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PubMed1984

Cushing's syndrome produced by a bronchial carcinoid tumor.

A case of bronchial carcinoid tumor with ectopic corticotropin production is described. Cushing's syndrome refractory to therapy, including pituitary irradiation and hypophysectomy, had been present for 12 years before the neoplasm was discovered at autopsy. The tumor was a small nodule localized in the pulmonary parenchyma and an adjacent hilar lymph node. Corticotropin, serotonin, and neuron-specific enolase were localized in the neoplasm by immunoperoxidase staining.

ACTH Syndrome, Ectopic↗
PubMed2000

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↗
PubMed1986

Effective and lasting growth-hormone suppression in active acromegaly with oral administration of somatostatin analogue SMS 201-995.

Oral administration of the long-acting somatostatin analogue, SMS 201-995 (Sandoz), was assessed in five patients with active acromegaly, four of whom had not responded to pituitary irradiation. Doses of 4-8 mg three times daily lowered mean 24 h growth-hormone concentrations by over 50% in every case, with suppression to below 10 mU/l for several hours after the morning dose. Despite effective suppression of serum insulin levels, deterioration in glucose tolerance was very slight, and the drug had no side-effects. Orally administered SMS 201-995 avoids the need for multiple daily injections and is potentially valuable in the medical treatment of acromegaly.

Acromegaly↗
PubMed2001

Fractionated stereotactically guided radiotherapy and radiosurgery in the treatment of functional and nonfunctional adenomas of the pituitary gland.

PURPOSE: We evaluated survival rates and side effects after fractionated stereotactically guided radiotherapy (SCRT) and radiosurgery in patients with pituitary adenoma. METHODS AND MATERIALS: Between 1989 and 1998, 68 patients were treated with FSRT (n = 63) or radiosurgery (n = 5) for pituitary adenomas. Twenty-six had functional and 42 had nonfunctional adenomas. Follow-up included CT/MRI, endocrinologic, and ophthalmologic examinations. Mean follow-up was 38.7 months. Seven patients received radiotherapy as primary treatment and 39 patients received it postoperatively for residual disease. Twenty-two patients were treated for recurrent disease after surgery. Mean total dose was 52.2 Gy for SCRT, and 15 Gy for radiosurgery. RESULTS: Overall local tumor control was 93% (60/65 patients). Forty-three patients had stable disease based on CT/MRI, while 15 had a reduction of tumor volume. After FSRT, 26% with a functional adenoma had a complete remission and 19% had a reduction of hormonal overproduction after 34 months' mean. Two patients with STH-secreting adenomas had an endocrinologic recurrence, one with an ACTH-secreting adenoma radiologic recurrence, within 54 months. Reduction of visual acuity was seen in 4 patients and partial hypopituitarism in 3 patients. None of the patients developed brain radionecrosis or radiation-induced gliomas. CONCLUSION: Stereotactically guided radiotherapy is effective and safe in the treatment of pituitary adenomas to improve local control and reduce hormonal overproduction.

Adenoma↗
PubMed2001

Radiation-induced glioma presenting as diffuse leptomeningeal gliomatosis: a case report.

BACKGROUND: Leptomeningeal gliomatosis is a rare and fatal disease. METHODS: Case report. RESULTS: We report the case of a man who was presented with severe intractable headaches, lymphocytic CSF pleocytosis, and spinal leptomeningeal enhancement on contrast MRI. Meningeal biopsy demonstrated diffuse infiltration by malignant glial cells, and symptom alleviation was achieved by CSF diversion. He later developed an enhancing thalamic tumor arising within the treatment field of a remotely irradiated pituitary adenoma. Subsequent management included chemotherapy and further radiotherapy with transient response, before death from leptomeningeal and parenchymal tumor progression 16 months after diagnosis. CONCLUSION: We report a unique case embodying two rare conditions: radiation induced glioma and leptomeningeal gliomatosis. Our patient's course is novel in that symptomatic relief was achieved with CSF diversion and a combination of chemotherapy and focal radiation allowed prolonged survival.

Adenoma↗
PubMed2002

Acromegaly and cancer risk: a cohort study in Sweden and Denmark.

OBJECTIVE: Several studies have suggested that patients with acromegaly have an increased risk of benign and malignant neoplasms, especially of the colon. To further investigate this relationship we evaluated cancer risk in population-based cohorts of acromegaly patients in Sweden and Denmark. METHODS: Nationwide registry-based cohorts of patients hospitalized for acromegaly (Denmark 1977-1993; Sweden 1965-1993) were linked to tumor registry data for up to 15-28 years of follow-up, respectively. Standardized incidence ratios (SIR) and 95% confidence intervals (CI) were calculated to estimate cancer risk among 1634 patients with acromegaly. RESULTS: The patterns of cancer risk in Sweden and Denmark were similar. After excluding the first year of follow-up, 177 patients with acromegaly had a diagnosis of cancer compared with an expected number of 116.5 (SIR = 1.5. 95% CI = 1.3-1.8). Increased risks were found for digestive system cancers (SIR = 2.1, 95% CI = 1.62.7), notably of the small intestine (SIR = 6.0, 95% CI = 1.2-17.4), colon (SIR = 2.6, 95% CI = 1.6-3.8), and rectum (SIR = 2.5, 95% CI= 1.3-4.2). Risks were also elevated for cancers of the brain (SIR = 2.7, 95% CI= 1.2-5.0). thyroid (SIR = 3.7, 95% CI = 1.8-10.9), kidney (SIR = 3.2, 95% CI = 1.6-5.5), and bone (SIR= 13.8, 95% CI= 1.7-50.0). CONCLUSIONS: The increased risk for several cancer sites among acromegaly patients may be due to the elevated proliferative and anti-apoptotic activity associated with increased circulating levels of insulin-like growth factor-1 (IGF-1). Pituitary irradiation given to some patients may have contributed to the excess risks of brain tumors and thyroid cancer. Our findings indicate the need for close medical surveillance of patients with acromegaly, and further studies of the IGF-I system in the etiology of various cancers.

Acromegaly↗
PubMed1997

Pituitary tumours presenting in the elderly: management and outcome.

OBJECTIVE: In elderly patients there are few data on the efficacy and safety of pituitary surgery and radiotherapy (DXT). The aim of the present study was to assess the mode of presentation, treatment and outcome of patients > 64 years with a pituitary tumour presenting to a regional neuroendocrine service. DESIGN: A retrospective case note review of all patients with a pituitary tumour, from 1986 to 1993, was performed with DXT information from computerized records. PATIENTS: Forty-four patients were identified: median age 70 (65-83) years; 25 males; followed for a mean of 34 (range 0-84) months. RESULTS: The commonest presenting symptom was with visual disturbance (24 patients) with a further 9 with asymptomatic visual field defects. Five patients had acromegaly and two prolactinoma. Thirty-two patients underwent transsphenoidal surgery (TSS) (with post-operative DXT in 14 cases) and 6 craniotomy. Two patients had DXT as the primary procedure and four were observed. Visual fields improved in 21 of 29 patients. Perioperative complications occurred significantly more often after craniotomy (5/6) than after TSS (6/32) (P < 0.01). Eight patients died during the follow-up period (three deaths tumour related; one death followed DXT). CONCLUSIONS: Pituitary adenoma is a remediable cause of visual disturbance in the elderly. Most tumours were non-functioning. Age alone is not a contraindication to active treatment particularly with transsphenoidal surgery and radiotherapy.

Adenoma↗
PubMed1998

Cognitive dysfunction in patients with pituitary tumour who have been treated with transfrontal or transsphenoidal surgery or medication.

OBJECTIVE: This study was carried out to examine the neuropsychological status of patients treated for pituitary tumour by transfrontal surgery, transphenoidal surgery or medical treatment only, with or without radiotherapy. DESIGN AND MEASUREMENTS: Three groups of 23 patients who had been treated for pituitary tumour were compared with 23 healthy controls on a range of neuropsychological measures. The surgical patients were also subdivided into two groups and compared. The neuropsychological measures were standardized psychological tests designed to assess aspects of attention, memory and executive function. PATIENTS: The patients were those who had been treated with transfrontal surgery (n = 23), transsphenoidal surgery (n = 23) and medication only (n = 23). The groups did not differ with respect to age, education or premorbid ability level as assessed by the National Adult Reading Test. All participants were free of known sources of cognitive impairment other than pituitary tumour. RESULTS: Comparison of the four groups revealed that nearly half of the transfrontal, one-third of the transsphenoidal and one-quarter of the non-surgical group had three or more neuropsychological tests scores below the 10th percentile compared to less than 5% of the controls. Impairments in memory and executive function were found in both surgical groups. The non-surgical patients appeared to have problems only on tasks requiring high levels of cognitive processing. Differences were found between the two surgical groups with respect to the severity of the cognitive impairment, the transfrontal patients having more severe impairment than the transsphenoidal. No significant negative effects on cognitive functioning were associated with radiotherapy; however, transfrontal surgery patients who had not been treated with radiotherapy were found to be more impaired than other patients. This was thought to be related to radical surgery. CONCLUSIONS: Many patients with treated pituitary tumour suffer significant cognitive impairment. The severity and nature of impairment differs between treatment groups, although the cause of this could not be addressed by this study. Recommendations are made for future research and clinical practice.

Adult↗
PubMed2001

The diagnosis of growth hormone deficiency (GHD) in successfully treated acromegalic patients.

Due to persistent qualitative abnormalities in GH secretion following treatment, and lack of a sensitive marker of GHD in mid-adult life it is extremely difficult to diagnose GHD in treated acromegalic patients. The diagnosis of GHD in patients with pituitary disease relies on provocative tests of GH reserve. Arginine releases GH by reducing somatostatin inhibition of GH release, whereas GH secretagogues (GHS) affect GH release by direct stimulation of the GHS receptor, though an intact GH releasing hormone (GHRH) axis is a prerequisite. The peak GH response to insulin-induced hypoglycaemia and arginine in acromegalic patients, in whom basal serum GH levels of less than 5 mU/l have been achieved, is greatly diminished in those treated by hypothalamo-pituitary irradiation. We aimed to study the response of successfully treated acromegalic patients to the growth hormone secretagogue hexarelin in view of its different putative mechanism of action, and in addition, to determine whether it has any value in the diagnosis of GH deficiency in this subset of patients. Nineteen acromegalic patients, in whom mean serum GH levels below 5 mU/l have been achieved through treatment, were recruited. Eight of the patients had been treated by surgery alone (Group A) and 11 had received primary or postoperative irradiation (Group B). All patients underwent 20 min blood sampling to provide a 24-h GH profile. Serum IGF-I was measured from a sample drawn between 0900 h and 1000 h. On a second visit arginine 20 g/m2 was infused over 30 min, blood samples were taken before commencing the infusion and at 30-min intervals thereafter for 180 min. At the final visit hexarelin 1.5 mcg/kg was administered as an intravenous bolus at t = 0. Blood was drawn at 15-min intervals from - 30 to 180 min. All patients in group A showed an increment in serum GH following hexarelin (DeltaGHHEX) > 20 mU/l, a normal response to arginine, and a mean 24-h GH > 0.5 mU/l. In group B only 4/11 achieved a DeltaGHHEX > 20 mU/l, 5/11 producing a response of < 2 mU/l. Four of the five patients with a DeltaGHHEX < 2 mU/l were also demonstrated to have a mean 24-h GH of < 0.5 mU/l and serum IGF-I SDS < + 0.5. All four patients in Group B who achieved a DeltaGHHEX > 20 mU/l, were observed to show an absent or minimal GH response to arginine. Despite loss of the GH response to arginine, the DeltaGHHEX is retained in a proportion of those patients in whom "safe" GH levels were achieved following irradiation. From the putative mechanisms of action of these provocative agents a plausible explanation would be that the GHRH axis is more resilient than endogenous somatostatin-secreting neurones to radiation-induced damage. Furthermore, GH secretagogues may have a role, in combination with serum IGF-I levels, in the diagnosis of GH deficiency in treated acromegaly.

Acromegaly↗
PubMed2002

Cerebrovascular mortality in patients with pituitary adenoma.

OBJECTIVE: To assess cerebrovascular mortality in a UK cohort of patients with pituitary adenoma known to have increased incidence of cerebrovascular accidents (CVA). METHODS: A total of 334 patients treated at the Royal Marsden Hospital (RMH) between 1962 and 1986 with surgery and postoperative radiotherapy were followed up via the NHS Central Register (NHSCR) to identify deaths and emigrations. The causes of death were assessed by NHSCR-based death certificates and coded according to the 9th revision of ICD. Follow-up was censored at age 85, on emigration or cancellation of NHSCR. Thirteen patients could not be traced. A total of 4982 person-years was accumulated in the cohort. Expected numbers of deaths were computed from the national age-, sex- and period-specific mortality rates for England and Wales. RESULTS: In the pituitary adenoma cohort, 128 deaths were observed compared to 80.9 expected [relative risk (RR) of death 1.58 (95% CI: 1.32-1.90)]. There were 33 cerebrovascular deaths compared with 8.04 expected (RR 4.11, 95% CI 2.84-5.75). Three deaths were from subarachnoid haemorrhage compared to 0.54 expected (RR 5.51, 95% CI 1.14-16.09). There was an increased cerebrovascular mortality in women (RR 6.93, 95% CI 4.29-10.60) compared to men (RR 2.4, 95% CI 1.24-4.20; P = 0.002) and in patients having debulking surgery (RR 5.19, 95% CI 3.50-7.42) compared to biopsy/no surgery (RR 1.33, 95% CI 0.27-3.88; P = 0.02). The RR in patients with nonsecretory tumours was 3.65 (95% CI 2.26-5.58), compared with 5.23 (95% CI 2.25-10.30) in secretory tumours (P = 0.4). The effect of age at radiotherapy was not significant (P = 0.4). CONCLUSION: Patients with pituitary adenoma treated with surgery and radiotherapy have an increased risk of cerebrovascular mortality compared to the general population, which mirrors the increased incidence of CVA. The possible risk factors include hypopituitarism, radiotherapy and extent of surgery but none are at present proven causes. The evaluation of new treatment strategies should not only assess intermediate end-points of tumour and endocrine control but should concentrate on long-term survival with particular emphasis on CVA incidence and mortality.

Adenoma↗