end2.10 - thyroid miscellany dr ss nussey © s nussey and ios
TRANSCRIPT
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END2.10 - Thyroid miscellany
Dr SS Nussey
© S Nussey and ios
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Thyroid hormone transport
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Thyroid hormonemetabolism
Box 3.29
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Thyroidhormoneassay
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TSHAssay
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Implications
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Thyroid hormone assay - potential problems
• Protein-tracer interactions e.g. immunoglobulins (IgG)
• Dilution effects and protein dependence• Substances competing with T4 for binding to
binding proteins or IgGs e.g. fatty acids• As a result the TSH assay is more robust in
many clinical situations (though more expensive)• Population screening?
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Non-thyroid illness
aka
‘Sick euthyroid syndrome’
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Drugs and the thyroidgland
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Clinical implications of non-thyroid illness
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Amiodarone and the thyroid
• Effects:– Source of iodine
– Thyroid cytotoxic
– Inhibitor of type 1 and 2 deiodinases
– Antagonise thyroid hormone action
• Clinically, may cause hypo- or hyper-thyroidism
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(‘Non-autoimmune’) Thyroiditis
• Includes - sporadic (silent); subacute (DeQuervain’s); post-partum; fibrous (Riedel’s)
• Genetic, clinical, histopathological differences
• Clinical course of transient thyrotoxicosis, hypothyroidism and then recovery
• Investigations show - elevated serum thyroid hormones, suppressed TSH, reduced 99mTc uptake and elevated Tg + elevated ESR
• Treatment
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Subclinical hyperthyroidism
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TSH assays
• Limits of detection– First generation - 1.0mU/l– Second generation - 0.1mU/l– Third generation - 0.01mU/l– Fourth generation - 0.001mU/l
• Normal range - 0.4-4mU/l
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Definition
‘Sustained thyrotrophin concentration <0.01mU/l with normal concentrations of free thyroxine and tri-iodothyronine in the absence of hypothalamo-pituitary dysfunction or non-thyroidal illness’
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Prevalence
• Large scale community studies - 2-16%
• Increases with: age, being female and nodular thyroid disease
• Most common cause - thyroid hormone replacement (~20-40%)
• In those not due to thyroid hormone treatment, progression to clinical hyperthyroidism is infrequent
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Effects
Lancet 2001, 358:861
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Circulatory disease
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Atrial fibrillation
Original Framingham cohort of 2007.Age >60Excluded those taking thyroxine or treated thyroid diseaseTSH assay - Low (<0.1mU/l), ‘Slightly low’ (0.1-0.4mU/l), Normal (0.4-5mU/l), High (>5mU/l)
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Atrial fibrillation
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Implications• Assuming that treatment prevents AF, 4.2 cases
would need to be treated to prevent 1 case of AF.
• Note:– there is only limited evidence that AF reverts
spontaneously or after DCC once the TSH has been normalised
– ranges of embolism in thyrotoxic AF - ‘negligible’ to 40% (mean 10-15%) - is the risk the same?
– no (clinical trial) evidence for efficacy of warfarin
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Bone density
• Clinical hyperthyroidism is known factor in osteoporosis
• Effects of subclinical hyperthyroidism are uncertain
• Needs longitudinal study
J Clin Endocrinol Metab 1996, 81:4278
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Subclinical hypothyroidism
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Definition
‘Sustained thyrotrophin concentration >4 mU/l with normal concentrations of free thyroxine and tri-iodothyronine in the absence of symptoms and signs of hypothyroidism’
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Prevalence
• Large scale community studies - 5-10%
• Increases with: age, being female and in areas of higher iodine intake
• Causes as for clinical hypothyroidism
• Progression to clinical hyperthyroidism is high (~5% per annum)
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Causes of hypothyroidism
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Implications
NB - Cross-sectional study- Previous smaller studies had failed to show an effect
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Treatment
BMJ 2001,323: 891
• Treatment in subclinical hypothyroidism:– reduces goitre by ~80%
– improves memory and wellbeing
– reduces total and HDL cholesterol slightly
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‘Hot topic’
Lancet 2001, 2034
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Background
• Thyroid diseases are more common in females and may be exacerbated by pregnancy
• Are these auto-immune or allo-immune i.e. graft-versus-host?
• In women with scleroderma there is an increase in male cells in the skin (presumably from fetal transfer)
• Is there a similar increase in male cells in the thyroid glands of women with thyroid disease?
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Methods
• Archival thyroid gland pathological paraffin sections 29 patients; controls from 8 necropsies
• FISH - X - red signal; Y - green signal
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Results
• Cells with both X and Y seen in 16 of 29 thyroid patients but none of controls
• 12 of 20 (63%) patients with at least one male child had male cells in the thyroid
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Origin of male cells in female thyroid
• Male stem cells from fetal-maternal transfusion during pregnancy, labour, delivery.
• Male stem cells from a twin gestation, organ transplant or blood transfusion
• Artefact