The document discusses several key points regarding endocrine diseases and pregnancy: 1) The thyroid gland has important functions in maintaining pregnancy, including increased T4 requirements by the mother and fetus' dependence on maternal hormones in early pregnancy. 2) Physiological changes include suppression of TSH and increases in thyroid hormones and binding proteins, maintaining normal free levels. 3) Iodine deficiency is a major cause of thyroid issues worldwide, and intake of 250 μg/day is recommended for pregnant women. 4) Hypothyroidism occurs in 1% of pregnancies and requires thyroxine treatment. Thyrotoxicosis also requires medication management to prevent complications.

1. Endocrine diseases and
pregnancy
Yu.A.Lyzikova

2. Physiological changes in thyroid gland function
• The thyroid gland has an
important function in
maintaining a viable
pregnancy.
• There are increased
requirements for T4 in
pregnancy, and the fetus
is totally dependent on
the placenta to provide
thyroxine until about 18
weeks gestation

3. Physiological changes in thyroid gland function
1. The structure of HCG is similar to TSH and
provides some stimulation to T4 production
These cause hyperplasia of the gland
2. This results in TSH being suppressed by the
negative feedback
3. Maternal serum iodine levels fall due to
increased renal loss and also due to
transplacental shift to the fetus. Iodine
deficiency is the commonest cause of thyroid
insufficiency worldwide

4. Physiological changes in thyroid gland
function
4. Thyroxin binding globulin (TBG) increases
due to estrogen stimulation till 20 weeks.
It remains unchanged until delivery
5. Total T4 and T3 are increased but free T4 and
T3 levels are unchanged. TSH remains
normal

5. Thyroid supply to the fetus
• The fetal thyroid begins concentrating iodine
at 10–12 weeks gestation.
• Although there is no functioning fetal thyroid
in early pregnancy, thyroid hormone is
important in the development of many
organs including the brain.
• Fetus is dependent on the maternal
hormones until about 17-18 weeks

6. Thyroid supply to the fetus
• Maternal circulating T4 crosses the placenta
into the fetus at all stages of pregnancy by
incompletely understood mechanisms but
involving both the type 2 and type 3
deiodinase enzymes, both expressed in the
placenta

7. • Type 3 deiodinase (D3),
may act as a ‘gatekeeper’
to prevent too much
thyroid hormone transport
• Type 2 deiodinase,
degrades T4 in the fetus to
provide T3 for tissue
growth and differentiation
and may have a role in
fetal implantation.

8. Iodine and pregnancy
• The recommended daily iodine intake in
pregnancy 250 μg/day
• Iodine deficiency during pregnancy is due to
the imbalance between the intake and
increased requirements for iodine during
gestation.

9. Iodine and pregnancy
• Clinical studies of children born to mothers
with known iodine deficiency clearly showed
impaired neurointellectual development,
sometimes to the extreme of cretinism in
severely deficient states.
• These defects can be corrected by iodine
administration before and even during
gestation and this should be performed in
areas of moderate to severe iodine
deficiency.

10. Iodine and pregnancy
• It is recommended that
women who are
pregnant, planning a
pregnancy or are breast
feeding should receive
250 μg of iodine daily

11. Thyroid Disease
• Definition
• Overt hypothyroidism is defined as a raised
TSH level in association with a decreased level
of free T4
• Subclinical hypothyroidism is diagnosed when
the TSH level is elevated, but T4 is still within
the normal range

12. Hypothyroidism
• Hypothyroidism complicates around 1% of
pregnancies.
• Most cases have been diagnosed previously
and patients are on replacement therapy.
• New diagnosis in pregnancy is rare.
• The commonest cause is autoimmune and
may be associated with other autoimmune
conditions.

13. Clinical Assessment
History
Women with overt hypothyroidism often suffer
from subfertility.
Women with subclinical hypothyroidism are
generally asymptomatic.
 Examination
Enlarged thyroid gland may be present.
Investigations: Thyroid function tests – TSH, T4,
and thyroid antibodies can be measured in a
sample of blood.

14. Treatment
• Medical
• Women with subclinical hypothyroidism,
should be treated with thyroxine, if the TSH
is ↑

15. Treatment
• Women with subclinical hypothyroid with
positive thyroid auto antibodies, overt
hypothyroidism should treated with
thyroxine
• Women who are on thyroid replacement
therapy pre pregnancy will often need to
increase the dose of thyroxine being taken

16. thyroxine
• 100 – 200 micrograms a
day
• The correct dose is
determined by
analyzing the levels of
thyroid hormnes in the
blood

17. Complications
• Hypothyroidism is associated with an
increased risk of hypertension, preeclampsia,
placental abruption, anaemia.
• There are also adverse outcomes for the
neonate including prematurity, low birth
weight, increased perinatal morbidity and
mortality, and cognitive and developmental
impairment.

19. Thyrotoxicosis
• The most common cause
is Graves’ disease (95%).
• This is an autoimmune
disease characterized by
the production of TSH
receptor stimulating
antibodies.
• Most women have been
diagnosed before
pregnancy and may be
on treatment.

20. Thyrotoxicosis
Clinical signs
• weight loss
• tremor
• persistent tachycardia
• eye signs
• Diagnosis is made by a
low TSH and high free
T4 or free T3 levels.

21. Thyrotoxicosis
Effect of thyrotoxicosis on pregnancy
• Maternal and fetal outcome usually good if
disease is controlled.
• Untreated or poorly controlled
thyrotoxicosis is associated with sub- fertility
(amenorrhoea due to weight loss), risk of
miscarriage, IUGR, and premature delivery.

22. Thyrotoxicosis
• With the stress of infection, operative
delivery a ‘thyroid storm’ can occur in poorly
controlled patients.
• This is a medical emergency, characterized by
pyrexia, confusion, and cardiac failure.

23. Thyrotoxicosis
• Thyroid storm, also referred to as thyrotoxic crisis, is
an acute, life-threatening, hypermetabolic state
induced by excessive release of thyroid hormones
(THs) in individuals with thyrotoxicosis.
• The clinical presentation includes fever,
tachycardia, hypertension, and neurological and GI
abnormalities.
• Hypertension may be followed by congestive heart
failure that is associated with hypotension and shock.
• Because thyroid storm is almost invariably fatal if left
untreated, rapid diagnosis and aggressive treatment
are critical.

25. Thyrotoxicosis
• Neonatal-fetal thyrotoxicosis occurs in up to 10% of
babies born to women with current or past history of
Graves’ disease (transplacental passage of thyroid
receptor stimulating antibodies).
• The probability of neonatal hyperthyroidism is high in
the babies of mothers that have ongoing antithyroid
requirement and higher antibody levels in the last
months of pregnancy.
• Clinical manifestation may be delayed by 7–17 days
because of the antithyroid drugs taken by the mother.
• Neonatal hyperthyroidism symptoms can be
confused with sepsis and congenital viral infections.

26. Treatment
 Antithyroid drugs: carbimazole and
propylthiouracil (PTU) are the two drugs used.
• The aim of treatment is to achieve clinical
euthyroid with T 4 at the upper limit of
normal.
• Use the lowest dose of drug to achieve this.
• Both drugs cross the placenta and may cause
fetal hypothyroidism in high doses.
• PTU is preferred for new cases as there is less
transfer across the placenta and into
breastmilk.

27. • Propylthiouracil inhibits the production of new
thyroid hormone in the thyroid gland
• It acts by inhibiting the enzyme thyroid
peroxidase, which usually functions to convert
iodide to iodine molecule
• Adults: Propylthiouracil is administered orally,
initially as 300 mg/day in three divided doses
every 8 hours (may reach up to 600 to 900
mg/day).
• The dose is adjusted to maintain normal TSH, T3,
and T4 levels.

28. • Pregnant: PTU is a pregnancy category D drug.
PTU can cross the placenta and can cause fetal
cretinism and goiter.
• Methimazole causes fetal anatomical
abnormalities; if it is necessary to use
antithyroid drugs in pregnancy, PTU is preferred
in the first trimester with the lowest possible
drug dose usage.
• Due to the increased reported risk of maternal
hepatotoxicity from PTU, methimazole should
be used in the second and third trimesters

29. Treatment
Surgery: thyroidectomy
• Indications : suspected carcinoma and
allergies to both antithyroid drugs.

30. Other thyroid diseases
Thyroid nodules
• Thyroid nodules are common, affecting 5%
of women in their reproductive years.
• A small proportion of thyroid nodules are
malignant.

31. Thyroid nodules
Investigations: thyroid
hormones, needle
aspiration for cytology
(cystic lesion), biopsy
(solid lesion).
Malignant lesions can be
surgically treated in the
2nd and 3rd trimesters,
and postoperatively
thyroxine can be safely
given.

32. Screening for thyroid dysfunction in
pregnancy
• Screening is a strategy to detect a disease in
asymptomatic individuals in order to improve
health outcomes by early diagnosis and
treatment.
• Endocrine Society: Screening should be
performed in those women at high risk for
thyroid disease.

33. Screening for thyroid dysfunction in
pregnancy
• A study to validate this strategy found that
restricting screening to these groups of women
would miss about one-third of women with
significant thyroid dysfunction
• A cost-effective analysis of screening pregnant
women for autoimmune thyroid disease
concluded that screening pregnant women in
the first trimester for TSH was cost effective
compared with no screening
• Screening using anti-TPOAbs was also cost
effective

34. Diabetes
Diabetes mellitus is a chronic metabolic
disorder due to either insulin deficiency
(relative or absolute) or due to peripheral
tissue resistance (decreased sensitivity) to
the action of insulin.

35. Diabetes
3 types are generally described.
Type–1 is characterized by young age onset
(Juvenile) and absolute insulinopenia.
Type–2 (NIDDM) is characterized by late age
onset, overweight woman and peripheral
tissue (skeletal muscle, liver) insulin
resistance (hyper insulinemia). Genetic
predisposition is also observed.
Type-3 – Gestational diabetes mellitus

37. Diabetes
Diabetes is the most common maternal
medical disorder complicating pregnancy with
significantly increased maternal complications
and fetal and neonatal risks.
• Type I, type 2, and gestational diabetes affect
5% of pregnancies. This rate is rapidly rising
• Of women who have diabetes during
pregnancy, it is estimated that approximately
87% have gestational diabetes (which may or
may not resolve after pregnancy), 7% have
type 1 diabetes and the remaining 6% have
type 2 diabetes.

38. Diabetes
• Without good glycaemic control there is
increased fetal and neonatal morbidity and
mortality.
• Glucose metabolism is altered by pregnancy.
• Many pregnancy hormones are diabetogenic
(human placental lactogen, cortisol,
glucagon, oestrogen, and progesterone).

39. Effect of diabetes on pregnancy
• Maternal hyperglycaemia: leads to fetal
hyperglycaemia.
• Fetal hyperglycaemia: leads to
hyperinsulinaemia (through β -cell
hyperplasia in fetal pancreatic cells).

40. Fetal hyperglycaemia

41. Fetal hyperglycaemia
• Insulin acts as a growth
promoter:
macrosomia,
organomegaly, fetal
polyuria
(polyhydramnios).

42. Complications of diabetes in
pregnancy
• Maternal
• Recurrent vulvovaginal candidiasis.
• Pregnancy-induced hypertension/pre-
eclampsia.
• Operative deliveries: CS and assisted vaginal
deliveries.
• Retinopathy
• Nephropathy.

43. Complications of diabetes in
pregnancy
• Fetal
• Miscarriage
• Congenital abnormalities: neural tube defects,
microcephaly, cardiac abnormalities, renal
abnormalities.
• Preterm labour.
• Polyhydramnios (25%).
• Macrosomia (25–40%).
• IUGR.
• Unexplained IUD.

44. Complications of diabetes in
pregnancy
• Neonatal
• Hypoglycaemia.
• Hypothermia.
• Birth trauma: shoulder dystocia, fractures,
asphyxia.
• Respiratory distress syndrome.

48. Diabetes: antenatal management
• Prepregnancy counselling
• Achievement of optimal control: keep fasting
blood glucose between 3.5 and 5.9mmol/L
and 1h post-prandial <7.8mmol/L
• Assessment of severity of diabetes: check for
hypertension, retinopathy , nephropathy,
neuropathy.

49. Diabetes: antenatal management
• General health: stop smoking, optimize
weight (aim for a normal BMI)
• Folic acid: risk of neural tube defects, so start
on 5mg folic acid.
• Contraception: ensure effective
contraception until good control achieved and
pregnancy desired.

50. Antenatal care
• Control: as for prepregnancy,
aim for normoglycaemia.
• Monitor glucose at least 4
times/day, usually before
meals.
• Women can alter their own
insulin based on their glucose.
Insulin can be given as SC
injections 2 or 4 times/day or
as a continuous infusion.

51. Antenatal care
• HbA1c every month:
this gives an objective
measurement of control
over the preceding
2mths.
• Dietitian review: low
sugar, low fat, high fibre
diet—low glycaemic
index.

52. HbA1c
• By measuring glycated haemoglobin (HbA1c),
clinicians are able to get an overall picture of
what average blood sugar levels have been
over a period of weeks/months.
• The HbA1c target for people with diabetes to
aim for is:
• 48 mmol/mol (6.5%)

53. Pre-conception assessment and
counselling
• Monthly HbA1c monitoring.
• Inform women that any reduction in HbA1c
may reduce risks
• less than 48 mmol/mol (<6.5%) if safe.
• Women with HbA1c 86 mmol/mol or more
(≥10%) should be advised to avoid a
pregnancy till better control is established.

54. Antenatal care
• Down’s syndrome screening
• 5–10-fold risk of congenital anomalies. Risk
depends on glycaemic control prior to
conception and early pregnancy.
• Serial USS every 2–4wks to detect
polyhydramnios, macrosomia, or IUGR.

55. Diabetes: labour and post-partum
care
• Timing and mode of delivery should be
individualized and based on obstetric factors
(previous mode of delivery, gestation,
glycaemic control, and antenatal
complications).
• 38–39wks if there are no maternal or fetal
complications and good glycaemic control.

56. labour and post-partum care
• Mode of delivery
• Vaginal delivery is preferred. Continuous
electronic fetal monitoring is advised in labour.
• Consider elective CS if EFW is >4.5kg.
• CS rates are high: 50–60%.
• Give antibiotic and thromboprophylaxis if CS is
carried out.
• Shoulder dystocia is more common at all birth
weights than in the non-diabetic population.

57. Post-partum care
• Encourage breast-feeding.
• Avoid oral hypoglycaemic drugs if breast-
feeding.
• Baby needs early feeding and glucose
monitoring.

58. Gestational diabetes
• The World Health Organization (WHO) now includes
gestational impaired glucose tolerance (IGT) with
gestational diabetes.
• A proportion of women diagnosed in pregnancy will
actually have previously unrecognized type 1 or 2
diabetes (20–30%).
• Selective screening should be based on risk factors.
• Risk factors for gestational diabetes
• BMI above 30kg/m
• Previous macrosomic baby weighing 4.5kg or above.
• Previous gestational diabetes.
• First-degree relative with diabetes.

59. Management
Measure glucose 4–6 times/day
Diet should be first-line treatment: aim for
normoglycaemia and avoid ketosis.
Start insulin if: pre-meal glucose >6.0mmol/L ,
1h post-prandial glucose >7.5mmol/L.
OGTT at 6wks post-partum
50% risk of developing type 2 diabetes mellitus
over next 25yrs (this risk can be reduced by
maintaining physical activity and avoiding
obesity).

60. Diagnostic criteria
Normal levels of blood glucose during
pregnancy:
Basal - 3.3 - 4.4 mmol / L
1 hour after the meal - less than 7.5 mmol /
L;
2 hours after eating - less than 6.7 mmol / l.
 less than 48 mmol/mol (<6.5%) if safeless
than 48 mmol/mol (<6.5%) if safe

61. Contraindication to pregnancy in
diabetic patients
Absolute:
- Proliferative retinopathy
- Diabetic nephropathy
- The combination of diabetes mellitus and
active pulmonary tuberculosis.