with a decreased FT4 concentration. Women with
  TSH levels of 10.0 mIU/L or above, irrespective
  of their FT4 levels, are also considered to have
  OH.
• Sub-clinical Hypothyroidism (SCH) in pregnancy is
  defined as a serum TSH between 2.5 and 10 mIU/L
  with a normal FT4 concentration.
• Isolated Hypothyroxinemia (IH) is defined as a
  normal maternal TSH concentration in conjunction
  with FT4 concentrations in the lower 5th or 10th
  percentile of the reference range.

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Prevalence

• 10-20 of all pregnant women in the first
  trimester of pregnancy are Thyroid
  Peroxidase (TPO) or Thyroglobulin (Tg) antibody
  positive and Euthyroid
• 16 of the women who are Euthyroid and positive
  for TPO or Tg antibody in the first
  trimester will develop a TSH that exceeds 4.0
  mIU/L by the third trimester, and 33-50 of
  women who are positive for TPO or Tg antibody in
  the first trimester will develop postpartum
  Thyroiditis
• 23 of apparently healthy, non-pregnant women
  of childbearing age have an elevated serum TSH.
  Among these healthy non-pregnant women of
  childbearing age it is estimated that 0.3-0.5
  of them would, after having Thyroid function
  tests, be classified as having OH, while 22.5
  of them would be classified as having SCH

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Specific adverse outcomes associated
with maternal Hypothyroidism include

• An increased risk of premature birth, low
  birth weight, and miscarriage. Such patients
  carry an estimated 60 risk of fetal loss when
  OH was not adequately detected and treated
• Negro and colleagues published data suggesting
  SCH also increases the risk of pregnancy
  complications in anti-thyroid peroxidase antibody
  positive (TPOAb) women
• Negro et al. reported a significantly
  higher miscarriage rate in TPOAb_ women with
  TSH levels between 2.5 and 5.0 mIU/ L
  compared with those with TSH levels below 2.5
  mIU/L

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Recommendations

• Women who are positive for TPOAb and have SCH
  should be treated with LT4
• Women with SCH in pregnancy, who are not
  initially treated, should be monitored for
  progression to OH with a serum TSH and FT4
  approximately every 4 weeks until 16-20 weeks
  gestation and at least once between 26 and 32
  weeks gestation
• Isolated Hypothyroxinemia should not be treated
  in pregnancy

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Recommendations

• Anti-Thyroid Peroxidase Antibody (TPOAb)
  measurements should be considered when evaluating
  patients with subclinical Hypothyroidism.
• If anti-thyroid antibodies are positive,
  Hypothyroidism occurs at a rate of 4.3 per year
  versus 2.6 per year when anti-thyroid antibodies
  are negative.
• Assessment of serum free T4, in addition to TSH,
  should be considered when monitoring L-thyroxine
  therapy.
• Treatment based on individual factors for
  patients with TSH levels between the upper limit
  of a given laboratorys reference range and 10
  mIU/L should be considered particularly if
  patients have symptoms suggestive of
  Hypothyroidism, positive TPOAb or evidence of
  atherosclerotic cardiovascular disease, heart
  failure, or associated risk factors for these
  diseases.

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Recommendations

• Patients whose serum TSH levels exceed 10 mIU/L
  are at increased risk for heart failure and
  cardiovascular mortality, and should be
  considered for treatment with L-thyroxine.
• Euthyroid women (not receiving LT4) who are TPOAb
  require monitoring for Hypothyroidism during
  pregnancy. In addition to the risk of
  Hypothyroidism, it has been described that being
  TAb constitutes a risk factor for miscarriage,
  premature delivery, Perinatal death , post-partum
  dysfunction, and low motor and intellectual
  development (IQ) in the offspring.

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TEST RANGE AVAILABLE
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References

1. Indian Journal of Endocrinology Metabolism.
   2011 Jul 15(Suppl2) S78S81.
2. Williams text book of Endocrinology, Eleventh
   edition
3. Tietz Textbook of Clinical Biochemistry, Fifth
   Edition
4. Clinical Practice Guidelines for Hypothyroidism
   in Adults Cosponsored by the American Association
   of Clinical Endocrinologists and the American
   Thyroid Association

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References

1. Negro R, Schwartz A, Gismondi R, Tinelli A,
   Mangieri T, Stagnaro-Green A 2010
   Universal screening versus case finding for
   detection and treatment of thyroid hormonal
   dysfunction during pregnancy. J Clin Endocrinol
   Metab 9516991707.
2. Negro R, Schwartz A, Gismondi R, Tinelli A,
   Mangieri T, Stagnaro-Green A 2010
   Increased pregnancy loss rate in thyroid antibody
   negative women with TSH levels between 2.5
   and 5.0 in the first trimester of pregnancy. J
   Clin Endocrinol Metab 95E448

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