ThyroidAnatomyPhysiologyExamination

PathologiesHamburger thyrotoxicosis

Presenting complaintsPharmacologyInvestigations

EmbryologyEpidemiology

EvolutionEthics

Social determinants

THYROID HORMONE

Hypothalamus

Anterior Pituitary

THYROID GLAND

+ TRH

+ TSH

T3: Triiodothyronine (more active)

T4: Thyroxine)

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• 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