Large Pituitary Tumors Research Articles

Selective extradural anterior clinoidectomy for supra- and parasellar processes

Removal of the anterior clinoid process (ACP) facilitates radical removal of tumors or radical neck clipping of aneurysms in the supra- and parasellar regions by providing a wide operative exposure of the internal carotid artery (ICA) and the optic nerve and by reducing the need for brain retraction. Over a period of 3 years, anterior clinoidectomy was performed in 40 patients, 30 of whom harbored aneurysms (18 of the ICA and 13 of the basilar artery [one patient had two aneurysms]) and 10 of whom had tumors (four large pituitary tumors, four craniopharyngiomas, and two sphenoid ridge meningiomas). The ACP was removed extradurally in 31 cases and intradurally in nine cases. Extradural clinoidectomy was performed in all cases of pituitary adenoma and craniopharyngioma and in most cases of basilar artery aneurysm. Intradural clinoidectomy was performed in two cases of ICA-ophthalmic artery aneurysm, two cases of ICA-posterior communicating artery aneurysm, two cases of ICA cavernous aneurysm, one case of basilar artery aneurysm, and two cases of sphenoid ridge meningioma. The outcome was satisfactory in all patients, except for one patient who underwent clipping of a basilar tip aneurysm and suffered a thalamic and midbrain infarction. Three patients who underwent extradural clinoidectomy suffered a postoperative diminution of visual acuity or a visual field defect on the side of the clinoidectomy. These deficits may have been caused either by drilling of the ACP or by other operative manipulation of the optic nerve. Cerebrospinal fluid rhinorrhea, which required reoperation, occurred in one patient. The authors' experience suggests that the extradural technique of ACP removal is easier and less time consuming than the intradural one and provides better operative exposure. It can be used routinely in treating lesions in the supra- and parasellar regions.

Hyperprolactinaemia in males: a heterogeneous disorder.

The literature suggests that men with prolactinomas typically present with pressure effects of large pituitary tumours and/or the clinical features of hypogonadism. A definitive study of the clinical features of hyperprolactinaemia in males is, however, lacking To identity the clinical, biochemical and radiological features of hyperprolactinaemia in males. Retrospective review of the case notes of 53 adult males with prolactinoma or idiopathic hyperprolactinaemia diagnosed 1980-1995. The mean age of the patients was 41 years (range 19-75). The presenting symptom was endocrine in nature in 57% of patients (loss of libido/potency 47%, gynaecomastia 6%, galactorrhoea 2%, sparse beard growth 2%), pressure effects of pituitary tumour in 28% (headache 13%, visual loss 13%, diplopia 2%), while 15% of patients presented incidentally. On physical examination, galactorrhoea was present in 8% of patients, gynaecomastia in 23% and abnormally sparse body hair in 21%. Testicular volume was normal (> or = 15 mL) in all but two patients, both of whom had evidence of delayed pubertal development. Visual loss was present in 17% of patients. Serum prolactin ranged from 800 to 1.7 million mU/L (median 20,000 mU/L, reference range < 500), and serum testosterone from 0.7 to 19.3 nmol/L (mean 7.8 nmol/L, reference range ten-35). Pituitary imaging by computed tomography (45%) or magnetic resonance imaging (55%) demonstrated macroadenomas in 70% of patients, microadenomas in 15%, and no detectable tumour in 15% of subjects. On bromocriptine treatment (47 subjects), 89% of patients reported improved sexual function. Follow up imaging in 36 patients with abnormal scans at presentation revealed tumour shrinkage in 89% of cases. Hyperprolactinaemia in males is a heterogeneous disorder. The majority of patients have prolactin-secreting macroadenomas, but there is wide variation in presenting symptoms, physical signs and results of biochemical and imaging investigations. Bromocriptine treatment is associated with symptomatic improvement and a reduction in tumour size in most cases.

A conformal technique for irradiation of pituitary tumors

We present a CT MRI based conformal radiotherapy technique for irradiation of pituitary tumors. In this technique, the patient is treated with three isocentric non-coplanar 18 MV photon beams, with the patient in a natural supine position. The radiation ports are designed based on beam's eye view projections of the CT MRI delineated target volume. This technique spares, completely from the primary beams, the lenses and retina, and a significant portion of the optic nerves, even for large pituitary tumors. The dose distribution in brain is comparable to coplanar arc techniques for standard field sizes (5 × 5 cm 2), but superior for larger field sizes (7 × 7 cm 2). The beams in the present technique yield a low skin dose by avoiding beam overlap in entrance and exit regions, thus eliminating clinical hair loss. The treatments are easily set-up on the treatment machines, resulting in improved efficiency and accuracy.

Impaired processing of proopiomelanocortin in corticotroph macroadenomas.

The regulation and secretion of the ACTH precursors POMC and pro-ACTH were assessed directly using a 2-site immunoradiometric assay in six patients with pituitary macroadenomas (> or = 1.2 cm in diameter) and 27 patients with Cushing's disease due to a microadenoma. ACTH precursor levels were elevated in patients with macroadenomas (150-3690 pmol/L; normal range, < 5-40 pmol/L) and significantly higher than those in microadenoma patients (median, 29 pmol/L; range, 9-104 pmol/L; P < 0.001). Patients with macroadenomas also had increased ACTH precursor/ACTH ratios (15-181:1) compared with microadenoma patients (median, 5:1, range, 0.7-18.5:1; P < 0.001). ACTH precursors were unresponsive to high dose dexamethasone in patients with macroadenomas, whereas ACTH and cortisol responses varied. After CRH administration, ACTH precursors were unchanged, whereas cortisol increased significantly, suggesting the release of biologically active ACTH. This study clearly demonstrates reduced processing of POMC to ACTH in large pituitary tumors, a characteristic usually associated with tumors causing the ectopic ACTH syndrome, and provides evidence for differential regulation of ACTH precursors and ACTH by glucocorticoid and CRH. Variation in the clinical symptoms of patients with corticotroph macroadenomas may be attributable to differences in biological potency between the ACTH precursors and ACTH.

Central diabetes insipidus in a dog with a pro-opiomelanocortin-producing pituitary tumor not causing hyperadrenocorticism.

Central diabetes insipidus was diagnosed by vasopressin measurements during hypertonic stimulation in a 9-year-old male giant Schnauzer with polyuria and polydipsia. The impaired release of vasopressin was believed to be caused by a large pituitary tumor, which was visualized by computed tomography. Studies of the function of the anterior lobe and the pars intermedia of the pituitary gland were conducted, and high concentrations of ACTH and alpha-melanotrophic hormone (alpha-MSH) were found without concomitant hyperadrenocorticism. Studies of the molecular size of the immunoreactive ACTH in plasma by gel filtration revealed that most of the circulating immunoreactivity was not ACTH but its precursor pro-opiomelanocortin (POMC) and low-molecular-weight POMC-derived peptides. The pituitary tumor of this dog probably originated from melanotrophic cells of the pars intermedia. The sensitivity of the pituitary-adrenocortical system for the suppressive effect of dexamethasone was unaffected.

Pituitary apoplexy after pituitary function test: a report of two cases and review of the literature

BACKGROUND Although most of pituitary apoplexy occur spontaneous, some precipitating factors have been reported. We experienced two cases of pituitary apoplexy after a pituitary function test. METHODS In order to clarify the causal relation between the pituitary function test and apoplexy, we presented our two cases and reviewed 20 cases in the literature. RESULTS(Case 1) A 48-year-old man with a pituitary macroadenoma received an injection of 500μg thyrotropin-releasing hormone (TRH), 100μg gonadrotopin-releasing hormone (GnRH), and 0.1U/kg insulin as a preoperative test of pituitary function. Fifteen minutes later, he complained of diminished vision and headache. (Case 2) A 54-year-old man with a large cystic adenoma had an administration of 500μg TRH and 100μg GnRH. Ten minutes later, he complained of blurring of his left eye and headache. Although, in both cases, CT scans showed neither intratumoral hemorrhage nor infarction, the surgical specimen showed necrotic and hemorrhagic adenoma. The patients made excellent clinical recoveries after surgical decomposition Twenty-two reports including our two cases were reviewed in 15 cases (68%), TRH was associated with apoplexy events and seemed to be the agent most likely to have an etiologic role because of its vasoactive properties. Eighteen patients (82%) had pituitary macroadenoma with suprasellar extension. In 72% of 18 surgical cases, some recovery of visual function was obtained. CONCLUSIONS An apparent relationship between the test and the apoplexy events raises the possibility of the development of pituitary apoplexy after a pituitary function test. Unless there is a specific indication, pituitary function test should be avoided especially in patients with a large pituitary tumor.

Post-translational processing of proopiomelanocortin (POMC) in mouse pituitary melanotroph tumors induced by a POMC-simian virus 40 large T antigen transgene.

Mice harboring a transgene composed of proopiomelanocortin (POMC) gene promoter sequences (nucleotides -706 to +64) ligated to the simian virus (SV) 40 early gene encoding large T antigen developed large POMC-expressing pituitary tumors. Histologically the tumors arose from the intermediate lobe, contained nuclear SV40 T antigen and POMC peptides, but did not express other pituitary hormones. POMC processing in the pituitary tumors was indistinguishable from normal mouse intermediate lobe melanotrophs and was characterized by high proportions of acetylated and carboxyl-terminal shortened beta-endorphins, and amino-terminal acetylated alpha-melanocyte-stimulating hormone, and virtually no adrenocorticotropic hormone (ACTH)(1-39), beta-lipotropin, or POMC. The tumors contained abundant levels of mRNA for the prohormone convertase PC2 and undetectable levels of PC1. Normal mouse neurointermediate lobe also has a high ratio of PC2/PC1 expression that is distinct from the relative abundance of PC1 in anterior lobe and AtT-20 corticotroph cells. In contrast, extracts from tumors transplanted subcutaneously in nude mice contained predominantly nonacetylated forms of beta-endorphin(1-31) and -(1-27), very little ACTH(1-39), almost no corticotropin-like intermediate peptide or alpha-melanocyte-stimulating hormone, and higher proportions of intact POMC. Surprisingly, despite the less efficient proteolytic cleavage, a transplanted tumor expressed both PC1 and PC2. These studies are the first biochemical documentation of a melanotroph pituitary tumor in a rodent species and provide a new model for the investigation of pituitary oncogenesis and the molecular basis of tissue-specific prohormone post-translational processing.

Large somatostatin-insensitive thyrotrophin-secreting pituitary tumour responsive to d-thyroxine and dopamine agonists

A unique thyrotrophin (TSH)-secreting pituitary tumour is described in a patient with a history of recurrent thyrotoxicosis. Unlike other previously reported TSHomas, the tumour is insensitive to octreotide, a somatostatin analogue. It does not accumulate [111In]octreotide but expresses functional dopamine receptors and responds to the D-isomer of thyroxine, two characteristics beneficial in the management of the patient.

Incidental Visualization of Pituitary Tumors During Brain SPECT Imaging with Tc-99m HMPAO

In three female patients, 70, 72, and 81 years old, with proven large pituitary tumors, Tc-99m hexamethylpropylene amineoxime (HMPAO) brain SPECT was performed because of clinical signs of disturbed brain perfusion. In all three cases, an increased uptake was found in the pituitary tumor; to our knowledge, this has not been reported in the literature. We did not see an increased uptake in other patients with various types of pituitary tumors.

Rapid resolution of visual abnormalities with medical therapy alone in patients with large prolactinomas

Large prolactin-secreting pituitary adenomas with suprasellar extension are often complicated by visual field defects, for which surgical decompression is the accepted treatment. However, surgical management of large prolactinomas is often not curative. This report describes a group of six unselected male patients who presented with visual field defects and reduced visual acuity due to large pituitary tumours with suprasellar extension. All six patients also had loss of libido and/or impotence. A rapid serum prolactin estimation enabled the diagnosis of prolactinoma to be made, and CT revealed a large pituitary adenoma with suprasellar extension. The patients were treated with bromocriptine, in doses increasing from 2.5 to 20 mg daily, as the sole therapy. Symptoms were relieved and serum prolactin levels were restored to normal or near normal; visual field defects resolved and visual acuity recovered in all patients. A repeat CT showed evidence of tumour shrinkage especially of the suprasellar extension, in all the patients. A diagnosis of prolactinoma should always be considered in a patient with a large pituitary tumour. The clinical history and a rapid prolactin assay will confirm the diagnosis. Treatment with bromocriptine leads to rapid improvement in perimetry and visual acuity as well as tumour shrinkage, obviating the need for pituitary surgery.

Pituitary tumor size, neurologic signs, and relation to endocrine test results in dogs with pituitary-dependent hyperadrenocorticism: 43 cases (1980-1990)

Summary Pituitary neoplasm was identified in 43 dogs with pituitary-dependent hyperadrenocorticism via necropsy (n = 33), diagnostic imaging with computerized tomography or magnetic resonance imaging (n = 5), or diagnostic imaging and necropsy (n = 5). All dogs had clinical signs and clinicopathologic test results typical of hyperadrenocorticism. Thirty-seven dogs had grossly visible pituitary tumors, and 6 dogs had microscopic pituitary tumors. Fifteen dogs had developed neurologic signs typical of those resulting from an enlarging pituitary mass. Twenty-three dogs had pituitary tumors ≥ 1 cm in diameter. Provocative testing of the pituitary-adrenocortical axis was performed on all dogs. Dogs with grossly visible pituitary tumors and dogs with neurologic signs had Significantly (P &lt; 0.05) higher mean plasma endogenous acth concentrations, compared with values from dogs with microscopic tumors and dogs without neurologic signs, respectively. Dogs with grossly visible pituitary tumors and dogs with tumors ≥ 1 cm in diameter had Significantly (P &lt; 0.05) lower adrenocortical responsiveness to exogenous acth, compared with dogs with microscopic pituitary tumors and dogs with tumors &lt; 1 cm in diameter, respectively. Despite these differences, there was overlap between test results among dogs. On the basis of endocrine test results, it would appear difficult to distinguish dogs with pituitary-dependent hyperadrenocorticism and large pituitary tumors from those with pituitary-dependent hyperadrenocorticism and microscopic pituitary tumors prior to onset of neurologic signs.

Growth hormone secreting pituitary carcinoma: a case report and literature review

Only five cases of growth hormone secreting pituitary carcinoma have been documented. We present a 49-year-old West Indian male with grossly elevated plasma growth hormone (760-10,400 mU/l), and a large aggressive pituitary tumour that continued to grow despite repeated pituitary surgery, radiotherapy and medical therapy (bromocriptine and somatostatin analogue). Thirteen years after diagnosis the patient died secondary to left ventricular failure. A post-mortem revealed a large locally invasive pituitary tumour, but in addition numerous tumour seedlings within the cerebrospinal fluid space, and a solitary intraparenchymal tumour deposit within the right temporal lobe, clearly separate from the primary tumour. Pituitary carcinoma should be considered in any acromegalic with grossly elevated plasma growth hormone levels who fails to respond to conventional therapy.

Modern management of pituitary prolactinomas

Although any form of pituitary tumour, either hormone-producing or non-functioning, can occur in women of reproductive age the most important clinically, and by far the most prevalent, are prolactin secreting pituitary tumours — prolactinomas. It is a fascinating phenomenon that the identification of prolactin as a hormone distinct from pituitary growth hormone, the availability of reliable radioimmunoassays for serum prolactin and the development of effective medical treatment to control hyperprolactinaemia all occurred virtually simultaneously in the early 1970s. Since then much has been learned about the pathogenesis, natural history and management of prolactinomas although the aetiology of these tumours still remains obscure. In the following pages the management of pituitary prolactinomas will be discussed with particular reference to induction of ovulation in women with hyperprolactinaemic amenorrhoea. There is persuasive evidence that medical management of hyperprolactinaemia, even when associated with the presence of a large pituitary tumour, is, in most cases, both effective and safe.

An ACTH and FSH Producing Invasive Pituitary Adenoma with Crooke's Hyalinization

We report on a patient with ACTH and FSH producing invasive pituitary adenoma complaining of cutaneous pigmentation. Elevations in plasma ACTH, beta-endorphin and cortisol levels as well as urinary 17-OHCS and cortisol excretion were found. Serum FSH concentration was just within the upper limit of the normal range, whereas serum LH level was reduced and alpha-subunit level was normal. Roentogenographic examination showed an almost complete loss of sellar floor and destruction of the posterior clinoids and dorsum sella. CT scan and MRI demonstrated an enlarged tumor invasion of the clivus and its extension to the sphenoid sinus. After subtotal removal of the large pituitary tumor, serum cortisol and plasma beta-endorphin levels as well as plasma ACTH concentrations returned to normal and serum FSH levels also remarkably decreased. Histologically, the tumor corresponded to a chromophobe, slightly PAS positive adenoma. These tumor cells exhibited positive immunostaining with antibody to ACTH (1-24), beta-LPH, beta-endorphin and FSH, while immunostaining of the adenoma cells was negative for LH, TSH, GH and prolactin. The immunogold technique also demonstrated ACTH and FSH particles in the secretory granules in the cytoplasm of the adenoma cells. Some of the tumor cells disclosed Crooke's hyalinization and type I microfilament occupied most of the cytoplasm. In the present study, a very rare case of ACTH and FSH producing invasive pituitary adenoma is reported.

Acute effects of Parlodel-LAR® and response to long-term treatment with bromocriptine in a patient with a follicle stimulating hormone-secreting pituitary adenoma

A 68-year-old male patient presented with visual impairment due to a large pituitary tumor. After transsphenoidal adenomectomy the elevated serum FSH levels were lowered but not normalized. Deterioration of the vision was detected five years later and tumor regrowth was evidenced. The patient was treated with the long-acting and repeatable form of bromocriptine (Parlodel-LAR). Three days after the first intramuscular injection it already resulted in an important improvement of the visual field defects. Serum FSH concentration was suppressed during a prolonged period, but no change in the size of the pituitary adenoma was recorded on CT scan. Long-term oral treatment with bromocriptine resulted in a sustained suppression of the serum FSH levels, without further visual improvement, but with a significant reduction of the volume of the adenoma. The rapid and prolonged effect of Parlodel-LAR upon the FSH secretion, with a possible correction of the visual field defects and a reduction of the tumor mass, could make this medication appropriate as adjunctive treatment in some gonadotroph cell adenomas.

Postoperative computed tomographic evaluation of patients with large pituitary tumors treated with operative decompression and radiation therapy

Thirty consecutive patients who underwent operative decompression and radiation therapy for large sellar and suprasellar pituitary tumors (greater than or equal to 2 cm) were studied in terms of the serial computed tomographic (CT) changes. There were 23 men and 7 women. The mean age was 49.6 +/- 2.5 years, and the mean follow-up was 45.3 +/- 3.9 months. Twenty-eight of the 30 patients had transsphenoidal surgery, and 27 had hormonally inactive tumors. Radiation therapy was begun within 1 month of surgery with a mean dose of 4855 +/- 70 cGy. Postoperative CT scans were obtained within 1 month of surgery and at 6- to 12-month intervals thereafter. Fourteen patients (45%) had no suprasellar tumor visualized in either the early postoperative CT scans or on subsequent scans. Eleven patients (35%) had a persistent suprasellar mass during the early postoperative period that resolved on serial CT evaluation. The mean time for resolution was 10.4 +/- 1.2 months. Six patients (20%) had a persistent suprasellar mass on serial CT evaluation. A persistent postoperative mass that subsequently resolved in many of the patients was thought to be caused by the gradual retraction of the postoperative packing and hematoma, as well as the effect of radiation on any residual tumor.

Postoperative Computed Tomographic Evaluation of Patients with Large Pituitary Tumors Treated with Operative Decompression and Radiation Therapy

Abstract Thirty consecutive patients who underwent operative decompression and radiation therapy for large sellar and suprasellar pituitary tumors (⩾2 cm) were studied in terms of the serial computed tomographic (CT) changes. There were 23 men and 7 women. The mean age was 49.6 ± 2.5 years, and the mean follow-up was 45.3 ± 3.9 months. Twenty-eight of the 30 patients had transsphenoidal surgery, and 27 had hormonally inactive tumors. Radiation therapy was begun within 1 month of surgery with a mean dose of 4855 ± 70 cGy. Postoperative CT scans were obtained within 1 month of surgery and at 6- to 12-month intervals thereafter. Fourteen patients (45%) had no suprasellar tumor visualized in either the early postoperative CT scans or on subsequent scans. Eleven patients (35%) had a persistent suprasellar mass during the early postoperative period that resolved on serial CT evaluation. The mean time for resolution was 10.4 ± 1.2 months. Six patients (20%) had a persistent suprasellar mass on serial CT evaluation. A persistent postoperative mass that subsequently resolved in many of the patients was thought to be caused by the gradual retraction of the postoperative packing and hematoma, as well as the effect of radiation on any residual tumor.

Is magnetic resonance imaging useful in guiding the operative approach to large pituitary tumors?

Forty-two patients with large pituitary tumors were studied with magnetic resonance imaging scans. Based on the operative findings, the tumors were divided into two groups. Tumors in Group 1 (n = 35) were soft or partially necrotic and were easily removed by suction and curettage. Tumors in Group 2 (n = 7) were firm and required sharp dissection or use of the laser for removal. Tumors were divided into two groups based on the long TR signal: a) isointense in comparison with white matter, or b) hyperintense in comparison with white matter. All 7 firm tumors (Group 2) had an isointense signal on long TR sequences. Thirty-two of 35 soft tumors showed a hyperintense signal on long TR sequences, and 3 an isointense signal. Based on these results, we recommend a transsphenoidal approach for the initial operation in patients with large pituitary tumors. If the tumor is largely isointense on the magnetic resonance imaging scan, we discuss with the patient preoperatively the possibility (70% in this series) that the tumor may be too firm to remove in a single transsphenoidal procedure. In these circumstances, a second, transcranial, procedure may be required to decompress the suprasellar structures adequately.

Is Magnetic Resonance Imaging Useful in Guiding the Operative Approach to Large Pituitary Tumors?

Abstract Forty-two patients with large pitutary tumors were studied with magnetic resonance imaging scans. Based on the operative findings, the tumors were divided into two groups, Tumors in Group 1 (n = 35) were soft or partially necrotic and were easily removed by suction and curettage, Tumors in Group 2 (n = 7) were firm and required sharp dissection or use of the laser for removal. Tumors were divided into two groups based on the long TR signal: a) isointense in comparison with white matter, or b) hyperintense in comparison with white matter. All 7 firm tumors (Group 2) had an isointense signal on long TR sequences. Thirty-two of 35 soft tumors showed a hyperintense signal on long TR sequences, and 3 an isointense signal. Based on these results, we recommend a transsphenoidal approach for the initial operation in patients with large pituitary tumors. If the tumor is largely isointense on the magnetic resonance imaging scan, we discuss with the patient preoperatively the possibility (70% in this series) that the tumor may be too firm to remove in a single transsphenoidal procedure. In these circumstances, a second, transcranial, procedure may be required to decompress the suprasellar structures adequately.

CISTERNOGRAPHY COMBINED WITH LINEAR TOMOGRAPHY FOR VISUALIZATION OF PITUITARY LESIONS IN DOGS WITH PITUITARY‐DEPENDENT HYPERADRENOCORTICISM

Cisternography combined with sagittal linear tomography was performed in eight dogs with pituitary‐dependent hyperadrenocorticism, in search of pituitary lesions. In one dog with a pituitary microadenoma, the dimensions of the pituitary gland were within normal limits. In six dogs the pituitary gland was enlarged. In the remaining dog the pituitary gland was also enlarged, but could not be measured due to absence of contrast medium in the cisternae around the pituitary gland. In these seven dogs large pituitary tumors were found at autopsy. With linear tomography the height of the pituitary gland could only be measured in the dog with the microadenoma. In all other dogs compression of the subarachnoid space at the dorsal aspect of the pituitary gland interfered with the assessment of the height of the pituitary lesion, and therefore with the assessment of the presence and extent of compression of the hypothalamus. It is concluded that cisternography combined with linear tomography provides information about the size of the pituitary gland and the presence of suprasellar expansion, although the present technique does not allow an assessment of the severity of the suprasellar expansion.