Simultaneous bilateral sampling of plasma from the inferior petrosal sinuses, with the adjunctive use of CRH, distinguishes patients with Cushing's disease from those with ectopic adrenocorticotropin secretion with high diagnostic accuracy.

Weight gain and growth retardation are common clinical characteristics of Cushing's syndrome in children and adolescents. Diagnostic evaluation of such patients with CRH stimulation alone and combined with inferior petrosal sinus sampling and imaging studies is accurate, and therapy is usually successful.

The medical records and arteriograms of 81 patients with spinal arteriovenous malformations (AVM's) were reviewed, and the vascular lesions were classified as dural arteriovenous (AV) fistulas or intradural AVM's. Intradural AVM's were further classified as intramedullary AVM's (juvenile and glomus types) and direct AV fistulas, which were extramedullary or intramedullary in location. Dural AV fistulas were defined as being supplied by a dural artery and draining into spinal veins via an AV shunt in the intervertebral foramen. Intramedullary AVM's were defined as having the AV shunt contained at least partially within the cord or pia and receiving arterial supply by medullary arteries. Of the 81 patients, 27 (33%) had dural AV fistulas and 54 (67%) had intradural AVM's. Several dissimilarities in clinical and radiographic findings of the two subgroups were evident. The patients with intramedullary AVM's were younger; the age at onset of symptoms averaged 27 years compared to 49 years for dural AV fistulas. The most common initial symptom associated with dural AV fistulas was steadily progressive paresis, whereas hemorrhage was the most common presenting symptom in cases of intramedullary lesions. No patients with dural AV fistulas had subarachnoid hemorrhage. Activity exacerbated symptoms more frequently in patients with dural lesions. Associated vascular anomalies occurred only in cases of intradural AVM's. In 96% of the dural lesions the AV nidus was in the low thoracic or lumbar region; in only 15% did the intercostal or lumbar arteries supplying the AVM also provide a medullary artery which supplied the spinal cord. In contrast, most intradural AVM's (84%) were in the cervical or thoracic segments of the spinal cord and all of them were supplied by medullary arteries. Transit of contrast medium through the intradural AVM's was rapid in 80% of cases, suggesting high-flow lesions. Forty-four percent of the patients with AVM's of the spinal cord had associated saccular arterial or venous spinal aneurysms. No dural AV fistulas displayed these characteristics. A good outcome occurred in 88% of patients with dural AV fistulas after nidus obliteration, while 49% of patients with intramedullary AVM's did well after surgery or embolization. These findings suggest that dural and intradural AVM's differ in etiology (acquired vs. congenital) and that they have different pathophysiology, radiographic findings, clinical presentation, and response to treatment.

Primary hyperparathyroidism is a common disorder with an annual incidence of approximately 0.5 in 1,000 (ref. 1). In more than 95% of cases, the disease is caused by sporadic parathyroid adenoma or sporadic hyperplasia. Some cases are caused by inherited syndromes, such as multiple endocrine neoplasia type 1 (MEN1; ref. 2). In most cases, the molecular basis of parathyroid neoplasia is unknown. Parathyroid adenomas are usually monoclonal, suggesting that one important step in tumour development is a mutation in a progenitor cell. Approximately 30% of sporadic parathyroid tumours show loss of heterozygosity (LOH) for polymorphic markers on 11q13, the site of the MEN1 tumour suppressor gene. This raises the question of whether such sporadic parathyroid tumours are caused by sequential inactivation of both alleles of the MEN1 gene. We recently cloned the MEN1 gene and identified MEN1 germline mutations in fourteen of fifteen kindreds with familial MEN1 (ref. 10). We have studied parathyroid tumours not associated with MEN1 to determine whether somatic mutations in the MEN1 gene are present. Among 33 tumours we found somatic MEN1 gene mutation in 7, while the corresponding MEN1 germline sequence was normal in each patient. All tumours with MEN1 gene mutation showed LOH on 11q13, making the tumour cells hemi- or homozygous for the mutant allele. Thus, somatic MEN1 gene mutation for the mutant allele. Thus, somatic MEN1 gene mutation contributes to tumorigenesis in a substantial number of parathyroid tumours not associated with the MEN1 syndrome.

Intra-arterial calcium stimulation with right hepatic vein sampling for insulin gradients is the most sensitive preoperative test for localizing insulinomas.