Intrasellar Pressure Research Articles

Intrasellar Pressure is Related to Endocrine Disturbances in Patients with Pituitary Tumors

The aim of this study was to investigate the association between intraoperative intrasellar pressure (ISP) and pre- and postoperative endocrine disturbances with focus on hyperprolactinemia and hypopituitarism in patients with pituitary tumors. The study is a consecutive, retrospective study with ISP collected prospectively. One hundred patients operated with transsphenoidal surgery due to a pituitary tumor, who had their ISP measured intraoperatively, were included. Data on patient endocrine status preoperatively and from 3-month postoperative follow-up were collected from medical records. The risk of preoperative hyperprolactinemia in patients with nonprolactinoma pituitary tumors increased with ISP (unit odds ratio 1.067, n= 70) (P= 0.041). Preoperative hyperprolactinemia was normalized at 3months after surgery. Mean ISP was higher in patients with preoperative thyroid-stimulating hormone (TSH) deficiency (25.3±9.2mmHg, n= 37) than in patients with intact thyroid axis (21.6±7.2mmHg, n= 50) (P= 0.041). No significant difference in ISP was found between patients with and without adrenocorticotropic hormone(ACTH) deficiency. No association was found between ISP and postoperative hypopituitarism at 3months after surgery. In patients with pituitary tumors, preoperative hypothyroidism and hyperprolactinemia may be associated with higher ISP. This is in line with the theory of pituitary stalk compression, suggested to be mediated by an elevated ISP. ISP does not predict the risk of postoperative hypopituitarism 3months after surgical treatment.

PMON130 Pituitary apoplexy presenting as left basal ganglia hemorrhage

Abstract Introduction The clinical manifestations of pituitary apoplexy (PA) are highly variable and are caused by a rapid increase in the size of intrasellar contents, leading to an increase in intrasellar pressure. Headache, visual disturbances, cranial nerve palsies, and pituitary insufficiency are the most frequent symptoms. Cerebral ischemia and hemorrhage are rare complications of PA. Here we present a case of a young male who presented with left basal ganglia hemorrhagic stroke and pituitary apoplexy. Case Presentation 39-year-old male presented to emergency department for acute onset of nausea, vomiting and right sided weakness for past 2-3 days. Soon after, patient became acutely confused. On examination, he was hypertensive, tachycardiac, tachypneic and obtunded. His pupils were 3 mm, equal, sluggish. He was moving left side but no movements on the right side of his body. In view of rapidly deteriorating mental status, he was intubated for airway protection. Computed tomography (CT) of the head was performed which showed acute left basal ganglia hemorrhage measuring 4.2 cm with vasogenic edema and midline shift of 4 mm. Also noted was markedly expanded sella with a cystic mass containing fluid level measuring up to 4.3 cm. Complete blood count, coagulation profile and liver function tests were unremarkable. His sodium levels were 140 mmol/L, potassium 2.9mmol/L, chloride 101mmol/L and bicarbonate 22 mmol/L. Endocrine workup revealed free T4 0.7 ng/dl, TSH 2.32 mIU/L, FSH 3.0 mIU/ml, LH 4.9 mIU/ml, estradiol 7 pg/ml, testosterone 59 ng/dl, random cortisol 8 ug/dl, ACTH 5.1 pg/ml, growth hormone <0.05 ng/ml, IGF-2 249 ng/ml and prolactin 10,470 ng/ml. MRI brain confirmed hemorrhagic pituitary macroadenoma and left basal ganglia parenchymal hematoma with mass effect and midline shift. Patient was diagnosed with hemorrhagic pituitary macroadenoma causing PA. He was started on intravenous steroids, levothyroxine, cabergoline and hypertonic saline. External ventricular drain was placed for obstructive hydrocephalus followed by left frontal burr hole for hematoma evacuation. Pathology was negative for infection, inflammation, neoplasm and amyloid angiopathy. CT angiography was negative for intracranial aneurysm, arteriovenous malformation, dural arteriovenous fistula, or tumor blushes. He subsequently underwent tracheostomy and gastrostomy placement and transferred to rehabilitation facility. Patient continued to improve neurologically, was subsequently decannulated. Discussion PA is reported to occurs in 2-12% of pituitary adenoma.1 Corticotropic deficiency is common and can be life threatening if left untreated. Empiric steroids should be administered to all patients with signs of PA without waiting for diagnostic confirmation. Intraparenchymal hemorrhage is an extremely rare complication of PA and thought to be related to vasospasm of the cerebral arteries. Reference 1. Briet C, Salenave S, Bonneville JF, et. Al. Pituitary Apoplexy. Endocr Rev. 2015 Dec;36(6): 622-45. doi: 10.1210/er.2015-1042. Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

Intrasellar pressure in patients with pituitary adenoma \u2013 relation to tumour size and growth pattern

BackgroundOnly a few earlier publications on intrasellar pressure (ISP) have not been able to fully clarify any association between ISP and pituitary adenoma size and growth pattern. The aim of the study was to determine if intrasellar pressure (ISP) is elevated in patients with pituitary adenoma, and if the pressure is associated with tumour size and growth pattern.MethodsThe study included 100 patients operated for suspected pituitary adenoma, who have had their ISP measured intraoperatively. All adenomas were classified on the basis of Knosp and SIPAP, from which further classification of invasiveness was performed. MRT examinations were used to calculate the tumour volume and diameter in three axes.ResultsAfter exclusions, 93 cases were analysed. The mean ISP was 23.0 ± 8.4 mmHg. There were positive correlations between ISP and tumour volume and tumour diameters along all three axes. Coronal tumour diameter showed the strongest correlation with ISP elevation in a multivariate effect test. Adenomas classified as parasellar invasive (Knosp grade 3–4) showed higher mean ISP than adenomas considered as non-invasive (Knosp 0–2).ConclusionsISP is affected by tumour anatomy and correlates positively with tumour volume. Tumour width, i.e. diameter in the coronal plane, appears to be the measure that most strongly affects the ISP. This is confirmed by the association between ISP elevation and parasellar growth.

The “Double-Peak” Pattern of Pituitary Adenoma Intrasellar Pressure and Its Effects on the Microvascular Structure

The purpose of the present study was to investigate the relationship between the intrasellar pressure (ISP) and the microvascular structure of pituitary adenomas. We retrospectively analyzed the ISP in 66 patients with pituitary adenomas. The corresponding microvascular structure was obtained using immunohistochemistry and analyzed for its correlation with the ISP. The average ISP was 25.89 ± 8.27 mm Hg, and the ISP was not related to the size of the adenoma (Pearson correlation coefficient, 0.103; P= 0.415). The ISPs of adenomas with different Knosp grades were significantly different (P < 0.05). From grade 0 to grade 4, at first, the ISP increased with the Knosp grade and reached the first peak at grade 2. It then decreased at grade 3 and increased again at grade 4, showing a "double-peak" pattern. The minimal diameter and perimeter of the microvessels and the vessel-covered area percentage were positively related to the ISP. When these parameters were compared among the adenomas of different Knosp grades, they also exhibited a "double-peak" pattern. In the present study, we found that with the increase in pituitary adenoma size and invasion of the surrounding tissues, the ISP of pituitary adenomas showed a "double-peak" pattern. The ISP and certain parameters of the microvascular structure are related, because the microvasculature adaptively changes its structure in response to the changing ISP to ensure a sufficient blood supply to the adenoma. The specific mechanism of this phenomenon requires further study.

MON-239 Pituitary Apoplexy Induced by Gonadotropin-Releasing Hormone Agonist Administration: A Rare Complication of Prostate Cancer Treatment

Background: Pituitary apoplexy is a potentially life-threatening clinical condition associated with bleeding and/or infarction into the pituitary gland, usually within a tumor. Gonadotropin-releasing hormone (GnRH) agonists, currently used in the treatment of advanced prostate cancer, have been described in the literature as a rare cause of pituitary apoplexy. Case: We report the case of a 69 year-old man with a known pituitary macroadenoma incidentally detected in 2016, without further investigation. He was diagnosed with prostate cancer in 2017 and underwent retropubic prostatectomy. Two years later there was evidence of histologic prostate tumor progression, so he started treatment with leuprorelin 45mg (GnRH agonist). Immediately after the first subcutaneous injection he presented with acute-onset severe headache, followed by left eye ptosis, diplopia and vomiting. Left cranial nerve III palsy was confirmed by examination in the emergency department. Head computed tomography showed a lesion in the sellar region; laboratory endocrine workup was significant for total testosterone 72.07 ng/dL (86.49 – 788.22), with no other abnormalities. Magnetic resonance imaging of the pituitary revealed tumor enlargement and a T1-hyperintense signal, compatible with recent haemorrhagic sellar content. The patient was managed conservatively with high dose steroids, and symptoms were significantly improved on discharge. Discussion: Pituitary apoplexy induced by GnRH agonist administration is a rare complication, described in only 20 documented cases to date. The pathophysiologic mechanism involved is not clearly established and several hypotheses have been proposed: a combination of metabolic hyperactivity, cell division/tumor growth and increased intrasellar pressure, inducing ischemia in a poorly perfused adenomatous tissue given the demand. Although uncommon, healthcare professionals should be aware of this serious consequence of GnRH agonist administration and recognize the signs, preventing a delay in diagnosis and treatment.

Contribution of Intrasellar Pressure Elevation to Headache Manifestation in Pituitary Adenoma Evaluated With Intraoperative Pressure Measurement.

Headache frequently occurs in patients with pituitary adenoma and is reported in large as well as small adenomas. However, the exact mechanism of headache derived from pituitary adenoma remains unknown. To evaluate the contribution of intrasellar pressure (ISP) to headache manifestation by using intraoperative ISP measurement. The records of 108 patients who had first-time transsphenoidal surgery for pituitary adenoma were reviewed retrospectively. Measurement of intraoperative ISP was undergone using intracranial pressure monitoring sensors and compared with radiological assessment. Among 30 patients with headache, 29 (96.7%) presented with significant headache (Headache Impact Score-6, 50 or greater). Intraoperative ISP measurement was conducted successfully in all cases, and revealed higher ISP in patients with headache (35.6 ± 9.2 mm Hg) than in those without headache (15.8 ± 5.2 mm Hg). The ISP reduction after sella floor decompression was greater in patients with headache than that in patients without headache. In patients with headache, the frequency of invasion into the cavernous sinus or sphenoid sinus was significantly lower, and the diameter of the foramen at the diaphragm sellae was narrower. In addition, intratumoral cyst or hematoma was more common in patients with headache. Postoperatively, headache was either diminished or improved in 28 patients (93.3%). Headache in patients with pituitary adenomas associated with ISP elevation, results from compromised dural integrity at the sella and intratumoral hemorrhage. The increased stretch force of the sella dura may be a notable etiology of headache in patients with pituitary adenoma.

A cadaveric model for measuring sinonasal continuous positive airway pressure-a proof-of-concept study.

Obstructive sleep apnea is a common respiratory disorder that can have negative effects on health and quality of life. Positive pressure therapy (CPAP) is the primary treatment. There is a lack of consensus on the risk of postoperative CPAP after endoscopic sinus or skull base surgery. We present a proof-of-concept cadaver model for measuring sinonasal pressure delivered by CPAP. Three fresh cadaver heads were prepared by removing the calvaria and brain. Sphenoidotomies were made and sellar bone was removed. Pressure sensors were placed in the midnasal cavity, sphenoid sinus, and sella. CPAP was applied and the delivered pressure was recorded at increasing levels of positive pressure. Paired t tests and intraclass correlation coefficients were used to analyze results. Increases in positive pressure led to increased pressure recordings for all locations. Nasal cavity pressure was, on average, 81% of delivered CPAP. Pressure was highest in the sphenoid sinus. The effect of middle turbinate medialization on intrasphenoid pressure was not statistically significant in 2 heads. Intrasellar pressure was 80% of delivered CPAP with lateralized turbinates and 84% with medialized turbinates. Pressure recordings demonstrated excellent reliability for all locations. All heads developed non-sellar-based cranial base leaks at higher pressures. Cribriform region leaks were successfully sealed with DuraSeal®. Our proof-of-concept cadaver model represents a novel approach to measure pressures delivered to the nasal cavity and anterior skull base by CPAP. With further study, it may have broader clinical application to guide the safe postoperative use of CPAP in this population.

Fatal Pituitary Tumor Apoplexy Presenting With Behavioral Disorder

Pituitary apoplexy (PA) is a rare but potentially fatal ischemic or hemorrhagic phenomenon, with an annual incidence around 1.2 per million. It is often misdiagnosed because most patients have subclinical pituitary adenomas and its presentation can be confused with neurological or, very rarely, psychiatric processes. Here, we present a 31-year-old man, with history of hypertension and chronic renal disease on hemodialysis of unknown etiology, admitted in the Department of Psychiatry of our Hospital with altered behavioral symptoms. Neuroimaging studies showed an increase of the pituitary gland due to an intraparenchymatous lesion. He was found dead on his room floor. In the autopsy, we observed a pituitary increased in weight and size, which in sagittal section showed an extensive hemorrhagic area located in the anterior lobe. Histological examination revealed a 9 mm adrenocorticotrophic adenoma (ACTH-secreting adenoma), with an extensive intratumoral hemorrhage. PA is often a difficult diagnosis, since it can mimic other clinical situations. Clinicopathologic effects of PA are caused by a rapid increase in the size of the contents of the pituitary fossa and the subsequent rise of intrasellar pressure, with additional pressure on the hypothalamus and midbrain. This would possibly explain the alteration of vital functions and consciousness. Pituitary hemorrhage normally produces an acute stroke which causes characteristic symptoms; the extremely rare case that we present exemplifies how it may also have subclinical/insidiously course for days. To our knowledge, this is the first time to report that a so obvious macroscopic image of post-mortem pituitary with this rare disease. J Endocrinol Metab. 2016;6(4):129-131 doi: http://dx.doi.org/10.14740/jem363w

Significant improvement of intractable headache after transsphenoidal surgery in patients with pituitary adenomas; preoperative neuroradiological evaluation and intraoperative intrasellar pressure measurement

Headache is the most common symptom of both primary and metastatic brain tumor, and is generally considered the primary symptom in patients with large pituitary adenomas. However, patients with small pituitary adenomas rarely complain of intractable headache, and neurosurgeons are unsure whether such small adenomas actually contribute to headache. If conventional medical treatments for headache prove ineffective, surgical removal of the adenoma can be considered as an alternative management strategy. We conducted a retrospective review of 180 patients who underwent transsphenoidal surgery (TSS) for pituitary adenomas at Kanazawa University Hospital between 2006 and 2014. Patients with acute phase intratumoral hemorrhage were excluded. We identified nine patients with intractable headache as the chief complaint associated with small pituitary adenoma (diameters 15.8 ± 2.6 mm, 11-20 mm), non-functioning in eight, and prolactin-secreting in one. The preoperative neuroradiological studies and headache characteristics were assessed retrospectively, and the intrasellar pressure evaluation was performed during TSS in the last seven patients. All nine patients had complete or substantial resolution of their formerly intractable headache after TSS. Headaches consisted of ocular pain ipsilateral to the adenoma localization within the sella in four cases and bifrontal headache in five. Magnetic resonance imaging of these patients revealed small diaphragmatic foramen, which were so narrow that only the pituitary stalk could pass. Computed tomography scans showed ossification beneath the sellar floor in the sphenoid sinus, presellar type in six cases, and choncal type in three. The adenomas included cysts in seven cases. There was no cavernous sinus invasion. Intrasellar pressure measurements averaged 41.5 ± 8.5 mmHg, range 34-59, significantly higher than in control patients without headache (n = 12), namely 22.2 ± 10.6 mmHg (16-30). In this study, the authors demonstrated the validity of TSS in the treatment of intractable headache associated with pituitary adenoma. The presence of ocular pain, especially ipsilateral to the adenoma, integrity of the diaphragm sella, and ossification in the sphenoid sinus, cyst or hemorrhage and the absence of cavernous sinus invasion were the indications for TSS for patients complaining of intractable headache and having pituitary adenomas.

Recurrent pituitary apoplexy due to two successive neoplasms presenting with ocular paresis and epistaxis.

SummaryA case of recurrent pituitary apoplexy is described in a 72-year-old man who initially presented with haemorrhage in a non-functioning pituitary adenoma. Five years later, he re-presented with a severe pituitary haemorrhage in an enlarging sellar mass invading both cavernous sinuses causing epistaxis and bilateral ocular paresis. Subsequent histology was consistent with a sellar malignant spindle and round cell neoplasm. Multiple pituitary tumours have previously been reported to coexist in the same individual, but to our knowledge this is the only case where two pathologically distinct pituitary neoplasms have sequentially arisen in a single patient. This case is also notable with respect to the progressive ocular paresis, including bilateral abducens nerve palsies, and the presentation with epistaxis.Learning points Ocular paresis in pituitary apoplexy can result from tumour infiltration of nerves, or by indirect compression via increased intrasellar pressure.Epistaxis is a very rare presentation of a pituitary lesion.Epistaxis more commonly occurs following trans-sphenoidal surgery, and can be delayed.

The pituitary stalk effect: is it a passing phenomenon?

Most patients with large pituitary tumors do not exhibit hyperprolactinemia as a result of pituitary lactotroph disinhibition (stalk effect). Studies have demonstrated that increased intrasellar pressure is associated with both "stalk effect" hyperprolactinemia and pituitary insufficiency. Our primary hypothesis was that, despite continued disinhibition, lactotroph failure is responsible for normoprolactinemia in patients with large macroadenomas. As a corollary, we proposed that the hyperprolactinemia phase, which presumably would precede the insufficiency/normoprolactinemic state, would more likely be discovered in premenopausal females and go unnoticed in males. Prospective, consecutive surgical series of 98 patients of clinically nonfunctional pituitary adenomas. Lactotroph insufficiency was inferred by the coexistence of insufficiency in another pituitary axis. The existence of pre-operative lactotroph disinhibition was inferred based on comparison of pre- versus post-operative prolactin levels. 87 % of patients with tumor size >20 mm and normoprolactinemia had pituitary insufficiency. Pre-operative prolactin in patients with pituitary insufficiency were lower than those with intact pituitary function. Prolactin levels dropped in nearly all patients, including patients with normoprolactinemia pre-operatively. Premenopausal women had smaller tumors and higher pre-operative prolactin levels compared to males. No premenopausal female exhibited evidence of pituitary insufficiency. Our study provides suggestive evidence that the "stalk effect" pathophysiology is the norm rather than the exception, and that the finding of normoprolactinemia in a patient with a large macroadenoma is likely a consequence of lactotroph insufficiency. In males, the hyperprolactinemia window is more likely to be missed clinically due to an absence of prolactin-related symptoms.

Pituitary apoplexy associated with an inverted papilloma of sphenoid sinus

A 42-year-old man had a severe progressive headache and visual field defects due to pituitary apoplexy. Transsphenoidal resection of a pituitary tumor (measuring approximately 8.7 cm 3 ) resulted in the complete relief of his symptoms. Histological examination revealed the presence of a pituitary adenoma and an inverted papilloma of the sphenoid sinus.This communication emphasizes the following: (1) mucosal thickening and an inverted papilloma of the sphenoid sinus can be a precipitating factor in pituitary apoplexy; (2) an inverted papilloma of the sphenoid sinus may increase intrasellar pressure and therefore increase the risk of acute pituitary apoplexy; (3) if imaging shows thickening of the sphenoid sinus mucosa, then a partial resection of the sphenoid sinus mucosa for histological evaluation should be performed during the transsphenoidal resection of the pituitary tumor.

Mean intrasellar pressure, visual field, headache intensity and quality of life of patients with pituitary adenoma

Intrasellar pressure (ISP) measurement technique has recently opened a new line of research in neuroendocrinology. The absolute and mean ISP values were investigated in 25 patients consecutively operated at the Brasilia University Hospital (DF). These data were correlated with serum prolactin levels, number of visual quadrant affected, tumor size, quality of life (measured through the SF-36 scale) and graded headache (measured through the HIT-6 scale). No correlation was observed. The p values were 0.887; 0.137; 0.892; 0.812 and 0.884; respectively. The HIT-6 values were inversely and moderately correlated with total RAND SF-36 and its mental and physical dimensions.

Headache associated with pituitary tumors

The objective of this study is to analyze the presence of headache in pituitary tumors and their characteristics, the relationship between pituitary tumor size, biological type, local extension and intrasellar pressure (ISP). This is a prospective study, of 64 consecutive patients presenting with primary pituitary masses at Neuroendocrinological Department of General Hospital of Fortaleza from October 2005 to December 2006. We analyzed sex, age, headache (laterality, site, severity, quality, frequency, duration, associated symptoms, time of onset, trigger, alleviating factors and familial history) and tumor characteristics (type, size, quiasmatic compression, cavernous sinus invasion, sella turcica destruction, cystic or solid mass and ISP). We observed a statistic significant factor between pituitary tumor and tumor size, optic compression, sellar destruction, cavernous sinus invasion and ISP. Biochemical-neuroendocrine factors, mainly in prolactinomas, seem to be an important factor in the determination of headache. The presence of headache in pituitary tumor is related to a combination of factors, including ISP, tumor extension, relationship with the sellar structures, patient predisposition, familial history, and functional disturbance within the hypothalamo-pituitary axis.

Intrasellar pressure and tumor volume in pituitary tumor: relation study

To determine if there was a relationship between intrassellar pressure (ISP) and pituitary tumor volume. Between August 2002 and May 2004, 60 patients aged between 13 and 75 years old (39 males), having a pituitary adenoma were submitted to an endoscope transseptal approach. During the surgery and before tumor resection, 2 mm of the sellas floor were removed and a 1.5 mm dural opening made to place a transducer into the pituitary adenoma. The transducer was connected to a pressure monitor. The intrasellar pressure, ranged from 2-51 mmHg and was measured based on the classification of Hardy-Vezina. The most elevated was in the type II macro adenomas with 32.6 mmHg, sharply superior to the value of a normal intracranial pressure. These values showed that the macroadenomas confined to the sella, without destruction of the floor and integrity of the diaphragm, type II of Hardy-Vezina, presented a value of ISP much higher than intra-extrasellar macroadenoma's.

Extreme Elevation of Intrasellar Pressure in Patients with Pituitary Tumor Apoplexy: Relation to Pituitary Function

The dominant mechanism for hypopituitarism and hyperprolactinemia commonly observed in patients with pituitary macroadenomas was postulated to be increased intrasellar pressure (ISP) caused by the slow and gradual expansion of adenomas within the sella turcica. Hemorrhagic infarction of adenomas (pituitary tumor apoplexy) is associated with a rapid, rather than gradual, increase in intrasellar contents. The impacts of the sudden increase in intrasellar contents on ISP and pituitary function are unknown. ISP and pituitary function were determined in 13 patients with pituitary tumor apoplexy who had surgical decompression within 1 wk of symptoms' onset. ISP measurements were remarkably high (median, 47 mm Hg), whereas serum prolactin (PRL) concentrations were generally low (median, 3.5 microg/liter). There was an inverse correlation (r = -0.76; P < 0.01) between ISP measurements and serum PRL concentrations. Postoperatively, partial recovery or maintenance of pituitary function was noted in seven of 13 patients. These seven patients had higher (P = 0.013) serum PRL levels (9.3 +/- 7.4 microg/liter) and lower (P < 0.001) ISP measurements (35.9 +/- 7.3 mm Hg) than the respective values in the remaining six with persistent postoperative hypopituitarism (1.6 +/- 0.6 microg/liter and 55.9 +/- 2.4 mm Hg, respectively). The low serum PRL levels in patients with tumor apoplexy suggested that ischemic necrosis of the anterior pituitary resulting from sudden and extreme elevation of ISP was commonly observed in this setting. A normal or elevated serum PRL level in patients with non-PRL-secreting macroadenomas indicates the presence of viable pituitary cells and the high likelihood of postoperative recovery of pituitary function.

Intrasellar pressure in pituitary tumors . Relation study: intrasellar pressure vs hypothalamic-pituitary function

Intrasellar pressure in pituitary tumors . Relation study: intrasellar pressure vs hypothalamic-pituitary function

Medical management of hypopituitarism in patients with pituitary adenomas.

Hypopituitarism is a disease complex with variable clinical manifestations. Recent studies have improved our understanding of its pathophysiology, particularly in patients with pituitary adenomas. In that setting, hypopituitarism was previously considered a permanent and irreversible process, requiring life-long hormone replacement therapy. While this could be true in some instances, recent data demonstrated recovery of pituitary function in a large number of patients with hypopituitarism following surgical decompression. Mechanical compression of portal vessels and the pituitary stalk, by the expanding adenoma was postulated to be the predominant mechanism causing hypopituitarism in this setting. Since portal vessels also provide blood supply to the anterior lobe, ischemic necrosis of portions of the pituitary can occur as a result of increased and prolonged compression by the expanding adenoma. Recent data demonstrated increases in intrasellar pressure (ISP) in patients with pituitary macroadenomas, particularly those with hypopituitarism. The data showed that ISP measurements correlated positively with the serum prolactin levels but not with tumor sizes. It is postulated that increased ISP has predominant role in the pathogenesis of hypopituitarism in patients with pituitary adenomas while. The increase in ISP results in decreased blood flow through the portal vessels and the pituitary stalk. The latter will result in diminished delivery of hypothalamic hormones to the anterior pituitary and may also cause ischemia and/or necrosis in some portions of the normal gland. Recovery of pituitary function can thus be anticipated after surgical decompression, in patients who have viable pituitary cells. Understanding the pathophysiology of hypopituitarism and recognizing the probability for recovery of function should be emphasized in the management of patients with this disease. An important aspect of the management is patients' education about their disease, including the use of medic alert identification. The managing physician should appreciate the variable clinical manifestations of the disease and the possible occurrence of other associated neuroendocrine, neurological and neuro-ophthalmologic signs and symptoms. Treatment of hypopituitarism should not be rigid but instead, always individualized. Management should take into consideration the patients' age, sex, education, original disease process and clinical history.

The Dominant Role of Increased Intrasellar Pressure in the Pathogenesis of Hypopituitarism, Hyperprolactinemia, and Headaches in Patients with Pituitary Adenomas*

Mild hyperprolactinemia frequently accompanies the hypopituitarism seen in patients with pituitary macroadenomas that do not secrete PRL. Recent data suggested that the hypopituitarism and mild hyperprolactinemia in this setting are largely due to compression of pituitary stalk and portal vessels. Headaches (HAs) are frequently seen in patients with large adenomas and at times in those with microadenomas. Because the walls of the sella turcica are relatively rigid, we postulate that tumor growth within the sella increases intrasellar pressure (ISP), which in turn impairs portal blood flow, resulting in mild hyperprolactinemia and hypopituitarism. We also postulate that increased mean ISP (MISP) contributes to the development of HAs. Normal MISP is not known but is unlikely to exceed normal intracranial pressure of less than 10-15 mm Hg. We determined MISP in 49 patients who had transsphenoidal surgery for pituitary adenomas. MISP was measured using a commonly available intracranial monitoring kit where a fiberoptic transducer was inserted through a 2-mm dural incision at the time of adenomectomy. Patients with deficient FSH, LH, ACTH, or TSH secretion were considered hypopituitary. Data on serum PRL levels were included for analysis only in patients whose adenomas had negative immunostaining for the hormone. MISP measurements ranged from 7-56 mm Hg, with a mean (+/-SD) of 28.8 +/- 13.5 and a median of 26 mm Hg. The pressure measurements were higher in patients with hypopituitarism than in those with normal pituitary function (P = 4.6013 x 10(-6)). Patients presenting with HAs had higher MISP than those who did not (P = 5.44 x 10(-7)), regardless of their pituitary function or tumor sizes. PRL levels correlated positively with MISP values (r = 0.715, P < 0.0001). Tumor size did not correlate with MISP or PRL levels. The findings of increased MISP in hypopituitary patients and the documented correlation with PRL levels, suggest that ISP is a major mechanism involved in the pathogenesis of hypopituitarism and hyperprolactinemia. Similarly, the increased MISP in patients with HAs, irrespective of tumor size or pituitary function, suggest that increased ISP is a major mechanism involved in the pathogenesis of this symptom. The data support the hypothesis that in patients with pituitary adenomas increased ISP is a major mechanism contributing to the development of hyperprolactinemia, hypopituitarism, and HAs. Increased ISP in these patients leads to compression of the portal vessels and the associated interruption of the delivery of hypothalamic hormones to the anterior pituitary. This would explain the reversibility of pituitary function observed in most patients after adenomectomy. However, increased ISP may also lead to decreased blood supply, resulting in ischemic necrosis in some regions of the pituitary. The latter could limit potential recovery of pituitary function after adenomectomy.

The Dominant Role of Increased Intrasellar Pressure in the Pathogenesis of Hypopituitarism, Hyperprolactinemia, and Headaches in Patients with Pituitary Adenomas

The Dominant Role of Increased Intrasellar Pressure in the Pathogenesis of Hypopituitarism, Hyperprolactinemia, and Headaches in Patients with Pituitary Adenomas