GDM - Screening methods, Glucose metabolism and Management 30 marks question in PG obs and gynce
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gestational diabetes mellitus screening glucose tolerance test GDM diagnosis
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Gestational Diabetes Mellitus (GDM): Screening, Glucose Metabolism & Management
A Complete 30-Mark PG Answer
DEFINITION
Gestational diabetes mellitus (GDM) is defined as carbohydrate intolerance of variable severity with onset or first recognition during pregnancy. It occurs in approximately 8% of all pregnancies and is one of the most common metabolic complications in obstetric practice. (Harrison's Principles of Internal Medicine, 22E)
PART I: GLUCOSE METABOLISM IN PREGNANCY
Understanding GDM requires appreciating the normal physiological changes in glucose metabolism during pregnancy.
A. Normal Glucose Metabolism in Pregnancy
Pregnancy induces a biphasic metabolic pattern:
Early Pregnancy (1st Trimester):
- Increased insulin sensitivity transiently at 12-14 weeks
- Enhanced peripheral glucose uptake
- Decreased fasting glucose and increased hepatic glycogen synthesis
- Rising estrogen and progesterone promote beta-cell hyperplasia
- Net result: mild hypoglycemia in fasting state - "accelerated starvation"
Late Pregnancy (2nd & 3rd Trimester):
- Progressive insulin resistance - glucose infusion rate falls significantly (see Fig. 59.4 - Creasy & Resnik)
- Insulin secretory response increases approximately 3-fold compared to pregravid state (2nd and 3rd phase insulin response)
- Despite increased secretion, insulin sensitivity falls markedly by 34-36 weeks
- The net effect is maintenance of normoglycemia in healthy women through compensatory hyperinsulinemia
Figure: Longitudinal changes in insulin sensitivity (glucose infusion rate) from pregravid state through early (12-14 weeks) and late (34-36 weeks) pregnancy - Creasy & Resnik
B. The Fetoplacental Unit and Glucose Handling
- The fetoplacental unit shunts glucose and amino acids to the fetus while the mother preferentially uses ketones and triglycerides
- Fetal glucose uptake causes maternal accelerated ketosis during fasting - lower glucose and higher hydroxybutyrate
- Placental hormones responsible for insulin resistance include:
- Human placental lactogen (hPL)
- Placental growth hormone variant
- Progesterone and cortisol
- TNF-alpha and leptin
- hPL peaks progressively and is the dominant anti-insulin factor
C. Mechanisms of Gestational Insulin Resistance (GDM-Specific)
(Creasy & Resnik's MFM, p.1429)
In women who develop GDM, specific metabolic defects are present:
- Increased basal endogenous glucose production - similar to type 2 DM
- Decreased insulin-mediated glucose uptake - insulin infusion assays show insulin's ability to suppress endogenous glucose production is reduced (~80% vs 95% in normal women)
- Impaired first-phase insulin secretion - failure of beta-cell compensation is the key defect
- Decreased insulin sensitivity - persists antepartum and postpartum; women with GDM have significantly lower insulin sensitivity than matched controls even after delivery
- Across the body weight spectrum, fasting insulin concentrations (especially in late gestation) are greater than in normal glucose-tolerant women - reflecting compensatory hyperinsulinemia
Key concept: GDM represents a failure of the beta-cell to fully compensate for the physiological insulin resistance of late pregnancy. Women with GDM carry a pre-existing beta-cell dysfunction or pre-diabetes that is unmasked by pregnancy.
PART II: SCREENING FOR GDM
A. When to Screen
- Universal screening at 24-28 weeks of gestation (recommended by ACOG, ADA, USPSTF - Grade B recommendation)
- High-risk screening at the first prenatal visit for women with risk factors:
- BMI ≥25 kg/m² (or ≥23 kg/m² in Asian populations)
- Prior history of GDM
- Prior macrosomic infant (>4 kg)
- First-degree relative with type 2 DM
- Polycystic ovarian syndrome
- Previous unexplained stillbirth
- Glycosuria on two occasions
- Ethnicity: South Asian, Hispanic, African American, Pacific Islander
B. Screening Strategies
There are two internationally recognized strategies:
ADA Screening Table: 1-step vs 2-step GDM diagnosis criteria
Strategy 1: One-Step (IADPSG/WHO 2013)
Adopted by IADPSG (International Association of Diabetes and Pregnancy Study Groups) and WHO. Used widely in India (DIPSI is a variant).
Test: 75-g OGTT (fasting), at 24-28 weeks
Diagnosis if ANY ONE value is met or exceeded:
| Timepoint | Threshold |
|---|---|
| Fasting | ≥92 mg/dL (5.1 mmol/L) |
| 1 hour | ≥180 mg/dL (10.0 mmol/L) |
| 2 hours | ≥153 mg/dL (8.5 mmol/L) |
- Based on data from the HAPO study (Hyperglycemia and Adverse Pregnancy Outcomes) - a landmark study of >25,000 pregnant women showing continuous linear relationship between maternal glucose and adverse outcomes
- Increased sensitivity, detects more GDM, but increases treatment burden and resource use
Strategy 2: Two-Step (ACOG / USA standard)
Step 1 - Screening Test (non-fasting):
- 50-g Glucose Challenge Test (GCT) at 24-28 weeks
- Single plasma glucose at 1 hour
- Positive screen: plasma glucose ≥130 mg/dL (or ≥135 or ≥140 mg/dL per local protocol)
- If positive → proceed to Step 2
Step 2 - Diagnostic Test (fasting):
- 100-g OGTT, with plasma glucose fasting and at 1h, 2h, 3h
Carpenter-Coustan Criteria (ACOG recommended):
| Timepoint | Threshold |
|---|---|
| Fasting | ≥95 mg/dL (5.3 mmol/L) |
| 1 hour | ≥180 mg/dL (10.0 mmol/L) |
| 2 hours | ≥155 mg/dL (8.6 mmol/L) |
| 3 hours | ≥140 mg/dL (7.8 mmol/L) |
Diagnosis requires 2 or more elevated values (ACOG allows 1 elevated value in some guidelines)
NDDG Criteria (older, less used):
- Fasting: 105 mg/dL | 1h: 190 | 2h: 165 | 3h: 145 mg/dL
C. DIPSI (Diabetes in Pregnancy Study Group India) Criteria
A practical, single-step, non-fasting test used widely in India - suitable for resource-limited settings:
- 75-g oral glucose regardless of fasting state
- Single 2-hour plasma glucose
- GDM: ≥140 mg/dL
- Impaired GDM: 120-139 mg/dL
D. Other Screening Methods
| Test | Notes |
|---|---|
| Fasting plasma glucose | ≥92 mg/dL = GDM per IADPSG; cheap, simple |
| HbA1c | Not reliable in pregnancy - red cell turnover is increased causing falsely low values; used at booking to detect pre-existing DM (≥6.5% = overt DM) |
| Random blood glucose | ≥200 mg/dL + symptoms = overt DM |
| Urine glucose (glycosuria) | Poor sensitivity and specificity; renal threshold lowers in pregnancy; not recommended as sole screening tool |
| Glycated proteins (fructosamine) | Research use |
E. Key Clinical Points for Screening
- GCT can be done non-fasting (50-g)
- OGTT must be done fasting (overnight fast ≥8 hours)
- Patient must have unrestricted carbohydrate diet for 3 days prior to OGTT
- Patient should remain seated during OGTT; smoking prohibited
- Venous plasma glucose is the standard (fingerstick glucometers are NOT acceptable for diagnosis)
PART III: MANAGEMENT OF GDM
Management follows a stepwise approach: Dietary modification → Physical activity → Medical therapy (insulin/oral agents) → Obstetric surveillance.
(Creasy & Resnik's MFM; Harrison's 22E)
A. Target Glucose Values in GDM
| Timepoint | Target |
|---|---|
| Fasting / pre-meal | 65-95 mg/dL (ADA: <95 mg/dL) |
| 1-hour postprandial | <140 mg/dL |
| 2-hour postprandial | <120 mg/dL |
| Mean blood glucose | <100 mg/dL |
HbA1c monitoring is of minimal utility in pregnancy due to increased red cell turnover causing falsely low values. Blood glucose self-monitoring (SMBG) is the standard.
B. Non-Pharmacological Management
1. Medical Nutrition Therapy (MNT)
- Cornerstone of initial GDM management
- Caloric intake tailored to pre-pregnancy BMI:
- Normal BMI: 30 kcal/kg/day
- Overweight: 25 kcal/kg/day
- Obese: 15-20 kcal/kg/day (minimum 1800 kcal/day)
- Carbohydrate restriction to 35-45% of total calories, spread over 3 meals + 2-3 snacks
- Complex carbs with low glycaemic index preferred
- Adequate protein (20%) and fat (35-40%)
- Approximately 50% of women achieve adequate glucose control with diet alone (McFarland et al.)
2. Physical Activity
- Moderate aerobic exercise for 30 min, 3-5 times/week
- Postprandial walking (15-30 min) significantly reduces postprandial glucose
- Resistance training also beneficial
- Reduces insulin resistance and aids gestational weight management
- Contraindicated in placenta previa, preterm labor risk, severe hypertension
Important timing point: Allow only 1-2 weeks of dietary management before initiating medical therapy. Waiting longer misses the critical window of 28-34 weeks (period of accelerated fetal fat accretion). By 4 weeks of dietary therapy, only an additional 10% of patients achieve control (McFarland et al.).
C. Pharmacological Management
1. Insulin - PREFERRED First-Line Agent
Insulin is the gold standard for GDM treatment due to:
- Does not cross the placenta (no direct fetal effect)
- Proven safety and efficacy
- Lower treatment failure rates than oral agents
- Recommended by both ACOG and ADA as preferred therapy
Key landmark trials:
- ACHOIS Trial (Crowther et al.) - 1000 women; insulin-treated GDM had significantly lower serious perinatal complications (1% vs 4%) and lower leptin concentration (indicating less fetal fat mass)
- Landon et al. multicenter RCT - Treatment of mild GDM with insulin significantly reduced LGA (7.1% vs 14.5%), birth weight >4000g (5.9% vs 14.3%), shoulder dystocia (1.5% vs 4.0%), CS rates (26.9% vs 33.8%), and preeclampsia
Types of Insulin in Pregnancy (Creasy & Resnik, Table 59.12):
| Insulin Type | Onset | Peak | Duration | Notes |
|---|---|---|---|---|
| Regular insulin | 30-60 min | 2-4h | 6-8h | Safe; standard bolus |
| Lispro (Humalog) | 5-15 min | 30-90 min | 3-5h | Rapid-acting; preferred bolus |
| Aspart (Novolog) | 5-15 min | 30-90 min | 3-5h | Rapid-acting; safe in pregnancy |
| NPH | 1-2h | 4-8h | 12-16h | Traditional basal; cheap |
| Detemir (Levemir) | 1-2h | Flat | 18-24h | Long-acting; safe in pregnancy |
| Glargine (Lantus) | 1-2h | Flat | 20-24h | Data supports safety; some concerns |
| Degludec (Tresiba) | Slow | Flat | >42h | Limited pregnancy data |
Insulin Regimens:
- Typical starting dose for GDM: 0.7-0.8 units/kg/day (1st trimester) → 0.8-1.0 units/kg (2nd trimester) → 0.9-1.2 units/kg (3rd trimester)
- Combination regimen: Basal insulin (NPH or detemir) + rapid-acting bolus at meals
- Insulin pump (CSII) may be used in selected patients with pregestational DM
- Doses require weekly or more frequent adjustment as pregnancy progresses
Fasting hyperglycemia → treat with bedtime NPH or long-acting insulin
Postprandial hyperglycemia → treat with rapid-acting insulin before meals
2. Metformin
- Not recommended as first-line by ACOG or ADA for GDM
- Mechanism: Reduces hepatic glucose output, improves insulin sensitivity
- Key concern: Significant transplacental passage - metformin crosses to fetal compartment; inadequate long-term offspring safety data
- Studies show higher adiposity measurements in metformin-exposed children in utero
- MiTy Trial (Feig et al.) - metformin added to insulin in T2DM pregnancy led to lower HbA1c, lower insulin requirements, less weight gain, fewer CS deliveries, fewer LGA infants - but more SGA infants and lower birth weight
- Equivalent to insulin in short-term efficacy for GDM when insulin is not feasible
- Acceptable alternative when patient declines or cannot reliably administer insulin
- Dose: 500 mg once daily, titrate to max 2500 mg/day in divided doses
3. Glyburide (Glibenclamide)
- Currently NOT recommended by ACOG or ADA due to inferior outcomes compared to insulin and metformin
- Crosses placenta; associated with neonatal hypoglycemia
- Higher rates of macrosomia and NICU admissions compared to insulin
- If used: 2.5-5 mg twice daily (given 2 hours before meals), maximum 20 mg/day
D. Antepartum Fetal Surveillance
| Assessment | Frequency |
|---|---|
| Ultrasound for growth | Every 4 weeks from 28 weeks |
| Fetal weight estimation | 32-36 weeks to detect macrosomia |
| Biophysical profile / NST | Weekly from 36 weeks (or 32 weeks if poorly controlled) |
| Amniotic fluid index | For polyhydramnios (sign of poor glycemic control) |
| Umbilical artery Doppler | If IUGR or suspected |
Ultrasound identification of a large for gestational age (LGA) fetus or polyhydramnios are indicators of suboptimal glycemic control.
E. Continuous Glucose Monitoring (CGM)
- CONCEPTT Trial (T1DM in pregnancy) - CGM showed mild improvement in HbA1c, reduced LGA births, shorter NICU stay, and reduced neonatal hypoglycemia
- Target ranges (TIR) for T1DM pregnancy:
- Target range 63-140 mg/dL: goal >70% time in range
- Time below range (<63 mg/dL): goal <4%
- Time above range (>140 mg/dL): goal <25%
- Role in GDM is growing but evidence base developing
F. Obstetric Management - Timing and Mode of Delivery
| Scenario | Management |
|---|---|
| Diet-controlled GDM, no complications | Allow labor up to 40-41 weeks; ACOG suggests delivery by 40+6 |
| Insulin-treated GDM, well controlled | Induce at 39-40 weeks |
| Poorly controlled GDM | Deliver at 37-38 weeks |
| Estimated fetal weight ≥4500 g | Elective CS to prevent shoulder dystocia |
| Macrosomia (EFW ≥4000 g with suboptimal control) | Consider early induction |
Intrapartum management:
- Tight glucose control during labor (target 80-110 mg/dL)
- IV insulin infusion if needed during active labor
- Monitor fetal heart rate continuously
G. Complications of GDM
Maternal:
- Preeclampsia (2-4x increased risk)
- Operative delivery
- Risk of type 2 DM (7-10x increased risk; 10% develop T2DM within 5 years of delivery)
- Recurrence in subsequent pregnancies (30-50%)
Fetal/Neonatal:
- Macrosomia and LGA
- Shoulder dystocia and birth trauma (brachial plexus injury)
- Neonatal hypoglycemia (fetal hyperinsulinemia)
- Polycythemia
- Respiratory distress syndrome
- Hyperbilirubinemia
- Long-term childhood obesity and metabolic syndrome
H. Postpartum Management
- All GDM patients should have a 75-g 2-hour OGTT at 4-12 weeks postpartum to screen for persistent diabetes or impaired glucose tolerance
- If normal, retest every 1-3 years lifelong
- Metformin reduces the risk of T2DM in high-risk GDM patients postpartum
- Breastfeeding encouraged - reduces maternal insulin resistance
- Exercise and weight loss reduce long-term diabetes risk
- Lifestyle modification: most effective intervention to prevent progression to T2DM
SUMMARY TABLE
| Aspect | Key Points |
|---|---|
| Prevalence | ~8% of pregnancies |
| Pathophysiology | Failure of beta-cell compensation for physiological insulin resistance; placental anti-insulin hormones (hPL, cortisol) |
| Screening timing | 24-28 weeks universal; first visit for high-risk |
| One-step (IADPSG) | 75g OGTT: F ≥92, 1h ≥180, 2h ≥153 mg/dL (any one) |
| Two-step (ACOG) | 50g GCT → if ≥130: 100g OGTT (C-C criteria: F 95, 1h 180, 2h 155, 3h 140) |
| DIPSI (India) | 75g non-fasting, 2h value ≥140 mg/dL |
| Glucose targets | Fasting <95, 1h postprandial <140, 2h <120 mg/dL |
| First-line Rx | Diet + exercise → Insulin (if targets not met) |
| Insulin dose | 0.7-1.2 units/kg/day (increases each trimester) |
| Metformin | Acceptable alternative, not first-line; crosses placenta |
| Glyburide | Not recommended (ACOG, ADA 2024) |
| Delivery | Well-controlled: 39-40 weeks; CS if EFW ≥4500g |
| Postpartum | 75g OGTT at 4-12 weeks; lifelong annual screening |
Sources: Creasy & Resnik's Maternal-Fetal Medicine: Principles and Practice (9780323828499); Harrison's Principles of Internal Medicine 22E (9781265977061); ADA GDM Screening Table (ADA Standards of Care)
Tumor markers in gynecology 10 marks question in PG obs and gynec exam
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Tumor Markers in Gynecology
A Complete 10-Mark PG Answer
DEFINITION
A tumor marker is a substance - protein, enzyme, hormone, or antigen - produced by a tumor cell or by the host in response to a tumor, that can be detected in serum, urine, or tissue, and used for diagnosis, monitoring, and prognosis of malignancy.
Ideal properties of a tumor marker:
- High sensitivity (detect early disease)
- High specificity (positive only in that cancer)
- Correlate with tumor burden
- Short half-life (rapid response to treatment)
- Easy to measure; cost-effective
In practice, NO tumor marker is 100% sensitive or specific. They are best used for monitoring known disease and detecting recurrence, not primary screening.
CLASSIFICATION OF GYNECOLOGICAL TUMOR MARKERS
I. EPITHELIAL OVARIAN CANCER MARKERS
1. CA-125 (Cancer Antigen 125) - Most Important Gynecological Marker
-
Nature: Large membrane glycoprotein of the mucin family; encoded by MUC16 gene
-
Normal value: <35 U/mL
-
Sensitivity:
- Stage I disease: ~50% (poor early detection)
- Advanced disease (Stage III/IV): 80-90% for serous carcinoma
-
Clinical uses:
- Monitoring response to chemotherapy in known ovarian cancer
- Detecting recurrence post-treatment (rising CA-125 precedes clinical recurrence by months)
- Pre-operative assessment of pelvic mass (Risk of Malignancy Index uses CA-125)
- NOT recommended for population screening (USPSTF recommends against routine ovarian cancer screening with CA-125 - no mortality benefit, moderate harms from false positives)
-
Causes of false positive elevation (non-malignant):
- Endometriosis
- Pelvic inflammatory disease
- Uterine fibroids
- Ascites (any cause - hepatic, cardiac, peritoneal TB)
- Menstruation (transient elevation)
- Pregnancy (first trimester)
- Liver cirrhosis, pancreatitis
- Pleural effusion
-
Other malignancies: Endometrial, cervical, pancreatic, breast, lung cancers
(Berek & Novak's Gynecology; Henry's Clinical Diagnosis and Management)
2. HE4 (Human Epididymis Protein 4)
- Nature: Whey acidic protein family; expressed in normal fallopian tube epithelium
- Normal value: <150 pmol/L (varies by menopausal status)
- More specific than CA-125 for epithelial ovarian cancer
- Less affected by endometriosis or benign gynecological conditions
- ROMA Score (Risk of Ovarian Malignancy Algorithm): Combines HE4 + CA-125 + menopausal status
- Pre-menopausal: High risk if ROMA ≥13.1%
- Post-menopausal: High risk if ROMA ≥27.7%
- Superior to CA-125 alone in distinguishing malignant from benign pelvic masses
II. GERM CELL TUMOR MARKERS
These are the most important markers in young women with ovarian masses.
3. Alpha-Fetoprotein (AFP)
- Nature: Major fetal serum glycoprotein synthesized by yolk sac and fetal hepatocytes
- Normal value: <10 ng/mL (adult)
- Tumors: Yolk sac tumor (Endodermal Sinus Tumor) - markedly elevated; also embryonal carcinoma, mixed germ cell tumor
- Important: AFP is also elevated in:
- Hepatocellular carcinoma
- Hepatoblastoma
- Normal pregnancy (used in maternal serum screening)
- Benign liver disease (transient)
- Use: Pre-operative baseline; monitor response to chemotherapy; detect recurrence
4. Beta-hCG (Human Chorionic Gonadotropin)
- Nature: Glycoprotein hormone; beta subunit is tumor-specific
- Tumors:
- Choriocarcinoma - markedly elevated (main marker)
- Gestational Trophoblastic Disease (GTD): Hydatidiform mole, invasive mole, choriocarcinoma, PSTT
- Dysgerminoma (mildly elevated)
- Embryonal carcinoma
- Mixed germ cell tumors
- Unique feature: β-hCG is the most clinically useful marker in gynecology because:
- Quantitative hCG tracks disease accurately
- Used for diagnosis, treatment monitoring, and cure criteria
- In GTD, normalization of hCG = remission; rise = recurrence
- Screening recommended in all women post-molar pregnancy
- Causes of false elevation: Phantom hCG (heterophilic antibody interference), physiological pregnancy
5. LDH (Lactate Dehydrogenase)
- Tumor: Dysgerminoma (pure) - the most common malignant germ cell tumor
- Also elevated in: Other germ cell tumors, non-Hodgkin's lymphoma
- Less specific but useful in combination
6. Placental Alkaline Phosphatase (PLAP)
- Tumor: Dysgerminoma; also seminoma
- Used as additional marker alongside LDH for dysgerminoma
III. SEX CORD-STROMAL TUMOR MARKERS
7. Inhibin A and B
- Nature: Dimeric proteins produced by granulosa cells
- Tumor: Granulosa cell tumor (most specific marker)
- Also Sertoli-Leydig cell tumors (mildly)
- Mucinous cystadenoma/carcinoma (minor elevation)
- Inhibin B is more sensitive than Inhibin A for granulosa cell tumor
- Post-menopausal women: Inhibin should be undetectable; any elevation is suspicious
- Used for monitoring recurrence of granulosa cell tumors (which have a tendency for late recurrence - 5-30 years)
8. AMH (Anti-Müllerian Hormone)
- Produced by granulosa cells of small growing follicles
- Elevated in Adult-type granulosa cell tumors
- More stable than Inhibin; useful for long-term monitoring
- Normal in post-menopausal women → elevated AMH = suspicious for granulosa cell tumor
9. Estradiol / Testosterone
- Granulosa cell tumors: Estradiol elevated (causes isosexual precocious puberty in children; endometrial hyperplasia/carcinoma in adults)
- Sertoli-Leydig cell tumors: Testosterone and DHEAS elevated (causes virilization, amenorrhea, acne, clitoromegaly)
IV. CERVICAL CANCER MARKERS
10. SCC Antigen (Squamous Cell Carcinoma Antigen)
- Normal value: <1.5 ng/mL
- Tumor: Squamous cell carcinoma of the cervix (most important marker for this cancer)
- Correlates with stage, tumor volume, depth of invasion, and lymph node status
- Rising levels predict recurrence
- Other markers for cervical cancer: CEA (cervical adenocarcinoma), CA-125, CYFRA 21-1, TPA
(Henry's Clinical Diagnosis and Management - Gynecological Tumors Table)
V. ENDOMETRIAL CANCER MARKERS
11. CA-125
- Elevated in advanced endometrial cancer (Stage III/IV)
- Predicts extrauterine disease and lymph node involvement pre-operatively
- Not useful for early-stage endometrial cancer
12. HE4
- Superior to CA-125 for endometrial cancer
- Elevated in early-stage disease; correlates with myometrial invasion
- Useful for preoperative risk stratification
VI. GESTATIONAL TROPHOBLASTIC DISEASE (GTD) - Special Mention
| Type | hCG level |
|---|---|
| Hydatidiform mole | Markedly elevated (>100,000 mIU/mL) |
| Invasive mole | Elevated |
| Choriocarcinoma | Very high (can be millions) |
| PSTT (Placental Site Trophoblastic Tumor) | Low hCG (mainly hPL elevated) |
Surveillance protocol post-molar pregnancy:
- Weekly hCG until 3 consecutive normal values
- Then monthly for 6-12 months
- Diagnosis of persistent GTN: hCG plateau for 3 weeks or rise for 2 consecutive weeks
SUMMARY TABLE: GYNECOLOGICAL TUMOR MARKERS
| Tumor Marker | Cancer Type | Normal Value | Clinical Use |
|---|---|---|---|
| CA-125 | Epithelial ovarian, endometrial | <35 U/mL | Monitoring, recurrence |
| HE4 | Epithelial ovarian, endometrial | <150 pmol/L | Pre-op pelvic mass assessment, ROMA |
| AFP | Yolk sac tumor, embryonal ca | <10 ng/mL | Diagnosis + monitoring |
| β-hCG | Choriocarcinoma, GTD, dysgerminoma | <5 mIU/mL | Diagnosis, treatment, cure |
| LDH | Dysgerminoma | Lab-specific | Monitoring |
| Inhibin B | Granulosa cell tumor | Undetectable (post-menopause) | Diagnosis, recurrence |
| AMH | Granulosa cell tumor | Undetectable (post-menopause) | Recurrence monitoring |
| Estradiol | Granulosa cell tumor | - | Clinical effect marker |
| Testosterone | Sertoli-Leydig tumor | - | Virilization assessment |
| SCC antigen | Squamous ca cervix | <1.5 ng/mL | Staging, recurrence |
| CEA | Cervical adenocarcinoma, mucinous ovarian | - | Monitoring |
LIMITATIONS OF TUMOR MARKERS (Important for PG Exam)
- No marker is 100% sensitive or specific
- False positives occur in benign conditions (CA-125 in endometriosis, hCG in normal pregnancy)
- Serial measurements from the same laboratory using the same assay are essential for monitoring
- Half-life must be considered when assessing post-treatment response:
- Wait at least 2 weeks (preferably 1 month) after surgery before re-checking
- Heterogeneous tumors may require multiple markers simultaneously
- Heterophilic antibody interference can cause falsely high values (particularly for hCG - "phantom hCG")
- Markers for screening vs. monitoring are different roles - CA-125 fails as a screening tool but succeeds as a monitoring tool
RISK OF MALIGNANCY INDEX (RMI) - Using CA-125 in Practice
RMI = U × M × CA-125
Where:
- U (ultrasound score): 0 = no features, 1 = one feature, 3 = two or more features
- M (menopausal status): 1 = pre-menopausal, 3 = post-menopausal
- Ultrasound features: Multilocular cyst, solid areas, bilateral lesions, ascites, intra-abdominal metastasis
Interpretation:
- RMI <25: Low risk (benign)
- RMI 25-250: Moderate risk
- RMI >250: High risk - refer to gynae-oncology centre
(RMI >200 has sensitivity ~85%, specificity ~97% for ovarian malignancy)
Sources: Berek & Novak's Gynecology (9781496380357); Henry's Clinical Diagnosis and Management by Laboratory Methods (9780323673204); Robbins & Cotran Pathologic Basis of Disease (9780443264528)
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