thyroid diseases Flashcards
what are the commonest endocrine disorders
thyroid disorders
prevalence of hyperthyroidism
2.5%
prevalence of hypothyroidism
5%
prevalence of goitre
5 - 15%
examples of thyroid autoimmunity
- focal thyroditis and/or positive TPO and thyroglobulin antibodies
- post partum thyroidits
- auto immune hypothyroidism
- graves’ disease
why are autoimmune thyroid diseases important
they are the first auto immune diseases to be described
they are associated with other serious autoimmune disorders
which antibodies are found in almost all patients with autoimmune hypothyroidism
thyroglobulin and thyroid peroxidase (TPO) antibodies
do healthy patients have thyroid autoantibodies
low levels are present in healthy individuals who are at risk of thyroid or other autoimmune disease
mechanism of thyroid cell destruction
cytotoxic t cell cd8+ mediated
thyroglobulin and TPO antibodies may case secondary damage, but have no effect alone
uncommonly - antibodies against the TSH receptor may block the effects of TSH
nomenclature of TSH receptor (TSH-R) antibodies
originally called long acting thyroid stimulates - LATS
now called thyroid stimulating antibodies
what causes graves’ disease
thyroid stimulating antibodies
can TSH-R antibodies cause hypothyroidism
Some TSH-R antibodies do not stimulate the receptor; instead they block the effects of TSH - these (rarely) can cause hypothyroidism
biggest risk fasvtor to thyroid autoimmunity
being female
onset o disease is common postpartum
which gene contribute to thyroid autoimmunity
HLA-DR3 and other immunoregulatory genes contribute (25% monozygotic twins concordant)
environmental factors that cause thyroid autoimmunity
stress, high iodine intake, smoking
some examples of autoimmune diseases associated with thyroid autoimmunity
• Type 1 diabetes mellitus
• Addison’s disease
• Vitiligo
• Alopecia areata
• Coeliac disease/ dermatitis herpetiformis
• Chronic active hepatitis
• Rheumatoid arthritis/ SLE/ Sjogren’s syndrome
• Myasthenia gravis (Graves’ disease)
where is thyroid associated opthalmopathy present
in most Graves and some autoimmune hypothyroidism patients
what is thyroid associated opthalmopathy
swelling in extraocular muscles
what causes thyroid associated opthalmopathy
Most likely due to an autoantigen in the extraocular muscle that cross reacts with, or is identical to, a thyroid autoantigen
what is GOITRE
palpable and visible thyroid enlargement
causes of GOITRE
variety
commonly sporadic or autoimmune
where is GOITRE endemic
in iodine deficient area
what is the commonest endocrine disorder (specific)
sporadic non toxic goitre
8.6% prevalence thyroid enlargement
define hyperthyroidism
excess of thyroid hormones in bloo
what are the 3 mechanisms of hyperthyroidism
a. overproduction thyroid hormone
b. leakage of preformed hormone from
thyroid
c. ingestion of excess thyroid hormone
3 common causes of hyperthyroidism
Graves’ disease (75- 80% of all cases)
Toxic multinodular goitre
Toxic adenoma
what can cause drug induced hyperthyroidism
• Iodine
• Amiodarone
• Lithium ?
• Radiocontrast agents
clinical features of hyperthyroidism
• Weight loss
• Tachycardia
• Hyperphagia
• Anxiety
• Tremor
• Heat intolerance
• Sweating
• Diarrhoea
• Lid lag + stare
• Menstrual disturbance
specific signs for grave disease
Diffuse goitre
Thyroid eye disease (infiltrative)
Pretibial myxoedema Acropachy
MNG specific signs
multinodular goitre
adenoma specific signs
solitary nodule
how to confirm biochemical hyperthyroidism
thyroid function tests
diagnosis of underlying cause - because treatment varies
are physical signs sufficient for diagnosis of hyperthyroidism.
yes
results of thyroid funciton tests for primary hyperthyroidism
increase in free t4
increase in free T3
suppresssed TSH
results of thyroid function tests in secondary hyperthyroidism
increased free T4
increased free T3
inappropriately high TSH
supporting investigations for hyperthyroidism
thyroid antibodies: TPO, Th, TRAb
isotope uptake scan
treatment for hyperthyroidism
- anti thyroid drugs (course or long term)
- radioidione 131I
- surgery (partial, subtotal thyroidectomy)
what are anti thyroid drugs
thionamides
decrease synthesis of new thyroid hormone
but do not treat underlying cause of hyperthyroidism
benefits of anti thyroid drug
immune modifying effects are seen (decrease IL6) and reduction in antibody titres
what are the regimens for thionamides
titration regimen: 12 - 18 months
block and replace regimen with T4: 6 - 12 months for graves’ disease
OR
short course to render euthyroid before 131I and surgery
OR
long-term treatment in patients unwilling to have131I or surgery
remission rates for anti thyroid drugs
30-50%
what are poor prognosis factors for anti thyroid drugs ie who is more likely to relapse
- severe biochemical hyperthyroidism
- large goitre
TRAb +ve at end of course of ATD - male sex
- young age of disease onset
side effects of thionamides
Common side effect:
- rash
• Less common:
- arthralgia
- hepatitis
- neuritis
- thrombocytopenia
- vasculitis
most serious side effects of thionamides
agranulocytosis
manifests as sore throat, fever, mouth ulcers
what is essential for thyroid hormone production
iodine
how is iodine transported
• I actively transported by Na/I symporter into thyroid follicular cells
what is 131i
• One of 20 isotopes of I (127I stable)
• Ideal for ablation
• Emits large B particles of moderate energy
• B particles non penetrating and deliver 90% of energy within a 1-2 mm zone to follicular cells
• Some gamma ray emission
• Half-life 8.1 days
how does 131I work
• Emission of B particles results in ionization of thyroid cells
• Direct damage to DNA and enzymes
• Indirect damage via free radicals
early effects of 131I
necrosis follicular cells
vascular occlusion
occur over weeks to months
long term effects of 131I
• shorter cell survival
• impaired replication cells
• atrophy and fibrosis
• chronic inflammation resembling Hashimoto’
• late hypothyroidism
what surgery for graves’ disease and MNG
near total thyroidectomy
what surgery for toxic adenoma
near total thyrodiuectomy/ love to my
define hypothyroidism
thyroid hormones levels abnormally low
3 types of hypothyroidism
primary
secondary
tertiary
what is primary hypothyroidism
- absence / dysfunction thyroid gland
1 - most cases due to Hashimoto’s thyroiditis
what is secondary/tertiary hypothyroidism
pituitary / hypothalamic dysfunction
causes of primary hypothyroidism
Hashimoto’s thyroiditis
131I therapy Thyroidectomy
Postpartum thyroiditis
Drugs
Thyroiditides
Iodine deficiency
Thyroid hormone resistance
causes of secondary/tertiary hypothyroidism
pituitary disease
hypothalamic disease
what’s drugs cause hypothyroidism
Iodine, inorganic or organic iodide
iodinated contrast agents amiodarone
Lithium
Thionamides
Interferon - a
causes of hypothyroidism in kids
Neonatal hypothyroidism
- Thyroid agenesis
- Thyroid ectopia
- Thyroid dyshormonogenesis
- Others
Resistance to thyroid hormone
Isolated TSH deficiency
clinical features of hypothyroidism
• Fatigue
• Wt gain
• Cold intolerance
• Constipation
• Menstrual disturbance
• Muscle cramps
• Slow cerebration
• Dry, rough skin
• Periorbital oedema
• Delayed muscle reflexes
• Carotenaemia • Oedema
describe thyroid levels in primary hypothyroidism investigation
increase TSH - most sensitive market
usually decreased free T4 and T3
T4/T3 may be low normal in mild hypothyroidism
positive titre of tpo antibodies in hashimotos
describe thyroid levels in secondary hypothyroidism investigation
TSH inapppuatelyt low for reduced T3/T4 levels
treatment for hypothyroidism
• Treatment of choice synthetic L-thyroxine (T4)
• Older treatments - dessicated thyroid (pig and beef extracts) - inconsistent from batch to batch
• ? T3 / T4 combination
• young adults - usual full replacement of
100 ig ugly ug
how to monitor treatment in primary hypothyrisum
dose titrated until TSH normalises
T4 half-life is long - check levels 6-8 weeks after dose adjustment
how to monitor treatment in secondary/tertiary hypothyroidism
TSH will always be low
T4 is monitored
are TPO and thyroglobulin antibodies specific
no they are sensitive but not specific
what causes graves’ disease
thyroid stimulating antibodies that may cross the placenta
