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Correspondence
Vemurafenib for Melanoma Metastases to the Brain
To the Editor: Vemurafenib is an inhibitor of the BRAF V600E mutation and has recently been approved by the Food and Drug Administration (FDA) for treatment of metastatic melanoma in adults in the absence of brain metastases.– Trials are currently under way involving the use of vemurafenib for…
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Case Records of the Massachusetts General Hospital
Case 31-2011 — A 55-Year-Old Man with Oligometastatic Lung Cancer
Presentation of Case. A 55-year-old man was seen in the cancer center at this hospital because of stage IV non–small-cell lung cancer (NSCLC). The patient had been well until approximately 5 months earlier, when headaches developed, followed by left-sided weakness, leftward drift while walking,…
- CME
Case Records of the Massachusetts General Hospital
Case 26-2011 — A 7-Year-Old Boy with a Complex Cyst in the Kidney
Presentation of Case. A 7-year-old boy was seen in an outpatient clinic at this hospital because of a complex cyst in the kidney. The patient was born by vaginal delivery after an uncomplicated 38-week gestation. His birth weight was 3.04 kg. A diagnosis of tuberous sclerosis complex (TSC) was made…
- CME
Original Article
NFKBIA Deletion in Glioblastomas
Glioblastoma multiforme is the most common and most deadly primary brain tumor. It is a complex disease, in which many signaling pathways are disrupted.– Almost all glioblastomas have excessive activation of the epidermal growth factor receptor (EGFR) pathway, often brought about by amplification…
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Original Article
Brief Report: AIP Mutation in Pituitary Adenomas in the 18th Century and Today
Pituitary adenomas are usually benign, slow-growing tumors that cause symptoms due to excess hormone release, local space-occupying effects, or both. Adenomas that secrete excess growth hormone cause acromegaly. Patients with acromegaly have numerous symptoms and signs, such as hyperhidrosis,…
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Gigantism results from the presence of a growth hormone–secreting pituitary adenoma before epiphyseal fusion. The authors identified a mutation in a gene extracted from the teeth of an 18th-century giant and from contemporary Northern Irish families with gigantism, acromegaly, or prolactinomas.
Original Article
Everolimus for Subependymal Giant-Cell Astrocytomas in Tuberous Sclerosis
The tuberous sclerosis complex, an autosomal dominant disorder with a prevalence approaching 1 in 6000 live births, is a potentially devastating disorder characterized by benign tumors (hamartomas) in multiple organ systems, including the brain, skin, kidney, lung, heart, and retina. Mutations in…
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Neurosurgical resection is standard for subependymal giant-cell astrocytomas (SEGAs) in tuberous sclerosis. Treatment with everolimus, which inhibits the mammalian target of rapamycin, a protein regulated by gene products involved in tuberous sclerosis, resulted in reduced SEGA volume and seizures.
Case Records of the Massachusetts General Hospital
Case 20-2010 — A 32-Year-Old Woman with Oligomenorrhea and Infertility
Presentation of Case. Dr. Elizabeth Guancial (Medicine): A 32-year-old woman was evaluated because of oligomenorrhea and difficulty becoming pregnant. Menarche had occurred at 12 years of age and menses were regular until the patient began taking oral contraceptives at 20 years of age. At 25 years…
A 32-year-old woman was evaluated because of oligomenorrhea and difficulty becoming pregnant. At 25 years of age, after 5 years of oral contraceptive use, irregular menstrual cycles developed, and she was unable to become pregnant. She reported acne and increased facial hair; results of laboratory tests were consistent with anovulation. She became pregnant after two cycles of clomiphene, gestational diabetes developed, she delivered a healthy infant, and she breast-fed normally. Glucose intolerance and amenorrhea persisted after delivery. A diagnostic test was performed.
Correspondence
Pasireotide Alone or with Cabergoline and Ketoconazole in Cushing's Disease
To the Editor: Cushing's disease, which is caused by an adrenocorticotropin-secreting pituitary adenoma, is associated with increased morbidity and mortality. Currently, there is no effective medical therapy for Cushing's disease. However, recent studies identified the somatostatin-receptor subtype…
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Case Records of the Massachusetts General Hospital
Case 13-2010 — An 18.5-Month-Old Girl with Watery Diarrhea and Poor Weight Gain
Presentation of Case. Dr. Sara V. Bates (Pediatric Service): An 18.5-month-old girl was seen in the pediatric gastroenterology clinic of this hospital because of watery diarrhea and poor weight gain. The patient was born to a multigravida mother after a full-term gestation. She was breast-fed for…
An 18.5-month-old girl was seen in the pediatric gastroenterology clinic of this hospital because of watery diarrhea and poor weight gain. The child had been healthy until 12 months of age, when chronic watery diarrhea developed. Six months later, her weight had decreased to the fourth percentile for her age. Extensive studies of stool, ultrasonography of the abdomen, and upper and lower endoscopic examinations were normal. A sweat test was interpreted as borderline. A diagnostic test result was received.
Clinical Practice
Prolactinomas
Foreword. This Journal feature begins with a case vignette highlighting a common clinical problem. Evidence supporting various strategies is then presented, followed by a review of formal guidelines, when they exist. The article ends with the author's clinical recommendations. Stage. A 42-year-old…
- CME
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A 42-year-old man presents with decreased libido, erectile dysfunction, and headaches. He reports no weight change, gynecomastia, fatigue, or other symptoms. He takes no medications. Testicular size is decreased. His prolactin level is 648 μg per liter (normal value, <15). Magnetic resonance imaging reveals a sellar mass (2.5 by 1.5 by 2.0 cm) that is 5 mm below the optic chiasm and that extends bilaterally into the cavernous sinuses. What are the diagnostic and therapeutic considerations?
Clinical Therapeutics
Stereotactic Radiosurgery for the Management of Brain Metastases
Foreword. This Journal feature begins with a case vignette that includes a therapeutic recommendation. A discussion of the clinical problem and the mechanism of benefit of this form of therapy follows. Major clinical studies, the clinical use of this therapy, and potential adverse effects are…
- CME
A 50-year-old man with a history of lung cancer presents with headaches and right-arm numbness; he is found to have a single brain metastasis. Stereotactic radiosurgery is recommended as part of his care. Stereotactic radiosurgery uses multiple narrowly focused beams of radiation to treat one or a few focal lesions while minimizing effects on the surrounding tissue.
Clinical Implications of Basic Research
Metabolism, Gliomas, and IDH1
Since the first description of a patient with an inborn error of metabolism was provided by Sir Archibald Edward Garrod more than 100 years ago, the study of rare disorders has received increasing attention. What started with the description of a single patient has evolved into a medical discipline…
Correspondence
IDH1 and IDH2 Mutations in Gliomas
To the Editor: Yan et al. (Feb. 19 issue) found that mutations of genes encoding isocitrate dehydrogenases (IDH1 and IDH2), as compared with no mutations, are associated with younger age and better prognosis in adults with gliomas. Their study and other, similar studies– prompted us to search for…
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Original Article
IDH1 and IDH2 Mutations in Gliomas
Gliomas, the most common type of primary brain tumors, are classified as grade I to grade IV on the basis of histopathological and clinical criteria established by the World Health Organization (WHO). This group of tumors includes specific histologic subtypes, the most common of which are…
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Isocitrate dehydrogenases, encoded by the IDH1 and IDH2 genes, catalyze the reduction of NADP+ to NADPH in the brain. One or the other of these two genes was found to be mutated in 70% of 445 gliomas of World Health Organization grade II or III. The mutations abolished the enzymatic activity of the IDH1 and IDH2 proteins. The evidence suggests that mutation of an IDH gene is an early event in the development of gliomas.
Editorial
Metabolic Enzymes as Oncogenes or Tumor Suppressors
Whether mutations in metabolic pathways contribute to the pathogenesis of cancer is controversial. Cancer cells have long been noted to preferentially metabolize glucose through glycolysis, a discovery that has been translated to the clinic through positron-emission-tomography imaging of 18F…
Correspondence
Antiemetic Properties of the Antiepileptic Drug Levetiracetam
To the Editor: Chemotherapy-induced nausea and vomiting is an important problem in patients with brain tumors. Because of the high prevalence of seizures, most patients are given antiepileptic drugs. Motivated by a case report, we investigated whether levetiracetam can suppress chemotherapy-induced…
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