Endocrine Flashcards
Discuss Addison’s in pregnancy
-Pathophysiology
-Presentation
-Diagnosis
-Effect of pregnancy on Addison’s
-Effect of Addison’s on pregnancy
-Management in pregnancy
- Pathophysiology
-Autoimmune destruction of adrenal gland leading to deficiency in (glucocorticoid) cortisol and (mineralcorticoids) aldosterone. - Presentation
-Hypotension, salt wasting, skin pigmentation, weight loss
-Associated with other autoimmune disease - T1DM, Graves - Diagnosis
-Loss of cortisol response to ACTH (Synacthen test)
-Hyperkalemia, hyponatremia, hypocalcemia
-Low morning cortisol (can be WNL in pregnancy) - Effect of pregnancy on Addison’s
-May mask symptoms but doesn’t generally affect it
-May deteriorate PP - Effect of Addison’s on Pregnancy
-No effect
-Adrenal antibodies do cross placenta but very rare to have adrenal insufficiency - Management in pregnancy
-Need to replace glucocorticoids and mineralocorticoids (hydrocortisone and fludrocortisone)
-Need stress dosing if hyperemesis, infection, stressful events
-Need stress dosing for labour
-Watch for profound hypotension with fluid shifts and diuresis PP. Manage with IV Saline
Discuss Conns in pregnancy
-Pathophysiology
-Presentation
-Diagnosis
-Management in pregnancy
- Pathophysiology
-Caused by primary hyperaldosteronism due to adrenal hyperplasia/adenoma/carcinoma - Presentation
-Hypertension, hypokalemia - Diagnosis
-High aldosterone
-Hypernatremia, hypokalemia - Management in pregnancy
-Control BP - manage same as chronic HTN
-Replace potassium
-Avoid ACEi and spironolactone as cause feminisation of male fetus.
-Defer surgery until after pregnancy
Discuss congenital adrenal hyperplasia in pregnancy
-Pathophysiology
-Presentation
-Diagnosis
-Effect of CAH on pregnancy
-Effect of pregnancy on CAH
-Management in pregnancy
- Pathophysiology
-Autosomal recessive condition with lack of adrenal enzymes.
-90% caused by lack of 21-hydrolase enzyme. Results in low cortisol and aldosterone and high androgens - Presentation for classic
-Masculinisation of female fetus, salt wasting crisis as neonate - Diagnosis
-17 hydroxyprogesterone levels are elevated
-Synacthen test. Cortisol will not respond to ATCH - Effects of CAH on pregnancy
-Increased miscarriage rates
-IUGR
-CS due to CPD from android pelvis
-PET, GDM - Effects of pregnancy on CAH
-Increased risk of female fetus having CAH and virilisation of genitalia - Management in pregnancy
-Pre-pregnancy counselling for genetics
-Continue fludrocortisone and hydrocortisone replacement in pregnancy
-Stress dose for hyperemesis, infection, labour
-Monitor for PET
-Consider dexamethasone from early pregnancy (before 6 weeks) to avoid virilisation of female fetus genitalia. Stop once sex known to be male as don’t need or CVS/Amnio show fetus not affected. Dexamethasone is not without fetal complications. Needs careful counselling
-Growth scans
-OGTT
-MDT - MFM, endocrinologists
Discuss management of phaeochromocytoma in pregnancy
-Pathophysiology
-Presentation
-Diagnosis
-Effects of phaeo on pregnancy
-Effects of pregnancy on phaeo
-Management
- Pathophysiology
-Tumour of the adrenal medulla producing excess catecholamines - Presentation
-Paroxysms of hypertension
-Headache
-Palpitations
-Sweating
-Anxiety
-Can mimic PET - Diagnosis
-Raised 24hr urinary catecholamines
-USS or MRI (best) to localise tumour (10% extramedullary) - Effects of phaeo on pregnancy
-Increased maternal and fetal mortality (25-60% if undiagnosed)
-Increased risk of arrythmia, CVA, pulmonary oedema, cardiogenic shock
-Increased risk GDM
-IUGR, acute/ chronic hypoxia, Abruption - Effect of pregnancy on Phaeo
-Potentially fatal HTN crises stimulated by labour, delivery, or pressure of gravid uterus on tumour when supine - Management
-MDT - endocrine, obstetrics, anaesthetics, neonatologist, surgeons
-Alpha blockade with prazosin / phenoxybenzamine
-Beta blockade for arrythmia but only once alpha blockers used.
-Cautions with meds which increase BP - metocloprimide, phenothiazides
-Surgical removal either <23 weeks or PP
-Delivery by CS. Half the risk of maternal mortality
What are the mechanisms in pregnancy which increase risk of DKA (4)
-Increased insulin resistance from placental hormones (human placental lactogen, cortisol, prolactin and progesterone)
-Increased carbohydrate absorption with reduced gut motility
-Predisposition for starvation with increased metabolic demands from utero-placental unit resulting in decreased fasting glucose and predisposition to ketoacidosis
-Limited buffering in blood with reduced bicarb (Increased renal loss), Predominance of respiratory alkalosis
What are the possible causes of DKA in pregnancy (5)
- Insulin withdrawal - faulty pump, non compliance
- New T1DM
- Increased metabolic demands - sepsis, trauma
- Reduced absorption - hyperemesis, fasting
- Drugs - beta mimetics, steriods
Discuss gestational diabetes
-Definition
-Incidence
-Risk factors (7)
- Definition
Impaired glucose tolerance with onset or first recognition in pregnancy. - Incidence
-10% - Risk factors
-PCOS
-FHx of >1 first degree relative with diabetes
-Previous GDM or macrosomia
-Medications - steroids, antipsychotics
-Obesity >30 BMI
-Ethnicity - Asian, Indian, Maori, Pacific, Aboriginal
-Advanced maternal age >40
Describe antenatal screening for GDM
-RANZCOG recommendation
-Australian cut offs for GDM
-Time for testing - high risk, and average risk
- RANZCOG recommendations
-2hr 75g diagnostic test (no screening test) - Australian cut offs
-Fasting glucose >5.1
-1Hr Glucose >10
-2Hr Glucose >8.5 - Time for testing
-Women at high risk - OGTT at first opportunity after conception and if negative 24-28 weeks
-Average risk women - OGTT 26-28weeks
Describe the New Zealand diagnostic pathway for GDM
-First antenatal HbA1c
-Screening cut off
-Diagnostic cut off
- First antenatal HbA1c
-HbA1c >=50 - probable undiagnosed diabetes. Immediate referral to specialist diabetes clinic. (WHO says >=48)
-HbA1c < = 40 - GCT
-HbA1c 41-49 - OGTT - GCT
-Positive if >=7.8 - proceed to OGTT
- >11.1 = diagnostic for GDM - OGTT
-Fasting >= 5.5
-2 hr >= 9.0
- Do OGTT directly if: BMI >30, Prev GDM, 1st degree relative with DM
Discuss risks associated with GDM
-Risk to mother during pregnancy (5)
-Risk to fetus
-Risk to mother PP
- Risk during pregnancy.
-HTN, PET, CS, SD, Birth injury, PPH
-At risk of all same issues as T2DM but to a much lesser degree - Risks to fetus
-IUGR, Macrosomia, NICU admissions, neonatal hypoglycemia,
-Not associated with congenital abnormalities - Maternal risks PP
-40-60% chance of developing T2DM in 10-15yrs
-30% risk of recurrent GDM
Discuss antenatal management of GDM
-Lifestyle advice
-Aim for glucose
-Medical management
-Fetal surveillance
-Maternal surveillance
- Lifestyle advice
-Dietary - reduce fat, increase fibre, low GI foods
-Moderate exercise 30mins / day
-Weight gain - if BMI >30 aim 5-9kg - Glucose targets
-Fasting <5
-1hr post food <7.4
-2hrs post food <6.7 - Medical management
-If levels persist above target for >2weeks consider medical
-Metformin: contra-indicated in IUGR, PET, Inadequate maternal wt gain. Crosses placenta. Not teratogenic
-Short acting insulin to bring down post parandial levels
-Intermediate acting to bring down high fasting levels - Fetal surveillance
-GS at time of diagnosis and 36-37 weeks - Maternal monitoring
-PET - BP and urinalysis
-BGL
Discuss timing of delivery for GDM
- If GDM without complications - IOL at 40/40
- If GDM with co-morbidities Aim IOL 38-39/40 (Macrosomia +/- poorly controlled diabetes)
- If GDM and EFW >4.5kg offer CS
Discuss labour and postpartum management of GDM
-Labour management
-Postpartum management
- Labour management
-Stop insulin when in labour
-If high BSL consider GIK
-Hourly BSL should be 4-7 - Postpartum management
-Following delivery stop insulin and all oral agents
-Monitor BSL for 24hrs to make sure no ongoing hyperglycemia
-Monitor baby’s BSL 1-2hrs after birth
-Discuss risk of GDM recurrence and T2DM in later life (up to 90%)
-HbA1c 3 months PP
-HBA1c or OGTT two yearly
What are the parameters for diagnosis of DM
-HbA1c parameters (2)
-Glucose levels (3)
- -HbA1c 41-49 = pre diabetes
-HbA1c 50 or more = diabetes - Glucose levels
-Random glucose >11
-Fasting glucose >7
-2 hr 75mg OGTT >11
What are the effects of pregnancy on diabetes (9 effects)
- Increased insulin requirements - 2x higher in term T1DM
- Increased risk of diabetic nephropathy - 30% if HTN
-If mild pre-existing nephropathy often reversible. If severe not reversible - Increased risk of progression to retinopathy
-T1DM >T2DM
-10% increased risk of progression if mild retinopathy
-50% increased risk of progression if proliferative retinopathy - Increased risk of HTN
- Increased risk of hypoglycemia
-Better control
-Increased insulin sensitivity in first trimester
-Increased unawareness of hypoglycemia - Diabetic ketoacidosis.
-Rare in pregnancy
-Triggered by infection, steroid use, hyperemesis - Worsening of autonomic neuropathy
- Worsening of Gastric paresis
- Normocytic normochromic anaemia
What are the effects of diabetes on pregnancy for mothers (6 effects)
- Increased miscarriage
- HTN and PET 3-4 x risk
- Infections
- Mode of delivery - more IOL and CS
- Increased perineal injury
- PPH if macrosomic
What are the effects of diabetes on pregnancy for fetus (11 effects)
- Congenital abnormalities
-4% incidence. 2 fold increase. 22% chance
-Cardiac 3 times risk
-NT defects 3 x risk
-Sacral agenesis - rare but specific to DM
-Situs inverts, renal anomalies
-Increased risk with increased HBA1c - Macrosomia
-Related to blood sugar control but can still have with excellent control - Polyhydramnios
-Related to fetal polyuria
-Increased risk of PTL, PPROM, Cord prolapse - Sudden intrauterine fetal demise - 5 fold increase
-Due to chronic hypoxia from accelerated metabolism
-High O2 requirements
-Uteroplacental vasculopathy
-Highest risk at term. RR 7.2
-CTG, BPP and doppler don’t predict - PTD - 5 times more likely to be born before 37/40
- Shoulder dystocia - 8% vs 3% in general population. Increased risk at any weight
- Fetal distress in labour
- Jaundice - polycythemia
- Respiratory distress syndrome
- Erbs palsy - 10 times risk
- IUGR from impaired placental perfusion
Discuss management of women with diabetes: preconception (9 points)
- Basic advice: smoking, exercise, optimise wt, immunisations
- Optimise BSL. Aim for HbA1c <48. Advise better outcomes with better control (miscarriage, anomilies, macrosomia, IUFD)
- Stop sulphonylureas. Switch to insulin
- Retinal screening - treat if proliferative retinopathy
- Renal function - BP, Cr, Urinalysis. If Cr >125 advise against pregnancy
- Assess cardiovascular risk.
- Stop statins and ACEi / switch if required
- Commence on 5mg folic acid
- Advise against pregnancy if IHD, untreated proliferative retinopathy, severe gastroparesis, severe renal impairment
What is the risk of a child having T1DM if:
1. The mother has it
2. The father has it
3. Both parents have it
- 2-3%
- 6-9%
- 20-30%
Discuss antenatal care for women with diabetes (7)
- MDT based care with obstetrician, physician, dietician, diabetic educator
- Education on diet and physical exercise.
- BSL monitoring
-HBA1c once a trimester
-Aim 4.0-5.3 fasting BSL
-Aim <7.8 1 hr post parandial - Hypoglycemia management
-Discuss risks
-Avoid starvation
-Educate partner
-Have hypo kits available - Pre-eclampsia prevention
-Aspirin 100mg PO OD 12-36 weeks
-Calcium 1.5 g PO OD 12 weeks onwards
-BP and urinalysis each visit - Retinal screening in first trimester +/- 3rd trimester
- Renal screening - serum Cr and PCR each trimester
Discuss fetal monitoring in diabetic women (6)
- Early dating scan for accurate dating
- Nuchal translucency - can help for cardiac anomalies
- Detailed anatomy 18-20. Can consider at 16/40 in addition to 20/40 anatomy scan if high risk or obese
- Fetal echo 24/40
- Growth scans at minimum 28,32,36 weeks
- Weekly CTG from 34/40
Discuss intrapartum care of diabetic women
1. Mode of delivery
2. Timing of delivery
3. BSL control
- Mode of delivery
-Aim for vaginal birth
-If EFW >4.5kg offer CS - risk of shoulder dystocia - Timing
-By term in DM without complications
-After 37 weeks depending on situation
-If delivering before 34 weeks may need GIK infusion with steroids
-Need to consider risk and benefits of delivery/prematurity - BSL control
-Hourly BSL monitoring aiming for 4-7 BSL
-Sliding scale of short acting insulin and dextrose infusions
-Give reduced long acting (1/2 to 1/3) and stop short acting insulin in labour or pre CS
Discuss post-partum care for diabetic women
1. T1DM women
2. T2DM women
3. Other PP care
- T1DM women
-Half insulin infusion after delivery if T1DM.
-Once eating normally can recommence pre-pregnancy sub cut regimen
-If breast feeding insulin dose reduced - T2DM women
-Recommend pre-pregnancy medications
-May need insulin if breast feeding - Other care
-Check neonatal BSL at hr and pre feeds
-Contraceptive advice
-Life style advice
-Biannual diabetes FU
Describe the physiological changes in pregnancy regarding calcium metabolism
-Is pregnancy hypocalcemic or hypercalcemic state?
-How does that state occur
-How is that state counter balanced
- Pregnancy is a relatively hypocalcemic state
- Hypocalcemia is driven by:
-Increased fetal uptake of calcium
-Increased maternal renal losses
-Reduced serum albumin so reduced protein bound calcium - Hypocalcemia is counter balanced by:
-Increased PTH
-PTH reduces renal clearance from kidneys
-PTH increase intestinal absorption of vit D
Describe hyperparathyroid in pregnancy
-Epidemiology
-Causes
-Clinical features
-Diagnosis
- Incidence
-Third most common endocrine disorder
-Rare in pregnancy 8:100,000
-Complications to mother 70%, complications to fetus 80% - Causes
-Adenomas, hyperplasia - Clinical features
-thirst, fatigue, constipation, depression, renal calculi, pancreatitis, HTN - Diagnosis
-Raised calcium, Raised PTH
-USS of the neck to look for adenomas
How does pregnancy affect hyperparathyroidism (3)
- Improvement in hypercalcemia as pregnancy is a hypocalcemic state
- Increased risk of pancreatitis
- Risk of acute hypercalcemic crisis especially post-partum due to abrupt end to calcium transfer to fetus
How does hyperparathyroidism affect the pregnancy (8)
- Increase in miscarriage
- IUFD
- PTL
- HTN and PET
- Polyhydramnios
- Suppression of fetal PTH by high maternal calcium can lead to fetal hypocalcemia and tentany
- Acute neonatal hypocalcemia
- IUGR
How should hyperparathyroid be manged in pregnancy
- Surgery
- If mild and asx can be conservative
-Encourage low calcium diet and increase PO fluid intake - Forced diuresis to increase renal clearance
-Loop diuretics- frusemide
-Dialysis if hypercalcemia is very severe
Discuss hypoparathyroid disorder in pregnancy
-Cause
-Diagnosis
-Impact of pregnancy on hypoparathyroidism
-Impact of hypoparathyroidism on pregnancy
-Management
- Cause
-Autoimmune disease or complication of thyroid surgery - Diagnosis
-Low Ca and PTH - Effect of pregnancy on hypoparathyroism
-Increased demand for vit D cannot be met. Need supplements - Effect of hypoparathyroid on pregnancy
-Increased miscarriage
-Fetal hypocalcemia
-Secondary hyperparathyroidism
-Bone demineralisation and ricketts - Management
-Vit D and calcium supplements
-Calcium and albumin levels monthly
-Reduced vit D dose PP
-Refer to endocrine
-D/W Neonatologists for PP testing
Discuss vitamin D deficiency
-Levels and severity (3)
-Risk factors (10)
- Levels and severity
-Profound deficiency - <25nmol/L
-deficient - <50nmol/L
-Insufficient <75nmol/L - Risk factors
-Vegan diet
-Pigmented skin
-Covered skin
-Regular sun screen use
-Obesity >30 BMI
-Antiepileptic drugs
-Liver or renal impairment
-Alcoholism
-Short birth interval
-Malabsorption
What is the impact of low vitamin D levels of pregnant women (7)
- Increased risk of reduced weight gain
- Hypocalcemia
- Osteomalcia
- GDM
- PET
- HTN
- CS delivery
What is the impact to the fetus of low vit D levels
- Poor fetal bone health
- Hypocalcemia and neonatal tetany
- Childhood asthma
- SGA
What are the RANZCOG guidelines for vit D supplementation (5)
- Do not test for vit D levels as part of routine AN screening unless maternal risk factors
- Do not re-test vit D in pregnancy irrespective of level
- Advise all women to take 400IU of vit D daily during pregnancy
- Advise women about safe sun exposure
- Exclusively breastfed infants should be given 400IU daily of vit D for at least the first 6 months of life. Not required in formula fed.
What does the research show regarding vit D supplementation (2 points)
- 2 big RCT found no improvement to neonatal or obstetric outcomes with supplementation
- Does improve wheeze in children up to 3 yrs
Discuss hyperprolactinemia in pregnancy
-Epidemiology
-Causes (3 groups)
-Clinical features
-Diagnosis
- Epidemiology
-Prolactin adenomas are the most common type of pituitary tumour in pregnancy
-Prolactinoma’s are rare 1:4500 pregnancies - Causes of hyperprolactinemia
-Decreased dopamine antagonism
-Dopamine antagonists (metocloprimide, phenothiazides)
-Increased prolactin production
-Pituitary micro/macroadenomas
-Increased lactotrophs
-Breastfeeding
-Decreased prolactin clearance
-Chronic liver and renal disease - Clinical features
-Menstrual irregularities
-Galactorrhoea
-Infertility
-Frontal headache, visual field changes - Diagnosis
-High serum prolactin (not reliable in pregnancy)
-Visual field testing
-Brain MRI
What is the effect of pregnancy on prolactinomas (2)
- Risk of enlargement during pregnancy
-Highest risk with untreated macroadenomas - Regression following cessation of breast feeding
What is the effect of prolactinomas on pregnancy (3)
- Infertility - treatment with dopamine agonist can help conception
- No impact on pregnancy
- No impact on lactation
Discuss management of prolactinomas in pregnancy
-Pre-conception
-Antenatal
-Intrapartum
-Postnatal
- Pre-conception
-Treat with dopamine receptor agonist or surgery
-Avoid pregnancy until treated (Meds not tetarogenic) - Antenatal
-If microadenomas - stop dopamine agonists
-If macroadenomas - continue. Can use carbergoline or bromocryptine.
-If develop sx for visual field testing and MRI - Intrapartum
-Nil changes to routine care - Postpartum
-Dopamine agonists may suppress lactation
-Lactation is safe
Discuss the fetal pituitary thyroid axis
-Fetal metabolism T4
-Fetal reliance on maternal T4
-Fetal reliance on maternal iodine
- Maternal T4 crosses the placenta and the fetus converts T4 to T3 in the brain
- Fetus needs T4 until 12/40 then limited transfer of maternal thyroid hormones
- Fetus thyroid control becomes independent of mother by 12/40
- Fetus needs maternal iodine for whole pregnancy
What thyroid hormones, thyroid medications and antibodies:
-Cross the placenta (4)
-Don’t cross the plalcenta (3)
- Cross the placenta
-TSI (thyroid stimulating immunoglobulin - Graves)
-Small T3/T4 until 12/40
-PTU (less than carbimazole)
-Carbimazole - Doesn’t cross the placenta
-TSH
-TPO (Thyroid peroxidase antibody - (Hashimoto’s or Graves)
-Thyroxine
Discuss hyperthyroid disease in pregnancy
-Incidence in pregnancy
-Causes (4)
-Clinical presentation
-Diagnosis
- Incidence = 0.2%
- Causes
-Graves -85% of cases - autoimmune disorder with TSI stimulating TSH receptor on thyroid gland
-Toxic multi nodular goitre
-Thyroiditis
-Thyroid cancer
-Drugs - amiodarone, lithium, iodine
-TSH producing adenoma, HCG producing tumor, teratoma - Clinical presentation
-Can look like pregnancy - heat intolerance, palpitations, vomiting, tachycardia, palmar erythema
-Discriminating features - weight loss, tremor, lid lag, exopthalmus (Graves) - Diagnosis
-Low TSH high free T4
-Difficult to diagnosis in early pregnancy secondary to biochemical supression of TSH by HCG
-TSI positive suggests graves
-TRAB (Thyroid receptor antibodies) - Graves
What is the effect of pregnancy on hyperthyroidism (4)
- Exacerbation in first trimester (Increased HCG or decreased absorption of medication)
- Improvement in 2nd and 3rd trimester due to immunosuppression
- Postpartum - may have exacerbation
- Labour, CS or infection can precipitate a thyroid storm
What is the effect of hyperthyroidism on pregnancy
-Maternal effects (6)
-Fetal effects (7)
- Maternal effects
-If well controlled outcomes are good
-If poorly controlled: HTN, PET, Abruption
-Subfertility
-Tachycardia and heart failure
-Thyroid storm especially around delivery
-Retrosternal goitre causing tracheal obstruction and difficult intubation - Fetal effects
Untreated hyperthyroidism
-Miscarriage
-Congenital abnormalities - oesophageal atresia, aplasia cutis
-Fetal goitre
-Fetal tachycardia, hydrops and cardiac failure
-IUGR
-PTD
-Perinatal mortality
-Antithyroid medication (Carbimazole >PTU) can cross the placenta and cause fetal hypothyroidism, agranulocytosis
-Carbimazole can cause aplasia cutis
-TSI can cross the placenta and cause fetal hyperthyroidism
Describe the management of hyperthyroidism in pregnancy
-Pre-conception (2)
-Antenatal (9)
-Intrapartum (1)
-Postpartum - fetal monitoring (3) and maternal monitoring (2)
- Pre-conception
-Aim for euthyroid for 3 months before conception
-Smoking cessation - makes exopthalmus worse - Antenatal
-Continue medication if pre-existing disease at lowest does to maintain euthyroid status with T4 at upper limit of normal
-If new diagnosis in pregnancy treat with high dose PTU daily for 4-6 weeks then reduce to lowest dose to maintain
-If new diagnosis in pregnancy consider propranalol for sympathetic control
-Monitor maternal TFTs monthly to three monthly
-Monitor LFTs monthly if on PTU (can cause liver toxicity)
-Monitor fetal growth, heart rate
-Scan for fetal goitre
-Measure maternal TSI/TRAB early and late in pregnancy(high levels associated with fetal hyperthyroidism)
-Radioactive iodine in pregnancy and breastfeeding is contra-indicated
-Consider thyroidectomy if resistant to medical intervention or sx of airway obstruction - Intrapartum
-Monitor for sx of a thyroid storm - Postpartum
-Cord bloods for TFTs and TRAB
-Monitor fetal sx for signs of hyperthyroidism
-Treat with anti thyroid medication. Self limiting until TSI cleared
-Monitor maternal TFT 6 weeks and3 months
-Encourage breastfeeding. Safe with carbimazole and PTU at low doses. PTU preferrable
Discuss hypothyroidism in pregnancy
-Incidence (2)
-Causes (4)
-Symptoms
-Diagnosis
- Incidence
-Subclinical hypothyroidism 3%
-Overt hypothyroidism 1% - Causes
-Autoimmune causes - TPO antibodies (Thyroid peroxidase antibodies). Hashimoto’s thyroiditis (Most common cause), atrophic thyroiditis
-Iodine deficiency (Second most common cause)
-Iatrogenic - post surgery, drugs
-Secondary - Sheenan’s syndrome
-Transient - subacute de Quervains or postpartum thyroiditis - Symptoms
-Overlap with pregnancy - weight gain, lethargy, hair loss, dry skin, constipation, fluid retention, goitre
-Discriminatory - cold intolerance, bradycardia - Diagnosis
-TSH levels most important.
-TSH of 4 is the upper limit of normal in all trimesters
-Overt - TSH >2.5 + low T4 or TSH >10
-Subacute TSH 2.5-10 normal T4
-TPO antibodies confirms autoimmune cause but also present in 20% of normal population
Effect of pregnancy on hypothyroidism (1)
- No effect
Effect of hypothyroidism on pregnancy
-When well controlled
-Maternal effects if untreated (5)
-Fetal effects if untreated (6)
- Effects to pregnancy when well controlled
-Nil effects if treated and euthyroid - Effects to mother if untreated
-Subfertility
-Miscarriage
-PET
-Abruption
-PPH / Anemia
-Postpartum depression
-Prematurity, perinatal mortality - Fetal effects - if untreated - very rare
-Growth restriction/ LBW
-Still birth
-Reduced neurodevelopment and IQ
-Cretinism
-Miscarriage
-Fetal goitre
Discuss management of hypothyroidism in pregnancy
-Pre-conception (4)
-Antenatal (5)
-Postpartum (4)
- Management preconception
-Check TFTs and optimise control
-Advise delay of pregnancy until good control is achieved
-Routine screening and treatment for subclinical hypothyroidism not recommended. No difference to outcomes
-Screen women with T1DM or lupus as high correlation - Antenatal management
-If pre-existing disease: Continue thyroxine to maintain euthyroid state
-If newly diagnosed commence on 100cmg of levothyroxine
-Check TFTs each trimester and 4-6 weeks post dose adjustment
-Test TSI/TRAb if iatrogenic hypothyroid and previously managed for graves as still have Abx and can cross to fetus causing hyperthyroidism
-Monitor fetal growth - Postpartum care
-Check TFT
-Up to 75% with TPO develop postpartum thyroiditis
-Monitor for postpartum depression
-Screen neonate for TSH
Discuss post partum thyroiditis
-Incidence (2)
-Causes (2)
-Clinical features
-Diagnosis
- Incidence
-5-10% of pregnancies
-3x higher in women with T1DM - Causes
-Autoimmune destruction of the thyroid gland
-Occurs in 50 -75% of women with TPO antibodies - Clinical features
-Usually presents 3-6months postpartum
-Sx often vague
-Biphasic with transient hyperthyroidism then prolonged hypothyroidism
-50% have small painless goitre - Diagnosis
-TFTs
-Check TSI/TRAb to distinguish from Graves flare
-Radioactive iodine scan - increased uptake in graves. Reduced uptake in postpartum thyroiditis. (Avoid Breastfeeding for 24hrs)
How should postpartum thyroiditis be managed (4) and what is the prognosis
- Management
-Spontaneous recovery by 1 yrs
-Treatment depends on sx not TFTs
-If Hyperthyroidism - beta blockers
-If hypothyroidism - thyroxine. Withdraw after 6-9 months to check recovery. If ongoing high TSH for 5yrs treatment
-Yearly TFT to determine if developing hypothyroidism - Prognosis
-3-4% remain hypothyroid
-10-25% have recurrent postpartum thyroiditis
-20-40% with TPO Abx develop overt hypothyroidism within 5 yrs
What are the RANZCOG recommendations for hypothyroid management in pregnancy (7)
- Women should take 150mcg iodine daily if planning pregnancy, are pregnant and are breastfeeding
- Targeted testing for overt hypothyroidism is recommended in pregnancy
- Women who have a personal history of thyroid disease or T1DM should be tested with TSH and T4
- Overt hypothyroidism should be treated in pregnancy
- Overt hypothyroidism is defined as TSH above the reference range with a decreased T4 or TSH >10mIU/L irrespective of T4 levels
- Screening for subclinical hypothyroidism or TPO antibodies and subsequent treatment with levothyroxine is not recommended
- Treatment of TPO antibodies in Euthyroid women does not reduce miscarriage rate and is not recommended
Discuss the HAPO trial
-Primary aim
-Study type
-Study population / inclusion criteria
-Study methodology
- Primary aim
To investigate the impact of maternal hyperglycemia less severe than overt DM on adverse pregnancy outcomes - Study type
Cohort
3.Study population
-23,000 pregnant women at 15 centers in 9 countries
->18 yrs, Sure of dates
-No pre-exisiting DM, IVF/ART, HIV/HEP, singleton pregnancy
4.Study methodology
-Undertook OGTT (75g) between 24-32/40
-Results were blinded unless high fasting and 2 hr glucose readings
-Categorised glucose levels into 7 categories of increasing BSL for fasting, 1hr PP and 2hrs PP - Primary outcomes
-BW >90%
-Primary CS delivery
-Neonatal hypoglycemia
-Cord blood C peptide >90% (Measure of neonatal beta cell function/ hyperinsulinemia) - Secondary outcomes
-Delivery before 37/40
-Shoulder dystocia
-Birth injury
-PET
-Hyperbillirubinemia
-Admission to NICU
Discuss the HAPO trial results
-Primary outcomes
-Secondary outcomes
Primary outcomes
-Increasing risk of all primary outcomes with increasing glucose category for fasting 1hr PP and 2hrs PP
-Significant association with increasing BSL at all three times and BW >90% dose response and Serum C peptide (dose response) (strongest association) for highest BSL category
-Significant association with fasting and 1hr PP and CS -weak and without clear dose response
-No clear association with neonatal hypoglycemia and BSL of any category at any time
Secondary outcomes
-Incremental increase in BSL associated with increased risk for PTB, Shoulder dystocia/birth injury, NICU admission, Hyperbillirubinemia, PET
-Strongest associations seen with PET and shoulder dystocia
-No association with perinatal death in any of the 3 time categories but not powered to asses
What are the limitations of the HAPO study (3)
- Observational study so cannot link outcomes to BSL
- Some confounders not measured so not controlled for in MVA - weight gain in pregnancy
- Participation was only 54%
Discuss the ACHIOS study
-Primary aim (1)
-Study type (2)
-Inclusion criteria (2)
-Exclusion criteria (3)
- Primary aim
To investigate if treatment of GDM reduces risk of perinatal complications - Study type
RCT - multicentre in Australia
Randomised to routine care (GDM dx not disclosed) vs monitoring and management of BSL as per standard GDM care - Inclusion criteria
-Singleton/twins 16-30wks with RF or +ve polycose and + OGTT 24-34 weeks - Exclusion criteria
More severe glucose intolerance,
Active chronic disease except ess HTN
Previous GDM
Discuss the ACHIOS study
-Primary outcomes (6)
-Secondary outcomes (6)
- Primary outcomes
-Composite measure of serious fetal complications (Still birth, SD, nerve palsy, fracture)
-IOL
-CS
-Admission to NICU
-Neonatal Jaundice
-Maternal 3/12 QoL - Secondary outcomes
-Birth weight (LGA, macrosomia)
-Mode of delivery
-Pregnancy induced HTN
-Perineal trauma, PPH
-Number of clinic visits
Discuss the ACHIOS study
-Number in study
-Results of primary outcomes (stat sig ones - 6)
-Results of secondary outcomes (stat sig ones - 3)
- Number in study
-Approx 500 in each group
-No loss to FU - Results of primary outcomes
-Increase in serious fetal complications in routine care group 4% vs 1% RR 0.33 NNT 34
-Increase in NICU admissions in intervention group 71% vs 61% RR 1.13 (Rx for hypoglycemia same)
-Increase in IOL in intervention group 39% vs 29% RR 1.36
-CS rates the same and for similar indications
-Lower rates of depression as per EPNDS in intervention group 8% vs 17% RR 0.46
-No difference in shoulder dystocia rates - Results of the secondary outcomes
-Less macrosomia in intervention group 10% vs 21% RR 0.47
-Less PET in intervention group 12% vs 18% RR0.7
-No difference in PPH/perineal trauma
Discuss the TARGET study
-Aim (1)
-Study design (2)
-Primary outcomes (1)
-Secondary outcomes (6)
- Aim
To assess whether tighter glycemic control of GDM lead to reduced perinatal and maternal morbidity - Study design
-Step wedge cluster RCT in 10 NZ hospitals
-Roll out of tighter glycemic control every 4 months (Fasting <5, 1hr <7.4 2hr <6.7) - Primary outcome
-Incidence of LGA babies - Secondary outcomes
-Composite measure of neonatal outcomes (Death, birth trauma, shoulder dystocia)
-Composite measure of PPH, coagulopathy, emboilism, obstetric complications)
-PET
-IOL
-CS
-Need for pharmacological treatment for GDM
Discuss the results of the TARGET study
-Number of women recruited
-Results of primary outcomes
-Results of secondary outcomes
- Number of women recruited
-1000 - Results from primary outcome
-No difference in rates of LGA between groups 14.7% vs 15.1% RR 0.96 - Results for secondary outcomes
-Reduced serious neonatal health outcomes in tight control group RR 0.23 NNT 47
-Reduced length of NICU stay in tight control
-Increased serious health outcomes for women in tight control group RR 2.28 NNTH 27)
-No difference in CS, IOL, PET
-Increased need for pharmacological input int he tighter control group
Discuss the MiG study
-Aim
-Methods
-Primary outcomes (1)
-Secondary outcomes (5)
- Aim
-To determine the efficacy and safety of metformin in the management of GDM - Methods
-Open RCT
-Metformin or metformin and insulin vs insulin
-Women between 20-33 weeks with GDM - Primary outcomes
-Composite measure of: Neonatal hypoglycemia, respiratory distress, Apgar scores, need for photo therapy, birth trauma and prematurity - Secondary outcomes
-Anthropromorphic measures
-Maternal glycemic control
-Maternal HTN complications
-Acceptability of Rx
-PP glucose tolerance
Discuss MiG study
-Number included in study
-Results from primary outcome
-Results to secondary outcomes
- Number included in the study
750 - Results from primary outcome
-No difference in composite outcome between groups 30 vs 32% - Results from secondary outcomes
-Higher acceptability in the metformin group for treatment (SS)
-No SS difference for other outcomes
-No SAE with metformin
