Endocrine Flashcards
Physiology of thyroid in pregnancy
Relative maternal iodine deficiency
- 2-fold increase in renal loss (increased GFR + decreased reabsorption)
- Active transport of iodine to fetus
Uptake of plasma iodide into the thyroid is increased 3-fold
- Insufficient dietary iodine –> cellular hyperplasia and goitre
Increased hepatic synthesis of thyroid-binding globulin (TBG) leads to:
- Increase in total thyroxine (T4)
- Increase in total tri-iodothyronine (T3)
- Free T4 (FT4) levels remain unchanged
HCG has weak thyroid stimulating activity as structurally similar to TSH
Normal increase in HCG in early pregnancy may cause a small transient increase in free T4 with subsequent TSH suppression
Iodine deficiency in pregnancy
Inadequate iodine –> inadequate thyroid hormone production –> hypothyroidism
most common cause of mental retardation and irreversible brain lesions
Thyroid hormone is essential for normal maturation of the central nervous system, particularly its myelination
For the first 12/40, the fetus is completely dependent upon maternal T4
Re-emergence of iodine deficiency appears to be due to:
Increased consumption of commercially-prepared foods
Declining use of iodine-containing sanitizers by the dairy industry
Less salt being used in home prepared foods as a response to the health messages to reduce salt intake
The iodine content of vegetables, fruits and grains generally reflect the iodine level of the soil in which they were grown
- Iodine content of NZ soil is low
Dietary sources of iodine
- Seafood (fish, shellfish, seaweed)
- Commercially prepared bread
- Iodised salt
- Milk
- Eggs
It is difficult for most New Zealanders to obtain adequate iodine from their normal diet, which is why commercially prepared bread must now have iodine added to it
RDI if pregnant, planning a pregnancy, or breast feeding: 150 micrograms/day
Primary hyperparathyroidism background
Increased PTH secretion –> increased serum Ca, however clinical hypercalcaemia only occurs in severe cases as pregnancy is a low Ca state
Causes: parathyroid adenomas or hyperplasia
Malignancy
MANAGEMENT Mainly conservative - Phosphate supplements - Low calcium diet - Hydration May require parathyroid surgery - Perform in second trimester
If untreated, risk of:
- PET
- Miscarriage
- FGR
- IUFD
- Neonatal hypocalcaemia through fetal PTH suppression
Graves pathogenesis
95% of thyrotoxicosis
0.1-1% of all pregnancies
Autoimmune disorder
Thyroid-stimulating hormone receptor-stimulating immunoglobulins / antibodies (TSI) –> growth of thyroid gland and hyperthyroidism
Genetic predisposition (50% of patients have a family history of autoimmune thyroid disease)
Environmental factors: smoking, high iodine intake, stress
If thyrotoxicosis occurs for the first time in pregnancy, it usually occurs late in the first or early second trimester
Diffuse, firm goitre
50% have ophthalmopathy
Pretibial or localised myxedema
Pregnancy effect on Graves
First trimester - Exacerbation may occur
- Increased HCG or decreased absorption of medication due to vomiting
Second / third trimester - Improvement in Graves’ disease
- Relative immunosuppression
Post-partum - Exacerbation may occur
- Especially if there has been improvement during pregnancy
Effect of thyrotoxicosis of pregnancy - maternal risks
Good pregnancy outcome if good control on medication or previous treated Graves’
If severe and untreated, thyrotoxicosis is associated with inhibition of ovulation and infertility
Poorly controlled disease may have:
- HTN
- PET
- Placental abruption
Arrhythmias - sinus tachycardia, supraventricular tachycardia, AF
Heart failure and ‘thyroid storm/crisis’ have maternal mortality of 25%
- Highest risk of thyroid storm at delivery
Effect of thyrotoxicosis of pregnancy - fetal risks
If untreated or newly diagnosis in pregnancy, increased risks of:
- Miscarriage
- Fetal growth restriction
- Preterm labour and birth
- Perinatal mortality
- Stillbirth
Transplacental TSI –> fetal or neonatal thyrotoxicosis in 1%
Higher risk if:
- Poorly controlled disease or high TSI titres
- Active disease in the third trimester
- May also occur in treated Graves’, following thyroidectomy or radioactive iodine
Perinatal mortality without treatment is 25%
Medications for hyperthyroid
- High doses may –> fetal hypothyroidism
- Carbimazole rarely causes aplasia cutis (patches of absent skin at birth, mainly on the scalp)
Doses of PTU <150mg/day and carbimazole <15mg/day are unlikely to cause problems in the fetus
Risks of PTU - maternal liver failure, 1 in 10,000
Suggest PTU first trimester, then switch to carbimazole
BETA BLOCKERS
- for symptoms of tachycardia and tremor, discontinue once anti-thyroid drugs take effect
Radioactive iodine CI in pregnancy and breastfeeding (avoid pregnancy for 4-6/12 after Rx)
Monitoring for hyperthyroid in pregnancy
TFTs monthly in newly diagnosed patient
3-monthly TFTs in stable patient
Measure maternal TSI titre early and late in pregnancy
Serial growth scans for growth, HR and goitre
Cord blood for TFTs
USS features of fetal thyrotoxicosis
Thyroid enlargement FGR Hydrops Presence of goitre Advanced bone age Tachycardia Cardiac failure
Key points of neonatal thyrotoxicosis
Results from transplacental passage of TSIs
Onset may be delayed for 14 days if the mother was on thionamides
Transient condition, lasting 2-3 months
Mortality rate up to 15% if untreated
Antithyroid treatment should begin promptly but only short term
Symptoms: Weight loss, tachycardia, irritability Hepatosplenomegaly Heart failure (faire) Goitre)
Gestational hyperthyroidism
1-3% of women in early pregnancy
Develops in early pregnancy and resolves before 20/40
HCG is structurally similar to TSH –> stimulates TSH receptor –> increased thryoid hormone production –> suppresses TSH
Women do not always have overt signs of hyperthyroidism
By definition, have negative thyroid receptor antibodies
~50% of cases occur with hyperemesis gravidarum
Subclinical hypothyroidism implications
Results for large cohorts and meta-analyses have not been consistent in demonstrating an association between SCH and adverse pregnancy outcomes
Increased risk of clinical hypothyroidism within 5 years, especially if thyroid autoantibodies
Association with childhood developmental delay has not been confirmed in prospective cohort data
No studies show thyroxine influences outcome
Routine screening and treatment not recommended
Overt hypothyroidism diagnosis
TSH >reference range with decreased T4, or
TSH >10mIU/L, irrespective of the level of FT4
Treat in pregnancy
Pathophysiology - hypothyroid
Autoimmune disease associated with thyroid peroxidase (microsomal) autoantibodies (TPA) –> lymphoid infiltration –> fibrosis and atrophy of the thyroid gland
- Hashimoto’s thyroiditis - Main cause of hypothyroidism in NZ and Australia, A/w other autoimmune diseases, e.g. T1DM
- Atrophic thyroiditis
Iatrogenic
- After radio-iodine
- Thyroidectomy
- Drugs - amiodarone, lithium, iodide, thionamides
Secondary hypothyroidism
- Sheehan syndrome (postpartum pituitary necrosis after PPH)
Transient
- Subacute de Quervain’s thyroiditis
- Postpartum thyroiditis
Iodine deficiency itself is associated with hypothyroidism and goitre
Hypothyroidism effects on pregnancy
Adequately treated hypothyroidism is not a/w any adverse maternal, fetal or neonatal complications TPA (thyroid peroxidase antibodies) does not affect the fetus Under treated women at risk of - Miscarriage - PET - Abruption - PPH - Anaemia - Low birth weight - Prematurity - Perinatal mortality - Stillbirth - Impaired neurological development - Low offspring IQ Congenital cretinism - syndrome of growth restriction, deafness, neuropsychological impairment, resulting from severe iodine deficiency or untreated congenital hypothyroidism
Antenatal management of hypothyroidism
Pregnant women receiving thyroxine will often require a 30-50% increase in their thyroxine dose from early in the first trimester
The goal for treatment of overt hypothyroidism should be to maintain serum TSH values within the lower half of trimester-specific pregnancy ranges
Iron or aluminium hydroxide antacids interfere with thyroxine absorption
In euthyroid women, check TFTs once each trimester
Following any dose adjustments, recheck every 4-6 weeks
In women on thyroxine following treatment of Graves’ disease, TSI should be measured in early and late pregnancy to predict fetal or neonatal thyrotoxicosis
If newly diagnosed or undertreated, do serial scans for growth and goitre
Postpartum management of hypothyroid
Check TFTs if thyroxine dose was adjusted
Up to 75% develop postpartum thyroiditis
Postnatal depression commoner in women with thyroid antibodies
TSH is measured in all neonates with a Guthrie card
Aetiology of postpartum thyroiditis
5-10% of pregnancies
Occurs in up to 75% of patients with thyroid peroxidase (micrsomal) autoantibodies (TPA)
25% have a first degree relative with authoimmune thyroid disease
Incidence is 3-fold higher in T1DM
