Patho revison 2

• Hormones


  Concentration can be low (10^-15 M to 10^-12 M) - femto to picomolar levels
• Hormones


  • Specific receptors 'see' them
  • Most glands secrete 2 or more hormones
• Action of hormones


  • LOCAL
  • SELF
  • DISTANT
• Action of hormones


  • Growth hormone
  • Somatostatin (regulation of insulin/glucagon)
• Action of hormones is not necessarily just ONE way of signalling, e.g. Testosterone – local AND endocrine effects
• Patterns of hormone secretion

  • Constant/chronic (e.g. Thyroxine)
  • Episodic/Acute (e.g. Epinephrine)
  • Cyclic (e.g. Cortisol)
• Factors affecting hormone release

  • Physical damage
  • Metabolic factors
  • Congenital
  • Up/down regulated receptors
  • Second messenger changes
  • Regulatory mechanism changes
• Diagnostic Tests for endocrine dysfunction include Immunoassay, Stimulation and suppression tests, Scans, ultrasound, MRI, and Biopsy
• Immunoassay


  Quick and accurate tests on-site and in the laboratory to detect specific molecules, relying on antibody binding to specific molecular structures
• Where hormones are made

  • T3, T4
  • Calcitonin
  • Parathyroid Hormone
• Amino acid derived hormones

  Fairly constant expression, 3/4x more active when converted as needed
• Thyroid hormone regulation


  1. Hypothalamus ↑s TRH secretion

  2. Pituitary ↑s TSH secretion

  3. TSH stimulates thyroid gland

  4. High T3/T4 levels inhibit TSH and TRH secretions
• Thyroid receptor isoforms


  • TRα1
  • TRα2
  • TRβ1
  • TRβ2
• Thyroid receptors


  • Tissue specific expression, α predominates in brain, β predominates in liver, can reflect development and vary 10 fold with age, ubiquitous and reflects many thyroid hormone effects
• Effects of thyroid hormones

  • Wakefulness
  • Memory
  • Alertness
  • Reflexes
  • Maintenance of emotional tone
  • Cardiac Output (heart rate/stroke volume, vascular resistance, systolic pressure)
  • Foetal neural development
  • Bone growth
  • Tooth development
  • Permissive role in male & female reproduction
  • Metabolic (BMR, O2 consumption, thermogenesis, protein turnover)
• Causes of hypothyroidism


  • Iodine deficiency
  • Autoimmune Hashimoto's thyroiditis
  • Damage to pituitary gland
  • Overtreatment for hyperthyroidism
  • Surgery on thyroid gland
  • Defect during development
• Hypothyroidism


  1. 2% of all adults, more common in women
• Hypothyroidism treatment


  Thyroxine replacement, e.g. levothyroxine
• Hypothyroidism lab values


  • TSH - High
  • Free T4 - Low
  • Free T3 - Low
• Hypothyroidism complications


  • Myxedema (swelling of body)
  • Myxedema coma (weakness, lethargy, confusion, non-responsiveness, feeling cold, low body temperature, difficulty breathing)
• Endemic goiter


  Caused by low soil/food iodine
• Goitrogens


  Naturally occurring substances that can interfere with thyroid gland function
• Why goiter develops


  Iodine deficit → ↓ T3/T4 synthesis → Hypothyroidism → Low blood T3/T4 → Hypothalamus ↑s TRH → Pituitary ↑s TSH → TSH stimulates thyroid gland → ↑ TSH → Enlarged gland = Goiter
• Hyperthyroidism


  More common in women, affects 5% of all women
• Causes of hyperthyroidism


  • Autoimmune Graves disease
  • Thyroiditis/inflammation of thyroid gland
  • Tumour/cancer
• Hyperthyroidism lab values


  • TSH - Low
  • Free T4 - High
  • Free T3 - High
  • Positive autoantibodies (Graves)
• Hyperthyroidism complications


  • Pretibial myxedema (Graves only)
  • Exophthalmos (Graves only)
  • Thyrotoxicosis (tachycardia, heart failure, delirium)
• Hyperthyroidism treatments


  • Surgery (partial/total gland removal/destruction)
  • Radioactive iodine (block hormone release)
  • Medication: thioureylenes (e.g. Carbimazole, ↓ T4 and T3 synthesis)
  • Medication: β blockers (inhibit effects of hyperactive thyroid)
• In Graves disease, T4 and T3 are produced even when TSH is low
• Effects of low vs high thyroid hormone levels

  • Basal metabolic rate (↓ vs ↑)
  • Carbohydrate metabolism (Gluconeogenesis ↓, Glycogenolysis ↓ vs ↑, ↑)
  • Serum glucose (↓ vs ↑)
  • Protein metabolism (Synthesis ↓, Proteolysis ↓ vs ↑, ↑)
  • Muscle wasting (↑)
  • Lipid metabolism (Lipogenesis ↓, Lipolysis ↓ vs ↑, ↑, ↓)
  • Serum cholesterol (↓ vs ↑)
  • Thermogenesis (↓ vs ↑)
  • Autonomic nervous system (Normal serum [catecholamines] vs ↑ β-ADR expression (↑ sensitivity to same [catecholamines]))
• Normal reference ranges


  • TSH: 0.5-4.7 mIU/L
  • T3: 1.1-2.0 nmol/L
  • T4: 180 nmol/L
• Adrenal hormones


  • Mineralcorticoids (e.g. Aldosterone)
  • Glucocorticoids (e.g. cortisol)
  • Sex steroids (e.g. testosterone)
• Adrenal receptors


  Found in almost all cells
• Cortisol levels at different times

  • 8am: 13-24 nmol/L
  • 4pm: 5-8 nmol/L
  • 1h into sleep: 1-3 nmol/L
• ACTH levels at different times

  • 8am: 10-60 pg/mL
  • 4pm: <10 pg/mL
  • 1h into sleep: <5 pg/mL
• Causes of Cushing's syndrome

  • Pituitary adenoma
  • Iatrogenic (large amounts of GCs)
  • Adrenal adenoma
  • Ectopic carcinoma
• Addison's disease


  Autoimmune, tumours, or infection causes low cortisol and high ACTH
• Effects of high cortisol

  • Catabolic (osteoporosis, ↓ protein synthesis, delayed healing)
  • Metabolic (↑ gluconeogenesis, IR, glucose intolerance, Na/water retention, hypertension, edema, hyperkalemia)
  • Immune (↓ to increase infection risk)
  • Erythrocyte (↑)
  • Psychiatric (emotional lability & euphoria)
• Effects of low cortisol

  • Metabolic (↓ blood glucose, weight loss, fatigue)
  • Electrolyte (low Na, reduced blood volume, hypotension, high K+ - arrhythmia)
  • Immune (↓ to increase infection risk)
  • Androgens (↓ hair loss)
  • ACTH (↑ due to low cortisol, hyperpigmentation)
• Hormones affecting glucose control

  • Glucagon (increase plasma glucose)
  • Insulin (decrease plasma glucose)
  • Growth hormone
  • Cortisol
  • Epinephrine (adrenaline)