Hyperthyroidism Hyperthyroidism

					Hyperthyroidism

Thyroid Hormone Synthesis                                                        Clinical Features




                                                                                 Symptoms
    Basal Membrane of Thyroid Cell pump Iodide actively into cell interior       General
       (main control point for Hormone Synthesis)(Stimulated by TSH)             Weight loss despite Normal, ↑ Appetite
                                       ↓
                                                                                 Heat Intolerance
       Thyroid Cells – Synthesize, Secrete Large Glycoprotein molecule
                                       ↓                                         Sweating
                  Thyroglobulin + Iodine → Thyroid Hormones                      Fatigue
                                       ↓                                         Osteoporosis (Fracture, Loss of Height)
               Iodine ions (converted to Oxidized form of Iodine)                Gastrointestinal
                                       ↓
                   Reaction is catalyzed by Peroxidase, H2O2                     Diarrhoea, Steatorrhoea, Hyperdefecation
                                       ↓                                         Anorexia
                 Peroxidase (located at Apical Cell Membrane)                    Vomiting
                                       ↓
                                                                                 Dysphagia
                        Organification of Thyroglobulin
                                                                                 Cardiorespiratory
                (Binding of Iodine with Thyroglobulin molecule)
                                       ↓                                         Palpitations
                        Thyrosine is Iodized to MIT, DIT                         Dyspnoea on exertion
                                       ↓                                         Angina
                          DIT + DIT → Thyroxine (T4)                             Ankle Swelling
                       DIT + MIT → Triiodotyronine (T3)                          Exacerbation of Asthma
Storage                                                                          Neuromuscular
After synthesis, Thyroid Hormones are stored in Follicles                        Anxiety, Irritability, Emotional Labilit, Psychosis
Amount is enough for 3-4 months’ supply                                          Muscle Weakness
Release                                                                          Insomnia
       Apical surfaces of Thyroid Cells form the Pseudopod around Colloid        Dermatological
                                       ↓
                                                                                 Pruritus
           Lysosomes in cell cytoplasm immediately fuse with vesicles
                                       ↓                                         Reproductive
               Multiple protease digest Thyroglobulin molecules                  Amenorrhoea, Oligomenorrhoea
                                       ↓
                                                                                 Infertility, Spontaneous Abortion
                 Free T3, T4 are released to enter blood stream                  Loss of Libido, Impotence
                                       ↓
                    ¾ Iodinated Tyrosine remain as DIT, MIT
                                       ↓                                         Signs
           Deiodinase enyzme cleaves, recycles Iodine from MIT,DIT               General
                                                                                 Goiter (with Bruit)
Definition                                                                       Cardiorespiratory
Hyperfunction of Thyroid Gland leading to                                        Tachycardia, Atrial Fibrillation
Excessive Production of Thyroid Hormones (T3, T4)                                Full Pulse
Thyrotoxicosis                                                                   Warm Vasodilated Periphery
Toxic symptoms due to ↑ Thyroid Hormone Activity                                 Systolic Hypertension
May not necessarily be Hyperfunction of Thyroid Gland                            Cardiomegaly
Hyperthyroidism                                                                  Cardiac Failure
Sustained Hyperfunction of Thyroid leading to Toxic Symptoms                     Neuromuscular
                                                                                 Tremor
Etiology                                                                         Hyperreflexia
             Primary (1°)                             Secondary (2°)             Dermatological
Graves’ Disease                            TSH-Secreting Pituitary Adenoma       Palmar Erythema
Thyroiditis                                Thyroid Hormone Resistance            Finger Clubbing (Thyroid Acropachy)
Toxic Multinodular Goiter                  Syndrome (occasionally, features of   Spider Naevi
Toxic Adenoma                              Thyrotoxicosis)                       Onycholysis
Functioning Thyroid Carcinoma              Chorionic Gonadotropin-secreting      Pigmentation
Metastases                                 Tumors                                Vitiligo
Activationg Mutation of TSH Receptor       Gestational Thyrotoxicosis            Reproductive
Activating Mutation of Gsα                                                       Gynaecomastia
(McCune-Albright syndrome)                                                       Occular
Struma ovarii (Hyperfunctioning                                                  Lid Retraction, Lid Lag
Ovarian Teratoma)                                                                Chemosis
Drugs - Iodine Excess                                                            Exophthalmos
(Jod-Basedow Phenomenon)                                                         Periorbital Oedema
                                                                                 Corneal Ulceration
                                                                                 Ophthalmoplegia                  Graves’ Disease
                                                                                 Papillooedema                    Hyperthyroidism
                                                                                                                  Mass in Neck         Lid Lag
                                                                                 Diplopia
                                                                                                                  Exophthalmos         Thyrotoxicosis
                                                                                 Loss of Acuity
Pathophysiology                                                                          Investigations
                                      Hyperthyroidism                                    Thyroid Stimulating Hormone (TSH)
                                               ↓
                                                                                         ↓ TSH – Hyperthyroidism
                         Stimulate Na+-K+ ATPase in all tissues                          TSH assay is the most sensitive test for diagnosis of Hyperthyroidism
                                               ↓
                                ↑ Oxygen Consumption                                     Can detect even tiny amounts of TSH in blood, most accurate available
                                               ↓                                         Useful in detecting Mild Hyperthyroidism
                                          ↑ BMR                                          Pituitary Gland Boosts TSH Production when
                           ↙                   ↓               ↘
                                                                                         Thyroid is not making enough Thyroid Hormone (respond by ↑ hormone)
       ↑ Appetite                     Loss of Weight                 ↑ Body Heat
                                                                           ↓             When body has enough Thyroid Hormone circulating in blood, TSH output ↓
                                                                   Heat Intolerance      In people who produce too ↑ Thyroid Hormone, Pituitary shuts down TSH
                                      Hyperthyroidism                                    production – lead to ↓ or undetectable TSH levels in blood
                                               ↓                                         Generally – TSH Levels
                               ↑ Thyroid Hormone (T3, T4)                                               Below Normal                           Above Normal
                     ↙                                              ↘
        ↑ Number, Affinity of                         ↑ Oxygen Consumption                 Hyperthyroidism                           Hypothyroidism
        β-Adrenergic Receptor                        ↑ Metabolism at Periphery           2. Free T4 (Free Thyroxine)
    (heart) towards Catecholamine                                   ↓                    Active Thyroid Hormone ↑ in blood
                     ↓
                                                                ↑ BMR                    In patients with unstable thyroid states, T4 are more accurate than TSH
      ↑ Heart Rate, Contractility                                   ↓                    With Mild Hyperthyroidism, Free T4 will remain ↑ in Normal range
      (Chronotropic, Inotropic)                         Peripheral Vasodilatation        3. Triiodothyronine (T3) Radioimmunoassay (RIA) or Free T3
         ↙                        ↘                                 ↓                    T3 is often ↑ to higher level in Severe Hyperthyroidism
   Tachycardia                  ↑ CO                    ↓ Peripheral Resistance          4. Thyroid Autoantibodies
                                           ↘                        ↓
                                                                                         TSH Receptor Antibodies (TRAb) or Thyroid-Stimulating Immunoglobulins (TSI)
                                                           ↑ Pulse Pressure
                                                                                         Antibodies present in >50% of Grave’s Disease, Stimulate Thyroid ↑ in size
                                      Hyperthyroidism
                                               ↓                                         5. Radioactive Iodine
                          ↑ Thyroid Hormone (T3, T4) due to                              (If Lab tests indicate Hyperthyroidism, imaging tests may be used)
                          Immune Reactivity to TSH Receptor                              Thyroid scan with
                                  (Graves Disease)                                             123I (Iodine 123)
                                               ↓
                                                                                               99mTc (Technetium-99m)
                     Specific Immune Response/ Autoimmune                                Test with Thyroid Scan (Procedure)
                                               ↓
                 Infiltration of Lymphocytic, Mucopolysaccharides,                             Take a Drink, Swallow a Pill containing Radioactive Iodine
                              Fluid, Glycosaminoglycans                                        Wait for Iodine to be taken up by Thyroid Gland
                                               ↓                                               Images are taken to show amount of Iodine taken up by Thyroid
        Fluid retention in Retrobulbar Soft Tissue, Extra-ocular Muscle                  Helps to determine cause of Hyperthyroidism
             ↙                                 ↓                           ↘
     Pressure to                      Bulging of Eyes                   Diplopia         Asses wither Thyroid Lumps, Nodules are actively producing Thyroid Hormone
     Optic Nerve                               ↓                                         Results
             ↓
                                      Proptosis/ Exophtalmee → Lid Retraction                          Increased Uptake                       Decreased Uptake
       Blindness                               ↓                           ↓               Graves Disease (Generalized)                Subacute Thyroiditis
                                          Lid Lag                  Corneal Exposure        Toxic Nodular Goiter (Localized)
                                                                           ↓

                                                                   Dryness of Corneal
                                                                    Irritation of Eyes
                                      Hyperthyroidism
                                               ↓
                               ↑ Thyroid Hormone (T3, T4)
                                               ↓
                      ↑ Metabolism of Steroid into Estrogen
                                               ↓
                                        ↑ Estrogen
                           ↙                   ↓               ↘
       Amenorrhoea                 Infertility             Loss of Libido
     Oligomenorrhea          Spontaneous Abortion           Impotence                                                           Radioactive Iodine Scan
Grave’s Disease                                                                          Radioactive Iodine Scan                Subacute Thyroiditis
Eye signs                                                                                Toxic Multinodular Goiter              (Hyperthyroid phase)
Pretibial Myxoedema                                                                      Patchy, Darker Appearance of           Little Iodine Uptake in Thyroid
Thyroid Acropachy                                                                        nodules that are producing excess      (due to Inflammation of Thyroid –
Elderly                                   Children                                       amounts of Thyroid Hormone             causing ↑ Thyroid Hormone in blood)
Atrial Fibrillation                       Excessive Growth Rate
Tachycardias, Cardiac Failure             Excessive Height
                                          Hyperactivity




                                                                                         Radioactive Iodine Thyroid Scan        Radioactive Iodine Thyroid Scan
                                                                                         Normal                                 Graves’ Disease
                                                                                                                                Overall ↑ Uptake throughout
                                                                                                                                Enlarged Thyroid Gland
Management                                                                      Complications
Antithyroid Drugs                                                               Thyroid Crisis/ Thyroid Storm
Thioamides (Carbimazole, Methimazole, Propylthiouracil)                         Rapid deterioration of Hyperthyroidism with
     Inhibit Oxidation of Iodide to Iodine                                          Hyperpyrexia
     Inhibit Formation, Coupling of Iodotyrosines in Thyroglobulin                  Severe Tachycardia
      (necessary for Thyroid Hormone Synthesis)                                      Extreme Restlessness
     Carbimazole/ Methimazole – Mild Immunosuppressive agent                        Cardiac Failure
     Propylthiouracil – Blocks Conversion of T4 → T3                                Liver Dysfunction
Iodides                                                                         Precipitated by
     Inhibit Organification of Iodine                                               Stress
     Inhibit Hormone release                                                        Infection
     ↓ Size, Vascularity of Hyperplastic Thyroid                                    Surgery in an unprepared patient
     Useful in Thyroid Storm, Preoperative preparation for Thyroid Surgery          Radioiodine therapy
     Should not be used alone                                                  Osteoporosis
     Avoid in Pregnancy (due to ability to cross placenta)                     ↑ Risk of Osteoporosis
Beta Blockers (Propanolol – does not have sympathomimetic activity)             (the only long-term risk of adequately treated hyperthyroidism)
     Due to manifestation of Hyperthyroidism (mediated via Sympathetic)        Atrial Fibrillation
     Rapid Symptomatic control                                                 ↑ Risk of Atrial Fibrillation (Persistently suppressed TSH levels)
     ↓ Peripheral Conversion of T4 → T3                                        Predispose to Thromboembolic Disease
     Should not be used alone                                                  Heart-related Complications
      (except if condition is self-limiting – eg. Subacute Thyroiditis)         Tachycardia
Management                                                                      Angina
      ‘Block and Replace’ Regimen                    Gradual Dose Titration     Congestive Heart Failure
  Full doses of Antithyroid drugs (eg.        Start on ↑ Dose (20-40mg) then    Cardiomyopathy
  Carbimazole 40mg daily)+ 100mg              gradually ↓ dosage according to   Surgery-related Complications
  Levothyroxine daily once                    patient’s condition               Scarring of Neck
  Euthyroidism is achived                     Discontinue when Euthyroid is     Hoarseness due to Nerve Damage to Voice Box
                                              achieved                          ↓ Ca2+ level due to damage to Parathyroid Glands
Radioactive Iodine (RAI) Therapy (131 Iodine)                                   Others
Accumulate in Thyroid                                                           Ophthalmopathy
Destroy the gland by Local Radiation
Orally as a single dose (capsule, liquid)
(patient must be rendered Euthyroid before treatment)
May take several months to be fully effective
Never administered to (cross placenta, excreted into milk)
     Pregnant women
     Lactating women
Not recommended in Children
Thyroidectomy
Subtotal/ Complete
Performed only in patients who have previously rendered Euthyroid
Stop Antithyroid drugs 10-14 days before surgery
Potassium Iodide – given to ↓ Vascularity of Gland
Complications
     Recurrent Laryngeal Nerve Palsy (1%)
     Transient Hypocalcemia (10%)
     Permanent Hypoparathyroidism (<1%)
     Hypoparathyroidism (10%/ year)