hypothyroidism

Introduction

hypothyroidism is a common chronic condition with an incidence of 3.5/1000 women and 0.6/1000 men.
subclinical hypothyroidism is detected in 4–8% of the general population and in up to 15–18% of women aged more than 60 years. 4–18% of patients will progress to overt hypothyroidism each year.
prevalence increases with age
finding high TSH levels in a symptomatic patient confirms the diagnosis and a cause is readily found.
lifelong thyroxine Rx relieves symptoms and restores “normal” thyroid hormone function.
commencing thyroxine can aggravate cardiac disease

Aetiology

endemic iodine deficiency is the most common cause worldwide
- interestingly, white people caused endemic cretinism affecting 15% of children in Papua New Guinea from the 1950's onwards when they supplied salt to the locals which saved them a 2 day trek to get their usual iodine-rich salt from salt pools. See Life in the fast lane blog on this story
- endemic cretinism results from maternal hypothyroidism as the early fetus cannot make its own T4, and affects development of the fetus throughout its development, especially brain development.
autoimmune thyroid disease
- in Australia and other iodine replete countries, autoimmune chronic lymphocytic thyroiditis (eg. Hashimoto's, and atrophic thyroiditis) is the most common aetiology
- may also have other auto-immune features such as vitiligo
thyroidectomy
radiotherapy (radio-iodine or external beam radiotherapy)
drug-induced
- lithium carbonate
  - lithium is taken up and concentrated by the thyroid, and like iodine, inhibits release of T4 resulting in a compensatory increase in TSH but usually euthyroid clinical status, however, many develop a goitre over time and those predisposed may develop clinical hypothyroidism.
  - acute lithium toxicity with its slow elimination of lithium, may precipitate hypothyroidism
- iodine-containing preparations
- amiodarone
  - amiodarone inhibits the peripheral conversion of T4 to T3, effectively reducing the amount of active hormone
  - it also inhibits uptake of thyroid hormone by cells, so measured levels may increase but tissue effects decrease
  - it is directly cytotoxic to follicular cells inducing thyroiditis, and it transiently increases TSH
  - net effect is that 20% on long term Rx develop hypothyroidism while 3% develop hyperthyroidism, though most cases are mild.
congenital hypothyroidism
- congenital hypothyroidism differs from endemic cretinism in that as it is caused by failure of the fetus to produce its own thyroid hormones in mid-late gestation, brain development in early gestation is not affected as this is dependent on maternal thyroid hormones.
disorders of thyroid hormone metabolism
secondary hypothyroidism due to some pituitary and hypothalamic diseases
long work hours
- study showed those who worked between 52 and 83 hours per week, the prevalence of hypothyroidism was more than double that among people who worked a 36- to 42- hour week, at 3.5% versus 1.4% ¹⁾
night shift work may increase risk of subclinical hypothyroidism²⁾
transient causes:
- subacute thyroiditis - generally have an enlarged, tender thyroid
- silent thyroiditis
- postpartum thyroiditis
- early post-ablative therapy

main clinical features of hypothyroidism

myxoedema refers to the thickened, non-pitting, oedematous skin and subcutaneous tissues seen in most patients with advanced hypothyroidism.
commonly, myxedema is used to refer to the clinical picture of hypothyroidism:
- lethargy, weakness, thinning hair, cold intolerance, weight gain, constipation, depression, hypothermia, delayed deep tendon reflexes, waxy, non-pitting oedema, pleural or pericardial effusions, husky voice, periorbital oedema, and bradycardia.
- neuropsychiatric dysfunction is common in overt hypothyroidism, and will improve over 6 months of therapy (although perhaps not completely resolve)
  - brain structure and function are altered in hypothyroid patients, with decreased hippocampal volume, cerebral blood flow, and function globally and in regions that mediate attention, visuospatial processing, working memory, and motor speed
  - fatigue, decreased feeling of quality of life, subtle defects of memory and executive function may occur even in subclinical disease ³⁾
  - slowing of thought and speech, decreased attentiveness, and apathy
  - rarely, severely hypothyroid patients present with agitation and frank psychosis (“myxedema madness”)
  - Overt hypothyroidism can affect a range of cognitive domains:
    - Memory is the most consistently affected domain with specific deficits in verbal memory
myxoedema coma is the most extreme form and is often precipitated by an acute stress such as anaesthesia, cardiac failure, stroke, or unusual cold exposure, and has a 50-70% mortality.
one should have a high suspicion of hypothyroidism in a patient aged > 55 years with altered mental state who is cold and has non-pitting oedema.

diagnosis of hypothyroidism

persistently high TSH with low free T4 suggest primary hypothyroidism
- free T3 levels don't add much
persistently high TSH (usually to 5-10IU/L) with normal free T4 suggest subclinical primary hypothyroidism and typical symptoms may be absent.
low free T4 without elevated TSH levels suggest secondary hypothyroidism due to pituitary disorders
low free T3 without elevated TSH levels has been called Low T3 syndrome
- usually also have higher levels of a hormone known as reverse T3
- appears to be present in less than 20% of CFS and it might play a role in worsening conditions like kidney disease or serious infections
if cause is not obvious then:
- high titres of antithyroid antibodies (thyroid peroxidase, antimicrosomal, or antithyroglobulin) indicate an autoimmune cause

Thyroxine Rx

half life 7-10 days but a much longer biological effect
once daily dosing
dose is dependent on body weight and age
children require larger doses per kg than adults who usually require 1.6 microgram/kg/day
most adults will maintain euthyroidism on 100-200 microgram/day
there may be a decline in thyroxine requirements in the elderly
a BMJ study in 2011 showed fracture risk of 2.5 to 3.5x in those over 70yrs taking > 0.044mg/day thyroxine - see also osteoporosis
a month's supply can be kept at room temperature - advice to refrigerate risks deterioration from moisture.

starting Rx

rate of introduction of thyroxine should be determined by duration of hypothyroidism & presence or risk of ischaemic heart disease (IHD) or congestive cardiac failure.
healthy adult patients who have undergone thyroidectomy can immediately start at or just below their predicted daily dose of 100-200 microgram.
the very frail and those with symptomatic angina should be started on 12.5 µg/day
other elderly pts and those with known heart disease should start with 25 microgram per day for 3-4 weeks with reassessment and further increments of 25 microgram per day every 3-4weeks as indicated until predicted dose is reached.
- worsening symptoms of cardiac disease should be controlled before increasing dose, and dose reduction may be needed.
other patients can be started on 50 micrograms/day and increase by 50 micrograms/day every 3-4 weeks.
pts should feel symptomatic improvement within 2wks starting Rx but full benefit may take 3-4 months
target TSH should be at lower end of normal range (0.4-5IU/L)
- takes at least 4 weeks for TSH to stabilise after a change in dose
consider variable daily dosing to minimise cutting the tablets