The recovery of the hypothalamo-pituitary-adrenal axis after transsphenoidal operation in three patients with Cushing's disease. The effect of prior external pituitary irradiation.
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We report on a 19 year old patient with clinical signs of hypogonadism (small testicles, missing pollutions and diminished beard growth) despite of normal testosterone levels. Further diagnostic procedures revealed panhypopituitarism with insufficiency of the gonadotrope, somatotrope and corticotrope axis due to a beta-HCG-producing suprasellar germinoma with intracerebral metastases. Paraneoplastic production of beta-HCG resulted in sufficient stimulation of Leydig cells with normal production of testosterone, which had partly masked clinical symptoms of gonatrope insufficiency. The patient was treated by combined radiochemotherapy and is in remission since 7 years.
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Trans-sphenoidal intrasellar implantation of radioactive rods was employed to treat Cushing's disease in our Institution between 1958 and 1981. The patients were followed at regular intervals after the procedure. The aim of this work is to assess retrospectively the results, comparing the short- (1 year) and long-term (average 21.8 years) effects of this treatment. Seventy-six patients received pituitary implantation of 90Y- and one of 198Au-labelled rods, delivering a dose of 100-150,000 rad. Complete remission was obtained in a few weeks to months in 57/76 patients (5 of whom required a second implantation); 2 patients died of meningoencephalitis and 3 of cardiovascular complications associated with hypercortisolism 1 to 2 months after surgery. In 12 patients bilateral adrenalectomy or external pituitary irradiation were required to achieve remission; one of them developed Nelson's syndrome 15 years after implantation. Two were lost at follow-up. Long-term follow-up was possible in 41 patients of the initial series. Of these, 40 were cured of the disease, with hypoadrenalism developing in 25, while recurrence was observed only in the patient treated with 198Au. The incidence of hypothyroidism was 50%, and that of hypogonadism 54%. Permanent diabetes insipidus developed in 1 subject. GH deficiency resulting in retarded growth was found in the youngest patient, who had been operated at the age of 14. In conclusion, interstitial irradiation of pituitary adenomas was a safe and effective procedure for the treatment of Cushing's disease.
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External beam pituitary irradiation has been frequently used in the treatment of growth hormone (GH) secreting pituitary adenomas. Many studies have demonstrated that serum GH declines rapidly and reliably following treatment and early "cure" rates, based on a basal serum GH below 10 micrograms/L were as high as 80%. The definition of "cure" has become more stringent over time and retrospective studies have indicated that GH must be below 2.5 micrograms/L for acromegalics to achieve mortality rates comparable to a normal population. Only 20% of irradiated patients will achieve this goal by 10 yr. Even fewer will achieve a normal serum insulin-like growth factor I (IGF-I) levels. Although pituitary irradiation still has a role in the control of tumor size, its importance as a treatment for normalizing serum GH is being reevaluated.
A 45-year-old male was diagnosed as having myelodysplastic syndrome (RAEB) in March 2001. He was admitted to our hospital because of cellulitis in his left lower limb in May. The blood cell count showed pancytopenia and immature myeloid cells were seen in the peripheral blood. Bone marrow aspiration showed the proliferation of myeloblasts (11.2%) and complex karyotypic abnormalities were detected including the long arm deletion of chromosome 7. The patient developed polyuria and polydipsia after admission and was diagnosed as having central diabetes insipidus. He was treated with DDAVP and the polyuria disappeared. In November, he underwent unrelated allogeneic bone marrow transplantation after conditioning with total body irradiation and cytarabine. After transplantation DDAVP was no longer required. Central diabetes insipidus has been reported as a rare complication of leukemia or myelodysplastic syndrome, but the underlying mechanism remains unclear. The complete remission of diabetes insipidus after bone marrow transplantation suggests that the infiltration of leukemic cells into the pituitary gland caused the diabetes insipidus in this case.
The normal functions of the pituitary gland may be suppressed when the gland is compressed onto the sella floor by arachnoid tissue extending through an impaired sella diaphragm. Interestingly, pituitary hormone hypo- and hypersecretion, including acromegaly, have been observed in patients with an 'empty sella'(1-4). This 'empty sella syndrome' has been classified into a primary form, in which no inciting factor (pituitary irradiation or surgery for a pituitary tumor) is present, and a secondary form, in which the empty sella occurs after pituitary procedures. In this report we describe a patient who presented with clinical and biochemical features of acromegaly and who had an empty sella on pituitary magnetic resonance imaging (MRI).
Mammary carcinomas were found at autopsy 98--100 days after irradiation in 12 of 14 (86%) multiparous Fischer female rats which had been adrenalectomized and given grafts of secretory pituitary tumor strain MtT-F4 soon after exposure to gamma-rays or fission neutrons. A single carcinoma was found in 1 of 10 unirradiated, MtT-bearing, adrenalectomized animals. When adrenalectomy was not done, no tumors were found in 8 unirradiated or in 13 irradiated MtT-bearing rats rats. In view of the well-established finding that Cortisol is essential for milk production, we suggested as a working hypothesis that, in the presence of high titers of mammotropic hormone and adrenal corticoids, differentiation of a given cell for milk secretion reduced that cell's proliferative potential. When such differentiation was precluded by adrenocorticoid deficiency, more irradiation-altered mammary epithelial cells retained their high proliferative potential and contributed to carcinoma formation.
PURPOSE: Three-dimensional treatment planning was performed to evaluate three standard coplanar irradiation techniques (two-field parallel-opposed, three-field, and 110 degrees bilateral arcs), the 330 degrees single rotational arc, and a four noncoplanar arc technique for the treatment of pituitary adenomas. We sought to identify the optimal technique for minimizing the dose delivered to the normal tissues around the pituitary gland. METHODS AND MATERIALS: Contours of the pituitary tumor and normal tissues were traced onto computed axial tomography (CT) scans and reconstructed in three dimensions using a three-dimensional planning system. A total dose of 45 Gy was delivered to the pituitary lesion with the five techniques using 6 MV and 18 MV photons, and dose-volume histograms were generated. RESULTS: The 18 MV photons delivered a lower dose to the temporal lobe than did the 6 MV photons in the two-field technique, but this advantage was not evident for the other techniques. The three-field technique improved dose distribution throughout the temporal lobes with low doses being delivered to the frontal lobe. The bilateral arc and the 330 degrees arc techniques were superior to stationary two- and three-fields techniques for sparing the temporal lobes. The four noncoplanar arc technique delivered less doses to the temporal and frontal lobes than did the other techniques. However, the lens dose (3.6 Gy/25 fractions) was higher compared to the other techniques. CONCLUSION: Analysis of the dose-volume histograms shows the various dosimetric advantages and disadvantages of the five techniques. Based upon individual considerations, including the patient's age and medical history, one can decide the optimal technique for treatment.
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The effect of lethal irradiation and transplantation of syngenic bone marrow in a dose of 1 x 10(7) cell/ml on the morphofunctional state of hypophysis at various stages of the posttransplantation period has been studied for 3 months using 100 linear male mice of a F1 (CBA x C57 B) line. The experiments conducted have shown that bone marrow transplantation reduces the intensity of the negative effect of irradiation on hypophysis and facilitates normalization of its histological structure. There was a correlation between changes in the number of secretory cells in the anterior lobe of the hypophysis and the level of corticosterone in irradiated and bone marrow-protected animals.
Previous studies support the existence of a central set point for target body size. The set point is a hypothetical fixed reference for body size. The present experiments were carried out to determine whether target body size and, by implication, the putative set point can be consecutively reset or whether, once set by an extraneous factor, it is refractory to another extraneous factor. Male and female rats were given 6.0 Gy whole head X-irradiation at two days of age or were sham-irradiated as controls. Significant permanent reduction of body weight, tibia length, and pituitary weight resulted from head-irradiation in both males and females; gonad weight was reduced in males but not significantly in females. At 41 days of age the irradiated animals were injected sc with cortisone acetate, 1 mg/25 g body weight/day, or saline. During cortisone treatment the head-irradiated rats had a decrease in body weight velocity; the effect was greater in males than in females. Following treatment growth velocity approached normal in treated males, and slightly exceeded normal in treated females. Treated males had significantly reduced body weight, tail length, and tibia length at the end of the study. Treated females showed a similar pattern of body weight growth to the treated males, but there was not a significant long term reduction of body weight or change in tail length or tibia length. Final pituitary and gonad size was not affected by cortisone treatment in either sex. The results indicate that the reset of target size after head-irradiation does not result from damage to putative control.(ABSTRACT TRUNCATED AT 250 WORDS)
Review of 484 records for colony Beagles revealed an association between hypothyroidism and diabetes mellitus. The average time between first notation of hypothyroidism and later development of diabetes mellitus was 2.8 years. An association was also made with hypothyroidism, renal amyloidosis, and thrombosis. Hypothyroidism was significantly related to thrombosis, thrombosis was significantly related to renal amyloidosis, but hypothyroidism and renal amyloidosis were not significantly related. Of 62 hypothyroid dogs, 11 were diabetic and 7 others had thrombosis. Six hypothyroid dogs had renal amyloidosis, 4 of which had thrombosis. One dog had renal amyloidosis and thrombosis in the absence of hypothyroidism. There does not appear to be an association with any of the lesions and previous low-dose, whole-body gamma, or sham irradiation.
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