The Efficacy of Anastrozole and Growth Hormone Therapy on Adult Height in Six Adolescent Males with Growth Hormone Deficiency or Idiopathic Short Stature

Background. Data on adult height outcomes of the use of Anastrozole and Growth Hormone (GH) in pubertal males with Growth hormone deficiency (GHD) and Idiopathic short stature (ISS) are limited. Objective. We examined the effect of Anastrozole and GH therapy on near adult height (NAH) with pubertal males with GHD or ISS. Methods. Retrospective review of 419 charts from 2008 to 2015. The primary outcomes are NAH compared to mid-parental target height (MPTH) and predicted adult height (PAH). Results. We identified 23 patients (5 SGA/IUGR, 1 Noonan syndrome, 6 GHD, and 11 ISS). Six patients (4 GHD; 2 ISS) achieved NAH. Prior to Anastrozole treatment, the mean chronological age was 13.9±0.2 years (range 13.7–14.4), bone age was 13.6±0.6 years (range 12.5–14), mean height SDS was -1.5±0.5 (range −0.8 to −2.3), and mean PAH was 162.6±5.9 cm (range 153.5–168.6). MPTH was 173.6 cm ± 7 (range 161.8–181.6). Patients received Anastrozole for an average of 30.5 months (range 19–36 months). At NAH, the mean chronological age was 16.7±0.8 years (range 15.9–18.1 years) and height was 170±1.8 cm (range 168.5–173.4 cm). The mean height SDS improved to +0.81±0.6 (range +0.08 to +1.92, p=0.002). Net height gain was 7.3 cm compared to pretreatment PAH (p<0.01) and overall the mean adult height remained 3.5 cm below MPTH. Conclusion. Anastrozole and GH therapy can be effective in augmenting adult height without significant side effects. However, the long-term safety and efficacy of aromatase inhibitor use in pediatrics remain limited.

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Adult height prediction by bone age determination in children with isolated growth hormone deficiency

Endocrine Connections ◽

10.1530/ec-20-0090 ◽

2020 ◽

Vol 9 (5) ◽

pp. 370-378

Author(s):

Thomas Reinehr ◽

Martin Carlsson ◽

Dionisios Chrysis ◽

Cecilia Camacho-Hübner

Keyword(s):

Growth Hormone ◽

Growth Hormone Deficiency ◽

Adult Height ◽

Age Determination ◽

Bone Age ◽

Hormone Deficiency ◽

Gh Treatment ◽

Height Prediction ◽

The Mean ◽

Tw2 Method

Background The precision of adult height prediction by bone age determination in children with idiopathic growth hormone deficiency (IGHD) is unknown. Methods The near adult height (NAH) of patients with IGHD in the KIGS database was compared retrospectively to adult height prediction calculated by the Bayley–Pinneau (BP) prediction based on bone age by Greulich–Pyle (GP) in 315 children and based on the Tanner-Whitehouse 2 (TW2) method in 121 children. Multiple linear regression analyses adjusted for age at GH start, age at puberty, mean dose and years of of GH treatment, and maximum GH peak in stimulation test were calculated. Results The mean underestimation of adult height based on the BP method was at baseline 4.1 ± 0.7 cm in girls and 6.1 ± 0.6 cm in boys, at 1 year of GH treatment 2.5 ± 0.5 cm in girls and 0.9 ± 0.4 cm in boys, while at last bone age determination adult height was overestimated in mean by 0.4 ± 0.6 cm in girls and 3.8 ± 0.5 cm in boys. The mean underestimation of adult height based on the TW2 method was at baseline 5.3 ± 2.0 cm in girls and 7.9 ± 0.8 cm in boys, at 1 year of GH treatment adult height was overestimated in girls 0.1 ± 0.6 cm in girls and underestimated 4.1 ± 0.4 cm in boys, while at last bone age determination adult height was overestimated in mean by 3.1 ± 1.5 cm in girls and 3.6 ± 0.8 cm in boys. Conclusions Height prediction by BP and TW2 at onset of GH treatment underestimates adult height in prepubertal IGHD children, while in mean 6 years after onset of GH treatment these prediction methods overestimated adult height.

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Should Skeletal Maturation Be Manipulated for Extra Height Gain?

Frontiers in Endocrinology ◽

10.3389/fendo.2021.812196 ◽

2021 ◽

Vol 12 ◽

Author(s):

Jan M. Wit

Keyword(s):

Growth Hormone ◽

Growth Hormone Deficiency ◽

Short Stature ◽

Precocious Puberty ◽

Adult Height ◽

Central Precocious Puberty ◽

Idiopathic Short Stature ◽

Hormone Deficiency ◽

Skeletal Maturation ◽

Gnrh Analogue

Skeletal maturation can be delayed by reducing the exposure to estrogens, either by halting pubertal development through administering a GnRH analogue (GnRHa), or by blocking the conversion of androgens to estrogens through an aromatase inhibitor (AI). These agents have been investigated in children with growth disorders (off-label), either alone or in combination with recombinant human growth hormone (rhGH). GnRHa is effective in attaining a normal adult height (AH) in the treatment of children with central precocious puberty, but its effect in short children with normal timing of puberty is equivocal. If rhGH-treated children with growth hormone deficiency or those who were born small-for-gestational age are still short at pubertal onset, co-treatment with a GnRHa for 2-3 years increases AH. A similar effect was seen by adding rhGH to GnRHa treatment of children with central precocious puberty with a poor AH prediction and by adding rhGH plus GnRHa to children with congenital adrenal hyperplasia with a poor predicted adult height on conventional treatment with gluco- and mineralocorticoids. In girls with idiopathic short stature and relatively early puberty, rhGH plus GnRHa increases AH. Administration of letrozole to boys with constitutional delay of growth puberty may increase AH, and rhGH plus anastrozole may increase AH in boys with growth hormone deficiency or idiopathic short stature, but the lack of data on attained AH and potential selective loss-of-follow-up in several studies precludes firm conclusions. GnRHas appear to have a good overall safety profile, while for aromatase inhibitors conflicting data have been reported.

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Height outcomes in children with growth hormone deficiency and idiopathic short stature treated concomitantly with growth hormone and aromatase inhibitor therapy: data from the ANSWER program

International Journal of Pediatric Endocrinology ◽

10.1186/s13633-020-00089-z ◽

2020 ◽

Vol 2020 (1) ◽

Author(s):

Bradley S. Miller ◽

Judith Ross ◽

Vlady Ostrow

Keyword(s):

Growth Hormone ◽

Aromatase Inhibitor ◽

Growth Hormone Deficiency ◽

Short Stature ◽

Bone Age ◽

Idiopathic Short Stature ◽

Inhibitor Therapy ◽

Hormone Deficiency ◽

Aromatase Inhibitor Therapy ◽

Epiphyseal Fusion

Abstract Background Treatment of children with growth hormone deficiency (GHD) or idiopathic short stature (ISS) using GH is only effective for bone growth prior to epiphyseal fusion. Aromatase inhibitor therapy (AIT) blocks estrogen production, thereby delaying epiphyseal fusion. The current study analyzed baseline characteristics and longitudinal data of male patients with GHD or ISS who were treated with GH and concomitant AIT. Methods Data were obtained from the observational American Norditropin® Studies: Web-Enabled Research (ANSWER) Program, which collected efficacy and safety data of patients treated with Norditropin®. A longitudinal cohort approach compared patient characteristics, including chronologic age, bone age, and height standard deviation score (HSDS), in GH-treated males before and after AIT initiation. Results A total of 142 GH-naïve patients with GHD (n = 115) or ISS (n = 27) with mean (± SD) baseline chronological ages of 12.10 ± 3.00 and 10.76 ± 3.07 years, respectively, were analyzed. The majority were classified at advanced Tanner stages II to V. Patients with GHD had mean HSDS of − 1.97 ± 0.78 at baseline and − 0.99 ± 0.88 prior to AIT initiation, while corresponding values for patients with ISS were − 2.15 ± 0.72 and − 1.04 ± 0.79, respectively. In patients evaluated after 2 years of concomitant AIT, mean HSDS had decreased to − 0.40 ± 1.16 and − 0.65 ± 0.52 for patients with GHD and ISS, respectively. Patients with GHD had a mean bone age/chronological age ratio (BA/CA) of 0.91 ± 0.11 at baseline and 0.97 ± 0.10 prior to AIT initiation, while corresponding values for patients with ISS were 0.85 ± 0.16 and 0.99 ± 0.10, respectively. In patients evaluated after 2 years of concomitant AIT, mean BA/CA values were 0.95 ± 0.10 and 0.96 ± 0.06 for patients with GHD and ISS, respectively. Conclusions In this real-world analysis, use of AIT with GH in males appeared to be associated with ongoing growth over 2 years, and AIT likely augmented growth potential as indicated by continued HSDS increase with decreased BA/CA after AIT initiation. Trial registration This trial was sponsored by Novo Nordisk and is registered with ClinicalTrials.gov (NCT01009905). Registered November 11, 2009; retrospectively registered

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Factors affecting bone age maturation during 3 years of growth hormone treatment in patients with idiopathic growth hormone deficiency and idiopathic short stature

Medicine ◽

10.1097/md.0000000000014962 ◽

2019 ◽

Vol 98 (14) ◽

pp. e14962 ◽

Cited By ~ 3

Author(s):

Min Jae Kang ◽

Eun Young Kim ◽

Young Suk Shim ◽

Hwal Rim Jeong ◽

Hye Jin Lee ◽

...

Keyword(s):

Growth Hormone ◽

Growth Hormone Deficiency ◽

Short Stature ◽

Growth Hormone Treatment ◽

Bone Age ◽

Hormone Treatment ◽

Idiopathic Short Stature ◽

Hormone Deficiency ◽

Factors Affecting ◽

Idiopathic Growth Hormone Deficiency

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GROWTH HORMONE THERAPY;

The Professional Medical Journal ◽

10.29309/tpmj/2013.20.02.627 ◽

2018 ◽

Vol 20 (02) ◽

pp. 182-187

Author(s):

COL NAYYAR AHMAD, ◽

COL. MOHAMMAD TARIQ NADEEM, ◽

MAJ. ZAMEER AHMAD NAYYAR,

Keyword(s):

Growth Hormone ◽

Growth Hormone Deficiency ◽

Short Stature ◽

Hormone Replacement ◽

Bone Age ◽

Hormone Deficiency ◽

Height Velocity ◽

Growth Hormone Replacement ◽

Female Ratio ◽

The Mean

Objective: To detect growth hormone deficiency in short stature children and to observe the response of growth hormonereplacement therapy in isolated GH deficient. Design: An interventional descriptive study. Place and Duration of Study: The study wascarried out in the Department of Pediatrics at Military Hospital Rawalpindi in collaboration with Armed Forces Institute of PathologyRawalpindi over a period of two years from Jan 2007 to Dec 2008. Patients and Methods: Thirty short children between three to fourteenyears of age having isolated growth hormone deficiency confirmed by laboratory investigation were included in the study prospectivelyand retrospectively. Growth hormone replacement therapy with recombinant GH was given to all children at the dose of 0.14iu/kg, sixdays a week subcutaneously. Each patient was assessed and evaluated after every three months. Results: The mean chronologic agewas 8.05 +/- 2.74 years with a height age of 4.02 years. The male to female ratio was 1.72:1. They were treated with recombinant GH in adose of 0.14iu/kg, six days a week, subcutaneously at evening. Response to GH was excellent and the mean growth speed had gone upfrom 2.53 +/- 0.87 cm per year before the treatment to 8.94 +/- 3.18 cm / year in the first twelve months of treatment and 6.8 +/- 1.6cm / year during the second year of treatment. During the first twenty four months of treatment, height standard deviation score increasedby 1.0 +/- 0.4 SD (p < 0.0001) The height velocity increased, the bone age / chronological age ratio and height SDS for chronologicalage decreased, while height SDS for bone age increased. There were no adverse reactions. Conclusion: Short stature with classic growthhormone deficiency is not uncommon. Early diagnosis and prompt treatment with growth hormone replacement has a very goodoutcome and the child attains a reasonable height.

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Pituitary volume in children with growth hormone deficiency, idiopathic short stature and controls

Journal of Pediatric Endocrinology and Metabolism ◽

10.1515/jpem-2015-0404 ◽

2016 ◽

Vol 29 (10) ◽

Cited By ~ 2

Author(s):

Marion Kessler ◽

Michael Tenner ◽

Michael Frey ◽

Richard Noto

Keyword(s):

Growth Hormone ◽

Magnetic Resonance ◽

Growth Hormone Deficiency ◽

Short Stature ◽

Hormone Secretion ◽

Growth Hormone Secretion ◽

Magnetic Resonance Images ◽

Idiopathic Short Stature ◽

Hormone Deficiency ◽

Significant Difference

AbstractBackground:The objective of the study was to describe the pituitary volume (PV) in pediatric patients with isolated growth hormone deficiency (IGHD), idiopathic short stature (ISS) and normal controls.Methods:Sixty-nine patients (57 male, 12 female), with a mean age of 11.9 (±2.0), were determined to have IGHD. ISS was identified in 29 patients (20 male, 9 female), with a mean age of 12.7 (±3.7). Sixty-six controls (28 female, 38 male), mean age 9.8 (±4.7) were also included. Three-dimensional (3D) magnetic resonance images with contrast were obtained to accurately measure PV.Results:There was a significant difference in the mean PV among the three groups. The IGHD patients had a mean PV 230.8 (±89.6), for ISS patients it was 286.8 (±108.2) and for controls it was 343.7 (±145.9) (p<0.001). There was a normal increase in PV with age in the ISS patients and controls, but a minimal increase in the IGHD patients.Conclusions:Those patients with isolated GHD have the greatest reduction in PV compared to controls and the patients with ISS fall in between. We speculate that a possible cause for the slowed growth in some ISS patients might be related to diminished chronic secretion of growth hormone over time, albeit having adequate pituitary reserves to respond acutely to GH stimulation. Thus, what was called neurosecretory GHD in the past, might, in some patients, be relative pituitary hypoplasia and resultant diminished growth hormone secretion. Thus, PV determinations by magnetic resonance imaging (MRI) could assist in the diagnostic evaluation of the slowly growing child.

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Síndrome de Klinefelter con deficiencia parcial de hormona de crecimiento.

Revista Medica Herediana ◽

10.20453/rmh.v10i1.2387 ◽

2015 ◽

Vol 10 (1) ◽

pp. 38

Author(s):

Carlos TORI TORI ◽

Carlos ROE B.

Keyword(s):

Growth Hormone ◽

Growth Hormone Deficiency ◽

Short Stature ◽

Klinefelter Syndrome ◽

Bone Age ◽

Hormone Deficiency ◽

Klinefelter’S Syndrome ◽

Klinefelter's Syndrome ◽

The Third ◽

Rare Association

We present a case of Klinefelter’s syndrome and short stature due to partial growth hormone deficiency. His height was below the third percentile for age and his bone age lagged behind four years. Cases like this are generally due to the presence of a an isochromosome Xq or to an isolated partial or total deficiency of growth hormone, or to partial or panhypopituitarism. We wish de emphasize the rare association between Klinefelter syndrome and growth hormone deficiency.

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