Remission of pituitary-dependent Cushing's disease after removal of nonneoplastyic pituitary gland.

Transsphenoidal hypophysectomy was performed on a 28-year-old woman with pituitary-dependent Cushing's disease. Both clinical and chemical resolution of the hypercortisolism was achieved in spite of no evident pituitary microadenoma or cell hyperplasia. Histologic examination revealed widespread Crooke's changes and normal relative numbers, size, and distribution of corticotrophs. We propose that rare patients with pituitary-dependent Cushing's disease may have excessive pituitary production of adrenocorticotropic hormone in the absence of an adenoma or corticotroph cell hyperplasia.

Pituitary function after removal of pituitary microadenomas in Cushing's disease.

Pituitary function has been studied sequentially after transsphenoidal removal of pituitary microadenomas in two men with Cushing's disease. Patient 1 gradually regained normal glucocorticoid levels with normal diurnal variation, metyrapone responsiveness, and low dose dexamethasone suppressibility (17-hydroxycorticosteroid, 6.5-0.9 mg/24 h). GH levels rose from 1 to 35 ng/ml during insulin hypoglycemia and from 2.3 to 27 ng/ml during arginine infusion. PRL secretion rose normally in response to thorazine, and gonadotropin and TSH levels remained normal. Patient 2 regained significant metyrapone responsiveness by 9 months postoperatively (11-deoxycortisol rose to 11.7 micrograms/dl), had a normal spontaneous nocturnal rise in PRL secretion, and normal levels of testosterone and thyroid hormones. The return to normal of cortisol-ACTH dynamics and GH responsiveness in Patient 1 and the normal nocturnal surge in PRL secretion in Patient 2 imply that in these patients the etiology of Cushing's disease was not related to hypothalamic dysfunction.

Transsphenoidal microsurgery in the treatment of acromegaly and gigantism.

Twenty-five patients with acromegaly and 3 patients with gigantism underwent transsphenoidal microsurgery in an attempt to remove the tumor and preserve normal pituitary function whenever possible. An adenoma was identified and removed in 27 of 28 patients. Evaluation 3--6 months postoperatively revealed a GH level less than 5 ng/ml in 29 patients, 5--10 ng/ml in 4 patients and 11--29 ng/ml in 4 other patients. Dynamics of GH secretion were normal in 11 patients who had normal pituitary function and are considered cured. Two patients with low or undetectable GH levels are also considered cured at the expense of being hypopituitary. Three of 7 patients with normal basal GH levels but abnormal dynamics of GH secretion relapsed within 1 yr. Eleven of the 13 patients considered cured did not have extrasellar extension, while 14 of the 15 patients not cured had extrasellar extension. Five patients who were not cured with surgery received radiation therapy. Three patients were treated with an ergot derivative, Lergotrile mesylate, after surgery and radiation therapy failed to normalize GH levels. Transsphenoidal microsurgery is an optimal form of therapy for patients with acromegaly or gigantism, especially those with no extrasellar extension. Dynamics of GH secretion are very useful in evaluating the completeness of adenoma removal.

Inhibitory action of bromocriptine and tamoxifen on the growth of human pituitary tumors in soft agar.

Human pituitary tumors were studied in vitro using the clonogenic stem cell assay. Mechanical dispersion was used to prepare single cell suspensions for plating. Colony formation occurred in 21 of 24 tumors plated. Bromocriptine (Brc; 10 nM) added to the medium resulted in a significant decrease in the number of colonies formed in 5 of 10 prolactinomas and in 1 tumor secreting both PRL and GH. However, PRL secretion was decreased in 8 of 9 tumors tested. Brc had no effect on either colony formation or hormone secretion in other tumors secreting GH (n = 2), ACTH (n = 2), or FSH (n = 1) or in nonsecreting tumors (n = 4). Tamoxifen (Tam; 10(-7) M) inhibited colony formation in 6 of 10 prolactinomas and in 1 tumor secreting GH and PRL. PRL secretion into the medium correlated with the changes in the number of colonies. Tam was not effective in any other tumor tested. In only 1 instance was there a synergistic action between Brc and Tam on inhibition of colony formation. Brc, but not Tam, caused a significant decrease in the size of the colonies formed from cells of PRL-secreting tumors. The least numbers of colonies per plate were found in 3 prolactinomas from patients treated preoperatively with Brc. We conclude that the soft agar clonogenic assay technique is a feasible method to study human pituitary tumors in vitro. Both Brc and Tam inhibited colony formation in this system in a significant proportion of tumors. The potential antiproliferative action of Tam in vivo needs to be studied in view of these results.

Spontaneous infarction in pituitary tumors: neurologic and therapeutic aspects.

In addition to progressive endocrine dysfunction and progressive visual loss, pituitary neoplasms may annouce their presence by the more catastrophic alternative of spontaneous tumor infarction. In two patients reported, illness due to the spontaneous infraction of pituitary tumors was heralded by sudden onset of focal headache associated with diplopia. Stupor, confusion, and evidence of increased intracranial pressure occurred without subarachnoid hemorrhage or massive extrasellar extension of tumor. One patient developed inappropriate antidiuretic hormone secretion with spontaneous infarction in a large but clinically silent chromophobe adenoma. In both patients, skull x-rays suggested a long-standing intrasella mass. Both underwent prompt treatment with endocrinologic replacement therapy and subsequent successful transsphenoidal removal of voluminous, infarcted, pituitary masses.

Gradual recovery of lactotroph responsiveness to dynamic stimulation following surgical removal of prolactinomas: long-term follow-up studies.

Prolactin-secreting pituitary adenomas were selectively removed through a transsphenoidal approach from 120 women. Basal serum PRL levels (measured one to six months after surgery) were normal in 96 patients and decreased appreciably but not to normal in the remaining 24 patients. Dynamics of PRL secretion were studied at three to four months in 81 patients who had normal basal PRL level. Two different patterns of response to provocative stimuli were noted in these patients. In one group (group I, n = 65), patients had greater than 100% rise in serum PRL following TRH or perphenazine (Pz) administration. However, when analyzed as a group, the mean +/- SEM incremental responses (delta PRL) to TRH and Pz in these patients (29.9 +/- 1.9, 20.4 +/- 1.5 ng/mL) were significantly less (P less than 0.005 and P less than 0.001) than those of normal women (38.8 +/- 5, 33 +/- 5 ng/mL, respectively). Nineteen of these patients were restudied 12 to 72 months after surgery. The responses to provocative stimulation at that time were improved and similar to normal women. In contrast, in the second group (n = 16) of patients (group II), the responses to stimulation with the same agents were blunted or absent and remained so during subsequent studies. Recurrence of the hyperprolactinemia was noted in 11 of the 16 patients in group II and in only two of 65 patients in group I. The daily serum PRL levels in the immediate postoperative period were higher in patients from group II than those from group I. We conclude that transsphenoidal surgery is an optimal form of therapy for patients with PRL-secreting adenomas.(ABSTRACT TRUNCATED AT 250 WORDS)

Hypophysectomy for stage IV breast cancer.

Transnasal, transsphenoidal microsurgical hypophysectomy is a useful therapeutic procedure for patients with Stage IV breast cancer which can be peformed in selected patients with minimal morbidity and mortality. Functionally complete hypophysectomy can be accomplished with regularity, and anything less than this is considered to be a technical failure despite the fact that remissions may occur after incomplete hypophysectomy. In view of the recent outstanding results with antiestrogen therapy in patients with breast cancer, we recommend this as the initial treatment in those patients who are good candidates for endocrine therapy. Hypophysectomy has been shown to induce improvement after antiestrogen treatment, particularly in those patients who have had an initial response to antiestrogens as well as in a few patients who failed to benefit. Estrogen receptor measurements in the tumor tissue have been shown to be useful in selecting patients for hypophysectomy as well as for antiestrogen therapy. Prolactin receptors have been found in about 50 per cent of human breast cancers, and their potential usefulness in selecting patients for hypophysectomy is being explored. Hypophysectomy is a definitive therapeutic procedure that should not be used as a last resort in the terminally ill patient.

Metastatic paraganglioma causing spinal cord compression.

SUMMARY OF BACKGROUND DATA: Paragangliomas are neoplasms that arise from the autonomic nervous system-associated paraganglia. Most often they are benign tumors. However, infrequently they have been reported to metastasize. Involvement of the spine is rare and usually is intradural at the level of the cauda equina. OBJECTIVES: The authors report two cases of metastatic paraganglioma to the spine, both of which resulted in myelopathy from extradural spinal cord compression. Also provided is a review of the literature. CONCLUSIONS: Paragangliomas rarely metastasize to the spine. Management of the two reported patients involved spinal cord decompression followed by spinal stabilization procedures. Long-term ambulatory status was maintained in both patients. Radiation therapy may be an important adjunctive treatment after surgical removal of these tumors.

The syndrome of acute central cervical spinal cord injury revisited.

Seven patients with acute central cervical spinal cord injury were operated upon during the subacute stages following injury, when their condition had improved and become stable for seven to ten days. Myelography in each case showed significant anterior compression of the spinal cord. The rapid improvement in function following the operation in these patients was gratifying and emphasizes the pathophysiological importance of spinal compression in this condition.

Colonic perforation by ventriculoperitoneal shunt tubing: a case of suspected silicone allergy.

BACKGROUND: A case of colonic perforation by a ventriculoperitoneal shunt is presented in a patient with several previous complications associated with shunt tubing. CASE DESCRIPTION: Initially managed by intravenous antibiotics, shunt externalization, and colonoscopy, the entire ventriculoperitoneal shunt system was subsequently replaced after cerebrospinal fluid cultures had grown Propionibacterium acnes and Streptococcus sanguis organisms. The patient has had three episodes of skin breakdown over his shunt tubing (two prior and one subsequent to colonic perforation) without evidence of shunt infection or malfunction. CONCLUSIONS: The etiology of these complications is consistent with silicone tubing allergy. Replacement with a polyurethane system produced no similar complications thus far, which further supports a possible silicone allergy to the ventriculoperitoneal shunt and possible etiology of this patient's colonic perforation.

The danger of intracranial wood.

Peri-orbital puncture wounds by sharp wooden objects are not rare, but can be dangerous when there is intracranial penetration by and retention of the wooden foreign body. Days to years after an apparently trivial initial wounding, serious intracranial complications can occur. The authors have reviewed 42 case reports from the literature. Morbidity-defined as permanent neurologic sequelae-occurred in 74% of the cases. Intracranial suppuration was the major complication, with brain abscess having occurred in nearly one-half of the cases. Mortality occurred in 25% of 28 cases occurring in the post-antibiotic era. The qualities of wood which make it especially hazardous as a wounding agent and foreign body are discussed. The role of orbital anatomy in affording easy access to the cranial contents is described. Surgical exploration in all those cases in which there is a reasonable suspicion of intracranial injury is recommended.

Vasospasm following transsphenoidal tumor removal associated with the arterial changes of oral contraception.

A case of fatal cerebral vasospasm after transsphenoidal removal of a pituitary macroadenoma with suprasellar extension is reported. On the second postoperative day the patient developed headache, lethargy, and cardiorespiratory arrest. Five days later, after recovery from this episode, she developed signs of involvement of the left hemisphere. At that time she demonstrated severe cerebral vasospasm, which was worse in the left supraclinoid segment of the internal carotid artery, and she died 19 days postoperatively. Postmortem examination showed left hemispheric and hypothalamic infarction with subsequent herniation. In addition, pathologic arterial changes usually related to use of oral contraceptives were present.

Excision of intramedullary arteriovenous malformation using intraoperative spinal cord monitoring.

We are presenting a patient whose intramedullary cervical arteriovenous malformation was successfully excised. The importance of monitoring somatosensory cortical evoked responses secondary to peripheral nerve stimulation is stressed.