ESE Clinical Practice Guideline on functioning and nonfunctioning pituitary adenomas in pregnancy.

Pregnancies are rare in women with pituitary adenomas, which may relate to hormone excess from secretory subtypes such as prolactinomas or corticotroph adenomas. Decreased fertility may also result from pituitary hormone deficiencies due to compression of the gland by large tumours and/or surgical or radiation treatment of the lesion. Counselling premenopausal women with pituitary adenomas about their chance of conceiving spontaneously or with assisted reproductive technology, and the optimal pre-conception treatment, should start at the time of initial diagnosis. The normal physiological changes during pregnancy need to be considered when interpreting endocrine tests in women with pituitary adenomas. Dose adjustments in hormone substitution therapies may be needed across the trimesters. When medical therapy is used for pituitary hormone excess, consideration should be given to the known efficacy and safety data specific to pregnant women for each therapeutic option. In healthy women, pituitary gland size increases during pregnancy. Since some pituitary adenomas also enlarge during pregnancy, there is a risk of visual impairment, especially in women with macroadenomas or tumours near the optic chiasm. Pituitary apoplexy represents a rare acute complication of adenomas requiring surveillance, with surgical intervention needed in some cases. This guideline describes the choice and timing of diagnostic tests and treatments from the pre-conception stage until after delivery, taking into account adenoma size, location and endocrine activity. In most cases, pregnant women with pituitary adenomas should be managed by a multidisciplinary team in a centre specialised in the treatment of such tumours.

[Diagnostics and treatment of acromegaly : Necessity for targeted monitoring of comorbidities]. / Diagnostik und Therapie der Akromegalie : Notwendigkeit der gezielten Überwachung von Komorbiditäten.

Acromegaly is a rare and severe condition, presenting with typical signs and symptoms. The diagnosis is often initially made years after the first manifestations of the disease. In more than 99% of patients the disease is caused by a benign pituitary tumor that secretes growth hormone (GH). The diagnosis is based on the presence of increased insulin-like growth factor 1 (IGF-1) levels and a lack of GH suppression in the oral glucose tolerance test. The standard imaging procedure for tumor detection is magnetic resonance imaging in the region of the sella turcica. Treatment includes surgical, drug and radiation therapy. Important factors are an intensive aftercare of the patient, controls for detection of tumor recurrence and pituitary insufficiency as well as assessment of various organ functions and risk constellations. Patient care should involve close cooperation between endocrinologists, neurosurgeons and general practitioners as well as other specialist disciplines.

[Ultrasonography of the prostate gland : From B­image through multiparametric ultrasound to targeted biopsy]. / Ultraschall der Prostata : Vom B­Bild über den multiparametrischen Ultraschall zur gezielten Biopsie.

BACKGROUND: Prostate cancer is the most frequent cancer in men. The diagnosis is normally achieved by a systematic prostate biopsy; however, this is a randomized approach by which a substantial number of significant carcinomas go undetected. For this reason, in recent years imaging techniques have been continuously developed, which enable visualization and therefore targeted biopsies. STANDARD PROCEDURE: The use of systematic biopsies is a standard procedure for the detection of prostate cancer. The quality of biopsies can be increased if the prostate is examined for the presence of suspected cancerous alterations during the biopsy. This can be carried out using multiparametric transrectral ultrasound. PERFORMANCE: Multiparametric ultrasound within the framework of a targeted biopsy increases the detection rate of significant prostate carcinomas with a simultaneous decrease in detection of insignificant carcinomas; however, the diagnostic reliability and the evidence level of multiparametric transrectal ultrasound are not yet sufficiently high to be able to replace a systematic biopsy. CONCLUSION: In the hands of a well-trained examiner multiparametric transrectal ultrasound represents a good method for detection of prostate carcinomas. With the progression in technical developments of ultrasound technology, the detection rate will presumably be further increased.

Strong association of serum- and glucocorticoid-regulated kinase 1 with peripheral and adipose tissue inflammation in obesity.

OBJECTIVE: The serum- and glucocorticoid-regulated kinase 1 (SGK1) is an early transcriptional target of glucocorticoids and is activated via insulin. Here we investigate the regulation of SGK1 expression in human obesity, diet-induced murine obesity and human monocytic cell line THP-1 monocytes. SUBJECTS AND METHODS: SGK1 expression was studied in subcutaneous and omental adipose tissue (AT) of 20 morbidly obese and 20 age- and gender-matched non-obese controls in murine diet-induced obesity and the THP-1 cell line. The regulation of SGK1 by inflammatory signals was tested in THP-1 cells. RESULTS: Murine diet-induced obesity is associated with a significant upregulation of Sgk1 in gonadal AT. Sgk1 expression is highest in the macrophage-rich stromal vascular fraction and lower in adipocytes. In humans, AT SGK1 is predominantly expressed in CD14(+) macrophages and significantly upregulated in omental and subcutaneous AT of obese subjects. SGK1 mRNA expression in both omental and subcutaneous AT correlates with body mass index, circulating leptin and C-reactive protein, and the local expression of inflammatory markers including monocyte chemotactic protein-1 and macrophage inflammatory protein-1α. The expression of SGK1 in THP-1 cells is upregulated by inflammatory signals, such as lipopolysaccharide and tumour necrosis factor-α, as well as during the induction of monocyte-to-macrophage maturation. CONCLUSIONS: Our data present the first link between SGK1 and obesity-associated inflammation. SGK1 expression is stimulated in response to inflammatory signals and increased in AT macrophages. The characterisation of SGK1 functions in obesity and immunity may help identify potential therapeutic targets in the treatment of obesity.

Serum uric acid is related to cardiovascular events and correlates with N-terminal pro-B-type natriuretic peptide and albuminuria in patients with diabetes mellitus.

BACKGROUND: Hyperuricemia is a risk factor for cardiovascular events and renal insufficiency. It correlates to intima-media thickness and microalbuminuria. In this study we evaluated uric acid as an independent marker for cardiac events in patients with diabetes. METHODS: In a prospective observational study we recruited 494 patients with diabetes. Patients were then followed for 12.8 months (mean follow-up) and hospitalizations as a result of cardiac events (ischaemic heart disease, arrhythmias, heart failure) were recorded. RESULTS: The median duration of diabetes was 11 ± 10.35 years. Patients were in the mean 60 ± 13 years old and mean HbA(1c) was 62 ± 13 mmol/mol (7.8 ± 3.3%). At baseline, mean uric acid was 321.2 ± 101.1 µmol/l (range 101.1-743.5 µmol/l), median N-terminal pro-B-type natriuretic peptide was 92 ± 412 pg/ml and median urinary albumin to creatinine ratio was 8 ± 361 mg/g; Uric acid significantly correlated to N-terminal pro-B-type natriuretic peptide (r = 0.237, P < 0.001) and urinary albumin:creatinine ratio (r = 0.198, P < 0.001). In a Cox regression model, including age, estimated glomerular filtration rate, gender, systolic blood pressure, smoking and alcohol consumption, uric acid was the best predictor of cardiac events (hazard ratio 1.331, confidence interval 1.095-1.616, P = 0.04). However, uric acid lost its prognostic value when the natural logarithm of N-terminal pro-B-type natriuretic peptide was added to the model. CONCLUSION: Serum uric acid is a predictor of cardiac events and correlates to N-terminal pro-B-type natriuretic peptide and albuminuria, underscoring the importance of uric acid as a cardiovascular risk marker in patients with diabetes.

Reduction of both number and proliferative activity of human endothelial progenitor cells in obesity.

OBJECTIVE: Circulating endothelial progenitor cells (EPCs), responsible for neoangiogenesis and vascular repair, negatively correlate with vascular dysfunction and atherosclerotic risk factors. Because obesity may have a crucial role in the development of endothelial dysfunction, this study evaluated the number and proliferative activity of circulating human EPCs in obese (body mass index (BMI)=48+/-9, n=45) compared with lean (23+/-2, n=45) volunteers. METHODS: EPCs were quantified after isolation of peripheral blood mononuclear cells (PBMCs) using fluorescence-activated cell sorting analyses. In addition, plated PBMCs developed colony-forming units (CFUs) from which 'outgrowth' endothelial cells (OECs) sprouted and differentiated into mature endothelial cells. Growth rates were monitored by periodical microscopic evaluation. Cell-cycle protein expression was determined by western blot analyses. RESULTS: BMI negatively correlated (P<0.01) with the number of CD34(+)/CD133(+)/KDR(+) (r=-0.442), CD34(+)/KDR(+) (r=-0.500) and CD133(+)/KDR(+) (r=-0.282) EPCs. Insulin, leptin, HbA(1c), high-sensitivity C-reactive protein and hypertension, as well as diminished high-density lipoprotein and apolipoprotein A1, were not only associated with obesity but also with significantly reduced EPC levels. Applying selective culture conditions, EPC-CFUs differentiated into OECs that proliferated more slowly when derived from obese compared with lean subjects (obese: 19.9+/-2.2% vs lean: 30.9+/-3.2% grown area per week, P<0.01). The reduced proliferation was reflected by decreased (P<0.05, n=24 for each group) expression of cell-cycle-promoting cyclins and E2F-1, by hypophosphorylation of retinoblastoma protein and by increased (P<0.05, n=24 for each group) expression of the cell-cycle inhibitor p21(WAF-1/Cip1). CONCLUSIONS: Reduced numbers of EPCs along with their premature senescence, as shown in this study, could function as early contributors to the development and progression of vascular dysfunction in obesity.

Reduced TGF-beta1 expression and its target genes in human insulinomas.

Aiming to identify signalling pathways relevant for ss-cell growth we performed an explorative micro-array analysis comparing the gene expression profiles of three human insulinomas and one normal pancreatic islet preparation. This revealed an insulinoma-associated down-regulation of the transforming growth factor beta 1 (TGF-beta1) and its target genes. Comparative quantitative real-time PCR (qRT-PCR) including an expanded sample number of both insulinomas (n=9) and pancreatic islet preparations (n=4) confirmed the decreased TGF-beta1 expression and its target molecules (TGFBI, NNMT, RPN2) in insulinomas. Similarly, TGF-beta1 immunofluorescence analysis revealed reduced expression in insulinomas when compared to pancreatic islets. In contrast, TGFBR2 (transforming growth factor beta receptor II) was found up-regulated. However, the consistent down-regulation of the TGF-beta1 targets TGFBI (transforming growth factor, beta-induced), NNMT (nicotinamide N-methyltransferase), RPN2 (ribophorin II) indicates that the parallel up-regulation of TGFBR2 does not compensate for the only marginal TGF-beta1 expression levels in insulinomas. TGFBR2 expression was confirmed at the protein level in insulinomas. SMAD2/3 protein expression was found at higher levels in human pancreatic islets when compared with insulinomas by dual colour confocal microscopy. TGF-beta1 signalling is known to be involved in cell replication and is abrogated in ductal pancreatic tumours. The down-regulation of TGF-beta1 expression and its target molecules in insulinomas is a new aspect of this cytokine. Our data underline parallels in endocrine and exocrine pancreatic tumour development, which may implicate common progenitor cells.

Insulin resistance has no impact on ghrelin suppression in pregnancy.

Ghrelin is reduced in various states of insulin resistance. The aim of this study was to examine the relationship between ghrelin and glucose metabolism during pregnancy - a natural insulin-resistant state - in women with normal glucose tolerance (NGT), impaired glucose tolerance (IGT) or gestational diabetes mellitus (GDM) and potential changes 3 months after delivery. A total of 54 women, 37 pregnant and with various degrees of insulin resistance and 24 postpartum (PP, seven of them also studied during pregnancy) were studied. Ghrelin plasma concentrations at fasting and 60' following glucose loading (75 g-2 h-oral glucose tolerance test), area under the curve of plasma glucose (G-AUC(OGTT)) and insulin sensitivity [homeostatic model assessment (HOMA) and oral glucose sensitivity index (OGIS) indices, respectively] were determined. Both baseline and 60' ghrelin concentrations were to a comparable degree ( approximately by 65%) suppressed in NGT, IGT and GDM as compared to the PP group (the latter being indistinguishable from NGT regarding glucose tolerance and insulin sensitivity). In all women studied both during and after pregnancy, ghrelin levels rose from pregnancy to PP (mean increase 313.8%; P < 0.03). There was no correlation between baseline ghrelin and insulin sensitivity as estimated from both baseline (HOMA) and dynamic (OGTT:OGIS) glucose and insulin data. Ghrelin is substantially decreased during pregnancy, but glucose-induced ghrelin suppression is preserved at a lower level. There is apparently no relation to the degree of insulin resistance.

Plasma adipocyte and epidermal fatty acid binding protein is reduced after weight loss in obesity.

AIM: Plasma adipocyte fatty acid binding protein (A-FABP) and epidermal fatty acid binding protein (E-FABP) concentrations have been linked to obesity and the metabolic syndrome. In this study, we investigated whether plasma A-FABP and E-FABP concentrations are altered by weight loss in obese patients. METHODS: In a prospective study, fasting plasma A-FABP and E-FABP concentrations were measured before and 6 months after gastric banding in 33 morbidly obese patients, with a body mass index (BMI) of 46 +/- 5 kg/m(2). Eleven healthy subjects with a BMI < 25 kg/m(2) served as controls. RESULTS: A-FABP and E-FABP plasma concentrations were higher in obese subjects (36.7 +/- 6.7 and 3.7 +/- 0.7 ng/ml, respectively) than in controls (18.1 +/- 0.6 and 2.6 +/- 0.5, respectively, p < 0.01). Gastric banding reduced BMI to 40 +/- 5 kg/m(2), A-FABP to 32.6 +/- 5.4 ng/ml and E-FABP to 1.9 +/- 0.7 ng/ml (all p < 0.05) after 6 months. Insulin sensitivity as estimated by the Homeostasis Model Assessment insulin resistance index was unchanged. A-FABP concentrations were significantly associated with BMI before and 6 months after surgery (p < 0.05, r = 0.42 and r = 0.37 respectively). CONCLUSIONS: Elevated plasma A-FABP and E-FABP concentrations in morbidly obese subjects are reduced after gastric banding-induced weight loss. This suggests that FABP may be associated with improvement of metabolic conditions over time.

Identification of DLK1 variants in pituitary- and neuroendocrine tumors.

In a gene chip analysis of common pituitary tumor types, one of the genes with the most impressive tissue-specific expression regulation was delta-like 1 (DLK1), which was strongly expressed in GH-secreting (GH-S) pituitary tumors. In addition to pituitary adenomas, various endocrine tumors were subjected to real-time-quantitative PCR revealing high expression of DLK1 in normal pituitary tissue, in GH-S-, in one prolactin-secreting pituitary adenoma and in pheochromocytomas. Additionally, three DLK1 gene-derived subvariants were identified. The first, lacking 204 bp--coding for epidermal growth factor-like domain 6 and parts of the juxtamembrane region--was named Secredeltin. In the other two splice variants (named Brevideltin and Brevideltinin), a stop codon is introduced due to a frame-shift, leading to truncated proteins of 204 and 213 aas, respectively.

Sleeve gastrectomy and gastric banding: effects on plasma ghrelin levels.

BACKGROUND: Different changes of plasma ghrelin levels have been reported following gastric banding, Roux-en-Y gastric bypass, and biliopancreatic diversion. METHODS: This prospective study compares plasma ghrelin levels and weight loss following laparoscopic sleeve gastrectomy (LSG) and laparoscopic adjustable gastric banding (LAGB) in 20 patients. RESULTS: Patients who underwent LSG (n=10) showed a significant decrease of plasma ghrelin at day 1 compared to preoperative values (35.8 +/- 12.3 fmol/ml vs 109.6 +/- 32.6 fmol/ml, P=0.005). Plasma ghrelin remained low and stable at 1 and 6 months postoperatively. In contrast, no change of plasma ghrelin at day 1 (71.8 +/- 35.3 fmol/ml vs 73.7 +/- 24.8 fmol/ml, P=0.441) was found in patients after LAGB (n=10). Increased plasma ghrelin levels compared with the preoperative levels at 1 (101.9 +/- 30.3 fmol/ml vs 73.7 +/- 24.8 fmol/ml, P=0.028) and 6 months (104.9 +/- 51.1 fmol/ml vs 73.7 +/- 24.8 fmol/ml, P=0.012) after surgery were observed. Mean excess weight loss was higher in the LSG group at 1 (30 +/- 13% vs 17 +/- 7%, P=0.005) and 6 months (61 +/- 16% vs 29 +/- 11%, P=0.001) compared with the LAGB group. CONCLUSIONS: As a consequence of resection of the gastric fundus, the predominant area of human ghrelin production, ghrelin is significantly reduced after LSG but not after LAGB. This reduction remains stable at follow-up 6 months postoperatively, which may contribute to the superior weight loss when compared with LAGB.

Impact of laparoscopic adjustable gastric banding on plasma ghrelin, eating behaviour and body weight.

BACKGROUND: Plasma ghrelin, an orexigenic peptide derived from the stomach and duodenum, increases following weight loss and might contribute to weight regain. The aim of the present study was to evaluate the effect of laparoscopic adjustable gastric banding (LAGB) on body weight and body composition as well as plasma ghrelin in relation to eating behaviour in morbidly obese patients. MATERIALS AND METHODS: This study was performed in 23 morbidly obese subjects who underwent standardized LAGB. Fasting plasma ghrelin was measured before and 6 months after surgery and was correlated with body weight, body composition, and eating behaviour. RESULTS: Six months after LAGB, body weight decreased significantly by -15.7 +/- 1.4 kg (mean +/- SEM, P = 0.0001) which was accompanied by an increased cognitive restraint of eating (P = 0.001), and by a decreased disinhibition of eating and susceptibility to hunger (P = 0.0001). Plasma ghrelin increased (P = 0.016) by 27.2% from 100.39 +/- 12.90 to 127.22 +/- 13.15 fmol mL(-1). The change in plasma ghrelin correlated with changes in body weight (r = -0.49, P = 0.02), BMI (r = -0.42, P = 0.048) and fat mass (r = -0.519, P = 0.013), but not with changes of fat-free mass and of the three dimensions of eating behaviour. CONCLUSION: Weight loss following LAGB leads to an increase in fasting plasma ghrelin and is accompanied by a decrease in hunger, disinhibition of eating and an increase in cognitive restraint. Thus, changes in eating behaviour, which promote reduction of food intake and not fasting ghrelin, determines weight loss achieved by LAGB.

Acute exercise has no effect on ghrelin plasma concentrations.

Exercise is a potent, dose-dependent stimulus of growth hormone (GH) secretion. The hypothalamic peptides, GH-releasing hormone (GHRH) and somatostatin are regarded as major regulators of this stimulation. The role of the stomach-derived peptide ghrelin, which has been shown to exert strong GH releasing effects, has not been fully characterized yet. We therefore studied GH and ghrelin plasma concentrations in response to graded levels of exercise in eight healthy young volunteers. After determination of their individual maximal exercise capacity, all individuals underwent a treadmill exercise at 50 %, 70 %, and 90 % of maximum oxygen consumption (VO (2)max) on different days. Maximal GH response to exercise was observed after 40 minutes at 50 % VO (2)max and after 20 minutes at 70 and 90 % VO (2max). GH serum concentrations increased significantly at all three exercise intensities (GH peak concentrations were 5.8 +/- 2.3 ng/ml, 12.0 +/- 3.2 ng/ml, and 9.8 +/- 4.7 ng/ml, respectively). In contrast, ghrelin plasma concentrations remained unchanged at all three workloads. Assuming that the sensitivity of the GH neuroendocrine/metabolic regulation of GH is unaltered, ghrelin does not participate in the regulation of the GH response to exercise in healthy males.

Pituitary function in patients with newly diagnosed untreated systemic lupus erythematosus.

OBJECTIVES: To determine whether hormonal dysfunction involving the hypothalamic-pituitary-adrenal (HPA) axis, prolactin (PRL) secretion, and sex hormone status contribute to development of systemic lupus erythematosus (SLE). METHODS: 11 patients with SLE and 9 healthy controls were tested for their total anterior pituitary gland reserve by simultaneous injection of corticotropin-, growth hormone- (GH), thyrotropin-, and gonadotropin-releasing hormone (GnRH). Serum concentrations of adrenocorticotropin (ACTH), cortisol, GH, thyroid stimulating hormone (TSH), PRL, luteinising hormone (LH), and follicle stimulating hormone (FSH) were measured at baseline and after injection. Baseline values of oestradiol, testosterone, and thyroxine were determined. RESULTS: Basal and stimulated serum concentrations of ACTH, cortisol, GH, and PRL were similar in both groups. In contrast, despite similar basal thyroxine levels the TSH response to TRH was significantly higher in patients than in controls. LH and FSH levels in premenopausal female patients of both groups were identical. In contrast, two of the three male patients were hypogonadal without compensatory increases of basal LH and FSH levels, but they retained excessive stimulatory capacity in response to GnRH. CONCLUSION: No significant alteration of the HPA axis was found in patients with SLE, which is inadequate in view of the continuing inflammation. GH and PRL secretion were normal. The pituitary-thyroid and pituitary-gonadal axes were affected in patients with newly diagnosed, untreated SLE.

[Growth hormone in the elderly man]. / Wachstumshormon beim älteren Mann.

Many symptoms being part of the growth hormone deficiency syndrome in adults like decrease in muscle mass and bone mineral content, increase in fat mass, and skin atrophy are observed also with ageing. Indeed, short term trials with growth hormone administration to persons over 60 years old revealed that many of these symptoms could be reversed by growth hormone. However, recent reports of an association of high insulin-like growth factor-1 (IGF-1)-concentrations and increased risk of prostate, lung, colon and breast cancer as well as a possible decrease of insulin sensitivity prohibit currently the use of growth hormone in an attempt to reverse a normal ageing process. Prospective, randomised and placebo-controlled long-term trials are necessary to prove safety and efficacy of growth hormone therapy in the ageing population before it can be recommended. In addition, no data are available as to the right growth hormone dose and the correct monitoring. Expectations of the society and the search for the fountain of youth should not motivate physicians to leave the firm ground of evidence based medicine and prescribe experimental therapies to healthy older persons.

Apoplexy of a pituitary macroadenoma with reversible third, fourth and sixth cranial nerve palsies following administration of hypothalamic releasing hormones: MR features.

Pituitary apoplexy in patients with pituitary macroadenomas can occur either spontaneously or following various interventions. We present a case of a 71-year-old woman who developed third, fourth, and sixth cranial nerve palsies following administration of the four hypothalamic releasing hormones for routine preoperative testing of pituitary function. The MR examination showed interval tumor growth with impression of the floor of the third ventricle. There were also changes in signal intensity characteristics of the mass, suggestive of intratumoral bleeding. A transsphenoidal surgery with subtotal resection of the pituitary adenoma was performed. Microscopical examination revealed large areas of necrosis and blood surrounded by adenomatous tissue. Third, fourth, and sixth cranial nerve palsies completely resolved within 4 months. We conclude that MR imaging is useful in the demonstration of pituitary apoplexy following preoperative stimulation tests, but we suggest that these tests should be abandoned in patients with pituitary macroadenomas.

Are wedge biopsies of cadaveric kidneys obtained at procurement reliable?

BACKGROUND: Single wedge biopsy of cadaveric kidneys from donors older than 55 is currently the standard method of evaluating their viability for transplantation. The degree of glomerulosclerosis presently determines whether a kidney can be transplanted, but most biopsies sample only the subcapsular region and may not accurately represent the true renal architecture. Our study evaluated the accuracy of transplant suitability determinations based upon the single wedge biopsy of cadaveric kidneys. METHODS: We took kidneys that were refused by UNOS centers on the basis of biopsy results, examined their histology in detail, and reviewed donor medical histories. Sections were taken from the upper, lower, and mid-portion of each kidney and stained with the periodic acid Schiff stain. Percentage and location of glomerulosclerosis and other relevant pathology were then determined in each section. We compared our findings with the results of the original wedge biopsies obtained at the time of procurement. RESULTS: Nine kidneys were obtained and examined. The wedge biopsies at the time of procurement showed glomerulosclerosis ranging from 8 to 36% (median 17%). The multiple kidney sections we analyzed showed fewer sclerosed glomeruli, ranging from 3 to 15% (median 7%, P<0.001), with most of the sclerosed glomeruli identified located in the immediate subcapsular region (P<0.001). CONCLUSIONS: Wedge biopsies of donor kidneys can overestimate the total amount of glomerulosclerosis, apparently because of a predominance of sclerosis in the kidney's subcapsular region, the area predominantly sampled by the usual wedge biopsy. These inappropriately high estimates of glomerulosclerosis can result in refusal of kidneys that might be suitable for transplantation.

Significance of laboratory findings for the diagnosis of neurosyphilis.

Our objective is to assess the specificity and sensitivity, and thus elaborate the relevance, of different laboratory findings for the diagnosis of neurosyphilis. One hundred and fourteen HIV-negative pairs of serum and cerebrospinal fluid (CSF) samples were examined by the Venereal Disease Research Laboratory (VDRL) test, a fluorescent treponemal antibody-absorption (FTA-ABS) test, microhaemagglutination assay with Treponema pallidum antigen (MHA-TP) test (serum) and Treponema pallidum haemagglutination assay (TPHA) test (CSF); further, albumin, total protein, and total IgG were determined and, in the CSF, cell count was performed. The donors were 60 patients with active neurosyphilis and 54 healthy persons with a former history of syphilis and with persisting positive results in the T. pallidum haemagglutination tests (serum: MHA-TP, CSF: TPHA), who supplied specimens for control. Albumin quotient, IgG index, TPHA index, modified TPHA index, Intrathecally produced T. pallidum Antigen (ITpA) index, its 2 modifications and, in 12 samples, the adenovirus group antibody (AVGA)/TPHA index were ascertained. The specificity and sensitivity of the TPHA index were 100% and 98.3%, of the modified TPHA index 50.0% and 96.7%, of the ITpA index 42.6% and 90.0%, of the modified ITpA indices 51.8% and 68.3% (first modification) and 53.7% and 63.3% (second modification). The AVGA/TPHA index yielded a specificity of 91.7% (11/12). The CSF VDRL test was positive in 55/60 (91.7%) of samples from patients with neurosyphilis and in none of the controls (0/54). A CSF-TPHA titre greater than 1:320 was observed in 59/60 (98.3%) of the neurosyphilis specimens and in none of the controls (0/54). A TPHA index above an outcome of 70, a positive CSF-TPHA test at a titre greater than 1:320 and, with lower sensitivity, the criteria of the Centers for Disease Control (CDC) guidelines yield the most reliable results for laboratory support to a diagnosis of neurosyphilis. The modified TPHA index, the ITpA index, and its 2 modifications produce results of minor sensitivity and poor specificity. Observations on the AVGA/THPA index are too limited yet for judgement. The diagnostic significance of a CSF-TPHA titre above 320 needs further confirmation on a greater number of observations made by different laboratories.