Neville A. Russell

Prolactinomas in familial multiple endocrine neoplasia syndrome type I: Relationship to HLA and carcinoid tumors

We studied four families with prolactin-secreting pituitary tumors as part of multiple endocrine neoplasia syndrome type I (MEN I). The propositus in family A had galactorrhea-amenorrhea and an enlarged sella turcica at the time of parathyroidectomy. Family studies showed that her mother had prolactinoma and primary hyper-parathyroidism, one of three uncles had primary hyperparathyroidism, and two sisters had prolactin-secreting adenomas, All affected family members shared the HLA haplotype: A1, B8, Cw-, DR3; linkage with HLA could not be excluded. The proband in family B had prolactinoma, primary hyperparathyroidism and primary hypothyroidism associated with a high-lying vestigial thyroid. The probands father had primary hyperparathyroidism and thymic carcinoid, and two uncles had primary hyperparathyroidism. The proband and father shared the haplotype A2, B8, Cw-, DR3. In family C the proband had primary hyperparathyroidism and prolactinoma. Three of her sisters had primary hyperparathyroidism. One sister, who also had carcinoid tumor of the lung and a prolactinoma, married an affected member of family D; a daughter had prolactinoma and metastatic thymic carcinoid. Both proband and sister were 46 xx/xo and shared the haplotype A1, B8, Cw-, DR3. The fourth propositus, a member of family D reputed to have familial primary hyperparathyroidism, was found to have a prolactinoma four years following parathyroidectomy. One of the patients affected uncles also had a pituitary tumor. The haplotype involved was Aw24, B35, Cw-. We conclude that (1) prolactinomas are an integral part of MEN I; (2) the syndrome may be associated with aberrant organ migration and chromosomal separation; (3) MEN I is associated with A1, B8; evidence for genetic linkage being inconclusive; (4) patients may harbor other tumors including thymic carcinoid.

Diastematomyelia in adults. A review.

A consecutive series of 45 cases of diastematomyelia in adults is analyzed. The majority of patients were females with a 3.4:1 female to male ratio. The ages ranged from 19 to 76 with a mean of 37.8 years. The lesion was usually located in the lumbar region. In 17 patients the development of symptoms was associated with specific incidents or events, usually trauma. Twelve patients had pre-existing static musculoskeletal or neurologic abnormalities and 20 had cutaneous spinal lesions suggesting dysphraphism. The symptoms and signs included pain and a variety of sensorimotor and/or sphincteric abnormalities. Metrizamide CT scanning proved to be the most useful diagnostic procedure. Only 4 patients were investigated by MRI and from the information available its role in the diagnosis of adult diastematomyelia is not established. Twenty-three of 24 patients treated by surgery showed marked improvement.

Combined intraarterial and systemic chemotherapy for intracerebral tumors.

Twenty-six patients with intracerebral tumors (predominantly gliomas) were treated with intraarterial BCNU, VM-26, and cisplatin combined with the systemic administration of VM-26, methotrexate, vincristine, bleomycin, and procarbazine. Oral glycerol was given before i.v. VM-26. Twelve patients responded (46% of all patients and 63% of the fully evaluable patients). The response rate for gliomas was 50% if all patients were considered and 71% if only fully evaluable patients were considered. The response rate did not seem to be affected by glioma grade, prior chemotherapy, or pretreatment performance status. Median time to tumor progression for responders was 19 weeks. Median survival from initiation of treatment was 21 weeks for evaluable patients and 17 weeks for all patients. Median survival from initial diagnosis was 55 weeks. Myelosuppression was dose-limiting for the systemic chemotherapy. Reversible neurological toxicity was common, but tolerable. One patient developed ipsilateral blindness, and two patients developed prolonged neurological toxicity. Pulmonary toxicity was also seen. Vertebral artery infusions proved feasible, although difficult and more toxic than carotid infusions. Overall, this regimen was not more active than the intraarterial combination of BCNU, VM-26, and cisplatin without the systemic chemotherapy. Further studies of more intensive intracarotid therapy combined with different systemic drugs are being initiated.

Familial intracranial gliomas

The pedigree of two interrelated families with 10 affected members suffering from malignant supratentorial gliomas is reported. In addition, three other unrelated families with two members each who were treated for different types of brain tumors are described. Genetic implications are discussed.