Download The Number Games and Thyroid Function

The Number Games and
Thyroid Function
Arshia Panahloo
Consultant Endocrinologist
St George’s Hospital
Presentation Today:
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Common thyroid problems and treatments
Pregnancy related thyroid problems
The ‘suppressed TSH’
Thyroid Cancer
Review of common pitfalls- QUIZ
HYPOTHALAMUS
Portal Circulation
HYPOTHALAMIC FACTOR
PITUITARY
PITUITARY
HORMONE
END ORGAN
HYPOTHALAMUS
Portal Circulation
HYPOTHALAMIC FACTOR
PITUITARY
PITUITARY
HORMONE
END ORGAN HORMONE
END ORGAN
Portal Circulation
PITUITARY
NEGATIVE
FEEDBACK
HYPOTHALAMUS
TRH
PITUITARY
TRI IODOTHYRONINE
TSH
THYROXINE
THYROID
Typical Thyroid Hormone Levels in Thyroid
Disease
TSH
T4
T3
Hypothyroidism
High
Low
Low
Hyperthyroidism
Low
High
High
Thyroid Hormone
• The plasma thyroid hormones are
– 3,5,3`,5`-tetraiodo L-thyronine (thyroxine T4)
– 3,5,3`-triiodo L-thyronine (triiodothyronine T3)
• Receptor is nuclear (type2)
• Circulate bound to protein
– Thyroid Binding Globulin
– Albumin
– Prealbumin
• Plasma half life T3 (1-3 days)
T4 (4-7 days)
• Dietary Iodine requirement 50μg/day
Thyroid Hormone Production
• 100 mcg of thyroid hormone are produced
daily
• Most as T4 and 10% as T3
• 80% of T4 converts to the more active T3
in the kidney and liver or reverse T3
• T3 is ten times more active than T4
• reverse T3 has little activity
Over production
Thyrotoxicosis
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Graves disease (80%)
Multinodular Goitre (15%)
Toxic Solitary Nodule (2%)
Thyroiditis (1%)
Rare
– TSH secreting pituitary tumour
– Excess Thyroxine ingestion
– trophoblast tumours
Robert James Graves
(1796- 1853)
Thyrotoxicosis
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Tachycardia
Palpitation
Lid Lag
Agitation
Increased
locomotor
Sympathetic
activity
Overactivity
• Weight loss
• Heat intolerance
• Fever
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Poor appetite
Myopathy
Increased Growth
Diarrhoea
• Grave’s
• thyroid eye disease:
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Pretibial Myxodema
Exopthalmos
Chemosis
lid lag
Diplopia on upgaze
Treatment
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Carbimazole
Propythiouracil
Beta Blockers
Surgery
Carbimazole vs. Propylthiouracil
•Serum half-life
•Duration of action
•Dosing
•Compliance
•Cost
•Side-effects
Carbimazole
PTU
4-6 hr
24 hr
1-2 x daily
Higher
£4.46 (20mg)
Lower
75 min
12-24 hr
2-3 x day
Lower
£74.79 (300mg)
Higher
Side-effects of Antithyroid Drugs
•Skin rash, itching
•Upper GI side-effects
•Arthralgia
•Vasculitis, SLE-like syndrome
•Blood dyscrasia
•Hepatotoxicity
•Congenital malformations
PTU and Liver Injury
•JCI 2009, 94:1881 Cooper et al..
•US FDA database:
severe liver injury in 22 adults in 20 years
•9 died, 5 needed transplant
• Severe liver injury in 12 children
•3 died, 6 needed transplant
•Estimated risk of severe liver failure: 1/1000
•Raised Liver enzymes: 15/54 (28%)
Hyperthyroidism in pregnancy
• Grave’s Disease affects 2 per 1000 pregnancies
• It is important to ensure patient euthyroid as soon as
possible, preferably prior to conception, to avoid
complications:
– Maternal
• Thyroid storm
• Congestive cardiac failure
• Pre-eclampsia
– Fetal
• Fetal growth restriction
• Prematurity
• stillbirth
The Foetal pituitary thyroid axis
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Controlled in similar way to adult
Iodine supplied transplacentally
< 12/40 maternal T4 but not T3 crosses placenta
T4 binds to foetal brain cells, and is converted
intracellularly to T3. This is important for brain
development.
• >12/40 fetal thyroid function is independent of mother,
provided mothers iodine intake is adequate.
Pregnancy specific thyroid
changes
• T4 synthesis increases 20-40%
• Half life of thyroid binding globulin increases from 15 min
to 3 days. Must measure only Free T4 and T3
• hCG and TSH have similar alpha sub-units and
receptors.
• In first trimester hCG can stimulate TSH receptor, and
can give a picture of hyperthyroidism.
• Worse in hyperemesis and multiple pregnancies and
trophoblastic disease
• Thyroid function must be interpreted with caution
Propylthiouracil or Carbimazole in
pregnancy?
• Both have similar placental transfer
• Earlier reports suggested carbimazole causes aplasia
cutis congenita of the scalp
• Rare congenital defect affecting 0.03% of the population
• Recent reports show that this is rare and should not
influence choice of drug in pregnancy
• No other teratogenicity
• Both drugs can cause agranulocytosis – patients must
report sore throats
Treatment of Hyperthyroidism in
pregnancy
• PTU first line in first trimester
• If intolerant to PTU, use carbimazole
• Switch to carbimazole second trimester due to liver
toxicity with PTU
• Lowest dose possible, as both drugs cross the placenta
• Propanolol can be used if tachycardia, tremor or anxiety
• Difficult to distinguish between signs of thyrotoxicosis
and pregnancy
• Serial TFT important every 6 -8 weeks
• Failure to gain weight despite good appetite, pulse rate
>100 are signs of thyrotoxicosis
Treatment of Hyperthyroidism in
pregnancy
• TSH receptor antibody falls in the second and third
trimester, and rises in the puerperium
• TFT should be measured 6 weekly
• Anti-thyroid medication titrated
• Most women can reduce their dose and a third stop
treatment in pregnancy
• This prevents fetal hypothyroidism
• Anti-thyroid medication will need to be started post
partum to avoid relapse
Lactation
• There are differences between PTU and carbimazole
during lactation
• 0.077% PTU and 0.47% carbimazole reaches breast
milk.
• High dose Carbimazole could cause neonatal
hypothyroidism
• Switch to PTU, may need monitoring of neonatal TFT if
patient on carbimazole
Fetal consequences of thyrotoxicosis
• TSH receptor antibodies can cross placenta and cause Graves
disease after 20 weeks (risk is low)
• Effect proportional to antibody titres
• Must be measured in all women who may have had Graves disease
treated in past with radioactive iodine or surgery at 22/40
• If titres high, should monitor for signs of fetal thyrotoxicosis:
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Fetal tachycardia
Growth restriction
Oligohydramnios
Fetal goitre can obstruct delivery
IUD
Hydrops fetalis
Hypothyroidism: Types
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Primary hypothyroidism
– From thyroid destruction
– Hashimotos Disease
– Post radioactive iodine
– Post surgery
– Thyroiditis
– Antithyroid drugs
Central or secondary
hypothyroidism
– From deficient TSH secretion,
– Generally due to sellar lesions
such as pituitary tumor or
craniopharyngioma
– Infrequently is congenital
• Central or tertiary
hypothyroidism
– From deficient TSH
stimulation above level
of pituitary
– Lesions of pituitary stalk
or hypothalamus
– Is much less common
than secondary
hypothyroidism
Hypothyroidism
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Bradycardia
Mental Slowness
Poor Memory
Decreased
locomotor
activity
Sympathetic
• Weight gain
Underactivity
• Cold intolerance
• Hypothermia
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Poor appetite
Myopathy
Decreased growth
Constipation
Dry skin and hair
• Hoarse voice
• Puffy face
• Menstrual
Irregularity
Hypothyroidism and Pregnancy
• Hypothyroid women have increase prevalence of:
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Infertility
Abortion
Anaemia
Gestational hypertension
Placental abruption
Post partum haemorrhage
• Adverse neonatal outcome:
– Premature birth
– Low birth weight
– Neonatal respiratory distress
• In one study women with sub-clinical hypothyroidism
also had ↑ preterm delivery and neonatal resp distress
Hypothyroidism
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0.3-0.5% of pregnancies
Sub-clinical hypothyroidism in 2-3%
Antibodies found in 5-15%
Most common cause autoimmune
thyroiditis, and iodine deficiency
Thyroid Function Tests Pregnancy
JCEM 2012
• If hypothyroid in pregnancy, adjust dose of T4,
so TSH ≤ 2.5
• Aim for normal TSH in preconception period
• Normal ↑ in thyroxine dose of 30%
• Universal screening for TPO antibodies in either
before or during pregnancy not recommended.
• But positive TPO are associated with increase
miscarriage, preterm delivery, hypothyroidism
and post-partum thyroiditis.
Thyroid Function Tests Pregnancy
• Only first trimester hypothyroidism influences
fetal wellbeing
• It is important to be euthyroid in the preconception period
• In hypothyroid women TFT should be checked in
each trimester
• Antenatal care is usually midwife led unless
other risk factors
Targetted TFT testing seeking pregnancy
or newly pregnant
• Women over 30
• With FH of autoimmune thyroid disease or
hypothyroidism
• Women with Goiter
• Positive antibodies
• Symptoms of thyroid disease
• Type-1 diabetes
• Infertility
• History of miscarriage and preterm delivery
• Head and neck irradiation and thyroid surgery
• On T4 replacement
Causes of Thyroiditis
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Hashimotos’s
Riedels
De Quervain’s
Silent
• Post Partum
• Drugs
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DXT
Lithium
Amiodarone
Interferon
• Superative
Post partum Thyroiditis
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Common 6 to 12 months postpartum
Patients present with transient thyrotoxicosis
Resolves by 12 months
Occurs in patient who are TPO Ab +,Grave’s
disease in remission, and chronic viral hepatitis
• Screen for TSH 3 and 6 months post-partum
• Annual TSH
• Increase risk of permanent hypothyroidism in 5
to 10 years
Carcinoma of the Thyroid
• Patients are initially treated with total thyroidectomy
• Followed by radio-iodine ablation therapy
• Followed by life-long suppressive thyroxine therapy to
prevent recurrence
• Please do not lower dose of Thyroxine in these patients.
Tumours of the anterior pituitary can
cause syndromes of hormone excess
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GH
ACTH
TSH
LH/FSH
• PRL
•Acromegaly
•Cushing’s disease
•Secondary thyrotoxicosis
•(Non-functioning pituitary
tumour)
•Prolactinoma
Suppressed TSH
PRIOR TO ADJUSTING MEDICATION
•Is the suppressed TSH secondary to thyroid
over-activity?
•Excess thyroxine replacement?
•Hypopituitarism and TSH deficiency?
•Has the patient had treatment for thyroid
Cancer?
Pitfalls in Interpreting Thyroid
Function
• Pregnancy
• Hypopituitarism
• Thyroid Cancer
Short QUIZ