Follow-up of Girls With Premature Thelarche and Precocious Puberty

Precocious Puberty Clinical Trial

Official title:

Follow-up of Girls With Premature Thelarche and Precocious Puberty: a Clinical and Paraclinical Study of Girls With Thelarche and Healthy Controls

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT01944475
• Other study ID #: 1-10-72-186-13
• Status: Not yet recruiting
• Phase: N/A
• First received: September 5, 2013
• Last updated: September 12, 2013
• Start date: September 2013
• Est. completion date: September 2014

Study information

• Verified date: September 2013
• Source: University of Aarhus
• Contact: Niels H Birkebæk, Dr.med, PhD
• Phone: +45 50860090
• Email: nielbirk[@]rm.dk
• Is FDA regulated: No
• Health authority: Denmark: The Regional Committee on Biomedical Research Ethics
• Study type: Observational [Patient Registry]

Clinical Trial Summary

Precocious puberty - the onset of signs of puberty before 8 years of age in girls - is be physically and emotionally devastating for kids and is sometimes caused by an underlying and medical condition. One sign of precocious puberty in small girls is breast development (thelarche). This can persist without other physical changes of puberty, it may continue into precocious puberty, or it may disappear. This project will improve the diagnostics of precocious puberty in girls and improve our ability to identify which girls with thelarche, who will develop precocious puberty and need medical treatment.

Description:

The purpose of the study is

1. To conduct an epidemiological study in which characteristics of 0-6 year-old girls with either premature thelarche or precocious puberty are described (as specified below)

2. To conduct a clinical and para-clinical re-examination of the before-mentioned (1))0-6 year-old girls

3. To compare the clinical and paraclinical parameters in point 1) mentioned 0-6 year-old girls with a control group of children at the same age, whiteout thelarche and precocious puberty. (Local Ethics Committee has approved the study of the control group, case number 1-10-72-631-12.)

The study includes a chart review of registered 0-6 year-old girls diagnosed with premature thelarche or precocious puberty from 1998 and until today at Dept. of Pediatrics A, AUH Skejby. The cohort has not earlier been examined and the number of girls in the cohort is estimated from our clinical experience with this patient group to be about 50 in total. The following characteristics from the patients records will be registered in a database:

Age at diagnosis, anthropometry (height and weight), Tanner stage - breast, Tanner stage - pubic hair, GnRH test (LH and FSH response), thyroid parameters, estrogen, prolactin, 17OHP, androstenedione, dihydroepiandrosteron (DHEA), testosterone, inhibin B, SHBG, AFP, kisspeptin, human chorionic gonadotropin (HCG), bone age, MRI of the cerebrum, US of internal genitalia, and exposures to environmental chemicals known to affect secondary sex characteristics.

The database will be developed in the program Access. The results will be reported as mean and standard deviation and minimum and maximum values for each age group by Tanner stage, if the data are normally distributed. Non-normally distributed data will be given as median and confidence intervals as well as minimum and maximum values for each Tanner stage. Data for previously studied children with suspected precocious puberty, will be reported in the same way. Statistical comparison between the groups will be made with u-paired t-test or equivalent non-parametric test, if the data is not normally distributed.

The Data Unit at Aarhus University Hospital, Skejby, identifies 0-6 year-old girls with diagnoses premature thelarche or precocious puberty in 1998 and onwards. Girls below 8 years of age at baseline of the project (1st of September 2013) will be contacted and requested to participate in a re-examination.

The follow-up is a clinical and paraclinical re-examination, where the following parameters are measured: anthropometry (height and weight), skinfold thickness, Tanner stage, bone age, GnRH test, p-estrogen, p-testosterone , p-SHBG, p- androstenedione, p-dihydroandrostendion, p-inhibin B, p-thyroid parameters, ultrasound examination of the genitalia interna and a blood sample for studies of polymorphism in the estrogen receptor gene and aromatase enzyme gene.

If the girls are unable or unwilling to attend the reexamination, they are requested to fill out a questionnaire instead as follows:

• name, social security number, date of completion the questionnaire

• current height, current weight, birth weight, origin

• date of onset of puberty if started, current pubertal development, menarche

• diseases/admissions

Regarding the mother:

• age at menarche, medicine during pregnancy/breastfeeding, diet during pregnancy/breastfeeding, use of cosmetics /cream/shampoo during pregnancy,

Regarding the family:

• others with early breast development/early puberty

The project is conducted at Dept. of Pediatrics A, Aarhus University Hospital, Skejby, Skejbygårdsvej 100, 8200 Aarhus N. The other pediatric wards in the Region of Midtjylland (located in Randers, Viborg and Herning) will be included in the project if they prefer to participate.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 50
• Est. completion date: September 2014
• Est. primary completion date: September 2014
• Accepts healthy volunteers: No
• Gender: Female
• Age group: N/A to 8 Years

Eligibility

Inclusion Criteria:

• Clinical diagnosis of precocious puberty or premature thelarche

• 0-6 year old girls at time of diagnosis for the medical record review

• 0-8 year old girls at baseline for the re-examination

Exclusion Criteria:

Study Design

Observational Model: Case-Only

Related Conditions & MeSH terms

• Excess; Development, Breast
• Precocious Puberty
• Puberty, Precocious

Locations

Country	Name	City	State
Denmark	Børneafdelingen A, AUH, Skejby	Aarhus N
Denmark	Børneafdelingen A, AUH, Skejby	Aarhus N

Sponsors (2)

Lead Sponsor	Collaborator
University of Aarhus	Aarhus University Hospital Skejby

Country where clinical trial is conducted

Denmark, 

References & Publications (10)

Atay Z, Turan S, Guran T, Furman A, Bereket A. The prevalence and risk factors of premature thelarche and pubarche in 4- to 8-year-old girls. Acta Paediatr. 2012 Feb;101(2):e71-5. doi: 10.1111/j.1651-2227.2011.02444.x. Epub 2011 Sep 23. — View Citation

Carel JC, Lahlou N, Roger M, Chaussain JL. Precocious puberty and statural growth. Hum Reprod Update. 2004 Mar-Apr;10(2):135-47. Review. — View Citation

Carel JC, Léger J. Clinical practice. Precocious puberty. N Engl J Med. 2008 May 29;358(22):2366-77. doi: 10.1056/NEJMcp0800459. Review. — View Citation

Curfman AL, Reljanovic SM, McNelis KM, Dong TT, Lewis SA, Jackson LW, Cromer BA. Premature thelarche in infants and toddlers: prevalence, natural history and environmental determinants. J Pediatr Adolesc Gynecol. 2011 Dec;24(6):338-41. doi: 10.1016/j.jpag.2011.01.003. — View Citation

de Vries L, Guz-Mark A, Lazar L, Reches A, Phillip M. Premature thelarche: age at presentation affects clinical course but not clinical characteristics or risk to progress to precocious puberty. J Pediatr. 2010 Mar;156(3):466-71. doi: 10.1016/j.jpeds.2009.09.071. Epub 2009 Nov 14. — View Citation

Herman-Giddens ME, Slora EJ, Wasserman RC, Bourdony CJ, Bhapkar MV, Koch GG, Hasemeier CM. Secondary sexual characteristics and menses in young girls seen in office practice: a study from the Pediatric Research in Office Settings network. Pediatrics. 1997 Apr;99(4):505-12. — View Citation

Houk CP, Kunselman AR, Lee PA. The diagnostic value of a brief GnRH analogue stimulation test in girls with central precocious puberty: a single 30-minute post-stimulation LH sample is adequate. J Pediatr Endocrinol Metab. 2008 Dec;21(12):1113-8. — View Citation

Michaud PA, Suris JC, Deppen A. Gender-related psychological and behavioural correlates of pubertal timing in a national sample of Swiss adolescents. Mol Cell Endocrinol. 2006 Jul 25;254-255:172-8. Epub 2006 Jun 27. — View Citation

Teilmann G, Pedersen CB, Jensen TK, Skakkebaek NE, Juul A. Prevalence and incidence of precocious pubertal development in Denmark: an epidemiologic study based on national registries. Pediatrics. 2005 Dec;116(6):1323-8. — View Citation

Tremblay L, Frigon JY. Precocious puberty in adolescent girls: a biomarker of later psychosocial adjustment problems. Child Psychiatry Hum Dev. 2005 Fall;36(1):73-94. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Exposure		Up till age 21.0 years	No
Primary	Tanner stage (breast and pubic hair)		Up till age 21.0 years	No
Secondary	weight		up till age 21.0 years	No
Secondary	height		Up till age 21.0 years	No
Secondary	Bone age		Up till age 21.0 years	No
Secondary	LH-peak after GnRH-test		Up till age 21.0 years	No
Secondary	Hormones (estrogen, prolactin, 17OHP, androstrendion, DHEA, testosterone, inhibin B, SHBG, AFP, kisspeptin, HCG, thyroid hormones)		Up till age 21.0 years	No
Secondary	Ultrasound of the internal genitalia		Up till age 21.0 years	No