Measurement Of Growth Hormone Research Articles

Lower levels of placental growth hormone in early pregnancy in women with type 1 diabetes and large for gestational age infants

ObjectiveTo evaluate whether levels of placental growth hormone (GH) and Insulin-like Growth Factor-I (IGF-I) are associated with development of LGA infants in pregnant women with type 1 diabetes. DesignObservational study of 103 consecutive pregnant women with long-term type 1 diabetes and median HbA1c 6.6% (range 4.9–10.5) (49mmol/mol (30–91)) in early pregnancy. At 8, 14, 21, 27 and 33weeks weight was recorded and blood was sampled for measurements of placental GH, IGF-I and HbA1c. LGA was defined as birth weight >90th percentile after adjustment for gender and gestational age. ResultsThroughout pregnancy placental GH levels were similar in 51 (50%) women delivering LGA infants compared with the remaining women except at 8weeks where placental GH levels were lower in women with LGA infants (1.1ng/ml (0.1–4.3) vs. 1.7 (0.3–11.7), p=0.04). IGF-I levels were similar in women with and without LGA infants (p=0.97). Gestational age at first blood sampling was similar in women with and without LGA infants (60days (37–89) vs. 61.5 (42–94), p=0.42). Placental GH levels at 14weeks correlated negatively with weight gain in early pregnancy (r=−0.32, p=0.002). As predictors of LGA infants, multivariate logistic regression analysis identified placental GH levels at 8weeks (OR 0.4 (95% CI: 0.2–0.9), p=0.02), HbA1c at 33weeks (3.6 (1.3–9.9), p=0.01) and parity ≥1 (3.1 (1.3–7.5), p=0.01) after adjustment for pre-pregnancy BMI. ConclusionsWomen delivering LGA infants had lower placental GH levels in early pregnancy. Growth factors and maternal weight gain in early pregnancy may be important for healthy fetal growth.

Perineal Body and Genital Hiatus in the Third Trimester and Risk of Perineal Laceration.

We aimed to determine whether pelvic organ prolapse quantification measurements of genital hiatus (gh) or perineal body (pb) obtained in the late third trimester are predictors of obstetric perineal laceration in nulliparous women. Nulliparous women with singleton gestation were prospectively recruited after 35-week gestation, and gh and pb measurements were obtained. After delivery, determination of the presence and degree of perineal laceration were recorded. Correlation of gh and pb measurements with risk of perineal laceration (defined as second, third, or fourth degree) was assessed using the Wilcoxon rank sum test. We recruited 224 patients and 133 met inclusion criteria after delivery. The mean (SD) age was 27.2 (4.0) years and mean (SD) prepregnancy body mass index was 24.1 (4.6) kg/m. Seventy patients (52.6%) had either a second-degree (n = 64) or third-degree (n = 6) laceration. No fourth-degree lacerations were recorded. We found no significant difference in the median gh (3.5 vs 3.0 cm, P = 0.34) and pb (3.5 vs 3.5 cm, P = 0.54) measurements among women with and without perineal lacerations. Our data suggest that antenatal measurement of gh and pb does not correlate with the risk of obstetric perineal laceration in nulliparous patients undergoing spontaneous vaginal delivery.

Acromegaly treatment in Romania. How close are we to disease control?

In Romania, no nationwide data for acromegaly treatment and control rate are available. Our objective was to assess the acromegaly control rate in a tertiary referral centre, which covers an important part of Romanian territory and population of patients with acromegaly. We reviewed the records of all 164 patients (49 males and 115 females; median age 55 [47, 63.5] years) with newly or previously diagnosed acromegaly, who have been assessed at least once in our tertiary referral centre between January 1, 2012 and March 31, 2016. This sample represents 13.6% of the total expected 1200 Romanian patients with acromegaly and covers 82.9% of the counties in Romania. Control of acromegaly was defined as a random serum growth hormone (GH) < 1 ng/mL and an age-normalised serum insulin-like growth factor-I (IGF-I) value. The GH and IGF-I values used for calculation of the control rate were those at the last evaluation. The same assays for GH and IGF-I measurement were used in all patients. There were 147 treated and 17 untreated patients. Of the 147 patients assessed after therapy, 137 (93.2%) had pituitary surgery, 116 (78.9%) were on medical treatment at the last evaluation, and 67 (45.5%) had radiotherapy. Seventy-one (48.3%) had a random GH < 1 ng/mL, 54 (36.7%) had a normalised, age-adjusted IGF-I, and 42 (28.6%) had both normal random serum GH and IGF-I. In Romania, acromegaly benefits from the whole spectrum of therapeutic interventions. However, the control rate remains disappointing.

Serial GH Measurement After Intravenous Catheter Placement Alone Can Detect Levels Above Stimulation Test Thresholds in Children.

GH stimulation testing is limited by poor specificity and reproducibility in identifying GH deficiency. Intravenous line placement (IVP) in pediatrics may be a stimulus for GH secretion. The objective of the study was to determine whether the measurement of GH at baseline as well as 15 and 30 minutes after IVP detects additional patients with sufficient peak GH concentrations who are not identified by a subsequent insulin tolerance test (ITT). The ITT protocol was modified to include GH measurement at the time of IVP (t = 0) and 15 (t = 15) and 30 (t = 30) minutes later. Insulin was administered at t = 30, and an ITT was performed as per standard protocols. Children were grouped according to the indication for ITT: initial evaluation of GH deficiency (group 1); and GH deficiency at transition to adulthood (group 2). Ninety-seven patients were included (76 in group 1, 21 in group 2). Of these, 27 (28%) had a peak GH concentration of 7 ng/mL or greater (19 in group 1, eight in group 2) either after IVP or ITT. Thirteen subjects (11 in group 1, two in group 2) had GH concentrations of 7 ng/mL or greater after IVP, without exceeding this on a subsequent ITT. Among the 11 group 1 patients, three of these GH peaks of 7 ng/mL or greater occurred at t = 0, 5 at t = 15, and 5 at t = 30, including one patient who had a peak GH of 7 ng/mL or greater at all three time points. Some children will not have a sufficient GH response to pharmacological stimuli but will have a robust response to IVP. We recommend GH measurement after IVP in children undergoing GH stimulation testing, particularly when there is a delay between IVP and the administration of the pharmacological stimulus.

Growth Hormone Dynamics in Healthy Adults Are Related to Age and Sex and Strongly Dependent on Body Mass Index

Background: Studies on 24-hour growth hormone (GH) secretion are rare. The influences of sex, age, and adiposity are well recognized but generally derived from specific, selected subject groups, not spanning sexes, many age decades, and a range of body weights. Objective: Our goal was to investigate GH dynamics in a group of 130 healthy adult subjects, both men and women, across 5 age decades as well as a 2.5-fold range of body mass index (BMI) values. Methods: GH was measured by a sensitive immunofluorometric assay. Secretion parameters were quantified by automated deconvolution and relative pattern randomness by approximate entropy (ApEn). Results: The median age was 40 years (range 20-77). The median BMI was 26 (range 18.3-49.8). Pulsatile 24-hour GH secretion was negatively correlated with age (p = 0.002) and BMI (p < 0.0001). Basal GH secretion negatively correlated with BMI (p = 0.003) but not with age. The sex- dependent GH secretion (greater in women) was no longer detectable after 50 years of age. Insulin-like growth factor (IGF)-1 levels were lower in women over 50 years of age compared with men of a similar age. ApEn showed an age-related increase in both sexes and was higher in premenopausal and postmenopausal women than in men of comparable age (p < 0.0001). A single fasting GH measurement is not informative of 24-hour GH secretion. Conclusions: BMI dominates the negative regulation of 24-hour GH secretion across 5 decades of age in this up till now largest cohort of healthy adults who underwent 24-hour blood sampling. Sex also impacts GH secretion before the age of 50 years as well as its regularity at all ages. Differences in serum IGF-1 partly depend on the pre- or postmenopausal state. Finally, a single GH measurement is not informative of 24-hour GH secretion.

60 YEARS OF NEUROENDOCRINOLOGY: Acromegaly.

Acromegaly (ACM) is a chronic, progressive disorder caused by the persistent hypersecretion of GH, in the vast majority of cases secreted by a pituitary adenoma. The consequent increase in IGF1 (a GH-induced liver protein) is responsible for most clinical features and for the systemic complications associated with increased mortality. The clinical diagnosis, based on symptoms related to GH excess or the presence of a pituitary mass, is often delayed many years because of the slow progression of the disease. Initial testing relies on measuring the serum IGF1 concentration. The oral glucose tolerance test with concomitant GH measurement is the gold-standard diagnostic test. The therapeutic options for ACM are surgery, medical treatment, and radiotherapy (RT). The outcome of surgery is very good for microadenomas (80-90% cure rate), but at least half of the macroadenomas (most frequently encountered in ACM patients) are not cured surgically. Somatostatin analogs are mainly indicated after surgical failure. Currently their routine use as primary therapy is not recommended. Dopamine agonists are useful in a minority of cases. Pegvisomant is indicated for patients refractory to surgery and other medical treatments. RT is employed sparingly, in cases of persistent disease activity despite other treatments, due to its long-term side effects. With complex, combined treatment, at least three-quarters of the cases are controlled according to current criteria. With proper control of the disease, the specific complications are partially improved and the mortality rate is close to that of the background population.

Insulin-like Growth Factor 1 (IGF-1) measurements recorded in the OZGROW database and their relation to growth response in children currently being treated with growth hormone

Aims IGF-1 is produced in a GH dependent fashion and measurement of IGF-1 has become increasingly common for both diagnosis of GH deficiency and to guide GH therapy. The OZGROW database records the results of IGF-1 tests performed on patients receiving GH or being assessed for GH treatment. The OZGROW database was used to determine the extent to which IGF-1 testing is performed in this population and to assess the relationship between IGF-1 levels and growth rate.

The Effect of Different Doses of Isotretinoin on Pituitary Hormones

Background: There are a limited number of studies investigating the side effects and effectiveness of various doses of isotretinoin (ISO). We have previously shown that high-dose ISO affects pituitary hormones. Objectives: To our knowledge, there is no study in the literature looking into the effects of various doses of ISO on pituitary hormones. We searched pituitary hormones in three groups of different doses in acne patients. Methods: We included 105 acne vulgaris patients from two different centers. We divided the patients into three groups; the first group received 0.5-1 mg/kg/day, the second 0.2-0.5 mg/kg/day and the third intermittent 0.5-1 mg/kg/day (only 1 week in 1 month) ISO treatment. Blood samples were collected for biochemistry and hormone analysis, before the treatment and after 3 months. Results: After 3 months of treatment with ISO, luteinizing hormone (LH) (p < 0.001), prolactin (p < 0.001), total testosterone (p < 0.001), adrenocorticotropic hormone (ACTH) (p < 0.001), cortisol (p < 0.001), insulin-like growth factor-binding protein 3 (p < 0.001), insulin-like growth factor 1 (IGF-1) (p = 0.002), growth hormone (GH) (p = 0.002) and free T3 (fT3) (p < 0.001) levels had decreased significantly. Furthermore, we split data into three different groups. Among the patients receiving intermittent-dose ISO, LH, ACTH, IGF-1, GH and fT3 measurements lost significance. Most of the significant measurements observed in the whole group were also significant among the patients receiving high-dose ISO. Additionally, dehydroepiandrosterone sulfate (p = 0.003) levels increased, and free T4 levels decreased significantly. Conclusions: ISO affects pituitary hormones at all of these three doses. The differences in pituitary hormones are more pronounced in high-dose treatment. The weakest effect was observed in the intermittent-dose group. Choosing lower doses of ISO may decrease side effects, however the effectiveness of the treatment may also be diminished. ISO, by affecting the PPARγ/RXR system, may affecting hormone systems. These changes in various hormone systems may be related to the effectiveness of ISO.

Potential risks of glucagon stimulation test in elderly people

The glucagon stimulation test (GST) is a reliable measure for assessing growth hormone (GH) and adrenocorticotropic hormone (ACTH) secretion. The GST is considered to be a safe test, with few mild side effects, especially in adults and in the elderly in whom underlying co-morbidities may be present. ObjectiveTo describe the side effects of the GST in elderly people. Design and settingThe study was performed with patients of the geriatric ambulatory of our hospital who were recruited to voluntarily participate in a research study concerning the GH and ACTH axis in the elderly people. Forty-two subjects (n=5 males and 37 females) aged 67–88 years, without hypothalamic–pituitary disease, were submitted to the GST. The GST was performed by intramuscular injection of 1mg of glucagon. Blood samples were collected at baseline, and 90, 120, 150, and 180min after glucagon injection for GH and cortisol measurements. ResultsDuring the test, 9 subjects (21.4%) had side effects, which included: nausea (14.2%), indisposition (11.9%), hypotension (9.5%), vomiting (7.1%), sweating (4.7%), and dizziness (2.3%). There were four cases of severe symptomatic hypotension, with inaudible blood pressure in two cases. In one case of severe hypotension, the subject suffered two episodes of generalized tonic seizures. Patients who had side effects at GST had statistically higher peak of cortisol (28.9±6.67μg/dL) and a statistical trend to higher GH peak (8.74±5.96μg/L). In the group of patients who did not have side effects, the mean cortisol and GH peak were 19.05±5.36μg/dL and 5.32±3.52μg/L, respectively. ConclusionAlthough the GST is a reliable alternative test to the ITT, it should be cautiously used in the elderly because this population may have co-morbidities including vascular and cardiac diseases that could be potentiated with side effects of the test, such as severe hypotension.

Clinical evidence-based cutoff limits for GH stimulation tests in children with a backup of results with reference to mass spectrometry.

Cutoff limits of GH stimulation tests to diagnose GH deficiency (GHD) in children and adolescents are not sufficiently validated by clinical studies due to discrepancies in the performance of GH immunoassays and lack of available study populations. We aimed to establish new cutoff limits for GH stimulation tests based on clinical evidence and compared these immunoassay-based values with an antibody-independent mass spectrometric method. In a retrospective study, GH cutoff limits for eight different immunoassays and isotope dilution mass spectrometry (ID-MS) were calculated from hGH peak concentrations of short-statured children with and without GHD. We compared the serum GH peak concentrations at GH stimulation test of 52 short-statured children and adolescents, who have normal GH secretion at initial workup and normal growth in the follow-up, with the serum GH peak concentrations of 44 GHD patients in the same age range, in order to optimize the cutoff limit calculation. Discriminant analysis of re-measured GH led to a new cutoff limit of 7.09 μg/l using the iSYS assay (IDS) and the limits for the other seven hGH assays varied between 4.32 and 7.77 μg/l. For ID-MS, cutoffs of 5.48 μg/l (22k GH) and 7.43 μg/l (total GH) were ascertained. The establishment of method-specific clinical evidence-based GH cutoff limits is of importance to ensure adequate clinical diagnosis and treatment of children and adolescents with GHD. ID-MS may become an important tool for providing both reliable and sustainable SI traceability of GH measurements in the future.

The effectiveness of analysis of octreotide-depo, a long-acting somatostatin analog, for the treatment of the patients presenting with active phase of acromegalia

This paper reports the results of the year-long treatment of 46 patients presenting with active phase of acromegalia (39 (85%) women and 7 (15%) men, at the age varying from 22 to 76 years) using the long-acting somatostatin analog octreotide-depo. The treatment was started using a dose of 20 mg with the measurement of GH and IGF-1 levels each 3 months; the dose was titrated as appropriate. The maximum dose of octreotide-depo amounted to 40 mg. The effectiveness of therapy was evaluated from the severity and frequency of the principle symptoms of acromegalia, viz. facial, hand, and leg soft tissue oedema, fatigue, excessive sweating, headache, arthralgia, elevated blood GH and IGF-1 levels. The target GH levels were considered to be below 2.5 ng/ml and those of IGF-1 within the normal age-specific concentration range. The most well-apparent regression of clinical symptoms was observed within the first 3 months after the onset of the treatment, concurrently with the maximum reduction of blood GH and IGF-1 levels. The values reached during the first 3 months remained unaltered up to the end of the study. Simultaneous normalization of the blood GH and IGF-1 levels was documented in 55% of the patients. The clinical symptoms most frequently disappeared in the patients with normal IGF-1 levels. The adverse reactions of octreotide-depo therapy included short-term diarrhea (45.6%), meteorism (25.1%), abdominal pain (26%), nausea (13.4%), constipation (10.8%). These conditions were not serious and did not require the withdrawal of the preparation.

Translational Neuroendocrinology: Control of Human Growth

Human growth is driven by both basic cell processes as well as hormones, in particular the growth hormone (GH)-insulin-like growth factor (IGF)-1 axis. Understanding how these mechanisms are coordinated is not only critical to achieving a normal growth rate, but also to recognising potential new causes of disordered growth and how they might be treated. We have demonstrated in healthy children that height is gained by periods of rapid growth interspersed by periods of very slow growth or even stasis. We have also shown that a lower order organism, Caenorhabditis elegans, grows in a similar manner. By contrast, secretion of GH from somatotrophs occurs on a daily basis in discrete pulses over a 24-h period. We have used the measurement of GH in urine as a surrogate marker of GH secretion to show that there are rhythms of GH output with frequencies of several days. We then assessed which attributes of these GH profiles were related to growth and found that disorderliness in the GH profile (as measured by approximate entropy) was related to better growth rate. This feature was then tested in the dwarf rat using different GH regimens to introduce variation into the administration of daily GH injections. Better long bone growth was associated with week-to-week or even random dose variation compared to the same amount of GH delivered as a standard daily dose. Understanding the control of growth has implications in clinical practice for modelling GH treatment regimens based on physiological principles.

Continuous positive airway pressure increases pulsatile growth hormone secretion and circulating insulin-like growth factor-1 in a time-dependent manner in men with obstructive sleep apnea: a randomized sham-controlled study.

To assess the time-dependent effect of continuous positive airway pressure (CPAP), on insulin-like growth factor-1 (IGF-1), IGF binding proteins (IGFBPs) and pulsatile growth hormone (GH) secretion. A randomized, double-blind, sham-controlled, parallel group study. Sixty-five middle-aged men with moderate to severe obstructive sleep apnea. Active (n = 34) or sham (n = 31) CPAP for 12 weeks, followed by 12 weeks of active CPAP (n = 65). Fasting morning IGF-1, IGFBP-3, and IGFBP-1 blood levels at 0, 6, 12, and 24 weeks. Overnight GH secretion was calculated by mathematical deconvolution of serial GH measurements from serum samples collected every 10 min (22:00-06:00) during simultaneous polysomnography in a subset of 18 men (active n = 11, sham n = 7) at week 12. Active, compared with sham, CPAP increased IGF-1 at 12 weeks (P = 0.006), but not at 6 weeks (P = 0.44). Changes in IGFBP-3 and IGFBP-1 were not different between groups at 6 or 12 weeks (all P ≥ 0.15). At week 24, there was a further increase in IGF-1 and a decrease in IGFBP-1 in the pooled group (P = 0.0001 and 0.046, respectively). In the subset, total (P = 0.001) and pulsatile (P = 0.002) GH secretion, mean GH concentration (P = 0.002), mass of GH secreted per pulse (P = 0.01) and pulse frequency (P = 0.04) were all higher after 12 weeks of CPAP compared with sham. Basal secretion, interpulse regularity, and GH regularity were not different between groups (all P > 0.11). Twelve weeks, but not 6 weeks, of CPAP increases IGF-1, with a further increase after 24 weeks. Total and pulsatile GH secretion, secretory burst mass and pulse frequency are also increased by 12 weeks. CPAP improves specific elements of the GH/IGF-1 axis in a time-dependent manner. Australia New Zealand Clinical Trials Network, www.anzctr.org.au, number ACTRN12608000301369.

The harmonisation of growth hormone measurements: Taking the next steps

For over 20years differences in results of growth hormone (GH) measurement have been recognised as being significant enough to lead to misdiagnosis and inappropriate management of patients with GH-related disorders. Whilst issues of method standardisation, variable antibody specificity, use of different reporting units with different conversion factors, and interference from GH binding protein have been acknowledged as contributing to the discrepancies, inconsistent approaches to method harmonisation have hampered opportunities to enhance the evidence base for GH measurements. Amongst the first steps to be taken, international collaboratives recommended the universal adoption of the International Standard 98/547 and the reporting of results in mass units. Whilst inter-method variability may have improved over the last 10years, clinically significant differences remain. A more recently recognised issue contributing to the discrepancies may be the differences in the matrix materials used by kit manufacturers to assign values to their calibrants. The establishment of an international harmonisation oversight group is recommended: its key roles to include identification of a commutable matrix reference material, assessing the clinical significance of assay interferents, the evaluation of liquid chromatography–mass spectrometry as a reference measurement procedure and the provision of acceptance criteria for the clinical application of GH methods.

Prevalence of thyroid diseases in patients with acromegaly: experience of a Brazilian center

Acromegaly is frequently associated with thyroid diseases. In this study, we evaluated the frequency of thyroid disorders in a series of acromegalic patients. We evaluated 106 acromegalic patients using thyroid ultrasonography (US) and measurements of GH, IGF-I, free T4, TSH and anti-thyroperoxidase antibody levels. IGF-I was expressed in mass units and age-related standard deviation scores (SD-scores). Fine-needle aspiration biopsy (FNAB) was performed on thyroid nodules with a diameter greater than one centimeter or with suspicious characteristics. Thyroid disorders were found in 75 patients. Eleven patients had diffuse goiter, 42 patients had nodular goiter, and 22 patients had unspecific morphological abnormalities. Four patients (3.8%) had thyroid carcinoma. Considering the patients with diffuse or nodular goiter, thyroid volume was greater in patients with active acromegaly, and was positively correlated with GH, IGF-I, and IGF-I SD-score. Our study confirmed that benign thyroid diseases are frequent in acromegalic patients. The prevalence of thyroid cancer was higher than in the overall population. We suggest that thyroid US should be routinely performed in patients with acromegaly.

Acromegaly and pregnancy: a prospective study

The interaction between pregnancy and acromegaly has been studied only retrospectively. We used prospective data to assess those interactions. Prospective, interventional, multicentric study. 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. Withdrawal of pharmacological treatment (octreotide and/or cabergoline and/or pegvisomant) following pregnancy diagnosis. 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. 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. 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.

The Quantitative Effect of Botulinum Toxin A Over Brow Height

Botulinum toxin type A (BTX-A) is currently used in temporal brow lifting. Reducing the activity of the superolateral portion of orbicularis oculi muscle causes lateral brow elevation. The objective of this study was to determine the quantitative brow elevation after paralysis of the superolateral portion of orbicularis oculi muscle. This study includes 10 female patients. Six units of BTX-A were injected into the superolateral portion of the orbicularis oculi in a serial manner into 3 points, below the lateral half of the brow at each side. Bilateral measurements were obtained by using calipers, immediately before and 2 weeks after the treatment. The medial canthus to the medial brow margin (AB), the lateral brow margin to the lateral canthus (CD), the medial brow margin to the lateral brow margin (BC), the brow apex to upper lid margin at the level of the lateral limbus (EF), the brow apex to the medial brow margin (EB), the brow apex to the lateral brow margin (EC), and upper eyelid margin to lower eyelid margin at the level of the pupil (GH), were measured. There were no statistically significant differences found between pretreatment and posttreatment left and right measurements. There were statistically significant increases in CD, EF, and GH measurements, which are point out brow elevation. There were no statistically significant differences found in other measurements. Same doses of BTX-A application did not disrupt symmetry. Applications of 6U BTX-A to the superolateral portion of orbicularis oculi provide brow elevation and increased interpalbebral distance and upper eyelid distance. Our study has confirmed that BTX-A treatment of superolateral portion of the orbicularis oculi muscle produces quantitative temporal brow elevation.

Novel Use of Endogenous GH-Measurement Directly after Transsphenoidal Microsurgery in Acromegaly Treated with Pegvisomant

The GH receptor antagonist pegvisomant is increasingly used as therapy in acromegaly. Pituitary surgery might be indicated on pegvisomant treatment, due to side effects, adenoma growth or intention to cure after primary treatment. This study was initiated to clarify if, and when, GH measurement could be useful postoperatively with an assay specific for endogenous GH that does not cross-react with pegvisomant. This study was designed as a prospective study in 2006 with the German Pituitary Working Group. Only 2 cases with potentially resectable adenomas from the German Pegvisomant Observational Study (GPOS) had been operated. Now with a post-operative follow-up of more than 5 years in these 2 cases, the usefulness of immediate pre-operative GH measurement shortly after pegvisomant treatment was evaluated. In both patients a steep decline of endogenous GH after transnasal microsurgery could be proven by using the special GH assay after near radical or radical removal, of the GH secreting adenomas respectively. Conventional GH assays showed no effect. GH half-life was more than 20 min in the patient with a small invasive residual adenoma and less than 20 min in the cured patient. Endogenous GH-levels declined to less than 1 ng/ml in the days after surgery in the patient with long-term cure. Measurement of endogenous GH in this special subgroup of patients under pegvisomant therapy can be used to decide upon early reoperation. Thus the beneficial effect of pegvisomant on acromegalic symptoms can be kept without interfering with post-operative monitoring of GH levels.

Detecting and solving the interference of pregnancy serum, in a GH immunometric assay

BackgroundHigh homology of GH with placental GH (pGH) and hPL frequently resulted in falsely high GH levels in competitive immunoassays during pregnancy. However, in immunometric assays, falsely high or low GH levels can result from GH-like molecules binding to both or only one monoclonal antibody. Since our GH-IFMA assay detected GH suppression in both normal and acromegalic pregnancies, we evaluated potential negative interference of pregnancy serum in the assay. MethodsGH was measured in samples from acromegalic patients with and without the addition of normal pregnancy serum using a sensitive in-house two-step GH-IFMA (no crossreactivity with pGH, Prolactin or hPL). Standard GH assay curves were run with and without pGH (20 and 22K). Pegvisomant, a GH-antagonist with high homology to GH, was also tested for cross-reactivity. ResultsAddition of pregnancy serum to acromegaly serum resulted in marked decrease in GH, but addition of pGH did not change GH measurements. Redesign of the routine assay by switching the positions of the antibodies (“inverted” assay) completely abrogated the interference of pregnancy serum. GH by both routine and inverted assays declined progressively throughout pregnancy in controls, with higher nadir levels in the “inverted” assay (median 0.03μg/L vs 0.50μg/L, P<0.05). GH suppression during acromegalic pregnancy previously found with the routine assay was not observed in the “inverted” assay. Pegvisomant does not cross-react with GH in the “inverted” assay. ConclusionsGH measurements in pregnancy by immunometric assays must be made after exclusion of pregnancy serum interference by dilutional tests. Redesigning a two-step immunometric GH assay by switching the positions of the antibodies can be a successful strategy to abrogate such interference.

1716 Effects on Growth of Inhaled Corticosteroids in Asthmatic Children

BackgroundCorticosteroids may inhibit growth hormone (GH) axis, reducing GH release, decreasing tissue expression of growth factors, inhibiting IGF-1 bioactivity, osteoblast activity, promoting bone resorption.ObjectivesEvaluating adverse effects of inhaled corticosteroids used...