Search PubMed⌕ Search

Biomedical subjects

W W de Herder

Publications and source records attributed to W W de Herder.

At least 19 recordsLinked to original sources
PubMed2006

[Cushing's syndrome. I. New diagnostic developments].

Over the past few years, new diagnostic tests for Cushing's syndrome have become available. Some of the other, older diagnostic tests have fallen into discredit as they could not distinguish conditions from one another sufficiently well. New biochemical tests include midnight salivary cortisol measurement and the combined dexamethasone-corticotropin releasing hormone (CRH) test. The high dose dexamethasone test and the CRH-stimulation test have been abandoned as they were unable to differentiate between hypophysial and ectopic secretion of adrenocorticotropic hormone (ACTH). For the detection of ectopic ACTH-secreting tumours new imaging techniques, such as somatostatin receptor scintigraphy and positron emission tomography with 5-hydroxytryptophan, have become available.

5-Hydroxytryptophan↗
PubMed2006

[Cushing's syndrome. II. New forms of treatment].

Several new therapeutic options both medicinal and surgical, have emerged for the treatment of Cushing's syndrome. In Cushing's disease caused by an adrenocorticotropin (ACTH) secreting pituitary adenoma, the introduction ofendoscopic pituitary surgery offers better visualization of the sella than does the traditional explorative surgery. However, at present it is unclear whether this will result in a better outcome. New drugs under investigation include universal somatostatin analogues such as SOM230, and a combination of a somatostatin analogue and dopamine agonist known as dopastatin. These agents may also be effective for the medicinal treatment of ectopic ACTH-secretion. Treatment with radioactive-labelled somatostatin-analogues such as 177lutetium octreotate is another option for these patients. The primary treatment for ACTH-independent Cushing's syndrome is laparoscopic adrenalectomy. In rare cases of bilateral adrenal hyperplasia, medicinal treatment aimed at new regulatory pathways of cortisol secretion can be applied.

ACTH-Secreting Pituitary Adenoma↗
PubMed2006

TNM staging of foregut (neuro)endocrine tumors: a consensus proposal including a grading system.

The need for standards in the management of patients with endocrine tumors of the digestive system prompted the European Neuroendocrine Tumor Society (ENETS) to organize a first Consensus Conference, which was held in Frascati (Rome) and was based on the recently published ENETS guidelines on the diagnosis and treatment of digestive neuroendocrine tumors (NET). Here, we report the tumor-node-metastasis proposal for foregut NETs of the stomach, duodenum, and pancreas that was designed, discussed, and consensually approved at this conference. In addition, we report the proposal for a working formulation for the grading of digestive NETs based on mitotic count and Ki-67 index. This proposal, which needs to be validated, is meant to help clinicians in the stratification, treatment, and follow-up of patients.

Biomarkers, Tumor↗
PubMed2006

Safety and efficacy of endoscopic retroperitoneal adrenalectomy.

BACKGROUND: Minimally invasive adrenalectomy has replaced open surgery in the treatment of benign adrenal tumours. Transperitoneal and retroperitoneal approaches have been advocated. However, long-term outcome data are rare. METHODS: Over a period of 8 years, 123 patients underwent surgery for benign adrenal lesions using the endoscopic retroperitoneal approach. Data were analysed retrospectively by review of medical charts. Long-term results were obtained by sending questionnaires to patients and contacting their primary physicians. RESULTS: One hundred and twenty-three patients underwent 126 endoscopic retroperitoneal adrenalectomies. Mean operating time for unilateral adrenalectomy was 115 min, whereas that for bilateral adrenalectomy was 208 min. The conversion rate was 4.8 per cent. Complications occurred after 15.9 per cent of adrenalectomies. One patient died during the postoperative period. Long-term results were obtained in 80 patients (74.8 per cent). Nine patients (11 per cent) reported chronic incisional pain and six patients (8 per cent) had chronic abdominal pain. Addisonian crisis after bilateral adrenalectomy occurred in three patients. Most patients (86 per cent) were satisfied with the cosmetic results. CONCLUSION: Endoscopic retroperitoneal adrenalectomy is a safe and effective procedure. Long-term outcome is acceptable and the procedure has excellent cosmetic results.

Adrenal Gland Diseases↗
PubMed2006

Expression of activin and inhibin subunits, receptors and binding proteins in human adrenocortical neoplasms.

OBJECTIVE: The growth and differentiation factors activin and inhibin can affect tumour formation and steroid production in the adrenal cortex. These factors bind to type I (Alk-4), type II (ActRIIA, ActRIIB) and type III (betaglycan) receptors or to the activin-binding protein follistatin. Expression of these activin-related mRNAs was measured in different types of adrenocortical tissues and tumours to study the relationship with tumorigenesis. DESIGN: Quantitative expression of activin-related mRNAs was investigated in patient adrenocortical samples. PATIENTS: Twenty-eight human adrenocortical samples from normal and hyperplastic adrenals and from adrenocortical adenomas and carcinomas were collected after surgery for study purposes. MEASUREMENTS: Using quantitative reverse transcription polymerase chain reaction (RT-PCR), we investigated the expression of inhibin alpha-, betaA- and betaB-subunits, follistatin, betaglycan, ActRIIA, ActRIIB and Alk-4 in the adrenocortical tissues. The expression of cytochrome P450c17 (CYP17) mRNA was also measured to investigate its association with inhibin and activin subunit expression. RESULTS: All genes studied were expressed in all tissues, with the exception of the inhibin alpha-subunit in one hyperplastic adrenal and three adrenocortical carcinomas. Expression of inhibin betaA-subunit, follistatin, betaglycan, ActRIIA, ActRIIB and CYP17 differed between nontumorous adrenals and carcinomas. CONCLUSIONS: These differences, together with correlation analysis, indicate parallel regulation of the expression of CYP17, the inhibin alpha-subunit, ActRIIA, ActRIIB, betaglycan and follistatin. We conclude that the expression of activin and inhibin subunits, receptors and binding proteins is affected by tumour formation in the adrenal gland and may play a role in tumorigenesis.

Activin Receptors, Type II↗
PubMed2006

Drug-induced hepatitis in an acromegalic patient during combined treatment with pegvisomant and octreotide long-acting repeatable attributed to the use of pegvisomant.

We report on a patient with acromegaly who developed severe drug-induced hepatitis during combined treatment with the long-acting somatostatin-analog octreotide and the GH receptor antagonist pegvisomant. The hepatic enzyme disturbances normalized after discontinuation of pegvisomant. After rechallenge with monotherapy pegvisomant, however, the hepatic enzyme disturbances reappeared within a few weeks, indicating that most likely pegvisomant alone and not the long-acting somatostatin analog or the combination of these two drugs was responsible for this case of drug-induced hepatitis. Clinicians should be aware of this potential severe adverse drug reaction and therefore frequent control of hepatic enzymes is mandatory during treatment with pegvisomant.

Acromegaly↗
PubMed2005

Postoperative evaluation of patients with acromegaly: clinical significance and timing of oral glucose tolerance testing and measurement of (free) insulin-like growth factor I, acid-labile subunit, and growth hormone-binding protein levels.

CONTEXT: It is not exactly known when patients with acromegaly should be evaluated for cure after transsphenoidal adenomectomy (TA). OBJECTIVE: The objective of this study was to define the optimal time point of postoperative evaluation by serial measurements of glucose-suppressed GH levels [oral glucose tolerance test (OGTT)] and the GH-dependent parameters IGF-I, free IGF-I, acid labile subunit (ALS), and GH-binding protein (GHBP). DESIGN: We describe a prospective study with 1-yr follow-up. SETTING: The study was conducted at a university hospital. PATIENTS: Seventeen patients with acromegaly were included in the study. MAIN OUTCOME MEASURES: The main outcome measures were OGTT results at 1, 2, 3, 8, and 12 wk after TA; weekly measured GH, (free) IGF-I, ALS, and GHBP levels up to 12 wk; and total IGF-I levels measured at 52 wk. RESULTS: Postoperatively, nine patients were in remission with an OGTT GH nadir of less than 0.5 microg/liter and normalized IGF-I levels, whereas eight patients had persistent acromegaly. In both cured and noncured patients, OGTT results at 1 wk after TA were highly reproducible over time. In contrast, early postoperative IGF-I levels fluctuated and only stabilized at 12 wk. In all cured patients, free IGF-I levels rapidly normalized within 2 wk after TA (specificity, 100%). Preoperative ALS levels were elevated in all patients and normalized only in the cured patients after TA (specificity, 89%). Preoperative GHBP levels were low and increased from 2 wk after surgery. CONCLUSIONS: We show that in the postoperative evaluation of patients with acromegaly, already 1 wk after surgery, an OGTT using 0.5 microg as the GH nadir cutoff value has a high predictive value for cure, whereas early IGF-I levels show varying patterns toward stabilization. Therefore, IGF-I should be measured as a predictive parameter not within 3 months after surgery. Free IGF-I and ALS levels may have an additional value in the postoperative assessment of disease activity.

Acromegaly↗
PubMed2005

[Adrenal incidentaloma: a clinical problem related to imaging].

Two female patients, 68 and 67 years of age, were referred for right abdominal pain and pyelonephritis, respectively. During the diagnostic work-up, an unsuspected adrenal mass was found in both patients. Hormonal evaluation and imaging showed a benign non-hyperactive functioning adenoma in one patient and a pheochromocytoma in the other. Both patients were successfully treated with endoscopic adrenalectomy. Wider application and improvement of abdominal imaging procedures have caused an increase of incidentally detected adrenal masses, posing a common clinical problem. Typically, a diagnosis can be made on the basis of the characteristic radiological image. The exact nature of the defect is often unclear and further evaluation is required to determine functionality and possible malignancy. An algorithm is presented for the management of adrenal incidentalomas.

Abdominal Pain↗
PubMed2005

Tumours of the midgut (jejunum, ileum and ascending colon, including carcinoid syndrome).

(Neuro-)endocrine tumours of the gastrointestinal tract are also called 'carcinoids'. (Neuro-)endocrine midgut tumours can be categorized according to their clinical behaviour. Most tumours are non-functioning. Functioning tumours are responsible for the carcinoid syndrome. The carcinoid syndrome is almost uniquely associated with midgut carcinoids. Symptoms of the carcinoid syndrome are caused by an excess of biogenic amines, peptides and other factors in the circulation. The typical symptoms of the carcinoid syndrome are diarrhoea, flushing, and carcinoid heart disease. Carcinoid heart disease involves the tricuspid and pulmonary valves and the endocardium. Serum chromogranin A and urinary excretion of 5-hydroxy-indoleacetic acid (5-HIAA) are biochemical markers. Carcinoid tumours express large numbers of high-affinity somatostatin receptors. These can bind the currently available octapeptide somatostatin analogues. In inoperable patients, biotherapy with somatostatin analogues and interferon-alpha is the treatment of choice. Somatostatin analogues and interferon-alpha significantly improve symptoms.

Carcinoid Tumor↗
PubMed2005

Neuroendocrine tumors and somatostatin: imaging techniques.

Tumors and metastases bearing the somatostatin receptor subtypes 2 (SSTR2) or SSTR5 can be visualized in vivo after injection of radiolabeled octapeptide somatostatin analogs like 111In-pentetreotide. The sensitivity of 111In-pentetreotide scintigraphy for the detection of carcinoid tumors is 86-95%. The sensitivity of 111In-pentetreotide scintigraphy for the detection of gastrinomas, vasoactive intestinal polypeptide-secreting tumors, and glucagonomas as well as clinically non-functioning lesions is 75-100%. However, for insulinoma this is 50-60%. 111In-pentetreotide scintigraphy generally has a lower detection rate for benign pheochromocytomas than 123I-MIBG scintigraphy, but it can have a complementary role for the staging of malignant pheochromocytomas. It can also be used for the detection of extra-adrenal pheochromocytomas and paragangliomas. Most GH- and TSH-secreting pituitary adenomas can be visualized using 111In-pentetreotide. 111In-pentetreotide scintigraphy is negative in microprolactinomas and ACTH-secreting pituitary microadenomas. 111In-pentetreotide scintigraphy has been successful for the localization of extra-pituitary ACTH-secreting tumors and their metastases, and especially for occult tumors. A large variety of lesions in and around the pituitary region express somatostatin receptors and, therefore, can be visualized by 111In-pentetreotide scintigraphy.

Carcinoid Tumor↗
PubMed2004

[Giantism. A historical and medical view].

Patients with giantism were displayed as curiosities to large audiences in the past. The (medical) histories of famous giants like Daniel Cajanus (born in 1702 or 1703, Finland), Charles Byrne (1761, Ireland), Edouard Beaupré (1881, Canada) and Robert Wadlow (1918, Illinois, USA) are well described in the international medical literature. Extensive data from the entertainment world and/or medical data exist on famous Dutch giants like Klaas van Kyeten (end of 13th century), Gerrit Bastiaansz. de Hals (1620), Albert Johan Kramer (1897) and Rigardus Rijnhout (1922). Famous Dutch giantesses are Trijntje Kornelisse Keever (1614) and Kaatje van Dijk (1904). In most giants, excessive growth was caused by a somatotroph pituitary adenoma, sometimes in combination with hypogonadotrophic hypogonadism. In the western world, it is unlikely that there will be many more people with fully developed giantism due to the current high level of medical care.

Adenoma↗
PubMed2004

Cerebrospinal fluid leakage during transsphenoidal surgery: postoperative external lumbar drainage reduces the risk for meningitis.

Postoperative meningitis is a well known complication of transsphenoidal surgery (TSS). The objective of this study was to evaluate whether postoperative external cerobrospinal fluid (CSF) drainage in case of intraoperative CSF-leakage, reduces the risk of postoperative meningitis. We retrospectively reviewed a series of 278 consecutive transsphenoidal operations. In all operations with intraoperative CSF leakage, an external lumbar drain (ELD) was inserted directly postoperatively, and removed after at least 5 days. The incidence of postoperative meningitis was compared with that in a previously studied series of 228 consecutive transsphenoidal operations, without insertion of an ELD in cases with intraoperative CSF leakage. In the present series, postoperative meningitis occurred in 2/278 (0.7%) operations, compared to 7/228 (3.1%) operations in the previous study period (P < 0.05). Intraoperative CSF leakage was noted in 70/278 (25.2%) operations. All these patients received an ELD immediately after surgery for at least 5 days. There were no reported complications of ELD insertion. In the present series, 1 of 70 (1.4%) patients with intraoperative CSF leakage developed meningitis, compared to 3 of 22 (13.6%) patients in the previous study (P < 0.05). The present report on 278 consecutive transsphenoidal operations shows that the routine insertion of an ELD in patients in whom intraoperative CSF leakage is observed significantly reduces the incidence of postoperative meningitis. Possibly, diversion of CSF prevents the formation of a CSF fistula and thereby the risk of infection. The role of prophylactic antibiotic treatment in patients with CSF rhinorrhea after TSS remains to be established.

Drainage↗
PubMed2004

Clinical endocrinology and metabolism. Gut endocrine tumours.

Endocrine tumours of the gastrointestinal tract and pancreas may present at different disease stages with either hormonal or hormone-related symptoms/syndromes, or without hormonal symptoms. They may occur either sporadically or as part of hereditary syndromes. In the therapeutic approach to a patient with these tumours, excessive hormonal secretion and/or its effects should always be controlled first. A team approach is needed to achieve a balanced opinion on the use of the different therapeutic options in patients with these tumours.

Animals↗
PubMed2004

Insulinoma.

More than 90% of insulinomas are benign tumors. Insulinomas cause hypoglycemia and thereby symptoms of neuroglycopenia and catecholamine response. During symptoms, blood glucose levels should be less than 40 mg/dl (less than 2.2 mmol/l), concomitant insulin levels should be > or =6 IU/ml (> or =43 pmol/l) and concomitant C-peptide levels > or =0.2 pmol/l. Most insulinomas can be identified intraoperatively by experienced surgeons. Initial therapy consists of administration of frequent meals and/or by glucose infusion. In patients with solitary insulinomas, complete surgical removal of the tumor should be the primary goal. In patients with metastatic insulinomas, symptoms of insulin hypersecretion will only completely disappear after complete resection of all metastases.

C-Peptide↗
PubMed2004

Considerations concerning a tailored, individualized therapeutic management of patients with (neuro)endocrine tumours of the gastrointestinal tract and pancreas.

Endocrine tumours of the gastrointestinal tract and pancreas may present at different disease stages with either hormonal or hormone-related symptoms/syndromes, or without hormonal symptoms. They may occur either sporadically or as part of hereditary syndromes. In the therapeutic approach to a patient with these tumours, excessive hormonal secretion and/or its effects should always be controlled first. Tumour-related deficiencies or disorders should also be corrected. Subsequently, control should be aimed at the tumour growth. Surgery is generally considered as first-line therapy for patients with localized disease, as it can be curative. However, in patients with metastatic disease the role of first-line surgery is not clearly established and other therapies should be considered, such as non-surgical cytoreductive therapies, biotherapy (with somatostatin analogues or interferon-alpha), embolization and chemoembolization of liver metastases, chemotherapy (with single or multiple dose regimens) and peptide receptor-targeted radiotherapy. The delicate balance of the use of the different therapeutical options in patients with endocrine tumours of the gastrointestinal tract and pancreas emphasizes the importance of team approach and team expertise.

Gastrinoma↗
PubMed2003

Treatment of patients with gastro-entero-pancreatic (GEP) tumours with the novel radiolabelled somatostatin analogue [177Lu-DOTA(0),Tyr3]octreotate.

Medical treatment and chemotherapy are seldom successful in achieving objective tumour reduction in patients with metastatic neuroendocrine tumours. Treatment with the radiolabelled somatostatin analogue [(90)Y-DOTA(0),Tyr(3)]octreotide may result in partial remissions in 10-25% of patients. The newer analogue [DOTA(0),Tyr(3)]octreotate (octreotate) has a ninefold higher affinity for the somatostatin receptor subtype 2 as compared with [DOTA(0),Tyr(3)]octreotide. Also, labelled with the beta- and gamma-emitting radionuclide (177)Lu, it has proved very successful in achieving tumour regression in animal models. The effects of (177)Lu-octreotate therapy were studied in 35 patients with neuroendocrine gastro-entero-pancreatic (GEP) tumours who underwent follow-up for 3-6 months after receiving their final dose. Patients were treated with doses of 100, 150 or 200 mCi (177)Lu-octreotate, to a final cumulative dose of 600-800 mCi, with treatment intervals of 6-9 weeks. Nausea and vomiting within the first 24 h after administration were present in 30% and 14% of the administrations, respectively. WHO toxicity grade 3 anaemia, leucocytopenia and thrombocytopenia occurred after 0%, 1% and 1% of the administrations, respectively. Serum creatinine and creatinine clearance did not change significantly. The effects of the therapy on tumour size were evaluable in 34 patients. Three months after the final administration, complete remission was found in one patient (3%), partial remission in 12 (35%), stable disease in 14 (41%) and progressive disease in seven (21%), including three patients who died during the treatment period. Tumour response was positively correlated with a high uptake on the octreoscan, limited hepatic tumour mass and a high Karnofsky Performance Score. Because of the limited efficacy of alternative therapies, many physicians currently adopt an expectant attitude when dealing with patients with metastatic GEP tumours. However, in view of the high success rate of therapy with (177)Lu-octreotate and the absence of serious side-effects, we advocate its use in patients with GEP tumours without waiting for tumour progression.

Abdominal Pain↗