Bone Age at Discontinuation of Medroxyprogesterone Acetate Therapy in Girls with Precocious Puberty: Effect on Final Height

We report 98 children who have reached final adult height in a long-term trial of LHRH agonist treatment. These children were 5.3± 2.1 yr old at the start of treatment and were treated with either deslorelin (4 μg/kg·d sc) or histrelin (4–10 μg/kg·d) for an average of 6.1 ± 2.5 yr. Final height averaged 159.8 ± 7.6 cm in the 80 girls, which was significantly greater than pretreatment predicted height (149.3 ± 9.6 cm) but still significantly less than midparental height (MPH) (163.7 ± 5.6). Final height averaged 171.1 ± 8.7 cm in the 18 boys, which was significantly greater than pretreatment predicted height (156.1 ± 14.2 cm) but still significantly less than MPH (178.3 ± 5.2 cm). However, the average adult height of the 54 children who had less than a 2-yr delay in the onset of treatment was not significantly different from their MPH, and 21 children exceeded MPH. Final height sd score correlated positively with duration of treatment (P < 0.01), midparental height (P < 0.001), predicted height at the start of treatment (P < 0.001), and growth velocity during the last year of treatment (P < 0.001) and correlated inversely with delay in the onset of treatment (P < 0.001), age at the start of treatment (P < 0.001), bone age at the start of treatment (P < 0.001), bone age at the end of treatment (P < 0.001), breast stage at the start of treatment (P = 0.02), and bone age minus chronological age at the start of treatment (P = 0.001). We conclude that LHRH agonist treatment improves the final height for children with rapidly progressing precocious puberty treated before the age of 8 yr for girls or 9 yr for boys. Less delay in the onset of treatment, longer duration of treatment, and lower chronological and bone age at the onset of treatment all lead to greater final height. All children with onset of pubertal symptoms before age 8 in girls and age 9 in boys should be evaluated for possible treatment. Treatment is appropriate in children with rapidly progressing puberty, accelerated bone maturation, and compromise of adult height prediction, regardless of bone age or chronological age at time of evaluation. However, once treatment is considered appropriate, it should be initiated quickly, because longer delays lead to shorter final height. In addition, the longer the treatment is continued, the greater is the final height outcome.

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Gonadotropin Suppression for 7 Years after a Single Histrelin Implant for Precocious Puberty

Journal of the Endocrine Society ◽

10.1210/jendso/bvab189 ◽

2022 ◽

Author(s):

Douglas Villalta ◽

Jose Bernardo Quintos

Keyword(s):

Standard Deviation ◽

Precocious Puberty ◽

Final Height ◽

Central Precocious Puberty ◽

Bone Age ◽

Genetic Potential ◽

Parental Height ◽

Hormone Analogs ◽

Lost To Follow Up

Abstract Gonadotropin releasing hormone analogs (GnRHas) are an effective treatment to address the compromise in height potential seen in patients with central precocious puberty. There is no evidence in the literature of a single GnRHa used for longer than 2 years before being removed or replaced. We describe a patient who was on continuous gonadotropin suppression for 7 years and despite this, achieved a height potential within one standard deviation of mid-parental height. A boy aged 10 years and 3 months presented to endocrine clinic with signs of precocious puberty and advanced bone age. Initial labs showed random LH 9.4 mIU/mL, FSH 16.3 mIU/mL, DHEAS 127 mcg/dl, and testosterone 628 ng/dL. He was initially started on Lupron injections before transitioning to a Histrelin implant. Follow-up laboratory results 5 months post-suppression showed pre-pubertal random LH 0.2 mIU/mL, FSH 0.1 mIU/mL, and testosterone 5 ng/dL. The patient was lost to follow-up and returned 5 years later presenting with gynecomastia and delayed bone age. He had continuous gonadotropin suppression with random LH 0.10 mIU/mL, FSH 0.16 mIU/mL, and testosterone 8 ng/dL. The Histrelin implant was removed and 4 months after removal labs showed random pubertal hormone levels with LH 5.6 mIU/mL, FSH 4.3 mIU/mL, and testosterone 506 ng/dl. The patient’s mid-parental height was 175.3 cm and the patient’s near final height was 170.6 cm which is within one standard deviation of his genetic potential. Further studies are needed to explore continuous gonadotropin hormone suppression with a single Histrelin implant beyond 2 years.

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Near-final height in patients with congenital adrenal hyperplasia treated with combined therapy using GH and GnRHa

Arquivos Brasileiros de Endocrinologia & Metabologia ◽

10.1590/s0004-27302011000800023 ◽

2011 ◽

Vol 55 (8) ◽

pp. 661-664 ◽

Cited By ~ 6

Author(s):

Carlos Alberto Longui ◽

Cristiane Kochi ◽

Luís Eduardo Procópio Calliari ◽

Maria Barcellos Rosa Modkovski ◽

Marisa Soares ◽

...

Keyword(s):

Congenital Adrenal Hyperplasia ◽

Precocious Puberty ◽

Combined Therapy ◽

Final Height ◽

Standard Deviation Score ◽

Central Precocious Puberty ◽

Bone Age ◽

Hormonal Control ◽

Adrenal Hyperplasia ◽

Gh Treatment

INTRODUCTION: Intrinsic limitations of glucocorticoid therapy in patients with congenital adrenal hyperplasia (CAH) determine frequent loss in final height. The association of secondary central precocious puberty and early epiphyseal fusion is also frequent. In these conditions, GnRHa treatment alone or in combination with GH has been indicated. OBJECTIVES: This is a retrospective study, describing the estatural findings of CAH patients with significant decrease in height prediction, who were submitted to combined GH plus GnRHa therapy up to near-final height. SUBJECTS AND METHODS: We studied 13 patients, eight females and five males, eight with the classical and five with the nonclassical form of the disorder. Treatment with hydrocortisone (10-20 mg/m²/day) or prednisolone (3-6 mg/kg/day) was associated with GnRHa (3.75 mg/months) for 4.0 (1.5) years, and GH (0.05 mg/kg/day) for 3.6 (1.4) years. RESULTS: Stature standard deviation score for bone age improved significantly after GH treatment, becoming similar to target height at the end of the second year of GH treatment. CONCLUSION: We conclude that combined GH plus GnRHa therapy can be useful in a subset of CAH patients with significant reduction of predicted final height associated with poor hormonal control and central precocious puberty.

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Van Wyk-Grumbach syndrome and oligosyndactyly in a 6-year-old girl: a case report

Journal of Medical Case Reports ◽

10.1186/s13256-020-02472-z ◽

2020 ◽

Vol 14 (1) ◽

Author(s):

Niranjalee Samanthika Egodawaththe ◽

Sumudu Nimali Seneviratne ◽

Suvini Gunasekara ◽

Sathika Manori Amarasekara ◽

Kumudu Weerasekara

Keyword(s):

Precocious Puberty ◽

Hormone Receptors ◽

Early Recognition ◽

Final Height ◽

Hormone Replacement ◽

Macrocytic Anemia ◽

Bone Age ◽

Breast Development ◽

Syndromic Diagnosis ◽

Stimulating Hormone

Abstract Background Van Wyk-Grumbach syndrome refers to the development of isosexual precocious pseudopuberty and multicystic enlarged ovaries in the presence of hypothyroidism and delayed bone age. It is a rare presentation of untreated hypothyroidism. The prepubertal response in Van Wyk-Grumbach syndrome is always isosexual and mediated by very high thyroid-stimulating hormone levels acting through the follicle-stimulating hormone receptors inducing a follicle-stimulating hormonal effect. Early recognition and thyroid hormone replacement can completely regress precocious puberty and ovarian enlargement, while improving the final height achievement. Oligosyndactly is a congenital bony abnormality and can manifest either as an isolated malformation or as a component of a syndromic diagnosis. However, development of hypothyroidism in children with this peculiar bony deformity has rarely been described in the medical literature, with the exception of Cenani-Lenz Syndactyly syndrome. Case presentation We report the case of a 6-year-old Sri Lankan girl who presented with a 2-day history of vaginal bleeding and exertional dyspnea. She had marked short stature (well below −3 standard deviations) with an upper segment to lower segment ratio of 1.47. This girl had isolated breast development of Tanner stage 2. She was diagnosed to have acquired hypothyroidism secondary to autoimmune thyroiditis and also had macrocytic anemia, pericardial effusion, gonadotropin-releasing hormone-independent precocious puberty with radiological evidence of pubertal changes in the uterus, and multicystic ovaries. Interestingly, she also had post-axial oligosyndactyly in both feet and right-sided clubfoot. The diagnosis of Van Wyk-Grumbach syndrome was made based on the clinical and laboratory features. Her symptoms were successfully managed with L-thyroxine therapy. Conclusions Acquired hypothyroidism is a relatively common endocrine disorder among children and early recognition is important to prevent serious complications like Van Wyk-Grumbach syndrome. Sexual precocity with delayed bone age and stunting should direct our minds toward this unique diagnosis. It is always necessary to identify the other associated anomalies in addition to the primary diagnosis since these features may direct to a syndromic diagnosis.

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Growth and development in girls with Turner's syndrome during early therapy with low doses of estradiol

Acta Endocrinologica ◽

10.1530/acta.0.112s157 ◽

1986 ◽

Vol 113 (4_Suppl) ◽

pp. S157-S163 ◽

Cited By ~ 8

Author(s):

K.W. KASTRUP ◽

_ _

Keyword(s):

Growth Velocity ◽

Final Height ◽

Bone Age ◽

Growth Spurt ◽

First Year ◽

Turner's Syndrome ◽

Turner’S Syndrome ◽

Early Therapy ◽

Group I ◽

Group Ii

Abstract Early therapy with a low dose of estrogen (estradiol-17β) was given to 33 girls with Turner's syndrome (T.s.) for a period of 4 years. The dose (0.25-2 mg/day) was adjusted every 3 months to maintain plasma estradiol in the normal concentration range for bone age. Growth velocity was compared with that of untreated girls with T.s. All girls were above age 10 years. Bone age was below 10 years in 11 girls (group I) and above 10 years in 22 girls (group II). Growth velocity in the first year of treatment in group I 7.5 ± 1.3 cm (SD) with mean SD score (SDS) of +4.3 and in group II 4.9 ± 1.3 with mean SDS of +3.5. Growth velocity decreased in the following years to 1.6 ± 1.0 cm, SDS -1.44 in group I and 0.9 ± 0.6cm, SDS -2.34 in group II during the fourth year. Withdrawal bleeding occurred in 16 girls of group II after the mean of 23 (range 15-33) months and in 3 girls of group I after 15 to 51 months of treatment. The treatment did not cause an inappropriate acceleration of pubertal development. Breast development appeared in most girls by 3 months of treatment. Pubic hair appeared by 12 months of treatment in group I; it was present in most girls in group II at start of treatment. Final height is known for 12 girls of group II; it was 144.2 ± 4.5 cm. The final height as predicted at the start of therapy was 142.2 ± 5.3 cm. Bone age advanced in the first year of treatment by 2 years. Early treatment with small doses of estrogens induces a growth spurt and normalizes the events of puberty. This will presumably decrease the psychological risks associated with abnormally delayed development.

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Rapid progressive central precocious puberty: diagnostic and predictive value of basal sex hormone levels and pelvic ultrasound

Journal of Pediatric Endocrinology and Metabolism ◽

10.1515/jpem-2019-0577 ◽

2020 ◽

Vol 33 (6) ◽

pp. 785-791

Author(s):

Valeria Calcaterra ◽

Catherine Klersy ◽

Federica Vinci ◽

Corrado Regalbuto ◽

Giulia Dobbiani ◽

...

Keyword(s):

Precocious Puberty ◽

Tanner Stage ◽

Central Precocious Puberty ◽

Bone Age ◽

Diagnostic Value ◽

Sex Hormone ◽

Pelvic Ultrasound ◽

Predictive Values ◽

Hormone Levels ◽

Ultrasound Parameters

AbstractObjectivesData on the predictive values of parameters included in the diagnostic work-up for precocious puberty (PP) remain limited. We detected the diagnostic value of basal sex hormone levels, pelvic ultrasound parameters and bone age assessment for activation of the hypothalamic-pituitary-gonadal axis in girls with PP, in order to help in the decision to perform GnRH testing.Patients and methodsWe retrospectively considered 177 girls with PP. According to puberty evolution, the girls were divided into two groups: rapid progressive central precocious puberty (RP-CPP) and non/slowly progressive/transient forms (SP-PP). In all patients we considered Tanner stage, basal luteinizing hormone (LH) and estradiol (E2) values, bone age, and pelvis examination. We assessed the diagnostic value of each variable and identified the number of pathological parameters that best identify patients with RP-CPP.ResultsBasal LH ≥ 0.2IU/L, E2 level ≥ 50 pmol/L, uterine longitudinal diameter ≥ 3.5 cm, transverse uterine diameter ≥ 1.5 cm, endometrial echo and ovarian volume ≥ 2 cm3 were significantly associated with RP-CPP (p ≤ 0.01). The ability to diagnose RP-CPP was enhanced with increasing number of pathological hormonal and instrumental parameters (p < 0.001). With more than three parameters detected, sensitivity and specificity reached 58% (95%CI 48–67) and 85% (95%CI 74–92), respectively, with a PPV = 86% (95%CI 76–93) and PPN = 54% (95%CI 43–54); the area under the ROC curve was 0.71 (95%CI 0.65–0.78).ConclusionDespite the availability of different tests, diagnosing RP-CPP remains difficult. A diagnosis model including at least three hormonal and/or ultrasound parameters may serve as a useful preliminary step in selecting patients who require GnRH testing for early detection of RC-PP.

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Efficacy of long-term growth hormone therapy in short non-growth hormone-deficient children

Journal of Pediatric Endocrinology and Metabolism ◽

10.1515/jpem-2016-0297 ◽

2017 ◽

Vol 30 (2) ◽

Cited By ~ 3

Author(s):

Lucia Schena ◽

Cristina Meazza ◽

Sara Pagani ◽

Valeria Paganelli ◽

Elena Bozzola ◽

...

Keyword(s):

Growth Hormone ◽

Final Height ◽

Standard Deviation Score ◽

Bone Age ◽

Gh Treatment ◽

Short Children ◽

Igf I ◽

Height Gain ◽

The Cost

AbstractBackground:In recent years, several studies have been published showing different responses to growth hormone (GH) treatment in idiopathic short stature children. The aim of the present study was to investigate whether non-growth-hormone-deficient (non-GHD) short children could benefit from long-term GH treatment as GHD patients.Methods:We enrolled 22 prepubertal children and 22 age- and sex-matched GHD patients, with comparable height, body mass index (BMI), bone age, and insulin-like growth factor 1 (IGF-I) circulating levels. The patients were treated with recombinant human GH (rhGH) and followed until they reach adult height.Results:During GH treatment, the two groups grew in parallel, reaching the same final height-standard deviation score (SDS) and the same height gain. On the contrary, we found significantly lower IGF-I serum concentrations in non-GHD patients than in GHD ones, at the end of therapy (p=0.0055).Conclusions:In our study, the response to GH treatment in short non-GHD patients proved to be similar to that in GHD ones. However, a careful selection of short non-GHD children to be treated with GH would better justify the cost of long-term GH therapy.

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Near Final Height after GnRH Agonist Treatment in Central Precocious Puberty

Journal of Pediatric Endocrinology and Metabolism ◽

10.1515/jpem.2000.13.s1.787 ◽

2000 ◽

Vol 13 (Supplement) ◽

Cited By ~ 2

Author(s):

M. Micillo ◽

M. Salerno ◽

A. Officioso ◽

E. Perna ◽

N. Gasparini ◽

...

Keyword(s):

Precocious Puberty ◽

Gnrh Agonist ◽

Final Height ◽

Central Precocious Puberty

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Assessment of gonadotropin concentrations stimulated by gonadotropin-releasing hormone analog by electrochemiluminescence (ECLIA) in girls with precocious puberty and premature thelarche

Hormone Research in Paediatrics ◽

10.1159/000521593 ◽

2021 ◽

Author(s):

Kamila Botelho Fernandes de Souza ◽

Melyna Shayanne Pessôa Veiga ◽

Gabriela Ráina Ferreira Martins ◽

Adriana Paula da Silva ◽

Lívia Grimaldi Abud Fujita ◽

...

Keyword(s):

Precocious Puberty ◽

Central Precocious Puberty ◽

Bone Age ◽

Gonadotropin Releasing Hormone ◽

Assay Method ◽

Premature Thelarche ◽

Releasing Hormone ◽

Cutoff Values ◽

Hormone Analog ◽

Hormone Analogs

Objective: The aim of this study is to determine the cutoff values of gonadotropin response to gonadotropin-releasing hormone analogs (GnRHas) corresponding to the activation of the hypothalamic–pituitary–gonadal axis that could differentiate central precocious puberty (CPP) from premature thelarche (PT) and using the electrochemiluminescence assay method. Methods: A total of 49 girls underwent the stimulation test with the intramuscular injection of 3.75 mg leuprolide acetate. Based on the clinical and laboratory characteristics, they were divided into two groups: CPP (n = 22) and PT (n = 27). Baseline estradiol, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) were collected before GnRHa administration, and LH and FSH at 60 and 120 min, respectively, after GnRHa administration. Results: The girls with CPP presented an increased height Z-score, advanced bone age, and higher baseline LH, FSH, estradiol, and LH/FSH ratio in relation to PT (p < 0.001). Stimulated LH differed significantly between the two groups, and the LH cutoff values were ≥4.29 IU/L (p < 0.001) and ≥3.95 IU/L at 60 and 120 min, respectively (p < 0.001). LH peak was found at 60 min after stimulation. Conclusions: The GnRHa test is effective in distinguishing CPP from PT, and a single sampling, at 60 min, with LH concentrations above 4.29 may be the parameter of choice with the advantage of greater convenience and practicality.

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Height Increment and Laboratory Profile of Boys Treated With Aromatase Inhibitors With or Without Growth Hormone

Hormone and Metabolic Research ◽

10.1055/s-0043-116944 ◽

2017 ◽

Vol 49 (10) ◽

pp. 778-785 ◽

Cited By ~ 1

Author(s):

Ludmila Pedrosa ◽

Joice de Oliveira ◽

Paula Thomé ◽

Cristiane Kochi ◽

Durval Damiani ◽

...

Keyword(s):

Growth Hormone ◽

Aromatase Inhibitors ◽

Adult Height ◽

Final Height ◽

Recombinant Human Growth Hormone ◽

Human Growth ◽

Bone Age ◽

Height Loss ◽

Retrospective Data Analysis ◽

Height Gain

AbstractAromatase inhibitors (AIs) have been used to recover height loss due to their capacity to delay growth plate closure. Long-term studies describing final heights are needed to determine the efficacy and safety profiles of these drugs for the treatment of impaired growth. This study aims to identify the therapeutic efficiency of AIs in improve growth and to describe potential adverse effects during treatment. Retrospective data analysis of 96 adolescents, among which 22 patients already attained near-final height, were followed at outpatient clinics of two referral centers. Patients were all in puberty and present idiopathic decrease in predicted adult height. Patients were treated with Anastrozole (ANZ: 1 mg/day) or Letrozole (LTZ: 2.5 mg/day) with/without recombinant human growth hormone (0.05 mg/kg/day) for 1.0 to 3.5 years (2.1±1.2 years). Height gain, body mass index, lipid, liver enzyme, gonadotropins and testosterone levels were described before and at the end of treatment. Predicted adult height (PAH) and NF height were compared with the TH. The height SDS (adjusted to bone age) significantly increased (p<0.05) in all groups [0.8±0.7 (ANZ), 0.7±0.7 (ANZ+GH), 0.3±0.5 (LTZ), and 1.2±0.8 (LTZ+GH)]; the latter group exhibited the highest increment of PAH and growth recovery to the TH (p<0.004). No significant side effects were observed. AI treatment, especially when used in association with GH was able to improve growth and the attainment of familial target height.

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