scholarly journals 6-Month Subcutaneous Leuprolide Acetate Effectively Suppresses Clinical Signs of Puberty in Children With Central Precocious Puberty

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A664-A665
Author(s):  
Erica A Eugster ◽  
Stuart Atkinson ◽  
Deborah Boldt-Houle ◽  
Bradley Scott Miller
Keyword(s):  
Clinical Signs ◽  
External Genitalia ◽  
Tanner Stage ◽  
Central Precocious Puberty ◽  
Pubic Hair ◽  
Development Stage ◽  
Leuprolide Acetate ◽  
Pubertal Maturation ◽  
Subcutaneous Injections ◽  
Tanner Staging

Abstract Objective: Gonadotropin-releasing hormone (GnRH) agonists, such as intramuscular leuprolide acetate, triptorelin and the subcutaneous histrelin implant, are standard treatment for central precocious puberty (CPP). Implants require surgery and sometimes anesthesia, while frequent intramuscular injections can be painful. A shift to longer acting-formulations and subcutaneous injections has been proposed for the treatment of CPP. Therapies with convenient administration, prolonged duration of action and favorable safety profile may be beneficial, improving patient adherence. 87% of subjects achieved stimulated LH suppression to <4 IU/L by Week (W) 24 in a Phase III trial evaluating the efficacy and safety of the first6-month subcutaneous injectable in situ gel leuprolide acetate for CPP. We present secondary analyses of bone age (BA) advancement, weight, BMI, and pubertal maturation from this trial. Methods: 62 children (60 girls, 2 boys) with CPP (naïve to treatment) received 2 doses of 45 mg subcutaneous leuprolide acetate at 24-week intervals, constituting the intent-to-treat population. Radiographs of the left hand and wrist were used to determine BA using the Greulich and Pyle method. BA was assessed by a blinded central reader. Rate of BA advancement was determined by the ratio of BA to chronological age (CA, BA/CA). Pubertal maturation was categorized with the Tanner staging system using breast development, external genitalia, and pubic hair. Safety outcomes were measured. Results: Mean age at onset of treatment was 7.5 ± 0.9 (SD) (range 4-9) years. BA/CA consistently declined throughout treatment, from 1.4 ± 0.2 at baseline, to 1.3 ± 0.1 at W24 and 1.3 ± 0.1 at W48. Although mean weight increased 8.7% from screening to W24 (34.8 kg vs 37.7 kg) and 16.9% from screening to W48 (40.4 kg), mean BMI remained stable throughout the study. The proportion of girls with early breast Tanner stage development (stage 1 and 2) increased from 9% at baseline to 37% at W48. The proportion of girls with late breast Tanner stage development (stage 4 and 5) decreased from 18% at baseline to 5% at W48. Both boys regressed from Tanner stage 3 to stage 2 for external genitalia development by W48. Tanner staging for pubic hair development remained stable for approximately 80% and decreased for 7% of children by W48. 52/53 treatment emergent adverse events were mild or moderate. Conclusions: 6-month 45 mg subcutaneous leuprolide acetate is a promising treatment for CPP. It effectively suppressed LH, suppressed clinical signs of pubertal maturation and demonstrated a good safety profile. It also has the beneficial features of subcutaneous administration, small injection volumeand twice a year dosing. This may be a welcome addition to the armamentarium given the proposed shift in CPP therapies towards longer-acting formulations and subcutaneous injections.

scholarly journals Urinary and salivary endocrine measurements to complement Tanner staging in studies of pubertal development

PLoS ONE ◽  
2021 ◽  
Vol 16 (5) ◽  
pp. e0251598
Author(s):  
Mandy Goldberg ◽  
Anna J. Ciesielski Jones ◽  
John A. McGrath ◽  
Christie Barker-Cummings ◽  
Deborah S. Cousins ◽  
...  
Keyword(s):  
Repeated Measures ◽  
Pubertal Development ◽  
Tanner Stage ◽  
Pubic Hair ◽  
Health Study ◽  
Final Visit ◽  
Tanner Staging ◽  
Non Invasive ◽  
Stage 1

Background Many studies investigating pubertal development use Tanner staging to assess maturation. Endocrine markers in urine and saliva may provide an objective, sensitive, and non-invasive method for assessing development. Objective Our objective was to examine whether changes in endocrine levels can indicate the onset of pubertal development prior to changes in self-rated Tanner stage. Methods Thirty-five girls and 42 boys aged 7 to 15 years were enrolled in the Growth and Puberty (GAP) study, a longitudinal pilot study conducted from 2007–2009 involving children of women enrolled in the Agricultural Health Study (AHS) in Iowa. We collected saliva and urine samples and assessed pubertal development by self-rated Tanner staging (pubic hair, breast development (girls), genital development (boys)) at three visits over six months. We measured dehydroepiandrosterone (DHEA) in saliva and creatinine-adjusted luteinizing hormone (LH), testosterone, follicle stimulating hormone (FSH), estrone 3-glucuronide (E13G) and pregnanediol 3-glucuronide (Pd3G) concentrations in first morning urine. We evaluated the relationships over time between Tanner stage and each biomarker using repeated measures analysis. Results Among girls still reporting Tanner breast stage 1 at the final visit, FSH levels increased over the 6-month follow-up period and were no longer lower than higher stage girls at the end of follow-up. We observed a similar pattern for testosterone in boys. By visit 3, boys still reporting Tanner genital stage 1 or pubic hair stage 1 had attained DHEA levels that were comparable to those among boys reporting Tanner stages 2 or 3. Conclusions Increasing concentrations of FSH in girls and DHEA and testosterone in boys over a 6-month period revealed the start of the pubertal process prior to changes in self-rated Tanner stage. Repeated, non-invasive endocrine measures may complement the more subjective assessment of physical markers in studies determining pubertal onset.

scholarly journals Obesity and secondary sexual maturity in boys

2016 ◽  
Vol 53 (5) ◽  
pp. 283
Author(s):  
Modella Rahmani Femina ◽  
Madarina Julia ◽  
Soeroyo Machfudz
Keyword(s):  
Sexual Maturity ◽  
Tanner Stage ◽  
Pubic Hair ◽  
Testicular Volume ◽  
Growth Charts ◽  
Pediatric Resident ◽  
Tanner Staging ◽  
Prepubertal Boys ◽  
The Mean ◽  
Secondary Sexual

Background Obesity induces earlier secondary sexual maturity in girls. However, results of studies in boys have been inconclusive.Objective To assess for an association between obesity and sexual maturity in boys.Methods This was a prospective cohort study on 133 obese and 133 matched-for-age, non-obese, prepubertal boys, aged 9 to 10 years. They were observed every 4 months for a two year period. Obesity was defined as the BMI ≥the 95th percentile, according to the Centers for Disease Control 2000 growth charts. Secondary sexual maturity was defined as testicular volume of ≥4 mL and Tanner staging of pubic hair of ≥P2. Two trained nurses and a pediatric resident collected the data.Results By the end of the study period, 106 (79.7%) obese boys had attained a testicular volume of 4 mL or more, vs. 85 (63.9%) non-obese boys (RR 1.78; 95%CI 1.19 to 2.67; P=0.004). Furthermore, 81 (60.9%) obese boys attained pubic hair states of Tanner stage P2 vs. 37 (27.8%) non-obese boys (RR 1.85 95%CI 1.46 to 2.34; P<0.001). The mean durations for achieving testicular volume of ≥4 mL were 21.25 (95%CI 20.75 to 21.74) months in obese boys and 22.26 (95%CI 21.80 to 22.72) months in non-obese boys (P=0.007). The mean durations for achieving Tanner stage P2 were 17.04 (95%CI 16.44 to 17.63) months in obese boys and 20.87 (95%CI 20.05 to 21.68) months in non-obese boys.Conclusion Obesity is associated with earlier onset of sexual maturity in boys.

Self-assessment of pubertal development in a puberty cohort

2018 ◽  
Vol 31 (7) ◽  
pp. 763-772 ◽  
Author(s):  
Andreas Ernst ◽  
Lea Lykke B. Lauridsen ◽  
Nis Brix ◽  
Camilla Kjersgaard ◽  
Jørn Olsen ◽  
...  
Keyword(s):  
Clinical Examination ◽  
Pubertal Development ◽  
Tanner Stage ◽  
Weighted Kappa ◽  
Pubic Hair ◽  
Kappa Statistics ◽  
Random Errors ◽  
Rater Agreement ◽  
Self Assessment ◽  
Tanner Staging

Abstract Background We evaluated the inter-rater agreement between self-assessed Tanner staging and clinical examination and the intra-individual agreement of self-assessed information on various puberty markers in late adolescents from the longitudinal nationwide Puberty Cohort, a sub-cohort of the Danish National Birth Cohort (DNBC). Methods We invited 715 children from the ongoing Puberty Cohort between June 2016 and January 2017. In total, 366 children (51%) returned an add-on questionnaire identical to the questionnaire used to collect information on puberty markers, including Tanner staging, in the Puberty Cohort. Of these, 197 (54%) also participated in a clinical examination with Tanner staging. We used percentage agreement and weighted kappa statistics to evaluate the inter-rater and intra-individual agreement. Results Due to late entry, more than 75% of children were Tanner stage 4 or above at clinical examination. In girls, the inter-rater agreement for pubic hair and breast staging was 54% and 52%, respectively, yielding weighted kappas of fair strength. In boys, pubic hair and genital staging agreed in 55% and 33%, respectively, corresponding to weighted kappas of fair to moderate strength. Boys tended to underestimate genitalia staging consistently. The intra-individual agreement on Tanner staging was 75–77% in girls and 69% in boys, whereas the intra-individual agreement on axillary hair and acne was above 92%. Conclusions Self-assessment of late stages of pubertal development may be misclassified, leading to random errors in studies of puberty timing. However, self-assessment continues to serve as an important time- and cost-saving tool in large prospective puberty cohorts.

Can we rely on adolescents to self-assess puberty stage? A systematic review and meta-analysis

2020 ◽  
Vol 105 (8) ◽  
pp. 2846-2856 ◽  
Author(s):  
Susan C Campisi ◽  
Josée D Marchand ◽  
Fahad Javaid Siddiqui ◽  
Muhammad Islam ◽  
Zulfiqar A Bhutta ◽  
...  
Keyword(s):  
Data Extraction ◽  
Meta Analysis ◽  
Pubertal Development ◽  
Tanner Stage ◽  
Pubic Hair ◽  
Cochrane Library ◽  
Self Assessment ◽  
Pubertal Stage ◽  
Tanner Staging ◽  
Stage 1

Abstract Context Clinicians, researchers, and global health advocates often include pubertal development in outcomes. However, assessments of pubertal stage can be challenging because of the sensitive nature and feasibility of clinical examinations, especially in larger settings. Objective To determine the accuracy of self-assessed Tanner staging when compared with physically assessed Tanner stages by a clinician. Data Sources MEDLINE, PubMed, Embase, Web of Science, Scopus, the Cochrane Library, CINAHL. Study Selection Studies were included if they reported 5 × 5 tables of self-assessment compared to clinician–assessment for the 5-stage Tanner scale. Data Extraction We extracted data to generate complete 5 × 5 tables for each study, including any subgroup eligible for the analysis, such as overweight/obese youth. Data Synthesis After screening, 22 studies representing 21,801 participants met our inclusion criteria for the meta-analysis. Overall agreement was moderate or substantial between the 2 assessments, with breast stage 1, female pubic hair 1, male pubic hair 1, and male pubic hair 5 having the highest agreement. When stages were collapsed into pre- (Tanner stage 1), in (stages 2,3), and completing (stages 4,5) puberty, levels of agreement improved, especially for pre- and completing pubertal development. Most included studies comprised Caucasian youth. More studies are needed which include a broader range of geographic and socioeconomic settings, as well as a greater diversity of racial/ethnic groups. Conclusions Self-assessment of puberty is most accurate when identifying Tanner stage 1, Tanner stage 5 and when development is categorized into prepuberty, in, and completing puberty phases. Use of self-assessment data should be structured accordingly. Protocol Registration PROSPERO # CRD42018100205

scholarly journals Precocious Puberty – A Case Report

2016 ◽  
Vol 30 (2) ◽  
pp. 109-112
Author(s):  
Poly Begum ◽  
Dipti Rani Saha ◽  
Md Kamrul Hassan
Keyword(s):  
Precocious Puberty ◽  
Pubertal Development ◽  
Tanner Stage ◽  
Central Precocious Puberty ◽  
Female Child ◽  
Pubic Hair ◽  
Breast Development ◽  
Average Height ◽  
Hypothalamic Pituitary Axis ◽  
Hair Development

The parents of a 04-year-old girl bring her to a Gynaecologist because of breast development, appearance of pubic hair and periodic per vaginal bleeding. Her medical history is unremarkable. The parents are of average height, and the mother reports first menstruating when she was 11 years old. At physical examination, the girl is 100 cm tall , weighs 17 kg, and has a bodymass index of 17. Her pubertal development is classified as Tanner stage 3 breast development and Tanner stage 2 pubic hair development. She was diagnosed as a case of precocious puberity. Appearance of secondary sexual development before the age of 9 in a male child and before the age of 8 in a female child is called precocious puberty. When the cause of precocious puberty is premature activation of the hypothalamic-pituitary axis, it is called central or complete precocious puberty and she was a case of central precocious puberty. After proper consult she was treated by GnRHa suppressor of pituitary till 11 years of age.Bangladesh J Obstet Gynaecol, 2015; Vol. 30(2) : 109-112

scholarly journals Phase 3 Trial of a Small-volume Subcutaneous 6-Month Duration Leuprolide Acetate Treatment for Central Precocious Puberty

2020 ◽  
Vol 105 (10) ◽  
pp. e3660-e3671
Author(s):  
Karen O Klein ◽  
Analía Freire ◽  
Mirta Graciela Gryngarten ◽  
Gad B Kletter ◽  
Matthew Benson ◽  
...  
Keyword(s):  
Precocious Puberty ◽  
Small Volume ◽  
Study Drug ◽  
External Genitalia ◽  
Central Precocious Puberty ◽  
Bone Age ◽  
Leuprolide Acetate ◽  
Open Label ◽  
Phase 3 ◽  
Pubertal Stage

Abstract Context Gonadotropin-releasing hormone agonists (GnRHas) are standard of care for central precocious puberty (CPP). A 6-month subcutaneous injection has recently been approved by the Food and Drug Administration. Objective Determine efficacy, pharmacokinetics, and safety of 6-month 45-mg subcutaneous leuprolide acetate for CPP. Design Phase 3 multicenter, open-label, single-arm study. Setting 25 sites in 6 countries. Subjects 64 GnRHa-naïve children with CPP (age: 7.5 ± 0.1 years) received study drug: 59 completed the study. Intervention(s) 2 doses of 45-mg subcutaneous leuprolide acetate (0.375 mL) at 0 and 24 weeks; children were followed for 48 weeks. Main Outcome Measure(s) Percentage of children with serum luteinizing hormone (LH) &lt;4 IU/L 30 minutes following GnRHa stimulation at week 24. Results 54/62 (87%) children achieved poststimulation LH &lt;4 IU/L at week 24; 49/56 (88%) girls and 1/2 boys maintained peak LH &lt;4 IU/L at week 48. Mean growth velocity decreased from 8.9 cm/year at week 4 to 6.0 cm/year at week 48. Mean bone age was advanced 3.0 years beyond chronological age at screening and 2.7 years at week 48. Breast pubertal stage regressed or was stable in 97% of girls and external genitalia development regressed in both boys. Adverse events were mild and did not cause treatment discontinuation. Conclusions A small volume of 45-mg subcutaneous leuprolide acetate administered at a 6-month interval effectively suppressed pubertal hormones and stopped or caused regression of pubertal progression. This long-acting GnRHa preparation of leuprolide acetate is a new, effective, and well-tolerated therapy for children with CPP.

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

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.

scholarly journals A Case of Swyer Syndrome Associated with Advanced Gonadal Dysgerminoma Involving Long Survival

2015 ◽  
Vol 8 (1) ◽  
pp. 179-184 ◽  
Author(s):  
Salete Da Silva Rios ◽  
Isabella Christina Mazzaro Monteiro ◽  
Larissa Gonçalves Braz dos Santos ◽  
Natasha Garcia Caldas ◽  
Ana Carolina Rios Chen ◽  
...  
Keyword(s):  
Sex Differentiation ◽  
Tanner Stage ◽  
Pubic Hair ◽  
Primary Amenorrhea ◽  
Histopathological Analysis ◽  
Current Case ◽  
Stage 4 ◽  
Ovarian Dysgerminoma ◽  
The University ◽  
Swyer Syndrome

Swyer syndrome is caused by abnormal sex differentiation during the embryonic period, resulting in incomplete intrauterine masculinization and undifferentiated gonads. The current case report describes a patient with Swyer syndrome associated with stage 3 gonadal dysgerminoma who has survived for 23 years. At age 18, this patient sought assistance for primary amenorrhea from the Gynecological Services Department of the University of Brasília Hospital. A physical examination revealed that the patient was at Tanner stage 4 with respect to axillary hair, breasts, and pubic hair; she presented with a eutrophic vagina and a small cervix. She was treated with a combination of estrogens and progestogens to induce cycling. Approximately 4 years later, a complex tumor was found and resected; a histopathological analysis revealed that this tumor was a right adnexal dysgerminoma with peritoneal affection. The patient was also subjected to chemotherapy. Her follow-up has continued to the present time, with no signs of tumor recurrence. In conclusion, this report describes an extremely rare case in which Swyer syndrome was associated with ovarian dysgerminoma; relative to similar patients, the described patient has survived for an unusually prolonged time.

INDEX OF SUSPICION

1992 ◽  
Vol 13 (11) ◽  
pp. 435-437
Author(s):  
Summer Smith ◽  
John L. Green ◽  
Susan K Lynch ◽  
Mark J. Polak
Keyword(s):  
Early Diagnosis ◽  
Physical Exertion ◽  
Tanner Stage ◽  
Pubic Hair ◽  
Acting Out ◽  
History Of ◽  
Prolonged Fatigue ◽  
Axillary Hair ◽  
Case Presentations ◽  
Diagnosed Diabetes

This section of Pediatrics in Review reminds clinicians of those conditions that can present in a misleading fashion and require suspicion for early diagnosis. Emphasis has been placed on conditions in which early diagnosis is important and that the general pediatrician might be expected to encounter, at least once in a while. The reader is encouraged to write possible diagnoses for each case before turning to the discussion, which is on the following page. We invite readers to contribute case presentations and discussions. Case 1 Presentation A 17-year-old boy is admitted to the hospital for evaluation and management of recently diagnosed diabetes mellitus. His mother expresses concern about his acting-out behavior and about frequent difficulties in drinking from a glass due to tremors. On examination he is found to be 68.5 inches tall, and he has a mild scoliosis. Evaluation of sexual development reveals axillary hair at Tanner stage III, pubic hair at stage V, penile length of 8 cm, left testicular volume of 3.0 x 1.8 cm, and an undescended right testicle. No breast tissue is palpable. Case 2 Presentation A 16-year-old girl is seen at your office with a history of prolonged fatigue and weakness. She has missed school frequently over the past 4 to 5 months, having had many vague complaints of "no energy," headaches, sore throats, aching knees, and the feeling that she will almost "pass out" if she does gymnastics or physical exertion of any kind.

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