RCSI Thyroid Function & Disease 2025 PDF

RCSI Royal College of Surgeons in Ireland Coláiste Ríoga na Máinleá in Éirinn Thyroid Function & Disease Department of Medicine LEARNING OUTCOMES Define hypothyroidism and hyperthyroidism Explain the pathophysiology of hyperthyroidism and hypothyroidism List the cardinal symptoms and signs o...

RCSI Royal College of Surgeons in Ireland Coláiste Ríoga na Máinleá in Éirinn Thyroid Function & Disease Department of Medicine LEARNING OUTCOMES Define hypothyroidism and hyperthyroidism Explain the pathophysiology of hyperthyroidism and hypothyroidism List the cardinal symptoms and signs of hyperthyroidism and hypothyroidism Explain how each symptom and sign is caused in hyperthyroidism and hypothyroidism Develop a differential diagnosis for hyperthyroidism and hypothyroidism Outline the overarching principles of investigation and management in thyroid disorders THYROID HORMONE Thyroid hormone affects nearly every organ in the body Increases basal metabolic rate and thermogenesis in response to stress CVS: increases expression of beta-receptors to increase cardiac output and contractility Respiratory: increases oxygenation by stimulating respiratory centres and increasing lung perfusion Skeletal muscle: increases expression of fast-twitch muscle fibres Metabolism: increases basal metabolic rate, metabolism of carbohydrates, anabolism of proteins Growth: During childhood, acts synergistically with growth hormone to stimulate bone growth CNS: Brain maturation in prenatal period. Affects mood, memory, sleep in adults Fertility, ovulation, menstruation HYPOTHYROIDISM Definition: Hypothyroidism is a pathological disorder in which insufficient thyroid hormones are synthesised and secreted by the thyroid gland Primary hypothyroidism (high TSH, low free T4) Thyroid gland failure Despite appropriate stimulation from the pituitary in the form of TSH, the thyroid gland is unable to respond and produce T4 Central or secondary hypothyroidism From deficient TSH secretion, generally due to pituitary lesions such as a pituitary tumor (low T4, normal or low TSH). Despite the low levels of T4, there is no compensatory increase production of TSH PRIMARY HYPOTHYROIDISM DIFFERENTIALS Congenital: Agenesis of the thyroid gland Part of heel-prick screening test at birth Thyroid tissue destruction: Autoimmune: – Hashimoto's thyroiditis: Thyroid peroxidase antibodies (TPO). Most common cause of hypothyroidism in iodine sufficient countries. – Reidel's thyroiditis: T cell/IgG4 mediated inflammation of thyroid gland leading to fibrosis, which extends beyond the thyroid capsule into the surrounding tissues. Creates a characteristic 'woody' hard goitre. Radiation: usually radioactive iodine treatment for thyrotoxicosis Post-thyroidectomy Infiltrative diseases of the thyroid: haemochromatosis Anti-thyroid drugs: lithium, iodine, iodine containing drugs, radiographic contrast material, amiodarone, checkpoint inhibitor immunotherapy HYPERTHYROIDISM Definition: Hyperthyroidism is a pathological disorder in which excess thyroid hormone is synthesised and secreted by the thyroid gland Thyrotoxicosis: the clinical state associated with excess thyroid hormone activity Primary hyperthyroidism: Elevated free T4 Suppressed / Undetectable TSH ( < 0.1 ) Secondary hyperthyroidism: Elevated T4 Elevated TSH PATHOPHYSIOLOGY Hypothalamic- Pituitary- Thyroid Axis TSH: Binds to TSH receptors on thyroid cells causing: 1. Production of T4 and T3 2. Hyperplasia/growth of gland T3 and T4 actions: affect most organs Increase metabolism Growth and development Increase catecholamine effects  HYPOTHYROIDISM Thyroid gland insufficiency/failure due to: Primary cause is the most common cause of hypothyroidism​ Pituitary and hypothalamus (secondary and tertiary) less commonly implicated Decline in T4 and T3 Increase release of Can cause Hypertrophy production TSH from pituitary and hyperplasia of thyroid tissue leading to goitre Iodine deficiency however is the most common cause worldwide (iodine is a basic structural element of thyroid hormones) Autoimmune (Hashimoto's) thyroiditis most common cause in developed/iodine sufficient countries.​ HYPOTHYROIDISM Symptoms related to decreased metabolic rate: Bradycardia Weight gain Cold intolerance Poor appetite Hair loss Cold dry skin Fatigue Constipation Myopathy May see delayed tendon reflexes on exam Children: 'Cretinism- old term'- short stature, intellectual disability HYPOTHYROIDISM HASHIMOTO'S THYROIDITIS Autoimmune inflammation of thyroid tissue Most common cause of hypothyroidism Females >males Gradual thyroid failure due to autoimmune-mediated destruction of the thyroid gland. With or without goiter formation- due to lymphocytic infiltration and scar tissue formation. Diagnosis: evidence of hypothyroidism, high serum concentrations of antibodies against thyroid antigen (TPO antibodies- aka thyroid peroxidase antibodies), along with an intense and diffuse lymphocytic infiltration of the thyroid. Follicular destruction is the characteristic pathologic hallmark of thyroiditis.  SUBCLINICAL HYPOTHYROIDISM Persistently high TSH with a normal T4 Very common –up to 8% Can progress to overt hypothyroidism (2-5% per year) Treat if TSH >10 Pre or during pregnancy Infertility Consider in symptomatic patients Questionable benefit if TSH 4-10 especially in older age Overt Hyperthyroidism Subclinical Subclinical Overt Hypothyroidism hyperthyroidism hypothyroidism High T4, Low TSH** Normal T4, Low TSH Normal T4, high TSH Low T4, high TSH** **TSH may be opposite in secondary causes HYPERTHYROIDISM DIFFERENTIALS Graves' disease Toxic multinodular goitre (MNG) Toxic adenoma Drug-induced: Amiodarone Excess exogenous use "factitious" Subacute viral thyroiditis Thyrotoxicosis/thyroid storm HYPERTHYROIDISM Excess thyroid hormone (T4 and T3)production Causes: Graves' disease: – Autoimmune Toxic multinodular goitre: – Multiple slow-growing nodules develop autonomous thyroid hormone production. – Almost always benign, but rare potential for malignancy Toxic adenoma: – Solitary autonomous nodule Viral thyroiditis: deQuervain’s (also known as subacute thyroiditis) – Subacute granulomatous thyroiditis, characterised by a tender diffuse goitre. – Predictable course: hyperthyroidism first, then hypothyroidism, then euthyroid (occasionally, hypothyroidism may be permanent) Less common: – Pituitary adenoma, Drug-induced (Amiodarone, checkpoint inhibitor immunotherapy), Factitious (excessive exogenous use) HYPERTHYROIDISM Hypermetabolism: Heat intolerance Weight Loss Increased appetite Sweating Palpitations: Tachycardia (Sinus, Atrial fibrillation) Hypertension Heart Failure Tremor Myopathy Restlessness, anxiety, depression HYPERTHYROIDISM  GRAVES’ DISEASE Antibodies produced against TSHR on thyroid cells (TSH receptor- expressed in thyroid predominantly, but also in adipocytes, fibroblasts, bone cells) Leads to inappropriate activation of thyroid cells (TSH agonist) causing increased T4 and T3 production. This stimulus cannot be overridden by negative feedback. Increased TSH receptor activation also causes hyperplasia/growth of the gland. Factors that predispose to development of Graves’ disease: genetic susceptibility, failure of immune tolerance, molecular mimicry, Females > males, smoking, drugs (Iodine and iodine- containing drugs such as amiodarone and computed tomography (CT) scan contrast media may precipitate Graves' disease) Overall incidence of Graves' disease: approximately 4.6 per 1000 during 10 years of observation Antibodies: TRAb: TSH receptor antibodies (aka thyrotropin receptor antibodies) (sensitivity and specificity over 90%) Manifestations (can have features of all or some): Hyperthyroidism: most common manifestation of Graves’ Goitre: usually diffusely enlarged, in response to activation of TSHR Thyroid eye disease Dermopathy: Pretibial myxedema Acropathy THYROID EYE DISEASE AKA Graves’ orbitopathy (occurs in approximately 25% of patients with Graves’- most patients have mild disease) Autoimmune disease of the orbit and retro-ocular tissues occurring in patients with Graves' disease and rarely in patients with Hashimoto's thyroiditis Activation of orbital fibroblast and preadipocyte TSHRs and IGF-1 receptors and initiating cellular expansion and orbital inflammation, leading to mucopolysaccharides accumulation, muscle swelling, and an increase in pressure within the orbit. The eyeball is pushed forward, leading to extraocular muscle dysfunction and impaired venous drainage causing periorbital swelling Exophthalmos Lid retraction Conjunctival inflammation Periorbital oedema THYROID EYE DISEASE Proptosis (exophthalmos): Bulging Conjunctival inflammation Proptosis Periorbital oedema Lid retraction, lagophthalmos (inability to close eyelids fully) Strabismus: extra-ocular muscles impaired Optic neuropathy: compression TED worsened by: Smoking Lagophthalmos Radioactive iodine: increased release of antigens Treatment: Depends on severity Mild disease- can consider selenium Moderate-severe disease- steroids, immunosuppressants, teprotumumab (if available) MYXOEDEMA Severe hypothyroidism- life threatening (rare presentation of hypothyroidism) Accumulation of mucopolysaccharide in subcutaneous tissues: thickening of skin ALL LOW! Hyponatraemia Hypoglycaemia Hypotension Hypothermia Heart failure Confusion, coma, high mortality Myxoedema coma: Treat with IV levothyroxine or IV T3 under specialist endocrine supervision. THYROID STORM/THYROTOXIC CRISIS Life threatening emergency, 10-30% mortality even with early recognition and treatment. Rare condition Acute severe thyrotoxicosis usually in patients with longstanding untreated hyperthyroidism, precipitated by stress e.g. Infection, surgery, trauma, childbirth Symptoms: Fever (heat intolerance extends into fever/pyrexia) Agitation, confusion, seizures, coma Tachycardia, AFIB Heart failure (high output) Treatment: Beta-blocker (selective), high dose thionamides, iodine solution to block thyroid, Corticosteroids  GOITRE Enlarged thyroid gland causing swelling in the anterior neck, midline Superior extension limited by the sternothyroid muscle- will grow downwards Can ultimately cause tracheal/oesophageal compression Common to both hypo and hyperthyroidism dependent on the underlying cause Multiple causes of enlargement: iodine-deficiency, excess TSH stimulus, inflammation, scarring, masses... Characteristics can be informative: Can be diffuse, e.g. Graves’ disease Multiple nodules: toxic multinodular goitre, less likely multiple masses Single palpable nodule: single mass e.g. Adenoma Tender: Acute thyroiditis INVESTIGATIONS THYROID FUNCTION TESTS INVESTIGATIONS Bloods: Thyroid function tests – TSH, T4 – Can also request send out tests: T3, free T4 Antibodies: – Anti-TPO: Hashimoto's thyroiditis – TSH receptor antibodies (TRAb): Graves’ disease – AKA Thyrotropin receptor antibodies Imaging: Thyroid Ultrasound -selected cases only Indications: palpable thyroid mass or certain types of hyperthyrodisim FNA- fine needle aspiration (if thyroid nodule meets criteria for FNA- will be taught further in thyroid nodule MDT) Radioiodine or technetium uptake – used for hyperthyroid patients with physical examination suggesting nodular thyroid disease. This will help determine the etiology of hyperthyroidism – High- most commonly with Graves’ disease or toxic multinodular goitre – Low- most commonly with thyroiditis TREATMENT: HYPOTHYROIDISM Levothyroxine, T4, (eltroxin brand name in Ireland), dose is approximately 1.6 mcg/kg body weight per day if complete thyroid failure. Dose titrated to achieve normal TSH in primary hypothyroidism Should be taken on an empty stomach with water. Should not be taken with other medications that interfere with its absorption (e.g- calcium, ferrous sulfate, soy products) “Start low and go slow “ in the elderly and those with unstable heart disease. Tip: ***exclude or treat adrenal insufficiency before commencing levothyroxine in patients with suspected central hypothyroidism- can induce adrenal crisis***, aim is to keep T4 in the middle of the normal range, ignore TSH SUBCLINICAL HYPOTHYROIDISM: WHEN TO TREAT TREATMENT- HYPERTHYROIDISM Taught in further detail in lecture “Agents to Treat Disorders of the Thyroid and Parathyroid Glands” Pharmacological: Thyroid hormone synthesis inhibitors: Carbimazole (methimazole) Propylthiouracil (PTU) SEs: rash, rare: agranulocytosis, hepatotoxicity Thyroid hormone secretion blockade (mainly in preparation for surgery or thyroid storm) Iodides (Lugols iodine, SSKI) Beta-adrenergic blockers: manage symptoms Propranolol, atenolol NSAIDs for treatment of pain in subacute thyroiditis Corticosteroids (for severe thyroiditis, myxedema, and thyroid storm) Procedural: Radioactive Iodine Ablation Surgical: Total thyroidectomy: Refractory disease, compressive features, cosmetic Complications: Hypothyroidism, hypoparathyroidism, RLN injury PSA SAMPLE QUESTION RESOURCES https://www.uptodate.com/contents/clinical-features-and- diagnosis-of-thyroid-eye- disease?search=graves%20disease&topicRef=7841&so urce=see_link https://www.ncbi.nlm.nih.gov/books/NBK482216/ https://www.uptodate.com/contents/diagnosis-of- hyperthyroidism https://www.ncbi.nlm.nih.gov/books/NBK519536/ https://www.thelancet.com/journals/landia/article/PIIS221 3-8587%2821%2900285-0/fulltext