Thyroid Gland

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Thyroid Gland
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• Anatomy
• The thyroid gland consists of two lateral lobes
  connected by an isthmus.
• It is closely attached to the thyroid cartilage
  and to the upper end of the trachea, and thus
  moves on swallowing.
• It is often palpable in normal women.
• Embryologically
• It originates from the base of the tongue and
  descends to the middle of the neck.
• Remnants of thyroid tissue can sometimes be found
  at the base of the tongue (lingual thyroid) and
  along the line of descent.
• The gland has a rich blood supply from superior
  and inferior thyroid arteries.

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• Histollogyically
• The thyroid consists of follicles lined by
  cuboidal epithelioid cells. Inside is the
  colloid, which is an iodinated glycoprotein(
  thyroglobulin) synthesized by the follicular
  cells. Each follicle is surrounded by basement
  membrane, between which are parafollicular cells
  containing calcitonin-secreting C cells.
• Biochemistry
• The thyroid hormones, T4 and T3, are synthesized
  within the gland.
• More T4 than T3 is produced, but T4 is converted
  in some peripheral tissues (liver, kidney and
  muscle) to the more active T3 by
  5'-monodeiodination an alternative
  3'-monodeiodination yields the inactive reverse
  T3 (rT3).

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• In plasma, more than 99 of all T4 and T3 is
  bound to hormone-binding proteins
  (thyroxine-binding globulinTBG thyroid-binding
  prealbuminTBPA and albumin).
• Only free hormone is available for tissue
  action, where T3 binds to specific nuclear
  receptors within the cell.
• Physiology of the hypothalamic-pituitary-thyroid
  axis
• 1. TRH is released in the hypothalamus and
  stimulates release of TSH from the pituitary.
• 2. TSH stimulates the TSH receptor in the thyroid
  to increase synthesis of both T4 and T3 and also
  to release stored hormone, producing increased
  plasma levels of T4 and T3.
• 3. T3 feeds back on the pituitary and perhaps
  hypothalamus to reduce TRH and TSH secretion

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HYPOTHYROIDISM
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• Pathophysiology
• Under activity of the thyroid is usually
  primary, from disease of the thyroid, but may be
  secondary to hypothalamic-pituitary disease
  (reduced TSH drive) . It is one of the most
  common endocrine conditions lifetime prevalence
  for an individual is higher - perhaps as high as
  9 for women and 1 for men with mean age at
  diagnosis around 60 years.

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Causes of hypothyroidism

• PRIMARY
• Congenital
• -Agenesis
• -Ectopic thyroid remnants
• Defects of hormone synthesis
• -Iodine deficiency
• -Dyshormonogenesis
• -Antithyroid drugs
• -Other drugs (e.g. lithium, amiodarone,
  interferon)
• Autoimmune
• -Atrophic thyroiditis
• -Hashimoto's thyroiditis
• -Postpartum thyroiditis
• Infective
• -Post-subacute thyroiditis

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• POST-SURGERY
• Post-irradiation
• -Radioactive iodine therapy
• -External neck irradiation
• Infiltration
• -Tumour
• SECONDARY
• -Hypopituitarism
• -Isolated TSH deficiency
• Peripheral resistance to thyroid hormone

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Atrophic (autoimmune) hypothyroidism

• This is the most common cause of hypothyroidism
  and is associated with antithyroid
  autoantibodies leading to lymphoid infiltration
  of the gland and eventual atrophy and fibrosis.
• Female to male ratio is 61 and the incidence
  increases with age.
• The condition is associated with other autoimmune
  disease such as pernicious anaemia, vitiligo and
  other endocrine deficiencies .
• In some instances intermittent hypothyroidism
  occurs with recovery antibodies which block the
  TSH receptor may sometimes be involved in the
  aetiology.

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Hashimoto's thyroiditis

• This form of autoimmune thyroiditis, again more
  common in women and most common in late middle
  age, produces atrophic changes with regeneration,
  leading to goitre formation.
• The gland is usually firm and rubbery but may
  range from soft to hard.
• Thyroid peroxidase (TPO) enzyme antibodies are
  present, often in very high titres (gt 1000 IU/L).
  
• Patients may be hypothyroid or euthyroid, though
  they may go through an initial toxic phase,
  'Hashi-toxicity'.
• Thyroxin therapy may shrink the goitre even when
  the patient is not hypothyroid.

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Postpartum thyroiditis

• This is usually a transient phenomenon observed
  following pregnancy and may involve
  hyperthyroidism, hypothyroidism or the two
  sequentially.
• It is believed to result from the modifications
  to the immune system necessary in pregnancy, and
  histologically is a lymphocytic thyroiditis.
• The process is normally self-limiting, but when
  conventional antibodies are found there is a high
  chance of this proceeding to permanent
  hypothyroidism.

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Iodine deficiency

• In mountainous areas (the Alps, Himalayas, South
  America, Central Africa) dietary iodine
  deficiency still exists, in some areas as
  'endemic goitre
• The patients may be euthyroid or hypothyroid
  depending on the severity of iodine deficiency.
• The mechanism is thought to be borderline
  hypothyroidism leading to TSH stimulation and
  thyroid enlargement in the face of continuing
  iodine deficiency.

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Dyshormonogenesis

• This rare condition is due to genetic defects in
  the synthesis of thyroid hormones patients
  develop hypothyroidism with a goitre.
• One particular familial form is associated with
  sensorineural deafness (Pendred's syndrome).

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Hypothyroidism large nose and facial folds. Note
a noncommunicative affect
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Hypothyroidism malar flush
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• Clinical features
• Hypothyroidism may produce many symptoms. The
  alternative term 'myxoedema' refers to the
  accumulation of mucopolysaccharide in
  subcutaneous tissues ? Effusion, hoarse voice,
  puffed-up face .
• Vitamin A? ? ? Sebaceous and sweat gland activity
  ?
• Dry, scaly skin
• ? Heat metabolism ? Energy metabolism ??
  Sensitivity to cold, ? Appetite and ?
  Erythropoiesis
• Impaired cerebral development ? ? Neuromuscular
  excitability ? Sensory disturbances in the form
  of Hyporeflexia, Depression and Clouded
  consciousness.
• ? Cardiac contractility Bradycardia.
• Reduced lipolysis ?Overweight.
• ? Intestinal motility ?Constipation and Reflux
  esophagitis.

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• Milder symptoms are, however, more common and
  hard to distinguish from other causes of
  non-specific tiredness. Many cases are detected
  on biochemical screening.
• Investigation of primary hypothyroidism
• Serum TSH is the investigation of choice a high
  TSH level confirms primary hypothyroidism.
• A low free T4 level confirms the hypothyroid
  state .
• Thyroid and other organ-specific antibodies are
  present.
• Other abnormalities include the following
• 1 - Anaemia, which is usually normochromic and
  normocytic in type but may be macrocytic
  (sometimes this is due to associated pernicious
  anaemia) or microcytic (in women, due to
  menorrhagia).

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• 2-increased serum aspartate transferase
  (AST)levels, from muscle and/or liver .
• 3-increased serum creatine kinase(CK) levels,
  with associated myopathy .
• 4-hypercholesterolaemia .
• 5-hyponatraemia due to an increase in ADH and
  impaired free water clearance.

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Treatment

• Replacement therapy with levothyroxin (thyroxin,
  i.e. T4) is given for life.
• The starting dose will depend upon the severity
  of the deficiency and on the age and fitness of
  the patient, especially cardiac performance.
• In the young and fit, 100 µg daily is suitable,
  while 50 µg daily (increased to 100 µg after 2-4
  weeks) is more appropriate for the young or old
  patients.
• Patients with ischaemic heart disease require
  even lower initial doses, especially if the
  hypothyroidism is severe and long-standing.
• Most physicians would then begin with 25 µg
  daily and perform serial ECGs, increasing the
  dose at 3- to 4-week intervals if angina does not
  occur or worsen and the ECG does not deteriorate.

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• Adequacy of replacement should be assessed
  clinically and by thyroid function tests after at
  least 6 weeks on a steady dose the aim is to
  restore T4 and TSH to the normal range.
• If serum TSH remains high, the dose of T4 should
  be increased in increments of 25-50 µg and the
  tests repeated 6 weeks later.
• This stepwise progression should be continued
  until TSH becomes normal .
• Clinical improvement on T4 may not begin for 2
  weeks or more and full resolution of symptoms may
  take 6 months.
• The importance of life long therapy must be
  emphasized

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• Borderline hypothyroidism or 'compensated
  euthyroidism
• Patients are frequently seen with low-normal
  serum T4 levels and slightly raised TSH levels.
• Sometimes this follows surgery or radioactive
  iodine therapy
• Treatment
• thyroxine is normally recommended where the TSH
  is consistently above 10 mU/L, or when possible
  symptoms, high-titre thyroid antibodies or lipid
  abnormalities are present.
• Where the TSH is only marginally raised, the
  tests should be repeated 3-6 months later.
  Conversion to overt hypothyroidism is more common
  in men or when TPO antibodies are present.
• In practice, vague symptoms in patients with
  marginally elevated TSH (below 10 mU/L) rarely
  respond to treatment, but a 'therapeutic trial'
  of replacement may be needed to confirm that
  symptoms are unrelated to the thyroid.

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• Myxoedema coma
• Severe hypothyroidism, especially in the elderly,
  may present with confusion or even coma.
• Myxoedema coma is very rare it is presented by
  hypothermia ,severe cardiac failure,
  hypoventilation, hypoglycaemia and hyponatraemia.
  
• The mortality was previously at least 50 and
  patients require full intensive care.
• Treatment is controversial
• most physicians would advise T3 orally or
  intravenously in doses of 2.5-5 µg every 8 hours,
  then increasing as above.
• Large intravenous doses should not be used.

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• Additional measures, though unproven, should
  include
• oxygen (by mechanical ventilation if necessary)
• monitoring of cardiac output and pressures
• gradual rewarming
• hydrocortisone 100 mg i.v. 8-hourly
• glucose infusion to prevent hypoglycaemia.
• 'Myxoedema madness
• Depression is common in hypothyroidism but
  rarely with severe hypothyroidism in the elderly
  the patient may become frankly demented or
  psychotic, sometimes with striking delusions.

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Screening for hypothyroidism

• The incidence of congenital hypothyroidism is
  approximately 1 in 3500 births.
• Untreated, severe hypothyroidism produces
  permanent neurological and intellectual damage
  ('cretinism').
• Routine screening of the newborn using a
  blood-spot, to detect a high TSH level as an
  indicator of primary hypothyroidism is efficient
  and cost-effective.
• cretinism is prevented if T4 is started within
  the first few months of life.

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• Screening of elderly patients for thyroid
  dysfunction has a low pick-up rate, is
  controversial and not currently recommended.
• However, patients who have undergone thyroid
  surgery or received radioiodine should have
  regular thyroid function tests, as should those
  receiving lithium or amiodarone therapy.