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L Schaaf

Publications and source records attributed to L Schaaf.

At least 19 recordsLinked to original sources
PubMed2004

Estradiol stimulates vascular endothelial growth factor and interleukin-6 in human lactotroph and lactosomatotroph pituitary adenomas.

Estrogens are considered to be critically involved in lactotroph and lactosomatotroph pituitary tumor development. In addition to direct effects, estradiol-induced tumor formation may involve alterations in growth factor and cytokine production. We have studied whether estradiol stimulates the production of the angiogenic vascular endothelial growth factor and the potential tumor progression factor interleukin-6 in 5 lactotroph (LA) and 5 lactosomatotroph (LSA) human pituitary adenoma cell cultures. All tumors secreted heterogenous basal amounts of VEGF (18.0 +/- 1.4 to 425 +/- 26 pg/ml per 24 h) and IL-6 (18.1 +/- 1.5 to 604 +/- 17 pg/ml per 24 h). Estradiol (100 nM) significantly enhanced VEGF release in all LA and LSA cell cultures (47 to 168 % above basal). IL-6 secretion was stimulated in 3 out of 5 LA and in all LSA cell cultures (31 to 287 % above basal). In cell cultures obtained from tumors from which sufficient cells could be isolated, a dose-dependent effect of estradiol (1 to 100 nM) on VEGF and IL-6 production was observed. Stimulation of IL-6 and/or VEGF secretion by estradiol in the majority of human lactotroph and lactosomatotroph adenoma cell cultures studied, suggests that estrogens may contribute to adenoma expansion through the stimulation of these auto-/paracrine-acting adenoma progression factors.

Adult↗
PubMed2003

Serum leptin monitoring in anorectic patients during refeeding therapy.

Circulating concentrations of leptin are exceedingly low in severe malnutrition as seen in the acute state of anorexia nervosa (AN). During refeeding therapy plasma leptin levels increase to normal and in some cases peak at values in excess of the BMI of matched controls even before a normal body weight has been achieved. Peak leptin levels are possibly the cause of an increased energy expenditure during this stage of the disorder and might predispose to renewed weight loss (rebound phenomenon). In this study we investigated the role of leptin fluctuations as a prognostic factor of therapeutic success in AN. In 11 anorectic female patients serum leptin levels, BMI and body fat percentage were evaluated in four-week intervals during a conventional refeeding program over three months (group 1). The results of the first two measurements were used to determine a range of increases in leptin levels in relation to increases in BMI. The values between the 25th and 75th percentiles determined the reference range. In a second group of 9 anorectic female patients serum leptin levels, BMI, body fat percentage and the increase in the leptin level in relation to the BMI of each subject were investigated for three months every two weeks. These patients were also treated according to the same conventional refeeding program, but the caloric intake was reduced or increased (+/-250 kcal/d) if the increase in the leptin level, in relation to the increase in the BMI, had exceeded or fallen short of the reference range. During the refeeding therapy every subject of each group experienced increases in serum leptin levels, BMI and body fat percentage. Six subjects of group 1 and six subjects of the second group had an increase in leptin levels in relation to the increase of the BMI out of the reference range at least once. To investigate the therapeutic outcome of leptin monitoring and the following alteration of caloric intake, weight gain of the patients of both groups during the whole treatment was compared. No significant difference was found. Our results probably do not support the findings that high leptin levels predispose to a renewed loss of weight. The outcome in our patients whose caloric intake was modified due to their serum leptin levels was not significantly improved.

Adipose Tissue↗
PubMed2002

Transforming growth factor-beta stimulates vascular endothelial growth factor production by folliculostellate pituitary cells.

TGF-beta isoforms are expressed in the anterior pituitary and modulate the growth and function of endocrine pituitary cells. Recently, TGF-beta has been shown to stimulate growth and basic fibroblast growth factor secretion in nonendocrine folliculostellate (FS) pituitary cells. We therefore studied whether the production of FS cell-derived vascular endothelial growth factor (VEGF), the most important regulator of vascular permeability and angiogenesis, is affected by TGF-beta. We observed by RT-PCR that TtT/GF cells, which are FS mouse pituitary tumor cells, synthesize TGF-beta1, -beta2, and -beta3. They also express TGF-beta receptors types 1 and 2, as well as Smad2, Smad3, and Smad4 proteins, which are essential for TGF-betabinding and signaling. Stimulation of TtT/GF cells with either TGF-beta1 or TGF-beta3 induced a rapid translocation of Smad2 into the cell nuclei. Both TGF-beta isoforms dose dependently stimulated VEGF production in TtT/GF cells, but not in lactosomatotroph GH3 cells. Time-course studies and suppression of TGF-beta-induced VEGF production by cycloheximide suggest that TGF-beta induces de novo synthesis of VEGF in folliculostellate cells, which is completely blocked by dexamethasone. In primary rat pituitary cell cultures, TGF-beta1 and -beta3 stimulated VEGF production. TGF-beta stimulation of VEGF production by folliculostellate cells could modulate intrapituitary vascular permeability and integrity as well as angiogenesis in an auto-/paracrine manner.

Animals↗
PubMed2002

Retention of dopamine 2 receptor mRNA and absence of the protein in craniospinal and extracranial metastasis of a malignant prolactinoma: a case report.

OBJECTIVES: The case presented here describes the clinical evolution of a malignant prolactinoma with occurrence of intra- and extra-cranial metastases. In this case, the presence of dopamine 2 receptor (D2R) was studied at the mRNA and protein level, in order to understand the pathological background of the resistance to treatment with different dopamine agonists. DESIGN: Together with an extensive description of the clinical history of this case, a combination of in vitro and in vivo techniques was performed to provide the basis of the dopamine resistance developed in the course of the disease. METHOD: A comparison of the D2R was performed in specimens obtained at presentation of the disease compared with autoptic specimens derived from local invasion and metastasis using in situ hybridization and immunohistochemical techniques. RESULTS: Intact D2R mRNA was found in the primitive tumor and metastatic tissues, whereas protein for the same receptor was present only in the tissues derived from neurosurgical operations and not in the metastases obtained post-mortem. CONCLUSION: This is the first report of the absence of D2R protein despite the retention of the transcript in an advanced stage of a malignant prolactinoma. The findings of this single case suggest the hypothesis that postranscriptional mechanisms may contribute to the development of dopamine resistance in prolactinomas.

Brain Neoplasms↗
PubMed2001

Limited sampling models for CPT-11, SN-38, and SN-38 glucuronide.

PURPOSE: We developed limited sampling models (LSMs) for predicting the area under the curve (AUC) of irinotecan (CPT-11) and its metabolites SN-38 and SN-38 glucuronide (SN-38G). PATIENTS AND METHODS: Regression models were developed based on data from a phase I clinical trial involving 34 patients with advanced solid tumor malignancies who received CPT-11 as a 90-min infusion on an every 3-week dosing schedule. Multiple stepwise regression procedures were supplemented by all possible subsets regression analysis. Alternative clinically based and empirically derived LSMs were determined via model validation assessment including bootstrap simulation testing. RESULTS: The best LSMs for CPT-11 AUC included concentrations recorded at the end of infusion and 4 h later with an option to include a blood draw at 7.5 h from infusion start. For SN-38 and SN-38G AUC, optimal LSMs included the additional metabolite concentration at 48 h after infusion. The LSMs were able to predict most patient AUC values to within 10% of the true value. CONCLUSION: CPT-11 AUC can be modeled with acceptable accuracy using only two or three plasma concentration time-points. A variety of LSM alternatives provided comparable accuracy in predicting AUC. Given the wide variety of LSM alternatives, clinical considerations and patient burden become more important performance parameters than statistical considerations for the choice of time-points in constructing LSMs.

Antineoplastic Agents, Phytogenic↗
PubMed2000

Nerve growth factor and retinoic acid inhibit proliferation and invasion in thyroid tumor cells.

NGF has anti-proliferative and anti-invasive effects in neuroendocrine tumors. In the present work we examined the effects of NGF and retinoic acid on cell proliferation and invasion in thyroid carcinoma cells. We found that NGF and retinoic acid do not affect cell proliferation on their own but in combination they produce a strong inhibition. We also found that retinoic acid regulates the matrix metalloproteinase 2 activity and invasion. In contrast, NGF inhibited invasion and reverted the effect of retinoic acid. This effect of NGF is likely mediated by an increase in adhesion to laminin and collagen IV and the inhibition of cell migration. NGF also induced the expression of the p75 NGF receptor. In conclusion, NGF and retinoic acid in combination inhibit proliferation and invasion of thyroid papillary carcinoma cells. These data open the possibility of a potential combined therapy for thyroid papillary carcinomas.

Antineoplastic Agents↗
PubMed2000

Concepts for screening and diagnostic follow-up in multiple endocrine neoplasia type 1 (MEN1).

The recent identification of MEN1 gene mutations as the molecular cause of familial multiple endocrine neoplasia type 1 syndrome (MEN1) has had a significant impact on clinical patient care. In the following consensus statement we will present recommendations for clinical screening and follow-up in patients and relatives with suspected or established MEN1 syndrome. MEN1 mutational analysis should be performed in individuals with newly diagnosed MEN1-typical endocrine neoplasia (e.g., primary hyperparathyroidism, gastroenteropancreatic tumor, pituitary adenoma) if additional diagnostic criteria are met (e.g., age <40 years; positive family history; multifocal or recurrent neoplasia; two or more organ systems affected). Genetic family screening is advisable in first degree relatives of MEN1 patients during early adolescence to reliably assess future MEN1 disease risk. In symptomatic individuals carrying MEN1 germ line mutations, annual clinical and biochemical (calcium, PTH, gastrin, prolactin) follow-up as well as routine pancreatic and pituitary imaging may be complemented as individually needed. In contrast, relatives without family-specific MEN1 mutation do not require routine follow-up. Diagnostic procedures and treatment in symptomatic MEN1 mutation carriers and patients may differ from that in sporadic endocrine neoplasia, calling for individual management. Genetic counselling and dedicated endocrine surgery should be integral parts of current medical care in MEN1 syndrome.

Genetic Testing↗
PubMed2000

Thyrotropin-releasing hormone time-dependently influences thyrotropin microheterogeneity--an in vivo study in euthyroidism.

Thyrotropin (TSH) is secreted not as one distinct hormone, but rather as a group of isohormones which differ in their oligosaccharide composition. Although the mechanisms regulating TSH glycosylation are not fully understood, there is strong evidence that TRH plays an important role. The aim of our study was to determine the dynamic influence of TRH on TSH microheterogeneity. Sera were obtained from euthyroid volunteers (n=20) before and 30, 60, 120, 180 and 240 min after intravenous, nasal and oral administration of TRH in three independent runs (randomized order, at a time-interval of 3 weeks between each run). TSH was immuno-concentrated and analysed by isoelectric focusing (IEF) and lentil lectin affinity chromatography. TSH immunoreactivity was measured by an automated second-generation TSH immunoassay. Overall, serum TSH concentrations reached maximal values 30 min after intravenous, 60 min after nasal and 180 min after oral TRH stimulation. IEF analysis revealed 63.3+/-3.3% of pituitary standard TSH (IRP 80/558) in the neutral pH range (8>pH>6). In contrast, 30 min after TRH stimulation 80.8+/-3.7% (P<0.001) and 60 min after TRH stimulation 44.9+/-2.2% (P<0.001) of the TSH of euthyroid probands were found in this pH range, whereas 180 min after TRH stimulation 58.4+/-2.3% (P<0.001) were detected in the acidic pH range (pH<6). This shift of TSH composition in euthyroidism after TRH stimulation was confirmed by lentil lectin analysis of TSH: core-fucose content of euthyroid TSH was 73.4+/-3.8% 30 min and 22.9+/-3.2% 120 min after TRH stimulation in contrast to basal (53.3+/-1.8%; P<0.001) and pituitary standard (IRP 80/558) TSH (63.0+/-0.9%; P<0.001). In conclusion, in euthyroidism, TRH stimulation time-dependently changes the distribution pattern of the TSH isoforms from an alkaline and neutral to a more acidic one. This corresponds to the secretion of isohormones with altered bioactivity which could influence the fine-tuning of thyroid function.

Administration, Intranasal↗
PubMed2000

Thyrotrophin receptor protein expression in normal and adenomatous human pituitary.

Thyrotrophin (TSH) synthesis and secretion is under the positive control of thyrotrophin releasing hormone and under the negative control of the thyroid hormones. However, it is hypothesised that TSH has a direct effect on the regulation of its own synthesis through an intrapituitary loop mediated by pituitary TSH receptors (TSH-R). The aim of this investigation was to study the expression of TSH-R in normal human pituitary at mRNA and protein levels, and to compare the pattern of protein expression between different pituitary adenomas. Using RT-PCR we were able to detect TSH-R mRNA in the normal pituitary, and immunohistochemical studies showed TSH-R protein expression in distinct areas of the anterior pituitary. Double immunostaining with antibodies against each of the intrapituitary hormones and S100 revealed that TSH-R protein is present in thyrotrophs and folliculostellate cells. Examination of 58 pituitary adenomas, including two clinically active and two clinically inactive thyrotroph adenomas, revealed TSH-R immunopositivity in only the two clinically inactive thyrotroph adenomas. This study shows, for the first time, the presence of TSH-R protein in the normal anterior pituitary and in a subset of thyrotroph adenomas. The expression of TSH-R in the thyrotroph and folliculostellate cell subpopulations provides preliminary evidence of a role for TSH in autocrine and paracrine regulatory pathways within the anterior pituitary gland.

Adenoma↗
PubMed1998

Modulation of human thyrotropin oligosaccharide structures--enhanced proportion of sialylated and terminally galactosylated serum thyrotropin isoforms in subclinical and overt primary hypothyroidism.

Enhanced sialylation of thyrotropin (TSH) prolongs its metabolic clearance rate and thus increases the hormone's in vivo bioactivity. This has been shown for hypothyroid rats and for recombinant human TSH, but there are few data on the sialylation of human serum TSH. The aim of this work was to further study sialylated human serum TSH, its precursors bearing terminal galactose residues, and the role of pharmacological doses of thyrotropin-releasing hormone (TRH) on their secretion under different degrees of primary hypothyroidism. We analyzed serum TSH in patients with subclinical (n = 9) and overt primary hypothyroidism (n = 13) compared with euthyroid individuals (n = 12) and human standard pituitary TSH (IRP 80/558). Blood was drawn before and 30 min after intravenous administration of 200 micrograms TRH, and TSH was purified by immunoaffinity concentration. The content of sialylated (sialo-) TSH and isoforms bearing terminal galactose (Gal-TSH, asialo-Gal-TSH) was measured by Ricinus communis (RCA 120) affinity chromatography in combination with enzymatic cleavage of sialic acid residues. TSH immunoreactivity was measured by an automated second generation TSH immunoassay. Pituitary TSH contained 16.5 +/- 0.8% Gal-TSH. In euthyroid individuals the proportion of Gal-TSH was 14.6 +/- 1.9%, whereas TSH in patients with subclinical and overt primary hypothyroidism contained 23.9 +/- 3.5% (P < 0.05 vs euthyroid individuals) and 21.1 +/- 1.7% Gal-TSH respectively. The mean ratio of asialo-Gal TSH was 23.8 +/- 0.6% for pituitary TSH, 35.7 +/- 4.2% in euthyroid individuals, 48.0 +/- 3.3% in patients with subclinical, and 61.5 +/- 3.8% (P < 0.001 vs euthyroid individuals) in patients with overt primary hypothyroidism. For pituitary TSH the calculated proportion of sialo-TSH was 6.5 +/- 0.2%, for euthyroid individuals 20.3 +/- 2.8%, for patients with subclinical hypothyroidism 24.1 +/- 3.0%, and for patients with overt primary hypothyroidism 40.7 +/- 3.0% (P < 0.001 vs euthyroid individuals). The proportions of Gal-TSH, asialo-Gal-TSH, and sialo-TSH did not differ significantly before and after TRH administration in the individuals studied. Our data show that patients with subclinical and overt primary hypothyroidism have a markedly increased proportion of serum TSH isoforms bearing terminal galactose and sialic acid residues, which may represent a mechanism for the further stimulation of thyroid function. Pharmacological doses of TRH cause an increased quantity of TSH to be released, but do not significantly alter the proportion of sialylated or terminally galactosylated TSH isoforms.

Adult↗
PubMed1997

Glycosylation variants of human TSH selectively activate signal transduction pathways.

The oligosaccharide chains of pituitary glycoprotein hormones such as human thyroid-stimulating hormone (hTSH) have been shown to be important in biosynthesis, subunit association, secretion and bioactivity. However, the exact biological significance of these glycosylation variants (isoforms) remains controversial. The aim of this paper is to investigate the role of hTSH glycosylation variants in signal transduction. Human pituitary standard TSH (2nd International Reference Preparation 80/558; IRP-hTSH) was treated with neuraminidase, fractionated by isoelectric focusing (IEF) and affinity chromatography using the lectins concanavalin A (Con A) and lentil. To determine the in vitro bioactivity of these hTSH isoforms, simultaneous measurement of cAMP formation and inositol phosphates release was applied in two different cell systems (CHO cells stably and Cos-7 cells transiently transfected with hTSHR cDNA). Desialylated TSH variants showed a significantly increased ratio of bioactivity to immunoreactivity for cAMP production in CHO-R cells (B/I ratio desialylated variants: 3.54 +/- 0.005; B/I ratio sialylated variants: 2.84 +/- 0.01 P < 0.05). Testing the bioactivity of hTSH glycosylation variants isolated by IEF, we found basic variants to be significantly more active than acidic ones in stimulating the cAMP formation in CHO-R cells (B/I ratio basic variants: 9.92 +/- 0.64; neutral variants: 5.98 +/- 0.07; acidic variants: 2.80 +/- 0.12; P < 0.01). There were no differences in stimulation of IP-release. High-mannose TSH variants (firmly bound to Con A) showed greater potency to stimulate cAMP formation and IP-release in both CHO-R and Cos-7 cells than biantennary TSH variants (weakly bound to Con A). Both core-fucosylated (lentil-bound) and core-unfucosylated (lentil-unbound) TSH variants proved to be strong stimulators of cAMP release in CHO and Cos-7 cells. In CHO-R (Cos-7) cells, 400 microU/ml core-fucosylated TSH stimulated cAMP formation 14(2.6)-fold, core-unfucosylated TSH 7.3(2.3)-fold over control values. In contrast to our findings of cAMP activation by both core-fucosylated and core-unfucosylated TSH variants, release of IPs was stimulated only by, core-fucosylated (lentil-bound) TSH variants and not by TSH variants lacking core-fucose residues (lentil-unbound TSH). This was true for both CHO-R and Cos-7 cells. The lentil-unbound TSH therefore showed an identical differential activation of signal transduction pathways in two different cell systems: strong stimulation of the cAMP-cascade without activation of IPs release (P < 0.05). In conclusion, we showed for the first time for TSH that the two dominant intracellular signal transduction systems (cAMP formation and IPs release) are activated to different degrees by hTSH glycosylation variants.

Animals↗
PubMed1997

Phase I study with the DNA sequence-specific agent adozelesin.

Adozelesin, a synthetic analog of the antitumor antibiotic CC-1065, is a novel cytotoxic agent which inhibits DNA synthesis by binding to the minor groove of the DNA helix. Preclinical studies have shown a broad spectrum of activity against a variety of murine and human tumor xenograft models. We conducted a phase I study of adozelesin to (i) determine a recommended dose for phase II testing using a 10 min i.v. infusion, (ii) characterize the toxic effects of the drug using this schedule and (iii) document any antitumor activity observed. Adozelesin was administered as an i.v. infusion every 6 weeks. CBC and biological parameters were performed weekly. The starting dose of 10 microg/m2, corresponding to 1/30 the mouse equivalent lethal dose, was escalated, according to a modified Fibonacci scheme, until dose-limiting toxicity was encountered. Forty-seven adult patients with solid malignancies were entered in the study. Successive dose levels used were 10, 20, 33, 50, 70, 105, 120, 150 and 180 microg/m2. The main toxic effect was myelosuppression, which was dose limiting. The maximally tolerated dose was defined as 180 microg/m2. A minor response with a 4 month duration was reported in one previously treated patient with melanoma. We conclude that the recommended phase II dose of adozelesin given as a 10 min infusion is 150 microg/m2, repeated every 4 weeks.

Adult↗
PubMed1996

Phase I clinical and pharmacokinetic study of irinotecan, fluorouracil, and leucovorin in patients with advanced solid tumors.

PURPOSE: To determine the maximum-tolerable dose (MTD) of fluorouracil (5FU) when given with fixed doses of leucovorin and irinotecan (CPT-11), to define the dose-limiting toxicities of this combination, and to evaluate the effect of 5FU on the pharmacokinetics of CPT-11. PATIENTS AND METHODS: CPT-11, leucovorin, and 5FU were administered in repeated 6-week cycles that consisted of weekly treatment with all three drugs for 4 consecutive weeks followed by a 2-week break. On day 1 of treatment, CPT-11 alone was given by 90-minute infusion, and pharmacokinetic sampling was performed over 24 hours. Leucovorin and 5FU were administered by brief intravenous injection on day 2. On days 8, 15, and 22, CPT-11 infusion was immediately followed by leucovorin and then 5FU. A second 24-hour pharmacokinetic sampling was performed on day 8, which permitted comparison of the pharmacokinetics of CPT-11 with and without 5FU. For the second 6-week cycle, leucovorin was administered first, followed by 5FU and then CPT-11, and a third pharmacokinetic sampling was performed. RESULTS: Forty-two patients were entered onto this trial. The CPT-11 dose was initially fixed at 100 mg/m2. Leucovorin was fixed at 20 mg/m2. 5FU doses of 210, 265, 340, 425, and 500 mg/m2 were studied. When the 500-mg/m2 dose of 5FU was found to be tolerable, this was then maintained and CPT-11 was escalated to 125 and then 150 mg/m2. This final CPT-11 dose exceeded the MTD. Neutropenia was the major dose-limiting toxicity. Diarrhea was common, but was rarely dose-limiting. Coadministration of 5FU had no substantial effect on the pharmacokinetics of CPT-11 or SN-38. Among the 38 patients with colorectal cancer, six partial responses (PRs) were seen in this predominantly 5FU-refractory patient population. CONCLUSION: 5FU does not substantially affect the metabolism of CPT-11 to its active metabolite, SN-38. The combination of CPT-11125 mg/m2, 5FU 500 mg/m2, and leucovorin 20 mg/m2 is feasible and tolerable on this schedule.

Adult↗
PubMed1995

Serum thyrotropin (TSH) heterogeneity in euthyroid subjects and patients with subclinical hypothyroidism: the core fucose content of TSH-releasing hormone-released TSH is altered, but not the net charge of TSH.

The aims of the present study were to determine the influence of brief subclinical hypothyroidism on the isoforms of serum thyrotropin (TSH) and to examine the net charge of TSH in different metabolic states. Sera were obtained from euthyroid subjects (n = 7) and from patients with subclinical hypothyroidism (n = 8) before and 30 min after the intravenous administration of 200 micrograms thyrotropin-releasing hormone (TRH). The TSH from human pituitary extracts (IRP 68/38), basal and TRH-stimulated serum TSH was immunoconcentrated and further analysed by isoelectric focusing (IEF) and lentil lectin affinity chromatography. TSH immunoreactivity was determined in each specimen or fraction with an automated highly sensitive chemiluminometric TSH assay. We found that basal TSH in subclinical hypothyroidism, and TRH-released TSH in euthyroidism and in subclinical hypothyroidism is distributed in a similar neutral to acidic pattern, which significantly differs from the more alkaline to neutral isoform pattern of intrapituitary TSH (P < 0.05). IEF analysis of pituitary standard TSH revealed 3 major peaks (pI values 7.5; 6.6; 5.8) whereas in most euthyroid or subclinically hypothyroid subjects 5 peaks were found. Lentil lectin affinity chromatography revealed that TRH-released TSH in euthyroid subjects has more core fucose residues than TSH from patients with subclinical hypothyroidism (64.6 +/- 6.7 vs 12.5 +/- 2.7%, P < 0.0001). Thus pituitary standard TSH seems to be less mature material than circulating TSH. Perhaps no alteration in the IEF pattern of TSH was detected during early hypothyroidism because sialylation of TSH was increasing as sulfatation was decreasing. Nevertheless, a change in the core fucose content of TSH was detectable by lentil analysis.

Adult↗
PubMed1994

[Diagnosis, therapy and screening of multiple endocrine neoplasia type I (MEN I) in four endocrinologic centers].

BACKGROUND: Multiple endocrine neoplasia type I (MEN I) is a hereditary disease characterised by involvement of several endocrine organs (parathyroid, anterior pituitary, pancreatic islet cells and other). In order to build up a German MEN I-register a questionnaire was developed. PATIENTS: In four centres we diagnosed 29 cases of MEN I (average age 53 years, range 27 to 72 years, 21 women, eight men). RESULTS: In 25 patients (86%) we found a primary hyperparathyroidism, in 15 patients (52%) an adenoma of the anterior pituitary (seven patients with growth hormone-secreting adenomas, five patients with prolactinomas, two patients with hormone-inactive and one patient with an ACTH-secreting adenoma), in ten patients (34%) a neoplasm of the pancreatic islet cells (six patients with gastrinomas, four patients with insulinomas and two patients with multihormone tumors) and in ten patients (34%) other endocrine tumors (five carcinoid tumors, three adenomas of the adrenal cortex, one papillary thyroid carcinoma and one thymic tumor). In nine cases nephrolithiasis was the leading symptom of primary hyperparathyroidism. All female patients with prolactinomas developed secondary amenorrhea. In three cases gastrinomas caused duodenal ulcers and three insulinomas were detected by fasting hypoglycemia. A primary hyperparathyroidism was most frequently combined with an adenoma of the anterior pituitary (21%). Detailed screening of 13 families early revealed MEN I in eleven cases. CONCLUSIONS: The manifestation of an endocrine disease in MEN I should initiate further diagnostics. Having established the diagnosis of MEN I, a meticulous work-up of all family members is warranted. The set-up of a register by the successfully tested questionnaire will support these activities and facilitate further research of new genetic markers, follow-up and treatment.

Adult↗
PubMed1993

Screening for thyroid disorders in a working population.

Subclinical thyroid disorders have received increasing attention in recent years due to refined laboratory methods and a stronger emphasis on the role of preventive medicine. We performed a screening for thyroid-stimulating hormone (TSH) on 6884 persons in a working population. In cases in which TSH was not within the normal range we also measured the levels of triiodothyronine (T3), thyroxine (T4), and thyroxine-binding globulin (TBG). All persons who did not present with exclusion criteria or other nonthyroidal illnesses (n = 59) and the controls (n = 39) were submitted to thyrotropin-releasing hormone (TRH)-testing. Additionally, sonography of the thyroid was performed on 120 persons (59 subjects with abnormal hormone levels and 61 controls) to determine thyroid size and rule out morphological abnormalities. Based on the TRH test and T3, T4, and TBG measurements we found a prevalence of 0.03% (2/6884) for overt hyperthyroidism, 0.33% (23/6884) for subclinical hypothyroidism, 0.09% (6/6884) for subclinical hypothyroidism, and 0.015% (1/6884) for overt hypothyroidism in the healthy population. In subjects with overt or subclinical hyperthyroidism the prevalence of goiters (thyroid volume > 18 ml in women, > 25 ml in men) was 28%. Of this group 48% had structural abnormalities. All persons with goiters and/or structural abnormalities were over 35 years of age. Among the euthyroid, 20% had thyroid enlargement, and the same proportion presented with structural abnormalities. There were no differences between the two age groups. In the group with overt/subclinical hypothyroidism 47% presented with structural abnormalities of the thyroid; however, none presented with thyroid enlargement. Thyroid nodules were found only in older persons (> 35 years) with euthyroidism or hypothyroidism.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗