OB3B Endocrine Disorders in Pregnancy

Renal Iodide Clearance in Pregnancy

Dr. Olivar  In pregnancy, the renal clearance of iodide increases
substantially because of an increased glomerular
THYROID GLAND filtration rate
 The thyroid gland compensates by enlarging its size
and increasing the plasma uptake of iodine to produce
sufficient thyroid hormones to maintain the euthyroid
state.

WHO Recommendation of Iodine Intake

NON-PREGNANT 100–150 µg/day

PREGNANT at least 250 µg/day

 Iodine deficiency during pregnancy can lead to:

o Hypothyroidism
o goiter

BINDING PROTEINS FOR THYROID HORMONES

TBG
THYROID FUNCTION CHANGES DURING PREGNANCY:  During pregnancy, the circulating concentration of TBG
 Moderate enlargement (50%) from glandular increases two- to threefold
hyperplasia & increased vascularity – does not cause  has a high affinity for thyroid hormones
impressive thyromegaly  Responsible for the transport of the majority of T4 (68%)
and T3 (80%)

Mechanism for Increase in TBG

FACTORS AFFECTING MATERNAL THYROID FUNCTION
 hCG
 Urinary iodide excretion
 TBG
Effect of hCG
 hCG has mild thyrotropic activit
 During the first trimester of pregnancy
o when hCG is at its greatest concentration,
serum TSH concentrations drop
 It has been estimated that a 10,000 IU/L increment in
circulating hCG corresponds to a mean free T4
increment in serum of 0.6 pmol/L (0.1 ng/dL) and in
turn, to a lowering of serum TSH of 0.1 mIU/L
 increase in hepatic synthesis of TBG
 estrogen-induced increase in sialylation, which
increases the half-life of TBG from 15 min to 3 days for
fully sialylated TBG
THYROID FUNCTION CHANGES DURING PREGNANCY:
  total albumin produced by the liver
 TBG
 total/ bound hormone levels
  daily thyroxine (T4) secretion, T3
Thyroid Function Tests:
 TSH, free T4, free T3
o measuring the bound T3 and T4 during
pregnancy may give a falsely elevated
results

THYROID PHYSIOLOGY DURING PREGNANCY

 Thyroid hormone is necessary for normal development
of the fetal brain and mental function
 There is an intimate relationship between maternal
and fetal thyroid function
 Throughout pregnancy, maternal T4 is transferred to
the fetus
 Maternal T4 is important for fetal brain development
 Fetal thyroid gland begins synthesizing hormone after
12 weeks of pregnancy
 Drugs that affect the maternal thyroid also affects the
fetal gland

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Medicine 3i - 2015
HYPERTHYROIDISM/THYROTOXICOSIS SURGERY AND ABLATION
 Maternal thyroidectomy – seldom done due to
DIAGNOSTIC SIGNS OF HYPERTHYROIDISM/ THYROTOXICOSIS: increased tendency of the mother to bleed
 tachycardia that exceeds that with normal pregnancy  Ablation with therapeutic radioactive iodine is
  sleeping pulse rate contraindicated during pregnancy because of
 thyromegaly possible fetal gland destruction
 exophthalmos
 failure to gain weight despite adequate food intake. PREGNANCY OUTCOME
 markedly  serum free T4 and markedly  TSH  Perinatal outcomes in neonates of women with
 Subclinical hyperthyroidism:  TSH thyrotoxicosis depend on whether metabolic control is
normal FT4 achieved
 Excess thyroxine may cause spontaneous miscarriage
HYPERTHYROIDISM / THYROTOXICOSIS AND PREGNANCY  Among untreated women, or in those who remain
hyperthyroid despite treatment, there is  incidence of
GRAVE’S DISEASE preeclampsia, heart failure and adverse perinatal
 an autoimmune process usually associated with thyroid outcomes
stimulating antibodies.
 activity of these antibodies usually decline during FETAL AND NEONATAL EFFECTS
pregnancy leading to chemical remission in many  The fetus or newborn may manifest with goitrous
women thyrotoxicosis caused by placental transfer of thyroid
stimulating antibodies
Management of Hyperthyroidism in Pregnancy  Hydrops and fetal demise
 antithyroid drugs or surgery  Tx: maternal administration of thioamide drugs
 absolute contraindication to the use of radioactive
iodine  The fetus may manifest with goitrous hypothyroidism
caused by maternally administered thioamides
Acute Management of Thyrotoxicosis  Thioamides carry an extremely small risk
Dosing Side Effects/ Complications Monitoring
Thionamides THYROID STORM AND HEART FAILURE
Propylthiouracil 100 - 150 mg Maternal TFT's q 4 wks
(PTU) po q 8 hrs  skin rash and adjust
(preferred in  agranulocytosis anti-thyroid
the 1° (0.5%) medication THYROID STORM an acute, life-threatening, hyper-metabolic
trimester)  hepatitis state
Methimazole 10-15 mg po q Fetal
(Tapazole) 8 hrs  hypothyroidism Patients typically present with a fever as high
(from 2nd  choanal atresia as 40 0C, marked tachycardia, prostration,
trimester  aplasia cutis
and severe dehydration
onwards)
Adrenergic Blockers
Propranolol 20 - 40 mg po Fetal HR precipitating factors are labor, cesarean
(Inderal) q 6 hrs  intrauterine section, or infection
growth
retardation up to 25% mortality rate, despite aggressive,
 respiratory distress and appropriate, medical management
 bradycardia
HEART FAILURE due to cardiomyopathy
 hypoglycemia
50 - 100 mg  hypothermia
Atenolol po q day Management:
Surgery  propylthiouracyl ( 1 gram then 200 mg q60)
Maternal TFT's  iodide (inhibits thyroidal release of T3/T4)
Thyroidectomy  miscarriage
IV (500mg – 1 gm q80),
 hypoparathyroidis
m Oral (SSKI) (5 drops orally q80)
 laryngeal nerve Lugol solution (10 drops orally q80)
paralysis  Lithium carbonate ( if with allergy to iodide)
 Dexamethasone – 200 mg IV q 60
THIONAMIDE (to further block peripheral conversion of T4 to T3)
 inhibit thyroid hormone synthesis by blocking iodination  B-blocker (propranolol) to control tachycardia
of the tyrosine molecule
 Thyrotoxicosis during pregnancy can nearly always be
controlled by thioamide drugs.

TREATMENT:

MEDICAL
 Generally, PTU and methimazole (MMI) have been
used interchangeably without evidence that one or
the other has clear therapeutic advantages
 Clinicians prefer propylthiouracil because it partially
inhibits the conversion of T4 to T3 and it crosses the
placenta less readily than methimazole.

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Medicine 3i - 2015
HYPOTHYROIDISM DIABETES MELLITUS IN PREGNANCY

 Often associated with infertility

 Those women who become pregnant have a high
incidence of preeclampsia, placental abruption low
birth weight & stillborn infants.
TYPE 1 DM Diabetes resulting from β-cell destruction,
 Usually results from glandular destruction by usually leading to absolute insulin
autoantibodies called antithyroid peroxidase deficiency
antibodies (Hashimoto thyroiditis) a. Without vascular complications
b. With vascular complications
(specify which)
Overt hypothyroidism  TSH,  FT3 and FT4 TYPE 2 DM Diabetes from inadequate insulin
Subclinical hypothyroidism  TSH, normal FT3 and FT4 secretion in the face of increased insulin
resistance
EFFECTS IN FETUS & INFANTS: a. Without vascular complications
 maternal hypothyroidism may impair fetal b. With vascular complications
neuropsychological development. (specify which)
 Children born to women with free T4 levels below the GESTATIONAL DM Genetic in origin, associated with
10th percentile were at increased risk for impaired pancreatic disease, drug-induced, or
psychomotor development. chemically-induced
OTHER TYPES OF Diabetes diagnosed during pregnancy
MANAGEMENT: DIABETES that is not clearly overt (type 1 or 2)
 Thyroxine replacement 50 – 100 µg daily diabetes
 Iodine Deficiency:
o RDA: 250 ug / day
o Mild deficiency: intellectual impairment
o Severe deficiency: endemic cretinism PREGESTATIONAL (OVERT) DIABETES
 Congenital Hypothyroidism:
o Detection is part of newborn screening

Regardless, the tentative diagnosis of over DM during pregnancy

based on these thresholds should be confirmed postpartum.

FETAL AND NEONATAL EFFECTS OF OVERT DIABETES

FETAL NEONATAL
Abortions Hypoglycaemia
Preterm Delivery Hypocalcemia
Malformations Hyperbilirubinemia
Altered fetal growth Polycythemia
Unexplained demise Cardiomyopathy
Hydramnios Cognitive development
Inheritance of diabetes

MATERNAL EFFECTS OF OVERT DIABETES:

 Preeclampsia
 Diabetes nephropathy
 Diabetic retinopathy
 Diabetic neuropathy
 Ketoacidosis
 Infection
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MANAGEMENT OF OVERT DIABETES: Table 52–4. American College of Obstetricians and
 The American Diabetes Association has defined Gynecologists 2001 Criteria for Diagnosis of Gestational Diabetes
optimal preconceptional glucose control using insulin Using the 100-g Oral Glucose Tolerance Test
to include self-monitored preprandial glucose levels of Plasma/Serum National Diabetes
70 to 100 mg/dL and postprandial values of less than Carpenter and Coustan Plasma Data Group
140 mg/dL and less than 120 mg/dL at 1 and 2 hours, Status mg/dL mmol/L mg/dL mmol/L
respectively.
Fasting 95 5.3 105 5.8
 Achieve a HgbA1C value of < 7.0 to avoid congenital
1 hr 180 10.0 190 10.6
malformation.
2 hr 155 8.6 165 9.2
1ST TRIMESTER 2ND TRIMESTER 3RD TRIMESTER 3 hr 140 7.8 145 8.0
Insulin a-fetoprotein Antenatal
CBG targeted UTZ scan surveillance *** Gestational DM – at least 2 are values are met or exceeded
Diet Fetal 2D -echo Labor induction
Cesarean section High Risk Patients
 Perform blood glucose testing as soon as feasible, if
one or more of these are present:
o Severe obesity
o Strong family history of Type II DM
o Previous history of GDM, IGM, or glucosuria
 If GDM is not diagnosed this time, repeat testing at 24-
28 weeks’ gestation or any time symptoms or signs
suggest hyperglycemia

MATERNAL EFFECTS:
 Preeclampsia – eclampsia increased 4x
 Increase risk for bacterial infection
 Macrosomic fetus – difficult delievery birth canal injury
GESTATIONAL DIABETES MELLITUS (GDM)  Hydramnios – cardiorespiratory symptoms
 Increase maternal mortality – complications of DM,
DIABETES MELLITUS IN PREGNANCY: HPN, infection & CS

PREGNANCY IS POTENTIALLY DIABETOGENIC: FETAL EFEECTS:

 Normal pregnancy is characterized by:  Fetal anomalies (NOT SUBSTANTIALLY INCREASED)
o mild fasting hypoglycaemia  Higher incidence of macrosomia
o postprandial hyperglycemia  elevated fasting glucose (>105 mg/dL) has been
o hyperinsulinemia associated with unexplained stillbirth similar to overt
diabetes
 In healthy pregnant women the fasting plasma glucose
concentration falls somewhat possibly due to increased MANAGEMENT ISSUES:
plasma levels of insulin.
ANTEPARTUM
PREGNANCY INDUCED STATE OF PERIPHERAL RESISTANCE TO I. NUTRITIONAL THERAPY
INSULIN  Weight management
  peripheral uptake of glucose due to insulin resistance  Lifestyle changes
  insulin response due to elevated glucose
II. BLOOD GLUCOSE MONITORING
Who are the culprits? Capillary Blood Glucose Targets for Pregnant Women
 Progesterone Preprandial ≤ 95 mg/dL (5.3 mmol/L)
 Estrogen 10 postmeal ≤ 140 mg/dL (7.8 mmol/L)
 Human Chorionic Somatomammotrpin 20 postmeal ≤ 120 mg/dL (6.7 mmol/L)
(human placental lactogen)
III. PHARMACOLOGICAL MGT.
SCREENING AND DETECTION
 Insulin, Glyburide, Metformin
 Universal screening for GDM is recommended for
Filipino gravidas
IV. FETAL SURVEILLANCE
 The Asia-Pacific region is at the forefront of the current
TECHNIQUES OF MONITORING
epidemic in DM
1. Fetal movement counting
SCREENING: 2. NST
 screening for gestational diabetes should be 3. Ultrasound Growth monitoring
performed between 24 and 28 weeks age of gestation BPS
 a 50-g oral glucose challenge test is followed by a Congenital scan
diagnostic 100-g oral glucose tolerance test if results Doppler studies
exceed a predetermined plasma glucose
concentration.
 Plasma glucose level is measured 1 hour after a 50-g
glucose load without regard to the time of day or time
of last meal.
 Determine plasma sugar after hour –
if 130 - 140mg/dl:
do 100 grams OGTT after 8- 14 hours fasting
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Medicine 3i - 2015
 TIME TEST POSTPARTUM
Pre-conception Maternal glycemic control
6-11 weeks CRL measurement  Women diagnosed with GDM or DM( during
16 weeks UTZ for growth pregnancy) should be screened for Type 2 DM using 75
gram OGTT at 6-12 weeks postpartum
20-24 weeks CAS/fetal echo
28 weeks Fetal movement counting
NORMAL IMPAIRED OVERT DIABETES
32 weeks UTZ for growth every 2 weeks GLUCOSE MELLITUS
BPS (FULL) TOLERANCE
- 2x/week if on insulin
Fasting < 100 mg/dL 100 – 125 ≥ 126 mg/dL
comorbids
mg/dL
- weekly or every 2
weeks if good control 2nd hour < 140 mg/dL ≥ 140 – 199 ≥ 200 mg/dL
mg/dL
Fetal Movement Record (Instructions) Hgb A1C < 5.7% 5.7 – 6.4% ≥ 6.5%
1. Count the baby’s movement EVERY NIGHT
2. A movement may be a kick, a swish or roll. Hiccups I. BREASTFEEDING
and small flutters not counted  All women, including those with prior GDM, should be
3. Start counting anytime in the evening when the baby is actively encouraged to exclusively breastfeed to the
active. BUT: COUNT EVERY NIGHT greatest extent possible during the first year of life
4. Count the baby’s movements while lying down  Benefits:
preferably on your left o  postpartum maternal glucose values
5. Mark down the time you feel the baby move for the first o Type 2 DM and Metabolic syndrome are
time and mark down the time you feel the 10th fetal lower among breastfed children
movement
6. You should at least feel 10 fetal movements within two II. CONTRACEPTION
hours. Call your physician immediately if:
o you do not feel 10 movements within 2 hours
o it takes longer and longer for your baby to Natural Methods
move 10 times Barrier Method
o you have not felt the baby move all day
IUD
 DO NOT WAIT UNTIL TOMORROW!
Combined Oral Contraceptive Pills
Progestin-only Oral Contraceptive Pills
INTRAPARTUM DMPA
Sterilization
I. TIMING OF DELIVERY
 The timing of delivery should be individualized  Both copper and levonorgestrel-releasing IUD’s can be
depending on the glucose control and whether the safely used in women with prior GDM
patient has any concomitant maternal and / or fetal
complications
 Labor is induced at 39 weeks among patients with
GDM requiring insulin
 Patients with well-controlled DM and no complicating
factors may await spontaneous labor but expectant
management beyond the expected date of delivery
(40 weeks) is NOT recommended
 Elective cesarean section in patients with GDM must be
performed at 39 weeks
 Deliver a patient with DM before 39 weeks AOG only
for compelling maternal or fetal indications

II. MODE OF DELIVERY

 GDM is NOT in itself an indication for CS.
 If vaginal delivery is attempted, continuous EFM is
recommended
 If CS is elective, this should be carried out in the early
morning to avoid prolonged fasting

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Medicine 3i - 2015