Klinische Bedeutung der Bestimmung der Bindung von Trijodthyronin an Serumproteine mittels Dextran-Gel-Filtration

Neben den bewährten älteren Verfahren zur Bestimmung des proteingebundenen127Jods und des Radiojodumsatzes hat sich die gleichzeitige Bestimmung des sog. freien und des proteingebundenen Anteils an in vitro mit Serum inkubiertem L-Trijodthyronin-131Jod mittels Dextran-Gel-Filtration klinisch zur Differentialdiagnose von Hyperthyreose und Euthyreose bewährt. Bei Ausnützung der Verdrängung von proteingebundenem L-Trijodthyronin-131Jod durch nichtmarkiertes Hormon und bei Variation der Dextran-Gel-Menge in der Säule bietet die Methode gute Differenzierungsmöglichkeiten auch für die Schilddrüsenfunktionszustände Euthyreose und Hypothyreose. Bei dem Verfahren wird der Patient nicht mit radioaktivem Jod belastet, ein für die Kinderklinik wichtiger Gesichtspunkt. Manche Störfaktoren, die den131Jodspeicherungstest und die Bestimmung des proteingebundenen Jods (PB127I) verfälschen, haben keinen Einfluß auf die mit der Dextran-Gel-Filtration untersuchten Proteinbindungsverhältnisse für L-Trijodthyronin-131Jod. So hat sich das Verfahren für die Untersuchung von Patienten mit operativ oder durch131Jodbehandlung verkleinerten Schilddrüsen, mit endokrinem Exophthalmus und in Fällen mit vorausgegangener Jodgabe, z. B. in Form von Kontrastmitteln, besonders bewährt. Mit der Bestimmung des sog. freien L-Trijodthyronin-131Jods wird ein physiologisch und pathogenetisch wichtiger Parameter der Schilddrüsenfunktion ermittelt. Die klinische Bedeutung der Bestimmung der Bindungs-und Transportverhältnisse für Trijodthyronin mittels Dextran-Gel-Filtration wird diskutiert.In addition to conventional methods of assay of protein bound iodine (PB127I) and of131iodine turnover in the thyroid, the simultaneous determination of socalled free and protein bound 1-triiodothyronine-131I, added in vitro to serum, using dextran gel filtration was found to be clinically helpful for diagnosis of euthyroidism and hyperthyroidism. Employing discharge effects of non-labelled triiodothyronine on protein bound 1-triiodothyronine-131I and varying the amount of dextran gel in the columns, the method provides reasonably good differentiation of euthyroid and hypothyroid states. No radioactive iodine is given to patients during this procedure, a fact of importance for pediatriciens. Some factors, that influence131iodine uptake or PB127I levels, do not disturb protein binding of 1-triiodothyronine-131I as determined by dextran gel filtration. The latter method was found to be especially useful for the examination of patients with surgically, or by therapy with131iodine dissected thyroid glands, with endocrine exophthalmos, and in cases of previous iodine administration (e.g. X-ray procedures). Determination of socalled free 1-triiodothyronine-131I provides information about a factor of physiological and pathogenetical significance, its clinical meaning is discussed

Pituitary responsiveness to LHRH and TRH in adolescent girls

Puberty is characterized by a progressive maturation of the hypothalamus-pituitary gonadal axis which, in girls results in menarche. The first menstrual cycles are usually irregular and anovulatory, and the subtle positive and negative regulation of sex steroids on the hypothalamus-pituitary axis has probably not reached adult maturity. An investigation has been carried out in 99 normal adolescent girls, divided into 3 groups: 1-2, 3-4 and 5 years after menarche, by measuring basal hormonal values as well as the responses to LHRH and TRH during the follicular and luteal phases. Basal FSH and LH values reached adult levels after the second year of menarche, while FSH and LH responses to 50microgram LHRH showed a regular and progressive increase from 1 to 5 years post-menarche, resulting, in the 5-year group and in spite of the half dose received, in definitely higher FSH and LH responses than those observed in the adult women after 100 microgram LHRH. This enhanced pituitary responsiveness to LHRH is due to still progressively increasing estradiol and progesterone secretions, the latter hormone remaining still lower than in the adults. Basal prolactin levels were significantly higher than those found in adult women with a slightly increased prolactin response to TRH and an exaggerated one of TSH, with normal T3 and T4 levels. These data show that from the onset of menarche to the complex and subtle adult menstrual cycle regulation, there is a continuing maturation of the hypothalamus-pituitary axis of the gonads which lasts approximately 5 years. It is characterized by increasing E2 secretion, low progesterone secretion and slightly increased prolactin levels, with a frequently impaired luteal phase. The enhanced pituitary sensitivity to releasing hormones is due to the positive feedback mechanism of E2 which is not yet associated with adequate progesterone secretion for a negative feedback, as in adult women. Thus, adolescence is still a maturation period, the onset of ovulation being the final step in this development

Maturation of the hypothalamo-pituitary-ovarian axis in adolescent girls

The first menstrual cycles after menarche are irregular and anovulatory. To determine whether these cycles reflect immature pituitary responsiveness to gonadotropin-releasing hormone (GnRH) in relationship to ovarian steroid secretion, we measured basal plasma estradiol (E2), progesterone (P), and gonadotropins as well as LH and FSH responses to GnRH in 90 healthy girls during the first 5 yr after menarche. During the first year postmenarche, sex steroids, basal gonadotropins, and responses to GnRH had not yet reached adult values. During the second year, the increase in E2 was accompanied by a higher secretion of gonadotropins, both basally and in response to GnRH, which was similar to that observed in control adult women during both phases of the menstrual cycle, although P remained low. From the third to the fifth postmenarchal years, there was a progressive increase in the luteal LH and FSH responses to GnRH, resulting in significantly higher responses than in adult controls. Despite the progressive increase in sex steroids there was still a low percentage of ovulatory cycles over the 5 postmenarchal yr (0-63%). When the data were classified according to luteal P levels, it was found that anovulatory cycles (P less than 0.9 ng/ml) with normal E2 levels (100 pg/ml) resulted in exaggerated responses to GnRH, while in ovulatory cycles with P levels greater than 10 ng/ml and normal E2 concentrations, a lower response was observed, suggesting that high concentrations of P exerted a negative feedback on LH and FSH secretion. In contrast, the association of lower E2 (less than 100 ng/ml) and P (less than 5 ng/ml) levels resulted in a synergistic positive action on gonadotropin secretion. These data extend to endogenous sex steroids the dose-dependent positive and negative actions on gonadotropin secretion previously demonstrated with exogenously administered steroids in women

Thyroid and pituitary secretory disorders in streptozotocin-diabetic rats are associated with severe structural changes of these glands

Streptozotocin diabetes in rats is associated with reduced function of the hypothalamo-pituitary-thyroid axis. The structure and hormone secretion of the thyroid and pituitary glands were studied in adult male rats 1 month after streptozotocin injection. The thyroid of diabetic rats was characterized by decreased follicle area and epithelial thickness. By electron microscopy, thyroid epithelial cells were characterized by flattened and almost empty rough endoplasmic reticulum cisternae, scanty exocytotic apical and endocytotic vesicles as well as degenerate mitochondria and rough endoplasmic reticulum. By immunohistochemistry, intracolloidal thyroglobulin and T3 as well as intraepithelial thyroglobulin were reduced. Electron microscopic and immunohistochemical analysis of pituitary glands showed that in diabetic rats thyrotrophs were mostly of type II, and the number of thyrotrophs (type I + type II) was greater than in controls. By radioimmunoassay (RIA), plasma T3, T4, and TSH levels were markedly reduced, and the TSH response to TRH was deficient in diabetic animals. The pituitary TSH concentration was increased, as expected from the morphological data. This study demonstrates severe structural changes in the thyroid and pituitary glands of diabetic rats which are accompanied by marked alterations of their secretory activity