Search

Purpose. – Some adrenal incidentalomas produce cortisol in mild excess (‘subclinical’ Cushing’s adenomas) and can potentially induce osteopenia. Their diagnosis is usually based on exclusive tumour uptake on adrenal scintigraphy using 131I-6β-methyl-iodo-19-norcholesterol and on inadequate cortisol response to dexamethasone (DXM) suppression tests. The aims of the present study were to evaluate bone mineral density (BMD) and metabolic markers of bone turnover in patients with incidentalomas and to test the effect of mild hypercortisolism on bone parameters.Methods. – Thirty-five patients (13 men, 22 postmenopausal women, 49–76 years) with unilateral incidentaloma were studied. BMD was measured by dual X-ray absorptiometry. Two biochemical markers of bone formation, serum osteocalcin (BGP) and bone alkaline phosphatase (bALP), and two markers of bone resorption, urinary free deoxypyridinoline (D-Pyr) and urinary carboxy-telopeptide of bone type 1 collagen (CTX), were measured by radioimmunoassay. D-Pyr and CTX were corrected for creatinine excretion.Results. – Median values of lumbar and femoral T-score were – 1.125 and – 0.920, respectively, whereas corresponding Z-score values where normal (0.105 and 0.120, respectively). Thirty-nine percent of patients had low serum BGP values and 3% had low bALP values; 16% showed elevated D-Pyr/creatinine values and 23% increased CTX/creatinine values. Patients both with suppression of the contralateral adrenal on scintigraphy and with an inadequate cortisol response to 1 mg DXM (> 50 nmol/L) (n = 14) presented a lower femoral T-score (P < 0.02) and, to a lesser extent, a lower femoral Z-score (P = 0.11) than other patients (n = 21). The proportion of increased values of CTX/creatinine (42% versus 11%, P = 0.08) also tended to be higher in the first than in the second group of patients. These two groups of patients were similar in terms of age, but tumour size was larger (P < 0.04) and plasma ACTH value was lower (P < 0.02) in patients with scintigraphic and endocrine abnormalities.Conclusion. – Subclinical hypercortisolism defined on the basis of scintigraphic and hormonal criteria seems to contribute to bone loss in patients with adrenal incidentaloma. As other possible side effects of mild hypercortisolism, these findings have to be taken into account in the therapeutic management of these patients. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the variation in measured glenoid inclination measurements between each of the most used methods for measuring the scapular transverse axis with computed tomography (CT) scans, and to investigate the underlying causes that explain the differences., Methods: The glenoid center, trigonum and supraspinatus fossa were identified manually by four expert shoulder surgeons on 82 scapulae CT-scans. The transverse axis was generated either from the identified landmarks (Glenoid-Trigonum line (GT-line), Best-Fit Line Fossa (BFLF)) or by an automatic software ( Y -axis). An assessment of the interobserver reliability was performed. We compared the measured glenoid inclination when modifying the transverse axis to assess its impact., Results: Glenoid inclination remained stable between 6.3 and 8.5°. The variations occurred significantly when changing the method that determined the transverse axis with a mean biase from -1.7 (BFLF vs. Y -axis) to 0.6 (BFLF vs. GT-line). The Y -axis method showed higher stability to the inclination variation ( p = 0.030). 9% of cases presented more than 5° of discrepancies between the methods. The manual methods presented a lower ICC (BFLF = 0.96, GT-line = 0.87) with the widest dispersion., Conclusion: Methods that determine the scapular transverse axis could have a critical impact on the measurement of the glenoid inclination. Despite an overall good concordance, around 10% of cases may provide high discrepancies (≥5°) between the methods with a possible impact on surgeon clinical choice. Trigonum should be used with caution as its anatomy is highly variable and more than two single points provide a better interrater concordance. The Y -axis is the most stable referential for the glenoid inclination.

Context: Alterations in semen characteristics and circulating Sertoli and Leydig cell hormones have been described in obese male adults. Whether hormonal alterations occur before adulthood has not been fully evaluated., Objective: We describe circulating Sertoli and Leydig cell hormone levels in overweight-obese (ow/ob) boys through childhood and adolescence in a cross-sectional study., Methods: Monocentric study in the Pediatric Endocrinology Unit of Angers University Hospital. Three hundred and fifty-one obese and overweight boys aged 5-19 years underwent physical examination, dual-energy X-ray absorptiometry for body composition, oral glucose tolerance test on insulin and glucose, and measurements of follicle-stimulating hormone, luteinizing hormone, anti-Müllerian hormone (AMH), inhibin B, testosterone, and estradiol. Hormonal levels were compared with normative data obtained from 652 healthy nonoverweight nonobese boys of similar age or Tanner stage., Results: Median inhibin B and testosterone levels during puberty were significantly lower in ow/ob than in healthy boys (1) from age >12 years and thereafter for inhibin B, and (2) from age >14 years and thereafter for testosterone. At Tanner stages 4 and 5, 26%, 31%, and 18% of inhibin B, testosterone, and AMH values were below the 5th percentile in ow/ob subjects (P < .01). In multiple regression analyses, estradiol and total bone mineral density Z-score were negative predictors of inhibin B, fat mass percentage was a negative predictor of testosterone, and insulin was a negative predictor of AMH., Conclusion: Lower Sertoli and Leydig cell hormone levels during puberty were observed in the ow/ob boys., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Rotator cuff fatty infiltration (FI) is one of the most important parameters to predict the outcome of certain shoulder conditions. The primary objective of this study was to define a new computed tomography (CT)-based quantitative 3-dimensional (3D) measure of muscle loss (3DML) based on the rationale of the 2-dimensional (2D) qualitative Goutallier score. The secondary objective of this study was to compare this new measurement method to traditional 2D qualitative assessment of FI according to Goutallier et al and to a 3D quantitative measurement of fatty infiltration (3DFI)., Materials and Methods: 102 CT scans from healthy shoulders (46) and shoulders with cuff tear arthropathy (21), irreparable rotator cuff tears (18), and primary osteoarthritis (17) were analyzed by 3 experienced shoulder surgeons for subjective grading of fatty infiltration according to Goutallier, and their rotator cuff muscles were manually segmented. Quantitative 3D measurements of fatty infiltration (3DFI) were completed. The volume of muscle fibers without intramuscular fat was then calculated for each rotator cuff muscle and normalized to the patient's scapular volume to account for the effect of body size (NV fibers ). 3D muscle mass (3DMM) was calculated by dividing the NV fibers value of a given muscle by the mean expected volume in healthy shoulders. 3D muscle loss (3DML) was defined as 1 - (3DMM). The correlation between Goutallier grading, 3DFI, and 3DML was compared using a Spearman rank correlation., Results: Interobserver reliability for the traditional 2D Goutallier grading was moderate for the infraspinatus (ISP, 0.42) and fair for the supraspinatus (SSP, 0.38), subscapularis (SSC, 0.27) and teres minor (TM, 0.27). 2D Goutallier grading was found to be significantly and highly correlated with 3DFI (SSP, 0.79; ISP, 0.83; SSC, 0.69; TM, 0.45) and 3DML (SSP, 0.87; ISP, 0.85; SSC, 0.69; TM, 0.46) for all 4 rotator cuff muscles (P < .0001). This correlation was significantly higher for 3DML than for the 3DFI for SSP only (P = .01). The mean values of 3DFI and 3DML were 0.9% and 5.3% for Goutallier 0, 2.9% and 25.6% for Goutallier 1, 11.4% and 49.5% for Goutallier 2, 20.7% and 59.7% for Goutallier 3, and 29.3% and 70.2% for Goutallier 4, respectively., Conclusion: The Goutallier score has been helping surgeons by using 2D CT scan slices. However, this grading is associated with suboptimal interobserver agreement. The new measures we propose provide a more consistent assessment that correlates well with Goutallier's principles. As 3DML measurements incorporate atrophy and fatty infiltration, they could become a very reliable index for assessing shoulder muscle function. Future algorithms capable of automatically calculating the 3DML of the cuff could help in the decision process for cuff repair and the choice of anatomic or reverse shoulder arthroplasty., (Copyright © 2021 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.)

Aims: The aim of this study was to describe a quantitative 3D CT method to measure rotator cuff muscle volume, atrophy, and balance in healthy controls and in three pathological shoulder cohorts., Methods: In all, 102 CT scans were included in the analysis: 46 healthy, 21 cuff tear arthropathy (CTA), 18 irreparable rotator cuff tear (IRCT), and 17 primary osteoarthritis (OA). The four rotator cuff muscles were manually segmented and their volume, including intramuscular fat, was calculated. The normalized volume (NV) of each muscle was calculated by dividing muscle volume to the patient's scapular bone volume. Muscle volume and percentage of muscle atrophy were compared between muscles and between cohorts., Results: Rotator cuff muscle volume was significantly decreased in patients with OA, CTA, and IRCT compared to healthy patients (p < 0.0001). Atrophy was comparable for all muscles between CTA, IRCT, and OA patients, except for the supraspinatus, which was significantly more atrophied in CTA and IRCT (p = 0.002). In healthy shoulders, the anterior cuff represented 45% of the entire cuff, while the posterior cuff represented 40%. A similar partition between anterior and posterior cuff was also found in both CTA and IRCT patients. However, in OA patients, the relative volume of the anterior (42%) and posterior cuff (45%) were similar., Conclusion: This study shows that rotator cuff muscle volume is significantly decreased in patients with OA, CTA, or IRCT compared to healthy patients, but that only minimal differences can be observed between the different pathological groups. This suggests that the influence of rotator cuff muscle volume and atrophy (including intramuscular fat) as an independent factor of outcome may be overestimated. Cite this article: Bone Jt Open  2021;2(7):552-561.

Background: Thyroglobulin (Tg) assay in washout fluids of fine needles, after cervical lymph nodes aspiration, is used for detecting metastases from differentiated thyroid carcinomas. Assay methods are the same as for Tg in serum. However, with non-serum samples, methods require extensive validation to notably check for the absence of matrix effect. This study fits this context. Our objectives were to assess analytic performances, in washout fluid, of eight different Tg assay methods and to compare them to validated data in serum., Methods: Eleven medical laboratories participated in this study. The matrix tested was phosphate-buffer saline containing 1% bovine serum albumin (PBS-1% BSA). Samples used were dilutions, in this buffer, of Certified Reference Material (CRM 457). We verified, for all methods, the limit of detection, precision, linearity, trueness and accuracy., Results: In PBS-1% BSA, the functional sensitivities (FS) were comparable to those expected for serum. All the methods were linear. The relative biases of trueness were between -24.5 and 10.2% around 1  µ g/L. Total analytical error was ≤40% near the functional sensitivity values., Conclusion: No quantitatively important matrix effect was observed. All the methods showed their ability to measure Tg in PBS-1% BSA, over the concentration range of interest, with acceptable total analytical error. We validated the functional sensitivity value as a decision threshold in thyroidectomized patients after treatment and with low concentrations of serum Tg.

Resistance to thyroid hormone (RTH) is a syndrome characterized by impaired sensitivity of tissues to thyroid hormone (TH). The alteration of TH-binding proteins, such as in Familial Dysalbuminemic Hyperthyroxinemia (FDH), can mimic the abnormal serum thyroid tests typical of RTH. We aimed to characterize a population referred to our center with suspected RTH and estimate the proportion of patients with FDH. For 303 different families, we collected clinical and hormonal data and sequenced the thyroid hormone receptor β gene ( THRB ) and exon 7 of the albumin gene ( ALB ). We found 56 THRB variants (i.e., 38% of the 303 index cases, called RTHβ group). Among the samples screened for FDH variants, 18% had the variant R218H in ALB (FDH group); in addition, 71% of the cases had neither variant (non-FDH/RTHβ group). Patients with FDH had significantly lower free T3 (fT3) and free T4 (fT4) levels and more often an isolated elevation of fT4 than RTHβ patients. Clinically, patients with FDH had fewer symptoms than patients with RTHβ. Our study suggests that FDH should be systematically considered when examining patients suspected of having RTH. In most cases, they present no clinical symptoms, and their biochemical alterations show an elevation of fT4 levels, while fT3 levels are 1.11 times below the upper limit of the assay.

Resistance to thyroid hormones syndrome is defined as increased thyroxine (T4) and triiodothyronine (T3) concentrations associated with normal or sometimes increased thyrotropin (TSH) concentration. This is usually due to a pathogenic variant with loss of function of the gene coding for thyroid hormone receptor β (THRB). This discrepancy in thyroid hormones (TH) and TSH concentrations is also frequently observed in the presence of analytical interference, notably alteration of TH transport proteins in serum. During 2017, 58 samples were sent to our laboratory in the Angers University Hospital Rare Thyroid and Hormone Receptor Disease Reference Center in order to identify an etiology for discrepant TSH and TH results. We sequenced the genes involved in TH regulation, action and transport (THRB,THRA, SECISBP2, SLC16A, ALB, TTR, SERPINA7). Free T4 and free T3 assay were performed with a second immunoassay (Siemens ADVIA Centaur). A genetic cause of discrepancy in TH and TSH concentrations, with mutation in THRB, was found in 26% of cases (15/58). Biological interference due to TH serum transport protein variant was found in 24% (14/58) of cases. No pathogenic variants were found in the other genes studied. Biological interference was also suspected in 26% of cases without genetic variant, in which the biological discrepancy was not confirmed by a second analytical technique (15/58). Finally, no etiology for the biological discrepancy could be found in 24% of cases (14/58). Clinically, patients in whom biological discrepancy was due to analytic interference were more often asymptomatic, and patients with no identified etiology tended to be older. To limit diagnostic errors associated with the finding of discrepant TSH and TH, we recommend initially conducting a second thyroid function test (TSH, free T4 and free T3) with a different assay, and then screening for a genetic variant in gene coding for thyroid hormone receptor β (THRB) and the TH serum transport proteins (ALB, TTR, SERPINA7)., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

Background: Twenty-four hour urinary free cortisol (UFC) determination can be used for screening and follow-up of Cushing syndrome (CS). As immunoassay methods lack specificity for UFC measurement, the use of high-performance liquid chromatography coupled to mass spectrometer (LC-MSMS) is recommended. The aim of our study was to compare UFC results using four LC-MSMS methods performed in four independent laboratories in order to evaluate interlaboratory agreement., Methods: Frozen aliquots of 24-h urine samples (78 healthy volunteers and 20 patients with CS) were sent to four different laboratories for analysis. Following liquid-liquid or solid-liquid extraction, UFC were determined using four different LC-MSMS assay., Results: UFC intra- and interassays variation coefficients were lower than 10% for each centre. External quality control results were not significantly different. UFC normal ranges (established from healthy volunteers) were 17-126, 15-134, 12-118 and 27-157 nmol/day, respectively. Classification of UFC from healthy volunteers and patients with CS using a 95th percentile threshold was similar. However, for extreme UFC values (<50 or >270 nmol/day), negative or positive bias was noted., Conclusions: Even for highly specific methods such as LC-MSMS, variations of results can be found depending on analytical process. Validation of LC-MSMS methods including determination of the reference range is essential.

We report the case of a newborn with neonatal hypotonia associated to a micropenis and a bilateral cryptorchidia. The discovery of severe hypoglycemia at 0.22 mmol/L led to further biological investigations that revealed sharply decreased levels of several hypophyseal hormones. Altered corticotropic, somatotropic, thyreotropic, and gonadotropic axes finally suggested congenital hypophyseal insufficiency. This diagnostic was confirmed by a brain MRI (magnectic resonance imaging), which revealed a total interruption of the pituitary stalk. Immediate substitutive hormonal treatment allowed a clinical improvement of the condition and limited the risk of further episodes of hypoglycemia. The pituitary stalk interruption syndrome (PSIS), a very rare congenital disorder, has an estimated incidence of about 1:200.000. This developmental anomaly of the hypophysis calls for urgent diagnosis since prognosis depends on the rapid implementation of substitutive hormonal therapy. The hormonal deficit in the newborn affected by PSIS is often of a multiple nature with a constant somatotropic deficit, thus requiring the exploration of the different antehypophyseal axes. Despite the fact that PSIS is a rare disorder, it should always be kept in the differential diagnosis of newborn presenting with hypoglycemia. Since the interpretation of hormonal assays is particularly delicate at birth, close clinico-biological cooperation is essential for rapid diagnosis of PSIS and appropriate adaptation of the short- and long-term therapeutic management of the newborn.

Context: Intrauterine programming of the somatotropic axis has been hypothesized in cases of intrauterine growth retardation., Objective: The objective of the study was to study the effects of birth weight and body composition on GH sensitivity., Design: This was a cross-sectional study with a single GH administration to assess GH sensitivity., Setting: The study was conducted at the Department of Pediatric Endocrinology of an academic medical center., Patients: One hundred normal short children aged from 4 to 17 years old (44 girls, 56 boys) separated into four groups: early childhood (aged 4-8 y, n = 14), late childhood (aged 9-12 y, pubertal stage 1, n = 30), early puberty (aged 10-15 y, stage 2, n = 32), and midpuberty (aged 12-17 y, stages 3 and 4, n = 24)., Intervention and Main Outcome Measure: Serum IGF-1 at baseline and 24 hours after a single administration of GH (2 mg/m(2)) were measured., Results: δIGF-1 significantly increased across the groups (P < .0001) with no gender difference, whereas the percentage of change in IGF-1 was similar (47% ± 32%). Independent predictors of δIGF-1 were birth weight SD score, fat percentage, fasting insulin (all positive predictors), and free fatty acids (negative predictor), with age, puberty, and baseline IGF-1 as adjusting variables (multiple R = 0.73, P < .0001). Independent predictors of the percentage of change in IGF-1 were birth weight SD score, fat percentage, and baseline IGF-1 (multiple R = 0.43, P < .001)., Conclusion: This study suggests that in cases of low birth weight, intrauterine programming of GH sensitivity may be an adaptation to an expected poor postnatal nutritional environment, serving to restrict the anabolic action of GH. Conversely, postnatal excess energy stores may promote the anabolic action of GH.

Steroid hormone measurement, first developed with radioimmunoassay, is now becoming easier with the use of automated platforms of immunoassay. However, some hormones remain uneasily detectable because of their low blood concentration, their structural homology or the presence of interferences. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) can be considered as an alternative to immunoassays. This approach allows the simultaneous determination of several parameters thanks to its selectivity led by the detector mass spectrometer and the separate dimension of chromatography liquid. In addition, recourse to UHPLC (ultra high performance liquid chromatography) allows improving selectivity and sensitivity while limiting the samples volumes. The "ready-to-use" kits are now available and added to the "homemade" techniques developed by laboratories, thus giving opportunity for measurement of a wide steroid panel with only one sample. Finally, mass spectrometry methods, including a prior extraction step, allow the use of varied biological fluids (blood, urine, saliva…). Also, several clinical indications could gain from mass spectrometry, especially when hormone levels are low, when several steroids have to be identified, when the sample volume is low. However, this technology represents an important financial investment and in-depth staff training. In addition, some steroids are not easily quantifiable by mass spectrometry. It is likely by immunoassay and mass spectrometry, well-matched technologies, that we could answer the best to clinical questions about steroids.

Context: Children with obesity [body mass index (BMI) > +2 sd score (SDS)] and children with constitutional tall stature [CTS; height > +2 SDS)] have normal-high serum IGF-I levels, associated with a low and broad range of GH secretion, respectively. This suggests increased sensitivity to GH, whereas children with idiopathic short stature (ISS; height < -2 SDS) are believed to have decreased GH sensitivity. OBJECTIVE, DESIGN, AND MAIN OUTCOME MEASURE: To compare the responsiveness to GH in 62 prepubertal children (43 females, 19 males) with obesity, CTS, or ISS and 26 controls (15 females, 11 males; height and BMI -2 to +2 SDS), we used an IGF-I generation test and studied the IGF-I concentration 24 h after a single injection of GH (2 mg/m2)., Patients: Twenty patients with obesity, 20 with CTS, 22 with ISS, and 26 controls were studied. The mean age was 8.3 +/- 2.9 yr, with no difference in age or gender between groups., Results: Compared with controls, the mean IGF-I increment was 80% higher in obese children and 36% higher in tall children (P < 0.05 obese or tall vs. control children; P = 0.05 obese vs. tall children). Conversely, the IGF-I increment was similar in short compared with control children, despite a mean baseline IGF-I 62% lower in short children (P < 0.05 vs. controls). In all groups, the IGF-I increment was correlated with the BMI SDS or the fat mass percentage (r = 0.51-0.58, P < 0.05)., Conclusion: Obese children tend to have greater GH responsiveness than tall children, and both have greater GH responsiveness than controls. GH responsiveness was similar in controls and short children, despite a lower baseline IGF-I in short children. Whether the differences in the IGF-I response to GH between these children reflect differences in the respective anabolic (growth promotion) and metabolic (i.e. insulin action modulation) roles of circulating IGF-I is unknown.

The goal of this study was to prove the reliability of computer-aided navigation for the surgical reconstruction of the anterior cruciate ligament (ACL) using an arthroscopic procedure. The study involved 50 patients preceded by a learning curve period. Computer-recorded data were compared with specific radiography measurements of the frontal and anteroposterior views. The radiographs were used to measure the position of the tibial tunnel in the frontal and sagittal plane, the angulation of the tibial tunnel in the frontal and sagittal plane, and the position of the femoral tunnel in the lateral condyle.

Aims: To investigate the role of ghrelin in maternal and fetal metabolism, we determined its value in maternal smoking, a specific cause of reduced placenta function and fetal growth., Methods: In 85 normal term pregnancies, 42 in smoking and 43 in non-smoking mothers, we measured ghrelin in the maternal blood at the onset of labor and in the cord blood of their 85 singletons immediately after birth. We determined the relationships between ghrelin and placental GH (PGH), pituitary GH (pitGH), and IGF-I., Results: The newborns of smoking mothers weighed 0.24 kg less (p < 0.05) than those of non-smoking mothers. Cord blood ghrelin was 71% higher and PGH and cord blood IGF-I were 34% and 32% lower, respectively, in the pregnancies of smoking compared with non-smoking mothers (p < 0.05). Cord blood ghrelin was unrelated to pitGH and cord blood IGF-I. Maternal ghrelin was unchanged in smoking mothers, increased with maternal fasting duration (r = 0.26, p < 0.05), showed no correlation with PGH and negative correlation with cord blood IGF-I (r = -0.42, p < 0.01)., Conclusion: The decrease in placental function and fetal growth in smoking mothers is associated with an increase in cord blood ghrelin, and no change in maternal ghrelin. Maternal ghrelin concentration increases with fasting, and is negatively correlated with cord blood IGF-I: it may signal a reduction in the level of nutrients available for placental transfer. No correlation supports a role for ghrelin in PGH or pitGH secretion., (Copyright 2006 S. Karger AG, Basel.)

Serum IGF-I levels in GH-treated subjects demonstrate a wide range of responsiveness to GH. However, the factors influencing GH sensitivity are not well known. The aim of this work was 1) to test whether body composition (determined by dual energy x-ray absorptiometry) or factors related to body composition (fasting blood glucose, FFA, C-peptide, leptin, and insulin sensitivity determined by an insulin tolerance test) influence GH sensitivity; and 2) to study the effect of sex steroid priming on GH sensitivity. We measured serum IGF-I at baseline and 24 h after a single administration of GH (2 mg/m(2)) in 60 healthy prepubertal and early pubertal children (height, -2.1 +/- 1.0 SD score). GH sensitivity, as estimated by the increase in serum IGF-I after GH administration (difference between stimulated and baseline serum IGF-I = delta IGF-I), was also determined after a short-term administration of oral ethinyl E2 in girls and im T in boys. The serum IGF-I concentration was 297 +/- 114 microg/liter at baseline and increased to 429 +/- 160 microg/liter, corresponding to a 46 +/- 29% increase over the baseline value (P < 0.0001, stimulated vs. baseline serum IGF-I). delta IGF-I was not different between gender or pubertal stage. There were positive correlations (P < 0.001) between delta IGF-I and adiposity (total body fat, r = 0.62; trunk fat, r = 0.62), fasting leptin (r = 0.64), and C-peptide (r = 0.54), and a negative correlation with fasting FFA (r = -0.33; P < 0.05) even after adjustment for age, gender, and pubertal stage. These factors remained significant independent predictors of the absolute as well as the percent increase in serum IGF-I in multiple regression analyses. Priming with T and ethinyl E2 had a similar stimulating effect on the serum GH peak in response to the insulin tolerance test. In boys, serum baseline IGF-I increased by 60%, and delta IGF-I was similar after vs. before T administration. By contrast, in girls, serum baseline IGF-I was similar, and delta IGF-I was 60% less after vs. before ethinyl E2 administration. This study indicates that 1) GH sensitivity is determined by fat mass, serum fasting leptin, C-peptide, and FFA; and 2) oral ethinyl E2 and im T have divergent effects on the IGF-I response to a single administration of GH.

The control of fetal growth depends on multiple hormones, including both IGF-I and placental GH (PGH) in the mother, and IGF-I rather than pituitary GH (pitGH) in the fetus. Leptin, which is produced by adipocytes and syncitiotrophoblast cells, has also been thought to influence fetal growth by an as yet unknown mechanism. This study assessed the relationships between the GH-IGF-I axis in mothers and newborns, and maternal smoking, neonate gender, and maternal and fetal leptin. We collected blood in 87 mothers at the onset of labor and cord blood immediately after birth in their 87 healthy full-term newborns. GH concentrations were log(10) transformed, and data were expressed as the geometric mean (-1, +1 tolerance factor). PGH was lower in the 30 smoking mothers, as compared with the 57 nonsmoking mothers [18.2 (11.5; 28.6) vs. 27.0 (15.1; 48.2) microg/liter, P < 0.01]. Cord blood IGF-I was lower in neonates from smoking mothers (90 +/- 44 vs. 135 +/- 65 microg/liter, mean +/- SD, P < 0.01), consistent with their lower birth weight percentile (P < 0.01). A gender effect was observed for PGH, which was higher when the newborn was female, and for newborn pitGH and newborn leptin, which were, respectively, lower and higher in females, even after adjustment for birth weight and maternal smoking category (P < 0.05 for all comparisons). Multiple regression analyses identified maternal leptin as a negative predictor of PGH (P < 0.05) and newborn leptin as a positive predictor of newborn IGF-I (P < 0.05). Maternal smoking is associated to decreased maternal PGH and cord blood IGF-I concentrations. A sexual dimorphism for PGH, newborn pitGH, and newborn leptin exists at the time of birth, but its physiological significance remains to be studied. The relationships between maternal leptin and PGH and between cord blood leptin and IGF-I are consistent with the hypothesis that leptin could contribute to the control of fetal growth.