The classification and molecular biology of pituitary adenomas.
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Adenoma↗
Biomedical subjects
E R Laws
Publications and source records attributed to E R Laws.
Surgical management of pituitary adenomas.
Surgical management of pituitary adenomas continues to be a safe and effective method, suitable for a large number of patients suffering from the effects of these lesions. Frequently surgery is just part of an overall programme that includes medical management and radiation therapy as well. It is important for the physicians and the patients to understand that surgery alone may not be totally successful, but that with careful follow-up and appropriate adjunctive management, patients with pituitary tumours may live normal lives, and may enjoy reversal of the endocrine and visual problems that had been caused by their tumours. Careful study of surgically managed patients has contributed to some of the advances that have occurred in the overall management of pituitary adenomas and in our understanding of their biology, pathophysiology and pathogenesis.
Adenoma↗
Long term follow-up of transsphenoidal surgery for the treatment of Cushing's disease in childhood.
Transsphenoidal removal of pituitary adenomas has become the accepted treatment for Cushing's disease. As Cushing's disease is rare in childhood, few reports describe extended follow-up after transsphenoidal surgery for this disease in children. Twenty-two patients less than 19 yr of age were diagnosed with Cushing's disease by standard testing. All patients underwent transsphenoidal surgery (TSS) as primary treatment at Mayo Clinic between 1975 and 1990. Follow-up was available in all patients and averaged 6.7 yr. Adenomas were identified pathologically in 19 patients and visualized by the surgeon in the remainder. There was 1 macroadenoma. Ten patients are considered cured with a mean follow-up of 5.5 yr. Five patients had evidence of persistent disease within 6 months of TSS and required further treatment. Seven patients had remission lasting greater than 6 months with subsequent relapse (mean time to recurrence, 7.0 yr). In children treated with TSS for Cushing's disease, the rate of cure with extended follow-up is only approximately 50%. This rate is much lower than that in adults and may indicate that Cushing's disease is more aggressive in childhood. As TSS is associated with low morbidity, we feel it is still the treatment of choice for Cushing's disease in children.
Adenoma↗
Acute presentation of an intracranial mass.
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Acute Disease↗
Tumoral calcium pyrophosphate dihydrate deposition disease mimicking a cervical spine neoplasm: case report.
A case of tumoral calcium pyrophosphate dihydrate crystal deposition disease involving the upper cervical spine is reported. It presented clinically, radiographically, and by preliminary intraoperative pathological evaluation as a possible malignant soft tissue tumor. An aggressive resection of the lesion was performed. This case differs from previous reports of calcium pyrophosphate dihydrate crystal deposition disease of the cervical spine by the size, location, and radiographic appearance of the lesion. We suggest that radical surgical procedures should not be performed without consideration of this diagnosis in lesions with similar presentations. A brief review of spinal and tumoral calcium pyrophosphate dihydrate crystal deposition is presented.
Adult↗
Delayed hyponatremia after transsphenoidal surgery for pituitary adenoma. Report of nine cases.
Hyponatremia, usually attributed to the syndrome of inappropriate secretion of antidiuretic hormone, typically occurs in a delayed fashion following transsphenoidal removal of a pituitary adenoma. In a series of 99 consecutive patients who underwent transsphenoidal surgery for pituitary adenoma, nine patients developed delayed hyponatremia, seven of whom were symptomatic. Of these seven patients, four had been discharged from the hospital and required readmission on postoperative Day 7 to 9. In the nine patients who developed hyponatremia, on the average, serum sodium levels began to fall on Day 4 and reached a nadir on Day 7 (mean serum sodium nadir 123 mmol/L). The development of delayed hyponatremia was associated with the presence of a macroadenoma in eight of the nine patients. Seven of the nine patients had serum sodium levels less than 130 mmol/L and required treatment. One patient was treated with fluid restriction alone and six were treated with both fluid restriction and intravenous urea therapy. Twenty-four and 48 hours after urea administration, serum sodium levels rose by an average of 6 and 10 mmol/L, respectively, and at discharge, levels averaged 136 mmol/L. Intravenous administration of urea provides a rapid yet safe means of correcting symptomatic hyponatremia when fluid restriction alone is inadequate. In this article, the authors discuss the pathogenesis of delayed hyponatremia.
Adenoma↗
Migration of fresh human malignant astrocytoma cells into hydrated gel wafers in vitro.
Individual astrocytoma cells expressing a cytoplasmic form of p185c-neu migrated along basement membrane lined surfaces after xenografing fresh low or high grade human malignant astrocytomas into host rat brain. We now study the migratory capacity of fresh human malignant astrocytoma cells seeded on hydrated gel wafers composed of artificial basement membrane or collagen I, a normal and lesion-related CNS extracellular matrix component. Approximately 10(7) mechanically disrupted cells (with small clumps) of 3 fresh low grade and 6 fresh high grade astrocytomas were seeded on the surface of artificial basement membrane and collagen I wafers (11 x 16 mm). The wafers were then prepared for scanning electron microscopy and immunohistochemistry at 1, 3, 5, and 7 days after seeding. Regardless of tumor grade, a morphologically similar class of cells was observed to migrate through collagen I gels in 24 hours and 0.5-1.5 mm into artificial basement membrane gels in 7 days. Immunohistochemistry revealed that the migrated cells from low and high grade astrocytomas were positive for glial fibrillary acidic protein (GFAP)) and expressed cytoplasmic human-specific p185c-neu. These data indicate that fresh human malignant astrocytoma cells that contain GFAP and express cytoplasmic p185c-neu have a high degree of migratory capacity and could be the cell in the tumor involved in intraparenchymal metastasis and poor patient survival in high grade astrocytomas of the human brain.
Astrocytoma↗
Transsphenoidal removal of craniopharyngioma.
Transsphenoidal microsurgical removal is appropriate therapy for a significant number of craniopharyngiomas. Favorable factors for the transsphenoidal approach are enlargement of the sella, cystic lesion and preoperative hypopituitarism. A series of 76 operative cases is presented. Long-term follow-up revealed successful results in 81% of patients.
Adolescent↗
Estrogen receptor expression in human pituitary: correlation with immunohistochemistry in normal tissue, and immunohistochemistry and morphology in macroadenomas.
Forty-one human pituitary adenoma specimens were examined for the presence of estrogen receptor (ER) messenger ribonucleic acid and protein using a combination of ribonuclease protection assay, [3H] estradiol ([3H]E2) binding, and ER immunohistochemistry. ER messenger ribonucleic acid prevalence was high in PRL-immunoreactive tumors (2 of 2), moderate in GH/PRL tumors (2 of 5), and low or absent (0 of 4) in GH tumors. In the GH/PRL-immunostaining tumors, the presence of the ER was uniformly associated with elevated serum PRL levels. Among the gonadotropin-immunostaining tumors, 10 of 17 were ER positive; within this group, those with gonadotroph adenoma characteristics were ER positive, whereas those with null cell/oncocytic characteristics were ER negative. Of the tumors that did not immunostain for any known anterior pituitary hormones, 3 of 11 were ER positive. ER immunohistochemistry in 14 tumors revealed a 100% correlation with ribonuclease protection assay results, whereas [3H]E2 binding, determined in 9 tumors, showed an 87% correlation. In summary, it appears that PRL and a specific class of gonadotropin-immunostaining tumors (identifiable by specific characteristics on electron microscope) contain ER, whereas GH-immunostaining tumors are ER negative. ER expression in normal pituitary paralleled that in macroadenomas (GH, 2.3%; PRL, 50%; FSH, 70%; LH, 83%; TSH, 4%; ACTH, 1%). The ER-positive tumors represent a subset whose growth and secretory profiles may be influenced by the gonadal steroidal milieu or by pharmacological agents that affect E2 levels or ER function.
Adenoma↗
Pituitary adenomas in childhood and adolescence.
A clinicopathological study of 56 pediatric patients with non-ACTH-secreting pituitary adenomas removed by a transsphenoidal neurosurgical approach was undertaken to better define the clinical presentation, to assess demographic factors, to determine the immunohistochemical staining characteristics of the tumors, and to evaluate the outcome of transsphenoidal surgical treatment and other adjuvant therapies. A separate analysis of prolactinoma patients was performed. All tumors were confirmed histologically and immunophenotyped for pituitary hormones. Forty-one patients had tumors that stained for PRL alone, eight patients had tumors that stained for PRL and GH, six patients had plurihormonal adenomas, and one patient had a tumor that stained for glycoprotein hormones. No tumors contained GH alone. Macroadenomas exceeded microadenomas (1.4:1). There were no male patients with microadenomas of any type. Females outnumbered males (3.3:1). Patients presented most frequently with headache, menstrual dysfunction (in females), galactorrhea, and hypopituitarism. All but one of the patients with hypopituitarism at presentation had macroadenomas. Tumor staining characteristics did not always correlate well with clinical status, especially with regard to GH-containing tumors. Pediatric pituitary tumors did not appear to be more invasive or more aggressive than adult pituitary tumors, contrary to some previous reports. The patients with microadenomas had a 70% operative cure rate and a 65% long term cure rate; the recurrence rate for microadenoma patients was 25%. Macroadenoma patients had a 33% operative cure rate, a 55% long term cure rate, and a recurrence rate of 33%. Thus, microadenoma and macroadenoma patients had similar long term cure rates, but macroadenoma patients required more aggressive adjuvant therapy (second surgery, radiation, or bromocriptine) and had higher rates of hypopituitarism (52% of macroadenoma patients vs. 0% of microadenoma patients required long term hormone replacement).
Adenoma↗
Magnetic resonance imaging measurements of pituitary stalk compression and deviation in patients with nonprolactin-secreting intrasellar and parasellar tumors: lack of correlation with serum prolactin levels.
Prolactin (PRL) Levels are frequently elevated in patients with non-PRL-secreting adenomas or other intrasellar and parasellar diseases ("pseudoprolactinomas"). This phenomenon is believed to result from a loss of dopaminergic inhibition on pituitary lactotrophs and is known as the "stalk-section effect." Using magnetic resonance imaging scans and a high-magnification sella technique, we measured a number of parameters indicative of the disruption of normal sellar structures. The investigator was blind to the patient's diagnosis and PRL level while collecting the data. Parameters measured were the tumor size, the angular deviation of the pituitary stalk, and the degree of compression of the pituitary stalk. Measurements were obtained from 44 patients with pathologically confirmed tumors that had no immunohistochemical reactivity to PRL. PRL levels were often higher than expected. Four patients (9%) had a PRL level of more than 150 ng/ml, and three patients (7%) had a PRL level of 200 ng/ml or more. One patient with a plasmacytoma eroding the sella floor had a PRL level as high as 504 ng/ml. There was no significant correlation of PRL level and the degree of pituitary stalk compression, stalk deviation, or tumor size. PRL levels were found to be markedly elevated in some patients with a tumor causing little distortion of the pituitary stalk. Conversely, PRL levels were often normal despite evidence of massive distortion of the stalk. Therefore, magnetic resonance imaging evidence of pituitary stalk distortion cannot be used to determine the diagnosis of prolactinoma versus pseudoprolactinoma in most cases.(ABSTRACT TRUNCATED AT 250 WORDS)
Adenoma↗
Novel features of tumors that secrete both growth hormone and prolactin in acromegaly.
The most prominent previously reported clinical features of growth hormone (GH) and prolactin (PRL)-secreting pituitary adenomas associated with acromegaly have included the high incidence of galactorrhea in women and a generally more favorable response to dopamine agonist therapy. The authors analyzed a consecutive series of 62 acromegalic patients treated with transsphenoidal microsurgery. GH-PRL tumors were found in 30% of the patients. There was a significant difference in sex distribution between acromegalics with the GH-PRL tumor subtype and all other acromegalics. Women represented 73% of the GH-PRL immunostain subtype, as compared with the overall sex distribution of 33 women (53%) and 29 men (47%) for the entire series of acromegalic patients. Individuals with the GH-PRL subtype had significantly higher postoperative GH levels than those with the GH subtype, and significantly higher postoperative GH levels when compared with all other acromegalics with a variety of immunostain subtypes. Linear regression analysis of the pre- and postoperative GH data revealed that the increased postoperative GH levels in the GH-PRL immunostain subtype were independent of the invasiveness of the tumor and of sex of the subject. When the same linear regression technique was used, lower preoperative levels of thyroxine and thyroid-stimulating hormone were observed in the GH-PRL subtype. These data suggest inherent differences characteristic of tumors that secrete both growth hormone and prolactin.
Acromegaly↗
Estrogen receptor gene expression in craniopharyngiomas: an in situ hybridization study.
Craniopharyngiomas are histologically benign epithelial neoplasms of the sellar region that frequently exhibit invasive and aggressive local growth. In this study, we have investigated the presence and cellular distribution of estrogen receptor messenger ribonucleic acid by in situ hybridization in 23 surgically removed craniopharyngiomas. All craniopharyngiomas studied, including 19 adamantinomatous and 4 papillary variants, uniformly expressed the estrogen receptor gene. In all cases, an intense estrogen receptor messenger ribonucleic acid hybridization signal was demonstrated; one localized exclusively to the epithelial cells of the tumor. Connective tissue and vascular elements were devoid of hybridization signal. Coexpression of the estrogen receptor protein was also studied by immunohistochemistry. Despite the relative abundance of estrogen receptor message in all cases studied, the estrogen receptor protein was focally but conclusively detected in only two tumors. The basis of this discrepancy is unclear. Progesterone receptor protein was also studied in all cases; however, its definitive presence was noted in only one instance and, in that case, in only occasional nuclei. The expression of the estrogen receptor gene by the proliferative epithelial elements of craniopharyngiomas raises the questions of a possible hormonal component to the genesis and/or progression of the craniopharyngiomas and a potential responsiveness to therapeutic hormonal manipulation.
Cell Division↗
Pituitary adenomas in childhood and adolescence. Results of transsphenoidal surgery.
Pituitary adenomas are uncommon in childhood. Between 1975 and 1988, 36 patients underwent transsphenoidal resection at the Mayo Clinic before their 17th birthday. Fifteen (41.7%) had prolactin (PRL)-secreting tumors, 16 (44.4%) had adrenocorticotropic hormone (ACTH)-secreting tumors (including two patients with Nelson-Salassa syndrome), and three (8.3%) had tumors secreting growth hormone (GH); two patients (5.6%) had clinically nonfunctioning tumors. Of the 36 patients, 21 (58.3%) were girls, and girls predominated in every group except that with ACTH-secreting tumors, where they accounted for only 37.5% of the patients. The average age at the time of surgery was 14.7 +/- 2.2 years, the youngest patient being 7.3 years old. The ACTH-secreting tumors were associated with an earlier onset of symptoms than the other tumor types: six (37.5%) of 16 patients became symptomatic before 10 years of age, compared with two (10.0%) of the 20 other patients. Presenting symptoms primarily reflected endocrine dysfunction, with neurological presentation (visual field deficits) occurring in only two patients. There were no deaths in this patient group. Significant operative morbidity included steroid-induced psychosis in one patient and diabetes insipidus in three, which resolved in two. Plurihormonal tumors, broadly defined as tumors producing more than one hormone, were common, comprising five (36%) of 14 PRL-secreting tumors, all three GH-secreting tumors, and one of two clinically nonfunctioning tumors, or 25.7% overall. Macroadenomas accounted for 89% of plurihormonal tumors. Long-term follow-up review (median > 5 years) revealed good control of PRL-secreting tumors (although five of 15 patients had received postoperative radiotherapy), contrasted with a 25% late recurrence rate for ACTH-secreting tumors, which had an 80% initial remission rate. The majority of patients had good endocrine function, including reproductive function. It is concluded that: 1) although pediatric pituitary adenomas occur primarily in adolescence, Cushing's disease is found at any age; 2) transsphenoidal surgery is feasible and safe in this age group; 3) plurihormonal tumors occur more frequently in the pediatric age group than in adults; and 4) long-term control rates in PRL- and ACTH-secreting tumors are probably similar to those seen in adults.
Adenoma↗
The binding influence of the Journal of Neurosurgery on the evolution of neurosurgery.
The author, who is currently a member of the Editorial Board of the Journal of Neurosurgery, examines the development of the specialty of neurosurgery and the timing of first publication of the Journal. He describes the role played by the Journal in the constantly advancing specialty and its importance to neurosurgery as a whole.
History, 20th Century↗
Lymphocytic hypophysitis: occurrence in two men.
Two men undergoing transsphenoidal exploration for pituitary adenoma were found to have lymphocytic hypophysitis. Both presented with frontal headaches, lethargy, and diminished libido. Laboratory investigations showed markedly depressed serum testosterone, and magnetic resonance imaging demonstrated pituitary enlargement, with optic chiasm involvement. Intraoperatively, the dura was adherent to the pituitary in each case. The resected glands were effaced by a dense lymphoplasmacytic infiltrate and fibrosis, without granulomas. Nonspecific peripheral enhancement on imaging suggested a diagnosis other than adenoma, but more experience with peripheral enhancement in lymphocytic hypophysitis is needed. The diagnosis was histological and required surgical intervention. Long-term pituitary replacement therapy is usually required.
Adenoma↗
Paresis of the abducens nerve after trivial head injury.
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Abducens Nerve↗
Chordoma of the mobile spine. A clinicopathologic analysis of 40 patients.
BACKGROUND: Chordomas are lobulated neoplasms composed of physaliphorous cells and their precursors; some have atypical, epithelioid, or spindle cell features. Fewer than one-sixth of chordomas arise in the mobile (cervical, thoracic, or lumbar) spine. Forty-eight percent originate in the sacrococcygeal region and 39% in the sphenoocciput. METHODS: The study included 40 patients, 27 men and 13 women (2:1), with chordoma of the mobile spine. Their clinical and histopathologic features are described. RESULTS: Nineteen tumors (48%) were located in the cervical spine, 7 (17%) in the thoracic spine, and 14 (35%) in the lumbar area. Most patients underwent subtotal removal of the tumor and postoperative irradiation. Variations in histologic appearance, including an occasional chondroid background, did not affect biologic behavior. Twenty-three patients (58%) were alive 5 years after surgery. Eventually, 25 patients (63%) died of tumor. Metastasis developed in two patients (5%). In contrast to some other studies metastasis was a rare occurrence. CONCLUSION: Chordoma of the mobile spine is a slow-growing, recurring neoplasm of low metastatic potential that incapacitates by locally aggressive growth.
Adult↗