2. References
• Management of Thyroid Dysfunction during
Pregnancy and Postpartum: The journal of clinical
endocrinology and metabolism
• William’s Obstetrics – 23rd edition
• Harrison’s Principles of Internal Medicine – 18th edition
• Goodman & Gilman's The Pharmacological Basis of
Therapeutics
• Samar Banerjee “Thyroid Disorders in Pregnancy”
- Supplement to JAPI • January 2011 • VOL. 59
• Mark E. Molitch, MD – Endotext.org “Pituitary and adrenal
disorders in pregnancy”
• Beverly M. K. Biller M.D. “Cabergoline - A New
Dopamine Agonist for the Therapy of Prolactinoma”
3. Topics covered
I. Thyroid disorders in pregnancy
II. Parathyroid disorders in pregnancy
III. Adrenal disorders in pregnancy
IV. Pituitary disorders in pregnancy
4. Introduction
• Among endocrinopathies in
pregnancy, diabetes mellitus – commonest
• Thyroid disorders are second
• Pituitary, adrenal and parathyroid disorders
are less common
• Basic pathology – disordered autoimmunity
- hypersecretion
– Fetal lymphocytes
– Fetal stem cells
– Fetal DNA
Reside in maternal endocrine
organs
5. I. THYROID DISORDERS IN PREGNANCY
Physiology
• Pregnancy has a substantial impact on
maternal thyroid physiology
• Symptoms of thyroid disease during
pregnancy may be confused as physiological
changes
• 2-5% pregnancies are complicated with
thyroid disease
6. • The most important physiological changes are
i. Thyroxine binding globulin (TBG) increases –
response to estrogen, also half life increases (15
min to 3 days)
ii. Increase in thyroid
stimulatory factors
of placental origin
(e.g.. hCG)
iii. Decreased iodine
availability –
enhanced excretion (increased GFR)
iv. BMR increases by 25% in pregnancy
7. Pathophysiology of autoimmunity
• Autoantibodies have one or more of the
following effects
– Stimulation
– Inhibition
– Inflammation & destruction
• Autoimmune phenomenon - follows a
precipitating event
– Viral infection
– Radiation exposure
– Inherent genetic predisposition
– Pregnancy itself
8. • Development of antibodies (Fetal – maternal cell
trafficking)
– Fetal lymphocytes (male fetus>female) enter maternal
circulation and act against the thyroid parenchyma
– Maternal microchimerism – SRY region of the male
fetal lymphocytes specifically target thyroid cells
• More commonly thyroid peroxidase antibodies
occur (10-20% pregnancies), 50% of these
patients develop autoimmune thyroiditis
• May ultimately develop thyroid failure.
9. A) Hyperthyroidism
• Symptomatic thyrotoxicosis occurs in 1/1000
or 1/2000 pregnancies
• Difficult to differentiate mild disease from
normal pregnancy symptoms
• Elevated T4 with markedly depressed TSH is
diagnostic
• Normal T3 and T4 with depressed TSH
indicates subclinical hyperthyroidism
10. • Thyrotoxic patients will have high Thyroid
stimulating antibodies
• However, since autoimmune remission occurs
due to pregnancy – and symptoms are
relieved
11. • Propylthiouracil was preferred (trans placental
passage) to Methimazole (aplasia cutis &
embryopathy - choanal atresia)
• Propylthiouracil – liver failure in pregnancy
• Carbimazole – used safely in EU (rarely associated
with GI anomalies)
Recommendations suggest:
• Propylthiouracil (100-600mg/day) – 1st line in 1st
trimester
• Methimazole (10-40 mg/day) in the 2nd and 3rd
• Both equally efficacious
12. • Dosage to be adjusted to maintain total T4 at
1 ½ times upper limit of normal
• TFT – every 2-4 weeks
• LFT – every 3-4 weeks (Propylthiouracil)
• CBC – to assess transient
leukopenia/agranulocytosis (Methimazole)
• Subtotal thyroidectomy
– Severe adverse reactions to medical therapy
– Persistent high doses are needed (>450mg PTU or
>30 mg MMI)
– Non-adherence to therapy
13. Fetal considerations of maternal hyperthyroidism
• Thyroid receptor antibodies freely cross placenta
• TRAb should be measured by 22 wks of gestation in
mothers with
– Graves’ disease
– h/o Graves’ with I131 therapy prior to pregnancy
– Previous neonate with Graves’ disease
– Previous documented TRAb
• If I131 is given inadvertently
– Suggest abortion
– Evaluate fetal hypothyroidism
14. Thyroid storm in pregnancy
• Rare
• Thyroxine induced myocardial effects – precipitated
by preeclamsia, anemia and sepsis
Treatment
• 1g Propylthiouracil orally/RT, then 200mg Q6H
• 500mg – 1g Sodium iodide or 8 drops of
supersaturated KI
• Dexamethasone 2mg iv Q6H for 4 doses
• β blockers for tachyarrythmias
15. B) Hypothyroidism
• Overt Hypothyroidism – High TSH and low T4
• Subclinical – High TSH and normal T4
• Hypothyroidism – Adverse outcomes in mother
and fetus
• Treatment is known to improve obstetric
outcome, however neurodevelopmental long
term effects are not known enough
• Potential benefits > risks – Replacement therapy
is indicated in subclinical hypothyroidism
16.
17. • Thyroxine requirement in pregnancy is higher
than in non pregnant state.
• 30% increase in dosage is needed (TBG
increased)
• Hypothyroidism diagnosed during
pregnancy, treated with 50-100 μg/day with
TFT at 4-6 week intervals
• Dose adjustment with 25-50 μg till TSH
maintained around 2.5 mIU/L (1st trimester)
and 3.0 mIU/L (2nd & 3rd trimesters)
• Soon after delivery, dose reduction is required
18. • Iodine deficiency may be a cause for
hypothyroidism.
• Daily requirement of 220 - 250 μg/day has to
be met (not >500 μg/day)
Fetal manifestations of maternal hypothyroidism
– Decreased school performance
– Impaired reading
– Reduced IQ
• Congenital thyroid screening – mandatory in
the US and EU, not in India.
19. C) Gestational Thyrotoxicosis
• Also called Transient hyperthyroidism
• Associated with hyperemesis gravidarum
• High serum thyroxine and low TSH levels
• High βhCG levels – structural similarity to TSH
• Gestational trophoblastic disease can also
present with hyperthyroidism
20. • Patients with hyperemesis should be
evaluated for T4, TSH and TRAb
• Anti thyroid drugs – not indicated
• β blockers for peripheral manifestations
• Anti thyroid drugs are to be given only if
Graves’ disease is diagnosed
– Free T4 > 1 ½ times > upper limit of normal
– TSH <0.01 μIU/ml
21. D) Post partum thyroiditis
• Transient autoimmune thyroiditis
• 5-10% of women within a year of childbirth
• Women with TRAb and anti-TPO antibodies
before pregnancy are more prone to develop
this condition
• Likelihood of developing post partum
thyroiditis is high in Type 1 diabetics and
patients with chronic viral hepatitis
22. Clinical features
• 30% chance of eventual permanent hypothyroidism
• Post partum depression is associated with
it, although not very conclusively
23. Recommended patient profiles for targeted
thyroid disease case finding in women seeking
pregnancy, or newly pregnant
24. E) Nodular Thyroid disease
• Small thyroid nodules – normal in pregnancy
• Some studies suggest these nodules turning
malignant
• Diagnosis is mainly by sonography & FNAC
• FNAC – if nodules > 1cm
–5mm to 1cm with suspicious/high risk history
25. • If nodules are detected early
• Surgery within 26 wks – after that, surgery can
stimulate preterm labour
Surgery
Suspicious cytology
Lymphadenopathy
Rapid growth
26. • If nodules are detected in the 3rd
trimester, surgery – after delivery.
• Papillary and follicular carcinomas are
relatively slow growing & surgery can wait
• Radio-iodine therapy at least 4 weeks after
cessation of breastfeeding and the lady asked
not to conceive for 6 months to a year
27. II. PARATHYROID DISORDERS
• Fetal Calcium needs –
300 mg/day
• Pregnancy – increased
renal loss
• Increased intestinal
absorption
• Serum albumin low,
Corrected Ca – normal
28. • Pregnancy has no significant effect on PTH
levels
• Vitamin D levels higher – especially 3rd
trimester
– Not due to PTH
– Due to PTHrP, estradiol, prolactin & placental
lactogen all stimulate 1α hydroxylase (renal)
29. A) Hyperparathyroidism
• As in non pregnant state – commonest
parathyroid adenoma
– Hyperemesis
– Renal calculi
– Psychiatric disorders
– Generalized weakness
• Pregnancy blunts the effects due to higher
calcium requirement by the fetus
• Soon after delivery, postpartum hypercalcemic
crisis can occur
• Still births and preterm deliveries higher.
30. Management
• Elective neck exploration well tolerated even
in 3rd trimester
• Asymptomatic women to be given 1 – 1.5g
phosphate orally/day in divided doses
• Patient in hypercalcemic crisis…
– Furosemide to maintain urine output >150ml/hr
– Mithramycin at 25μg/kg once and 24 hrs later
– Calcitonin 100U every 6 hrs/8 hrs (sc or im)
31. B) Hypoparathyroidism
• Commonest cause – post thyroid/parathyroid surgery
• Facial muscle spasms, muscle cramps, paraesthesia of
lips, tongue, fingers, feet.
• Chronic hypocalcemia – multiple bone fractures in the
neonate
Treatment
• Calcitriol is the treatment of choice
• Vitamin D – 50,000 – 150,000 U/day to increase levels
of calcitriol
• Calcium gluconate 3-5 g/day
• Low phosphate diet
32. C) Pregnancy associated osteoporosis
• Increased calcium demand and poor oral
intake during pregnancy – reduced bone
mineral density
• Incidence is 4/million pregnancies
– Back pain
– Hip pain
– Difficulty in weight bearing
• Treatment is with calcium and Vitamin D
supplements
33. III. ADRENAL DISORDERS
• ACTH and cortisol
progressively increase
• Cortisol and progesterone
– antagonistic
• Mineralocorticoid action
needed to increase plasma
volume (cortisol &
aldosterone)
• Protects from natriuretic
effect of progesterone
Serial increases in serum
cortisol (blue line) and ACTH
(red line) during pregnancy.
34. A) Phaeochromocytoma
• These chromaffin tumours are rare but
dangerous
• Maternal death higher – undiagnosed
antepartum
• Patients can die during labour or during
induction of anaesthesia
• Biggest diagnostic problem is attributing
hypertension to PIH/preeclampsia
35. • As the fetus grows, uterus compresses the
tumour and cause
• Hemorrhage into the neoplasm
• Severe hypertension
• Hemodynamic compromise
• Myocardial infarction
• Arrhythmias
• Congestive cardiac failure
• Index of suspicion must be high – especially
• Severe/uncontrolled/paroxysmal hypertension
• Orthostatic hypotension
• Families associated with MEN-2A
• Thyroid nodules – medullary carcinoma (MEN 2A)
• Neurofibromatoses
36. • 24 hr urine VMA or Metanephrine to diagnose
adrenal phaeochromocytoma (labetalol &
methyl dopa should be stopped)
• MIBG (I-metaiodobenzyl guanidine) for
extra-adrenal masses
• MR imaging
37. Treatment
• α blocker – phenoxybenzamine 10 – 30 mg 2-4
times a day
• β blocker only after α blockade achieved and if
tachycardia/arrhythmias persist
• Hypertensive emergencies treated with
phentolamine.
• In the 3rd trimester, C-section + tumour
excision or
• Post partum excision of tumour is done
38. B) Cushing syndrome
• Commonest cause is long term steroid therapy
• Bilateral adrenal hyperplasia due to ACTH
producing adenomas (<1cm microadenomas)
• Most patients have corticotropin dependant
Cushing syndrome and in such cases…
Prevents
pregnancy
Anovulation
Androgen
excess
40. However, diagnosis when it occurs is difficult
• Weight gain, fatigue, emotional lability, glucose
intolerance, edema
• Serum cortisol levels will be raised anyway (Urine
cortisol >3 times normal – can be diagnostic)
• Suppression and stimulation tests haven’t been studied
in pregnancy
Treatment
• Long term therapy not indicated – Resection of the
adenoma is definitive
• Metyrapone and Ketoconazole can be used till surgery
is planned
• Mifepristone cannot be used in pregnancy
41. C) Adrenal Insufficiency
• Primary adrenocortical insufficiency
(Addison’s) is rare
• Secondary to tuberculosis usually and
histoplasmosis rarely
• May be a part of “Polyglandular autoimmune
syndrome”
• Symptoms again overlap with normal
pregnancy – addisonian hyperpigmentation
mimics chloasma of pregnancy
42. • Since pregnancy is a hyper-cortisolemic state,
low cortisol levels must prompt an ACTH
stimulation test
• During labour – stress dose of hydrocortisone
i.e. 100mg 8th hourly
• Shock due to hemorrhage/sepsis – should be
ruled out
43. D) Primary aldosteronism
• Progesterone blocks aldosterone action
• Normal pregnancy will ameliorate symptoms
• Potassium supplements and antihypertensives
• Spironolactone cannot be used –
antiandrogenic effects
• Tumour resection in 2nd trimester is safe and
curative
44. E) Congenital adrenal hyperplasia
• CAH – mutations in genes encoding
steroidogenesis
• 21-Hydroxylase deficiency CYP21A–
commonest (90-95% of cases in pregnancy)
• The spontaneous abortion rate is twice more
common, congenital anomalies are frequent
• CPD due to android pelvis
• Fertility is improved with glucocorticoid
therapy – must for conception
45. Fetal risk of CAH
• Depends on carrier status of the father
• Dexamethasone 20 μg/kg/day upto 1.5 mg daily
in 3 divided doses – starting <9 wks of gestation
• Maternal plasma and/or urinary estriol levels
reflect fetal adrenal synthesis – assess efficacy
• Only 25% female fetuses affected – treatment
must be discontinued in male fetus/unaffected
female fetus
• CVS (9-11 wks) or amniocentesis for
androstenedione/17 (OH) Progesterone (14-16
wks) for early gender determination
46. IV. PITUITARY DISORDERS
• The pituitary gland enlarges by about 135%
• Vision impairment due to this normal
enlargement is very rare
• Attributed mainly to lactotrophs
• The gland involutes post partum – returns to
normal by 6 months
47. A) Prolactinoma
• Prolactin secreting tumours are quite common
• Microadenoma - <10 mm
• Macroadenoma - >10 mm
• In normal pregnancy,
– Prolactin levels increase markedly
– Reaches 10 times normal at term
– Levels decrease soon after delivery, despite breast
feeding
– Pulsatile bursts of prolactin occur in response to
suckling.
48. • Symptomatic tumour enlargement – rare with
microadenomas in pregnancy
• More frequent with macroadenomas (15-35%)
• Headache and vision loss – more common in
macroadenomas and such symptoms should
be assessed
• Vision testing in each trimester and MR
imaging should be done
49. • Microadenomas respond to Bromocriptine
• Some studies recommend Cabergoline
• Lesser side effects
• Longer half life (once a week dose)
• However, no adverse effect of bromocriptine
has been known to complicate such a
pregnancy
• Macroadenomas respond on to surgery (trans-
nasal endoscopic resection)
50. B) Acromegaly
• During normal pregnancy GH levels decrease, as
GH like peptides are secreted by the placenta
• Acromegaly is due to an acidophillic pituitary
adenoma
• Diagnosis is by failure of GH supression with oral
GTT
• Just like in prolactinomas – vision testing/MR
imaging is warranted
• Octreotide has shown some benefit
• Surgery may be indicated with symptomatic
tumours
51. C) Diabetes Insipidus
Central Transient Nephrogenic
• Central DI – spontaneous – enlarging pituitary adenoma
• Transient AVP resistant DI – production of vasopressinase
– Acute fatty liver of pregnancy or acute viral hepatitis can worsen DI –
hepatic degeneration of vasopressinase is reduced
– AVP levels fall – worsens symptoms
• Congenital nephrogenic DI is rare – thiazides to be used with
extreme caution
52. • Intranasal administration of desmopressin is
safe in pregnancy
• Dose may be increased if liver disease co-
exists in pregnancy
• By 4th week post partum, disease usually
resolves completely
53. D) Sheehan’s syndrome
• Pituitary necrosis secondary to ischemia within
hours of delivery
• Secondary to hypotension & shock following
obstetric haemorrhage
• Physiological gland size increase predisposes to
ischemic necrosis
– Hypotension & tachycardia persists even with
adequate blood replenishment
– Lactation fails, hypoglycaemia ensues
– Delayed symptoms are loss of
libido, amenorrhea, breast atrophy
54. • MRI reveals partial/completely empty sellae
• Replacement therapy is the only option
• Rare with good obstetric practise
Two distinct forms have been identified
55. E) Lymphocytic hypophysitis
• Autoimmune infiltration of pituitary parenchyma
by lymphocytes & plasma cells
• Associated with hypopituitarism and mass effects
• Imaging cannot distinguish it from pituitary
adenoma
• Hormone replacement therapy – usually only
option
• Spontaneous regression possible – most develop
panhypopituitarism
• Surgery only indicated to debulk and reduce mass
symptoms
56. Take home messages
• Physiology of pregnancy alters the course of
most endocrine disorders
• Index of suspicion must be high in pregnancy
mainly due to overlapping normal symptoms
of pregnancy
• Thyroid screening in pregnancy is
important, especially to prevent fetal
hypothyroidism
