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Phase 2a - Endocrinology > Endocrinopathies in pregnancy > Flashcards

Endocrinopathies in pregnancy Flashcards

1
Q

True or false?

All women of reproductive age with endocrine disease should have access to preconception specialist to make choices about pregnancy.

A

True

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2
Q

What hormone is produced during pregnancy?

A

Human chorionic gonadotrophin hCG

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3
Q

In the first trimester what hormones are produced?

A

Progesterone
Oestradiol
Free estriol
Human placental lactogen

These can affect TSH levels.

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4
Q

Is there a separate pregnancy range for TSH?

A

Yes

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5
Q

What are the metabolic changes in pregnancy?

A
  • Increased erythropoetin, cortisol, noradrenaline
  • High cardiac output
  • Plasma volume expansion
  • High cholesterol and triglycerides
  • Pro thrombotic and inflammatory state
  • Insulin resistance
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6
Q

Name some of the gestational syndromes

A
  • Pre-Eclampsia
  • Gestational Diabetes
  • Obstetric cholestasis
  • Gestational Thyrotoxicosis
  • Transient Diabetes Insipidus
  • Lipid disorders
  • Postnatal depression
  • Postpartum thyroiditis
  • Postnatal autoimmune disease
  • Paternal Disease
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7
Q

When does foetal thyroid follicle and thyroxine synthesis occur?

A

Weeks 10.

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8
Q

The hypothalamus-pituitary-thyroid axis matures by when?

A

At 15-20 weeks.

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9
Q

What regulates neurogenesis, migration and differentiation between weeks 0-12?

A

Maternal T4

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10
Q

Describe the relative changes in maternal and foetal thyroid function during pregnancy.

A

The effects of pregnancy on the mother include a marked and early increase in hepatic production of thyroxine-binding globulin (TBG) and placental production of hCG.

The increase in serum TBG in turn increases T4 concentration.

hCG has thyrotropin-like activity and stimulates maternal T4 secretion.

The transient hCG-induced increase in serum free T4 inhibits maternal secretion of thyrotropin.

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11
Q

What happens in women with normal thyroid function during pregnancy?

A

Increase in T3 (triiodothyronine) and T4 (thyroxine). This inhibits TSH in the first trimester due to high hCG.

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12
Q

Why does high hCG level inhibits TSH production?

A

Because there is partial structural similarity so hCG stimulates TSH-R.

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13
Q

Why are thyroxine requirements higher in pregnancy?

A

A large plasma volume and thus an altered distribution of thyroid hormone, increased thyroid hormone metabolism, increased renal clearance of iodide, and higher levels of hepatic production of thyroxine-binding globulin (TBG) in the hyperestrogenic state.

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14
Q

TSH, LH, FSH, hCG have what in common?

A

Their alpha subunit is the same but they differ in the beta subunits.

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15
Q

Prevalence of Hypothyroidism during pregnancy

A

During pregnancy: 2-3%
Overt hypothyroidism: 0.3-0.5%
Subclinical: 2-3%

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16
Q

What are the signs and symptoms of hypothyroidism?

A

Predate the pregnancy.

Weight gain, cold intolerance, poor concentration, poor sleep pattern, dry skin, constipation, tiredness.

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17
Q

What is the TSH specific range for the first trimester?

A

0.1-2.5 mlU/L

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18
Q

What is the TSH specific range for the second trimester?

A

0.2-3.0 mlU/L

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19
Q

What is the TSH specific range for the third trimester?

A

0.3-3.0/3.5 mlU/L

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20
Q

How often are patients seen for 20 weeks of gestation?

A

4 weekly

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21
Q

How does levothyroxine dosage changes during pregnancy?

A

It goes up during pregnancy - then needs to go back to pre-pregnancy levels after delivery.

Requirements go up in the beginning up to a 125 micrograms until test can be carried out.

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22
Q

In high risk women, TSH needs to be checked as soon as pregnancy is confirmed with TPOAb if TSH is what?

A

If TSH is between 2.5-10 mU/L.

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23
Q

What are the primary causes of hypothyroidism

A

Autoimmune
Hashimoto’s disease
Atrophic thyroiditis
Drugs
Lithium
Amiodarone
Iodine deficiency
Congenital
Toxic nodule

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24
Q

What are the transient causes of hypothyroidism?

A

Post partum thyroiditis
Subacute thyroiditis

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25
What is the secondary cause of hypothyroidism?
Hypopituitarism
26
How does hypothyroidism affect pregnancy?
Inadequate treatment: - Gestational hypertension - Placental abruption - Post partum haemorrhage If untreated: - Low birth weight - Preterm delivery - Neonatal goitre - Neonatal respiratory distress
27
What is the course of action in hypothyroidism during pregnancy?
Preconception counselling ideal pre-conception TSH <2.5 mIU/L Increase dose by 30 % arrange TFT early preg and titrate women require a dose increase in their thyroxine during pregnancy If overt in pregnancy aim to normalise asap Commence at 50-100mcg measure TFT at 4-6 weeks.
28
Targeted screening
Age >30 BMI >40 Miscarriage preterm labour Personal or family history Goitre Anti TPO Type 1 DM Head and neck irradiation Amiodarone, Lithium or contrast use
29
What is the prevalence of Hyperthyroidism in pregnancy?
0.1-0.4%
30
Which gender is more affected?
Females 2%
31
Hyperthyroidism is 1 in how many pregnancies?
1 in 500
32
What is the main cause of hyperthyroidism?
Graves' disease (85-90%
33
What re the less common causes of hyperthryoidism?
Toxic adenoma MNG Gestational thyrotoxicosis Trophoblastic neoplasia TSH-oma
34
How does hyperthyroidism affect the pregnancy?
If inadequately treated: - IUGR (intrauterine growth restriction) - Low birth weight - Pre-eclampsia - Preterm delivery - Risk of stillbirth - Risk of miscarriage
35
How does pregnancy affect hyperthyroidism?
Tends to worsen in the first trimester. Improves in the latter half of pregnancy.
36
Symptomatic treatment of hyperthyroidism in pregnancy?
Beta blockers, i.e. propranolol 10-20 mg TDS
37
What other medication can be used for hyperthyroidism?
Anti-thyroid medication
38
What is the choice of anti-thyroid medication?
Propylthiouracil PTU
39
How does Carbimazole work?
Prevents thyroid peroxidase enzyme coupling and iodinating tyrosine residues on thyroglobulin = reduce T3 and T4.
40
Is radioactive iodine therapy an option?
No - contraindicated during pregnancy.
41
What is the optimal timing for surgery if PT is intolerant?
2nd trimester.
42
Side effects of carbimazole
2-4 % teratogenic at 6-12 weeks Increased risk of congenital abnormalities Aplasia cutis Choanal atresia Intestinal anomalies Embryopathy
43
PTU side effects
2-3 % early Rare hepatotoxicity Renal abnormalities Head and neck Crosses the placenta risk fetal hypothyroidism
44
What is the management of hyperthyroidism in pregnancy?
Breastfeeding- PTU and Carbimazole cross over PTU safer (carbimazole doses over 20 mg may affect baby). Individualised plans weekly foetal heart rate monitoring from 20 weeks. Serial growth scans in the 3rd trimester. Risk hydrops, foetal goitre and growth restriction. Tricky situation if foetal thyrotoxicosis identified mortality =15 %.
45
Are TSH-receptor antibodies measured?
Measured at the beginning and again 22-26 weeks. If raised 2-3 fold or present fetal/neonatal thyrotoxicosis risk increased and surveillance needed.
46
Surveillance is needed even if PT had...
Euthyroid/Surgery or RAI previously.
47
Who to test for antibodies?
Current or past Graves Previous neonate with Graves.
48
Describe foetal thyrotoxicosis
Transplacental cross over of TSH-R antibodies. Occurs in 0.01 % of cases. Management options anti-thyroid medication.
49
What is foetal thyrotoxicosis associated with?
IUGR Fetal goitre Fetal Tachycardia Fetal hydrops Preterm delivery Fetal demise (=stillbirth)
50
What is the guideline for maternal hyperthyroidism that is gestational thyrotoxicosis and subclinical hyperthyroidism?
Avoid treatment and continued clinical monitoring.
51
Algorithm for clinical hyperthyroidism (symptoms) in first trimester.
PTU as first line. Thyroidectomy is recommended in 2nd trimester if dose required is >450 mg/day or in case of intolerance to PTU.
52
Algorithm for clinical hyperthyroidism (symptomatic) in the 2nd and 3rd trimesters.
Methimazole or PTU if allergic to PTU. Thyroidectomy is recommended in second trimester if doses > 30 mg/day or intolerance to Methimazole.
53
Gestational Transient Thyrotoxicosis (GTT)
Limited to the first half of the pregnancy. Due to HCG. Raised T4, Low/suppressed TSH. Absence of thyroid autoimmunity. Associated with hyperemesis gravidarum. 5-10 cases/1000 pregnancies. Multiple gestation. Hydatidiform mole (=a rare mass or growth that forms inside the womb (uterus) at the beginning of a pregnancy). Hyperplacentosis. Choriocarcinoma.
54
What are the issues with GTT?
Benefits of treating. Hyperemesis gravidum. Extreme- Wernicke’s encephalopathy electrolyte imbalance low K and IUGR. Thyrotoxicosis risks.
55
In which disease do symptoms predate pregnancy: Graves or GTT?
Graves ++
56
Which disease has worse symptoms during pregnancy, Graves or GTT?
Graves +++
57
Nausea and vomiting is more common in which disease?
GTT
58
Goitre with bruit is present in which disease?
Graves
59
TSH-R antibody is present in which disease?
Graves
60
Port partum thyroiditis
Prevalence 7 %. High risk women are. Type 1 diabetics. Graves disease in remission. Chronic viral hepatitis. Measure TSH 3 months post partum.
61
Nodular thyroid disease and pregnancy.
Hormone stimulation increases the size of the thyroid in pregnancy. Relative immunosuppression and iodine deficiency. Nodule investigation similar to non pregnant. TFT and USS. Surgery 2nd trimester if cancer.
62
Microprolactinoma
Common <10mm rarely encroach chiasm Low risk enlargement risk 2-3%
63
What medications are used to treat microprolactinoma?
Bromocriptine and cabergoline safe in early pregnancy. No increase in fetal losses/malformations. Can discontinue when pregnancy confirmed.
64
Pituitary macroadenomas
Common >10mm can encroach chiasm Higher risk - enlargement risk 20-30%.
65
Management of pituitary macroadenomas?
Bromocriptine and cabergoline safe in early pregnancy can continue. Anaesthetist enlargement risk. Each trimester visual fields. MRI without contrast/Discuss in Pituitary MDT.
66
Pituitary insufficiency is due to
Previous pituitary surgery. Radiotherapy. Adenomas, infarction or lymphocytic hypophysitis.
67
Pituitary insufficiency can lead to
Subfertility
68
Management of pituitary insufficiency
Adequate hormonal replacement pre-pregnancy. Steroids- increase by 25 % in final trimester. Thyroxine FT4 in upper ¾ reference range.
69
Diabetes insipidus in pregnancy
In up to 1 in 30,000 pregnancies. Can predate the pregnancy, CDI or NDI. Can worsen as a result of placental vasopressinase (pvp) production and reduction in ADH. Can be transient and resolve 6 weeks post partum if result of pvp. Can also result if hepatic issues as liver breakdowns pvp. ADH use may need higher than normal doses. Oxytocin implication for delivery plan increase rate of uterine atony and failure to progress in labour.
70
Acromegaly in pregnancy
Uncommon. Needs careful reviews MDT. Assays after pregnancy to diagnose as placental growth hormone measured. IGF-1 also elevated in pregnancy. Risks: GDM,CAD, cardiomyopathy. SSA/DA agonists/GH receptor ligand usage. TSH second trimester. Tumour expansion.
71
Primary parahyperthyroidism in pregnancy?
8/100,000 child bearing age. BP or PET up to 25 % affected pregnancies. Can be complicated with mortality and morbidity from: Pancreatitis Hypercalcaemia crises Confusion Stones Fetal mortality 40 %- miscarriage, IUGR, stillbirth, neonatal tetany, neonatal death. Keep Adj Ca <2.85 mmol/L Study 109 who had parathyroidectomy in pregnancy had reduced fetal complications I second trimester.
72
Hypothyroidism in pregnancy
Rare and mainly complication of previous thyroidectomy. Active vitamin D calcitriol or alfacalcidol. Monitor bloods 4 weekly post partum and during breast feeding. Increase in demand for calcium in pregnancy for felt skeleton and during lactation. Undertreatment can lead to: - Hypocalcaemia which maybe asymptomatic or cause: cramps, tetany, seizures, CCF. - Abortion preterm labour and dysfunctional labour. - Fetal mineralisation abnormalities, fractures, intracranial bleeds and primary hyperparathyroidism.
73
Cushing's syndrome in pregnancy
Rare. GC excess from any causes. Cushing’s disease from a pituitary lesions. Cushing’s adrenal lesions (rarely carcinoma). Features: Weight gain, fatigue, glucose intolerance, BP, Red purple striae, proximal myopathy, fractures, hyperandrogenism, hirsuitsm,acne.
74
Cushing's syndrome results in
Greater incidence of BP in pregnancy 68% PET 9% Preterm delivery 43 % Still birth 6% Neonatal adrenal insufficiency Investigation is warranted and treatment and surgery if indicated MDT discussion
75
Conn's syndrome
Primary hyperaldosteronism: Rarely reported in pregnancy. Reflects underdiagnosis. Suspect in BP, hypokalaemia, and metabolic alkalosis. Adrenal adenoma most common cause 75 %. High rates PET, placental abruption, preterm delivery. Investigate, treat with caution spironolactone, amiloride, eplenronone, palaroscopic adrenalectomy in pregnancy has been used to reat.
76
Congenital adrenal hyperplasia
Group of disorders enzymatic defects in adrenal steroid synthesis. Common 21-hydroxylase def 90 % 11-Hydroxylase Def 8-9%. Classical rare autosomal recessive. If couple have ¼ risk. CAH pregnancy increased risk miscarriage, preg induced BP, GDM, IUGR. GC, Mineralocorticoid replacement and sick day rules.
76
Phaeochromocytoma
Rare catecholamine secreting tumour of the adrenal medulla. Unrecognised mortality of 50% in labour or GA induction. Catecholamines cause uteroplacental vasoconstriction, placental insufficiency or abruption.
76
Management of CAH
Pre-conception counselling and testing in case partner is a carrier. High dose steroids to prevent masculization if a female fetus is identified start preconception 1-1.5mg/day of dex only 1/8 may benefit. CVS at 10-11 weeks.
77
Adrenal insufficiency
If diagnosis in pregnancy. Nausea, vomiting, weakness, hyponatraemia, weight loss, hyperpigmentation, and greater magnitude of hyponatraemia >5 mmol/L or hypoglycaemia, collapse or postural hypotension. Known increase 25 % steroid dose in final trimester and cover for sections and labour. Sick day rules.
78
PPGL can lead to
Can cause hypertensive crisis or CCF. Paroxysms of hypertension, Palpitations, headache or flushing may occur. Plasma mets and urinary cats/mets MRI scan. Alfa blockade. CS planning delivery paramount.
79
Adrenal adenomas / non-functioning
Usually no harm - but review the endocrine bloods.
80
Amiodarone induced thyrotoxicosis
Amiodarone -Iodine Rich often used to treat Atrial fibrillation. SE: pulmonary, GI, ophthalmic, neurologic, dermatologic (pigmented grey appearance), thyroid. Incidence AIT 3 % M>F AIH 22 % F>M Prognosis Dronedarone does not contain Iodine
81
Type 1 AIT
AIT type 1 Latent pre-existing Low iodine areas Iodine induced excess Thyroid hormone release Jode-Basedow phenomenon
82
Type 2 AIT
AIT Type 2 Normal Thyroid Destructive
83
Ipilimumab Hypophysitis
Can occur as early as 4 weeks after. Median 11 weeks. Most remain on Glucocorticoids. Males>Females (unlike lymphocytic hypophysitis). More frequent with increased usage given overall survival benefit. Strategies for early detection.

Phase 2a - Endocrinology (11 decks)

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