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PubMed1985

Different responses of growth hormone secretion to guanfacine, bromocriptine, and thyrotropin-releasing hormone in acromegalic patients with pure growth hormone (GH)-containing and mixed GH/prolactin-containing pituitary adenomas.

There is great variability in the GH secretory responses to different stimuli in patients with acromegaly. In the present study, we compared the effects on GH secretion of two compounds (bromocriptine and TRH), which presumably act directly at the pituitary level, with the effect of the centrally acting alpha-adrenergic agonist guanfacine in 14 untreated acromegalic patients. These in vivo responses of GH release were correlated with the results of immunocytochemical studies of the pituitary adenomas. In nine patients with pure GH-containing adenomas, GH secretion was suppressed by bromocriptine by more than 50% in one patient, while TRH stimulated GH release by more than 100% in another patient. Guanfacine (2 mg, orally) did not elicit a change in circulating GH levels in any of these nine patients. In the group of five patients with mixed GH/PRL-containing adenomas, however, bromocriptine suppressed GH levels by more than 50% in all patients, and TRH stimulated GH release by more than 100% in four of them. Guanfacine stimulated GH secretion significantly in four of these five patients. Guanfacine inhibited GH secretion significantly in five other acromegalic patients who had been treated 5-10 yr previously by external pituitary irradiation. We conclude that in acromegaly, the presence of PRL within the GH-secreting pituitary adenoma makes GH secretion more sensitive to bromocriptine and TRH, while normal sensitivity to hypothalamus-mediated stimulation (alpha-adrenergic agonist) is retained to some extent. In contrast, pure GH-secreting tumors responded little or not at all to bromocriptine, TRH, or guanfacine.

Acromegaly↗
PubMed1988

Preoperative treatment of acromegaly with long-acting somatostatin analog SMS 201-995: shrinkage of invasive pituitary macroadenomas and improved surgical remission rate.

Ten patients with previously untreated acromegaly and invasive pituitary macroadenomas were treated with the long-acting somatostatin analog SMS 201-995 (Sandoz) for 3-30 weeks before transsphenoidal or subfrontal pituitary adenomectomy. Preoperatively, treatment with SMS 201-995 reduced mean 24-h plasma GH concentrations from 8.5-66.7 to below 4.6 micrograms/L in eight patients and by 60-80% in the remaining two patients. Pituitary tumor size decreased 20-54%. Morphologically, the tumors showed decreased total cell, cytoplasmic, and nuclear areas; varying degrees of perivascular fibrosis; and dense granularity. Postoperatively, plasma GH and insulin-like growth factor I concentrations fell into the normal range, and GH dynamics became normal in eight patients. In the remaining two patients mild GH hypersecretion persisted after surgery (mean fasting and random plasma GH, 6.1 and 7.9 micrograms/L), and in one of them GH secretion became normal 1 yr after pituitary irradiation. Thus, preoperative administration of SMS 201-995 consistently induced shrinkage of GH-producing pituitary tumors, and the apparent remission rate was high in the treated patients.

Acromegaly↗
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↗
PubMed1980

Glycoprotein hormone alpha subunit secretion by pituitary adenomas: influence of external irradiation.

In ninety-nine patients with pituitary adenomas, forty-six with acromegaly, the serum level of the glycoprotein hormone alpha subunit was elevated in eighteen cases. Thirteen of these were acromegalic and one had an FSH-producing tumour. Alpha levels varied little during the day, from one day to the next and over a 6 month period. In twenty-five patients with a variety of other hypothalamic-pituitary disorders examined, one patient with a craniopharyngioma had a mildly elevated alpha level. External pituitary irradiation was followed by an acute and often transient fall in alpha level in several of these patients. Of the fifty-four patients with pituitary adenomas who had received external irradiation before testing, only five had elevated alpha subunit levels compared with thirteen patients of the forty-five who had not been irradiated. This difference in incidence of elevated alpha level was statistically significant (P less than 0.025). We conclude that external irradiation may reduce alpha subunit level chronically in many patients with pituitary adenoma.

Acromegaly↗
PubMed1976

Recurrent hyperthyroidism in an acromegalic patient previously treated with proton beam irradiation: Graves' disease as probable etiology based on follow-up observations.

A 56-year-old woman presented in 1973 with hyperthyroidism and partial anterior pituitary insufficiency. Three years before she had undergone pituitary irradiation for acromegaly and hyperthyroidism, the latter was attributed at the time to excessive TSH secretion because of elevations in plasma TSH. During the present 11/2 years of observation, TSH levels were appropriately low and did not respond to iv TRH when the patient was hyperthyroid. Moreover, they did not rise during treatment, even as the patient became borderline hypothyroid. It is concluded that hyperthyroidism probably has always been due to Graves' disease.

Acromegaly↗
PubMed1976

Prolactin-secreting pituitary tumor in early adolescence: hormonal and electron microscopical studies.

A 13-year-old boy was evaluated for an enlarged sella. There were no consistent visual field defects, and carotid arteriograms and pneumoencephalograms showed no extrasellar abnormality. The endocrine workup demonstrated a subnormal growth hormone reserve. The only other, but most striking abnormality, was an excessively high serum prolactin level, which was partially suppressed with levodopa. A chromophobe pituitary tumor was removed that had histological features suggestive of malignant neoplasm. Characteristics of a prolactin-secreting tumor were confirmed by electron microscopy. The serum prolactin levels decreased substantially after surgery and further after a course of pituitary irradiation; however, they continue to be elevated above normal. Prolactin determinations play in integral part in the evaluation for a possible pituitary tumor-not only for diagnostic purposes, but also to provide a parameter of future tumor activity in an established case. Electron microscopical studies are helpful in identifying the tumor as source of the excessive prolactin secretion.

Adenoma, Chromophobe↗
PubMed1984

Growth hormone releasing factor: comparison of two analogues and demonstration of hypothalamic defect in growth hormone release after radiotherapy.

Human pancreatic growth hormone releasing factor (hpGHRF(1-40] stimulates the release of growth hormone in normal subjects and some patients with growth hormone deficiency. A study comparing the shorter chain amidated analogue hpGHRF(1-29) with an equivalent dose of hpGHRF(1-40) in seven normal subjects showed no significant difference in growth hormone response between the two preparations. Six patients with prolactinomas were also tested; these patients had received megavoltage radiotherapy previously but had developed growth hormone deficiency as shown by insulin induced hypoglycaemia. In all six patients 200 micrograms hpGHRF(1-40) or hpGHRF(1-29)NH2 produced an increase in the serum growth hormone concentration. These data suggest that hpGHRF(1-29)NH2 may be useful for testing the readily releasable pool of growth hormone in the pituitary and that cases of hypothalamo-pituitary irradiation resulting in growth hormone deficiency may be due to failure of synthesis or delivery of endogenous GHRF from the hypothalamus to pituitary cells.

Adult↗
PubMed1983

Hyperthyroidism due to thyrotropin-secreting pituitary tumors. Diagnostic and therapeutic considerations.

Hyperthyroidism may be caused by the inappropriate secretion of thyroid-stimulating hormone (TSH) from a pituitary tumor. Of 33 reported cases, 17 have occurred in women and 16 have occurred in men. All patients had large tumors, and secretion of a second hormone (growth hormone or prolactin) has been common. Diagnosis requires the detection of TSH in the serum when patients are clinically and biochemically hyperthyroid. Ancillary tests supporting the diagnosis include an alpha-subunit to TSH molar ratio greater than 1.0, an absent TSH response to protirelin, suppression of serum TSH (but not alpha-subunit) by glucocorticoids, and a lack of suppression of serum TSH by dopaminergic agonists. Successful treatment of this disorder requires pituitary surgery and/or pituitary irradiation.

Adolescent↗
PubMed1978

Incidence of pituitary tumors following adrenalectomy. A long-term follow-up study of patients treated for Cushing's disease.

The long-term follow-up of 21 patients who had undergone bilateral adrenalectomy for Cushing's disease has revealed eight definite and two suspected cases of pituitary tumors. The average time from adrenalectomy to the diagnosis of the pituitary tumor was 6 1/2 years, with a range of 1 1/2 to 12 years. The incidence of tumors in this study (38%) is higher than that reported by others and may reflect (1) that none of these patients received pituitary irradiation in addition to adrenalectomy, (2) the length of follow-up, and (3) the high index of suspicion and early diagnosis of pituitary tumors in recent years. These data raise the question of whether bilateral adrenalectomy alone is an acceptable form of therapy for Cushing's disease. For patients treated in this way, a life-long commitment should be made to undergo annual reexamination for the possible occurrence of a pituitary neoplasm.

Adenoma↗
PubMed1980

Pituitary surgery for endocrine disorders.

The use of pituitary surgery for patients with over-production of growth hormone, corticotrophin and prolactin is reviewed. The value of specialized neuroradiological techniques is discussed including computerized tomography, air-encephalography and cavernous sinus venography. The indications for transcranial as opposed to trans-sphenoidal surgery are considered. The place of trans-sphenoid surgery in the treatment of acromegaly is emphasized and the indications for surgical treatment are reviewed. The two syndromes due to over-production of ACTH are considered--Cushing's disease and Nelson's syndrome. The increasing use of pituitary surgery for the treatment of Cushing's syndrome due to increased ACTH production is noted, but a warning is given about the small ACTH-secreting pulmonary carcinoid tumour that may closely mimic Cushing's disease. The difficulties encountered in trying to treat patients with Nelson's syndrome are stressed. It is recommended that in the rate case where total adrenalectomy is required in Cushing's disease, pituitary irradiation should be given before or shortly after adrenalectomy. The present position relating to the surgical treatment of the small prolactin-secreting pituitary tumour is reviewed. Published data and personal experience suggests that for many of these patients, treatment with bromocriptine is preferable to trans-sphenoidal surgery. Large prolactinomas usually need transfrontal surgery and X-ray therapy, sometimes followed by bromocriptine treatment. The need for steroid cover for pituitary surgery is discussed and it is suggested that a glucocorticoid with less salt-retaining action than cortisol should be used. The importance of post-operative endocrine assessment is emphasized and a convenient method suggested. The incidence of complications after transsphenoidal surgery is low, although panhypopituitarism occurred in 14% of the cases reported.

Acromegaly↗
PubMed2003

Gonadal function and pubertal development after treatment of a childhood malignancy.

As survival rates for childhood cancer have improved, the importance of assessing gonadal dysfunction caused by alkylating agents and radiotherapy in children treated for cancer has increased. Infertility is the major long-term side effect of chemotherapy (CT) in males, whereas Leydig cell function is less affected. Our studies confirm that prepuberty does not protect the male gonad from the late effects of CT and that protocols less gonadal-lesive (such as ABVD regimens) should be preferred. Ovaries are less affected, but early depletion of follicles and premature menopause may occur. High-dose busulfan conditioning regimens cause ovarian failure in young females. The role of gonadal irradiation is discussed: high dosages (>2000 cGy) provoke sterility, impaired testosterone secretion in males and estradiol release in females. High dosage hypothalamic-pituitary irradiation causes delayed puberty and hypogonadism in males and females, whereas lower dosages may be associated with early puberty, particularly in females.

Antineoplastic Agents↗
PubMed1986

Women with prolactinoma--effect of pregnancy and lactation on serum prolactin and on tumour growth.

Thirty-five women with prolactinoma have been investigated during 41 pregnancies and 35 lactation periods. Nine of the women had a macroadenoma; 4 of them underwent transsphenoidal microsurgery and one was treated with external pituitary irradiation before pregnancy. All nine were given bromocriptine to induce ovulation. Four women with a microadenoma became pregnant without medical treatment, one shortly after pituitary microsurgery. The other 22 women were treated with bromocriptine only for varying periods before conception. Tumour complications developed in 7 women (20%); 3 had signs of optical nerve compression and 4 showed increased sella volume after pregnancy. All women with tumour complications had been treated with bromocriptine for less than 12 months before conception. Serum prolactin (Prl) was measured every four weeks during pregnancy and after cessation of lactation. In contrast to normal pregnancy, the mean serum Prl did not increase during the second and third trimester of pregnancy in women with pretreatment serum Prl levels above 60 micrograms/l. The lactation period did not have any harmful influence on tumour development. It is concluded that neither pretreatment serum Prl nor radiological changes of the sella turcica can predict tumour development during pregnancy. Treatment with bromocriptine for more than 12 months before conception seems to reduce the risk of tumour progress.

Adenoma↗
PubMed1998

Gamma-knife surgery for secreting pituitary adenomas.

We report our preliminary results concerning 25 patients with secreting pituitary adenomas treated with stereotactic radiosurgery after partial transsphenoidal surgery and followed over a 6-36 month-period. Among the 15 acromegalic patients, a decrease of 65% in mean GH levels was achieved after 6 months and of 77% at 12 months after radiosurgery. Presently, only 3 patients (20%) are considered as in remission (mean GH and IGF1 level into the normal range). A decrease of 46% and 64% was observed at 6 and 12 months after radiosurgery in 4 patients with prolactinomas although no normalization of PRL levels occurred. Presently, 3/4 patients have individual PRL level slightly above the normal range. A normalization of Urinary Free Cortisol (UFC) was noticed in 4/6 (66%) patients with Cushing's disease within 6-12 months. No pituitary deficiency was noticed in this series with the exception of 4/25 patients (16%) who received subtotal or total pituitary irradiation for post-operative remnants of secreting adenomas poorly defined on MRI. One woman, who had undergone previously a conventional irradiation and presenting with a cavernous sinus adenoma reaching the optic nerve, developed an optic neuropathy. A second woman, with a cavernous sinus remnant, presented a cranial nerve palsy (VI) after the irradiation. We can conclude that radiosurgery using the Cobalt-60 Gamma-unit is, at least, as effective as conventional radiotherapy in the control of pituitary hormone hypersecretion from postoperative adenomas remnants with less adverse effects.

Acromegaly↗
PubMed1993

Control of prolactin-secreting macroadenomas with parenteral, long-acting bromocriptine in 30 patients treated for up to 3 years.

OBJECTIVE: We investigated the effect of intramuscular injections of long-acting bromocriptine in patients with macroadenomas. STUDY DESIGN AND PATIENTS: Thirty patients with PRL-secreting pituitary macroadenomas were treated with repeated 4-weekly intramuscular injections of 50 or 100 mg of a long-acting, repeatable bromocriptine formulation for six to 37 injections, amounting to a total of 473 injections. Twenty patients received parenteral bromocriptine as primary therapy, ten had persisting hyperprolactinemia after previous therapies including pituitary surgery (n = 7), oral bromocriptine (7), and pituitary irradiation (2). MEASUREMENTS: A PRL day profile was obtained and the patients' clinical status and history were documented, at intervals. Detailed clinical, laboratory, and radiological (pituitary nuclear magnetic resonance or computed tomography scan) evaluations were performed at baseline, after 1 injection and every 6th injection thereafter. RESULTS: In all patients PRL was suppressed from a mean +/- SEM pretreatment level of 32,620 +/- 8680 to 4480 +/- 1140 mU/I on the third day after the first injection. In 12 patients PRL levels normalized (< 400 mU/I) with the first to fourth injection, in three additional patients PRL levels normalized after 8-15 months. In 19 patients PRL was suppressed to less than 1000 mU/l. In three patients PRL did not decrease to less than 50% of pretreatment; in two of them on oral bromocriptine prior to this study there had been a comparable low efficacy. Of 28 patients with macroadenomas (median height 22 mm) tumour shrinkage was evident in 15 by nuclear magnetic resonance or computed tomography scan 28 days after the first injection, and in three additional patients after 6 months. There was further regression in seven cases after 12, 18 or 24 injections. Adenoma size (mean +/- SEM) decreased to 66 +/- 7% of the pretreatment value. The 40 adverse events noted in 20 of 30 patients during 24 hours after the first injection were similar to known side-effects of oral bromocriptine, nausea and postural hypotension being the most frequent. With repeated injections, on average 0.6 adverse events were noted per injection (mostly mild asthenia). There were no local adverse reactions at the injection site. CONCLUSION: We conclude that long-acting repeatable bromocriptine in patients with macroprolactinomas offers a safe and efficacious primary treatment that ensures compliance and gives long-term control. Adverse reactions are comparable to oral bromocriptine but subside with repeated injections.

Adolescent↗
PubMed1998

Management of pituitary tumors.

Management of pituitary tumors has improved in the past decade since the introduction of novel therapeutic agents. As a result, several treatment options are now available. Dopamine agonists are the preferred treatment for both symptomatic microprolactinomas and macroprolactinomas; these drugs result in normalization of hormone levels and tumor shrinkage in most treated patients. New formulations (such as cabergoline and parenteral bromocriptine) with prolonged duration of action offer improved compliance with treatment and cure rates. For acromegaly and adrenocorticotropin hormone (ACTH)-secreting, thyroid-stimulating hormone (TSH)-secreting, and nonfunctional adenomas, surgery often results in cure. Octreotide and the long-acting, slow-release somatostatin analogues are effective medical alternatives to or adjuvants for transsphenoidal surgery in patients with growth hormone-secreting and TSH-secreting tumors. No drug treatment is available for symptomatic nonfunctional tumors, and patients with ACTH-secreting adenomas may benefit from cortisol-lowering drugs after surgical failure. Pituitary irradiation may be required after surgery for ACTH-secreting, TSH-secreting, and nonfunctioning tumors; it is less commonly required for acromegaly. Although many pituitary tumors are successfully resected, functional adenomas may not be cured by surgery. As more-effective drugs are introduced for the management of pituitary tumors, more patients with hormone-secreting adenomas are being successfully treated medically.

Adenoma↗
PubMed1993

Bilateral adrenalectomy: low mortality and morbidity in Cushing's disease.

OBJECTIVE: We assessed the current role of bilateral adrenalectomy in the overall management strategy of hypercortisolism. DESIGN: Retrospective review of case notes. PATIENTS: Twenty-six patients (20F/6M); mean age 46 years (range 15-70 years), median duration of follow-up 5.25 years (0.6-19.1 years) who had undergone bilateral adrenalectomy at the Royal Victoria Hospital since 1972. Eighteen had had prior transsphenoidal surgery which did not control the hypercortisolism. MEASUREMENTS: Morbidity, mortality, incidence of Nelson's syndrome. RESULTS: Surgery was performed through bilateral postero-lateral incisions (20 patients) or a long epigastric incision (six patients). The mean combined weight of the adrenals at surgery was 11.2 g. Twenty patients received subcutaneous heparin and 18 antibiotic prophylaxis peri and post-operatively. There was no operative mortality. Minor complications included one post-operative wound infection and a small pneumothorax requiring drainage. Major complications occurred in two other patients, both with pre-existing invasive pituitary tumours and considered at high risk because of age and general debility. One patient had a massive pulmonary embolus and the other a subphrenic abscess post-operatively. This latter patient, the only mortality, died from an unrelated cause three years post-operatively. Six patients have subsequently undergone pituitary surgery and three have received external pituitary irradiation therapy for expanding tumours. CONCLUSIONS: Bilateral adrenalectomy, in experienced hands, is a relatively safe and useful management option in patients with hypercortisolism. Growth of a pituitary adenoma post-operatively is now the most worrying complication.

Adolescent↗
PubMed2006

Late development of intraventricular papillary pituitary carcinoma after irradiation of prolactinoma.

BACKGROUND: Intracranial dissemination of pituitary adenomas is a rare event that does not equate malignancy. Most of the cases have been reported as metastases from pituitary carcinoma. A case of papillary pituitary carcinoma developed 12 years after radiotherapy for prolactin-secreting hormone pituitary adenoma is presented. CASE DESCRIPTION: A 37-year-old woman was admitted for the second time with neurologic disturbance and hypertension. A gadolinium-enhanced magnetic resonance scan of the brain demonstrated a 50-mm enhanced mass (absent on previous studies) on the lateral ventricle, involving the left temporal lobe. The patient underwent a craniotomy and biopsy of the lesion that was consistent with pituitary carcinoma; it was immunoreactive to follicle-stimulating hormone, adrenocorticotropic hormone, pituitary tumor-transforming gene, and epithelial cell adhesion molecule. Transmission electron microscopy analysis confirmed the secretory pituitary tumor diagnosis. CONCLUSIONS: The tumor was considered a primary pituitary papillary carcinoma. The clinical course indicated that this tumor was the seedling of a pituitary tumor, although it could be interpreted as metastases from a pituitary carcinoma.

Adult↗