END2.10 - Thyroid miscellany

Dr SS Nussey

© S Nussey and ios

Thyroid hormone transport

Thyroid hormonemetabolism

Box 3.29

Thyroidhormoneassay

TSHAssay

Implications

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?

Non-thyroid illness

aka

‘Sick euthyroid syndrome’

Drugs and the thyroidgland

Clinical implications of non-thyroid illness

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

(‘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

Subclinical hyperthyroidism

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

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’

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

Effects

Lancet 2001, 358:861

Circulatory disease

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)

Atrial fibrillation

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

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

Subclinical hypothyroidism

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’

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)

Causes of hypothyroidism

Implications

NB - Cross-sectional study- Previous smaller studies had failed to show an effect

Treatment

BMJ 2001,323: 891

• Treatment in subclinical hypothyroidism:– reduces goitre by ~80%

– improves memory and wellbeing

– reduces total and HDL cholesterol slightly

‘Hot topic’

Lancet 2001, 2034

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?

Methods

• Archival thyroid gland pathological paraffin sections 29 patients; controls from 8 necropsies

• FISH - X - red signal; Y - green signal

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

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