Hyperthyroidism, Hypothyroidism/Thyroiditis Flashcards
primary thyroid disease
-Disease affecting thyroid gland itself
-Can occur with goitre (goitrous) or without (non-goitrous)
-Autoimmune thyroid disease most commonly
Secondary thyroid disease
-Hypothalamic or pituitary disease
-No thyroid gland pathology
Measuring thyroid hormones (7)
Thyroid stimulating hormone (TSH)
-Also called thyrotropin
-Released by thyrotroph cells in anterior pituitary in response to thyrotropin releasing hormone (TRH)
-Reflects tissue thyroid hormone action
Free T4 (~80% of thyroid hormone secreted)
Free T3 (remaining 20%)
~99% of T4 and T3 bound to plasma proteins (TBG, albumin and pre-albumin)
primary hyperthyroidism (4)
Primary (over-reactive thyroid gland):
thyroid overreactive, produces more T3 and T4 → negative feedback signals sent to pituitary → decreased TSH produced, increased T3/4
Free T3/4 high
TSH low
secondary hyperthyroidism (4)
Secondary
(excessive stimulation of thyroid gland by TSH):
elevated TSH stimulating thyroid due to abnormality in feedback loop →
increased TSH, inc or normal T3/4
Free T3/4 high
TSH high (or ‘normal’)
Hyperthyroidism
conditions in which overactivity of the thyroid gland leads to thyrotoxicosis
Thyrotoxicosis
clinical, physiological and biochemical state arising when the tissues are exposed to excess thyroid hormone
Causes of hyperthyroidism- graves (4)
Graves disease (primary hyperthyroidism) - 85% cases, too much T3 and T4
- Accounts for 85% of cases
- Higher incidence in females - 10:1
- Usually presents between 20-40 years
Causes of hyperthyroidism- genes (4)
Genetic factors
- Increased incidence in family members
- associated with certain HLA haplotypes - class II
- Polymorphisms in immune regulation associated genes e.g. CTLA-4, PTPN-22 have also been linked to Graves’ disease
Other causes of thyrotoxicosis associated with hyperthyroidism (8)
Excessive thyroid stimulation
- Hashitoxicosis - transient hyperthyroidism caused by inflammation associated with Hashimoto’s thyroiditis, patient will then develop hypothyroidism
- Thyrotropinoma - TSH secreting pituitary adenoma (very rare)
- Thyroid cancer - only very rarely cause thyrotoxicosis
- Choriocarcinoma - trophoblast tumour secreting hCG
Thyroid nodules
- Toxic solitary nodule
- Toxic multinodular goitre
Causes of thyrotoxicosis not associated with hyperthyroidism (10)
Thyroid inflammation (thyroiditis)
- Subacute (de Quervain’s) thyroiditis
- Post-partum thyroiditis
- Drug-induced thyroiditis (e.g. amiodarone)
Exogenous thyroid hormones
- Over-treatment with levothyroxine
- Thyrotoxicosis factitia
Ectopic thyroid tissue
- Metastatic thyroid carcinoma
- Struma ovarii (teratoma containing thyroid tissue)
Clinical features of hyperthyroidism -general (8)
symps
-Weight loss despite increased appetite
- Frequent, loose bowel movements
- Sweating and heat intolerance
- Goitre - diffuse in Graves, goitre with firm nodules if toxic multinodular goitre
- If goitre is tender and painful → de quervain’s thyroiditis
signs
- Thyroid bruit - associated only with large goitres
- Reflective of hypervascularity of thyroid
- Auscultate over the thyroid
Clinical features of hyperthyroidism-systemic (7)
Eyes
- Double vision
- Graves ophthalmopathy
Cardiovascular
- Increased pulse rate
- Palpitations, AF
- Rarely cardiac failure
Musculoskeletal
- Fine tremor of the outstretched fingers
- Muscle weakness, especially in thighs and upper arms
Neuropsychiatric
- Increased nervousness and excessively emotional
- Sleep disturbance
- Depression
- Insomnia
Hair and skin
- Hair change (thin, brittle hair)
- Rapid fingernail growth
Reproductive
- Menstrual cycle changes, including lighter bleeding and less frequent periods
Thermogenisis
- Intolerance to heat - “do you feel hot compared to others around you?’
Management of hyperthyroidism- B blocker(4)
Mechanism: β-adrenoceptor blockade, reduced activity of sympathetic nervous system
Propranolol is the drug of choice
Use with caution in those with asthma
-Risk of provoking bronchospasm
-CCB (e.g. diltiazem) can be used instead
Useful for immediate symptomatic relief of thyrotoxic symptoms
Treatment of hyperthyroidism – radioiodine (5)
1st choice treatment for relapsed Graves’ disease and nodular thyroid disease
Safe, no increased risk of thyroid cancer
Contraindicated in pregnancy
Relatively contraindicated in active thyroid eye disease (can be used with steroid cover)
High risk of hypothyroidism when used in Graves’ disease
Treatment of hyperthyroidism – thyroidectomy (3)
Useful when radioiodine is contraindicated
Scar
Surgical/anaesthetic risks
-recurrent laryngeal nerve palsy
-Hypothyroidism
-Hypoparathyroidism
Graves’ disease (4)
-(20-50yrs)
-Interacting susceptibility genes (70%) plus environmental factors
-Sisters and children of women with Graves’ have a 5-8% risk of developing autoimmune thyroid disease (Graves’ or autoimmune hypothyroidism)
-Smoking important
Graves’ disease – clinical features triad (3)
Triad:
-hyperthyroidism
-ophlamopathy
-dermopathy
(thyroid eye disease, thyroid acropachy, and pretibial myxoedema)
Graves’ disease – other clinical features
- Pretibial myxoedema (also occasionally seen in Hashimoto’s thyroiditis)
- Thyroid arcropachy - thickening of the extremities manifested by digital clubbing, soft tissue swelling of the hands and feet, and periosteal new bone formation
- Graves eye disease - Exophthalmos
Graves’ disease – laboratory investigations (4)
↓TSH and ↑fT4/3 – cardinal abnormalities
Other abnormalities
-Hypercalcaemia and ↑Alkaline phosphatase
-Leucopenia (↓white cell count)
-TSH receptor antibody (TRAb)
Scintiscan
Graves disease - smooth symmetrical goitre, looks like butterfly
Treatment graves disease (10)
Antithyroid drugs:
- 1st line: carbimazole
- Side effect (carbimazole + PTU !!!): Agranulocytosis- inc infection susceptibility, sore throat
- Mech of action: Inhibits thyroid peroxidase
- If 1st trimester pregnancy: PTU(Propylthiouracil)
- Gradual dose regimen lasts 12-18 months, block and replace regimen takes 6 months
- ~50% relapse rate
Management of Graves’ eye disease
- Mild disease treated topically e.g. lubricants
- More severe disease: steriods, radiotherapy, surgery
Thyroid storm (8)
Medical emergency, so… A,B,C!
Severe hyperthyroidism
Respiratory and cardiac collapse
Hyperthermia
Exaggerated reflexes
May require mechanical ventilation
Typically seen in hyperthyroid patients with an acute infection/illness or recent thyroid surgery
Treatment: Lugol’s Iodine, glucocorticoids, PTU, β-blockers, fluids, monitoring
Thyroiditis
-inflammation of the thyroid
-Hashimoto’s
-De Quervain’s/subacute (viral)
-Post-partum
-Drug-induced (amiodarone, lithium)
-Radiation
-Acute suppurative thyroiditis (bacterial)
Subacute thyroiditis
-Ages 20-50 years
-May be triggered by viral infection
-May be associated with neck tenderness, fever, or other viral symptoms
-Usually self limiting (over a few months)
-Scintigraphy scan – low uptake throughout
Hypothyroidism
results from any disorder that results in insufficient secretion of thyroid hormones from the thyroid gland
Myxoedema
refers to severe hypothyroidism and is a medical emergency
Pretibial myxoedema
rare clinical sign of Graves’ disease, an autoimmune thyroid disease which results in hyperthyroidism
Primary hypothyroidism
Free T3/4 low
TSH high
Increased CK + LDL
Hypoonatraemia
Hyperprolactinaemia
Secondary hypothyroidism
Free T3/4 low
TSH low (or ‘normal’)
Hypothyroidism risk factors
higher in white populations compared to Hispanic or African-American ones
Incidence higher in areas of high iodine intake
Primary causes of hypothyroidism (15)
Goitrous
-Chronic thyroiditis (Hashimoto’s thyroiditis)
-Iodine deficiency
-Drug-induced (e.g. amiodarone, lithium)
-Maternally transmitted (e.g. antithyroid drugs)
-Hereditary biosynthetic defects
Non-goitrous
-Atrophic thyroiditis
-Post-ablative therapy (e.g. radioiodine, surgery)
-Post-radiotherapy (e.g. for lymphoma treatment)
-Congenital developmental defect
Self-limiting
-Following withdrawal of antithyroid drugs
-Subacute thyroiditis with transient hypothyroidism
-Post-partum thyroiditis
Secondary causes of hypothyroidism
Diseases of the hypothalamus and pituitary gland (multiple!)
-Infiltrative
-Infectious
-Malignant
-Traumatic
-Congenital
-Cranial radiotherapy
-Drug-induced…
Autoimmune hypothyroidism (Hashimoto’s thyroiditis) (6)
-Most common cause of hypothyroidism in the Western world
-Autoimmune destruction of thyroid gland and reduced thyroid hormone production
-Often a family history of autoimmune thyroiditis or other autoimmune disorders
-Characterised by=
-Antibodies against thyroid peroxidase (TPO)
-T-cell infiltrate and inflammation microscopically
Clinical features of hypothyroidism (8)
Hair and skin
-Coarse, sparse hair
-Dull, expressionless face
-Periorbital puffiness
-Pale cool skin that feels doughy to touch
-Vitiligo may be present
-Hypercarotenaemia
Thermogenesis
-Cold intolerance
Fluid Retention
-Pitting oedema
Other systems clinical features or hypothyroidism (7)
Metabolic rate
Decreased appetite + Weight gain
GI
Constipation
(Megacolon and intestinal obstruction) + (Ascites)
Respiratory
Deep hoarse voice, Macroglossia + OSA
Cardiac
Reduced heart rate, Cardiac dilatation,
Pericardial effusion + Worsening of HF
Metabolic
Hyperlipidaemia
Neurology/CNS
Gynae/reproductive
Management of hypothyroidism (4)
Normal metabolic rate should be restored gradually
Rapid restoration of metabolic rate may precipitate cardiac arrhythmias
Check TSH 2 months after any dose change
Once stabilised, TSH should be checked every 12-18 months
Younger patients treatment
start levothyroxine at 50-100 μg daily
Elderly patients treatment
with a history of IHD: start levothyroxine at 25-50 μg daily, adjusted every 4 weeks according to response
hypothyroidism pharmalogical management (6)
-Main treatment is levothyroxine (T4)
-No benefit with combination of T4 + T3
-T4 preferably taken before breakfast
-T3 therapy is rarely used: 20μg T3 = 100μg T4
-T3 effects develop within a few hours and disappear within 24-48 hours of discontinuation
-Dose requirements may increase by 25-50% in pregnancy (↑TBG
Myxoedema coma
affects elderly women with long standing but frequently unrecognized or untreated hypothyroidism
Mortality up to 60% despite early diagnosis and treatment
Myxoedema coma findings (3)
ECG: bradycardia, low voltage complexes, varying degrees of heart block, T wave inversion, prolongation of the QT interval
Type 2 respiratory failure: hypoxia, hypercarbia, respiratory acidosis
Co-existing adrenal failure is present in 10% of patients
Myxoedema coma treat (6)
Intensive care, remember – A, B, C!
Passively rewarm: aim for a slow rise in body temperature
Cardiac monitoring for arrhythmias
Close monitoring of urine output, fluid balance, central venous pressure, blood sugars, oxygenation
Broad spectrum antibiotics
Thyroxine cautiously (hydrocortisone)
