Hypothyroidism Flashcards
What are the TFT patterns in primary hypothyroidism?
=Increased TSH
=FT4 decreased
=TT3 decreased or normal
What is the epidemiology of primary hypothyroidism?
0.3-2% women and <0.15% men
More common as we get older
What are the symptoms of hypothyroidism?
- Tired (lethargic)
- Weight gain, puffy eyes and skin
- Feeling cold
- Slow heart rate
- Constipation
- Dry hair and skin
- Heavy periods (menorrhagia)
- Hyperlipidaemia
- (Enlarged thyroid = goitre, high TSH so stimulation of thyroid)
What are the common causes of primary hypothyroidism (90%)?
-Hashimoto’s thyroiditis
=Antibodies (thyroid peroxidase antibodies) attack thyroid and make it underactive
=Permanent
=Tendency can run in families
-Iatrogenic (post surgery or radioactive iodine)
-Spontaneous atrophic
What are the other causes of primary hypothyroidism?
-Temporary thyroiditis
=Eg Viral thyroiditis, Postpartum thyroiditis
-Congenital (screening programme, heel prick)
-Iodine deficiency (not UK)
-Drug-induced (e.g lithium)]
What is Derbyshire neck?
- Iodine deficiency
- Cannot manufacture enough thyroid hormone without iodine
- TSH rises in response to fall in T4
- High TSH stimulates hypertrophy (growth) of the thyroid gland
How do the thyroid hormones change throughout the day?
- FT4 usually stable throughout day except low in early morning and rise from 6 to 10 am
- FT3 and TSH dip in afternoon, rises in late evening to peak during the night
Describe thyroid hormone replacement with thyroxine
- Up to 3% of UK population are on thyroid hormone replacement
- The vast majority of patients are treated with (and feel fine on) once daily levothyroxine (T4)
- A small proportion of patients feel considerably less well on levothyroxine than when they had a normally functioning thyroid
How is thyroxine taken and managed?
- Half life levothyroxine approximately 7 days
- Once daily dosing results in stable fT4 and fT3 levels
- Commonly around 100 mcg thyroxine (1.6 mcg/kg/day)
- Taking on empty stomach before breakfast preferable to with breakfast or before bed (best result on TSH)
- Aim to normalise TSH
- Usually managed by GPs
- No further Inx needed for hypothyroidism if TSH increase (scans do not change Mx)
- Large body of evidence on safety and effectiveness of thyroxine
How to we monitor thyroxine therapy?
- Annual TFTs once stable
- If dose change, wait at least 6/52 before rpt TFTs
What over the counter medications and commonly prescribed drugs impair T4 absorption?
- PPIs eg omeprazole/lansoprazole
- H2 antagonists eg ranitidine
- Iron, calcium, aluminium
- Don’t take T4 <4h after these
-Increased T4 requirement if start oestrogen (OCP, HRT) (as less thyroid hormone available for use) or anticonvulsants- activate liver enzymes so faster metabolism of hormone
Are there other ways of treating hypothyroidism other than levothyroxine?
- Current alternatives do not have strong evidence of greater effectiveness (eg combination T3/T4, desiccated thyroid extract)
- T3 (liothyronine) peaks at 2 – 4 hours and has a half-life of 1 day
- At least 3x daily dosing is required to achieve stable levels
- Concerns around effects of rapid peaks of highly active thyroid hormone
- What dose? What ratio of T3:T4?
- Difficult to achieve ‘blinding’ in studies
Describe DTE
- DTE, “Natural thyroid”, Armour thyroid, Dessicated Thyroid Extract
- Contains T3 and T4
- Human thyroid T4:T3 is 14:1
- One ‘grain’ (60mg) contains 38μg T4 and 9μg T3 (4:1 ratio)
- Pork thyroid extract is clearly not natural for humans
- Pig thyroid extract contains other substances beyond T3 and T4
Compare DTE with levothyroxine
- A short-term study (16 weeks) compared DTE with levothyroxine
48. 6% preferred DTE, 18.6% preferred levothyroxine and 32.9% expressed no preference - DTE group was 3lb lighter but HDL (“good”) cholesterol was worse. No other clinically significant differences between groups
- No long-term studies so safety has not been established
- Potential placebo effect.
How does genetics contribute to hypothyroidism?
- Hypothyroid patients with less active deiodinase 2 had slightly better response to combination T3 and T4 than T4 alone
- In the future, genetic markers may help guide therapy
- Overall, levothyroxine considered adequate for most patients
What are the TFT patterns in subclinical/compensated hypothyroidism?
- Increased TSH (more sensitive marker of thyroid function than T4 as earliest change)
- Normal FT4, TT3
Describe subclinical hypothyroidism
- Prevalence 4-10%
- Main cause is autoimmune chronic thyroiditis (early stages of hashimoto’s)
- No convincing evidence that it causes symptoms
- However, TFTs often checked because of symptoms that MAY relate to thyroid so patients often convinced that the two are linked
What are the adverse effects of subclinical hypothyroidism?
- Lipids increase
- BP increase
- Other CV risks eg CRP, arterial stiffness
- No hard end-points evidence (ie no evidence that it increases heart attacks or strokes)
Describe the results of the Whickham study
- Prevalence and incidence much higher in women than in men
- More common with increasing age
- Risk factors= persistently raised TSGH, thyroid peroxidase antibodies
=Treat if TSH >10 on 2 occasions and/or if TPOs strongly positive
What are the TFT patterns in secondary hypothyroidism?
- Decreased T3 and T4
- Low/ normal TSH
Describe secondary hypothyroidism
- In pituitary disease TSH is low or (inappropriately) normal
- In hypopituitarism, adequate replacement with thyroxine is judged by fT4 levels
- Dx of primary hypothyroidism should be made only if TSH is high
What is NTI (non-thyroidal illness)
- All thyroidal hormones low/ decreased
- Impact on thyroid hormone metabolism
What patterns can be identified in NTI?
- TSH: can be suppressed acutely then rise on recovery.
- tT3 falls (impaired T4 hepatic uptake and T4 to T3 conversion).
- Illnesses affects thyroid hormone binding proteins, which reduces total hormone and raises free hormone fraction.
- fT4 usually stays within reference range or is modestly raised.
- Severity and duration of illness often correlated with the degree of abnormality observed in TFTs.
- Low T3 found in NTI may be an adaptive response (diminish basal metabolic rate; conserve essential -body protein stores).
What are the mechanisms of NTI?
-TSH: can be suppressed in acute phase of severe illness by range of mechanisms then rise on recovery until normal thyroid hormone concentrations are restored. =IL-1 =TNFa =Glucocorticoids (cortisol) =Dopamine =low TRH =TETRAC =TRIAC =Somatostatin
