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PubMed2003

Radiation-induced growth hormone deficiency.

Deficiency of one or more anterior pituitary hormones may follow treatment with external irradiation when the hypothalamic-pituitary axis falls within the fields of irradiation. Hypopituitarism occurs in patients who receive radiation therapy for pituitary tumours, nasopharyngeal cancer and primary brain tumours, as well as in children who undergo prophylactic cranial irradiation for acute lymphoblastic leukaemia, or total body irradiation for a variety of tumours and other diseases. The degree of pituitary hormonal deficit is related to the radiation dose received by the hypothalamic-pituitary axis. Thus, after lower radiation doses isolated growth hormone deficiency ensues, whilst higher doses may produce hypopituitarism. The timing of onset of the radiation-induced pituitary hormone deficit is also dose-dependent. The main site of radiation damage is the hypothalamus rather than the pituitary, although the latter may be affected directly.

Adolescent↗

PubMed1997

MIB1 immunopositivity is associated with rapid regrowth of pituitary adenomas.

Pituitary adenomas are generally regarded as benign tumours, but they may recur. We identified eight patients with pituitary adenomas that showed rapid regrowth within 2 years of initial surgery. We estimated the percentage of cells in each specimen that showed positive immunostaining for MIB1 (a novel anti-Ki-67) and compared the values to those of 40 adenomas that showed no regrowth. The mean MIB1 index for 40 adenomas that showed no evidence of regrowth was 0.19 +/- 0.06%. This was significantly (p < 0.0001) lower than that for adenomas that showed rapid regrowth (1.27 +/- 0.31%), based on the initial resected specimens. Immediately after detection of rapid regrowth and in adenomas that were resistant to bromocriptine or irradiation, the MIB1 index was always greater than 1.0%. Most patients with rapidly regrowing adenomas were well controlled by radiation therapy. Our results suggest that a MIB1 index greater than 1.0% may be a useful predictor of rapid regrowth of pituitary adenomas and may be useful for planning of therapy.

Adenoma↗

PubMed2002

Neurohypophyseal germinoma histologically misidentified as granulomatous hypophysitis.

We report a case of neurohypophyseal germinoma appearing as predominantly granulomatous reaction in the first histological examination. A 12-year-old boy presented with diabetes insipidus, panhypopituitarism, and bitemporal hemianopsia. Transsphenoidal exploration for the intrasellar mass lesion extending to the suprasellar region was performed in May 1999. Histological examination revealed granulomatous hypophysitis and corticosteroid therapy was initiated. Six months later, the lesion relapsed despite corticosteroid therapy. Subtotal removal of the lesion was performed via an anterior interhemispheric approach in December 1999. Histological examination revealed typical germinoma. Subsequently, the patient underwent irradiation of 20 Gy to the tumour site and 24 Gy to the whole brain. Magnetic resonance imaging confirmed tumour remission. We must consider the possibility of neurohypophyseal germinoma in patients with granulomatous hypophysitis which does not respond to corticosteroid therapy, and perform re-exploration for more specimens to achieve the correct diagnosis.

Adolescent↗

PubMed1990

[The results of the radiation treatment of cervical cancer using low, sensitizing doses of radiation].

Combined radiation treatment for cervical cancer is associated with radiation injury to the intestine, bladder, hemopoietic system and suppression of T-system, nonspecific immunity and thyroid function. Modified gamma-ray teletherapy was suggested which included low-dose (0.1 Gy) sensitizing irradiation of tumor and zones of regional dissemination prior to delivering therapeutic dose (1.9 Gy). The procedure assured lower incidence of radiation-induced reactions and complications, leukopenia and T-lymphocyte function suppression, stimulated nonspecific resistance and thyrotropic function of the pituitary, and provided normal function of the thyroid. As a result, five-year survival rate in patients with stage III cancer increased by 14%.

Adult↗

PubMed2001

Relative contributions of inferior petrosal sinus sampling and pituitary imaging in the investigation of children and adolescents with ACTH-dependent Cushing's syndrome.

Selective transsphenoidal microadenomectomy is the first line treatment of childhood Cushing's disease, with accurate preoperative localization of the corticotroph adenoma an important step in its investigation. Inferior petrosal sinus sampling (IPSS) for ACTH after CRH stimulation is a recognized investigation in adults, but there are few data in the pediatric age range. We report the relative contributions of IPSS and pituitary imaging in 11 patients, aged 10.7-18.8 yr, presenting with Cushing's disease. All underwent transsphenoidal surgery (TSS). IPSS was performed without complication. Sampling was from the inferior petrosal sinuses in 7 patients and the high jugular veins in 4 (patients 2, 4, 5, and 10). The central to peripheral ACTH (IPS/P) ratios were more than 2 (2.5-157.2) in 10 of 11 patients, confirming central ACTH secretion. In 3 patients with high jugular sampling, IPS/P ratio ranged from 2.5-21.1. In the fourth patient with high jugular sampling (IPS/P ratio, 0.95), a central adenoma was identified surgically, and the patient was cured after TSS. The interpetrosal sinus ACTH gradient (IPSG) was more than 1.4 (2.1-20.8) in 10 patients, indicating lateralization of ACTH secretion to the right side in 6 patients and to the left in 4. IPSG ratios were 2.1-8.5 in 3 patients with high jugular sampling. Pituitary imaging (computed tomography and or magnetic resonance imaging) was reported to identify an adenoma in 5 of 11 patients. At operation a tumor was visualized by the same surgeon in all 11 cases. In 9 patients with lateralization on IPSS, the correct side of the tumor was confirmed at surgery. In a 10th patient with a negative IPSG, a central tumor was present. Thus, IPSS gave a 91% prediction of correct tumor localization. In only 1 of 5 patients with an adenoma reported on pituitary imaging was this localization confirmed at surgery, a prediction rate of only 9%. After TSS, 8 patients were cured, 1 was in remission, and 2 required pituitary irradiation. In 73% of patients undergoing IPSS, localization of the adenoma was followed by surgical cure or remission. Pituitary scanning was therefore relatively unhelpful in localizing the adenoma. In experienced hands, however, IPSS was feasible in this age group, safe, and strongly predictive of the site of the adenoma, leading to a high rate of successful surgical outcome.

Adenoma↗

PubMed1985

Six year remission of ACTH-dependent Cushing's syndrome using bromocriptine.

A patient with ACTH-dependent Cushing's syndrome remained in clinical and biochemical remission six years after pituitary irradiation and while on bromocriptine therapy. When bromocriptine was discontinued urinary free cortisol values became elevated, and were not suppressed by dexamethasone. After reintroduction of the drug, remission was again obtained. It is concluded that bromocriptine is responsible for continuing longterm remission in this case. The possible use of bromocriptine as an adjunctive therapy in ACTH-dependent Cushing's syndrome is discussed.

Adrenocorticotropic Hormone↗

PubMed2000

Gamma knife radiosurgery as a primary treatment for prolactinomas.

OBJECT: The purpose of this study was to estimate the efficacy of gamma knife radiosurgery (GKS) in controlling tumor growth and endocrinopathy associated with prolactinomas. METHODS: Between 1993 and 1997, 164 of 469 patients with pituitary adenomas treated by GKS harbored prolactinomas. The dose to the tumor margin ranged from 9 to 35 Gy (mean 31.2 Gy), and the visual pathways were exposed to a dose of less than 10 Gy. The mean tumor diameter was 13.4 mm. The mean follow-up time for 128 cases was 33.2 months (range 6-72 months). Tumor control was observed in all but two patients who underwent surgery 18 and 36 months, respectively, after GKS. Clinical cure was achieved in 67 cases. Clinical improvement was noted with a decrease in the hyperprolactinemia after GKS. Nonetheless, in 31 (29%) of 108 patients who were followed for more than 2 years no improvement in serum prolactin levels was demonstrated, although this could be normalized by bromocriptine administration after treatment. Nine infertile women became pregnant 2 to 13 months after GKS and all gave birth to normal children. There was no visual deterioration related to GKS. Five women experienced premature menopause. In these patients there was subtotal disappearance of the tumor and an empty sella developed. CONCLUSIONS: Gamma knife radiosurgery as a primary treatment for prolactinomas can be safe and effective both for controlling tumor growth and for normalization of prolactin hypersecretion. A higher margin dose (> or = 30 Gy) seemed to be associated with a better clinical outcome. Gamma knife radiosurgery may make prolactinomas more sensitive to the bromocriptine.

Humans↗

PubMed2004

Expression of PAC1 receptor in rat thymus after irradiation.

In the present work, PAC1-R (G-protein-coupled receptor specific for PACAP) was detected on cells in the normal thymus. Immunohistochemically PAC1-R was expressed strongly in stromal cells of the thymic medulla. Positive cells were also observed in the thymus of fetal and old adult rats. After 8 Gy irradiation to 9-week-old rats, PAC1-R expressions in the thymus decreased and almost recovered by day 21. The expression of PAC1-R mRNA was weak in the thymus and decreased further after irradiation. The expression almost recovered by day 28. Hip and hip/hop variants, which were not expressed in the normal thymus, were expressed in the thymus on days 3, 5 and 21 after irradiation. The expressions of IL-6 and IL-10 tended to increase initially after irradiation then decreased. Histologically, the thymic structures were destroyed on day 3 after irradiation and the thymus almost recovered by day 21. Thus PACAP is thought to be one of the important factors for cross-talk between cells involved in thymic regeneration.

Animals↗

PubMed2000

Growth hormone response to a growth hormone-releasing hormone stimulation test in a population-based study following cranial irradiation of childhood brain tumors.

Children with brain tumors are at high risk of developing growth hormone deficiency (GHD) after cranial irradiation (CI) if the hypothalamus/pituitary (HP) axis falls within the fields of irradiation. The biological effective dose (BED) of irradiation to the HP region was determined, since BED gives a means of expressing the biological effect of various irradiation treatment schedules in a uniform way. Hypothalamic versus pituitary damage as cause of GHD was distinguished in 62 patients by comparing the growth hormone (GH) peak response to an insulin tolerance test (ITT)/arginine stimulation test and the GH response to a growth hormone-releasing hormone (GHRH) stimulation test. Peak GH response to a GHRH test was significantly higher (median 7.3 mU/l; range: 0.5--79.0 mU/l) than that of an ITT/arginine test (median 4.7 mU/l; range: 0.01--75.0 mU/l) (p = 0.017). Peak GH after a GHRH test was significantly inversely correlated to follow-up time (r(s) = -0.46, p < 0.0001) and to BED (R(s) = -0.28, p = 0.03), and both were found to be of significance in a multivariante regression analysis. We speculate that a significant number of patients developed hypothalamic radiation-induced damage to the GHRH secreting neurons, and secondary to this the pituitary gland developed decreased responsiveness to GHRH following CI in childhood.

Adolescent↗

PubMed1978

Plasma steroid dynamics in Cushing's syndrome.

The dynamics of five plasma steroids were studied by CPB and RIA in twenty patients with Cushing's syndrome of differing etiologies: pituitary induced adrenal hyperplasia (10), recurrence after adrenal surgery or pituitary irradiation (4), adrenal carcinoma (4) and adrenal adenoma (2). Basal mean values of plasma steroids, showed increase of cortisol in hyperplasia and cancer groups, increase of 17-hydroxyprogesterone (17-OH-P) in recurrence and cancer groups and decrease of testosterone in male patients. In hyperplasia, the changes in 11-desoxycortisol and 17-OH-P (respectively by CPB assay and RIA after LH-20-Sephadex separation) were the reverse of those for cortisol 2 h and 24 h after metyrapone administration. Adrenalectomy determined in all but one patients, significant decrease of cortisol and in male patients, parallel gradual increase of testosterone.

Adrenal Gland Neoplasms↗

PubMed1985

Precocious puberty secondary to cranial irradiation for tumors distant from the hypothalamo-pituitary area.

This retrospective study is the first report of the occurrence of central precocious puberty in 6 children having received cranial irradiation. Pubertal development took place at a mean age of 7 5/12 years (6 10/12-7 10/12 years in 5 girls and at 9 years in 1 boy). They had received 2,400-4,500 rad at a mean age of 5 2/12 years. In addition, 5 children had GH deficiency so that their growth spurt was blunted and 3 of them were left with an extremely short stature. This condition would require a therapeutic approach combining the use of an LHRH analogue and hGH therapy when necessary in order to protect from too rapidly progressing bone maturation.

Adolescent↗

PubMed1987

Inappropriate secretion of thyrotropin by the pituitary.

Inappropriate secretion of thyrotropin (IST) is characterized by elevated serum free thyroid hormone and unsuppressed thyrotropin (TSH) levels, and results from either a TSH-secreting pituitary tumor (nIST) or a selective resistance to thyroid hormone action (nnIST). Although in most patients TSH levels are definitely high, in a quarter of the cases they are within the 'normal range'. In some of these cases, TSH had an elevated biologic activity and an apparent molecular weight smaller than in normals. The current availability of ultrasensitive TSH immunoradiometric assay, able to distinguish suppressed from unsuppressed TSH levels enables the recognition of the disease. The distinction between nnIST and nIST rests on clinical, neuroradiological, and biochemical criteria, the most useful of which are the alpha-subunit:TSH molar ratio (increased in nIST), and the evaluation of the TSH responses to thyrotropin-releasing hormone and high doses of 3,5,3'-triiodothyronine, both qualitatively normal in nnIST, while absent in nIST. The therapy of choice for patients with nIST is pituitary surgery, followed by irradiation in case of surgical failure. Chronic administration of bromocriptine is effective in a minority of cases. The long-acting somatostatin analogue SMS 201-995 has given promising results in 2 patients. In nnIST, bromocriptine is frequently uneffective, while small doses of 3,5,3'-triiodothyronine or 3,5,3'-triiodothyroacetic acid, a thyroid hormone derivative with a strong inhibitory effect on TSH secretion but poor thyromimetic activity on peripheral tissues, are effective in controlling TSH hypersecretion.

Humans↗

PubMed1981

Endocrine function in children with intrasellar and suprasellar neoplasms: before and after therapy.

The records of 23 children with intrasellar and suprasellar neoplasms were reviewed for the results of endocrine evaluations before and after treatment with surgery, irradiation, and/or chemotherapy. Deficiency of at least one pituitary hormone was present in 13 patients before treatment and in 22 patients after treatment. Growth hormone deficiency, the most common endocrine abnormality in the pretreatment period, was present in 12 of 17 patients before treatment and in 17 of 21 patients after treatment. In the posttreatment period, thyroid-stimulating hormone deficiency was as common as growth hormone deficiency and was found in 17 of 21 patients evaluated. Hypothalamic-pituitary-gonadal dysfunction and deficiencies of adrenocorticotropic hormone and antidiuretic hormone also occurred in both the pretreatment and posttreatment periods, but were less common.

Adenoma, Chromophobe↗

PubMed1975

Influence of adrenalectomy, total body x-irradiation and dexamethasone on the amount of CRF-granules and "classical" neurosecretory material in the rat neurohypophysis.

In 195 female Wistar rats the influence of adrenalectomy, total body X-irradiation and dexamethasone treatment on the amount of CRF-granules in the external zone of the median eminence and "classical" neurosecretory material (NSM) in the internal zone of the median and in the posterior lobe of the hypophysis has been studied. In the normal rat only very few CRF-granules occur. 15 days after adrenalectomy increased amounts of CRF-granules but normal amounts of "classical" NSM are found. X-irradiation leads to a slight diminishment of "classical" NSM in normal rats. In adrenalectomized animals X-irradiation causes no changes in the amount of "classical" NSM but a marked decrease in the amount of CRF-granules. Application of dexamethasone from the 15th to 18th day after adrenalectomy enhances the augmentation of CRF-granules in irradiated and non-irradiated rats but does not influence the amount of "classical" NSM. The findings show that no correlation exists between the quantitative changes of CRF-granules and "classical" NSM under the experimental conditions used. Therefore it is to be assumed that the release of the two substances is regulated by different control mechanisms and that the substances have a different functional significance. The observations do not exclude the possibility that CRF-granules and "classical" NSM are biochemically identical.

Adrenalectomy↗

PubMed1992

Intracranial germ-cell tumor with synchronous lesions in the pineal and suprasellar regions: report of six cases and review of the literature.

The features of intracranial germ-cell tumor with synchronous lesions in the pineal and suprasellar regions (GCTSPS) in six patients were investigated. GCTSPS accounted for 12.8% of all germ-cell tumors (GCT) in our brain tumor study group. In all cases, the initial symptoms were attributable to the suprasellar lesion, and symptoms due to the pineal GCT developed only after admission. Five of the six cases were histologically diagnosed as germinoma. In all cases, tumors of both regions disappeared after irradiation, resulting in no recurrence for an average of 55.3 months. Our experience and reports in the literature suggest that GCTSPS is highly sensitive to radiation in most cases, although some reports indicated that recurrence is frequent after radiation therapy alone. It is suggested that histological diagnosis in one of the GCTSPS lesions is undertaken to make a plan for the following treatment.

Adolescent↗

PubMed1982

Cyclic AMP and cyclic GMP response to stress in brain and pituitary: stress elevates pituitary cyclic AMP.

Male rats were exposed to six stressors (saline injection, cold, forced running, Formalin injection, immobilization, electric footshock) for 15, 30, or 60 min. Following sacrifice by microwave irradiation, cyclic AMP and cyclic GMP levels were measured in pituitary, pineal and 8 regions of rat brain. All stressors except saline increased plasma corticosterone, plasma prolactin and pituitary cyclic AMP levels compared to control animals. The magnitude of the pituitary cyclic AMP response was highly correlated with the intensity of the stress as determined by the levels of plasma prolactin. Electric footshock increased pituitary cyclic AMP levels over 10 fold and plasma prolactin over 60 fold. Cyclic AMP levels in other brain regions were not altered. Cerebellar cyclic GMP was increased only by stressors that involved increased motor activity.

Animals↗

PubMed1980

Adrenal myelolipoma associated with Cushing's disease.

An 18-year-old man with a history of Cushing's disease was treated with a total right and a near total left adrenalectomy in 1956. Pathologic examination of the operative specimen revealed bilateral adrenal hyperplasia. After 13 years, recurrence of symptoms of cortisol excess necessitated cobalt irradiation to the pituitary, which was without clinical effect. After an initial response to the adrenolytic agent, o,p'-DDD, partial relapse occurred. At this time, the recognition of an abdominal mass prompted abdominal exploration revealing a huge adrenal myelolipoma containing adrenal cortical cells distributed diffusely throughout the tumor. Symptoms of adrenal insufficiency developed, and adrenal steroid secretion did not respond to exogenous adrenocorticotropic hormone postoperatively. The case illustrates that adrenal myelolipomas may become very large with continued stimulation by adrenocorticotropic hormone, may contain significant amounts of adrenal cortical tissue, and may be associated with clinical hypercortisolism.

17-Hydroxycorticosteroids↗

PubMed1993

The effects on basal anterior pituitary hormone concentrations by cranial irradiation in patients with nasopharyngeal carcinoma.

Hypopituitarism occurring in patients who received external cranial radiation therapy (RT) have been increasingly recognized. Fourteen healthy patients were collected as control Group I, and 25 patients with nasopharyngeal carcinoma (NPC) were enrolled as Group II. Another 18 NPC patients were enrolled as Group III. Blood was sampled from Group I, Group IIB (before RT), Group IIA (one week after RT) and Group IIIA (1 to 1.5 years after RT). The basal samples were taken for growth hormone (GH), adrenocorticotropic hormone (ACTH), cortisol, follicle stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL), thyrotropin (TSH), triiodothyronine (T3) and thyroxine (T4). The results showed the T3 level was statistically low in Group IIB compared with Group I. The serum GH and FSH (male only) levels were higher and with statistical significance in Group IIA compared Group IIB. Both GH and ACTH levels decreased and PRL increased with statistical significance in Group IIIA compared with Group IIA. The ACTH decreased with statistical significance in Group IIIA compared with Group IIB. Clinical damage to the pituitary is usually manifested months to years after RT. Therefore, a careful exclusion of these glands from radiation treatment fields is recommended whenever possible.

Adult↗