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Reduction of pituitary-tumour size in patients with prolactinomas and acromegaly treated with bromocriptine with or without radiotherapy.

69 patients with prolactin-secreting or growth-hormone-secreting pituitary tumours were treated with bromocriptine with or without pituitary irradiation and followed up for 6 months to 6 1/2 years. Of 26 patients with prolactinomas, 11 had external pituitary irradiation in addition to bromocriptine. There was evidence of shrinkage of the pituitary tumour (either a reduction in fossa size or loss of visual-field defects) in 6 of these patients (23%), 3 of whom had been treated with bromocriptine alone. Of 43 acromegalic patients, 30 received external pituitary irradiation. 8 (19%) showed evidence of shrinkage of the pituitary tumour, including 2 who had received no radiotherapy. 1 patient treated with bromocriptine alone showed striking reduction in the size of his suprasellar extension, as assessed by serial computed-tomography scans over 11 months. At the same time his visual-field defects resolved and his deficient corticotrophin and thyrotrophin reserves returned to normal. Bromocriptine can reduce the size of both prolactin-secreting and growth-hormone-secreting pituitary tumours, and this is of potential importance in their management.

Acromegaly↗

A conformal technique for irradiation of pituitary tumors.

We present a CT/MRI based conformal radiotherapy technique for irradiation of pituitary tumors. In this technique, the patient is treated with three isocentric non-coplanar 18 MV photon beams, with the patient in a natural supine position. The radiation ports are designed based on beam's eye view projections of the CT/MRI delineated target volume. This technique spares, completely from the primary beams, the lenses and retina, and a significant portion of the optic nerves, even for large pituitary tumors. The dose distribution in brain is comparable to coplanar are techniques for standard field sizes (5 x 5 cm2), but superior for larger field sizes (7 x 7 cm2). The beams in the present technique yield a low skin dose by avoiding beam overlap in entrance and exit regions, thus eliminating clinical hair loss. The treatments are easily set-up on the treatment machines, resulting in improved efficiency and accuracy.

Humans↗

Effects of reserpine treatment on pituitary-adrenocortical axis in patients with Cushing's disease.

Effects of reserpine treatment, not associated with pituitary irradiation, on the pituitary-adrenocortical axis in a total of 37 untreated patients with Cushing's disease were evaluated. With short-term treatment (2 mg daily for 2 weeks, n = 36), basal excretion of urinary 17-OHCS significantly decreased from 11.2 +/- 5.2 mg/day/m2 (body surface area) (mean +/- SD) to 9.6 +/- 4.4 mg/day/m2 (P < 0.01), and metyrapone-induced incremental responses of urinary 17-OHCS decreased from 58.4 +/- 41.4 mg/3 days/m2 to 45.9 +/- 29.8 mg/3 days/m2 (P < 0.05). Long-term treatment (1.7 +/- 0.3 mg/day for a mean of 15.8 +/- 19.9 weeks) induced a marked reduction in plasma cortisol, and 24-h urinary 17-OHCS and/or free cortisol in 4 of 8 patients examined. Long-term reserpine administration caused normal suppression of plasma cortisol (or 11-OHCS) in 3 of 9 patients with 1 mg, and in all of 5 patients with an 8 mg overnight dexamethasone suppression test. Plasma ACTH response to CRH was evidently decreased in one patient evaluated one month after the initiation of reserpine. The circadian rhythm of plasma cortisol was normal in one patient when the basal glucocorticoid level became normal with reserpine treatment. The present findings suggest that reserpine itself contributes in a causal fashion to the effectiveness of our regimen, reserpine and pituitary irradiation, for some Cushing's disease patients in whom it is effective.

17-Hydroxycorticosteroids↗

Carcinoma of the prostate; diagnosis and treatment.

About 28 per cent of men between the ages of 71 and 75 have cancer of the prostate. Many of them do not die of the disease, but with the life span ever increasing, this problem is becoming more important. In the early stages the condition is asymptomatic; when the symptoms of urinary obstruction arise, the cancer is usually too advanced for cure. Cure depends on early diagnosis and, therefore, on routine rectal examination. The solitary hard nodule of early prostatic cancer becomes a stony hard fixed prostate as the condition progresses. X-ray and acid phosphatase studies are of help only after the cancer has metastasized. As many as 50 per cent of patients with rectally palpable early carcinoma of the prostate can be cured by radical perineal prostatectomy. Often, simple enucleation or transurethral resection is sufficient to effect cure in the case of occult carcinoma. However, some observers believe that when cancer is detected by microscopic examination of a prostate that has been removed, a radical operation should be done as soon after the initial operation as feasible. Early orchidectomy and estrogen therapy are of considerable help in slowing the process of advanced prostatic cancer and may postpone the need of transurethral resection to relieve obstruction. When these measures fail, bilateral adrenalectomy, cortisone therapy, pituitary irradiation, and pituitary extirpation have been employed, with moderate success, in an effort to diminish the androgen level.

Carcinoma↗

Pituitary function after selective adenomectomy for Cushing's disease.

This retrospective analysis was undertaken to determine whether selective adenomectomy for Cushing's disease can achieve acceptable cure rates while causing minimal pituitary dysfunction. Tumour size, histology and pituitary function were evaluated in 34 consecutive patients (26 F: 8 M, mean age 33.6 years) undergoing transphenoidal adenomectomy for Cushing's disease from 1975 to 1992. Follow-up averaged 5.8 years. Cure was defined as resolution of symptoms and signs and normalization of urinary cortisol excretion. Sixty-three per cent of patients achieved cure after selective adenomectomy, repeat adenomectomy cured an additional four patients. Twenty-eight per cent required bilateral adrenalectomy and/or pituitary irradiation. Postoperative pituitary function remained completely intact in 81%. Secondary hypogonadism occurred in 8%, hypothyroidism in 155 and permanent diabetes insipidus in 4%. There was recurrence in 26% after a mean of 4.6 years (range 1-7). It is concluded that selective adenomectomy can achieve acceptable cure rates with a low prevalence of postoperative hypopituitarism, although an increase of recurrence may be the result of conservative surgery.

Adenoma↗

Megavoltage irradiation of pituitary macrotumors in dogs with neurologic signs.

OBJECTIVE: To assess the efficacy and determine prognostic factors of megavoltage irradiation for pituitary macrotumors in dogs with neurologic signs. DESIGN: Prospective clinical trial. ANIMALS: 24 dogs with pituitary macrotumor syndrome; 19 ACTH-secreting and 5 clinically endocrine-inactive tumors. PROCEDURE: Dogs were treated with 48 Gy of radiation during 4 weeks on an alternate-day schedule of 4 Gy/fraction. Three (12.5%) dogs did not complete the planned treatment because of progression of neurologic signs. RESULTS: A significant correlation was found between relative tumor size (i.e., size of tumor relative to calvarium size) and severity of neurologic signs and between relative tumor size and remission of neurologic signs after irradiation. In dogs with pituitary-dependent hyperadrenocorticism, a significant correlation was found between relative tumor size and plasma endogenous ACTH concentrations. Prognostic factors that independently affected duration of remission of neurologic signs were relative tumor size and endocrine activity. The prognostic factor that independently affected overall survival time was severity of neurologic signs. Prognostic factors of duration of eucortisolism were not found. Use of a large field of irradiation was associated with substantial damage to brain tissue. CLINICAL IMPLICATIONS: Because radiation therapy was effective for treatment of tumors of small relative size in dogs, early treatment of pituitary tumors should improve prognosis. Further improvements may be obtained, using protocols in which higher total radiation doses and smaller radiation dose fractions are given. Irradiation was effective for long-term control of functional pituitary macrotumors and resulted in acceptably low complication rates when small fields of radiation were used.

Adrenocortical Hyperfunction↗

Surgical experience with Cushing's disease.

During the period 1952 to 1976 at Vanderbilt University Hospital 119 patients with pituitary-dependent hypercortisolism or Cushing's disease were studied. The less severe cases, which constitute a majority, were treated by pituitary irradiation with endocrinologic cure or improvement in two-thirds of the treated patients. Bilateral total adrenalectomy was reserved for the most severe cases and for failures of pituitary irradiation. In 29 patients with total bilateral adrenalectomy there was one postoperative death. Two of 28 survivors had incomplete relief of hypercortisolism and required additional therapy for its control. One patient with recent operation is improved and another with early improvement died suddenly at home three months after operation. The 24 other adrenalectomized patients, followed 6 months to 20 years, were considered endocrinologic cures of Cushing's disease. One patient in the group who had not received pituitary irradiation developed signs of expanding pituitary tumor after adrenalectomy (Nelson's syndrome) with satisfactory response to radiation therapy.

Adolescent↗

[Neurologic and electroencephalographic evaluations after a single irradiation of pituitary adenomas with protons having 1000 MeV of energy].

The brain was examined (on the basis of neurological and electroencephalographic findings) in 43 patients with hypophysis adenomas both before and at various intervals after a single exposure of the tumour to protons with an energy of 1,000 MeV. The irradiation was performed by the stereotaxic convergent method. The radiation dose absorbed by the tumour was 100 Gy. The local character of the proton action, absence of irreversible changes in the brain, temporary, transient changes on the part of the oculomotor nerves (25.5%) and temporal lobes (9.3%) are demonstrated. The objective remission of the disease was attained in 97.7% of the cases.

Adenoma↗

Pregnancy in patients presenting with hyperprolactinaemia.

Ninety-two pregnancies occurred in 76 hyperprolactinaemic patients treated with bromocriptine. Half conceived within three months of attempted conception. There was no evidence of an increased rate of spontaneous abortion, fetal abnormality, or multiple pregnancy; the three twin pregnancies occurred in women who were additionally treated with clomiphene and human chorionic gonadotrophin. Thirty-one patients had radiological evidence of a pituitary tumour; 14 with major radiograph changes in the pituitary fossa or serum prolactin concentrations greater than 100 ng/ml received pituitary irradiation before conception. None of the latter showed evidence of enlargement of the tumour during pregnancy. In contrast two of the four patients with similar tumours but who were not irradiated developed visual field defects, one with gross destruction of the pituitary fossa. Prophylactic treatment to limit subsequent tumour expansion during pregnancy in patients with prolactinomas is indicated, and pituitary irradiation before conception appears to be a safe and effective method to achieve this goal.

Bromocriptine↗

Risk factors for cerebrovascular deaths in patients operated and irradiated for pituitary tumors.

Vascular mortality, especially cerebrovascular disease (CVD), are the most pronounced cause of mortality in women with hypopituitarism. In a cohort of 342 patients operated and irradiated for pituitary tumors, 31 died from CVD (CVD patients) between 1952 and 1996. The study assessed whether the radiation regimens and duration of symptoms of hypopituitarism before operation differed between the 31 CVD patients and the 62 matched patients from the same cohort who had not died from CVD (control patients). Furthermore, the infarction/hemorrhage ratio, type of clinical stroke syndrome, and time to death after stroke were investigated in the CVD patients and in matched controls from the general population who had died from CVD (population controls). No significant differences in maximum or centrally absorbed dose, maximum or central biological equivalent dose, field size, or number of fraction were recorded between CVD and control patients. A significant difference in the duration of symptoms of hypopituitarism before operation was recorded, but only in women (P = 0.01). There were no significant differences in the infarction/hemorrhage ratio (P > 0.3) of lacunar or posterior circulation syndrome compared with middle cerebral artery syndrome with cortical features (P = 0.22) or the proportion of patients who died within the first month after stroke onset (60% vs. 59%, respectively) between CVD patients and population controls. In conclusion, no significant effect on CVD deaths could be detected for any radiation parameter. A long history of unsubstituted pituitary insufficiency may be a contributing factor to the very high CVD mortality among women. There were no indications of significant differences in type of stroke, clinical stroke syndromes, or stroke fatality between the CVD patients and the population controls.

Adult↗

[Detection of pituitary autoantibody in patients with pituitary tumors and hypopituitarism].

UNLABELLED: In 80 patients, 73 cases of pituitary tumours and 7 cases of hypopituitarism, we performed pituitary autoantibodies assays in serum samples because in our previous studies we had found a high prevalence of pituitary autoantibodies in several autoimmune endocrine disorders. To detect the presence of pituitary autoantibodies we applied 2 methods, radioimmunoassay (RIA) and immunoblotting. The RIA was performed by solid phase technique in human pituitary microsome-coated polyethylene tubes. Following incubation with diluted sera of the patients labelled 125I-protein A was added to the tubes to detect the retained antibodies. In the sera of 33 patients we detected the presence of antibodies; in the other 47 patients no antibodies were found. The majority of the patients with positive antibody results were previously treated by pituitary irradiation. To evaluate the molecular weights of pituitary autoantigens the microsomal proteins were separated on SDS PAGE, then electrophoretically transferred to nitrocellulose membranes and reacted with diluted sera of 30 antibody-positive patients. The nitrocellulose strips were incubated with labelled 125I-protein A and autoradiographed. Using immunoblotting, 13 out of these 30 patients we found autoantibodies reacting with pituitary microsomal antigens of different molecular weights, most frequently reacting with a 68 kDa autoantigen. CONCLUSIONS: The prevalence of pituitary autoantibodies in patients with pituitary diseases is 41% lower than in autoimmune endocrine diseases. Pituitary autoantibodies usually appear in patients after pituitary irradiation or after neurosurgery followed by irradiation, but occur rarely in untreated patients with pituitary adenomas.

Adenoma↗

Growth hormone deficiency in patients with histiocytosis X.

Twenty-two patients with biopsy proved histiocytosis X, aged 10 months to 14 years (median 2 years) at the time of diagnosis, were observed for 6 months to 13 years (median 4 years). One patient who had received 3000 rads irradiation directly to the hypothalamic-pituitary area had clinical and biochemical evidence of growth hormone deficiency and responded to GH therapy. Thirteen patients had normal stature, normal growth velocity, and no diabetes insipidus. The GH response to insulin-induced hypoglycemia was studied in three of these 13 patients (group 1), in three children with short stature and no diabetes insipidus (group 2), and in five patients with diabetes insipidus but normal stature and growth velocity (group 3). Peak GH responses were normal (greater than 5 micrograms/L) in all patients in groups 1 and 2, but three of the five patients in group 3 had subnormal GH responses to insulin-induced hypoglycemia and to arginine, L-DOPA/propranolol, and exercise. Their growth rates continue to be normal over 6 to 14 years follow-up. Thus, although impaired GH responses were observed in four of the 12 patients tested, true growth failure occurred only in association with direct hypothalamic-pituitary irradiation. This experience and the observation that GH deficiency was diagnosed in fewer than 1% of children with histiocytosis in Canada during a 15-year period (accounting for less than 1% of all children with GH deficiency) suggest that classic GH deficiency is not a common complication of histiocytosis unless direct hypothalamic-pituitary irradiation has been given.

Child↗

Visual complications following irradiation for pituitary adenomas and craniopharyngiomas.

Of 55 patients with pituitary adenomas or craniopharyngiomas treated with irradiation, a retrospective study revealed that 5 sustained a visual loss compatible with radiation damage to the optic nerve. No patient who received less than 250 rads/day fractions showed such visual loss. Within the range of total dosages used in this series, total dose was not an important determinant of this complication. The time to occurrence of visual disturbance ranged from 5 to 34 months following therapy.

Adenoma↗

Recurrence of Cushing's disease in childhood after radiotherapy-induced remission.

A 16-year-old female patient with recurrent Cushing's disease (CD) underwent successful treatment with pituitary irradiation. Within one year after radiotherapy, cortisol levels had returned to normal (but with continued absence of diurnal variation), growth velocity improved, and puberty ensued. Five years after treatment, the patient developed clinical and biochemical evidence of recurrent CD. The high baseline evening corticotropin level (9 pmol/L [40 pg/mL]) was unresponsive (maximum level, 10 pmol/L [46 pg/mL]) to stimulation with ovine corticotropin-releasing hormone (CRF). In patients with CD treated with radiotherapy, the corticotropin response to CRF stimulation may not be reliably compared with that of normal control values. After pituitary adenomectomy, the corticotropin concentration was still unresponsive to CRF. We suggest that the pituitary tumor was secondary to abnormal hypothalamic CRF regulation not corrected by pituitary irradiation; therefore, CD may recur despite pituitary irradiation.

Adenoma↗