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The need for adjunctive focused radiation therapy in pituitary adenomas.

In pituitary adenomas radiation therapy regardless of the technique should be limited to surgical failures. The delayed onset of beneficial effects and the high rate of pituitary insufficiency have to be weighed against the good surgical and/or medical results in the treatment of these tumours. Unfortunately surgical outcome is almost invariably correlated with invasive growth. Invasiveness is statistically significantly correlated with tumour size, as well as with high proliferation rates, which can be measured by immunohistological methods such as mAB KI-67. Owing to the good results of medical treatment, radiation therapy is usually unnecessary in prolactinomas. Patients with persistent hypersecretion of growth hormone after unsuccessful surgery may represent the ideal candidates for radiation therapy, whereas patients with persistent Cushing's disease need cure for hypercortisolism without delay. In patients with residual tumour due to non functioning adenomas, radiation therapy should only be given if the proliferation rate is high.

Adenoma↗

Pituitary adenomas: results of 684 surgically treated patients and review of the literature.

BACKGROUND: The outcome of patients with pituitary adenomas who were treated surgically with or without postoperative radiotherapy was analyzed. The purpose of this study was to determine the factors that strongly influence (A) tumor control, (B) the efficacy of surgery, and (C) radiotherapy based on the hormonal activity of adenomas and its invasion characteristics. METHODS: Between 1982-1996, 684 patients with the diagnosis of pituitary adenoma were operated on. The mean age was 38 years and the mean follow-up time was 40.5 months. A total of 516 patients who were followed for more than 1 year were studied to analyze the effect of treatment modalities and invasion characteristics on tumor control. There were 297 patients with prolactinomas, 118 patients with somatotropinomas, 45 with corticotropinomas, 17 with mixed adenomas, two with thyrotropinomas, and 205 with null cell adenomas. All patients were classified according to Hardy's modified radiological classification scheme and analyzed in invasive and noninvasive groups individually based on this classification system. In the early postoperative period, 230 of these patients were given conventional radiotherapy with a mean dose of 4400 cGy. The following factors were analyzed for prognostic significance in tumor control: the effects of surgery and radiotherapy based on tumor types and invasion characteristics, the existence of histologically proven invasion of the dura mater overlying the sellar floor, and the early results of topical bromocriptine application in macroprolactinoma patients. RESULTS: Overall surgical complications and mortality rate were similar to those of large series reported in the literature. Except for the invasive somatotropinomas and null cell adenomas, statistical analysis demonstrated the ineffectiveness of radiotherapy on tumor control. We did not detect any positive correlation between the recurrence rate and mean recurrence time or dural invasion of the sellar floor. Topical bromocriptine application seemed to improve tumor control in 21 selected macroprolactinoma patients. CONCLUSION: Conventional radiotherapy is not as effective as expected, considering its adverse effects. The increased side effects of radiotherapy in cases with supra-parasellar extension, especially to the optic pathway and hypothalamus, limit its benefits, which could be demonstrated only in invasive somatotropinomas and null cell adenomas. In contrast with our current beliefs, tumoral infiltration of the sellar dura mater is not a prognostic factor for recurrence and therefore should not be a criterion for radiotherapy after surgery. Topical application of bromocriptine into the sellar cavity after tumor removal seems to provide superior results compared with the conventional treatment modalities.

Adenoma↗

Growth and endocrine disorders in multisystem Langerhans' cell histiocytosis.

INTRODUCTION: Langerhans' cell histiocytosis is a rare disorder, with diabetes insipidus occurring in up to half of patients. Causes of growth failure include the illness itself, treatments used and growth hormone insufficiency. PATIENTS AND METHODS: We identified all patients with an endocrinopathy secondary to Langerhans' cell histiocytosis (LCH). Growth data were analysed from all patients with multisystem involvement. RESULTS: Of 144 patients with multisystem LCH, 50 had an endocrinopathy, 49 of whom had diabetes insipidus. Growth hormone insufficiency (GHI) was present in 21 patients, seven of whom had other anterior pituitary deficiencies as well (gonadotrophin deficiency + GHI n = 2, gonadotrophin deficiency + TSH deficiency + GHI n = 2, panhypopituitarism n = 3). GH insufficiency, the development of which appeared to be independent of pituitary radiation, occurred at a median age of 8.3 years (4.7-18 years) and at a median interval of 3.5 years (0-11.8 years) after diagnosis of LCH. The median height SDS at diagnosis of growth hormone insufficiency was -2.9. Thirteen of the patients with growth hormone insufficiency attained final height with a median height SDS of -1.2. The final height SDS of 15 patients without GH insufficiency was closer to target height SDS, but not statistically different from that of the GH insufficient group. CONCLUSIONS: GH therapy significantly improves growth in GH insufficient patients with Langerhans' cell histiocytosis. Early institution of GH therapy may further improve height outcome. However, most children with Langerhans' cell histiocytosis regardless of endocrine function, failed to reach target height.

Adolescent↗

Results of treatment of pituitary disease in multiple endocrine neoplasia, type I.

OBJECTIVE: The aim of the present study was to examine the clinical and pathological features of pituitary disease in patients with multiple endocrine neoplasia, Type I (MEN I) and to assess the prognosis. METHODS: Fifty-two patients with pituitary disease and MEN I were studied retrospectively. Medical records were reviewed, and all of the patients known to be alive were sent a questionnaire to ascertain current disease status. RESULTS: In 12 patients, pituitary disease was the initial manifestation of MEN I. The most common lesion was prolactinoma, followed, in frequency, by acromegaly and nonsecretory adenoma. Thirty-four of the patients had surgical treatment at the Mayo Clinic, Rochester, MN, as primary treatment, 3 had radiotherapy, and 12 received no specific therapy. Twelve patients had adjunctive radiotherapy postoperatively. Of the 34 patients receiving surgical treatment, 33 had adenoma and 1 had adenoma and pituitary hyperplasia. Immunocytochemical examination demonstrated that many tumors showed reactivity for more than one pituitary hormone. On survival analysis, no excess pituitary-related mortality was found, either in the surgically treated group or in the group as a whole. CONCLUSION: On the basis of this study, we conclude that pituitary disease is frequently the initial manifestation of MEN I; that adenomas, particularly prolactinomas, are the rule and hyperplasia is rare; that a significant proportion of tumors are plurihormonal; and that excess pituitary-related mortality is not a factor in patients with MEN I.

Acromegaly↗

Serum growth hormone levels and the response of diabetic retinopathy to pituitary ablation.

Serum growth hormone levels were measured during insulin tolerance tests in 36 patients after yttrium-90 pituitary implantation for diabetic retinopathy. The response of the new blood vessels was more clearly related to loss of growth hormone function than was the improvement of retinal haemorrhages and microaneurysms. The overall response of the retinopathy was greatest when growth hormone function was lost.Since the loss of growth hormone function was related to the loss of other aspects of anterior pituitary function, a unique role of growth hormone in the response of diabetic retinopathy to pituitary ablation could not be established.

Diabetic Retinopathy↗

Cell kinetic investigations in craniopharyngioma: preliminary results and considerations.

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.

Adolescent↗