Serum neuron-specific enolase in patients with pituitary adenoma.
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Adenoma↗
Biomedical subjects
W F Young
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Pheochromocytoma: issues in diagnosis & treatment.
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Adult↗
Transforming growth factor-beta, transforming growth factor-beta receptor II, and p27Kip1 expression in nontumorous and neoplastic human pituitaries.
Transforming growth factor (TGF)-beta has been implicated in the regulation of normal and neoplastic anterior pituitary cell function. TGF-beta regulates the expression of various proteins, including p27Kip1 (p27), a cell cycle inhibitory protein. We examined TGF-beta, TGF-beta type II receptor (TGF-beta-RII), and p27 expression in normal pituitaries, pituitary adenomas, and carcinomas to analyze the possible roles of these proteins in pituitary tumorigenesis. Normal pituitary, pituitary adenomas, and pituitary carcinomas all expressed TGF-beta and TGF-beta-RII immunoreactivity. Reverse transcription polymerase chain reaction analysis showed TGF-beta 1, -beta 2, and -beta 3 isoforms and TGF-beta-RII in normal pituitaries and pituitary adenomas. Pituitary adenomas cells cultured for 7 days in defined media showed a biphasic response to TGF-beta with significant inhibition of follicle-stimulating hormone secretion at higher concentrations (10(-9) mol/L) and stimulation of follicle-stimulating hormone secretion at lower concentrations (10(-13) mol/L) of TGF-beta 1 in gonadotroph adenomas. Immunohistochemical analysis for p27 protein expression showed the highest levels in nontumorous pituitaries with decreased immunoreactivity in adenomas and carcinomas. When nontumorous pituitaries and various adenomas were analyzed for p27 and specific hormone production, growth hormone, luteinizing hormone, and thyroid-stimulating hormone cells and tumors had the highest percentages of cells expressing p27, whereas adrenocorticotrophic hormone cells and tumors had the lowest percentages. Immunoblotting analysis showed that adrenocorticotrophic hormone adenomas also had the lowest levels of p27 protein. Semiquantitative reverse transcription polymerase chain reaction and Northern hybridization analysis did not show significant differences in p27 mRNA expression in the various types of adenomas or in nontumorous pituitaries. In situ hybridization for p27 mRNA showed similar distributions of the gene product in nontumorous pituitaries, pituitary adenomas, and carcinomas. These results indicate that TGF-beta and TGF-beta-RII are widely expressed in nontumorous pituitaries and in pituitary neoplasms and that TGF-beta 1 regulates pituitary hormone secretion. The levels of the TGF-beta-regulated protein p27 decreases in the progression of normal to neoplastic pituitaries. In contrast, the mRNA levels of p27 remained relatively constant in nontumorous pituitaries, pituitary adenomas, and carcinomas, indicating that p27 protein levels in adenomas and carcinomas are regulated by translational and post-translational mechanisms.
Adenoma↗
Clinical spectrum and outcome of functional extraadrenal paraganglioma.
Functioning extraadrenal paragangliomas represent more than 10% of all pheochromocytomas, occur at diverse anatomic locations, and are said to have a higher malignancy rate than intraadrenal pheochromocytomas. Sixty-six patients had surgery for catecholamine-producing paragangliomas between 1952 and 1992. Median follow-up was 8.8 years. Median age was 40 years (11-67 years); the male/female ratio was 29:37. Familial disease occurred in 9 patients (13.6%), and 10 patients (15.2%) also developed adrenal pheochromocytoma. Solitary paragangliomas occurred in 52 patients: 46 abdominal, 4 thoracic, and 2 head and neck. Fifty-three tumors developed in 14 patients with multiple paragangliomas: 38 abdominal and 15 thoracic. Of 28 patients with solitary tumors undergoing localization studies over the past 10 years accurate localization was achieved in 27. There was one operative death; 15 patients had persistent disease; and 50 were cured postoperatively. Of those cured, nine developed recurrence, disease-free survival being 86%, 80%, and 80% at 5, 10, and 20 years. Metastatic disease was found in 14 patients (21%), 7 of whom have died. An additional 10 patients (15%) had locally invasive disease, of whom 4 have died. Cause-specific survivals at 5, 10, and 20 years were 90%, 83%, and 72%. Risk factors for death from pheochromocytoma were tumor size > 5 cm (p = 0.0002), metastatic disease (p = 0.001), and tumor invasion (p = 0.0023). Cause-specific survival for patients with tumors > 5 cm was 59% at 15 years compared to 100% among patients with tumors </= 5 cm (p = 0.0003). Functional paragangliomas are frequently malignant and are associated with a high incidence of persistent or recurrent disease. Tumor size > 5 cm and the occurrence of invasive or metastatic disease are strong predictors of outcome. Most tumors are abdominal, and imaging is highly successful for localization.
Abdominal Neoplasms↗
Gonadotroph adenoma of the pituitary gland: a clinicopathologic analysis of 100 cases.
OBJECTIVE: To determine the clinical and pathologic features in a large cohort of randomly selected patients with gonadotroph pituitary adenomas. DESIGN: We retrospectively reviewed clinical, surgical, and pathologic findings in 100 patients (79 men and 21 women, 30 to 82 years old) with this tumor. RESULTS: Diagnosis of a pituitary tumor was prompted by visual loss (43%), symptoms of hypopituitarism (22%), headache (8%), or a combination of these findings (10%); 17% of the patients were asymptomatic. Visual field defects were present in 68% of the study group, and complete or partial anterior pituitary failure was present in 77%. Serum prolactin concentrations were increased (maximum, 110 ng/mL) in 33% of patients. Hypersecretion of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) was documented in 11 and 5 patients, respectively. The serum level of alpha-subunit was increased in 1 of 29 patients in whom it was measured. All patients had pituitary macroadenomas, only 21% of which were grossly invasive. The surgical approach was transsphenoidal in all but two patients, who underwent transfrontal craniotomy; gross total tumor resection was achieved in 90%. By definition, all tumors had at least 10% immunoreactivity for LH, FSH, or both. All tumors were chromophobic. Ultrastructurally, the tumors were characterized as gonadotroph adenomas of "male" (45%) or "female" (9%) type as well as null-cell adenomas of the oncocytic (35%) or nononcocytic (11%) type. After a median follow-up of 4.3 years, 69% of the patients who had had visual field defects noted normalization or improvement. Persistent or clinically recurrent pituitary tumor tissue was present in 42%. A second pituitary surgical procedure was required in eight patients. CONCLUSION: Most patients with clinically evident gonadotroph pituitary tumors have loss of vision and hypopituitarism. Hypersecretion of FSH or LH is unusual, and no distinct hormone-dependent clinical phenotype is present. Transsphenoidal surgical treatment generally yields normalization or improvement of visual field defects.
Adenoma↗
Coexistence of bilateral adrenal phaeochromocytoma and idiopathic hyperaldosteronism.
The coexistence of phaeochromocytoma and primary aldosteronism is rare. In the four cases reported in the English literature, adrenal gland involvement was unilateral. The case we report is unusual in that both adrenal glands were affected. Our patient was a 63-year-old man who presented with long-standing hypertension and hypokalaemia. Evaluation for secondary hypertension showed biochemical evidence of both phaeochromocytoma and primary aldosteronism. Bilateral adrenal masses were found on imaging studies. Right total and left partial adrenalectomy were performed. Pathological examination revealed bilateral phaeochromocytomas, with cortical findings consistent with mild cortical hyperplasia. Annual biochemical evaluation over a 2-year period has shown no evidence of recurrent disease. To our knowledge, this is the first reported case in the English-language literature of phaeochromocytomas involving both adrenal glands coexisting with hyperaldosteronism.
Adrenal Gland Neoplasms↗
Pancreastatin secretion by pituitary adenomas and regulation of chromogranin B mRNA expression.
Pancreastatin, a carboxyl-terminal amidated peptide derived from chromogranin (Cg)A, inhibits secretion of insulin and parathyroid hormone. Our recent studies found significant amounts of immunoreactive pancreastatin in all pituitary adenomas except prolactin adenomas. To analyze the effects of pancreastatin on pituitary cell function, 17 cultured pituitary adenomas were examined for immunoreactive pancreastatin and pancreastatin secretion by the tumors. The effects of pancreastatin on pituitary hormone secretion and on pituitary hormone (follicle-stimulating hormone and prolactin), CgA, and CgB mRNA levels were also examined. Immunoreactive pancreastatin and CgA were present diffusely in gonadotroph and null cell adenomas, but only a few prolactin adenoma cells expressed pancreastatin or CgA. When cells were treated with hypothalamic peptides, gonadotroph adenomas were the only group that released increased amounts of pancreastatin in response to gonadotropin-releasing hormone (10(-7) mol/L). Pancreastatin (10(-7) mol/L) treatment did not stimulate pituitary hormone secretion significantly. In situ hybridization analyses showed that gonadotropin-releasing hormone and pancreastatin treatment led to significant increases in CgB and follicle-stimulating hormone mRNAs in gonadotroph adenomas, whereas CgA mRNA levels did not change significantly. These results show that there is a differential distribution of pancreastatin secretion in pituitary adenomas and that the hypothalamic hormone gonadotropin-releasing hormone and the CgA-derived peptide pancreastatin can regulate CgB mRNA in gonadotroph adenomas, suggesting an autocrine effect of pancreastatin on pituitary tumor function.
Adenoma↗
Primary aldosteronism: adrenal venous sampling.
BACKGROUND: In primary aldosteronism, high-resolution adrenal computed tomography (CT) increasingly identifies subtle anatomic abnormalities. To interpret the functional significance of adrenal micronodular changes on CT scan, we have reevaluated selective adrenal venous sampling. METHODS: Thirty-four patients with primary aldosteronism were selected prospectively for adrenal venous sampling on the basis of CT findings: normal findings or minimal thickening of an adrenal limb (n = 15), unilateral microadenoma (n = 6), bilateral adrenal nodules (n = 9), or atypical unilateral adrenal macroadenoma (n = 4). RESULTS: Both adrenal veins were catheterized in 33 of 34 patients. Six (40%) of 15 patients with normal or minimal adrenal limb thickening had a unilateral source of aldosterone. Six patients with apparent unilateral microadenoma had ipsilateral aldosterone-producing adenomas. Four (44%) of nine patients with bilateral adrenal masses had a unilateral source of aldosterone secretion. Three of four patients with unilateral atypical adrenal macroadenomas had ipsilateral aldosterone-producing adenomas. CONCLUSIONS: A unilateral source of aldosterone excess may be found in selected patients with adrenal glands that appear normal or show a minimally expanded adrenal limb on CT scan. Findings on adrenal venous sampling are crucial in determining the source of aldosterone excess in patients with bilateral adrenal masses or atypical-appearing macroadenomas.
Adenoma↗
Intraoperative stimulation of pedicle screws: a new method for verification of screw placement.
Pedicular fixation of the lumbosacral spine has become a popular procedure for improving fusion rates. Even in experienced hands, it can be associated with a significant rate of screw malpositioning and potential nerve root injury. In this report, we describe a technique for improving screw localization utilizing evoked electromyography responses from direct stimulation of pedicle instrumentation.
Adult↗
Adrenal surgery for hypercortisolism--surgical aspects.
BACKGROUND: Patients with endogenous hypercortisolism are thought to be at high risk for adrenalectomy and may experience significant postoperative surgical mortality/morbidity. METHODS: From 1981 through 1991, 91 patients underwent adrenal resection for endogenous hypercortisolism. Causes were adrenal-dependent Cushing's syndrome (50%), pituitary-dependent Cushing's syndrome (27%), and an ectopic adrenocorticotropic hormone-secreting tumor (23%). Causes of adrenal-dependent Cushing's syndrome were adrenocortical adenoma (72%), bilateral nodular hyperplasia (20%), and adrenocortical carcinoma (8%). Comparative mean length of hospitalization for patients undergoing unilateral anterior versus posterior approach was 8 versus 6 days, and bilateral anterior versus posterior was 11 versus 6 days. RESULTS: Operative mortality was 2.6%. Only one patient had a wound infection, and no patient had either a venous thrombosis or a pulmonary embolism. Delayed wound healing occurred in three patients. CONCLUSIONS: (1) Adrenal surgery can be performed today with low morbidity/mortality. (2) Although there is an effect of hypercortisolism on wound healing, infection, diabetes, hypertension, coronary artery disease, and pulmonary embolism, it was possible to perform adrenalectomy surgically with acceptable morbidity and mortality. (3) These results may serve as a standard against which laparoscopic adrenalectomy may be compared.
Adenoma↗
Safety and efficacy of long-term octreotide therapy of acromegaly: results of a multicenter trial in 103 patients--a clinical research center study.
One hundred and three acromegalic patients from 14 medical centers were enrolled in this study to determine the efficacy and safety of the somatostatin analog, octreotide acetate, during long term treatment. Seventy percent of the patients had undergone previous surgery or radiation treatment. Octreotide was initiated at a dose of 100 micrograms, sc, every 8 h and gradually increased to a maximum of 1500 micrograms daily depending upon the individual patient's clinical and biochemical response [GH and insulin-like growth factor I (IGF-I) reduction]. The mean duration of treatment was 24 months (range, 3-30 months). However, most patients were treated for a mean of 30 months, because this study took place after an initial 6-month study previously reported. Mean serum GH fell from 30.9 micrograms/L (range, 2.7-350) to 5.7 micrograms/L (range, 0.6-59) at the 3 months visit and remained suppressed (P < 0.001). Plasma IGF-I concentrations were also significantly reduced and remained in the normal range for at least half of the treatment visits in 56 of 87 patients (64%) treated for 12-30 months. Patients with higher initial GH concentrations were less likely to normalize IGF-I concentrations during treatment (P < 0.001). There was no evidence of drug tachyphylaxis in those patients who continued taking stable doses of medication. With some exceptions, dose increments above 800 micrograms daily in 31 patients did not provide additional benefit in terms of GH and IGF-I reduction. Headache, excessive perspiration, fatigue, and joint pain were ameliorated in 83-95% of patients. Mean finger circumference was decreased significantly at the 12 month visit (P < 0.05). The most common adverse events reported were diarrhea, abdominal discomfort, loose stools, and nausea; these symptoms usually disappeared within 3 months of treatment. Five patients discontinued octreotide because of adverse events. Of 102 patients with normal baseline ultrasound examinations of the gallbladder, 24 patients (23.5%) developed gallstones (usually during the first year of treatment), and 21 patients developed sludge alone. Gallstone formation was not related to the dose of octreotide. Most patients with cholelithiasis were asymptomatic, and none developed cholecystitis. These observations suggest that octreotide is a valuable long term medical treatment for acromegaly.
Acromegaly↗
Papillary craniopharyngioma: a clinicopathological study of 48 cases.
Two distinct clinicopathological variants of craniopharyngioma exist: the classic adamantinomatous type and a recently described papillary form that predominates in adults and reportedly behaves in a less aggressive manner. The present study describes the clinicopathological features of 48 patients with papillary craniopharyngioma treated at the Mayo Clinic between 1910 and 1994. An additional four tumors were found to have histological features of both adamantinomatous and papillary craniopharyngioma. Whereas adamantinomatous tumors typically occur in adolescent patients, the mean age of the 48 patients (23 males and 25 females) with papillary craniopharyngioma was 44.7 years (range 10 to 74 years). Presenting clinical features included visual impairment (84%), headache (68%), and pituitary insufficiency (anterior 42%; posterior 27%). Preoperative computerized tomography (CT) and magnetic resonance (MR) imaging in 17 patients typically revealed a noncalcified, partially cystic mass that enhanced peripherally and contained mural nodules (67%). Many (41%) of the lesions involved or extended into the third ventricle on imaging. At first surgery, gross total tumor removal was achieved in 17 patients (36%) and subtotal resection in 30 patients (64%) in whom tumor resection was attempted. Tumor recurrence was noted in two patients who underwent gross total removal. Tumor-free survival rates of 100% and 78% were obtained in patients who underwent gross total and subtotal resection at initial surgery, respectively. Postoperative radiation therapy was beneficial to patients having undergone a subtotal resection, with an increase in tumor-free survival from 26% to 86%. Aside from well-documented morphological distinctions, papillary craniopharyngiomas differ from adamantinomatous tumors in several important respects. These include the almost exclusive occurrence of papillary tumors in adulthood and their more uniform appearance on both CT and MR imaging. However, a preliminary analysis of our data suggests there are no significant differences between the two lesions with respect to resectability, efficacy of radiation therapy, and overall survival.
Adolescent↗
False-positive inferior petrosal sinus sampling in the diagnosis of Cushing's disease. Report of two cases.
Inferior petrosal sinus sampling (IPSS) for adrenocorticotropic hormone (ACTH) levels in patients with Cushing's syndrome has become a useful method to distinguish ACTH-secreting pituitary tumors (Cushing's disease) from other causes of the syndrome, principally ectopic adrenocorticotropin secretion by an occult tumor. Although the test is generally regarded as highly specific, the authors recently encountered two patients whose IPSS measurements were false-positive for Cushing's disease. The results of IPSS suggested a pituitary origin of ACTH secretion in both patients, but transsphenoidal surgery failed to disclose a pituitary adenoma or to improve postoperative plasma cortisol levels. Both patients subsequently were found to have an ACTH-secreting carcinoid tumor of the lung. The false-positive IPSS studies were due to periodic hormonogenesis. The patients must be hypercortisolemic at the time IPSS is performed for the study to be valid.
Adrenocorticotropic Hormone↗
Spells: in search of a cause.
OBJECTIVE: To determine the cause of spells, present clinical features, and discuss diagnostic approaches. DESIGN: Relevant medical literature is reviewed, and three illustrative cases are presented. RESULTS: Spells are a sudden onset of a symptom or symptoms that are stereotypic, self-limited, and recurrent. A spell involves both subjective perceptions and objective findings. In the assessment of patients who have spells, use of a systematic approach is important in determining the cause. The causes of spells include endocrine, cardiovascular, psychologic, pharmacologic, neurologic, and other miscellaneous disorders. A comprehensive history, physical examination, and basic laboratory studies are important in the initial assessment. Specialized testing is usually needed and directed by clinical suspicion based on the spell "phenotype" (for example, a pheochromocytoma, carcinoid syndrome, or mast cell disease) and the type of facial flush or pallor. CONCLUSION: In the assessment of the patient who has spells, the clinician should cast a wide but defensible diagnostic net. Initial studies should be directed by the clues obtained from the history and physical examination.
Adrenal Gland Neoplasms↗
Analysis of the chromogranin A post-translational cleavage product pancreastatin and the prohormone convertases PC2 and PC3 in normal and neoplastic human pituitaries.
Several members of the chromogranin/secretogranin (Cg/Sg) family are post-translationally processed in neuroendocrine cells and tumors to smaller peptides, some of which are biologically active. For example, CgA is processed to pancreastatin, parastatin, and other peptides. We analyzed the distribution of pancreastatin and CgA proteins in normal and neoplastic pituitaries as well as the prohormone convertases PC2 and PC3/1 (PC3), the putative processing enzymes for the Cg/Sg family, in 35 pituitary adenomas and 4 non-neoplastic pituitaries by immunohistochemistry and immunoblotting with highly specific antisera. CgA and CgB mRNAs were also examined. Pancreastatin was present in all subtypes of pituitary tumors, although prolactin-secreting adenomas expressed this peptide less frequently than did other tumor types. CgA protein and CgA mRNA expression were also restricted in prolactin adenomas and in normal prolactin cells, as shown by combined in situ hybridization and immunostaining. The prohormone convertases PC2 and PC3 were present in pituitary tumors and in non-neoplastic pituitaries. Immunoblot analysis and immunostaining showed a principal approximately 69-kd PC3 band and a approximately 68-kd PC2 band. Adrenocorticotrophic hormone-secreting adenomas expressed mainly PC3 as determined by immunoblotting and immunohistochemistry, whereas all other adenoma groups expressed predominantly PC2. These results indicate that the enzymes capable of processing CgA and other members of the Cg/Sg family to peptides with biological activity such as pancreastatin are widely expressed in human pituitary adenomas and in non-neoplastic pituitaries, with adrenocorticotrophic hormone tumors expressing predominantly PC3 and other adenomas expressing mainly PC2. The infrequent expression of CgA protein and pancreastatin peptides in normal and neoplastic prolactin cells suggests a unique role of CgA in these tumors.
Adult↗
Preservation of post-compression spinal cord function by infusion of hypertonic saline.
We tested the hypothesis that the administration of hypertonic saline, following traumatic injury to the spinal cord, could enhance blood flow to the cord and preserve function. Rats were used as the experimental model. Direct compression of the spinal cord for a period of 10 min was done to produce the injury. Somatosensory evoked potentials (SSEPs) and spinal cord blood flow were measured using a laser Doppler flow meter throughout the experiment. Comparisons of the blood flow values and SSEPs were made among four different groups of animals. The control group received no fluid resuscitation after injury. A second group received a bolus injection of isotonic saline (0.5 ml/100 g) as an i.v. infusion over a period of 1 min. A third group received a bolus infusion of 7.5% NaCl (0.5 ml/100 g) over a period of 1 min. The final group received 4 ml/100 g of 0.9% NaCl over a period of 10 min. The administration of hypertonic saline significantly reduced spinal cord vascular resistance during the first 10 min after infusion. During the first 30 min after the removal of compression, spinal cord blood flow was greater in the hypertonic saline group than in the other three groups. The hypertonic saline group had a reactive hyperemia whereas the flow in the other groups remained at or below control values. Beginning 10 min after injury and for the remainder of the 1-h observation period, the latency of the cortical peak of the SSEP in the group receiving hypertonic saline was significantly shorter than in any of the other three groups. These results indicate that the administration of hypertonic saline enhances blood flow and preserves spinal cord conduction following traumatic injury to the spinal cord.
Animals↗
Diagnosis and management of occipital condyle fractures.
The authors recently treated three cases involving fractures of the occipital condyle. First described by Bell in 1817, this lesion has proven to be very rare, with only 32 cases previously reported in the literature. Plain films often do not reveal any abnormality, making diagnosis difficult. High-resolution computed tomography has been demonstrated to be very sensitive in diagnosing this lesion. This fact was borne out in the authors' series. All of the authors' patients were managed either with a Philadelphia collar or with halo fixation, with excellent outcomes.
Adult↗
Long-term outcome of bilateral adrenalectomy in patients with Cushing's syndrome.
BACKGROUND: Bilateral adrenalectomy provides an effective surgical option for patients with Cushing's syndrome. Knowledge of the long-term outcome of the patient who has undergone adrenalectomy is an important factor in determining management strategy in this situation. METHODS: Fifty consecutive patients undergoing bilateral adrenalectomy (1980 to 1991) were studied. Twenty-five had Cushing's disease, 18 ectopic adrenocorticotrophic hormone production, and seven primary adrenal hyperplasia. Median age was 43 years (range, 14 to 82 years); male-to-female ratio was 13:37. At follow-up 17 patients had died; the remaining 33 were interviewed at a median of 62 months after operation. RESULTS: Operative mortality was 4%. Late mortality included two patients with Cushing's disease who died of progressive pituitary disease and eight patients with ectopic adrenocorticotrophic hormone production who died of metastatic disease. Five-year survival was: 100% for patient with adrenal hyperplasia, 86% for patients with Cushing's disease, and 39% for patients with ectopic adrenocorticotrophic hormone production. Of 33 survivors followed for a median of 62 months, three (9%) were hospitalized with acute steroid deficiency. The principal complaint among survivors was chronic fatigue (60%). Only 10 (30%) patients had no symptoms. No steroid-related complications resulted after 16 surgical procedures subsequently performed. Of 20 survivors of Cushing's disease, three had Nelson's syndrome. CONCLUSIONS: Bilateral adrenalectomy for Cushing's syndrome is associated with occasional morbidity and mortality consequent to adrenal insufficiency. These patients suffered a high incidence of chronic physical complaints that may reflect the residual sequelae of chronic Cushing's syndrome. An active program of long-term rehabilitation is essential.
Adolescent↗