Diabetes insipidus and syndrome of inappropriate antidiuresis (SIADH) after pituitary surgery: incidence and risk factors.

Electrolyte disorders are relatively frequent and potentially serious complications after pituitary surgery. Both DI (diabetes insipidus) and SIADH (syndrome of inappropriate antidiuresis) can complicate and prolong hospital and intensive care unit stay, and the latter may even be preventable. We aim to assess the incidence of both electrolyte disorders and their risk factors. From a prospective registry of patients who underwent endoscopic transnasal transsphenoidal surgery (TSS) for pituitary adenoma, patients with postoperative DI and SIADH were identified. Univariable and multivariable statistics were carried out to identify factors independently associated with the occurrence of either DI or SIADH. A total of 174 patients were included, of which 73 (42%) were female. Mean age was 54 years (range 20-88). During postoperative hospital stay, 13 (7.5%) patients presenting with DI and 11 (6.3%) with SIADH were identified. Patients who developed DI after surgery had significantly longer hospital stays (p = 0.022), as did those who developed SIADH (p = 0.002). Four (2.3%) patients were discharged with a diagnosis of persistent DI, and 2 (1.1%) with the diagnosis of SIADH. At the last follow-up, 5 (2.9%) patients presented with persistent DI, while none of the patients suffered from SIADH. Younger age (odds ratio (OR) 0.97, 95% confidence interval (CI) 0.94-1.01, p = 0.166) and pituitary apoplexy (OR 2.69, 95% CI 0.53-10.65, p = 0.184) were weakly associated with the occurrence of DI. We identified younger age (OR 0.96, 95% CI 0.92-0.99, p = 0.045) and lower preoperative serum sodium (OR 0.83, 95% CI 0.71-0.95, p = 0.008) as independent risk factors for SIADH. Although we found a weak association among age, pituitary apoplexy, and the occurrence of DI, no independent predictor was identified for DI. For postoperative SIADH however, lower age and preoperative serum sodium were identified as significant predictors. None of these findings were sufficiently supported by preexisting literature. Both electrolyte disorders are exquisitely hard to predict preoperatively, and further research into their early detection and prevention is warranted.

Pituitary adenoma apoplexy with initial presentation mimicking bacterial meningoencephalitis: a case report.

Pituitary apoplexy is a rare but life-threatening disorder. Clinical presentation of this condition includes severe headache, impaired consciousness, fever, visual disturbance, and variable ocular paresis. Signs of meningeal irritation are very rare. However, if present and associated with headache, fever, and pleocytosis, meningeal irritation may lead to misinterpretation as infectious meningoencephalitis. To the best of our knowledge, pituitary apoplexy with an initial presentation mimicking infectious meningoencephalitis had rarely been reported in the literature. Here, we report a 57-year-old man who had acute severe headache, high fever, neck stiffness, disturbance in consciousness, and left ocular paresis. Laboratory data showed leukocytosis, an elevated C-reactive protein level, and neutrophilic pleocytosis in the cerebrospinal fluid. Because bacterial meningoencephalitis was suspected, empiric antibiotic therapy was administered but in vain. Further examinations indicated a diagnosis of pituitary adenoma with apoplexy. After the immediate administration of intravenous corticosteroid supplement and surgical decompression, the patient recovered.

Cerebrospinal fluid rhinorrhea following trans-sphenoidal pituitary macroadenoma surgery: experience from 592 patients.

OBJECTIVES: To determine the incidence, risk factors, diagnostic procedures, and management of cerebrospinal fluid (CSF) leaks following trans-sphenoidal pituitary macroadenoma surgery. METHODS: Retrospective analysis of 592 patients. RESULTS: Intra- and post-operative CSF leaks occurred in 14.2 and 4.4% of patients, respectively. Surgical revision, tumor consistency, and tumor margins were independently associated with intra-operative leaks, while the tumor size, consistency, and margins were risk factors of post-operative leaks. The intra-operative leak rate of ACTH adenomas was greater than all other types combined; the incidence of post-operative CSF leaks was highest for FSH adenomas. There were no significant differences among various techniques and we achieved an initial repair success rates of 83.3 and 92.9% for intra- and post-operative CSF leaks, respectively. Of the 26 patients with post-operative CSF leaks, five were complicated by meningitis and four by post-infectious hydrocephalus which required ventriculoperitoneal shunts. CONCLUSIONS: CSF leaks have a propensity to occur in cases with fibrous tumors or tumors with indistinct margin and may have some relationship with the tumor type. Endoscopic and microscopic repairs were shown to be effective techniques in managing these types of leaks. Post-infectious hydrocephalus may influence the outcome of the repair and ventriculoperitoneal shunts were necessary in some cases.

[Metabolic pool of free amino acids in the blood and cerebrospinal fluid of patients with pituitary adenoma before and after proton therapy]. / Metabolicheskii fond svobodnykh aminokislot krovi i spinnomozgovoi zhidkosti u bol'nykh adenomoi gipofiza do i posle protonnoi terapii.

A pool of free amino acids was studied in blood and cerebrospinal fluid of 34 patients with adenoma of hypophysis before proton therapy and within 3 years after the treatment. The course of proton therapy was shown to cause a regression of the disease, a decrease in content of somatotropic hormone in blood as well as to normalize the metabolic pool of amino acids in blood and cerebrospinal fluid.

LH and FSH in human cerebrospinal fluid.

LH and FSH of cerebrospinal fluid (CSF) and serum were radioimmunologically measured. Samples were obtained simultaneously from 116 subjects of the following groups: A. 22 patients with non-endocrine diseases, B. 18 patients with cranial diabetes insipidus (DI) of whom 4 with metastatic carcinomas, C. 5 patients with primary empty sella syndrome, D. one with hydatiform mole, and E. 70 patients with pituitary adenomas, i.e. growth hormone--or prolactin-secreting or "non-secreting" adenomas, of whom 38 patients with invasive and 32 with enclosed adenomas. LH and FSH are normal constituents of CSF and their CSF levels poorly correlates with the serum ones (LH r = 0.477 p less than 0.01). Enclosed adenomas with SSE showed low levels of LH in CSF. High CSF-gonadotropins concentrations (above 4.0 mIU/ml) with a low serum/CSF ratio (below 3) was frequently, but not constantly found in patients with invasive adenomas and are not indicative per se of this diagnosis. Some patients with brain metastasis from breast carcinoma and DI, or with non-tumoral diseases and DI showed similar high patterns of CSF gonadotropins though the serum levels were within normal range. This suggests that local vascular mechanisms, including the retrograde circulation of gonadotropins from the pituitary to the hypothalamus, influence the blood-brain barrier much more than the release of gonadotropins into the systemic blood circulation.

Adenohypophyseal hormone levels in the cerebrospinal fluid of patients with pituitary disease.

Measurement of adenohypophyseal hormones in the cerebrospinal fluid (CSF) was recently proposed as an useful procedure to differentiate pituitary intra and extrasellar tumors. So far, data reported are conflicting. We measured the concentrations of GH, TSH, LH and PRL in CSF and plasma in 30 controls and in 37 patients with various pituitary diseases (18 intrasellar adenomas, 14 extrasellar adenomas and 5 empty sella syndromes). The concentrations of examined hormones in CSF were very low or undetectable in all control subjects. In most patients with pituitary tumors, adenohypophyseal hormones were found to be present in CSF, in great amounts. No significant differences were found between intra and extrasellar tumors. In agreement with recently reported data, no significant correlation was found between GH, TSH, FSH and LH levels in CSF and plasma, while a significant correlation (p less than 0.01) was obtained between CSF and plasma levels of PRL, either in all patients or in those with extrasellar tumors only. All patients bearing an empty sella had PRL detectable in CSF: in 2 cases PRL levels were very high. In conclusion our data do not confirm that measurement of adenohypophyseal hormones in CSF represents an useful screening to differentiate tumors with extrasellar extension. PRL data deserve interest in order to gain understanding of the hormone dynamics between CSF and vascular compartments.

Polyamine levels in CSF from patients with pituitary tumors or nonneoplastic pituitary disease.

Cerebrospinal fluid polyamine determinations were performed in 21 patients harboring pituitary tumors and six patients with nonneoplastic pituitary disease. Although CSF putrescine levels were significantly elevated in some patients harboring tumors, other patients showed no elevation. Polyamine levels did not correlate with tumor size, as assessed by the presence or absence of suprasellar extension. Data on patients harboring nonneoplastic pituitary disease were variable. Compared with other findings from this laboratory on the use of polyamine levels for the diagnosis and management of other brain tumors, these findings suggest that CSF polyamine levels will not have a significant diagnostic role in the treatment of patients suspected to have pituitary disease.

[Measurement of methionine-enkephalin-like substance in CSF from normal subjects and patients with pituitary adenoma (author's transl)].

Methionine-enkephalin-like substance was measured in CSF by the radioreceptor-assay established by Furui et al. Samples were obtained from preoperative 20 cases, in which were included 11 cases of pituitary adenoma, 3 cases of craniopharyngioma, 2 cases of pseudtumor cerebri and 4 normal cases, by lumbar puncture. Also postoperative measurement of this substance and pre- and postoperative measurement of ACTH in plasma were performed in 5 cases of Cushing's disease. Five ml of CSF was chromatograpied on two successive columns, lyophilized and assayed for opiate receptor affinity against 3H-dihydromorphine. Measured values were expressed as methionine-enkaphalin equivalents using the displacement curve run in parellel. Methionine-enkephalin-like substance level ranged from less than 0.5 to 20.0 pmoles/ml in all cases and mean value was 2.6 pmoles/ml (+/- 1.0 S.E.) in normal subjects. In Cushing's disease the level was not elevated preoperatively (2.1 +/- 0.3) and did not significantly decrease postoperatively (1.6 +/- 0.4 pmoles/ml) in contrast to the decrease of ACTH in plasma. It is suggested that methionine-enkephalin-like substance in CSF is not derived from ACTH producing cells of pituitary gland. One case of craniopharyngioma showed very high value. This case revealed diabetes insipidus at sampling. The possibility of participation of methionine-enkephalin in secretion of antidiuretic hormone was discussed.

[Determination of pituitary hormones in cerebrospinal fluid in normal subjects and in hypothalamo-pituitary diseases. Secreting or non-secreting pituitary adenoma, empty sella syndrome, hypothalamic syndromes]. / Le dosage des stimulines hypophysaires dans le liquide céphalo-rachidien chez le sujet normal et en pathologie hypothalamo-hypophysaire. Adénome hypophysaire sécrétant ou non sécrétant, selle turcique vide, syndromes hypothalamiques.

Cerebrospinal fluid (CSF) and serum concentrations of TSH, ACTH, FSH, LH, GH and PRL were measured simultaneously in 34 subjects divided into 3 groups: I--12 normal subjects (6 males and 6 females); II--12 prolactin adenomas (3 males and 9 females); III--5 empty sella syndromes; 3 hypothalamic disorders; 1 chromophobe adenoma; 1 pituitary dwarfism. It is concluded that:--pituitary hormones are the normal constituents of CSF but the level can be undetectable and in any case lower than the serum level; --there is a positive correlation between serum and CSF concentration of PRL when serum PRL is higher than 20 ng/ml, indicating that the CSF level is influenced by serum level; --in prolactin adenomas only prolactin is elevated in the CSF; --there is no correlation between the high level of CSF-PRL and a suprasellar extension of the adenoma.

[Determination of 6 pituitary hormones in the cerebrospinal fluid. Control subjects, prolactin adenomas, empty sella syndrome and hypothalamic disorders (author's transl)]. / Dosage de 6 stimulines hypophysaires dans le liquide céphalo-rachidien. Sujets normaux, adénomes à prolactine, selles vides, syndromes hypothalamiques.

Cerebrospinal fluid (CSF) and serum concentrations of TSH, ACTH, FSH, LH, GH and PRL were measured simultaneously in 34 subjects divided into 3 groups: I-12 normal subjects (6 males and 6 females); II-12 prolactin adenomas (3 males and 9 females); III-5 empty sella syndromes, 3 hypothalamic disorders, 1 chromophobe adenoma, 1 pituitary dwarfism. It is concluded that: 1) pituitary hormones are the normal constituents of CSF but the level can be undetectable and in any case lower than the serum level. 2) there is a positive correlation between serum and CSF concentration of PRL when serum PRL is higher than 20 ng/ml, indicating that the CSF level is influenced by serum level. 3) in prolactin adenomas, only prolactin is elevated in the CSF. 4) there is no correlation between the high level of CSF-PRL and a suprasellar extension of the adenoma.

Spectrum of total fatty acids in cerebrospinal fluid determined by gas chromatography.

A simple gas-liquid chromatographic method for the determination of the spectrum of fatty acids in a small volume of cerebrospinal fluid (CSF) is presented. In a group of 49 neurological patients it has been found that in the CSF of the controls (n = 12) there are the following main fatty acids: oleic (27.28%), palmitic (23.23%), stearic (12.21%), linoleic (7.66%), myristic (5.02%), and palmitoleic (4.51%). Altogether 28 fatty acid methyl esters (FAME'S) from 12:0 to 22:2 have been tentatively identified. The majority of them appeared irregularly, sometimes in less than in 10% of cases. The composition of FAME'S in the CSF of patients with lumbar discopathy and with acute ischaemic cerebrovascular accidents does not differ from the control group. A significant difference (P less than 0.01) has been found in the group of hypophyseal adenomas in which the amounts of practically all saturated FAME'S with an odd carbon number are elevated. The same applies to the 18:0 and 20:0 compounds. In the group of atrophic and degenerative CNS processes the palmitic and stearic acids predominated to the detriment of oleic and linoleic acids.

Suprasellar extension of tumour associated with increased cerebrospinal fluid activity of LH and FSH.

A 65 year old man with pituitary adenoma, partial hypopituitarism and normal serum FSH and LH concentration is described. LH (but not FSH) partially increased following the administration of LH-RH. Subsequent FSH and LH assays of the cerebrospinal fluid, however, showed a high and correctly predicted suprasellar extension of the tumour.

Prolactin in human cerebrospinal fluid.

PRL was measured radioimmunologically in plasma and cerebrospinal fluid (CSF) samples obtained simultaneously in 31 patients with various neurological or infectious, but non-endocrine diseases (group A), 12 patients (7 pregnant women and 5 newborns) with physiological hyperprolactinemia (group B),10 psychiatric patients with pharmacologically induced hyperprolactinemia (group C) 12 normoprolactinemic patients with pituitary adenoma and suprasellar extension (SSE) (group D), And 14 hyperprolactinemic patients with pituitary adenoma with and without SSE (group E). Plasma PRL and CSF PRL concentrations (ng/ml, mean and range in brackets) of the various groups were: group A, 6.2 (1.3-14.5) and 1.3 (0.6-4.7); group B, 85.2 (31-200) and 13.2 (3-28); group C, 54.3 (3.5-160) and 6.5 (0.7-18); group D, 17.2 (5.4-30) and 9.7 (2.7-34); and group E, 2,529 (115-10,000) and 1,449 (6-13,000). The plasma to CSF concentration ratios (mean and range in brackets) were: group A, 5.2 (1.4-13.0); group B, 7.0 (2.9-10.3); group C, 7.3( 3.9-11.3); group D, 2.6 (0.9-7.1); and group E, 10.9 (0.2-34.9). The ratio was greater than 3 in 87% of the non-tumor patients; in 42% of the tumor patients the ratio was less than 3. The correlation between plasma and CSF PRL levels of all 53 subjects without a pituitary tumor (groups A, B, and C) was positive (r=0.9097; P=0.00001); in the 26 tumor patients (groups D and E) the correlation was also positive (r=0.7141; P=0.00002). These results indicate that 1) PRL is a normal constituent of CSF, 2) the CSF PRL level is a function of the plasma level, 3) detectable, or even high, CSF PRL levels per se are not indicative in the presence of a pituitary tumor, with or without SSE, and 4) abnormally low ratios may be found in patients with a pituitary tumor with SSE.

[Endocrinological evaluation of sellar and suprasellar tumor cases (the ninth report)--on the PRL levels in the CSF (author's transl)].

Prolactin (PRL) levels in the cerebrospinal fluid (CSF) and plasma of 25 patients with sellar and suprasellar tumors, i.e. 5 of PRL secreting adenoma, 5 of GH secreting adenoma, 7 of so-called non-functioning pituitary adenoma, 5 of tuberculum sellae meningioma and 3 of craniopharyngioma, were studied in relation to the size of suprasellar extension measured by our own method on pneumoencephalograms. Plasma and CSF samples were obtained simultaneously at the time of lumbar puncture for pneumoencephalography. 1) Five patients of PRL secreting adenoma, whose plasma PRL levels ranged from 530 to 4,000 ng/ml, showed high PRL levels over 50 ng/ml in the CSF. On the contrary, 20 patients of the other tumors, whose plasma PRL levels were lower than 30 ng/ml, showed low PRL levels in th4 CSF, being below the sensitivity limit in the majority. 2) In 3 out of 5 PRL secreting adenomas, the PRL level in the CSF was higher than the plasma level and they showed a fairly large extrasellar extension. However in the remaining 2 the PRL level in the CSF was lower than a tenth of that in the plasma, and these revealed relatively small suprasellar extension. From these facts the presence of PRL at a high level in the CSF seems to be specific in the PRL secreting adenomas, and there seems to be a relationship between the CSF-plasma ratio of PRL level and the extrasellar extension in these cases.