17. thyroid gland
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17. thyroid gland 17. thyroid gland Presentation Transcript

  • Thyroid gland The name "thyroid" comes from the Greek word which means "shield"
    • Thyroid gland , the largest single endocrine gland (20-25 g), is
    • located just below the level of the larynx
    • It has two lobes joined by a central isthmus at tracheal rings 2, 3, 4
    • Blood flow is ~ 5mL/min from superior and inferior thyroid arteries
    • Composed of numerous spherical follicles with outer layer of cuboidal
    • epithelium and filled with proteinous colloid ( proteinaceous depot of thyroid
    • hormone precursor )
    • A few C cells ( parafollicular cells ) are seen in the walls of the
    • follicles that produce calcitonin , a hypocalcemic hormone
    Ca ++
    • About 80 μg/day of iodine is utilized for thyroid hormone synthesis
    • Activity of the gland is regulated by TRH-TSH axis
    • TRH ( a tripeptide ) thyrotrops
    • TSH T 4 , T 3
    • T 4 , T 3 TSH receptors on thyroid gland
    • T 4 , T 3
    • TSH stimulates all steps of thyroid hormones synthesis
    • TSH binds with membrane receptors adenylate cyclase
    • c-AMP protein kinases effects
    • T 4 , T 3 TSH secretion
    • Circulating T 4 & T 3 act directly on the anterior pituitary (negative
    • feedback loop)
    • Hypothalamus receives input and sends a
    • signal to the Anterior Pituitary via TRH
    • Thyrotrophin Releasing Hormone .
    • TRH stimulates the Anterior Pituitary to
    • release TSH .
    • Thyrotrophin which travels in the blood to
    • the Thyroid Gland.
    • Thyrotrophin increases I- uptake and
    • stimulates production of M.I.T., D.I.T. And
    • hence production of T 3 and T 4 .
    • Somatostatin released by the Hypothalamus
    • inhibits TRH release .
    • Protirelin is a synthetic compound that mimics TRH.
  • Thyrotrophin There is negative feedback between Thyrotrophin and T 4 secreted by the Thyroid gland. Thyrotrophin stimulates follicle cell receptors, which leads to:
    • increased uptake of I- (main mechanism of action)
    • stimulates cAMP production inside the follicle cells
    • increases synthesis of thyroglobulin
    • leads to generation of H 2 O 2 for the iodination of iodine
    Plasma Iodide Concentration
    • This has a pronounced effect on Thyroid function.
    • Daily intake of Iodide (70mg) is required to maintain T 4 production.
    • Decreased Iodide in the diet causes decreased hormone production and stimulates
    • TSH release.
    • Very slow response (weeks) to changed Iodide levels in the blood.
    • C an take a long time for imbalances to manifest in symptoms .
  • Hormone synthesis
    • Iodine trapping and organification:
    • extracellular iodide is trapped into follicular cells oxidesed (peroxidase in
    • presence of H 2 O 2 ) iodine + tyrosine molecule in thyroglobulin
    • MIT & DIT
    • Coupling (peroxidase enzyme):
    • MIT + DIT T 3 ( triiodothyronine )
    • 2 DIT T 4 ( thyroxine )
    • T 3 & T 4 remain stored in the colloid
    • Release:
    • T4, T3, MIT, DIT on thyroglobulin endocytosis lysosomes
    • (stimulated by TSH) proteolysis of the thyroglobulin molecule T 4 , T 3
    • secreted
    • - MIT & DIT are deiodinized iodine is reused for thyroid hormone synthesis
  • Steps of thyroid hormone synthesis Iodine trapping (using iodide pump); thyroglobulin synthesis; oxidation of iodide to iodine; iodination of tyrosine molecules within the thyroglobulin molecule to give MIT and DIT at the apical border of the cell; coupling of MIT and DIT to give T3 and T4 still within the thyroglobulin molecule in the colloid; pinocytosis of thyroglobulin and proteolysis of thyroglobulin and release of T3 and T4
  • Transport of Thyroid Hormones Once T 3 and T 4 are released into the blood they are bound to a serum protein, thyroxine-binding globulin (TBG) , albumin and prealbumin Only free (unbound) hormone is metabolically active Total hormone level increases when TBG increases (in pregnancy or with oral contraceptive treatment) Concentrations of T 3 and T 4 are quite different in blood and inside cells: T 3
    • Small pool in the body
    • Mostly found inside tissue cells
    • Fast turnover rate in the body
    T 4
    • Large pool in the body
    • Mostly found in the blood
    • Slow turnover rate in the body
    • T 4 is often regarded as a prohormone as it is converted to T 3 once inside cells.
  • Effects of thyroid hormones
    • T 3 /T 4 enter the target cell cytoplasm T 3 binds to nuclear receptors
    • messenger RNA protein synthesis effects on cellular function
    • Calorigenic effects:
    • oxygen consumption (exception – brain, testes, pituitary) & heat production
    • basal metabolic rate (BMR)
    • Metabolic effects:
    • cellular & gastrointestinal absorption of glucose, glycolisis & gluconeogenesis
    • catabolism of free fatty acids + depletion of fat stores & blood lipids (cholesterol)
    • protein synthesis & breakdown
    • conversion of ß-carotene to vitamin A
    • CNS:
    • CNS activity and alertness
    • CVS:
    • enhanced effects of catecholamines cardiac output & heart rate systolic blood
    • pressure, peripheral resistance, diastolic blood pressure mean pressure is little
    • affected
    • - ß-adrenergic receptors number & affinity
    • Genitourinary:
    • deficiency / excess menstrual disturbances
    • Growth:
    • essential for growth and development
    • congenital deficiency thyroid dwarf/ cretinism
    • skeletal growth in childhood
    • promotion of normal brain development in early postnatal period, deficiency mental
    • retardation in cretins
    • Alimentary tract:
    • excess diarrhea
    • deficiency constipation
    • Muscle:
    • excess muscle weakness (thyrotoxic myopathy)
    • Mammary gland:
    • milk production
    • Bone marrow:
    • - deficiency anemia
  • Effects of Thyroid Hormone on Basal Metabolic rate T 3 GI activity Fat and carbohydrate mobilization Heart rate BMR Metabolic waste products Oxygen consumption Metabolic fuels Cardiac output Respiration Active hyperemia
  • Abnormalities of Thyroid Function
    • Essentially there are 2 main cases:
    • Hyperthyroidism ( elevation of Thyroid
    • Hormones )
    • 2. Hypothyroidism ( suppression of Thyroid
    • Hormones )
    • The reasons may be varied and the symptoms
    • can include any organ system .
  • Hyperthyroidism (Thyrotoxicosis)
    • Excess activity of the Thyroid Gland leads to elevations of T 3 and T 4 .
    • The effects are often metabolic, but they can affect growth and
    • development if elevated in children.
    • Increased BMR and hence O 2 c onsumption
    • Hot flushes, or difficulty thermoregulating, sweating, heat sensitive
    • Agitated, tremor, weight loss, increased appetite
    • Fatigue, tachycardia, hypertension etc.
    • There are 2 common conditions associated with elevations in
    • Thyroid hormones:
    • 1. Diffuse Toxic Goitre (or Grave's Disease)
    • 2. Toxic Nodular Goitre
    • Diffuse Toxic Goitre (or Grave's Disease)
    • Organ specific autoimmune disease
    • Thyroid-stimulating immunoglobulins (IgG) targeting the
    • receptor
    • May also involve mutations in the TRH receptor
    • Often see protruding eyes (exophthalmos)
    • Often patients are sensitive to catecholamines
    • Classic increases in metabolic processes
    • Toxic Nodular Goitre
    • Usually associated with benign neoplasm, adenoma of thyroid
    • May occur in patients with chronic simple goitre
    • There is no exophthalmos seen in this condition
    • There are at least 2 conditions commonly associated with reduced
    • thyroid hormone production:
    • 1. Simple Goitre (or Non-Toxic Goitre)
    • 2. Myxoedema
    • 3. Hashimoto's Thyroiditis Simple Goitre (or Non-Toxic Goitre)
    • Simple Goitre (or Non-Toxic Goitre)
    • Most often associated with reduced dietary iodine intake
    • This stimulates Thyrotrophic Hormone release and the
    • thyroid gland follicles make more thyroglobulin and the gland
    • hypertrophies.
    • May manifest as Cretinism if iodine deficiency occurs in children.
    • Myxoedema
    • Immunological in origin
    • Symptoms include :
    • - Low metabolic rate
    • - Slow speech
    • - Deep hoarse voice
    • - Lethargy
    • - Bradycardia
    • - Sensitivity to cold
    • - Mental impairment
    • - Thickening of the skin
    Hashimoto's Thyroiditis Simple Goitre (or Non-Toxic Goitre)
    • This is a chronic autoimmune disease where thyroglobulin is attacked or another
    • part of thyroid tissue
    • Often leads to hypothyroidism and myxoedema Simple Non-Toxic Goitre
    • Most often associated with reduced iodine
    • Leads to accumulation of thyroglobulin in the gland an it hypertrophies
  • The Parathyroid Gland and Calcium Homeostasis
    • In humans, Calcium balance is maintained by three major hormones
    • parathyroid hormone
    • calcitonin
    • calcitriol
    • These hormones regulate Calcium levels by controlling the rate of
    • absorption and excretion of Calcium from the body.
    • Calcium enters the body by absorption of dietary Calcium from the
    • gut and is lost mainly through urinary excretion.
  • Physiological functions of Calcium in the body include:
    • Maintenance of membrane permeability
    • Maintenance of excitability of nerve & muscle
    • Release of neurotransmitters, many hormones & exocrine secretions
    • Muscle contraction
    • Formation of bone and teeth
    • Coagulation of blood
    • Activity of many enzymes
  • The total body calcium in adult male amounts to ~ 1200 g (30,000 mmol)
    • ~ 99% of body calcium & 80% of phosphorus is found in bone
    • Only 1% is found in soft tissues & body fluids
    • The exchangeable calcium pool in bone amounts to ~4000 mg (100 mmol)
    • The plasma calcium level ranges between 9.00 and 10.5 mg/dL
    • (2.1 and 2.6 mmol/L)
    • ~50% is mainly bound to plasma albumin
    • The rest (1.0 – 1.3 mmol/L) is found in ionized form
    • This range is kept almost constant by a delicate regulatory mechanism,
    • involving parathyroid hormone (PTH), calcitonin and calcitriol
    • For Calcium balance to maintained, an intake of 12.5-20 mmol/day
    • is recommended for infants/adults
    • Higher daily intake (25 – 37.5 mmol) is recommended for adolescents and for
    • women during pregnancy, lactation and after menopause
    • Intestinal absorption of calcium occurs mainly in the duodenum
    • Both intestinal absorption and urinary excretion of calcium are under
    • hormonal control.
  • Parathyroid hormone
    • Parathyroid hormone (PTH) is a polypeptide, secreted by chief cells
    • of four parathyroid glands located posterior to the lobes of the
    • thyroid gland
    • PTH is responsible for the tight control of free Calcium in ECF –
    • is essential for life
    • plasma Calcium levels PTH secretion
    • plasma Calcium levels PTH secretion ( negative feedback )
    • levels of calcitriol PTH secretion ( negative feedback )
  • Actions of parathyroid hormone (PTH)
    • PTH plasma Calcium
    • PTH plasma Phosphate
    • In the bone PTH activates osteoclasts mobilezes Ca&PO4
    • In the kidney PTH
    • - PO 4 excretion
    • - tubular reabsorption of Calcium
    • - converts 25-hydroxycholecalciferol active 1,25-dehydroxycholecalciferol
    • (calcitriol) promotes intestinal calcium absorption, also mobilizes Calcium
    • from the bone
  • Calcitonin
    • Calcitonin , a poly-
    • peptide hormone,
    • is secreted by the
    • “ C cells” of thyroid
    • gland
    • Calcitonin secretion
    • is stimulated by:
    • - hypercalcemia
    • ( plasma Calcium-
    • major)
    • - gastrin
    • - cholecysokinin (CCK)
    • - glucagon
    Actions of calcitonin
    • Produces rapid in plasma Calcium by:
    • suppressing bone osteoclasts mobilization of bone Calcium
    • the activity of osteoblasts meneralization of bone ECF Calcium
    • in the long term, number of osteoclasts in bones
    • has inhibitory effects on the transport of Calcium from the intracellular fluid to the
    • extracellular fluid
  • Vitamin D
    • Vitamin D is a fat soluble vitamin which comes from the diet (main
    • source) and the skin (vitamin D 3 /cholecalciferol)
    • UV radiation from sunlight 7-dehydrocholesterol
    • vitamin D 3 (in skin ) 25-hydroxycholecalciferol (25-(OH)-D )
    • in the liver 1,25-hydroxychlecalciferol (calcitriol) in the kidney
    • Formation of calcitriol is stimulated by:
    • - PTH
    • - plasma Calcium
    • - plasma PO 4
  • Vitamin D metabolism Actions of calcitriol
    • the rate of calcium uptake
    • from the gut
    • Stimulate PO 4 reabsorption
    • from the gut
    • Stimulates Calcium and PO 4
    • reabsorption from the kidney
    • High doses osteoclastic
    • bone resorption
  • Clinical Primary hyperparathyroidism ( PTH)
    • Results from failure of the negative feedback of plasma Calcium on
    • parathyroid secretion
    • Often caused by PTH-secreting tumor
    • Plasma Calcium is elevated ( hypercalcemia )
    • PO 4 is reduced
    • Bone erosions & cyst formation
    • Renal calcium formation
    Hypoparathyroidism ( PTH)
    • May be caused by:
    • - parathyroid autoantibodies or
    • - accidental damage during thyroid surgery
    • Hypocalcemia
    • Elevated plasma PO 4 levels
    • Neuromuscular excitability muscle tetany, laryngeal spasm &
    • convulsions
  • Vitamin D deficiency
    • May be due to:
    • - inadequate intake
    • - lipid malabsorption (vitamin D is a fat-soluble vitamin)
    • - patients with chronic renal failure
    • Demineralization of bone osteomalacia with bone pain in adults
    • Skeletal deformations (rickets) in children
  • Calcium pool
  •