Ca Lâm Sàng 9

Major takeaway
Molar pregnancies have a typical “snowstorm appearance” on ultrasound. A fundal height that is large for dates and an abnormally elevated ßhCG level are suggestive of this diagnosis.

Main explanation
A woman presenting early in pregnancy with a greater than expected fundal height and the absence of a fetal heart sound is suggestive of a molar pregnancy.

Molar pregnancies occur due to abnormal fertilization of an ovum. They may be complete (no maternal genetic material) or partial moles (maternal and paternal genetic material). Partial moles may contain fetal tissue however complete moles do not.

Confirmation of this diagnosis is achieved with ultrasonography. The “snowstorm appearance” pictured below is typical of a molar pregnancy. The primary lab abnormality seen in a molar pregnancy is an elevated serum human chorionic gonadotropin (hCG).

CA-125 levels are not associated with molar pregnancy. CA-125 is a tumor marker for ovarian cancer and is not part of the standard laboratory workup during pregnancy.

The serum human chorionic gonadotropic (hCG) level would be expected to be abnormally high in a molar pregnancy due to excessive trophoblastic growth.

The TSH levels would be either normal or LOW given the hCG stimulation of the thyroid gland in molar pregnancies.

The serum human chorionic gonadotropic (hCG) level would be expected to be abnormally high in a molar pregnancy due to excessive trophoblastic growth.

Bupropion exerts its action through norepinephrine agonist effects and antagonism of nicotinic receptors. It has evidence for use in obesity. It has also been shown to reduce the seizure threshold, which is impaired in anorexic and bulimic patients. Thus, it is not recommended for any indication in this population.

Clonazepam, a slow-acting benzodiazepine which binds to the gamma-aminobutyric acid receptor and increases its activity, is most commonly used for short term relief of anxiety symptoms. In preclinical models, there is some evidence that benzodiazepinesincrease binge eating behaviors.

Major takeaway
The only approved antidepressant for treatment of bulimia is the SSRI fluoxetine, which has been shown to reduce the frequency and severity of the classic binge-purge behavior.
Main explanation
Bulimia is a complicated disease that is classically thought to consist of a binge and purge cycle. The vomiting increases the risk of hypokalemia, which can cause weakness, fatigue, muscle cramps, and arrhythmias. The stereotypical bulimia patient is not underweight. The current guidelines, in fact, recommend anorexia as the major diagnosis for any patient with a BMI below 18.5 kg/m2, even if they follow the classic binge and purge behavior. The only approved antidepressant for the treatment of bulimia is fluoxetine, which appears to reduce the frequency and severity of the binge-purge cycle. As might be expected, other related selective serotonin reuptake inhibitors (SSRIs) have similar data, but they have not been approved by the FDA. Anorexia and bulimia are best treated by a combination approach. This includes behavioral interventions including refeeding therapy (for anorexia), family therapy, andcognitive-behavioral therapy.

Olanzapine is an atypical antipsychotic with inverse agonist effects on the 5-HT2A receptor, though many other serotonin and muscarinic receptors are also affected. The current evidence does not support the use of olanzapine for weight gain in patients with eating disorders.

Ondansetron is a 5-HT3 receptor antagonist with antiemetic effects. There are some studies on ondansetron in bulimic patients, with mixed results, and therefore has not been approved for treatment of bulimia.

Although the presence of brain tumor/mass must be excluded, this diagnosis is unlikely given the age of the patient and a lack of focal signs on physical exam.

Pseudotumor cerebri can be distinguished from classic migraine in the above case by the presence of papilledema, which is demonstrated by progressive blurriness and vision changes.

Cluster headaches are unilateral and very severe. They occur in clusters (such as 4 in one week and then none in 2 months) and are usually treated 1st line with supplemental oxygen.

Major takeaway
The diagnosis of pseudotumor cerebri, or idiopathic intracranial hypertension, is commonly found in a young obese woman who presents with recurrent morning headaches and evidence of papilledema.

Main explanation
This patient is presenting with symptoms of idiopathic intracranial hypertension, which is also known as pseudotumor cerebri. This diagnosis is typically made in an obese female of childbearing age who presents with morning headaches that are recurrent along with nauseaand vomiting. Patients with this condition often have papilledema noted on physical examination. When a patient presents with concerning symptoms, such as an increasing frequency of pounding headaches and evidence of potential cranial nerve abnormalities with no obvious cause, physicians often order imaging studies of the head to rule out the presence of tumors, among other possibilities. Computed tomography and magnetic resonance imaging typically appear normal in this condition. The diagnosis is often made when a subsequent lumbar puncture shows increased opening pressure and results in immediate relief of the headache. Excess vitamin A may be a cause. It can be effectively treated with carbonic anhydrase inhibitor diuretics such as acetazolamide or cerebrospinal fluid shunting.

Tension headaches are generally mild and require treatment with anti-inflammatory medications. They often develop in the occipital portion of the head and are felt bilaterally.

Major takeaway
Amyotrophic lateral sclerosis (ALS or Lou Gehrig disease) is a disorder that involves the death of neurons that control voluntary muscles. ALS is characterized by stiff muscles, muscle twitching, and gradually worsening weakness due to muscles decreasing in size.This results in difficulty speaking, swallowing, and breathing.

Main explanation
Amyotrophic lateral sclerosis (ALS or Lou Gehrig disease) is a disorder that involves the death of neurons that control voluntary muscles. The cause is not known in 90-95% of cases and about 5–10% of cases are inherited from a person’s parents. A defect on chromosome 21, which codes for superoxide dismutase 1 (SOD1), is associated with about 20% of familial cases of ALS, or about 2% of ALS cases overall. Diagnosis is made with clinical reference, with a nerve conduction study, and electromyography. ALS is characterized by stiff muscles, muscle twitching, and gradually worsening weakness due to muscles decreasing in size. This results in difficulty speaking, swallowing, and breathing. No cure for ALS is known but it is often treated with riluzole in attempts to slow the progression of the disease. Riluzole works by decreasing presynaptic glutamate release, thereby limiting cytotoxic effects of this neurotransmitter. Non-invasive ventilation results in improved quality and length of life. ALS starts around the age of 60 and in inherited cases around the age of 50. The average survival from onset to death is 3 to 4 years. About 10% survive >10 years and most die from respiratory failure.

Beck syndrome (anterior spinal artery syndrome) is characterized by loss of motor function below the level of injury, loss of sensations carried by the anterior columns of the spinal cord, and preservation of sensations carried by the posterior columns.

Brown-Sequard syndrome is characterized by ipsilateral loss of vibration, ipsilateral spastic paresis below the lesion, ipsilateral flaccid paralysis at the level of the lesion, and contralateral loss of pain and temperature below the lesion.

Syringomyelia is related with Arnold-Chiari malformations and is characterized by bilateral loss of pain and temperature one level below the lesion and also bilateral flaccid paralysis at the level of the lesion.

Vitamin B12 deficiency causes bilateral loss of vibratory sensation and bilateral spastic paresis that affects the legs before the arms. It is commonly seen in vegetarians.

FISH testing on chromosome 22 is for DiGeorge syndrome, which presents with the physical symptoms of congenital heart defect, thymic aplasia, immune deficiency, hypocalcemia and facial palate abnormalities .

Major takeaway
Prader-Willi syndrome is caused by abnormal methylation and paternal deletion of chromosome 15q11-13. It can be definitevely diagnosed by fluorescence in situ hybridization(FISH) tesing.

Main explanation
The patient in this question is exhibiting the classic symptoms of Prader-Willi syndrome. Prader-Willi syndrome (PWS) is the most common syndromic form of obesity. It is caused by absence of expression of the paternally active genes in the long arm of chromosome 15, with the majority of cases occur sporadically. PWS is characterized by hypotonicity with poor feeding during the newborn period, which then progresses to hyperphagia and obesity by childhood. In addition, there is a global developmental delay, with a range of intellectual disabilities as well as behavioral problems later on in development, which is seen in this patient in the form of manipulating his grandmother to provide him food. Physically, patients with PWS have short stature, small hands and feet, low muscle tone, almond shaped eyes, narrow face diameter, down-turned mouth, and underdeveloped sex organs. Typically, the syndrome can be confirmed with FISH testing, looking for the paternal deletion on chromosome 15q11-13.

Low dose dexamethasone test can be used to diagnose Cushing syndrome, which also is associated with obesity but does not explain the patient’s initial newborn hypotonic period. With Cushing syndrome you would also expect to see physical findings such as a buffalo hump or moon facies.

Pseudohypoparathyroidism is known present as short, round faced and developmentally delayed children. This disorder typically has a defect of the adenylate cyclase/cyclic AMP system. This is unlikely to be the cause of the patient’s obesity, given lack of hyperphagia associated with the disorder.

A sweat test is the diagnostic gold standard to asses for cystic fibrosis, a disease caused by a mutation in the gene coding for the cystic fibrosis transmembrane conductance regulator (CFTR).

Agranulocytosis is an acute condition involving a severe and dangerous leukopenia, most commonly of neutrophils. The concentration of granulocytes drops below 500 cells/mm³ of blood.

Malignant hypertension (systolic over 180 or diastolic over 120) is hypertension with acute impairment of one or more organ systems (especially the central nervous system, cardiovascular system and/or the renal system) that result in irreversible organ damage.

Neuroleptic malignant syndrome (NMS) is a life-threatening neurological disorder most often caused by an adverse reaction to neuroleptic or antipsychotic drugs. NMS consists of muscle rigidity, fever, autonomic instability, and cognitive changes such as delirium, and is associated with elevated plasma creatine phosphokinase.

Major takeaway
Tardive dyskinesia (TD) is a difficult-to-treat and often incurable form of dyskinesia, a disorder resulting in involuntary, repetitive body movements. In this form of dyskinesia, the involuntary movements are tardive, meaning they have a slow or belated onset.
Main explanation
Tardive dyskinesia (TD) is a difficult-to-treat and often incurable form of dyskinesia, a disorder resulting in involuntary, repetitive body movements. Involuntary movements are tardive, meaning they have a slow or belated onset. This neurological disorder occurs as the result of long-term (usually at least 3 months duration) or high-dose use of antipsychotic drugs, or in children and infants as a side effect from usage of drugs for gastrointestinal disorders, typically metaclopramide. First generation antipsychotics such as fluphenazine, haloperidol, and pimozide are particularly implicated.
TD is characterized by repetitive and involuntary movements (e.g. grimacing, tongue movements, lip smacking, lip puckering, pursing of the lips, and excessive eye blinking). The exact mechanism of the disorder remains largely uncertain. The most compelling line of evidence suggests that TD result primarily from neuroleptic-induced dopamine super sensitivity in the nigrostriatal pathway, with the D2 dopamine receptor being most affected. Currently, there are no FDA approved drugs for treating TD, though some have shown efficacy in studies like tetrabenazine, reserpine, ondansetron, clonidine, Botox injections, and benzodiazepines, among others. TD most commonly occurs in patients with psychiatric conditions who are treated with antipsychotic medications for many years. The average prevalence rate has been estimated to be around 30% for individuals taking antipsychotic medication.

Tourette syndrome is an inherited neuropsychiatric disorder with onset in childhood, characterized by multiple physical (motor) ticsand at least one vocal (phonic) tic. These tics characteristically wax and wane, can be suppressed temporarily, and are preceded by a premonitory urge.

Since lymph node biopsy showed Reed-Sternberg cells, it is likely this patient has lymphoma rather than leukemia. Leukemiausually presents with symptoms of bone failure such as anemia and hemorrhage. AML is a type of leukemia that involves neoplasm from the myeloid lineage rather than lymphoid lineage.

Burkitt lymphoma usually presents in adolescents or young adults. Non-Hodgkin lymphomas typically have involvement of multiple peripheral nodes in a noncontiguous spread. On peripheral blood smear, Burkitt lymphoma shows a sheet of mature B cells with numerous tingible macrophages interspersed. In this image, interspersed macrophages are not seen.

Although the patient is in the peak age range for CML (45-85 years), the lymph node biopsy showed Reed-Sternberg cells, which likely leans towards lymphoma rather than leukemia. CML also involves neoplasm from the myeloid lineage, and is often associated with the Philadelphia chromosome (t[9;22], BCR-ABL).

Hairy cell leukemia typically occurs in adult males and is histologically characterized by the presence of mature B-cells with abnormal, hair-like projections. The most common symptoms include pancytopenia, due to bone marrow involvement, and splenomegaly. Reed-Sternberg cells are not common in this condition.

Major takeaway
Reed-Sternberg cells are characteristic tumor giant cells of B cell origin that are seen in Hodgkin lymphoma. Hodgkin lymphoma is also associated with localized, contiguous spread of lymph nodes rather than noncontiguous spread seen in non-Hodgkin lymphoma.
Main explanation
The patient’s age, constitutional symptoms, presence of non-tender, contiguous lymphadenopathy, and presence of Reed-Sternberg cells on lymph node biopsy suggest Hodgkin lymphoma. Hodgkin lymphoma has an epidemiological bimodal distribution, thus younger adults and teens, as well as older adults are most commonly affected. As opposed to non-Hodgkin’s lymphoma, which has non-contiguous lymphadenopathy, Hodgkin lymphomausually has contiguous lymph node involvement. The non-tender lymph nodes suggest the lymphadenopathy is caused by a neoplasm, rather than an acute infection. As denoted by the Ann Arbor staging system, Hodgkin lymphoma with B staging means the patient presents with constitutional symptoms such as low-grade fever and night sweats, which the patient in this case exhibited. Reed-Sternberg cells are also a characteristic finding in Hodgkin lymphoma.

Cardiogenic shock resulting from acute myocardial infarction can cause pulmonary edema. However given this patient’s recent blood transfusion, this is not the most likely cause of this woman’s shortness of breath.

Anaphylaxis after transfusion can cause dyspnea, but this usually occurs under 45 minutes after beginning the transfusion and involves prominent wheezing with a normal chest X-ray (CXR).

Allergic reactions are a common transfusion reaction, resulting from histamine release, they often cause urticaria, itching, and wheezing but a normal chest X-ray.

Major takeaway
Transfusion-Related Acute Lung Injury (TRALI) occurs within 6 hours of a blood transfusion, and is usually associated with plasma products. It causes flash pulmonary edema, which results in shortness of breath.
Main explanation
This patient’s chest X-ray shows pulmonary edema and they have a transfusion-related acute lung injury (TRALI). TRALI is characterized by acute respiratory distress within 6 hours of a transfusion. It is typically associated with plasma products such as fresh frozen plasma or platelets. A chest X-ray will show pulmonary edema which can rapidly progress to complete “white-out” of the lung fields (as shown in the image below). The pathophysiology of this transfusion reaction has not been fully elucidated, but the classical hypothesis is that transfusion of plasma containing donor anti-HLA (human leukocyte antigens) or anti-HNA (human neutrophil antigens) antibodies causes complement activation in the patient. This results in an influx of neutrophils to the lungs, which become activated and release cytotoxicagents. This causes endothelial damage in the lungs and capillary leakage, leading to pulmonary edema and dyspnea. Treatment for this condition is mainly supportive. Supplemental oxygen is given in mild cases, while aggressive ventilatory support, and vasopressors are reserved for severe cases. TRALI should be suspected in all cases of shortness of breath following transfusion.

Transfusion of bacteria-contaminated products can cause sepsis, which would leave to pulmonary edema. This would cause breathlessness due to increased capillary permeability in the lungs, but usually first results in fever and hypotension, rather than acute lung injury.

Major takeaway
Meconium plug syndrome is a functional colonic obstruction in a newborn, characterized by intestinal dilation from delayed passage (>48 h) of meconium. Patients with meconium plug syndrome have a higher incidence of Hirschsprung’s disease.

Main explanation
Meconium plug syndrome presents in infants within their first few days of life with failure to pass stools, abdominal distention, and vomiting. The syndrome can occur in otherwise healthy infants, but is common in infants of diabetic mothers. There is an incidence of 40-50% in mothers who were treated with magnesium sulfate. It is a transient disorder of the newborn colon which is characterized by delayed passage (>48 h) of meconium and intestinal dilation. The disease is a diagnosis of exclusion.
The primary differential consideration is Hirschsprung disease (HD), which is eventually diagnosed in approximately 10-30% of patients with apparent meconium plug syndrome – a rectal biopsy can rule in or out HD.
Of note, unlike meconium ileus, microcolon is not typically seen on X-ray with meconium plug syndrome. Ruling out cystic fibrosis would not be the next step, as the patient likely has meconium plug syndrome, not meconium ileus.

While sepsis can complicate neonatal bowel obstruction and cause delayed meconium passage, blood cultures are unlikely to be useful in this case as the patient is not characterized by signs of infection.

This patient is characterized by the classic symptoms of meconium plug syndrome, the major differential of which is Hirschsprung disease. Neither of these disorders is diagnosed using serum chemistries.

Surgical decompression is rarely necessary to treat the plugs, and should not be used in the diagnosis of the patient.

This patient is unlikely to have abdominal distention and vomiting caused by elevated glucose levels. Infants of diabetic mothers are more likely to experience hypoglycemia.

Children with hypertrophic pyloric stenosis often present dehydrated secondary to protracted vomiting and require aggressive rehydration and electrolyte replacement; however, this would be the initial treatment, not the definitive treatment.

Appendectomy is indicated to treat acute appendicitis, a rare condition in infants. The clinical presentation is consistent with hypertrophic pyloric stenosis.

Children with hypertrophic pyloric stenosis often present dehydrated secondary to protracted vomiting and require aggressive rehydration and electrolyte replacement; however, this would be the initial treatment, not the definitive treatment.

Children with hypertrophic pyloric stenosis often present dehydrated secondary to protracted vomiting and initially require aggressive rehydration and electrolyte replacement. The definitive treatment is pyloromyotomy.

Major takeaway
Infantile hypertrophic pyloric stenosis often presents as an “infant with projectile vomiting.” This is associated with a peristaltic fluid wave and is often caused by idiopathic thickening of gastric pyloric musculature. Standard treatment for this is Ramstedt (open) pyloromyotomy.

Main explanation
This infant with projectile vomiting represents a case of infant hypertrophic pyloric stenosis(IHPS) associated with a peristaltic fluid wave but lacking a description of the classic “olive-shaped” abdominal mass that is virtually diagnostic for pyloric stenosis. Children with hypertrophic pyloric stenosis often present dehydrated, with a hypokalemic hypochloremic metabolic alkalosis secondary to protracted vomiting. Emesis is non-bilious because the obstruction is proximal to the common bile duct.

Sonographic thickness of the pyloric muscle wall or a length >13 mm can confirm the diagnosis of infant hypertrophic pyloric stenosis. The classical treatment for IHPS is Ramstedt (open) pyloromyotomy. Laparoscopic pyloromyotomy is also growing in popularity.