2d:I[856015,["/_next/static/immutable/chunks/1xzisbplk9czp.js","/_next/static/immutable/chunks/3j2i1faptc_-9.js","/_next/static/immutable/chunks/0fma7nlq6immz.js","/_next/static/immutable/chunks/08tq8rmv423j5.js","/_next/static/immutable/chunks/1chr5wkk3j58k.js","/_next/static/immutable/chunks/37kmmh_zm4dov.js","/_next/static/immutable/chunks/311zvdjfxff-f.js","/_next/static/immutable/chunks/1a_hqhrsle_n_.js"],"default"] 2e:T57f6,

Category	Details
Risk Factors	First pregnancy, molar pregnancy (gestational trophoblastic disease), multiple gestation, history of hyperemesis in prior pregnancy, family history, obesity, female fetus
Etiology	Exaggerated physiologic response to rapidly rising beta-hCG levels in early pregnancy; exact mechanism incompletely understood but strongly correlated with hCG-mediated stimulation of the chemoreceptor trigger zone
Patient Presentation	Pregnant woman (typically 6 to 9 weeks gestation) with intractable nausea and vomiting, unable to tolerate oral intake, with documented weight loss of 5% or more from pre-pregnancy baseline
Classic Physical Exam	Signs of dehydration (dry mucous membranes, poor skin turgor, tachycardia, orthostatic hypotension), muscle wasting in severe cases, ptyalism (excessive salivation)
Key Diagnostic Results	Ketonuria on urinalysis, hypochloremic hypokalemic metabolic alkalosis, elevated urine specific gravity, elevated hCG (disproportionately high in molar pregnancy), possible elevated liver transaminases and amylase/lipase in severe cases, low TSH with mildly elevated free T4 (gestational transient thyrotoxicosis)
Management	IV fluid resuscitation (normal saline with dextrose and electrolyte repletion), thiamine supplementation before dextrose to prevent Wernicke encephalopathy, antiemetics (ondansetron, metoclopramide, promethazine), nutritional support
Keywords	"Intractable vomiting in pregnancy," "weight loss >5%," "ketonuria," "unable to tolerate oral intake," "dehydration in first trimester"

1. Pathophysiology

Hyperemesis gravidarum represents the severe end of the nausea-vomiting spectrum in pregnancy. While up to 80% of pregnant women experience some degree of nausea during the first trimester, hyperemesis gravidarum is defined by persistent vomiting leading to dehydration, ketonuria, and weight loss exceeding 5% of pre-pregnancy body weight. The condition typically peaks between weeks 8 and 12, correlating with the peak of serum beta-hCG.

The central driver is beta-hCG, which structurally resembles TSH and acts on the chemoreceptor trigger zone in the area postrema. This explains two important exam-relevant phenomena. First, conditions that produce abnormally high hCG levels (molar pregnancy, multiple gestations) carry a higher risk of hyperemesis. Second, the structural homology between hCG and TSH means that very high hCG levels can cross-stimulate the TSH receptor on thyroid follicular cells, producing a state called gestational transient thyrotoxicosis. This results in a suppressed TSH and mildly elevated free T4 without true hyperthyroidism. This is a self-limited condition that does not require antithyroid treatment, and distinguishing it from Graves disease is a classic exam trap.

The relentless vomiting leads to loss of gastric hydrochloric acid, producing the hallmark electrolyte pattern: hypochloremic hypokalemic metabolic alkalosis. Chloride and hydrogen ions are lost directly in the vomitus. The kidney compensates by retaining hydrogen ions at the expense of potassium, worsening hypokalemia. Severe volume depletion triggers an aldosterone response that further drives potassium wasting.

A critical downstream complication arises from thiamine (vitamin B1) depletion. Prolonged inability to eat depletes thiamine stores, and if dextrose-containing IV fluids are administered before thiamine repletion, the glucose load accelerates thiamine consumption in glycolysis, precipitating Wernicke encephalopathy (confusion, ophthalmoplegia, ataxia). This is the single most dangerous and most testable complication of hyperemesis gravidarum.

2. Classification and Clinical Manifestation

Severity	Clinical Features	Lab Findings
Mild (nausea and vomiting of pregnancy)	Intermittent nausea with occasional vomiting, tolerates some oral intake, no weight loss, normal daily function	Normal electrolytes, no ketonuria
Moderate hyperemesis	Frequent vomiting (>3 times/day), reduced oral intake, weight loss 5% from baseline, mild dehydration	Ketonuria, mildly elevated urine specific gravity, early electrolyte derangement
Severe hyperemesis	Intractable vomiting, complete oral intolerance, weight loss >10%, clinical dehydration, inability to perform daily activities	Marked ketonuria, hypochloremic hypokalemic metabolic alkalosis, elevated BUN/creatinine (prerenal azotemia), elevated liver enzymes, possible elevated amylase/lipase
Complicated hyperemesis	All features of severe disease plus neurologic symptoms (confusion, nystagmus, ataxia) suggesting Wernicke encephalopathy, or evidence of central pontine myelinolysis from overly rapid electrolyte correction	Severely depleted thiamine, profound electrolyte disturbances

The key clinical discriminator between normal pregnancy-related nausea and hyperemesis gravidarum is the presence of weight loss, ketonuria, and inability to maintain hydration through oral intake. Exam vignettes will emphasize these features to signal that the patient has crossed from physiologic nausea into a pathologic state requiring intervention.

It is also worth noting the typical timeline. Symptoms that begin after 10 to 12 weeks, or that persist well into the second trimester, should raise concern for alternative diagnoses such as gastroparesis, biliary disease, pancreatitis, or a CNS lesion.

3. Diagnostic Workup

Test	Purpose	Expected Findings
Urinalysis (Best Initial Test)	Assess hydration and ketosis	Ketonuria, elevated specific gravity
Basic metabolic panel	Evaluate electrolyte status and renal function	Hypochloremia, hypokalemia, metabolic alkalosis, elevated BUN/creatinine ratio (prerenal pattern)
Serum beta-hCG	Quantify hCG level; screen for molar pregnancy if disproportionately elevated	Elevated; markedly elevated in molar pregnancy
Thyroid function tests (TSH, free T4)	Rule out primary hyperthyroidism; identify gestational transient thyrotoxicosis	Low TSH, mildly elevated free T4 (no TPO/TSI antibodies)
Liver function tests	Assess hepatic involvement in severe cases	AST/ALT elevated up to 2 to 3 times normal in severe hyperemesis
Pelvic ultrasound	Confirm viable intrauterine pregnancy; exclude molar pregnancy and multiple gestation	Normal gestational sac or findings of hydatidiform mole / twins
Amylase/Lipase	Rule out pancreatitis if abdominal pain is prominent	May be mildly elevated in hyperemesis itself; markedly elevated suggests pancreatitis

Urinalysis is the best initial test because it is rapid, noninvasive, and immediately confirms two hallmarks of the diagnosis: ketonuria (indicating starvation physiology) and concentrated urine (indicating dehydration). A urine dipstick positive for ketones in a first-trimester pregnant woman with persistent vomiting and weight loss essentially clinches the clinical diagnosis.

The basic metabolic panel follows to guide fluid and electrolyte management. The classic pattern of low chloride, low potassium, and elevated bicarbonate reflects the metabolic alkalosis from gastric acid loss. A prerenal pattern (BUN-to-creatinine ratio >20:1) confirms volume depletion.

Thyroid function tests are important to order early, not because you expect true thyroid disease, but because the suppressed TSH is a predictable finding in hyperemesis and should not trigger unnecessary antithyroid therapy. The distinguishing features from Graves disease include: absence of thyroid antibodies (anti-TSH receptor antibody/TSI), absence of goiter or ophthalmopathy, and spontaneous resolution as hCG levels decline after the first trimester.

Pelvic ultrasound is ordered to confirm the pregnancy and, critically, to rule out a molar pregnancy. If a patient presents with hyperemesis gravidarum and a uterus that is large for gestational age with a "snowstorm" pattern on ultrasound, the underlying cause is gestational trophoblastic disease, which changes management entirely.

There is no single "gold standard" confirmatory test for hyperemesis gravidarum. It is a clinical diagnosis based on the triad of intractable vomiting, weight loss exceeding 5%, and ketonuria in the context of early pregnancy, after exclusion of other causes.

4. Management and Treatment

Step	Intervention	Details
1. IV Fluid Resuscitation	Normal saline (0.9% NaCl)	Bolus 1 to 2 liters, then maintenance; add KCl 20 to 40 mEq/L once renal function confirmed
2. Thiamine Repletion	Thiamine 100 mg IV	Must be given BEFORE any dextrose-containing fluids; continue daily for at least 3 days
3. Dextrose Supplementation	D5NS or D5 half-normal saline	Only after thiamine has been administered; corrects ketosis and provides caloric substrate
4. Antiemetics (first-line)	Ondansetron 4 mg IV/PO every 8 hours	Safe in pregnancy; most commonly tested first-line agent
5. Antiemetics (alternatives)	Metoclopramide 10 mg IV/PO every 6 to 8 hours, or promethazine 12.5 to 25 mg IV/IM every 4 to 6 hours	Metoclopramide also has prokinetic effect; promethazine causes sedation
6. Pyridoxine with doxylamine	Pyridoxine (vitamin B6) 10 to 25 mg PO every 8 hours + doxylamine 12.5 mg PO every 8 hours	Recommended as first-line outpatient therapy for mild to moderate cases
7. Corticosteroids (refractory)	Methylprednisolone 16 mg IV/PO every 8 hours for 3 days, then taper	Reserved for cases failing all other therapies; avoid before 10 weeks gestation due to cleft palate risk
8. Nutritional Support	Enteral feeding via nasogastric/nasoduodenal tube, or TPN in extreme cases	TPN is the last resort due to line infection and metabolic complication risks

Acute stabilization begins with aggressive IV hydration. Normal saline is preferred because it directly replaces the chloride lost in vomiting and corrects the metabolic alkalosis. Potassium repletion is added once urine output is confirmed adequate.

The single most important management pearl is the sequencing of thiamine before dextrose. This is tested repeatedly. Thiamine is a cofactor for pyruvate dehydrogenase and transketolase. When dextrose is infused into a thiamine-depleted patient, the sudden glycolytic load exhausts remaining thiamine stores, triggering acute Wernicke encephalopathy. The correct sequence is always: thiamine first, then dextrose.

For outpatient management of milder presentations, the pyridoxine-doxylamine combination is first-line. Pyridoxine (vitamin B6) is given at 10 to 25 mg three times daily, and if insufficient, doxylamine (an antihistamine with antiemetic properties) is added. This combination has the longest safety track record in pregnancy.

When patients fail oral therapy and require hospitalization, ondansetron becomes the most commonly tested first-line parenteral antiemetic. It is a serotonin 5-HT3 receptor antagonist that acts on the chemoreceptor trigger zone. There has been some concern about a small risk of cleft palate with first-trimester use, but current guidelines consider it acceptable when benefits outweigh risks.

Corticosteroids are reserved for truly refractory cases. Methylprednisolone should not be used before 10 weeks of gestation due to an association with oral clefts. The mechanism is thought to involve suppression of the immune and inflammatory pathways that may contribute to the nausea cascade.

Electrolyte correction should be gradual. Rapid correction of hyponatremia, if present, risks osmotic demyelination syndrome (central pontine myelinolysis). Sodium should not be corrected faster than 8 to 10 mEq/L per 24 hours.

5. Differential Diagnosis and Distractors

Differential Diagnosis	Why It Looks Similar	Key Discriminator
Molar pregnancy (gestational trophoblastic disease)	Also presents with severe vomiting in early pregnancy, elevated hCG	Uterus large for dates, "snowstorm" appearance on ultrasound, no fetal heart tones, markedly elevated hCG (often >100,000 mIU/mL), vaginal bleeding with grape-like vesicles
Graves disease	Both show suppressed TSH with elevated free T4	Graves has positive TSI/anti-TSH receptor antibodies, goiter, ophthalmopathy, and symptoms persist beyond first trimester; gestational thyrotoxicosis resolves spontaneously and has no antibodies
Acute cholecystitis	Nausea, vomiting, right upper quadrant pain in a pregnant patient	Fever, positive Murphy sign, gallbladder wall thickening and pericholecystic fluid on ultrasound; pain is the dominant feature, not vomiting
Pancreatitis	Nausea, vomiting, elevated amylase/lipase	Epigastric pain radiating to the back is the cardinal symptom; lipase is markedly elevated (>3 times upper limit of normal), not just mildly elevated
Gastroparesis	Persistent nausea and vomiting	Usually in patients with longstanding diabetes or post-surgical; diagnosed by gastric emptying scintigraphy; no ketonuria or weight loss pattern typical of hyperemesis
Addisonian crisis (adrenal insufficiency)	Nausea, vomiting, hypotension, electrolyte disturbances	Hyperkalemia (not hypokalemia), hyponatremia, hyperpigmentation, cortisol level is low; metabolic acidosis rather than alkalosis
Diabetic ketoacidosis	Vomiting, ketonuria, dehydration	Metabolic acidosis with anion gap (not alkalosis), hyperglycemia, Kussmaul breathing, history of type 1 diabetes

The most dangerous distractor on the exam is molar pregnancy, because it can present identically to hyperemesis gravidarum. A vignette with a first-trimester patient who has intractable vomiting, a uterus larger than expected, and an extremely high hCG should prompt you to select molar pregnancy (or at least pelvic ultrasound as the next step) rather than simply treating hyperemesis.

The Graves disease versus gestational transient thyrotoxicosis distinction is tested as a "do not treat" question. The correct answer is observation, not methimazole or propylthiouracil, when the thyroid abnormality is in the context of hyperemesis with no antibodies and no eye findings.

6. Traps and High-Yield Pearls

The single most tested trap in hyperemesis gravidarum is the thiamine-before-dextrose rule. A vignette will describe a dehydrated, vomiting pregnant woman and ask for the next best step. The temptation is to order D5 normal saline immediately for both hydration and caloric support. The correct answer is to give thiamine first. Administering glucose to a thiamine-depleted patient precipitates Wernicke encephalopathy, a devastating and preventable complication. If the question stem mentions any neurologic symptom (confusion, gaze palsy, ataxia) in a patient with prolonged hyperemesis, you are being tested on whether you recognize iatrogenic Wernicke encephalopathy from premature dextrose administration.

The second major trap is mistaking gestational transient thyrotoxicosis for Graves disease. Both show low TSH and elevated free T4, but the appropriate management in the context of hyperemesis is reassurance and supportive care. Initiating antithyroid drugs in this scenario is a wrong answer designed to catch students who reflexively treat every abnormal TSH.

A third pearl involves the electrolyte pattern. If a vignette gives you a pregnant woman with vomiting and asks you to predict the electrolyte abnormality, the answer is hypochloremic hypokalemic metabolic alkalosis. If the patient instead has metabolic acidosis with an anion gap, the diagnosis is not hyperemesis but rather diabetic ketoacidosis or another acidosis-producing condition.

Finally, always check the gestational age and uterine size in the vignette. Hyperemesis peaks at 8 to 12 weeks and typically resolves by 20 weeks. If the uterine size is discordant (larger than expected for dates), suspect molar pregnancy or multiple gestation as the underlying driver. The core competency being tested across all these scenarios is your ability to sequence the workup and treatment correctly, recognize when a common diagnosis is masking a more dangerous one, and avoid initiating unnecessary or harmful therapies based on laboratory findings taken out of clinical context.

1e:["$","$L2d",null,{"article":{"id":"5746e9c1-9589-4c96-b229-aba083c8b376","title":"Hiperemesis Gravidarum","content":"$2e","category":"Reproduksi","created_at":"2026-05-16T07:04:22.702778+00:00","status":"published","subcategory":null},"questionCount":3,"sections":[{"id":"section-pathophysiology","num":"01","title":"Pathophysiology"},{"id":"section-classification-and-clinical-manifestation","num":"02","title":"Classification and Clinical Manifestation"},{"id":"section-diagnostic-workup","num":"03","title":"Diagnostic Workup"},{"id":"section-management-and-treatment","num":"04","title":"Management and Treatment"},{"id":"section-differential-diagnosis-and-distractors","num":"05","title":"Differential Diagnosis and Distractors"},{"id":"section-traps-and-high-yield-pearls","num":"06","title":"Traps and High-Yield Pearls"}],"hasSummaryTable":true}]