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Endocrine Pathology

associated with
pregnancy

Hyper- and Hypothyroidism
During Pregnancy

INTRODUCTION

Thyroid diseases are more prevalent in women
 relatively common in pregnancy

Pregnancy may affect the course of thyroid disorders
conversely..
Thyroid diseases may affect the course of pregnancy

Thyroid disorders & their management
may affect the mother & fetus

that regulate metabolism • TRH and TSH concentrations are inversely related to the level of T3 & T4 99% circulating T3 & T4 is bound to TBG.Control of Thyroid Function By a negative-feedback loop: • The hypothalamus releases TRH • TRH acts on the pituitary to release TSH • TSH acts on the thyroid gland to release T3 and T4 . 1% circulate in the Free form. (only the free forms are biologically active) .

 HCG can weakly turn on the thyroid and the high circulating hCG levels in the first trimester may result in a slightly low TSH.What are the normal changes in thyroid function associated with pregnancy?  Thyroid function tests change during pregnancy due to the influence of two main hormones: human chorionic gonadotropin (hCG). . the TSH will be slightly decreased in the first trimester and then return to normal throughout the duration of pregnancy. When this occurs. the hormone that is measured in the pregnancy test and estrogen.  Estrogen increases the amount of thyroid hormone binding proteins in the serum which increases the total thyroid hormone levels in the blood since >99% of the thyroid hormones in the blood are bound to these proteins. the main female hormone.

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FT4 = free thyroxine. TSI = thyroid stimulating immunoglobulins. FT3 = free triiodothyronine. TSH = thyroid stimulating hormon. TT4 = total thyroxine .Results of Thyroid Tests in Different Clinical Situations TT4 TT3 FT4 FT3 Anti- TSI TSH TPO Nonpregnant N N N N N (-) N Normal pregnancy   N N N (-) N Hyperthyroidism      ( +) ? Gestasional Transient Thyrotoxicosis (GTT)      (-) N Hypothyroidism  N  N  ( +) N Subclinical hypothyroidism N N N N  ( +) N Chronic thyroiditis N N N N N ( +) N Anti-TPO = antithyroid peroxidase antibodies.

fisiologis (non-autoimun) Sering disertai dengan hiperemesis (waktu kadar HCG mencapai puncaknya) Gejala hipertiroid tidak selalu muncul. -.  Berhubungan dengan lamanya dan tingginya kadar HCG        FT4 sementara -.Hipertiroidisme Gestasional  = Gestational transient thyrotoxicosis (GTT ) Prevalensi : 2 -3% dari seluruh kehamilan. biasanya sampai 2 bulan .± 50% ibu dengan GTT Tidak perlu terapi spesifik untuk hipertiroid Gejala yang berat (jarang). diatasi dengan PTU sampai gejala hilang.

Gestasional Hipertiroidisme .

palpitations. 3. Thyroid enlargement . Widened pulse pressure. Eye signs of Graves' disease 4. Typical symptoms : Thyroid enlargement. Pulse rate > 100 / mnt. 2.Graves' disease in a pregnancy History 1. 2. emotional lability. weight loss. History of hyperthyroidism in the patient or her family. Accentuation of normal symptoms of pregnancy: heat intolerance. fatigue Physical Exam. 3. 1.

Signs Signs and and Symptoms Symptoms Of Of Hyperthyroidism Hyperthyroidism Nervousness Irritability Difficulty Sleeping Hoarseness or Deepening of Voice Persistent Sore or Dry Throat Difficulty Swallowing Rapid or Irregular Heartbeat Bulging Eyes/Unblinking Stare Swelling (Goiter) Infertility Menstrual Irregularities or Weight Loss Light Period Heat Intolerance Frequent Bowel Movements Warm. Moist Palms Increased Sweating First-Trimester Miscarriage Family History of Excessive Vomiting in Pregnancy Thyroid Disease or Diabetes .

gangguan pertumbuhan .lahir prematur .partus prematur .lahir mati .pre-eklamsi .abortus spontan  Komplikasi pada janin : .Komplikasi Hipertiroidisme pada Kehamilan  Komplikasi pada ibu : .

Adverse Pregnancy Outcome of Maternal Hyperthyroidism Poor control Adequate control 14-22% 7% CHF 60% 3% Thyroid storm 21% 2% Preterm delivery 88% 8% LBW 23% 10% Preeclampsia .

 takikardi .Respons baik : pertumbuhan janin normal.  TSI dapat melewati plasenta terikat pada reseptor TSH pd tiroid janin.Hipertiroidisme pada Janin  Ibu dengan Graves yg sudah Eutiroid. merangsang tiroid janin -. mungkin TSI di dalam darahnya masih tinggi.Tanda : gangguan pertumbuhan intrauteri dan takikardi. .Terapi : pemberian OAT pada ibu.hipertiroidisme pada janin  Hipertiroidisme pada janin . .

  Waktu paruh reseptor TSH hanya beberapa minggu  hipertiroidisme pada bayi hanya sementara (±1.Hipertiroidisme pada Neonatus  Hipertiroidisme pada bayi/neonatus .Jarang (< 1% )  Terjadi bila ibu masih mempunyai kadar TSI yang tinggi.3bulan) .III digunakan sebagai prediktor timbulnya hipertiroidisme pada bayi. TSI yang tinggi pada trim.

40 mg/hari (dibagi 2 dosis/hari) Dosis disesuaikan dg respons Klinik & Lab Efek samping : Gatal /kemerahan di kulit (3 –5% pasien) Efek samping lain (jarang) : agranulositosis .Obat Anti-tiroid (OAT)  OAT :    Dosis awal:     propylthiouracil (PTU) methimazol (MTZ) : Thyrozol PTU 150 – 450 mg/hari (dibagi 3 dosis/hari) MTZ 20 .

Pengobatan hipertiroidisme pada kehamilan

Tujuan :

Pemantauan berkala:

mempertahankan FT4 pada batas atas normal

Lab. tiap 2 minggu pd awal terapi
setelah target tercapai Lab. tiap 4 minggu

OAT:

Jangan dihentikan sebelum hamil 32 minggu (umumnya relaps)
Dihentikan pada beberapa minggu terakhir kehamilan,
bila struma kecil & dosis obat minimal

Pengaruh Obat Anti-tiroid
terhadap Janin

MTZ dan PTU dapat melewati plasenta

Dosis besar dapat menyebabkan
struma & hipotiroidisme pada janin

Struma pada janin --dideteksi dengan USG

Operasi dan Ablasi Tiroid
pada Kehamilan

Operasi tiroidektomi
Jarang dilakukan, kecuali bila :
- Dosis OAT sangat besar
(PTU > 600mg atau MTZ > 40 mg/hr)
- Alergi terhadap OAT
- Pasien tidak taat berobat
- Struma yang sangat besar

Terapi ablasi ( Iodium radioaktif )
- Kontraindikasi - dapat melewati plasenta
- Risiko: hipotiroidisme pd bayi, mungkin retardasi mental
- Pencegahan: lakukan tes kehamilan sebelum ablasi

• Do not attempt to normalize serum TSH -.4 mU/L are appropriate • Communicate regularly with obstetric providers.TSH 0. but both types can be used.  often discontinued during the 3rd trimester  ATD will often need to be reinstituted or increased after delivery.0. TSH every 2-4 weeks  Titrate ATD as necessary  ATD:  PTU is usually preferred to MTZ. FT4 . – Especially fetal pulse & growth in the 2nd half of gestation .  Use the lowest dosage of that will maintain the patient in a euthyroid or mildly hyperthyroid state.Treatment guidelines for Graves' disease during pregnancy  Monitor  Pulse.1 .  Usually the ATD dose can be adjusted downward after 1st trim. weight gain.

Kesimpulan  Pemeriksaan Lab. perlu dipantau efek obat sehingga tidak timbul akibat iatrogenik terhadap ibu dan janin.  Perlu diingat : ada perubahan fisiologis fungsi tiroid pada kehamilan normal.  Penatalaksanaan gangguan fungsi tiroid pada kehamilan sebaiknya melibatkan beberapa ahli secara multidisiplin . uji fungsi tiroid diperlukan untuk menegakkan diagnosis.  Bila memberi terapi. sebelum menentukan kondisi ibu hamil yang patologis.

TSH. increases early in pregnancy. but rise in autoimmune thyroiditis. the thyroid microsomal antigen. are elevated in autoimmune thyroiditis. High TSI in the mother is strongly predictive of fetal or neonatal hyperthyroidism Transient hyperthyroidism of hyperemesis gravidarum is the most common . stimulates the thyroid gland to prod. hCG Human chorionic gonadotropin rises in pregnancy and binds to the TSH receptors in the thyroid gland. THHG immunoglobulins TSI are antibodies that block the TSH receptors. Normal serum level in nonpregnant adult is 5-12 mcg/dL FT4 Free thyroxine FT4 is the biologically active thyroxine.3ng/Dl. globulin is  during pregnancy ( secretion from the liver and  peripheral breakdown. producing an enlarged thyroid without clinical symptoms of goiter.0mcU/mL. which declines in the 1st trim.5-3. of pregnancy and returns to normal in the 2nd . does not cross the placenta. Normal serum level is 0 antibodies AntiTPO Antithyroid peroxidase antibodies to thyroid peroxidase.4mg/dL TSI Thyroid stimulating TT4 Total thyroxine TT4 or L-thyroxine. Normal serum level in nonpregnant adult is 0.5-5.8-2.AMA Antimicrosomal normally are nondetectable in serum. thyroid hormon.) Normal serum level in nonpregnant adult is 1. suppressing TSH levels in the 1st trimester TRH Thyroid releasing hormon TRH crosses the placenta while TSH does not TBG Thyroxine binding TBG= a glycoprotein that carries T3 &T4. Normal serum level is 0 TSH Thyroid stimulating hormon produced by pituitary gland. Normal is 0. rises in pregnancy.

HIPOTIROIDISME pada KEHAMILAN .

Sheehan’s syndr.Causes of Hypothyroidism PRIMARY: • Iodine deficiency: most common • Hashimoto’s thyroiditis most common in developed countries.Radioactive iodine therapy .hydroxide) . Somatostatin :  TSHthat inhibit absorption of Thyroid Drugs medication • Fe.Cholestyramin • Antacids (Al.Thyroidectomy .Viral thyroiditis SECONDARY / CENTRAL: • Pituitary tumor.Sucrafate.sulfate. .Antithyroid antibodies (antimicrosomial Ab & antithyroglobulin Ab) • Other: . • Medication: Lithium :  thyroid function Thionamide.

Patchy Skin Heavy Period Weight Gain Infertility Cold Intolerance Constipation Elevated Cholesterol Muscle Weakness or Cramps .Signs and Symptoms of Hypothyroidism Tiredness Forgetfulness/Slower Thinking Moodiness/ Irritability Depression Puffy Eyes Swelling (Goiter) Hoarseness/ Deepening of Voice Persistent Dry or Sore Throat Inability to Concentrate Thinning Hair or Hair Loss Loss of Body Hair Difficulty Swallowing Slower Heartbeat Menstrual Irregularities/ Dry.

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fatigue) can overlap with common pregnancy complaints Among pregnant hypothyroid patients: – 1/3 have few or no symptoms – 1/3 have moderate symptoms – 1/3 have classical presentation of hypothyroidism .Hypothyroidism in Pregnancy May Be Difficult to Diagnose Signs and symptoms (weight gain.

• normal FT4 & FT3 .Laboratory Tests Because symptoms does not reliably distinguish hypothyroidism from normal pregnancy… Lab test are the standard for diagnosis Overt Hypothyroidism: Subclinical hypothyroidism: • symptomatic patient • asymptomatic •  TSH level •  TSH •  FT4 & FT3.

Autoimmune disorder  Family history of thyroid disease .Risk Factors for Hypothyroidism in Pregnant Women  Previous therapy for hyperthyroidism  Previous external neck irradiation  Goiter .

T3 & TSH pass across the placenta in small and decreasing amounts as gestation progress. but TSI. • Fetus relies on Maternal T4 : Exclusively (until 12 ws) By 20 weeks gestational age : • The fetal thyroid is fully responsive to • Thyroid stimulating immunoglobulin (TSI) • Antithyroid drugs • Maternal T4.Fetal Thyroid Function During early gestation: • The Fetus needs T4 for brain / neurologic development • Fetal Thyroid development begin at 10 -12 ws. Fetus does not produce its own T4 until 12 ws. Iodides are readily transferred to the fetus .

.depends on the severity of the condition.Consequences of Hypothyroidism in Pregnancy  Miscarriage  Preterm delivery  Anemia  Placental abruption  Fetal complications The impact -.

• Mental retardation.  newborn screening for congenital hypothyroidism !! . • Other neuropsychologic deficits If cretinism is identified & treated in the first 3 months of life: near-normal growth and intelligence can be expected.Consequences of Hypothyroidism in Pregnancy Congenital cretinism: • Growth failure.

An inverse correlation between TSH level during pregnancy and the IQ of her offspring (Klein et al.9 yrs (Haddow et al. • Subclinical hypothyroidism ~ to be complicated by placental abruption & preterm birth (Casey.  IQ scores in the offspring at age 7 . 1999).  Psychomotor development in infants ( Pop et al. 2006) Subclinical hypothyroidism •  IQ of the children whose mothers were not treated (Mitchell & Klein. . Neurodevelopmental abnormalities can be identified as early as 3 weeks of age (Kooistra et al. 1991). 2005).Evidence ? Asymptomatic Overt Hypothyroidism Women with Hypothyroidism (TSH & FT4) but do not have symptom 1. 3. 2004). 2.1999) 4.

Therapy of Hypothyroidism  Choice of medication  Adjustment of therapy  Follow-up care L-Thyroxine :   Adjustment of therapy : careful titration Follow-up care • • Clinical evaluation Laboratory monitoring (TSH) .

a kFT4 in upper third of normal JA rena ka ad p TSH Dose Adjustment TSH  but < 10  50 ug/d TSH  10-20  50-75 ug/d TSH  > 20  100 ug/d  FT4) .Treatment of Hypothyroidism  Many Causes. : ) i g o  Levothyroxine – Euthyrox. monitoring every 4 weeks a N h e TSHN between GA a1l-a2s mU/L. One Treatment. d s n i n a a i ro i d n k a r d u e rt i b g e u p Estrogen   TBG  g o/H(i  Thyroxin dosehas li kpregnancynprogresses g (A e Hip ilan m an-. Thyrax l o s n u an s l kri oncendaily: 2oug/kg/d i d m e n a s E h n n eplacenta e o a k Safe Very little thyroxin cross the Safe in in pregnancy.. Very thyroxin cross the placenta m K pregnancy.To maintain m euthyroid state Lab.

During Pregnancy: Regular monitoring and Fine-tuning of treatment .

other autoimmune disease).Screening at age 35 yrs and every 5 years thereafter.Closer attention to patients who are at high risk (eg. .  The American Association of Clinical Endocrinologists TSH measurements of all women of childbearing age before pregnancy or during the first trimester. .Recommendations  The American Thyroid Association recommends: .  The US Preventive Task Force concludes : The Evidence is insufficient to recommend for routine screening for thyroid disease in adults (Grade I recommendation). pregnant. women >60 yrs.

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Yunus Tanggo SpPD.PhD .GESTATIONAL DIABETES MELLITUS Dr.

Definition  Gestational Diabetes mellitus is defined carbohydrate intolerance of varying degrees of severity with onset or first recognition during pregnancy  GDM is associated with a variety of maternal and fetal complications .

000 cases per year prevalence may range from 1 to 14% All pregnancies complicated by diabetes. GDM accounts for ~ 90%.Epidemiology of GDM     GDM affects 7% of all pregnancies > 200. .

For the WHO criteria.or 75-g OGTT must be met or exceeded to make the diagnosis of GDM. one of the two values from the 75-g OGTT must be met or exceeded to make the diagnosis of GDM .ADA and WHO Criteria for the Diagnosis of GDM ADA ADA WHO 100-g OGTT 75-g OGTT 75-g OGTT Fasting (mg/dl) 1-hour (mg/dl) 2-hour (mg/dl) 3-hour (mg/dl) 95 180 155 140 95 126 180 155 — — 140 — For the ADA criteria. two or more of the values from either the 100.

insulin sensitivity falls by until 50% .Pathophysiology (1)   Pregnancy is a condition characterized by progressive insulin resistance that begins near midpregnancy and progresses through the third trimester In late pregnancy.

and progesterone . estrogen.Pathophysiology (2)   Two main contributors to insulin resistance include increased maternal adiposity and the insulin desensitizing effects of hormones produced by the placenta The placenta produces human chorionic somatomammotropin (HCS. formerly called human placental lactogen). bound and free cortisol.

the first.and second phase insulin responses compensate for this reduction in insulin sensitivity. and this is associated with b-cell hypertrophy and hyperplasia .Pathophysiology (3)   HCS stimulates pancreatic secretion of insulin in the fetus and inhibits peripheral uptake of glucose in the mother In non diabetic pregnant women.

3) occurring on a background of insulin resistance (as is most common). women who have a deficit in this additional insulin secretory capacity develop GDM b-Cell dysfunction in women diagnosed with GDM may fall into one of three major categories: 1) autoimmune. . 2) monogenic.Pathophysiology (4)   However.

Because insulin does not cross the placenta. whereas impaired suppression of hepatic glucose production is responsible for fasting hyperglycemia when present.Pathophysiology (5)   The loss of the first-phase insulin response leads to postprandial hyperglycemia. the fetus is exposed to the maternal hyperglycemia .

.Pathophysiology (6)   The fetal pancreas is capable of responding to this hyperglycemia The fetus thus becomes hyperinsulinemic. which in turn promotes growth and subsequent macrosomia.

Screening strategy for detecting gestational diabetes mellitus (1)  Low risk Blood glucose testing not routinely required if all of the following characteristics are present ● Member of an ethnic group with a low prevalence of GDM ● No known diabetes in first-degree relatives ● Age <25 years ● Weight normal at birth† ● Weight normal before pregnancy ● No history of abnormal glucose metabolism ● No history of poor obstetric outcome .

Screening strategy for detecting gestational diabetes mellitus (2)  Average risk ††Perform blood glucose testing at 24–28 weeks in the following ● All subjects not classified as low risk or high risk ● Subjects initially designated high risk that did not have GDM at early testing .

or at any time a patient has symptoms or signs that are suggestive of hyperglycemia .Screening strategy for detecting gestational diabetes mellitus (3)  High risk Perform blood glucose testing as soon as feasible after booking if one or more of the following characteristics are present ● Severe obesity according to local standards ● Strong family history of Type 2 diabetes mellitus ● Previous history of GDM or glucose intolerance outside of pregnancy ● Glucosuria If GDM is not diagnosed. blood glucose testing should be repeated at 24–28 weeks.

Two-step approach: A. while the sensitivity is further increased to 90% by a threshold of 130 mg/dl. A glucose threshold after 50-g load of 140 mg/dl identifies 80% of women with GDM. Perform initial screening by measuring plasma or serum glucose 1 h after a 50-g oral glucose load. B. Perform a diagnostic 100-g OGTT on a separate day in women who exceed the chosen threshold on 50-g screening .Two approaches may be followed for GDM screening at 24–28 weeks (1) 1.

One-step approach (may be preferred in clinics with high prevalence of GDM): Perform a diagnostic 100-g OGTT in all women to be tested at 24–28 weeks.0 mmol/l) 2 h: 155 mg/dl (8.8 mmol/ .3 mmol/l) 1 h: 180 mg/dl (10.6 mmol/l) 3 h: 140 mg/dl (7. A diagnosis of GDM requires at least two of the following plasma glucose values: Fasting: 95 mg/dl (5.Two approaches may be followed for GDM screening at 24–28 weeks (2) 2.The 100-g OGTT should be performed in the morning after an overnight fast of at least 8 h.

Complications  Maternal complications     Antepartum morbidity in women with GDM mostly consists of higher risk for development of hypertensive disorders and preeclampsia GDM increases the risk of cardiovascular disease (CVD) increased risk of cesarean delivery GDM have an increased risk of developing diabetes after pregnancy compared to the general population .

 Respiratory distress syndrome.  Polycythemia.Complications  Fetal complications Macrosomia  Neonatal hypoglycemia  Perinatal mortality  Congenital malformation  Hyperbilirubinemia.  . hypocalcemia.

and 2-hour postprandial glucose < 120mg/dl .Treatment(1)  Glucose Monitoring       The goal of monitoring is to detect glucose concentrations elevated enough to increase perinatal mortality The Fourth International Workshop Conference on Gestational Diabetes Mellitus recommends maintaining the following capillary blood glucose values: preprandial glucose < 95 mg/dl. 1hour postprandial glucose < 140 mg/dl.

provide sufficient calories for appropriate maternal weight gain.Treatment(2)  Medical Nutrition Therapy(MNT)  The goals of MNT are to provide adequate nutrition for the mother and fetus.and avoid ketosis . maintain normoglycemia.

 .Treatment(3)  Insulin Insulin therapy is the most commonly used treatment when MNT fails to maintain blood glucose levels at the desired ranges or when there is evidence of excessive fetal growth  insulin lispro was as effective as regular insulin in controlling glucose levels with fewer episodes of hypoglycemia.

Thank You .