jslum.

com | Medicine
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 imme diately 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 Li bido, Impoten ce
↓
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 d ue 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-Based ow Phenomen on) Periorbital Oedema
Corneal Ulceration
Ophthalmoplegia Graves’ Disease
Papillooedema Hyperthyroidism
Mass in Neck Lid Lag
Diplopia
Exophthalmos Thyrotoxicosis
Loss of Acuity
 jslum.com | Medicine

Pathophysiol ogy 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 Consu mption 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
↙ ↘
Hyperthyroidism Hypothyroidism
↑ Number, Affinity of ↑ Oxygen Consu mption
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, In otropic) 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 Autoantibodie s
↘ ↓
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 Rea ctivity to TSH Receptor Thyroid scan with
(Graves Disease) • 123I (Iodine 123)
↓ • 99mTc (Tech netium-99 m)
Specific Immune Response/ Autoimmune Test with Thyroid Scan (Procedure)
↓
Infiltration of Lymphocytic, Mucop olysaccharides, • 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
↙ ↓ ↘
Asses wither Thyroid Lumps, Nodules are actively producing Thyroid Hormone
Pressure to Bulging of Eyes Diplopia
Results
Optic Nerve ↓
Increased Uptake Decreased Uptake
↓ Proptosis/ Exophtalmee → Lid Retraction
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 Li bido
Oligomenorrhea Spontaneous Abortion Impotence Radioactive Iodine Scan
Grave’s Disease Subacute Thyroiditis
Radioactive Iodine Scan
Eye signs (Hyperthyroid phase)
Toxic Multinodular Goiter
Pretibial Myxoedema Little Iodine Uptake in Thyroid
Patchy, Darker Appearance of
Thyroid Acropachy (due to Inflammation of Thyroid –
nodules that are producing excess
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
 jslum.com | Medicine

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 Immunosuppres sive 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 recommende d 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)