Turner syndrome: final height, glucose tolerance, bone density and psychosocial status in 25 adult patients.

The information available on the medical and psychosocial status of patients with Turner syndrome beyond the paediatric age group is scarce. We therefore studied 25 unselected women with cytogenetically proven Turner syndrome (age 20-50 years), who never received any growth-promoting therapy, and ten control women (25-48 years). In addition to anthropometric measurements, an oral glucose tolerance test was performed, auto-antibodies to endocrine tissues were studied, bone mineral density of the forearm was measured by single photon densitometry, and information about the psychosocial distress of the patients was obtained. Adult height averaged 148.7 +/- 1.1 cm (mean +/- SE), which was 16 cm below the mean of adult women from a similar background. In Turner patients, final height correlated significantly with mid-parental height (final height = 0.67 x MPH + 32.1; r = 0.69). Body mass index was increased in Turner patients (25.6 +/- 1.3 kg/m2) compared to controls (21.4 +/- 0.6; P < 0.006). Six patients (25%) had impaired glucose tolerance or overt diabetes mellitus (one patient). Insulin release was augmented but delayed in the Turner group, and the area under the insulin stimulation curve was correlated to body mass index (r = +0.54, P < 0.01). Thyroid antibodies were detected in nine patients (37.5%). On average, bone density of the forearm was only marginally reduced compared to the age-dependent normal range. All women were employed, while only one of the Turner women was married. As a group, the subjects expressed greater distress due to infertility compared to short stature.(ABSTRACT TRUNCATED AT 250 WORDS)

The somatotropin-somatomedin axis in adult patients with Turner syndrome: measurement of stimulated GH, GH-BP, IGF-I, IGF-II and IGFBP-3 in 25 patients.

So far, few studies have addressed the regulation of GH and GH-dependent growth factors in adult patients with Turner syndrome. We therefore studied a group of 25 genetically proven patients with Turner syndrome (age 20-50 years) and 10 control women (25-48 years). Turner patients were significantly shorter (148.7 +/- 1.1 cm vs. 169.1 +/- 2.3 cm; mean +/- SE; p < 0.0001) and more overweight [body mass index (BMI)] 25.6 +/- 1.3 vs. 21.4 +/- 0.6 in controls; p < 0.01). No significant differences were present when the integrated GH response to stimulation with arginine and the serum levels of GH-binding protein (GH-BP), IGF-I, IGF-II and binding protein 3 for IGFs (IGFBP-3) were compared between the two groups. However, more detailed analysis revealed significant abnormalities of the somatotropic axis in Turner patients. Pituitary GH secretion was negatively and serum GH-BP positively related to the degree of overweight in normal patients. In Turner patients, no such relationship was present, while IGF-II significantly increased with BMI. IGFBP-3 was positively related to adult height in normal women but not in Turner patients. While serum testosterone values did not affect any of the somatotropic parameters measured, there was a previously unreported, inverse relation between serum estradiol and GH-BP in controls but not in Turner patients. While adult patients with Turner syndrome do not display endocrine features of GH insufficiency, a detailed analysis reveals several abnormalities of the interrelation between anthropometric parameters, sex steroids and the pituitary-somatomedin axis.

[FSH-producing hypophyseal tumor in a 13-year-old girl]. / FSH-produzierender Hypophysentumor bei einem 13jährigen Mädchen.

We report on a 13 year old girl with a FSH, secreting pituitary tumour, who was presented with recurrent bleeding disorders. Gynaecological examination revealed large cystic ovarian tumours on both sides. The endocrinological work-up showed high serum levels of oestradiol and FSH, and low serum levels of testosterone and LH. Computed tomography demonstrated a pituitary tumour of 3 cm diameter.

Radioimmunoassay of somatostatin in human plasma.

A radioimmunoassay procedure for determination of somatostatin immunoactivity in human plasma is described. Labelling of tyrosine-1-somatostatin is performed by chloramine T. Specific activity of the tracer is 1.34 mol iodine for 1 mol of somatostatin. The immunoreactivity is 85%. Antisera are produced in rabbits at a titre of 179 X 10(-12) mol somatostatin per ml antiserum. Human plasma is extracted by n-butanol/2 mol/l acetic acid. Recovery rate is 85-105%. The intra-assay CV varies from 12% to 1.7%, the inter-assay CV from 16% to 7.5%, depending on the concentration of somatostatin.

Somatostatinoma syndrome. Clinical, morphological and metabolic features and therapeutic aspects.

A case of somatostatinoma syndrome in a 30-year-old woman is presented. Basal levels of growth hormone and of pancreatic and gastric hormones were reduced and the response of growth hormone, insulin and C-peptide to stimuli such as arginine, glucose, glibenclamide and calcium was virtually abolished. Similarly, gastric acid secretion, pancreatic exocrine function and intestinal absorption were significantly reduced. On the other hand, basal and stimulated levels of adrenocorticotropic hormone (ACTH), luteinizing hormone (LH), follicle-stimulating hormone (FSH) and thyroid-stimulating hormone (TSH) were within the normal range. Plasma somatostatin-like immunoreactivity was increased to 600-2,000 pg/ml (normal: 88-140 pg/ml). Immunocytochemical studies demonstrated the presence of somatostatin immunoreactive material in the primary tumour in the head of the pancreas and in the liver metastases. In spite of two courses of chemotherapy with streptozotocin and 5-fluorouracil the patient died due to liver failure 5 months after the first admission to hospital.

Dependence of human somatotropin activity on interchain disulfide bridges.

The importance of the disulfide bridges for human somatotropin activity is investigated. The activity of somatotropin is tested by the tibia, radioimmuno-, and radioligand assays. The cleavage of disulfide bridges by sulfitolysis, reduction with dithiothreitol, or oxidation with performic acid does not completely abolish hormone activity. There is only one exception: in the radioligand assay, oxidized somatotropin is not able to displace native somatotropin from rat liver membranes. The diminution of hormone activity is independent of the charges of the groups introduced to the cysteine residues. The radioimmuno- and radioligand assays are more sensitive to conformational alterations in the somatotropin molecule than the biological test system.

Potency of biosynthetic human insulin determined in vitro.

Biosynthetic human insulin (BHI) obtained from separately synthesized A- and B-chains by recombinant DNA technology with Escherichia coli fermentation was compared with human and pork insulin of high purity in vitro. Applying four biologic tests (glucose oxidation and glucose incorporation into the lipids by rat epididymal fat pads, inhibition of lipolysis, and ATP depletion of isolated fat cells) and three receptor assays (binding competition with human fat cells, IM-9 lymphocytes, and rat liver cell plasma membranes), we could not discern significant differences of the half-maximum response by these seven methods. The only variance occurred with the ATP-depletion assay. This method disclosed 10% greater maximum reversion of isoproterenol-induced ATP depletion by BHI when compared with pork insulin.

Studies on the pituitary "Fettstoffwechselhormon". VIII. Radioimmunoassay of the lipolytic factor P-LF II D.

A radioimmunoassay of the lipolytic peptide P-LF II D from porcine pituitaries is described. The assay is performed with 125-iodine labeled P-LF II D and with antisera either from guinea pigs or from rabbits. Bound antigen is separated from the free by double antibody technique. No cross reaction is observed with gamma lipotropin, peptide B, secretin, glucagon, isoproterenol. Due to contamination P-LF II C, beta lipotropin and human growth hormone displace the tracer when added at large doses. Complete cross reaction is observed between porcine 1-39 ACTH and P-LF II D. Specificity of this reaction is demonstrated by the increase of cross reaction, when ACTH fragments of increasing length of the polypeptide chain are used (1-23 ACTH, 1-24 ACTH and 1-28 ACTH).

Growth hormone radiologand assay unresponsive to human prolactin.

A specific and sensitive radioligand assay for growth hormone with female rat liver plasma membranes is presented. Growth hormones of different species are able to displace labelled human growth hormone from membrane binding sites with parallel standard curves. Human prolactin V-L-S is not equal to 1 and the international human prolactin standard MRC 71/222 do not affect the assay. Human prolactin preparations with different growth hormone content displace human growth hormone tracer only to the same extent as they contain growth hormone when measured by radioimmunoassay.

Immunological identity of human and porcine growth hormones. Application to determination of growth hormone in porcine serum.

In two radioimmunoassay systems with iodinated human growth hormone as tracer and anti-human growth hormone or anti-porcine growth hormone as binding site, the standard curves for human and for porcine growth hormone were parallel. In both systems the porcine growth hormone preparation had to be added in about the same excess as compared to the human hormone. It was concluded that the human and the porcine hormones behave in an identical way and that the values obtained in radioimmunoassay for human growth hormone represent the amount of immunologically active molecules in the porcine growth hormone preparation. As parallel standard curves were obtained with porcine serum, the concentration of growth hormone is porcine serum may be determined by radioimmunoassay for human growth hormone.

Immunological relatedness of human and porcine growth hormones.

The immunological relatedness of human and porcine growth hormones is examined by means of labelled human growth hormone and guinea pig antiserum. 1) Labelled human growth hormone is found in the precipitate after reaction with antiserum against porcine growth hormone. Parallel dilution curves are obtained with antisera against human and porcine growth hormones. 2) After addition of antiserum against porcine growth hormone, all the radioactivity is eluted from Sephadex G-100 with the void volume. 3) The addition of an excess of porcine hormone displaces labelled human growth hormone from antibodies against human growth hormone to the same extent as an excess of non-labelled human growth hormone does. 4) The standard radioimmunoprecipitation curves for porcine and human growth hormones obtained in the assay system for the human hormone are parallel in slope, provided that the human hormone and our preparation of the porcine hormone are introduced at a proportion of 1 to 560. 5) In a double diffusion test in agarose gel layers, with human and porcine growth hormones diffusing against guinea pig anti-porcine serum, cross reaction is observed. The conclusion is drawn that with guinea pig antisera, human and porcine growth hormones behave immunologically in a similar fashion. Labelled human growth hormone seems to have only such immunodeterminants as are also found in porcine growth hormone.