Hypothyroidism

Question 1

What are the TFT patterns in primary hypothyroidism?

Answer 1

=Increased TSH
=FT4 decreased
=TT3 decreased or normal

Question 2

What is the epidemiology of primary hypothyroidism?

Answer 2

0.3-2% women and <0.15% men

More common as we get older

Question 3

What are the symptoms of hypothyroidism?

Answer 3

• 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)

Question 4

What are the common causes of primary hypothyroidism (90%)?

Answer 4

-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

Question 5

What are the other causes of primary hypothyroidism?

Answer 5

-Temporary thyroiditis
=Eg Viral thyroiditis, Postpartum thyroiditis
-Congenital (screening programme, heel prick)
-Iodine deficiency (not UK)
-Drug-induced (e.g lithium)]

Question 6

What is Derbyshire neck?

Answer 6

• 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

Question 7

How do the thyroid hormones change throughout the day?

Answer 7

• 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

Question 8

Describe thyroid hormone replacement with thyroxine

Answer 8

• 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

Question 9

How is thyroxine taken and managed?

Answer 9

• 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

Question 10

How to we monitor thyroxine therapy?

Answer 10

• Annual TFTs once stable

- If dose change, wait at least 6/52 before rpt TFTs

Question 11

What over the counter medications and commonly prescribed drugs impair T4 absorption?

Answer 11

• 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

Question 12

Are there other ways of treating hypothyroidism other than levothyroxine?

Answer 12

• 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

Question 13

Describe DTE

Answer 13

• 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

Question 14

Compare DTE with levothyroxine

Answer 14

• 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.

Question 15

How does genetics contribute to hypothyroidism?

Answer 15

• 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

Question 16

What are the TFT patterns in subclinical/compensated hypothyroidism?

Answer 16

• Increased TSH (more sensitive marker of thyroid function than T4 as earliest change)
• Normal FT4, TT3

Question 17

Describe subclinical hypothyroidism

Answer 17

• 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

Question 18

What are the adverse effects of subclinical hypothyroidism?

Answer 18

• 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)

Question 19

Describe the results of the Whickham study

Answer 19

• 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

Question 20

What are the TFT patterns in secondary hypothyroidism?

Answer 20

• Decreased T3 and T4

- Low/ normal TSH

Question 21

Describe secondary hypothyroidism

Answer 21

• 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

Question 22

What is NTI (non-thyroidal illness)

Answer 22

• All thyroidal hormones low/ decreased

- Impact on thyroid hormone metabolism

Question 23

What patterns can be identified in NTI?

Answer 23

• 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).

Question 24

What are the mechanisms of NTI?

Answer 24

-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

Question 25

How is TSH affected by carbohydrate residues?

Answer 25

Carbohydrate residues on TSH dictate its biological activity and plasma half-life. In NTI, the carbohydrate moieties on TSH are modified, leading to diminished bioactivity.

Question 26

How are deiodinases affected by illness?

Answer 26

Conversion of T3 to T4 by deiodinases is impaired in NTI so T3 levels fall. Deiodinases may be affected by oxidative stress, altered redox state of the cell and cytokine release

Question 27

Describe hypothyroidism in pregnancy

Answer 27

- Fetus needs T4 from 4-5/40 - Uses maternal T4 exclusively up to 10/40 and partially thereafter. - T4 requirements can increase by 50% by 20/40 then plateau - Increase T4 dose when pregnancy confirmed - TFTs each trimester =Oestrogen =Foetus requirement

Question 28

What is untreated overt hypothyroidism associated with in pregnancy?

Answer 28

- Infertility, miscarriage - Pre-eclampsia, Premature delivery - Increased foetal mortality, impaired neurological development

Question 29

What is mild/ subclinical hypothyroidism associated with in pregnancy?

Answer 29

Neurodevelopmental delays, placental abruption

Question 30

What is checked pre-pregnancy?

Answer 30

Check TFTs pre-pregnancy in autoimmune disease (eg DM), current or PHx/FHx thyroid disease, features of thyroid disease eg Goitre

Question 31

What happens in pregnancy with those with current or previous Grave's disease?

Answer 31

- TRAb checked at antenatal booking and pre-delivery. | - TRAbs can cross placenta and act on the foetal thyroid gland by 20 weeks to cause hyperthyroidism

Question 32

What is Hyperemesis gravidarum?

Answer 32

-Very high HCG – induces transient hyperthyroidism =vomiting =HCG has similar structure to TSH -Symptomatic treatment: no thyroid drugs needed -Sometimes propranolol =Very low TSH, elevated T4 and T3 (as a result of oestrogen)

Question 33

How do we manage hypothyroidism in pregnancy overall?

Answer 33

-Established hypothyroidism =Increase T4 dose by 25 micrograms -Newly diagnosed =Start on 100 micrograms of T4

Question 34

What is Riedel's thyroiditis?

Answer 34

-Chronic thyroiditis caused by dense fibrosis (fibroblasts), IgG4 mediated =elevated thyroid antibodies, ultrasound and fine needle aspiration fibrosis =Treat with levothyroxine and corticosteroids