The surgical and irradiation treatment of pituitary adenomas.
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The effect of ovarian X-irradiation of the rhesus monkey upon menstrual cycle length, duration of menstrual bleeding, excretion of gonadotrophin in the urine, concentration of gonadotrophin in the pituitary gland, ovarian histology, and breeding performance was investigated. Doses below 4000 R had no significant effect upon the above criteria. By contrast, doses of 4000 to 7000 R rapidly induced amenorrhoea in most animals, but unexpectedly these animals did not excrete greater than normal amounts of gonadotrophin. The pituitary content of gonadotrophin in cyclic and non-cyclic animals was not significantly different. Some births occurred in the animals which had been X-irradiated.
After a whole-body irradiation of Wistar and Siv-50 rat males and females with 600 to 900 R, the survival times and the development of weight of the irradiated animals were determined and compared. The development of body weight was influenced by the dose administered as well as by age, sex and breed of the animals. Furthermore, the weight curves showed also characteristic analogies. During a period of 30 days after the irradiation, there are generally two phases with a considerable weight loss which are both accompanied by a reduced absorption of drinking-water and the appearance of a gastrointestinal and hemopoietic irradiation damage as well as the resulting activity increase of the pituitary gland and the cortex of the suprarenal gland. The weight recovery occurring after sublethal radiation doses is also influenced by the administered dose and the age of the animals. The dropping weight curves of dying animals are equally dependent on the administered dose. With regard to the survival time in days in dependence upon the administered dose and the age of the animals, the authors proved that the survival time of the finally dying animals becomes longer as their radioresistance increases. During the last phase of the 30 days' experimentation, females show a markedly increased death rate whereas males seem to have continually better survival chances when they are still alive at the last phase.
TSH tumors are associated with both hypothyroid and hyperthyroid states. The proposed mechanism of thyrotroph secretion is illustrated in Figure 8. Pituitary enlargement in hypothyroidism is usually due to reactive hyperplasia and correlates with the degree of TSH elevation. Although this often translates to long-standing hypothyroidism and severe symptoms, this is not always the case. Patients may be asymptomatic or present with other endocrine syndromes. Children may have precocious puberty, and adults may have amenorrhea or decreased libido. One important message to remember is that whenever a patient has evidence of a pituitary tumor, a serum T4 and TSH level must be obtained. The dramatic reduction in pituitary size and resolution of endocrine dysfunction with thyroid hormone is gratifying. Thyrotropinomas producing thyrotoxicosis are autonomous tumors. Given their infrequent occurrence, one could question the cost effectiveness of ordering a serum TSH on all new patients with hyperthyroidism. Features that might favor the possibility of there being a tumor include male sex, headaches, visual impairment, and the absence of ophthalmopathy. Unfortunately, these are not reliable clinical features to suggest the presence of this disorder, and the diagnosis requires a serum TSH determination. Fortunately, the newer assays available are able to provide the sensitivity needed. Therapy should be aimed at the pituitary gland, but currently it is less than optimal. Surgery with or without external irradiation offers the best prognosis and, hopefully, will yield better results when cases are identified earlier. Medical therapy to suppress TSH is still in its infancy. More effective agents will hopefully be discovered in the near future.
Positron emission tomography (PET) with various tracers provides physiologic and biochemical information of living organs. Since radiologic examinations are usually avoided in pregnant women, mainly because of the radiation risk to the fetus, little is known about the effect of pregnancy on cerebral blood flow and metabolism. This paper reports findings of a 11C methionine PET scan of the pituitary gland in a woman after an abortion. The patient was a 31-year-old woman who suffered a seizure in the 9th week of her second pregnancy. On admission, computed tomography showed an abnormal mass lesion in the right frontal lobe, and a brain tumor was suspected. The patient and her family asked that that pregnancy be terminated. Seven days after a surgical abortion, methionine PET was performed. The scan showed high methionine uptake in the pituitary gland as well as in the right frontal lobe tumor. We suspected that another tumor was present in the pituitary gland. The right frontal tumor was partially resected, and pathologic examination of the resected specimen showed an astrocytoma (grade 2). After the operation, the patient received 50 Gy irradiation and chemotherapy. Two months after the operation, we performed a second methionine PET scan, which showed high uptake in the residual right frontal tumor but not in the pituitary gland. Results of other radiologic studies of the pituitary gland were normal. These findings suggest that the transport of 11C methionine into the pituitary gland may increase during pregnancy. Moreover, the pituitary gland of pregnancy should be a part of the differential diagnosis of pituitary adenomas in PET scanning. The change in physiologic uptake by the female pituitary gland should be taken into account in the diagnosis of pituitary adenoma with methionine PET.
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The authors reported a rare case of sellar germinoma which was misdiagnosed as nonfunctioning pituitary adenoma. A 32-year-old woman was admitted to our hospital because of amenorrhea and disturbance of left visual acuity. She had become amenorrhagic after her second delivery two years before. Neurological examination revealed she was normal except for diminished left visual acuity (Rt. = 1.2, Lt. = 0.5). The general condition was good. Urine volume and its specific gravity were within normal range. Endocrinological examination showed hyperprolactinemia (PRL 72 ng/ml) accompanied with impairment of GH, TSH, LH and FSH's reserve. Basal levels and reserve of the blood cortisol were normal. AFP and hCG were within normal range. CT scan revealed a homogenously enhanced intrasellar tumor which had a suprasellar portion (vertical length: 15 mm). T1 weighted MRI revealed low intensity tumor, and T2 weighted image revealed high intensity tumor. Sagittal MR image with gadolinium enhancement showed the pituitary gland anterior to the tumor. Transsphenoidal removal was performed. The histological diagnosis was pure germinoma. After the operation, the intracranial and spinal disseminations were disclosed. Complete neuraxis irradiation resulted in the complete remission of the tumor. Sellar germinoma without diabetes insipidus is considered to be very difficult to diagnose preoperatively. However, the authors proposed that anterior shift of the pituitary gland in sagittal MR image may be a clue to the diagnosis of sellar germinoma.
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OBJECTIVE: Determine the frequency and changes in thyroid hormones in Cushing's disease. METHODS: Free thyroxin and thyrotropin levels were measured in 11 patients (age range 17 to 60 years) with Cushing's disease both before and after resection of the pituitary adenoma. RESULTS: Free thyroxin levels were low (8.3 to 11.7 pmol/l) in 7 patients. These patients had no clinical manifestations of hypothyroidism. In 4 patients, cure of the pituitary adenoma led to normalization of the thyroid hormones 10 days after operation (13 to 55 pmol/l); in the other cases surgical cure was unsuccessful and thyroxin levels remained low. Cortisol levels were finally normalized in these patients after irradiation of the pituitary, a second pituitary operation, or bilateral resection of the adrenal glands in 2 patients. Normal thyroxin levels were thus achieved. There was no correlation between serum cortisol and free thyroxin. CONCLUSION: Thyroid hormones should be assayed regularly in patients with Cushing's disease as a supplementary control of treatment effectiveness.
This study is a further investigation of radiation dose to various head structures in the children given X-ray therapy for tinea capitis (ringworm of the scalp). In this work, estimates of the dose to the thyroid and pituitary gland were obtained with lithium fluoride thermoluminescent dosemeters using a child's head phantom. Doses were also measured for the parotid gland and several skin sites where skin tumours developed in the irradiated cases. In a previous study, brain and scalp doses of 140 and 500-800 rad had been estimated for the treated group using this same head phantom. In this work dosemeters were also placed in the same brain locations so that comparisons could be obtained between the two studies. The thyroid dose was estimated to be 6 +/- 2 rad and the pituitary dose was 49 +/- 6 rad for the conventional tinea capitis treatment. The dose to the parotid gland was 39 rad and the dose to skin sites on the face and neck where tumours occurred ranged from 20 to 40 rad. The data for the thyroid adenoma response from this and other studies involving irradiation of children suggests a linear dose-response relationship within the first 30-40 years after exposure with a risk of about 0-04% per rad.
Three cases of panhypopituitarism and five of isolated growth hormone deficiency which occurred following previous external irradiation of tumours distant from the adenohypophysis are described. The hypothalamic pituitary region received between 2800 and 12 000 rads in each case, 1-9 years before endocrine deficiency was recognized. Evidence is presented that the site of damage is in the region of the hypothalamus rather than the pituitary gland itself. Individuals treated with X-ray therapy in whom the hypothalamic-pituitary region is exposed to irradiation would appear to be at risk of developing some degree of delayed hypothalamic-pituitary dysfunction.
The aim of the study was to reveal alterations in the macrocellular neurosecretory system of the rat which occur under the influence of X-radiation. The experiment was carried out on 15 male Wistar rats, divided into 1 control and 4 experimental groups. The animals were subjected to total-body-X-irradiation in a dose of 300R. Brains and cerebral pituitaries were collected after decapitation and fixed in Bouine's fluid. Staining with haematoxylin & eosin and paraldehyde fuchsin was applied. A reduction in the neurosecrete content was found after 7 days following irradiation both in the area of perikarya and nerve processes of SON and PVN. In animals dissected on the 14th and 21st day following irradiation, a shift of neurosecrete along the neurosecretory path was observed (via nerve processes to the posterior lobe of cerebral pituitary). On the 28th day, the morphological picture of the system examined was similar to the control one. The above results indicate that initially X-radiation causes a decrease in the production of neurosecrete within SON and PVN; later, however, the amount of neurosecrete is increased, like in control nuclei.
Cushing's syndrome is the common clinical presentation of three unique disorders that give rise to hypercortisolism. In most cases neoplasms underly each of these disorders. Clinical features are highly variable and not accounted for by cortisol alone; indeed, the multihormonal basis for much of the clinical syndrome remains uncertain. Demonstration of sustained, excessive cortisol production is essential and depends on a pattern of repeated measurements and several different procedures. Plasma adrenocorticotropin, although not helpful in establishing the diagnosis, has proved valuable in differentiating the three major entities that cause hypercortisolism. The renewed significance of pituitary microadenomas and their improved detection by sella tomography has accompanied recent, impressive advances in transsphenoidal microsurgery. This may become the preferred treatment for pituitary Cushing's syndrome in the adult, particularly where the appropriate equipment and skills are available; for children, external pituitary irradiation seems to offer safe and effective therapy.
Seventeen children (11 M, 6 F) with acute leukaemia and myeloproliferative disorders were investigated for growth and endocrine dysfunction. All had undergone bone marrow transplantation prepared with cyclophosphamide and single fraction total body irradiation (900-1000 cGy) between 1.5 and 3.8 (mean 2.2) years previously. The majority of children exhibited growth failure, which was of multiple aetiology. Ten patients, of whom eight had had previous prophylactic cranial irradiation, had evidence of growth hormone deficiency based on the reduced growth hormone response to insulin induced hypoglycaemia. Three patients had evidence of hypothalamic damage as shown by their growth hormone response to 200 micrograms GHRH (1-29) NH2 intravenously. Gonadal failure was common, assessed clinically, and biochemically by basal gonadotrophin and sex steroid concentrations. All four girls of adolescent age (10.6-14.1 years) had ovarian failure requiring sex steroid replacement. Of the eight boys of adolescent age (12.3-18.3 years), two had testicular failure requiring sex steroid supplements. Both of these had had previous testicular irradiation. Five others had compensated gonadal failure, and one had normal Leydig cell function. Abnormalities of the TSH response to TRH occurred in 10 patients but only three had overt hypothyroidism. Unlike growth hormone deficiency, gonadal and thyroid dysfunction showed no correlation with previous cranial radiotherapy.
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