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Background: Multiple-endocrine-neoplasia-type-1 (MEN1) is an autosomal-dominant inherited disorder characterized by the combined occurrence of primary hyperparathyroidism (pHPT), gastroenteropancreatic neuroendocrine tumors (GEP), adenomas of the pituitary gland (APA), adrenal cortical tumors (ADR) and other tumors. As the tumors appear in an unpredictable schedule, uncertainty about screening programs is persisting. Objective: To optimize screening and to analyze possible differences in sporadic versus familial cases. Methods: We analyzed data of 419 individuals including 306 MEN-1 patients (138 isolated and168 familial cases out of 102 unrelated families). Results: A total of 683 tumors occurred consisting of 273 pHPT, 138 APA, 166 GEP, 57 ADR, 24 thymic- and bronchial-carcinoids as well as 25 neoplasms of other tissues. The age-related penetrance was determined as 10%, 35%, 67%, 81% and 100% at 20, 30, 40, 50 and 65 years respectively. Although pHPT being the most frequent first manifestation (41%), also GEP (22%) or APA (21 %) were found to be the first presentation. APA occurred significantly more frequent (p

OBJECTIVE: Familial isolated primary hyperparathyroidism (FIHP) is defined as hereditary primary hyperparathyroidism without the association of other diseases or tumors. Linkage analyses suggest that different genotypes can lead to the same phenotype of primary hyperparathyroidism. Hereditary syndromes associated with primary hyperparathyroidism are multiple endocrine neoplasia type 1 and type 2 (MEN 1 and MEN 2). In MEN 1, multiple parathyroid adenomas occur in more than 90% of the patients. Therefore, it has been suggested that FIHP could represent a variant or partial expression of MEN 1. DESIGN: We report on a large FIHP kindred with a MEN1 gene mutation. Nineteen family members (aged 10 to 87 years) were screened. Furthermore, statistical comparison by Fisher's exact tests of FIHP families with MEN1 gene mutations and MEN 1 families with two or more endocrinopathies was carried out to investigate genotype-phenotype correlations. METHODS: Mutational analysis of leucocyte DNA was carried out by direct sequencing of the complete coding region of the MEN1 gene. Screening of MEN 1 manifestations was carried out by determination of serum calcium, phosphate, parathyroid hormone, prolactin, ACTH, cortisol, IGF-I, gastrin, glucose, insulin, glucagon, serum potassium, aldosterone, plasma renin and urinary hydroxyindoleacetic acid. RESULTS: We detected an in-frame deletion mutation in exon 8 of the MEN1 gene resulting in the deletion of one glutamine acid residue at position 363. It was found in eight individuals. Two of these family members (aged 42 and 60 years) were operated for primary hyperparathyroidism, and three (aged 13 to 40 years) showed mild hypercalcemia and parathyroid hormone levels within the upper normal range or slightly elevated, without any clinical symptoms. Two individuals (aged 12 and 19 years) were normocalcemic. One could not be tested. None of them had clinical evidence of other MEN 1 manifestations. Statistical comparison of the mutation types in families with FIHP and families with two or more MEN 1-associated endocrinopathies reported in other studies reveals a significant difference. In families with FIHP, missense/in-frame mutations have been found in 87.5% of cases whereas in families with tumors in various endocrine glands these mutation types occur much less frequently (21-34%, P

In contrast to primary hyperparathyroidism, parathyroid carcinoma is a rare disease. In patients with hyperparathyroidism jaw tumor (HPT-JT) syndrome, caused by germline mutations in HRPT2, the development of parathyroid carcinoma is estimated to be 10-15%. This review summarizes the clinical and molecular genetic data of about 100 patients in the literature and three of our own cases. Unfortunately, osteofibromas, which might enable timely diagnosis of HPT-JT syndrome, occur in only about 30% of patients; about 80% have uniglandular disease. Based on the current data, a general recommendation to perform prophylactic parathyroidectomy cannot be given. However, thorough screening of patients at risk is mandatory. Of note in patients thought to have sporadic parathyroid carcinoma, germline HRPT2 mutations are found in up to 20%. Hence, any patient with parathyroid carcinoma should undergo HRPT2 mutation analysis.

Carl-Adolph von Basedow described the typical clinical features of immune-mediated hyperthyroidism (tachycardia, proptosis, goiter) in 1840 and termed it the "Merseburg trias". Graves' disease is an autoimmune disease with thyroidal and extra-thyroidal manifestations such as endocrine orbitopathy, which is caused by a dense lymphocytic infiltrate. A genetic predisposition combined with so far unidentified environmental factors and a complex immunological process seem to be important for its pathophysiology. The pathognomonic histopathophysiological picture is characterised by the typical lymphocytic infiltration of the ocular muscles and retrobulbar connective and adipose tissues leading to the classical exophthalmus. No specific therapy is available. The goal of therapy is therefore the correction of the hyperthyroidism and inhibition of the immune-mediated orbital inflammation which can be achieved by early interdisciplinary team work of endocrinologists, ophthalmologists and radiation therapy.

The objective of the present study was the ascertainment of correct data related to growth prognosis in asthmatic children. For this purpose, 210 young asthmatics including 153 males and 57 females ranging in age from 1.7 to 18.9 years were evaluated. Data were specified for the parameters: chronological age (CA); bone age (KA); height age (LA); height (KH); severity of illness; target adult height (GZG) and predicted adult height (PEG). Among this group, 5.9 % of the boys and 3.5 % of the girls, were found to be of small stature (KH- 2 s). This corresponds to about 2.5 and 1.5 times the average in a normal distribution. Children with the highest severity of illness showed the strongest negative deviation for the KH-SDS values (boys - 0.59 plus minus 1.1, girls - 0.97 plus minus 0.8). This proved to be statistically significant for females. Development of CA, KA and LA continued unremarkably until the age of 4 years. From age 5, partially a significant growth retardation of KA and LA could be observed in both sexes. To age 16, KA values and, after that LA values, were more strongly affected. Comparison of the GZG and PEG average values within the degree of severity groups made it clear that the PEG values for both sexes, independent of the severity of illness, were without exception, smaller than the GZG. The differences of both parameters proved to be statistically significant for the group with the most severe symptoms of the boys (180.8 plus minus 6.5 cm to 175.8 plus minus 6.2 cm, p0.01) and for the entire groups of both sexes (boys 180.2 plus minus 5.3 cm to 178.6 plus minus 7.3 cm, p0.05, girls 167.7 plus minus 4.4 cm to 165.8 plus minus 6.8 cm, p0.05). However, a separate comparison of GZG and PEG average values, respectively, among the severity groups showed no significant differences. The results argue for a growth-inhibiting influence from bronchial asthma. The cause has to be severity of illness but direct effects of the atopy on skeletal development is also taken in consideration. Confirmation of these findings requires investigation of a larger group of asthmatics and clarification of the pathophysiological processes in the growing skeletons of atopic children.

Children suffering from asthma display a tendency to retarded growth and development, which also includes bone structure. The reason for this phenomenon has not been clarified. There seems to be an adaptative regulatory hypersomatotropism which can be regarded as a disturbance of peripheral growth hormone activity. We studied the question whether this is influenced by theophylline, a preparation often used in the treatment of asthma, since theophylline has been accused of growth hormone inhibition as a result of in vivo studies in adults. In 9 prepubertal boys suffering from atopic asthma we determined the growth hormone concentrations during 24 hours each before and during intravenous administration of theophylline. With this dosage the median values of the 24-hour profile (10.3 +/- 1.5 to 5.2 +/- 0.9 ng/ml), the 8-hour sleep phase (12.7 +/- 1.9 to 5.7 +/- 1.0 ng/ml) and of the maximal growth hormone peak (38.9 +/- 7.0 to 17.6 +/- 2.8 ng/ml) were significantly lower than on the first day on which theophylline was not administered. The multiple possibilities by which theophylline may be exercising this effect, are discussed. Prospective long-term clinical studies will have to clarify whether the effect is clinically significant.

Asthmatic children tend towards hyposomia. Although quite a number of suggestions have been made, the real cause of this phenomenon has not yet been revealed. Investigation of the growth hormone secretion and the IGF-I serum levels aims at clarifying whether an atopy-caused disturbance in the interaction between both the hormones is responsible for retardations in the growth and development of asthmatic children.In 19 prepubertal extrinsic asthmatics the spontaneous growth hormone secretion was reviewed in form of a 24 h-profile. In addition, the IGF-I serum levels were measured.With a mean 24 h-secretion of 10.7 +/- 1.0 ng/ml and a maximum growth hormone peak of 39.5 +/- 5.8 ng/ml prepubertal extrinsic asthmatics showed an increased hormone secretion which, however, could not be observed with all the children. The IGF-I mean values were in 11 asthmatics within the normal range, decreased in 5 cases and increased in only 3 children.

It is reported on the clinical experiences in the care of 19 patients with insulinoma. The relatively simple proof of the existence of an insulinoma which is possible by the determination of insulin is performed by the recognition of a pathognomonic insulin--blood glucose--quotient in fasting state and in the fasting test, respectively. Stimulation tests are less evident and do not lead to any further clinically relevant information. The difficulty of the diagnosis consists in the localisation of the tumour. Without clinically urgent necessity an operation without localisation of the tumour should not be performed.

72 of 413 adults and 55 of 112 children with intact function of the hypophysis revealed secretions of the growth hormone already in the preparation time for a clinical test. These variations of the HGH basal levels must be regarded as conditioned on test. In the judgment of the function of the anterior lobe of the pituitary gland with the help of the dynamics of the HGH-secretion the changes in the pretest-period should be included in order to avoid false diagnoses. From the secretion of the growth hormone conditioned on stress hitherto no conclusions can be made to the following course of the HGH-secretion.

In 119 children and adolescents with restricted growth whose secretion of growth hormone (hGH) was investigated in the insulin hypoglycaemia test, different hGH-secretion patterns were found. 52.1% of the investigated persons showed a prestimulatory stress-conditioned hGH-secretion. There were no relations to age or to sex. The hypoglycaemia-conditioned secretion of hormone following this spontaneous release has quantitatively no relation to the size of the decrease of blood sugar. However, it is also determined by the trend of secretion in the pretest-phase. Different modes of synthesis and release are the cause for this behaviour. High spontaneous hGH-levels decrease the hypoglycaemia effect of the intravenously applied insulin. In 33.9% of the cases the levels of the growth hormone are lower during the proper test phase or only as high as in the preparation time. Twelve times the poststimulatory values simulated a hyposomatotropism. The eventual importance of the secretion patterns remains up to now unclear for the longitudinal growth.

In a retrospective investigation 228 obese persons with healthy metabolism and diabetics (NIDD) were invited to a check-up 4-10 years after a reduction of weight which was performed during a clinical treatment in the 2nd Medical Clinic of Halle University. 95 patients did not comply with the invitation, 9 patients had died in the meantime. Among the 24 obese persons examined were 9 patients with NIDD. In other 19 patients a diabetic metabolic disturbance had become manifest in the meantime. 78 obese persons underwent a clinical examination, among them 9 NIDD. 60 patients had a normal and 18 a pathological carbohydrate tolerance. Of these 18 patients in 9 patients an up to now unknown diabetes mellitus could be proved. The obesity coincides with a relatively high rate of disturbed carbohydrate tolerance and a larger proportion of manifest diabetics compared with the normal population. In the own group of patients the morbidity of diabetes among the obese persons increases from 10.5 to 30% after on an average 7 years. Obese persons who had essentially exceeded their initial weight in the meantime and show further metabolic disturbances are particularly endangered.

It is reported on a female patient with a classical homocystinuria who showed all typical symptoms of the cystathionine-synthesis-insufficiency, such as tall stature, phacetomy, arachnodactyly, kyphoscoliosis, generalized osteoporosis and thromboembolisms. While homocystin in the blood plasma and the urine could be proved only in the patient, the concentration of plasma methionine was much increased also in the clinically completely inconspicuous sister.

It is reported on a now 48-year-old male with a multiple endocrine neoplasia (MEN I). The most impressive symptomatology issued from a relapsing organic hyperinsulinism the cause of which were multiple islet cell tumours. Up to now the hyperparathyroidism was not mastered by the removal of two adenomas of the parathyroid gland. As third fact in this clinical picture, called also Hiob syndrome, the hypophyseal manifestation developed in form of a space occupation with a hypersomatotropism, the course and final clarification of which are still open.

In 11 patients with acromegaly the peripheral thyroid hormones were determined and a TRH-TSH-test was carried out. Depending on the result of the determination of the growth hormone the patients were classified into two groups (active and inactive acromegaly). The serum thyroxin level and the T3-binding capacity were normal. Only in a few patients decreased triiodotyronine levels were found. Independent of the degree of activity of the acromegaly positive as well as negative TRH-TSH-tests were found. The struma in patients with acromegaly which is frequently to be observed seems to be in a causal connection with this disease. The examination show altogether that the control of the function of the thyroid gland and the TRH-TSH-test do not deliver an essential contribution for the diagnostics of acromegaly itself.

Behaviour of human growth hormone (HGH) during preparation for a clinical test. 172 adults and 63 children were examined for the behaviour of their HGH basic values during preparation for a clinical test. Even before the beginning of the stimulation itself 11% of the adults and 47,5% of the children showed a fluctuation of the HGH levels in the serum. Neglect of these HGH movements involves the risk of misinterpretation and thus of false diagnosis. It therefore appears to be essential, especially for judging stunted-growth forms in childhood, to make tests for "empty stomach" values for the purpose of HGH determination at least 30 minutes before and immediately at the beginning of the stimulation test. The behaviour of the basic values must be included in the assessment of the test.

It is reported on the possibilities of the application of anti-androgenics, especially of cyproterone acetate. The indication extends to hirsutism, sexual deviations, growth disturbances in pubertas praecox as well as diseases of the prostate. Particularly strong standard are to be applied in the treatment of fertile women, as there exists the danger of an intrauterine feminisation of male foetuses, when a pregnancy was not absolutely excluded. Side-effects and results of animal experiments are mentioned. The therapeutic mechanism of the anti-androgenics can be explained with the help of a concurrency mechanism at the androgen receptor or acceptor.