Download Graves Disease

CTLA4
Risk Factors
Trigger
Blurred
Vision
Pulling on
Optic Nerve
Diplopia
Mechanical
Thyroid Storm
Retro-Orbital Volume
1I
2I
- Clubbing
- Periosteal Bone Formation
- Finger Swelling
Retrosternal Goitre
-?%
- Jugular Vein Engorgement
- Dullness to Percussion
SVC
Pemberton’s Sign
- Facial Plethora
- Stridor
- Cyanosis
Pyramidal
Lobe
DIT
Proteases in
Lysosome Break
down TG
Follicular
Lumen
- TPO
- TG
- Iodine
- DIT
- MIT
Goitre
Thyroid
Follicle
MIT
T4
-
T3
- <0.5%
- Bioactive
Posterior
T3 (10%), rT3 (<1%),
T4 (90%) Released
into Circulation
99.5% of TH Bound
to TBG or Albumin
T3
T4
Iodine Uptakes
Into Follicular Cells
of Thyroid
- Preferentially taken up by Thyroid
Follicular Cells
- Deficiency
- May lead to Hypothyroidism &/or Goitre
- Maternal Deficiency leads to Cretinism in Child
- Limits T3/T4 Synthesis
- If in Excess Thyroid limits uptake
Hyperthyroid
(Thyrotoxicosisism)
Ant. Pituitary
- Produced in Ant. Pituitary by Thyrotroph Cells
- Stimulation via TRH from Hypothalamus
- Inhibition via TH (T3/T4), Somatostatin, DA, Cortisol, GH
- Small noctural increase in release
- Stimulates synthesis & release of TH
- Stimulates hypertrophy & hyperplasia of Thyroid
10 - Graves 85%
- Multinodular Goitre
- Thyroid Adenoma
- Iodine Induced
0
2 - TSH Pituitary Adenoma
Apathetic Hyperthyroidism
- Elderly Patients w co-morbidities
- Less signs & symptoms
Hypothalamus
TRH
TSH
TSH
- Bio inactive, Cannot Enter Cells
- Acts as Circulating Pool
Iodine
Iodine in Diet
- Kelp, Iodised Salt
Osteoporosis
Thyroid
Myopathy
- Proximal Muscle
Weakness
Intracellular
Iodine
- T3 (x4) > T4 > T3 (Inactive)
- Effects function of most systems
- Constant levels required
- Calorigenic
- Fuels for ATP over Storage
- Effects Growth & Development
- B12 & Viatmin A Absoprtion
- Sympathomimetic
Negative Feedback
to Anterior Pituitary
Deiodinases
Iodine & TG
Exocytosis into
Colloid
Perosity of Cortical Bone
Volume of Trabecular Bone
Free T3, T4
Passive
DIT, MIT
Parathyroid
Gland
Anterior
Cardiac
Contracatility
Thyroid Gland
- Endocrine Organ
- Located over Cricoid
Cartilage (C5 - C7)
Lateral
Lobe
T4 Converted to
T3 (33%) & rT3 (45%)
- Tachycardia
- Palpitations
Bone Resorption
Colloid
DIT, MIT
Liver
Kidney
Pituitary
Membrane Bound
T3/T4 Receptor
TG
Follicular
Cells
Isthmus
- Enters ICF First
- Then Nucleus Via
Nuclear Receptor
Bioactivity
Colloid Droplets
fuse with Lysosome
Parafollicular Cells
- Calcitonin
(Thyroid
Enlargement)
- Stridor
- Dysphagia
- SVC Obstruction
T3/T4 Receptor
Complex
Gastrointestinal Tract
- Hypermobility
- Diarrhoea
- Malabsorption
- Polyphagia
CO
SV
- Iodine Trap
- Energy Pump
Local Mass Effect
- Binding to Genes
- Steroid Hormone Like
- Slow Onset of Effect
Iodine Uptake
- Hyperplasia
- Hypertrophy
Obstruction
Gene Transcription
TG Synthesis
- Tyrosine Residues
- Stored in Colloid
- Inhibits or Stimulates
- Stimulates Epithelial
Growth
Vascularisation
BMR
Weight Loss
Cardiomegaly
TG Uptaken by Endocytosis
into Follicular Cells from Colloid
(Colloid Droplets)
Prevents TSH
Binding to TSHR
- Lipid
- Glycogen
- Protein
- Arythmias
- Thyrotoxic Dilated
Cardiomyopathy
- CHF
- AF
Systolic
BP
TPO Activity
TGI
Thyroid Scan
- Diffuse Uptake
>x?
Large Pulse Pressure
- Bounding Pulse
Calorigenesis
Diastolic BP
TBII
Thyroid
Bruit
- Obligatory (RMR)
- Adaptive (esp Cold)
- DIT + DIT
G Protein
2nd Messenger
Follicular Epithelial
Growth
Thermogenesis
T4
Binds & Stimulates
TSH Receptor (TSHR)
on Thyroid
TSI
Acropachy
TPO
DIT
Autoantibodies
to TSH Receptor
Peripheral
Vascular
Resistance
- MIT + DIT
TPO
- Alternative route for H+ re-entry
into Mitochondrial membrane
- Heat produced rather than ATP
β Adrenergic
Receptors
T3
MIT
Uncoupling Protein (UCP)
ATP
Oxygen
Demand
Peripheral
Vasodilation
Tyrosine
+
Iodine
- Inflamatory Exudate
- Extra-occular Muscle
Swelling
- <10% pts
- Maculopapular rash
- Pau d’orange
- ECM Component
Accumulation
- Fatty Infiltration
- Ca Leakage from SER
- SERCA Pumps Back in
- Futile Biochem. Cycle
- Sweating
- Heat Intolerance
Soft, Flushed
Warm Skin
Infiltrative
Opthalmopathy
Pretibial Myxoedema
SERCA in Muscles
Gluconeogenesis
(SNS) Competes with
Glycolysis (TH)
Chemosis
(Eye Oedema)
- Gritty Eyes
- Conjunctival
Injection
Grave’s Disease
B Cell
Activation
- Heat Produced
- No Useful Work
Eye Protrusion
- Exopthalmosis
- Ptosis
- Hyperthyroidism
- Opthalmopathy
- Dermopathy
- Peak onset 20-40 yrs
T Cell Infiltration
- Thyrod Gland
- Retro-Orbital
ATP Consumed
Sympathomimetic
SNS Activity
HR
- Stress causing Catacholamine
Release
- Severe T3/T4 Levels
- More common in Graves
- Death from Arthymias
Autoreactive
T Cells
Grave’s Disease
Levator Palpebrae
Superioris Overactivity
- Lid Lag
- Lid Retraction
(Staring Gaze)
Opthalmoplegia
Central & Peripheral
Tolerance Impaired
Problem 7.01
- Emotional Liability
- Hyperactivity
- Poor Co-ordination
- Insomnia
- Tremor
- Anxiety
- Inhibits Co-stimulation of T cells
- Inhibits T Cell proliferation
- HLABB
- HLADR3
- CTLA4
- Female 7:1 Male
- Other AID (Thyrogastric)
in Patient or Family
- Infection
- Drugs
SERCA = SER Calcium ATPase
TPO = Thyroid Peroxidase
TG = Thyroglobulin
MIT = Mono-Iodo Tyrosine
DIT = Diodo Tyrosine
TBG = Thyroid Binding Globulin
SVC = Superior Venae Cavae
TCR = T Cell Receptor
TSH
Thyroid
T3/T4
TRH = TSH Releasing Hormone
TSH = Thyroid Stim. Hormone
TSHR = TSH Receptor
TH = Thyroid Hormone
TSI = Thyroid Stimulating Ig
TBII = Thyroid Binding Inhib. Ig
TGI = Thyroid Growth Stim. Ig