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ThyroidAnatomyPhysiologyExamination
PathologiesHamburger thyrotoxicosis
Presenting complaintsPharmacologyInvestigations
EmbryologyEpidemiology
EvolutionEthics
Social determinants
THYROID HORMONE
Hypothalamus
Anterior Pituitary
THYROID GLAND
+ TRH
+ TSH
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)
- Stress
+ Cold, infants
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
• Swelling• Swallowing• Scars• Skin• Veins
Examination - Feel
• 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)
ExaminationOther organs / systemic signs
• Pulse• Heart murmurs• Lungs• Legs• Reflexes• Neuropathy
• Eyes• Skin• Hair• Hands• Sweating• Tremor
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 symptomsThyrotoxic Hypothyroid
General FatigueHeat intoleranceIrritabilityFine tremor
Generalised fatigueListlessnessCold intoleranceWeight gainDistinctive facies
CVS TachycardiaAFPalpitations
BradycardiaDecreased cardiac outputNon-pitting edemaCool, pale skin (decreased blood flow)
GI Weight loss AppetiteThirst Bowel movements
Decreased appetite/anorexiaConstipation
Neuro Proximal muscle weaknessHypokalemic periodic paralysis
ApathyMental sluggishness/poor memorySlow speech
GU Scant menses Fertility
Menstrual abnormalities
Dermatology Fine hairSkin moist & warmVitiligoSoft nails with onycholysis
Dry skin (decreased sweating)Thickened skinHair lossBrittle 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 comaPresentation with confusion or coma in severe hypothyroidism
Most commonly occurs in elderly
Patients will often have:HypothermiaSevere heart failureHypoventilationHypoglycaemiaHyponatraemia
Treatment:
OxygenMonitor cardiac output and pressuresGradual rewarmingHydrocortisoneGlucose infusion
Investigations
• 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