Sex Steroid Priming Research Articles

Correspondence on "Sex steroid priming for growth hormone stimulation testing in children and adolescents with short stature: A systematic review".

Duncan et al. reviewed the response to growth hormone stimulation testing after priming in peripubertal children. The concern is that there is little research documenting the response to growth hormone treatment in patients with sex hormone primed growth hormone stimulation testing and those unprimed. The controversy about priming or not can be summarized as follows: if one wants to know if the production of growth hormone during puberty will be adequate in terms of peak growth hormone responses then stimulation with priming should be done.

Sex steroid priming in short stature children unresponsive to GH stimulation tests: Why, who, when and how.

Despite decades of experience, the diagnosis of growth hormone deficiency (GHD) remains challenging, especially in peripubertal children. Failure to respond to GH stimulation tests (GHSTs) is needed to confirm GHD, but long-standing controversies regarding the number of tests needed and the interpretation of GH peaks are still a matter of debate worldwide. Diagnostic workup is even more problematic in short children with slow growth and delayed sexual development: they often exhibit low GH peaks under GHST, which often normalize as puberty progresses. Consequently, this transient suboptimal response to GHST may result in GH overtreatment, carrying both health and economic concerns. Considering the complex and bound link between GH axis and sex steroids, the use of sex steroid priming prior to GHST might be helpful in peripubertal setting. However, its use is still controversial. There is no consensus regarding patient selection, timing, dose, and preparation of sex steroids. In this review, we aim to overview the use of sex steroid priming in clinical practice, highlighting the need to develop appropriate guidelines in order to overcome diagnostic pitfalls in peripubertal age.

Association of Sex Steroid Priming on Growth Hormone Stimulation Test in Tertiary Care Hospital Settings Rawalpindi

Objective: To determine association of Sex steroid priming on Growth hormone stimulation test in tertiary care hospital settings Rawalpindi. Study design: Cross sectional study. Place and duration of study: Department of Chemical Pathology and Endocrinology, Armed Forces Institute of Pathology (AFIP) Rawalpindi from January 2018 to June 2018. Methodology: This study was a cross-sectional study conducted after the Institutional Review Board (IRB) approval at AFIP from January 2018 to June 2018. Data was collected from 149 children of 9-13 year of age reported to endocrinology clinic AFIP, after informed consent. Inclusion criteria included healthy adults with age of 9-13 years with no minor or subclinical illness or endocrinology disorders like hypothyroid, Cushing syndrome or Addison disease. Patients with comorbidity like cancer, tuberculosis and bed ridden patients were excluded from study. Sampling technique was non probability convenience sampling which was done in endocrine clinic of AFIP. Results: A total of 149 patients were inducted in study who visited Endocrine clinic in AFIP. Mean age of participants was 9.9 ± 3.9 year while 96 (64.4%) were male and 52 (34.9%) were female. Total of 149 patients there were 100 (67.1%) patients were below 3rd percentile, while 44 (29.5%) were above 3rd percentile but below 50th percentile and 4 (2.7%) were at 50th percentile. Independent T test was applied for Priming and response level after growth hormone stimulation test and it gives significant level (P value=0.00) which is considered significant (P value <0.05). Conclusion: This study concluded that priming after sex steroids can effect on growth hormone level in pre pubertal children’s and it will help in appropriate diagnosis of growth hormone deficiency.

Basal characteristics and first year responses to human growth hormone (GH) vary according to diagnostic criteria in children with non-acquired GH deficiency (naGHD): observations from a single center over a period of five decades.

Background Children with non-acquired (na) growth hormone deficiency (GHD) diagnosed over decades in one center may provide perspective insight. Methods naGHD is divided into idiopathic GHD (IGHD), GHD of known cause (cGHD) and GHD neurosecretory dysfunction (NSD); time periods: <1988 (I); 1988-1997 (II); 1998-2007 (III); 2008-2015 (IV). Descriptive analyses were performed at diagnosis and during first year GH treatment. Results Patients (periods, N): I, 87; II, 141; III, 356; IV, 51. In cGHD (all), age, maximum GH, insulin-like growth factor-I (IGF-I), and insulin-like growth factor-binding protein-3 (IGFBP-3) (5.1 years, 3.6 μg/L, -5.3 standard deviation score [SDS], -3.7 SDS) were lower than in IGHD (all) (6.8 years 5.8 μg/L, -2.5 SDS, -1.0 SDS), but not height (-3.1 vs. -3.2 SDS). Characteristics of NSD were similar to that of IGHD. Patients with IGHD - not cGHD - diagnosed during 2008-2015 (IV) were the youngest with most severe GHD (maxGH, IGF-I, IGFBP-3), and first year height velocity (HV) and ∆ IGF-I (10.5 cm/year, 4.0 SDS) but not ∆ height SDS were the highest on recombinant human growth hormone (rhGH) (27 μg/kg/day). Conclusions Although during 1988-2007 patient characteristics were similar, the recently (>2008) stipulated more stringent diagnostic criteria - HV before testing, sex steroid priming, lower GH cut-off - have restricted diagnoses to more severe cases as they were observed before the rhGH era.

Clinical and laboratory parameters predicting a requirement for the reevaluation of growth hormone status during growth hormone treatment: Retesting early in the course of GH treatment

ObjectiveWe aimed to define the predictive criteria, in the form of specific clinical, hormonal and radiological parameters, for children with growth hormone deficiency (GHD) who may benefit from the reevaluation of GH status early in the course of growth hormone (GH) treatment. Design and MethodsTwo hundred sixty-five children with growth hormone deficiency were retested by GH stimulation at the end of the first year of GH treatment. The initial clinical and laboratory characteristics of those with a normal (GH≥10ng/ml) response and those with a subnormal (GH<10ng/ml) response were compared to predict a normal GH status during reassessment. ResultsSixty-nine patients (40.6%) out of the 170 patients with isolated growth hormone deficiency (IGHD) had a peak GH of ≥10ng/ml during the retest. None of the patients with multiple pituitary hormone deficiency (MPHD) had a peak GH of ≥10ng/ml. Puberty and sex steroid priming in peripubertal cases increased the probability of a normal GH response. Only one patient with IGHD who had an ectopic posterior pituitary without stalk interruption on MRI analysis showed a normal GH response during the retest. Patients with a peak GH between 5 and 10ng/ml, an age at diagnosis of ≥9years or a height gain below 0.61 SDS during the first year of treatment had an increased probability of having a normal GH response at the retest. ConclusionEarly reassessment of GH status during GH treatment is unnecessary in patients who have MPHD with at least 3 hormone deficiencies. Retesting at the end of the first year of therapy is recommended for patients with IGHD who have a height gain of <0.61 SDS in the first year of treatment, especially those with a normal or ‘hypoplastic’ pituitary on imaging. Priming can increase the likelihood of a normal response in patients in the pubertal age group who do not show overt signs of pubertal development.

Overcoming the need for a second test: an evaluation of anthropometric, biochemical, and radiological parameters in the diagnosis of GH deficiency

• Poor reproducibility • Variability of different GH assays • Invasive • Time consuming • Expensive ~ £1,000 per test • Potential risks & side effects (dependent on test): hypoglycaemia, hypotension, anaphylaxis, vomiting, nausea, hypokalaemia • Validity: arbitrary cut off regardless of stimulus/ assay (USA <10 μg/l, UK <6.7 μg/l) • Dependent on age, body composition, pubertal status, nutritional status, GH secretion prior to testing • False negatives (“fail”) in prepubertal children: no consensus on sex steroid priming • Non-physiological. 1. To interrogate clinical, biochemical and radiological parameters in the diagnosis of IGHD and Idiopathic Short Stature (ISS) in an attempt to reduce the need for dynamic function testing, and therefore the need for confirmatory testing. 2. To determine what proportion of children diagnosed with IGHD continue to be GH deficient after attaining their final height

Current practice in diagnosis and treatment of growth hormone deficiency in childhood: a survey from Turkey.

Objective:Approaches to diagnosis and treatment of growth hormone deficiency (GHD) in children vary among countries and even among centers in the same country. This survey, aiming to facilitate the process of preparing the new consensus on GHD by the Turkish Pediatric Endocrinology and Diabetes Society, was designed to evaluate the current practices in diagnosis and treatment of GHD in different centers in Turkey. Methods:A questionnaire covering relevant items for diagnosis and treatment of GHD was sent out to all pediatric endocrinology centers.Results:Twenty-four centers returned the questionnaire. The most frequently used GH stimulation test was L-dopa, followed by clonidine. Eighteen centers used a GH cut-off value of 10 ng/mL for the diagnosis of GHD; this value was 7 ng/mL in 4 centers and 5 ng/mL in 2 centers. The most frequently used assay was immunochemiluminescence for determination of GH, insulin-like growth factor-1 and insulin-like growth factor binding protein-3 concentrations. Sex steroid priming in both sexes was used by 19 centers. The most frequently used starting dose of recombinant human GH (rhGH) in prepubertal children was 0.025-0.030 mg/kg/day and 0.030-0.035 mg/kg/day in pubertal children. Growth velocity was used in the evaluation for growth response to rhGH therapy in all centers. Anthropometric measurements of patients every 3-6 months, fasting blood glucose, bone age and thyroid panel evaluation were used by all centers at follow-up. Main indications for cessation of therapy were decreased height velocity and advanced bone age. Fourteen centers used combined treatment (rhGH and gonadotropin-releasing analogues) to increase final height.Conclusion: Although conformity was found among centers in Turkey in current practice, it is very important to update guideline statements and to modify, if needed, the approach to GHD over time in accordance with new evidence-based clinical studies.

Sex steroid priming in differential diagnosis between idiopathic GH deficiency and constitutional delay of growth and puberty

Sex steroid priming in differential diagnosis between idiopathic GH deficiency and constitutional delay of growth and puberty

The pros and cons of sex steroid priming in growth hormone stimulation testing

Diagnosing growth hormone deficiency (GHD) remains a challenge, and the role of sex steroid priming in the diagnosis of GHD continues to be debated. This review examines existing data on sex steroid priming during GHD diagnosis. Primary literature was reviewed in the area of sex steroid priming and growth hormone stimulation tests. Studies supporting sex steroid priming suggest improved diagnostic efficiency with reduced false diagnosis of GHD in peripubertal children. Those that do not support sex steroid priming note the potential for underdiagnosis of GHD and the lack of standardization in sex steroid priming procedures. To date, there is no consensus on the use of sex steroid priming prior to performing growth hormone stimulation tests in the evaluation of GHD. A more targeted approach to using sex steroid priming may be reasonable; however, the decision of whether or not to use sex steroid priming should remain with the individual clinician.

Growth Hormone Deficiency in Children

The foundation for the diagnosis of growth hormone (GH) deficiency in childhood must be auxology, that is, the comparison of the child's growth pattern to that of established norms for gender and ethnicity. It is only in those growing considerably more slowly than average that testing for GHD makes sense. Assessment of laboratory tests, whether static, for example, the measurement of growth factors or their binding proteins, or dynamic, for example, secretagogue-stimulated GH secretion is confir- matory. One must be cognizant of the assay used to determine GH, for there may be a 3-fold difference in the concentration of GH among commercially-available assays. Controversy still exists concerning the measure- ment of spontaneous GH release and whether sex-steroid priming is appropriate in prepubertal children. Imaging analysis may prove helpful in some children with con- genital GHD or to detect a space-occupying lesion in the area of the hypothalamus and pituitary. The final diagnosis is based on multiple parameters and occasionally on a therapeutic trial of GH therapy to determine if there is a significant acceleration of growth velocity.

Sex Steroid Priming for Induction of Puberty in Thalassemia Patients with Pulsatile Reversible Hypogonadotrophic Hypogonadism

Growth and pubertal disturbances are the most common causes of morbidity, affecting 60–80% β-thalassemia major (β-TM) patients worldwide, due mainly to hypogonadotrophic hypogonadism (HH). We undertook a 6-year prospective study of 55 Indian β-TM children with stunted growth and absent or arrested puberty, aged 15–18 years with pulsatile HH, to evaluate the role of low dose sex steroid priming (6–12 months) for physiological induction of puberty. Eighty percent responded favorably with increase in height, growth spurt and completed pubertal maturation [Tanner stage 4–5 (T4-T5)] and 20% moved from T2 to T3. There was biochemical improvement in maturation of hypothalamic-pituitary (H-P) axis. Those younger than 15 years with minimal iron load had the best outcome. Our data suggest that sex steroid priming is a feasible method of induction of physiological puberty in β-TM patients with sexual infantilism and reversible apulsatile HH, especially in younger patients with minimal iron loads.

Yes, I am ready now: differential effects of paced versus unpaced mating on anxiety and central oxytocin release in female rats.

Sexual activity and partner intimacy results in several positive consequences in the context of stress-coping, both in males and females, such as reduced state anxiety in male rats after successful mating. However, in female rats, mating is a rewarding experience only when the estrous female is able to control sexual interactions, i.e., under paced-mating conditions. Here, we demonstrate that sex-steroid priming required for female mating is anxiolytic; subsequent sexual activity under paced mating conditions did not disrupt this anxiolytic priming effect, whereas mating under unpaced conditions increased anxiety-related behavior. In primed females, the release of the neuropeptide oxytocin (OT) within the hypothalamic paraventricular nucleus was found to be elevated and to further increase during paced, but not unpaced mating. Central administration of an OT receptor antagonist partly prevented priming/mating-induced anxiolysis indicating the involvement of brain OT in the anxiolysis triggered by priming and/or sexual activity.These findings reveal that the positive consequences of mating in females are dependent on her ability to control sexual interactions, and that brain OT release is at least in part the underlying neurobiological correlate.

Growth hormone deficiency in children

The foundation for the diagnosis of growth hormone (GH) deficiency in childhood must be auxology, that is, the comparison of the child's growth pattern to that of established norms for gender and ethnicity. It is only in those growing considerably more slowly than average that testing for GHD makes sense. Assessment of laboratory tests, whether static, for example, the measurement of growth factors or their binding proteins, or dynamic, for example, secretagogue-stimulated GH secretion is confirmatory. One must be cognizant of the assay used to determine GH, for there may be a 3-fold difference in the concentration of GH among commercially-available assays. Controversy still exists concerning the measurement of spontaneous GH release and whether sex-steroid priming is appropriate in prepubertal children. Imaging analysis may prove helpful in some children with congenital GHD or to detect a space-occupying lesion in the area of the hypothalamus and pituitary. The final diagnosis is based on multiple parameters and occasionally on a therapeutic trial of GH therapy to determine if there is a significant acceleration of growth velocity.

Divergent Effect of Endogenous and Exogenous Sex Steroids on the Insulin-Like Growth Factor I Response to Growth Hormone in Short Normal Adolescents

The lower responsiveness to GH in women than in men is probably due to a divergent effect of gonadal steroids. It is unknown, however, how the progressive increase in sex steroid production that occurs during puberty affects this responsiveness. To compare the effects of puberty and sex steroid administration on responsiveness to GH, we used the IGF-I generation test, in which the peak IGF-I level 24 h after a single injection of GH (2 mg/m2) was studied in 117 healthy short subjects (56 females and 61 males). The subjects, aged 8-16 yr, were divided into four groups: prepuberty, early puberty, midpuberty, or pubertal delay. In the latter group, the IGF-I response was determined before and after priming with oral 17beta-estradiol in girls and im testosterone in boys. We also tested for an association between body composition (by dual energy x-ray absorptiometry) and the IGF-I response to GH. The IGF-I increment in response to GH (change in IGF-I from baseline) was correlated with the growth velocity sd score (P < 0.05). Progression throughout puberty was associated with an increase in both baseline IGF-I (P < 0.05) and the IGF-I increment in response to GH (P < 0.05), with no gender difference. Pubertal category (pre-, early, and midpuberty; P < 0.05) and fat percentage (P < 0.05) were the main positive predictors of the IGF-I increment in response to GH, expressed as micrograms per liter as well as sd score, independently of baseline IGF-I. After sex steroid priming, both the GH peak in response to insulin-induced hypoglycemia and baseline IGF-I were increased (P < 0.05, after vs. before sex steroid). However, the IGF-I increment in response to GH decreased after oral 17beta-estradiol (P < 0.05), whereas it was unchanged after testosterone administration. Endogenous gonadal steroid secretion appears to result in increased responsiveness to GH in peripubertal girls and boys. By contrast, exogenous estrogen and testosterone, respectively, produce a relative decrease and no change in responsiveness to GH in similar populations, possibly through the achievement of sex steroid concentrations exceeding physiological ranges for age. Fat percentage was a positive determinant of the responsiveness to GH, suggesting a link between the energy stores and the anabolic action of GH.

Body composition, fasting leptin, and sex steroid administration determine GH sensitivity in peripubertal short children.

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.

Body Composition, Fasting Leptin, and Sex Steroid Administration Determine GH Sensitivity in Peripubertal Short Children

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/m2) 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 = δ 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 μg/liter at baseline and increased to 429 ± 160 μg/liter, corresponding to a 46 ± 29% increase over the baseline value (P < 0.0001, stimulated vs. baseline serum IGF-I). δ IGF-I was not different between gender or pubertal stage. There were positive correlations (P< 0.001) between δ 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 δ IGF-I was similar after vs. before T administration. By contrast, in girls, serum baseline IGF-I was similar, and δ 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.

Increased insulin sensitivity in young, growth hormone deficient children.

Although growth hormone (GH) has well documented insulin antagonistic effects, GH deficient adults often demonstrate insulin resistance. In young GH deficient children, increased susceptibility to hypoglycaemia might indicate increased insulin sensitivity; however, this has not been documented. We therefore determined insulin sensitivity in GH deficient and GH sufficient children. Prospective study of children undergoing insulin tolerance tests for clinical investigation of GH or cortisol secretion at a regional Paediatric Endocrine/Growth Clinic between October 1986 and December 1997. Ninety-one tests were performed in children with GH deficiency and 142 tests in children with normal GH response to insulin (peak GH > or = 20 IU/l). The standard insulin tolerance test was modified to permit frequent measurements of glucose (0, 5, 10, 15, 20, 30, 45, 60 and 90 minutes). Rate of log glucose disappearance in the first 15 minutes was calculated as a direct measure of insulin sensitivity. GH deficient children were more insulin sensitive than GH sufficient children (P = 0.004) and had lower glucose nadirs post-insulin (P = 0.005). Subgroup analysis revealed that these differences were greater in younger (< 12 years old) or pre/early pubertal children. In 14 prepubertal children, exogenous sex steroid priming resulted in lower insulin sensitivity (P < 0.05) compared to nonprimed tests. Young GH deficient children were more insulin sensitive than children with normal GH secretion. This difference attenuated with age and puberty, possibly secondary to pubertal sex steroids; however, insulin resistance as reported in GH deficient adults, was not observed in adolescents.

X-linked agammaglobulinemia, growth hormone deficiency and delay of growth and puberty.

Coinheritance of X-linked agammaglobulinemia and growth hormone deficiency (XLA/GHD) has been classified as an independent primary immune deficiency. We evaluated the pattern of growth and endocrine function in seven XLA subjects (ages 10.9-20.1 years); four belonged to two different XLA pedigrees and three represented sporadic XLA cases. Three had reached adulthood (final stature 176.0, 173.5 and 165.0 cm, respectively) and their retrospective growth showed delay in growth and puberty during adolescence. In the other four subjects, growth hormone production was measured by growth hormone pharmacological stimulation tests (clonidine, arginine): three of four patients had insufficient growth hormone responses (peak growth hormone < 10 micrograms/l); all three had delayed puberty; their growth hormone responses increased after "priming" with testosterone, reaching values > 10 micrograms/l in two of them and allowing diagnosis of "true" growth hormone deficiency in the third. The fourth was a normally growing subject who showed a normal growth hormone response both before and after testosterone priming. Six out of the seven subjects showed a growth pattern consistent with delay in growth and puberty. Our results suggest that true XLA/GHD is rarer than previously supposed and that subnormal responses to growth hormone stimulation tests may be found without sex steroid priming of the test in adolescence. The most probable growth pattern in XLA appears to be delay in growth and puberty, as has already been described for other chronic diseases.

GROWTH IMPAIRMENT AND DELAYED PUBERTY IN THALASSEMIA

Children affected by thalassemia major frequently present growth disturbances. To investigate the role of delayed sexual development in the growth impairment associated with thalassemia. we studied 29 patients (age range 10.7-19.5 years) with short stature (< 3rd centile), reduced growth velocity (< 10th centile) and delayed bone age. All patients were under regular transfusion and chelation therapy according to standard protocols. Growth hormone (GH) secretion was evaluated by peak GH response to arginine-insulin. Results are shown in the Table. Patients were divided in subgroups based on bone age, pubertal status and whether they had been submitted to sex steroid priming. Patients in group 4) where tested both before and after priming. Patients in group 5) were already on sex steroid treatment. Responders are patients who exhibited a peak GH level > 10 ng/ml at least to 1 stimulus.We have treated twelve patients belonging to groups 2) and 5) for 6-21 months (mean 11±4) with sex steroid in the attempt to increase growth velocity and induce puberty. Treatment consisted of monthly injection of 50-100 mg of testosterone enanthate for boys and transdermic estrogens (0.025-0.05 mg/die) for girls. We observed a significant increase of growth velocity during treatment (2.6±0.8 cm /yr vs. 6.1±1.3 cm/yr; P <0.01): bone age advanced from −2.6 to −1.7 SDS. These data suggest that GH deficiency is not frequent among short thalassemic patients and when present is mainly due to delayed puberty: in addition sex steroids therapy is effective in inducing a significant growth acceleration in these patients.

Sex steroid priming effects on growth hormone response to pyridostigmine throughout the menstrual cycle

Sex steroid priming effects on growth hormone response to pyridostigmine throughout the menstrual cycle