Rudolf A. Kristof

Lymphocytic hypophysitis: non-invasive diagnosis and treatment by high dose methylprednisolone pulse therapy?

Criteria for the non-invasive diagnosis of lymphocytic hypophysitis (LyHy) and the results of the first prospective trial of high dose methylprednisolone pulse therapy (HDMPT) in nine patients are presented. In three patients, the diagnosis was established histologically, and in the others by clinical and endocrinological assessment, MRI, CSF examination, and measurement of thyroglobulin autoantibody concentration. After HDMPT, adenopituitary function improved in four of the nine patients and diabetes insipidus ceased or improved in all four concerned patients. The MRI findings improved in seven patients. LyHy has to be considered in the differential diagnosis of sellar lesions. The presumptive non-invasive diagnosis of LyHy seems possible in a high proportion of patients. HDMPT may result in the improvement of clinical, endocrinological, and MRI findings.

Does Octreotide Treatment Improve the Surgical Results of Macro-Adenomas in Acromegaly? A Randomized Study

Summary It is not clear whether the pre-operative treatment of GH-secreting pituitary adenomas with Octreotide improves the surgical remission rates of acromegaly. In a prospective controlled study the results of transsphenoidal surgery in newly diagnosed GH-secreting macro-adenomas were compared in patients with (n=11, group A) and without (n=13, group B) preoperative Octreotide treatment. During the treatment with a daily dosage of 470±160 μg Octreotide for 16, 5±10 weeks, the GH- and IGF-1-values of group A dropped significantly from 38, 9±34, 1 to 6, 8±4, 9 μg/l and from 2, 7±1 to 1, 7±0, 7 arbitrary units respectively. The adenoma-shrinkage from 5, 9±5, 8 to 4, 7±4, 9 cm3 missed statistical significance by little. There was no statistically significant difference between the postoperative acromegaly remission rates of 55% in group A and 69% in group B. Of the adenomas that postoperatively were not in remission, 80% in group A and 75% in group B disclosed an infiltrative growth pattern not influenced by the Octreotide pretreatment. All other patients not cured presented with initial GH-values of >50μ{\rm g/l}. There was no statistically significant difference between the postoperative anterior pituitary function in the two patient groups. In this study Octreotide was not beneficial in improving the results of GH-secreting pituitary macro-adenoma surgery. However, larger prospective controlled studies are needed to address this issue.

Incidence, clinical manifestations, and course of water and electrolyte metabolism disturbances following transsphenoidal pituitary adenoma surgery: a prospective observational study.

OBJECT The authors prospectively studied the incidence, spectrum of clinical manifestations, course, and risk factors of water and electrolyte disturbances (WEDs) following transsphenoidal pituitary adenoma surgery. METHODS From the preoperative day to the 14th postoperative day, 57 successive patients undergoing transsphenoidal adenomectomy were monitored daily for body weight, balance of fluids, serum electrolytes, plasma osmolality, plasma antidiuretic hormone (ADH) levels, urinary sodium excretion, urinary osmolality, and subjective sensation of thirst. The type of adenoma operated on and the intraoperative manipulation of the neurohypophysis were also recorded. RESULTS Fifty-seven patients (mean age 55 years, 61.4% females) harbored 30 clinically hormone-inactive and 27 hormone-secreting pituitary adenomas. Postoperative WED occurred in 75.4% of the patients: in 38.5% as isolated diabetes insipidus (DI); in 21% as isolated hyponatremia; and in 15.7% as combined DI-hyponatremia. The maximum of medians of diuresis (5.750 L) in patients with isolated DI occurred on postoperative Day 2. Nadir of medians of hyponatremia (132 mmol/L) in patients with isolated hyponatremia occurred on postoperative Day 9. In patients with combined DI-hyponatremia, maximum of medians of diuresis (5.775 L) occurred on the 2nd day and nadir of medians of hyponatremia (130 mmol/L) on the 10th postoperative day. Altogether, 8.7% of the patients had to be treated with desmopressin because of DI persisting for >3 months. Of all the patients with hyponatremia, 42.8% were treated by transient fluid-intake restriction due to an IH of <130 mmol/L with or without clinical symptomatology. Transient acute renal failure occurred in one of these patients. Generally, the occurrence of postoperative WEDs was linked to the intraoperative manipulation of the neurohypophysis. Increased thirst correlated significantly with DI (p=0.001 and 0.02, respectively) and decreased thirst with the hyponatremic episode in patients with combined DI-hyponatremia (p=0.003). Decreased urine osmolality correlated significantly with the presence of DI (p=0.023). Electrolyte-free water clearance and urinary Na+ excretion were not correlated with DI and hyponatremia. Antidiuretic hormone was not suppressed during hyponatremia. CONCLUSIONS Water and electrolyte disturbances occurred in the majority of patients undergoing transsphenoidal adenomectomy and were usually transient. Diabetes insipidus is more frequent than hyponatremia. Diabetes insipidus usually occurs during the 1st postoperative day and resolves in the majority of cases within 10 days. In few patients, DI may persist and require therapy with ADH analogs. Hyponatremia usually occurs at the end of the 1st postoperative week and resolves in most cases within 5 days. Very few patients will need treatment other than fluid-intake restriction to avoid serious complications. Thus, careful monitoring of the WEDs in patients undergoing transsphenoidal pituitary adenoma surgery is mandatory for the first 10 postoperative days.

Endocrinological Outcome Following First Time Transsphenoidal Surgery for GH-, ACTH-, and PRL-Secreting Pituitary Adenomas

Summary.Background: To study remission rates and pituitary functions following transsphenoidal surgery of newly diagnosed GH-, ACTH-, and PRL-secreting pituitary adenomas.Methods: Out of a series of 329 newly diagnosed pituitary adenomas, 131 (39.8%) were hormone (67 GH-, 27 ACTH-, 37 PRL-) secreting. PRL-secreting adenomas were subjected to surgery because they failed to respond to previous medical treatment therapy. The data on secreting adenomas, regarding the results of standardised endocrinological testing, MRI findings and water metabolism disturbances, were extracted retrospectively from the pituitary data-base of the hospital. The mean follow-up was 3.7 years.Results: The overall remission rate for PRL-secreting adenomas (27%) was significantly lower than for GH- (71.6%) and ACTH-secreting (81.5%) ones. Remission rates correlated negatively with the magnitude of preoperative hormone excess (not in Cushings disease), tumour size (not in prolactinoma) and invasiveness. Generally, the improvement of the adenopituitary functions was statistically significant during the first three postoperative months, and thereafter remained unchanged. Diabetes insipidus persisting for more than three months occurred with similar frequency in the three patient groups (in 9.4% of GH-, in 6.7% of ACTH-, and in 10% of PRL-secreting adenomas). Tumour regrowths occurred more often in PRL-(20%) than in ACTH- (9.1%) and GH- (0%) secreting tumours.Conclusions: In GH- and ACTH-secreting pituitary adenomas, remission rates were significantly higher and recurrence rates lower than in PRL-secreting adenomas, which had failed to respond to previous medical therapy. The overall postoperative adenopituitary function was improved in all patient groups. Diabetes insipidus occurred with similar frequency in all patient groups. When reporting on results of surgery for secreting pituitary adenomas, not only remission and recurrence rates, but also the results of the pituitary function should be included.

Cerebrospinal fluid leakage into the subdural space: possible influence on the pathogenesis and recurrence frequency of chronic subdural hematoma and subdural hygroma.

OBJECT The purpose of this study was to clarify whether cerebrospinal fluid (CSF) leakage into the subdural space is involved in the genesis of chronic subdural hematoma (CSDH) and subdural hygroma (SH) and to clarify whether this leakage of CSF into the subdural space influences the postoperative recurrence rate of CSDH and SH. METHODS In this prospective observational study, 75 cases involving patients treated surgically for CSDH (67 patients) or SH (8 patients) were evaluated with respect to clinical and radiological findings at presentation, the content of beta -trace protein (beta TP) in the subdural fluid (betaTPSF) and serum (betaTPSER), and the CSDH/SH recurrence rate. The betaTPSF was considered to indicate an admixture of CSF to the subdural fluid if betaTPSF/betaTPSER>2. RESULTS The median beta TPSF level for the whole patient group was 4.29 mg/L (range 0.33-51 mg/L). Cerebrospinal fluid leakage, as indicated by betaTPSF/betaTPSER>2, was found to be present in 93% of the patients with CSDH and in 100% of the patients with SH (p=0.724). In patients who later had to undergo repeated surgery for recurrence of CSDH/SH, the betaTPSF concentrations (median 6.69 mg/L, range 0.59-51 mg/L) were significantly higher (p=0.04) than in patients not requiring reoperation (median 4.12 mg/L, range 0.33-26.8 mg/L). CONCLUSIONS As indicated by the presence of betaTP in the subdural fluid, CSF leakage into the subdural space is present in the vast majority of patients with CSDH and SH. This leakage could be involved in the pathogenesis of CSDH and SH. Patients who experience recurrences of CSDH and SH have significantly higher concentrations of betaTPSF at initial presentation than patients not requiring reoperation for recurrence. These findings are presented in the literature for the first time and have to be confirmed and expanded upon by further studies.

Clinical, radiological, and therapeutic features of pleomorphic xanthoastrocytoma: report of three patients and review of the literature.

Two out of three patients with pleomorphic xanthoastrocytoma were initially misdiagnosed and correctly interpreted only at tumour recurrence, with progression to malignancy in one. The third patient presented with a remarkably long history of epilepsy. Pleomorphic xanthoastrocytoma is a low grade astrocytoma that is still confused with other tumours. Because pleomorphic xanthoastrocytoma can become malignant even after many years of benign behaviour, a long term follow up is necessary.

Pituitary apoplexy with spontaneous cure of acromegaly and its possible relation to Gd-DTPA-administration.

SummaryA case of pituitary apoplexy occurring after Gd-DTPA-administration for contrast enhanced MRI in a patient with an hGH-producing macro-adenoma is presented. Within days the initially increased hGH level fell to the normal range, the oral glucose tolerance test (OGTT) showed a normal suppression of hGH and complete anterior pituitary insufficiency developed. At this time repeated MRI suggested a haemorrhagic infarction of the macroadenoma. Fourteen months later re-examination confirmed spontaneous cure of the acromegaly, improvement of adenopituitary function and shrinkage of the sellar content. The causal linkage between the pituitary adenoma apoplexy and Gd-DTPA-administration is unclear. It might be due to contrast induced blood pressure and endothelial permeability changes, possibly promoted by pre-existing diabetes mellitus associated vasculopathy.

Sarcoidosis presenting as an intra- or extra-axial cranial mass: report of two cases

Abstract Sarcoidosis may also present as an extra- or intra-axial mass involving the central nervous system. These lesions are sometimes operated upon, because a neoplasm is suspected. We report two cases of unusual tumour-like extra- and intra-axial sarcoidosis. The extra-axial mass was just medial to the jugular foramen. Its morphology and signal characteristics differed from the more common lesions in this area. The intra-axial mass was in the temporal lobe, with only minor leptomeningeal involvement. Extra-axial sarcoidosis can be confused with a meningioma because these lesions can give relatively low signal on T2-weighted images. Intra-axial masses are presumed to represent a propagation and fusion of multiple leptomeningeal granulomas through the Virchow-Robin spaces in the brain; this pattern can be sought on contrast-enhanced T1-weighted images.

The regional oxygen saturation of pituitary adenomas is lower than that of the pituitary gland: microspectrophotometric study with potential clinical implications.

OBJECTIVETo study the regional oxygen saturation (rSO2) of pituitary adenomas, in comparison with that of the pituitary gland. METHODSMicrospectrophotometric (MSP) measurements of rSO2 in adenomas and pituitary tissue were performed for a series of patients undergoing first-time transsphenoidal pituitary adenoma surgery, in a standardized anesthesia setting. The areas of measured tissue were sampled for histopathological and immunohistochemical (CD34 and CD45) assessments. The results of MSP measurements were compared with the results of the histopathological and immunohistochemical assessments. RESULTSThirty-six MSP measurements and tissue samples were obtained among 22 patients with pituitary macroadenomas, including 14 from adenoma tissue, 17 from the anterior pituitary lobe, and 5 from the posterior pituitary lobe. The rSO2 of adenoma tissue (mean ± standard deviation, 43.3 ± 23.2%) was statistically significantly (P = 0.001) lower than the values for the anterior pituitary lobe (mean ± standard deviation, 71.8 ± 18.3%) and posterior pituitary lobe (mean ± standard deviation, 74.9 ± 4.8%). The difference between the rSO2 values for the anterior pituitary lobe and posterior pituitary lobe was not significant. There were no statistically significant differences in microvessel density (as assessed with CD34 staining) or lymphocyte density (as assessed with CD45 staining) among the three tissue types. CONCLUSIONAs assessed with MSP measurements, the rSO2 of adenoma tissue was significantly lower than that of the pituitary gland, indicating differences in their blood supply and/or metabolism in pituitary macroadenomas. Further studies are needed to determine whether MSP measurements can reliably facilitate intraoperative delineation of adenoma and pituitary tissue, in the effort to achieve complete tumor removal with minimal injury to pituitary tissue.

Intracerebral capillary telangiectasia and venous malformation: A rare association

BACKGROUND The vascular malformations of the brain have been classified into arteriovenous, venous, cavernous, and capillary malformations as four discrete entities. Various combinations of two discrete malformations in one lesion have been reported, some of which can be considered as established associations, while others appear to be very rare. Mixed vascular malformations evoke reflections on possible interrelations in the pathogenesis of the discrete components. CASE DESCRIPTIONS We report a case of intracerebral capillary telangiectasia associated with a venous malformation in a supratentorial paraventricular location in a 45-year-old woman with a history of headache. The capillary telangiectasia was diagnosed by stereotactic biopsy. Magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA) strongly suggested the presence of a venous malformation by demonstrating a transcerebral draining vein running through the center of the capillary telangiectasia. The association of capillary telangiectasia and venous malformation has been reported only twice before and exclusively in the posterior fossa, as opposed to the more frequent, established associations of capillary telangiectasia and cavernous malformation, and venous malformation and cavernous malformation, respectively. CONCLUSIONS Against the background of the established associations, this rare observation possibly places capillary telangiectasias, cavernous malformations, and venous malformations within the spectrum of a single disease. The common pathogenetic role of a focal venous outflow obstruction is discussed.