Craniopharyngioma: the controversy regarding radiotherapy.
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In vitro determination of 3H-thymidine labeling index (LI%) was carried out in craniopharyngiomas from 16 patients submitted to repeated surgical procedures. This study showed a poor correlation between LI% values and prognosis, but allowed to detect a high LI% variation in the same tumor investigated in serial different times. The spatial distribution of S-phase proliferative cells in squamous epithelium of cystic components suggests a rationale for intracavitary treatment of cystic and mixed craniopharyngioma and may help explain its success.
Craniopharyngiomas, although histologically benign, are usually so intimately associated with the hypothalamus that total extirpation of these tumors was generally followed by death from hypotension and gross endocrine deficiencies. During the first half of the present century, those recording their tribulations include the famous names of Grant, Bailey, Bucy, Peet, Kahn, Olivecrona, Norlen, Sjöqvist, Rougerie and Northfield. Matson and Sweet were the first to achieve major reductions in mortality by giving massive doses of cortisone plus meticulous dissection, which took advantage of the reactive glial envelope which surrounds the great majority of these tumors.
Craniopharyngiomas can be divided into sellar, prechiasmatic, retrochiasmatic and giant tumors. The initial approach to a craniopharyngioma should be an attempt at its removal. Only if surgical therapy fails to deal with the tumor should more conservative approaches utilizing radiotherapy be used. The use of intracystic injection of bleomycin in craniopharyngiomas has proven to be a valuable adjunct in helping to remove these tumors.
The records of 61 children treated for primary craniopharyngioma at the Children's Hospital in Boston and The Joint Center for Radiation Therapy from 1970 to 1990 were reviewed to determine if any information could be obtained regarding the efficacy of surgery versus radiotherapy or a combination of these modalities for this tumor. A select group of 9 children treated without biopsy by radiation therapy alone were all alive without disease progression at follow-up. Although 9 of the 15 children who underwent surgery alone had tumor recurrence, 7 of the 37 children treated with radiotherapy following surgery have also recurred. Treatment morbidity occurred in all groups, but the 10-year actuarial survival for all patients was 91%. Early postoperative imaging and pre- and posttreatment endocrine and neuropsychologic evaluations need to be carried out in all prospective studies of the treatment of craniopharyngioma in children.
A Multimodality Protocol for the treatment of craniopharyngiomas, where stereotactic methods are used preferentially, give long-term results not inferior to those reported when microsurgical removal has been the first therapeutic choice. Case material, treated in accordance with this protocol, is presented in a long-term perspective. The features of the protocol are discussed.
11 acromegalics were treated with bromocriptine for 2--18 months. Their hormonal response was assessed by an acute suppression test with bromocriptine (AST), an oral glucose tolerance test (GTT), and by measuring growth hormone (GH) concentrations during a day of hospital life. The GTTs and the 24-hour profiles were performed before and after bromocriptine. During the AST all patients showed a decrease of GH concentrations ranging from 33 to 86% of the basal. Following bromocriptine, the mean GH concentration was lowered in 7 out of 11 patients during the GTT, and in 8 out of 11 during the profile, but it was within the normal range in 4 patients only during the GTT, and in 1 during the profile. Bromocriptine normalises radioimmunoassayble GH levels in a percentage of patients (12%) which is less than those following conventional treatment of acromegaly, surgery (80%) and pituitary irradiation (70%). Clinically, however, bromocriptine was more effective than judged by the changes of GH levels. Subjective and objective symptoms of acromegaly, such as articular pain, excessive sweating, hypertension, amenorrhoea, urinary hydroxyproline excretion and heel pad thickness decreased in our patients after bromocriptine. A specific action of bromocriptine on the degradation rate of 'little' GH may result in a selective reduction of the bioactive monomeric component of GH and may explain the discrepancy between the clinical and the biochemical response to bromocriptine. This discrepancy might also be explained by a specific action of bromocriptine on the somatomedin levels.
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Pulmonary function was assessed in 11 patients with acromegaly, 8 of whom were previously treated by external pituitary irradiation. None of the patients had any overt respiratory ailment. Ventilatory function tests were normal in all patients and all had normal total lung capacity ranging from 75 to 123% (mean, 98.18 +/- 4.69%). Eight of ten patients (80%) had hypoxemia with a partial pressure of oxygen in arterial blood ranging between 58 and 90 mmHg (mean, 76.0 +/- 4.2). Calculated alveolar-arterial differences for oxygen ranged between 5.25 and 46.0 (mean, 26.0 +/- 4.7). In 4 of 5 patients in whom lung perfusion scans were performed, perfusion defects were found. There was a significant correlations (p < 0.05) between the presence of hypoxemia and the known duration of acromegaly, but not with the present growth hormone levels or previous therapy. The results indicate that pneumomegaly is not common in acromegaly. However, most patients have some degree of hypoxemia present usually as subclinical disease and it is probably due to a ventilation-perfusion derangement, which is probably a direct effect of the prolonged oversecretion of growth hormone.
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A 50-yr-old woman presented with a 7-yr history of Cushing's syndrome. She had high urinary free cortisol levels (711 micrograms/day) and a positive response to metyrapone and suppression with 8 mg dexamethasone, suggesting pituitary ACTH-dependent adrenocortical hyperfunction. Plasma cortisol and ACTH levels showed marked temporal variation. Samples obtained at 2-h intervals revealed that plasma ACTH and cortisol levels surged during periods lasting approximately 12 h and fell to levels below normal during the remainder of the 24-h cycle. When urinary free cortisol was measured in urines collected in 12-h aliquots, the corresponding surge in free cortisol excretion was also evident. These cycles were not affected by a 2.5-month course of cyproheptadine. Pituitary irradiation and mitotane therapy resulted in remission of Cushing's syndrome, with disappearance of the peaks of ACTH and cortisol secretion. This case represents an unusual example of the abnormal circadian rhythm of ACTH secretion on Cushing's disease.
Three years after radiation therapy for an intrasellar tumor, a 42-year-old housewife presented with headache, lethargy, and remarkable plain skull roentgenograms, in which dilated lateral and third ventricles were filled with air. Air apparently had entered the cranium through the sphenoid sinus and eroded sellar floor, extending directly through intrasellar remnants of the chromophobe adenoma and into the floor of the third ventricle. Frontal exploration showed an empty sella turcica and no residual tumor. She made an excellent recovery and has done well for 5 years after operative closure of the defect.
A 32-year-old woman with secondary amenorrhea was found to have an elevated level of serum prolactin, partial diabetes insipidus, and a subtle visual field defect. A primary intrasellar tumor was noted on the computed tomographic scan. Although the tumor had some characteristics of a prolactinoma, transsphenoidal exploration revealed a primary germinoma. The tissue diagnosis led to appropriate treatment with radiotherapy. The tumor regressed, and the patient had a spontaneous pregnancy. Had dopamine agonists been used initially, amelioration of the hyperprolactinemia and delay in the proper diagnosis and treatment would have occurred.
A case of pituitary adenoma associated with unilateral exophthalmos is reported. An intraorbital infiltrative tumor growth was verified by histopathological study. The mechanism of exophthalmos is discussed, and edema of the intraorbital tissue secondary to an inflammatory reaction or venous stasis associated with tumor cell infiltration is considered to be the cause of exophthalmos in this patient.