Thyroid
Anatomy
Physiology
Examination
Pathologies
Hamburger thyrotoxicosis
Presenting complaints
Pharmacology
Investigations
Embryology
Epidemiology
Evolution
Ethics
Social determinants
THYROID HORMONE
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- Stress
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Hypothalamus
+ Cold, infants
+ TRH
Anterior Pituitary
+ TSH
THYROID GLAND
T3: Triiodothyronine (more active)
T4: Thyroxine)
• Foetal development – enhances CNS & skeletal growth
• Metabolism -  O2 consumption & heat production ( MR) plus  hepatic glucogneogenesis,
glycogenolysis and cholesterol synthesis & degradation
• CV – Positive inotropic & chronotropic effects ( HR and force of contraction   CO)
• Sympathetic – increase sensitivity to Ad (more receptors in heart, muscle, adipose, lymphocytes)
• Pulmonary – Maintain normal hypoxic & hypercapnic drive in the respiratory centre
• Haematopoietic -  EPO due to increased O2 consumption
• GI – Gut motility,  intestinal glucose absorption
• Skeletal -  bone turnover, growth (enhances GH/IGF-1 effects)
• Endocrine – increases metabolic turnover (cortisol, sex hormones – infertility)
WTF so complex?
(Oxford Handbook of Clinical Medicine)
Why are symptoms of thyroid disease so various, and so subtle?
Almost all cell nuclei have high affinity T3 receptors:
– TRα-1 is abundant in muscle and fat
– TRα-2 is abundant in brain
– TR β-1 is abundant in brain, liver, and kidney.
These receptors, influence transcription of various enzymes, affecting:
– The metabolism of substrates, vitamins, and minerals.
– Modulation of all other hormones and their target-tissue responses.
– Stimulation of O2 consumption and generation of metabolic heat.
– Regulation of protein synthesis, and carbohydrate and lipid
metabolism.
– Stimulation of demand for co-enzymes and related vitamins.
Embryology
Congenital defects – cysts and accessory tissue
Hormone
Hormone
Hormone
AP anterior pituitary C thyroid colloid F thyroid
follicle H Herring body PP posterior pituitary S
fibrous septum
Examination - Look
(Adapted from McGee S, Evidence-based physical diagnosis, 2nd edition, St Louis, Saunders, 2007.)
Examination - Look
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Swelling
Swallowing
Scars
Skin
Veins
Examination - Feel
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Back, front, swallow
Size
Shape
Consistency
Tenderness
Mobility
Thrill
Cervical nodes
Examination –
Percuss, Ausculate, Special
• Percuss across manubrium
• Listen for bruit
– Distinguish from carotid bruit and venous hum
• Listen for stridor (compress lateral lobes)
• Pemberton’s sign (thoracic inlet obstruction)
Examination
Other organs / systemic signs
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Eyes
Skin
Hair
Hands
Sweating
Tremor
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Pulse
Heart murmurs
Lungs
Legs
Reflexes
Neuropathy
T3, T4, Transport
• Mostly T4 released from thyroid (20:1)
• T3 has short life. Plasma T4:T3 about 50:1
• Mainly protein bound in plasma
– Mainly thyroxine binding globulin (TBG)
• T4 converted to T3 in target cells (deiodinase
enzymes, eg TPO)
DNA binding
DNA activation/repression
T3 effect in nucleus
• Increases
– Transcription of Na+-K+-ATPase
– Transcription of uncoupling proteins, leading to increased
fatty acid oxidation and heat generation without
production of ATP
– Protein synthesis and degradation, contributing to growth
and differentiation
– Adrenaline-induced glycogenolysis and gluconeogenesis,
affecting insulin-induced glycogen synthesis and glucose
utilisation
– Cholesterol synthesis and LDL receptor regulation
• Net result is increased BMR
Organ specific effects
• Bone - Activation of osteoclast and osteoblast
activities, stimulating bone growth and development
• Heart and vessels - Increases cardiac output and blood
volume; decreases systemic vascular resistance
• Fat - Stimulates proliferation and differentiation;
stimulates lipolysis
• Liver - Regulates triglyceride and cholesterol
metabolism and lipoprotein homeostasis; modulates
cell proliferation and mitochondrial respiration
• Pituitary - Regulates synthesis of pituitary hormones,
stimulates GH production, decreases TSH
• Brain - Stimulates axonal growth and development critical during foetal and neonatal development
Thyroid signs and symptoms
Thyrotoxic
Hypothyroid
General
Fatigue
Heat intolerance
Irritability
Fine tremor
CVS
Tachycardia
AF
Palpitations
GI
Weight loss
 Appetite
Thirst
 Bowel movements
Generalised fatigue
Listlessness
Cold intolerance
Weight gain
Distinctive facies
Bradycardia
Decreased cardiac output
Non-pitting edema
Cool, pale skin (decreased blood flow)
Decreased appetite/anorexia
Constipation
Neuro
Proximal muscle weakness
Hypokalemic periodic paralysis
GU
Scant menses
 Fertility
Dermatology
Fine hair
Skin moist & warm
Vitiligo
Soft nails with onycholysis
Apathy
Mental sluggishness/poor memory
Slow speech
Menstrual abnormalities
Dry skin (decreased sweating)
Thickened skin
Hair loss
Brittle nails and hair
Hyperthyroid
• Hyperthyroidism
– excess production of thyroid hormone
• Thyrotoxicosis
– response to elevated thyroid hormone
• Graves disease
– Activating antibodies to TSH receptors
– Also affects other tissues
• Toxic multinodular goitre
• Exogenous thyroxin
• Adenoma
Thyroid storm
• Acute onset of severe hyperthyroidism
– Usually occurs in patients with underlying Graves
disease, probably due to acute elevation in
catecholamines, e.g. surgery, trauma, infection, stress
– Present with fever, tachycardia (out of proportion to
fever) and extreme restlessness
– Is a medical emergency - patients can die of
arrhythmias
• Requires immediate propranolol with potassium iodide,
antithyroid drugs, corticosteroids and full supportive
treatments
Hypothyroid
• Autoimmune
– Hashimoto thyroiditis
• Congenital
– Inborn errors (often with thyroid peroxidase)
• Iodine deficiency
• Iatrogenic
– Surgery
– Drugs
– Radioablation
Myxoedema coma
Presentation with confusion or coma in severe hypothyroidism
Most commonly occurs in elderly
Patients will often have:
Hypothermia
Severe heart failure
Hypoventilation
Hypoglycaemia
Hyponatraemia
Treatment:
Oxygen
Monitor cardiac output and pressures
Gradual rewarming
Hydrocortisone
Glucose infusion
Investigations
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T3, T4 levels
TSH levels
Thyroid antibodies (Hashimoto’s)
TSH receptor antibodies (Grave’s)
Iodine kinetics
Scintillation imaging (hot vs cold nodules)
Treatment
• Thyroxine (exogenous thyroid hormone)
• Iodine
– correct deficiency,
– or blocks hormone release?
• PTU (anti thyroid peroxidase)
• Carbimazole (anti thyroid hormone)
• β blockers
– ↓ adrenergic tone, ↓ T4→T3 conversion)
• Surgery