Thyroid Improved Flashcards
Thyroid hormone control
Hypothalamus –> TRH –> pituitary –> TSH –> Thyroids –> T3 and T4
Thyroid negative feedback
T3 + 4 negative feedback to pituitary (stop TSH release) and Hypothalamus (stop TRH release)
Thyroid hormone action
T4 manufactured in thyroid + deiodinated in periphery to T3
T3 diffuses through cellular membranes
Binds to nuclear thyroid hormone receptor –> effects on gene transcription
Thyroid hormone function
Affect:
Basal metabolic rate
Tissue sensitivity to catecholamines
Neural development in the foetus
Hyperthyroidism also known as
Thyrotoxicosis
Thyrotoxicosis General symptoms
Tired
Anxious
Sweating
Thyrotoxicosis CVS symptoms
Palpitations
AF
Heat intolerance
Thyrotoxicosis Abdo symptoms
Weight loss
Frequency
Increased appetite
Thyrotoxicosis GU symptoms
Oligomenorrhoea
Thyrotoxicosis CNS symptoms
Terror
Eye problems
Muscle weakness
Emotional/agitated
Thyrotoxicosis PMH
Other autoimmune conditions
IHD
Thyrotoxicosis DH
Amiodarone ( contains iodine)
Lithium (mimics iodine)
Interferon
Retrovirals
Thyrotoxicosis FH
Autoimmune disease
Thyrotoxicosis ROS
Other autoimmune conditions
Onset- acute or insidious?
Thyrotoxicosis Acute onset
Graves
Thyrotoxicosis Insidious onset
Multinodular Goitre
Thyrotoxicosis + parietal cells
Can have gastric parietal cell antibodies –> associated risk of developing pernicious anaemia
Thyrotoxicosis Exam- general
Agitated
Thin
Tremor
Vitiligo
Thyrotoxicosis Exam- thyroid
Goitre (smooth? (Graves) nodular? (toxic MNG))
Toxic MNG= hyperthyroidism
Thyrotoxicosis Exam- CVS
Tachyardia
AF
Thyrotoxicosis Exam- CNS
Lid retraction
Lid lag
Brisk reflexes
Proximal myopathy
Thyrotoxicosis Exam- other
Signs of Graves- lid lag, lid retraction, ophthalmoplegia, proptosis, pre-tibial myxoedema, acropachy), cardiac failure, high BP, fever
Grave’s disease
Thyroid dysfunction in the presence of thyroid stimulating antibodies
Thyrotoxicosis investigation
High free T4
Low (undetectable) TSH
Thyroid antibodies to prove thyroid autoimmunity
Gastric parietal cell antibodies
Annual B12 levels to predict onset of pernicious anaemia
Thyrotoxicosis differentials
Grave's Toxic Multinodular Goitre Toxic adenoma Destructive thyroiditis Excessive iodine (Jod-Basedow) Drugs Thyroid hormone Resistance TSH producing pituitary tumour - secondary hypothyroidism- raised TSH and FT4
Grave’s disease
Autoimmune disease consisting one or more of: Thyroid dysfunction Ophthalmopathy Pre-tibial myxoedema Acropachy
Graves thyroid
Diffuse smooth goitre Bruit FH Other autoimmune (T1DM, Addison's, hypoparathyroidism, premature ovarian failure) Thyroid stimulating antibodies
Graves- Eyes- history + exam
Often smoker Pain Tearfulness + grittiness Dry Diplopia Prior to loss of visual acuity, loss of colour vision Redness Proptosis Lid lag + retraction
Graves Eyes Investigations
MRI orbits
TFTs
Graves eyes treatment
High dose Steroids
Radiotherapy
Surgery
Thyrotoxicosis treatment
Medical
Radioiodine
Surgery
Thyrotoxicosis treatment- medical
Graves- 18 months of treatment
Carbimazole
Propylthiouracil
Propanolol non selective BB (reduces acute symptoms as blocks catecholamine sensitive symptoms)
Carbimazole SEs
1 in 100 rash
1 in 1000 agranulocytosis- warn about sore throat
Thyrotoxicosis treatment- radioiodine
Iodine 131 radiation- destroys gland Need to be away from children 2-3 weeks Can lead to hypothyroidism, so need to take thyroxine If Graves eyes, can deteriorate Used when carbimazole fails to cure
Thyrotoxicosis treatment- surgery
In presence of large goitre
Need to be on thyroxine for rest of life
Risk of damage to recurrent laryngeal- hoarseness
Risk of damage to parathyroid glands- Vit D
Hypothyroidism history- general
Tired
Cold
Dry skin + hair
Hypothyroidism history- Abdo
Weight gain
Constipation
Hypothyroidism history- GU
Menorrhagia
Hypothyroidism Exam
Puffy Peaches and cream face Cold dry skin Goitre Bradycardia Slow relaxing reflexes In extremis- coma, hypothermia
Hypothyroidism Investigations
Low FT4
High TSH
Positive thyroid antibodies (Hashimoto’s)
Cortisol
Cortisol + hypothyroidism
If somebody has low Cortisol + ACTH, and give thyroxine to treat hypothyroidism, can precipitate into Addisonian crisis
Hypothyroidism causes
Iodine deficiency (2 billion ppl worldwide) Hashimoto's thyroiditis Congenital hypothyroidism (1 in 4000) Iatrogenic Post-partum thyroiditis
Hypothyroidism + iodine
If give iodine to those that are iodine deficient hypothyroidism, can become rapidly thyrotoxic
CT contrast + hypothyroidism
CT contrast is predominally iodine- if give CT contrast to someone with multinodular goitre, very likely to induce thyrotoxicosis
Hypothyroidism treatment
Levothyroxine- titrated to target TSH
Titrate to make FT4 within upper half of reference (15-25 pmol/L) range, and TSH in lower half of reference range (0.5-2.5mU/L)
Hypothyroidism treatment consideration
Consider cause
How severe
Does patient have co-morbidities
High TSH with normal FT4
Intercurrent illness
Inadequate dose
malabsorption
Poor concordance with therapy
Different Thyroid Goitres
ANY thyroid enlargement
1) Multi-nodular- more common in low iodine area
2) Secondary to autoimmune overactive or underactive thyroid (Grave’s + Hashimoto)
If it is toxic MNG, due to hyperthyroidism
Thyroid MNG History
Lump in neck- how long, has it changed, if sudden onset (bleed), slow onset (NG) Any thyrotoxicosis symptoms Dysphagia Cough/dyspnoea/stridor Sudden enlargement or pain
Thyroid MNG Exam
Size
Retrosternal extension (percuss over sternum)
Thyroid status
Signs of airway compromise
Thyroid MNG Investigations
TFT Lung function- tracheal compression CXR Ultrasound scan CT (without scan)
Thyroid MNG Treatment
Watch + wait
Surgery (thyroidectomy)
Radioiodine (smaller goitre, can cause swelling so don’t do on big one, can reduce 30-50%)
Thyroid Neoplasia History
Neck lump/swelling
Radiation exposure?
Thyroid neoplasia exam
Soft/firm/hard
Mobile/tethering
Thyroid neoplasia investigation
Ultrasound scan +/- fine needle aspiration
Check calcitonin- raised in medullary cancer of thyroid
Chest XR
Thyroid neoplasia surgery
Diagnostic hemithyroidectomy
Near-total thyroidectomy
Thyroid neoplasia Differential
Follicular adenoma (non-malignant)
Papillary (lymphatic)
Follicular (blood)
Medullary (linked to multiple endocrine neoplasia type 2)
Anaplastic- poor prognosis
Lymphoma- rare
10 year disease free > 90% for papillary/follicular types
Thyroid neoplasia treatment
Near-total thyroidectomy helps to confirm histology- whether papillary/follicular cancer
Adjunctive therapy- Iodine 131 ablation
Suppressive thyroid replacement- high dose thyroxine to supress TSH + reduce recurrence
External beam radiotherapy
Serum thyroglobulin useful tumour marker- rising levels = recurrence
TBG levels pregnancy
Increased (oestrogen inhibits hepatic breakdown)
Still normal T3/4 as increased total
TBG in liver failure
Decrease
TSH effect
Increase T3/4
Hypertrophy + hyperplasia of thyroid follicular cells
Increased BF thyroid
T3/4 on BMR
Increase Na/K ATPase activity to increase O2 production and heat
T3/4 on Metabolism
Increased glucose uptake and absorption Increased glycogenolysis Increased Gluconeogenesis Increased insulin Increased FA oxidation Decreased cholesterol in plasma Decreased muscle mass
T3/4 on CR
Increased HR and CO
Increased vasodilation
Increased ventilation
T3/4 on CNS
Increase DNS activity
Mental state: hyper- anxiety, nervous, hypo- sluggish
T3/4 on skeletal
Increased growth plate chondrocytes and osteoblasts
Increase osteoclast activity (in thyrotoxicosis –> osteoporosis)
T3/4 on reproductive
Thickens endometrium in females
Hypo associated with infertility
T3/4 on Development
Potentiates growth
Potentiates foetal and neonatal brain development
Hypothyroidism
High TSH
Low T4
Treated hypothyroidism or subclinical hypo
High TSH
Negligible T4
TSH secreting tumour or thyroid hormone resistance
High TSH
High T4
Slow conversion of T4 to T3 (deiodinase deficiency; euthyroid hyperthyroxinaemia) or thyroid hormone antibody artefact
Low TSH
High T4
Low T3
Hyperthyroidism
Low TSH
High T4 or 3
Subclinical hyperthyroidism
Low TSH
Negligible T4 and 3
Central hypothyroidism
Low TSH
Low T4
Sick euthyroidism or pituitary disease
Low TSH
Low T4 and 3
Toxic adenoma
Solitary focal, diffuse hyperplasia of follicular cells
Secrete thyroid hormones
Toxic multinodular goitre
Most common cause of thyrotoxicosis in iodine-deficient areas
Also seen in elderly patients
Nodules secrete excess thyroid hormones
Thyroiditis
Hormone synthesis not increase but instead destruction of thyroid follicular cells–> transient increase in thyroid hormones –> once they are ‘exhausted’ the patient becomes hypothyroid
Thyroid cysts
Benign solitary nodule that creates pressure symptoms
May be painful if bleedsd
Hyperthyroidism in pregnancy
Increase in thyroid hormones- may trigger Graves
1st half- aggravated
2nd half- ameliorated
Postpartum- recurrence
Subclinical Hyperthyroidism
Normal T3 and T4 but suppressed TSH
Increases risk of AG
Endogenous causes – toxic adenoma, multinodular goitre
Exogenous causes – levothyroxine
Thyroid hormone resistance
Mutation in receptor at pituitary- rise in T3 + 4 fails to suppress TSH
Differential- TSHoma
MNG relapse
Patients with MNG always relapse
Hyperthyroidism Management complications
HF Angina AF Osteoporosis Ophthalmopathy Gynaecomastia Thyroid Storm
Thyroid storm
Rare but life-threatening complication of thyrotoxicosis
It is typically seen in patients with established thyrotoxicosis and is rarely seen as the presenting feature
Thyroid storm precipitants
Recent thyroid surgery or radioiodine therapy
Infection
MI
Trauma
Thyroid storm presentation
Severe hyperthyroidism Fever Agitation Confusion Coma Tachycardia AF D+V Goitre Thyroid Bruit Acute abdomen HF
Thyroid storm treatment
symptomatic treatment e.g. paracetamol
treatment of underlying precipitating event
beta-blockers: typically IV propranolol
Anti-thyroid drughs- carbimazole 15-25mg/6h PO + after 4h give Lugol’s iodine solution 0.3ml/8h PO to block thyroid
Dexamethasone - 15-25mg/6h PO- blocks the conversion of T4 to T3
Treat infection if suspected- co-amoxiclav
Thyroid storm treatment aim
Counteract peripheral effects of thyroid hormones
Inhibit thyroid hormone synthesis
Treat systemic complications
Thyroid storm Treatment continuation
After 5 days reduce carbimazole to 15mg/8h PO
After 10 days stop propranolol + Lugol’s iodine and adjust carbimazole
If no significant progress in 24hr, thyroidectomy
Thyroid carcinoma- Papillary
70% Associated with radiation Young ppl (20-40) Females Follicular cell origin Ig Tumour markers Spreads- lymphatics, sometimes lung/bone mets Total thyroidectomy + node excision + radioiodine Prognosis- good, especially in young
Thyroid carcinoma- Follicular
20% More common females (3:1) 40-60 Origin- follicular cells Ig Tumour markers Spread- haematogenous to lung/bone Treatment- total thyroidectomy + T4 suppression + radioiodine Prognosis- good if resectable
Thyroid carcinoma- Medullary
5% 30% familial (MEN2) Affects young men 40-50 Origin- parafollicular cells Tumour markers- CEA + calcitonin Spread- local + metastases Treatment- thyroidectomy, node clearance +/- radioiodine Prognosis- poor, but indolent course
Thyroid carcinoma- Anaplastic
<5%
Women (3:1), >60yrs
Rapid + aggressive growth + spread
Origin- undifferentiated follicular cells
Spread- locally invasive
Treatment- palliative- can try thyroidectomy +/- radioiodine
V poor prognosis
Thyroid carcinoma- Lymphoma
2%
In situ autoimmune thyroiditis or systemic lymphoma
Origin- lymphocytes
Treatment- chemo + radio
Non-thyroid neck swelling
Thyroglossal cyst Branchial cyst Lymphadenopathy Pharyngeal pouch Dermoid cyst Lipoma Fibroma Salivary gland swelling Vascular- carotid body tumour or aneurysm
Diffuse Goitre
Uniform overall enlargement
Simple euthyroid goitre- pregnancy, puberty
Autoimmune thyroid disease- firm diffuse goitre seen in Hashimoto + Grave
Thyroiditis- acute pain + tenderness in De Quervain’s
Nodular goitre
Occurs after loss of thyroid structure
Certain areas fibrosed + underactive
MNG
Solitary node- rule out malignancy, normally benign
Malignant goitre
Adenomas/carcinomas felt as lump
Iodine deficiency + goitre
Low iodine –> hypothyroidism –> increased TSH –> growth of gland forming diffuse goitre –> some areas fibrose –> multinodular toxic goitre –> hyperthyroidism
Iodine excess + goitre
high iodine (amiodarone, class 3 antiarrhythmic) –> destructive thyroiditis –> T4 and 3 release –> hyperthyroidism –> may become hypo after few months due to depletion + inhibition of deiodinase by drug
Hypothyroidism epidemiology
More common than hyper
More common women (6:1)
Excellent prognosis if treated
Untreated –> Heart disease, dementia etc
Primary atrophic hypothyroidism
Diffuse lymphocytic infiltration of thyroid –> atrophy (no goitre)
Hashitoxicosis
Rare initial period of hyperthyroid in hashimoto’s thyroiditis
Secondary hypothyroidism
Not enough TSH due to hypopituitarism
Hypothyroidism signs- BRADYCARDIC
Bradycardia Reflexes relax slowly Ataxia Dry thin hair/skin Yawning/drowsy/coma Cold Ascites +/- pitting oedema +/- pericardial or pleural effusion Round puffy face/double chin/obese Defeated demeanour Immobile CCF
Hypothyroidism associations
Autoimmune- T1DM, Addisons, primary aldosteronism, primary biliary cholangitis Turners and Downs CF Ovarian hyperstimulation POEMS syndrome Genetic
Myxoedema coma- precipitants
Infection MI Stroke Trauma Thyroidectomy Radioiodine Pituitary surgery
Myxoedema coma presentation
Looks hypothyroid Often >65 Hypothermia Hyporeflexia Decreased glucose Bradycardia Psychosis Coma Seizures
Myxoedema coma exam
Goitre Cyanosis Hypotension CCF Sign of precipitants
Myxoedema coma treatment
Bloods ABG for PaO2 Correct hypoglycaemia Give T 5-30 microg/12h IV slowly Give hydrocortisone if pituitary hypo suspected Infection- Abx fluid caution for heart Active warming
Hypothyroid treatment young patients
Levothyroxine 50-100 microg/daily PO before breakfast
Review at 12 weeks
Adjust every 6 weeks
Once normal, check TSH yearly
Hypothyroid treatment aim
TSH 0.5-2.5mU/L (lower ½ of RR) and free T4 15-25pmol/L (upper ½ of RR)
Hypothyroid CIs
Enzyme inducer increase levothyroxine metabolism
Iron reduces absorption of levothyroxine, give at least 2 hours apart
Hypothyroid treatment elderly + IHD patients
Start with Levothyroxine 25g/daily PO
Increase dose by 25g/4wks
Take caution as may precipitate angina or MI
hypo + pregnancy treatment
increase in dose of 25-50microg is often needed to maintain normal TSH levels
Levothyroxine SEs
Hyperthyroidism
Decreased bone mineral density
Worsening angina
AF
