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Objective: To evaluate the maternal–fetal outcomes of CAB-induced pregnancies in patients with prolactinoma in a large cohort. Methods: The prevalence of tumor growth, miscarriage, preterm, low birth weight, congenital malformations and impairment in neuropsychological development in children among women treated with CAB were assessed in a Brazilian multicentre retrospective observational study, Results: We included 194 women with a mean age of 31 (17–45) years, 43.6% presenting microadenomas and 56.4% macroadenomas, at prolactinoma diagnosis. In 233 pregnancies, CAB was withdrawn in 89%, after pregnancy confirmation. Symptoms related to tumor growth occurred in 25 cases, more frequently in macroadenomas. The overall miscarriage rate was 11%, although higher in the subgroup of patients with CAB maintainance after pregnancy confirmation (38% vs. 7.5%). Amongst the live-birth deliveries, preterm occurred in 12%, low birth weight in 6% and congenital malformations in 4.3%. Neuropsychological development impairment was reported in 7% of cases. Conclusions: Our findings confirm previous results of safety in maternal and fetal outcomes in CAB-induced pregnancies; nevertheless, CAB maintenance after pregnancy confirmation was associated with higher miscarriage rate; result that must be further confirmed. [ABSTRACT FROM AUTHOR]

In order to establish whether long-term itraconazole therapy can affect adrenal or testicular function, the adrenal response to corticotrophin and testosterone was evaluated by radioimmunoassay in 15 patients undergoing treatment for chromoblastomycosis. Mean cortisol and testosterone concentrations were 12.4 microg/dL and 454 ng/dL respectively at baseline and 15.4 microg/dL and 480 ng/dL respectively after 12.4+/-5.2 months of treatment with itraconazole (200-400 mg daily). Results were analysed using Student's t-test. There was no clinical or laboratory evidence of steroidogenic or androgenic impairment. [ABSTRACT FROM AUTHOR]

The 13th Acromegaly Consensus Conference was held in November 2019 in Fort Lauderdale, Florida, and comprised acromegaly experts including endocrinologists and neurosurgeons who considered optimal approaches for multidisciplinary acromegaly management. Focused discussions reviewed techniques, results, and side effects of surgery, radiotherapy, and medical therapy, and how advances in technology and novel techniques have changed the way these modalities are used alone or in combination. Effects of treatment on patient outcomes were considered, along with strategies for optimizing and personalizing therapeutic approaches. Expert consensus recommendations emphasize how best to implement available treatment options as part of a multidisciplinary approach at Pituitary Tumor Centers of Excellence.

Objective: The aim of the Acromegaly Consensus Group was to revise and update the consensus on diagnosis and treatment of acromegaly comorbidities last published in 2013., Participants: The Consensus Group, convened by 11 Steering Committee members, consisted of 45 experts in the medical and surgical management of acromegaly. The authors received no corporate funding or remuneration., Evidence: This evidence-based consensus was developed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system to describe both the strength of recommendations and the quality of evidence following critical discussion of the current literature on the diagnosis and treatment of acromegaly comorbidities., Consensus Process: Acromegaly Consensus Group participants conducted comprehensive literature searches for English-language papers on selected topics, reviewed brief presentations on each topic, and discussed current practice and recommendations in breakout groups. Consensus recommendations were developed based on all presentations and discussions. Members of the Scientific Committee graded the quality of the supporting evidence and the consensus recommendations using the GRADE system., Conclusions: Evidence-based approach consensus recommendations address important clinical issues regarding multidisciplinary management of acromegaly-related cardiovascular, endocrine, metabolic, and oncologic comorbidities, sleep apnea, and bone and joint disorders and their sequelae, as well as their effects on quality of life and mortality., (© Endocrine Society 2019. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: Obesity constitutes a serious global health concern reaching pandemic prevalence rates. The existence of functional brown adipose tissue (BAT) in adult humans has provoked intense research interest in the role of this metabolically active tissue in whole-body energy balance and body weight regulation. A number of environmental, physiological, pathological, and pharmacological stimuli have been proposed to induce BAT-mediated thermogenesis and functional thermogenic BAT-like activity in white adipose tissue (WAT), opening new avenues for therapeutic strategies based on enhancing the number of beige adipocytes in WAT., Hypothesis: Recent evidence support a role of l-menthol cooling, mediated by TRPM8 receptor, on UCP1-dependent thermogenesis and BAT-like activity in classical WAT depots along with the recruitment of BAT at specific anatomical sites. l-Menthol-induced BAT thermogenesis has been suggested to occur by a β-adrenergic-independent mechanism, avoiding potential side-effects due to extensive β-adrenergic stimulation mediated by available beta receptor agonists. l-Menthol has been also linked to the activation of the cold-gated ion channel TRPA1. However, its role in l-menthol-induced UCP1-dependent thermogenic activity in BAT and WAT remains undetermined. White adipose tissue plasticity has important clinical implications for obesity prevention and/or treatment because higher levels of UCP1-dependent thermogenesis can lead to enhanced energy expenditure at a considerable extent. We hypothesize that chronic dietary l-menthol treatment could induce TRPM8- and TRPA1-dependent WAT adaptations, resembling BAT-like activity, and overall improve whole-body metabolic health in obese and overweight individuals., Conclusions: The putative impact of chronic l-menthol dietary treatment on the stimulation of BAT-like activity in classical WAT depots in humans remains unknown. A detailed experimental design has been proposed to investigate the hypothesized l-menthol-induced browning of WAT. If our hypothesis was to be confirmed, TRPM8/TRPA1-induced metabolic adaptations of WAT to BAT-like activity could provide a promising novel therapeutic approach for increasing energy expenditure, regulating body weight, and preventing obesity and its related co-morbidities in humans., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Chronic obstructive pulmonary disease (COPD) is associated with low aBMD as measured by DXA and altered microstructure as assessed by bone histomorphometry and microcomputed tomography. Knowledge of bone matrix mineralization is lacking in COPD. Using quantitative backscatter electron imaging (qBEI), we assessed cancellous (Cn.) and cortical (Ct.) bone mineralization density distribution (BMDD) in 19 postmenopausal women (62.1 ± 7.3 years of age) with COPD. Eight had sustained fragility fractures, and 13 had received treatment with inhaled glucocorticoids. The BMDD outcomes from the patients were compared with healthy reference data and were correlated with previous clinical and histomorphometric findings. In general, the BMDD outcomes for the patients were not significantly different from the reference data. Neither the subgroups of with or without fragility fractures or of who did or did not receive inhaled glucocorticoid treatment, showed differences in BMDD. However, subgroup comparison according to severity revealed 10% decreased cancellous mineralization heterogeneity (Cn.CaWidth) for the most severely affected compared with less affected patients (p=0.042) and compared with healthy premenopausal controls (p=0.021). BMDD parameters were highly correlated with histomorphometric cancellous bone volume (BV/TV) and formation indices: mean degree of mineralization (Cn.CaMean) versus BV/TV (r=0.58, p=0.009), and Cn.CaMean and Ct.CaMean versus bone formation rate (BFR/BS) (r=-0.71, p<0.001). In particular, those with lower BV/TV (<50th percentile) had significantly lower Cn.CaMean (p=0.037) and higher Cn.CaLow (p=0.020) compared with those with higher (>50th percentile) BV/TV. The normality in most of the BMDD parameters and bone formation rates as well as the significant correlations between them suggests unaffected mineralization processes in COPD. Our findings also indicate no significant negative effect of treatment with inhaled glucocorticoids on the bone mineralization pattern. However, the observed concomitant occurrence of relatively lower bone volumes with lower bone matrix mineralization will both contribute to the reduced aBMD in some patients with COPD., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Context and Objective: The interaction between pregnancy and acromegaly has been studied only retrospectively. We used prospective data to assess those interactions., Design: Prospective, interventional, multicentric study., Patients: TEN PREGNANCIES IN EIGHT ACROMEGALIC PATIENTS WERE INCLUDED ACCORDING TO THE FOLLOWING CRITERIA: previous diagnosis of acromegaly; and active acromegaly before pregnancy. Sellar magnetic resonance image (MRI), GH, and IGF1 measurements were carried out before pregnancy. The exclusion criterion was radiotherapy., Intervention: Withdrawal of pharmacological treatment (octreotide and/or cabergoline and/or pegvisomant) following pregnancy diagnosis., Main Outcome Measures: Clinical/biochemical evaluations throughout pregnancy/puerperium and sellar MRI after delivery; and GH and IGF1 measurements before pregnancy. GH was measured by an interference-free IFMA assay during pregnancy and IGF1 by measured by Immulite 2000 assay in patients and 64 control pregnancies., Results: No tumor growth was observed. Nine deliveries were at term and one at 35 weeks (preeclampsia). All newborns were healthy. Mean IGF1 levels before and during pregnancy were similar, but increased significantly during puerperium. As IGF1 in controls increased after midgestation, the prevalence of controlled IGF1 rose significantly from 2/10 (<20 weeks) to 9/10 (>30 weeks). Diabetes mellitus and hypertension/preeclampsia developed in one patient in each group; both complications were nonsignificantly (P=0.06) associated with IGF1 >1.3 ULN before pregnancy., Conclusions: Acromegaly control usually improved and tumor growth was not stimulated during pregnancy in spite of withdrawal of drug treatment. Drug treatment can be discontinued in most patients. Uncontrolled disease before pregnancy may pose a higher risk for diabetes and hypertension.

Recombinant human thyroid-stimulating hormone (rhTSH) enhances 131I uptake, permitting a decrease in radiation for the treatment of multinodular goiter (MNG). Our objective was to evaluate the safety and efficacy of a single 0.1-mg dose of rhTSH, followed by 30 mCi 131I, in patients with MNG. Seventeen patients (15 females, 59.0 +/- 13.1 years), who had never been submitted to 131I therapy, received a single 0.1-mg injection of rhTSH followed by 30 mCi 131I on the next day. Mean basal thyroid volume measured by computed tomography was 106.1 +/- 64.4 mL. 131I 24-h uptake, TSH, free-T4, T3, thyroglobulin, anti-thyroid antibodies, and thyroid volume were evaluated at regular intervals of 12 months. Mean 131I 24-h uptake increased from 18.1 +/- 9.7 to 49.6 +/- 13.4% (P < 0.001), a median 2.6-fold increase (1.2 to 9.2). Peak hormonal levels were 10.86 +/- 5.44 mU/L for TSH (a median 15.5-fold increase), 1.80 +/- 0.48 ng/dL for free-T4, 204.61 +/- 58.37 ng/dL for T3, and a median of 557.0 ng/mL for thyroglobulin. The adverse effects observed were hyperthyroidism (17.6%), painful thyroiditis (29.4%) and hypothyroidism (52.9%). Thyroid volume was reduced by 34.3 +/- 14.3% after 6 months (P < 0.001) and by 46.0 +/- 14.6% after 1 year (P < 0.001). Treatment of MNG with a single 0.1-mg dose of rhTSH, followed by a fixed amount of radioactivity of 131I, leads to an efficacious decrease in thyroid volume for the majority of the patients, with a moderate incidence of non-serious and readily treatable adverse effects.

The aim of this study was to evaluate the proportion of non-22 kDa GH isoforms in relation to total GH concentration after a repeated GHRH stimulus in healthy subjects. We studied 25 normal volunteers (12 males and 13 females, mean age 13.1 years, range 6-35), who received two GHRH bolus (1.5 mug/kg body weight, i.v.) administered separately by an interval of 120 minutes. The proportion of non-22 kDa GH was determined by the 22 kDa GH exclusion assay (GHEA), which is based on immunomagnetic extraction of monomeric and dimeric 22 kDa GH from serum, and quantitation of non-22 kDa GH isoforms using a polyclonal GH assay. Samples were collected at baseline and at 15-30 min intervals up to 240 min for total GH concentration. Non-22 kDa GH isoforms were measured in samples where peak GH after GHRH was observed. Total GH peaked after the first GHRH bolus in all subjects (median 37.2 ng/ml; range: 10.4-94.6). According to GH response to the second GHRH stimulus, the study group was divided in "non-responders" (n=7; 28%), with GH peak levels lower than 10 ng/ml (median GH: 8.7 ng/ml; range 7.3-9.6) and "responders" (n=18; 72%), who showed a GH response greater than 10 ng/ml (median 17 ng/ml; range 10.1-47.0). The median proportion of non-22 kDa GH on the peak of GH secretion after the first GHRH administration was similar in both groups ("responders" median: 8.6%, range 7-10.9%; "non-responders" median: 8.7%, range 6.7-10.3%), independently of the type of response after the second GHRH. In contrast, the median proportion of non-22 kDa GH was greater at time of GH peak after the second GHRH bolus in the "non-responders" (median 11.4%; range 9.1-14.3%) in comparison with the "responders" (median 9.1%; range 6.7-11.9%; p=0.003). A significant negative correlation between the total GH secreted and the percentage of non-22 kDa isoforms was seen in the "non-responders" (p=0.003). These differences in GH response to repeated GHRH stimulation and in the pattern of GH isoforms at GH peak among subjects might be due to distinct recovery patterns of somatrotrophic function and/or differences in metabolic clearance of GH isoforms.

Growth hormone (GH) consists of several isoforms. We have studied the proportion, expressed as percentage of total GH concentration, of non-22kDa (non-22K) GH isoforms and 20K GH during 8-week oral treatment with MK-677 25mg daily in 12 obese males. The proportion of non-22K GH isoforms in peak total GH samples after the initial MK-677 administration was higher than that after 2 and 8 weeks (p<0.01 and p<0.05, respectively). In selected non-peak total GH samples after the initial MK-677 administration, however, the proportion of non-22K GH isoforms was similar to that in the peak total GH samples after 2 and 8 weeks. The proportion of 20K GH in 2-h samples after the initial MK-677 administration was lower than that after 2 and 8 weeks (p<0.01 and p<0.05, respectively). We concluded that the proportion of non-22K GH isoforms was higher in peak, but not in non-peak, total GH samples after the initial MK-677 administration than that observed after multiple doses. The proportion of 20K GH in 2-h samples after the initial MK-677 administration was lower than that after 2 and 8 weeks. These moderate changes in the proportion non-22K GH isoforms are likely of small importance for the clinical response to MK-677 treatment.

GH is being used by elite athletes to enhance sporting performance. To examine the hypothesis that exogenous 22-kDa recombinant human GH (rhGH) administration could be detected through suppression of non-22-kDa isoforms of GH, we studied seventeen aerobically trained males (age, 26.9 +/- 1.5 yr) randomized to rhGH or placebo treatment (0.15 IU/kg/day for 1 week). Subjects were studied at rest and in response to exercise (cycle-ergometry at 65% of maximal work capacity for 20 min). Serum was assayed for total GH (Pharmacia IRMA and pituitary GH), 22-kDa GH (2 different 2-site monoclonal immunoassays), non-22-kDa GH (22-kDa GH-exclusion assay), 20-kDa GH, and immunofunctional GH. In the study, 3 h after the last dose of rhGH, total and 22-kDa GH concentrations were elevated, reflecting exogenous 22-kDa GH. Non-22-kDa and 20-kDa GH levels were suppressed. Regression of non-22-kDa or 20-kDa GH against total or 22-kDa GH produced clear separation of treatment groups. In identical exercise studies repeated between 24 and 96 h after cessation of treatment, the magnitude of the responses of all GH isoforms was suppressed (P < 0.01), but the relative proportions were similar to those before treatment. We conclude: 1) supraphysiological doses of rhGH in trained adult males suppressed exercise-stimulated endogenous circulating isoforms of GH for up to 4 days; 2) the clearest separation of treatment groups required the simultaneous presence of high exogenous 22-kDa GH and suppressed 20-kDa or non-22-kDa GH concentrations; and 3) these methods may prove useful in detecting rhGH abuse in athletes.

Circulating GH consists of multiple molecular isoforms, all derived from the one gene in nonpregnant humans. To assess the effect of a potent stimulus to pituitary secretion on GH isoforms, we studied 17 aerobically trained males (age, 26.9 +/- 1.5 yr) in a randomized, repeat measures study of rest vs. exercise. Exercise consisted of continuous cycle ergometry at approximately 80% of predetermined maximal oxygen uptake for 20 min. Serum was assayed for total, pituitary, 22-kDa, recombinant, non-22-kDa, 20-kDa, and immunofunctional GH. All isoforms increased during, peaked at the end, and declined after exercise. At peak exercise, 22-kDa GH was the predominant isoform. After exercise, the ratios of non-22 kDa/total GH and 20-kDa GH/total GH increased and those of recombinant/pituitary GH decreased. The disappearance half-times for pituitary GH and 20-kDa GH were significantly longer than those for all other isoforms. We conclude that 1) all molecular isoforms of GH measured increased with and peaked at the end of acute exercise, with 22-kDa GH constituting the major isoform in serum during exercise; and 2) the proportion of non-22-kDa isoforms increased after exercise due in part to slower disappearance rates of 20-kDa and perhaps other non-22-kDa GH isoforms. It remains to be determined whether the various biological actions of different GH isoforms impact on postexercise homeostasis.

We report an uncommon case of a 20-year-old man, who noted a painless, growing mass in his neck, which appeared in a weekend, associated with moderate dysphagia and weakness. Laboratory examination revealed an elevated serum thyrotropin of 25 mU/L, normal serum triiodothyronine and thyroxine levels, and high titers of antithyroglobulin and antithyroid peroxidase antibodies. The neck lesion showed a depressed iodine uptake in the left thyroid lobe, which had an asymmetrical pseudocystic pattern associated with poor vascularization in the ultrasound scan. Cytologic examination showed a lymphocyte thyroiditis in association with lymphoma of large cell arising from mucosa-associated lymphoid tissue (MALT-lymphoma or maltoma). The patient underwent a left thyroid lobectomy while being treated with levothyroxine for Hashimoto's thyroiditis, and the surgical treatment was further complemented with chemotherapy using fludarabine. The histologic examination confirmed the cytologic findings and the immunohistochemistry showed a B-cell type maltoma. Additional investigation provided no evidence of disease in other tissues. The clinical course has been favorable in the first 2 years of follow-up, with no evidence of local or systemic recurrence of the disease.

The neonatal and postpartum periods are characterized by alterations in pituitary GH secretion. We have investigated the proportion of circulating non-22kDa GH isoforms in newborns, in women within the early postpartum phase (just after the disappearance of placental GH from the maternal circulation) and in women during late postpartum (during the somatotroph recovery phase). We studied 10 newborns (7 males; 3 females; median postnatal age, 45h), who had been admitted because of polycythaemia, 10 women in the early postpartum phase (median, 48h after delivery; range, 42-54h), 18 women in the late postpartum phase (median, 10 weeks after delivery; range, 3-25 weeks) and 9 healthy non-pregnant women. The proportion of non-22kDa GH isoforms was determined by the 22kDa GH exclusion assay, which is based on immunomagnetic extraction of 22kDa GH from serum, and quantitation of non-22kDa GH isoforms using a polyclonal GH assay. In newborns, non-22kDa GH isoforms were measured in two arterial blood samples obtained with a 5-6h interval. In the other groups, serum samples were obtained 40min after an i.v. bolus administration of the GH secretagogue, GH releasing peptide-1 (GHRP-1). In newborns, the median proportion of non-22kDa GH isoforms was 10% (range, 7. 2-19.4%) and the values were similar in samples collected at different times. In early postpartum women, total GH levels after GHRP-1 were lower and the proportion of non-22kDa GH isoforms was higher compared with the values in non-pregnant and late-postpartum women. In late postpartum, there was a partial recovery of GH response to GHRP-1, as shown by an increment in total GH levels, which was associated with a decrease in the fraction of non-22kDa GH isoforms. In conclusion, we found that (i) the proportion of non-22kDa GH isoforms in the newborn is comparable to that in the adult (non-pregnant women), (ii) in early postpartum, the non-22kDa fraction is high within the small pool of readily releasable GH, (iii) in late postpartum, recovery of pituitary GH responsiveness is associated with a relative decrease in the release of non-22kDa GH isoforms.

The proportion of non-22 kDa GH isoforms was evaluated in 93 healthy children (48 boys aged 6.8-18.4 years and 45 girls aged 3.9-18.4 years) of normal stature (height +/- 2 s.d. score) at different stages of puberty. In addition, correlations among the proportion of non-22 kDa GH isoforms, auxology, spontaneous GH secretion and biochemical measurements were investigated. Serum non-22 kDa GH levels, expressed as percentage of total GH concentration in the samples, were determined by the 22 kDa GH exclusion assay, in which monomeric and dimeric 22 kDa GH are removed from serum and the non-22 kDa GH isoforms are quantitated using a polyclonal antibody GH assay. Samples were selected from spontaneous GH peaks in 24-h GH profiles. For boys, the median proportion of non-22 kDa GH isoforms was 8.5% (range 3.2-26.6%) and for girls it was 9.6% (1.8-17.4%), with no influence of age and no sex-related difference in prepubertal (boys, 7.2%; girls, 8.8%) or pubertal children (boys, 9.1%; girls, 9.9%). However, the median proportion of non-22 kDa GH isoforms was significantly higher in pubertal boys (9.1%) than in prepubertal boys (7.2%; P = 0.03). In pubertal boys, height S.D. scores (SDS) were inversely correlated to the proportion of non-22 kDa GH isoforms (r = -0.38; P = 0.02), especially at mid-puberty (r = -0.7; P = 0.01), indicating that the presence of increased amounts of circulating non-22 kDa GH isoforms was associated with less growth. In prepubertal children, positive correlations between non-22 kDa GH and weight SDS (r = 0.46; P = 0.03), weight-for-height SDS (r = 0.51; P = 0.01) and body mass index (r = 0.42; P = 0.04) were observed. No significant correlations were seen with spontaneous GH secretion or measurements of IGF-1, IGF-binding protein-3, insulin and leptin. These findings in normal children indicate that the proportion of circulating non-22 kDa GH isoforms may have physiologic significance for growth and metabolism in different stages of development, and emphasize the importance of evaluating the circulating ratio of 22 kDa and non-22 kDa GH in children with growth disorders.

The impact of the adoption of the new biosynthetic growth hormone (GH) WHO International Reference Preparation (IRP 88/624), and the recommendation to report results in microgram/L instead of mU/L, is described. Conversion factors were determined by comparing both the linear and nonlinear relations of the GH values. The Pharmacia polyclonal IRMA (p-IRMA) and the DELFIA monoclonal time-resolved immunofluorometric assay (trIFMA) with kit calibrators calibrated either against the pituitary-derived WHO IRP 80/505 or the new 88/624 were evaluated. Conversion factors of 4.17 mU/L = 1 microgram/L for the p-IRMA and 4.31 mU/L = 1 microgram/L for the trIFMA were necessary. Different cross-reactivity patterns for the deaminated and dimer 22-kDa, 20-kDa, and 17-kDa GH isoforms were found. Expected GH recovery was similar when the measured values were adjusted according to the results of the cross-reactivity study.

So far, the clinical evaluation of short children has focused on the measurement of immunoreactive growth hormone (GH) in the blood to determine if the growth retardation is due to GH deficiency. However, GH-dependent short stature may be caused by defects in either the secretion of bioactive GH or by the inability to respond to GH. Both GH secretion and GH responsiveness should, therefore, be evaluated when investigating the cause of short stature. Recent advances in molecular biology have generated new ways of studying different molecules involved in growth regulation, and new genetic defects have been identified in short children.

Human growth hormone (GH) exists in a variety of isoforms. In the pituitary, the most abundant isoform is 22-kD GH (22 K GH), while other isoforms (non-22 K GH) are present in variable amounts. In human plasma, the GH heterogeneity contributes to the wide variability in GH levels measured by different immunoassays. The physiological role of the non-22 K GH isoforms is poorly understood, but they may represent a spectrum of agonists or antagonists of the GH receptor. It is possible that increased amounts of non-22 K GH isoforms in the circulation contribute to the growth failure observed in some short children and may be involved in the pathophysiology of acromegaly and other unrelated diseases. Currently, there is no method available to evaluate the ratio of non-22 K GH isoforms to total GH in large sets of serum samples. In this report, a novel assay procedure is described in which monomeric and dimeric isoforms of 22 K GH are removed from serum and non-22 K GH isoforms are quantitated. The 22 K GH exclusion assay (22 K GHEA) was established as a screening method to identify conditions in which the ratio of non-22 K GH isoforms to total GH in human blood is altered. A 22 K GH-specific monoclonal antibody (MCB) is used for binding to 22 K GH in serum. Magnetic beads coated with rat anti-mouse immunoglobulin G and a magnetic device are used to remove the 22K GH-MCB complexes from serum. The non-22 K GH isoforms are measured by a polyclonal antibody-based immunoradiometric assay (GH-IRMA). The assay procedure was optimized systematically by statistical experimental designs. In serum spiked with monomeric or dimeric 22 K GH, the 22 K GH extraction was efficient at GH levels up to 100 microg/l (range 96.3-100%). The intra- and interassay precision for non-22K GH levels of 3.9 microg/l were 2.6% and 8.7%, respectively, while for levels of 0.6 microg/l, which were very close to the detection limits of the assay, the coefficients were 17.0% and 21.6%, respectively. The percentage of non-22 K GH isoforms determined in serum samples from three different groups of subjects showed clearly distinctive values. The 22 K GHEA is a new method for evaluation of non-22 K GH isoforms in human blood under different physiological and pathophysiological conditions.

Experiments for uptaking and distribution of the culm stabiliser "camposan" with the agens ethephon are very important to tell something about the dwarf behaviour of the treated plants of rye. The radioactive labelled ethephon is infiltrated through the roots, leaves and cuttings of culms. Uptaking through the roots is more complete than those about the foliar dissepiment. Otherwise uptaking through the foliar dissepiment is higher than about the leaves only. After radioautographic experiments, culmcutting-experiments and experiments with intact rye in the 5--6 leaf-stage we have found that the agens is transported acropetal in the xylem of the plants after uptaking by the roots up to 3 days. The labelled ethephon is translocated in a higher concentration in the phloem after foliar dissepiment application. The concentration of the agens decreases in the investigated plants up to the 5th day enormously (40--50% and after then slightly following the degradation to gaseous compounds. During 4 days ethephon is metabolized to about 5--15% ethylene and additional to about 18--20% carbondioxide.