Thyroid

• Thyroid Glands


  • 2 lobes connected by isthmus
  • Relatively large endocrine gland - 18-60g in adults
  • Location: caudal to larynx, adherent to front of trachea
  • Able to concentrate iodine from blood stream
• Follicle (acinus)


  Sac of stored hormone (colloid)
• Acinar cells


  • Produce iodine-containing thyroid hormones Thyroxine (T4; tetraiodothyronine) / Triiodothyronine (T3)
  • Inactive gland - acinar cells are thin, flattened
  • Overactive/hyperactive gland - acinar cells are tall, columnar
• Parafollicular cells


  • Produce calcitonin
• Production of Thyroid Hormone

  1. Follicular cells trap iodide, active, against steep concentration gradient

  2. Synthesise glycoprotein thyroglobulin (TGB)

  3. Release TGB into colloid

  4. Iodination of tyrosine in colloid

  5. Formation of T3 & T4 by coupling

  6. Uptake & digestion of colloid containing TGB by follicle cells (TGB degraded)

  7. Secretion of thyroid hormone into blood
• Thyroid hormones


  • 80-90% T4, 10-20% T3
  • Only 0.03% T4 & 0.3%T3 free (unbound)
  • Most bound to thyroxine-binding globulin (also transthyretin, albumin)
• Synthesis of Thyroid Hormones

  1. Tyr in TGB is iodinated to form monoiodotyrosine (MIT)

  2. MIT is iodinated to form diiodotyrosine (DIT)

  3. Coupling then occurs: MIT+DIT = T3; DIT+DIT = T4
• Control of Thyroid Hormone Secretion

  1. Thyrotropin-releasing hormone (TRH) from hypothalamus

  2. Thyroid-stimulating hormone (TSH) from anterior pituitary (thyrotroph cells)
• Actions of Thyroid Hormones

  • T3 & T4: ↑ Metabolic rate, ↑ Protein synthesis, ↑ Breakdown of fats, ↑ Use of glucose for ATP production
  • Calcitonin: Responsible for building of bone
• Administration of thyroid hormones increases BASAL METABOLIC RATE (BMR) in adults
• Concentration of circulating thyroid hormones relatively constant - Contrast to most other hormones
• Thyroid hormones are essential for normal growth and development
• In adult, virtually every body tissue requires thyroid hormones - Principal site of action is cell nucleus
• Actions of Thyroid Hormones

  • Calorigenic - increases oxygen consumption of most tissues
  • Effect on nerves - brain maturation during foetal development
  • Synergistic with catecholamines (adr., noradr.) - heart rate
  • Effect on carbohydrates - increase uptake from GI tract
  • Growth & development - need for correct growth
  • Effect on skeletal muscle - need for muscle strength
  • Effect on heart muscle - heart v. sensitive to thyroid hormones
  • Cholesterol lowering - lowers blood cholesterol
• Thyroid Hormone Properties


  • Thyroid secretes mostly T4 (80 μg/d) in adult human (T3, 4 μg/d)
  • T3 probably the true hormone - more active, faster turnover, better T3 receptor binding
  • T4 largely a prohormone - Easily converted to T3 (deiodinase), Up to 80% T4 converted to T3 outside thyroid (liver, kidney, spleen)
• Hypothyroidism


  • ↓ BMR, Slow pulse, Feel cold, want extra clothing, Weight gain, Sluggishness, Coarse skin, Myxoedema
• Causes of Hypothyroidism


  • Simple goitre - Usually due to iodine lack in diet, Naturally occurring goitrogens, eg cassava (not soaked)
  • Acquired hypothyroidism - Autoimmune attack on thyroid e.g. Hashimoto's thyroiditis (antibodies against thyroid cells or TGB)
  • Congenital hypothyroidism - Irreversible brain damage, Cretinism, Severely stunted physical & mental growth, Usually due to genetic defect e.g. incomplete development, or complete absence of thyroid
• Treatment of Hypothyroidism


  1. Levothyroxine sodium (T4) – generally 100μg/day (oral)

  2. Liothyronine sodium (T3) - 20-60 μg/day (oral or inject)

  3. Increase dose slowly until reach equilibrium

  4. Monitor therapy via blood T4 & TSH levels

  5. Caution in patients with heart disease
• Goitre


  • Thyroid is dependent upon constant supply of dietary iodide
  • In iodine deficiency, gland swells in response
  • Gland appears nodular with irregular outline
  • Grossly enlarged
  • Treatable with iodine in diet
  • More common inland and before iodised salt
• Hyperthyroidism


  • Overactivity of thyroid gland ( T3 & T4), ↓ TSH
  • Usually due to Graves' disease (Autoimmune disease, Auto-IgGs stimulate the TSH receptor on follicular cells, 80% of cases)
  • Thyroid toxic adenoma
• Symptoms of Hyperthyroidism


  • ↑ BMR
  • ↑ b-adrenergic overactivity
  • Goitre (thyroid growth due to lack of –ve feedback)
  • Weight loss
  • Anxious, irritable
  • Restless, cannot sleep & easily fatigue
  • Hyperphagia (excess eating)
  • Heat intolerance, increased body temperature
  • Excess sweating, warm soft skin
  • Increase irregular heart rate
  • Tremours in fingers
  • Some get protruding eyes (exophthalmia)
  • Fine hair
  • Rapid growth in children
  • Nails thin & brittle
  • Menstrual irregularities
  • Diarrhoea
• Treatment of Hyperthyroidism


  1. Block coupling (inhibit thyroid peroxidase, e.g. oral carbimazole in UK)

  2. Block conversion of T4 to T3 (propylthiouracil)

  3. Block TGB synthesis

  4. 2 regimes: "titration" (18 months) or "block and replace" (6 months)

  5. Antithyroid drugs (preferred in <40yr age): Synthesis blockers e.g. carbimazole, propylthiouracil (thioureylenes), Iodine uptake blockers e.g. perchlorate

  6. Radioactive iodine (preferred in older patients, 1st line in USA): Single dose of 131I by mouth (up to 90% respond), Destroys thyroid; 6 m for full effect; long-term hypothyroidism, Not for pregnant women

  7. Surgery: For severe hyperthyroidism, or large goitre, Partial thyroidectomy after ultrasound scan and pretreatment with carbimazole, b blockers also used, e.g. propranolol, Monitor via blood T4 & TSH
• Diagnosis of Thyroid Disorders

  1. Plasma T4 & T3 (free & total)

  2. Plasma TSH (low indicates high T4 & T3 )

  3. Also can measure TRH to establish where defect comes from

  4. Disease of thyroid itself (primary) or

  5. Lack of stimulation from pituitary (secondary)
• Functioning Adenoma of Thyroid Gland


  • Note atrophy of the left lobe with protruding tumour
  • Right lobe may hypertrophy to compensate for left lobe function loss
  • Can produce sufficient thyroid hormone to cause thyrotoxicosis - Independent of TSH