Many diseases are closely tied to deficient or subnormal metabolic and secretory cell functions. Milder forms of these diseases can be managed by a variety of treatments. However, it is often extremely difficult or even impossible to imitate the moment-to-moment fine regulation and the complex roles of the hormone, factor or enzyme that is not sufficiently produced by the body. Immunoisolated transplantation is one of the most promising approaches to overcome the limitations of current treatments. Non-autologous (transformed) cell lines and allogeneic and xenogeneic cells/tissues that release the therapeutic substances are enclosed in immunoprotective microcapsules. The microcapsules avoid a lifetime of immunosuppressive therapy while excluding an immune response in the host. Research in this direction has shown the feasibility of microcapsules based on hydrogels (particularly of alginate) for transplantation of non-autologous cells and tissue fragments. Numerous technical accomplishments of the immunoisolation method have recently made possible the first successful long-term clinical applications. However, realizing the potential of immunoisolated therapy requires the use of several factors that have received limited attention in the past but are important for the formulation of hydrogel-based immunoisolation systems that are highly versatile, potentially economical and can gain medical approval.

We observed several cases of patients who believed they were free of symptoms or signs of primary hyperparathyroidism (pHPT) preoperatively. reported a change of complaints following parathyroidectomy (PTX). We, therefore, decided to examine a larger group of patients to discover if these findings were incidental or of more general significance. The role of PTX in these patients with asymptomatic pHPT remains controversial. In 1991 criteria were defined at a NIH-consensus conference, according to which patients qualify for either operative therapy or long term medical surveillance. Until now, it was generally believed that the majority of asymptomatic patients would never develop symptoms. In a epidemiological cohort-study, the perioperative data of 582 consecutive patients with pHPT, including 116 asymptomatic patients (20.9%), who underwent parathyroidectomy between 1987 and 1998 were evaluated by uni- and multivariate analysis. At a median of 72 months postoperatively, all patients underwent a planned follow-up which included a standardised, validated questionnaire, physical examination and laboratory investigations. Eighty-six patients who were asymptomatic preoperatively were available for follow-up. Only eight (9.3%) were definitely asymptomatic, 4.6% of the entire, representative cohort. Postoperative improvement was reported in 81.4% of the "asymptomatic" patients. Multivariate analysis did not reveal a single or a set of preoperative measurements, that would allow to predict the retrospectively definitely asymptomatic patient. PTX resulted in normocalcaemia in 98.8% of preoperatively asymptomatic patients, with an operative morbidity of 1.2% and no mortality. Many apparently asymptomatic patients with pHPT will only realise that they did in fact have preoperative symptoms in retrospect, following PTX. This study suggests that using an up-to-date definition of asymptomatic pHPT, there are only a small number of truly asymptomatic patients and that these cannot be predicted preoperatively, as their symptoms may become apparent only after PTX. "Asymptomatic" patients with pHPT may share the same objective and subjective benefits from PTX as symptomatic patients. They should be operated as soon as the diagnosis is established.

Recently, the European Neuroendocrine Tumor Society (ENETS) held working sessions composed of members of the advisory board and other neuroendocrine neoplasm (NEN) experts to attempt to identify unmet needs in NENs in different locations or with advanced/poorly differentiated NENs. This report briefly summarizes the main proposed areas of unmet needs in patients with functional and nonfunctional pancreatic NENs.

Primary adrenal hyperplasia, which may occur as a familial disorder, is a rare cause of ACTH-independent Cushing's syndrome. In most of these cases the underlying pathology is primary adrenocortical micronodular dysplasia. Very few cases of familial Cushing's syndrome due to primary macronodular adrenal hyperplasia have been described. We report a family with seven affected family members. The pedigree indicates an autosomal dominantly inherited disorder. Interestingly only female family members developed the clinically apparent syndrome. The only available obligatory male gene carrier failed to adequately suppress his plasma cortisol level on overnight dexamethasone suppression test. His adrenal glands showed nodular enlargement on abdominal computed tomographic imaging. Screening of the MEN 1 gene and genetic analysis of the hot spot regions of the GNAS 1 (codons 201 and 227) and GNAI 2 (codons 179 and 205) genes did not show any mutations in the constitutional DNA or the adrenal tissue DNA of the index patient. In conclusion, this family is the largest kindred reported in the literature with ACTH-independent Cushing's syndrome due to autosomal dominant inherited macronodular adrenocortical hyperplasia. Four currently alive and affected family members in two generations and further careful observation of the yet unaffected members of the third available generation might offer the opportunity to identify the still unknown gene defect in the future.

Glucagon-like peptides (GLP) 1 and 2 are hormones derived from the post-translational processing of proglucagon in the intestinal L cells that influence intestinal motility and small bowel growth, respectively. We describe a patient with a neuroendocrine tumor of unknown primary origin with peritoneal carcinomatosis and diffuse liver metastases, who presented with constipation and nocturnal itching for over 3 years. Small bowel follow-through showed decreased small intestinal motility and marked intestinal hypertrophy. Biopsies from mesenterial lymph nodes showed, histologically, a well-differentiated neuroendocrine tumor (G1), with positive immunostaining for chromogranin A, GLP-1, GLP-2 and polypeptide YY (PYY). Jejunal biopsy demonstrated marked intestinal mucosal hypertrophy. HPLC analysis combined with RIA of tumor and serum extracts revealed that the tumor was producing and releasing fasting levels of GLP-1 of 738±20.7 pg/ml (normal levels (nl) <100 pg/ml), GLP-2 of 3,150±9 pg/ml (nl <100 pg/ml) as well as PYY 550 pg/ml (nl <100 pg/ml). Octreotide administration decreased levels of GLP-1 and GLP-2 and reduced small intestinal transit time from 150 to 50 min. However, tumor growth was not inhibited by octreotide, interferon or dacarbazine therapy and the patient died 8 months later. This is the first case report demonstrating the overproduction of GLP-1, GLP-2 and PYY from an neuroendocrine tumor, in a patient with intestinal hypertrophy and delayed intestinal transit time.