Precocious Puberty: Causes, Consequences, Daily Environmental Factors, and the need for Community/Societal Support

Precocious puberty, otherwise described as a group of medical conditions that cause early puberty onset, such as a pre-adolescent boy presenting with adult pattern of penile and testicular enlargement or a pre-adolescent girl presenting with mature breast development and onset of menses. Although the sexual and physical characteristics for this condition are well-described in medical literature, the causes are very rarely known. Nevertheless, it has substantial impacts on children’s lives. This is a review on sexual development, premature sexual development, the social complications children suffer from due to early onset puberty, and the associations with daily environmental exposures as possible influences for developing precocious puberty.

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MKRN3 Levels in Girls with Central Precocious Puberty during GnRHa Treatment: A Longitudinal Study

Hormone Research in Paediatrics ◽

10.1159/000493134 ◽

2018 ◽

Vol 90 (3) ◽

pp. 190-195 ◽

Cited By ~ 1

Author(s):

Anna Grandone ◽

Grazia Cirillo ◽

Marcella Sasso ◽

Gianluca Tornese ◽

Caterina Luongo ◽

...

Keyword(s):

Precocious Puberty ◽

Ring Finger ◽

Central Precocious Puberty ◽

Serum Levels ◽

Breast Development ◽

Control Group ◽

Ring Finger Protein ◽

Finger Protein ◽

17Β Estradiol ◽

Puberty Onset

Background: Recently, mutations of makorin RING finger protein 3 (MKRN3) have been identified in familial central precocious puberty (CPP). Serum levels of this protein decline before the pubertal onset in healthy girls and boys and are lower in patients with CPP compared to prepubertal matched pairs. The aim of our study was to investigate longitudinal changes in circulating MKRN3 levels in patients with CPP before and during GnRH analogs (GnRHa) treatment. Methods: We performed a longitudinal prospective study. We enrolled 15 patients with CPP aged 7.2 years (range: 2–8) with age at breast development onset < 8 years and 12 control girls matched for the time from puberty onset (mean age 11.8 ± 1.2 years). Serum values of MKRN3, gonadotropins, and 17β-estradiol were evaluated before and during treatment with GnRHa (at 6 and 12 months). The MKRN3 gene was genotyped in CPP patients. In the girls from the control group, only basal levels were analyzed. Results: No MKRN3 mutations were found among CPP patients. MKRN3 levels declined significantly from baseline to 6 months of GnRHa treatment (p = 0.0007) and from 6 to 12 months of treatment (p = 0.003); MKRN3 levels at 6 months were significantly lower than in the control girls (p < 0.0001). Conclusions: We showed that girls with CPP had a decline in peripheral levels of MKRN3 during GnRHa treatment. Our data suggest a suppression of MKRN3 by continuous pharmacological administration of GnRHa.

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Early puberty in end stage renal failure and renal transplant recipients

Journal of Pediatric Endocrinology and Metabolism ◽

10.1515/jpem-2019-0050 ◽

2019 ◽

Vol 32 (6) ◽

pp. 577-583

Author(s):

Carmit Avnon Ziv ◽

Shimrit Tzvi-Behr ◽

Efrat Ben-Shalom ◽

Choni Rinat ◽

Rachel Becker-Cohen ◽

...

Keyword(s):

Renal Transplantation ◽

Renal Transplant ◽

Precocious Puberty ◽

Breast Development ◽

Delayed Puberty ◽

Renal Transplant Recipients ◽

Transplant Recipients ◽

Early Puberty ◽

Release Formulation ◽

Triptorelin Acetate

Abstract Background Delayed puberty and hypogonadism are common in children with chronic kidney disease and in renal transplant recipients, but precocious puberty has rarely been reported in these populations. We describe six girls with precocious and/or early-onset, rapidly progressive puberty before and following renal transplantation. Methods Of 112 children under the age of 18 years (67 boys, 45 girls) who received renal transplants between 2010 and 2018, six girls presented with precocious or rapidly progressive early puberty at ages 6–7/12, 7–2/12, 7–4/12, 8, 8–8/12 and 8–11/12 years. Clinical evaluation included measurements of height, weight, body mass index (BMI), Tanner staging and bone age assessment. Gonadotropin responses to intravenous gonadotropin releasing hormone (GnRH) or intramuscular triptorelin acetate were determined. Results Tanner breast stage 3 was noted at 2–6 years following renal transplantation in five girls, four with preserved kidney function. One girl began puberty before renal transplantation. Peak luteinizing hormone (LH) and follicular stimulating hormone (FSH) levels were 6.5, 20.2, 7.83, 19.1, 9 and 2.2 mIU/mL and 13, 8.3, 8.01, 7.5, 8.1 and 7.7 mIU/mL, respectively. Treatment with an intramuscular slow-release formulation of triptorelin acetate every 4 weeks slowed progression of breast development. Conclusions Although delayed puberty is more common in children with renal disease, precocious puberty can also be seen. Evaluation of growth and puberty by a pediatric endocrinologist should be part of the routine care for all children following kidney transplantation.

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Organochloride Pesticides in Macedonian Girls With Premature Sexual Development

Balkan Journal of Medical Genetics ◽

10.2478/v10034-007-0008-3 ◽

2007 ◽

Vol 10 (1) ◽

pp. 43-48

Author(s):

M Krstevska-Konstantinova ◽

M Kocova ◽

C Charlier ◽

J Bourguignon

Keyword(s):

Precocious Puberty ◽

Sexual Development ◽

Positive Association ◽

Serum Levels ◽

Mean Value ◽

Control Group ◽

Early Puberty ◽

Premature Thelarche ◽

Negative Results ◽

Organochloride Pesticides

Organochloride Pesticides in Macedonian Girls With Premature Sexual DevelopmentPremature sexual development (PSD) in girls describes the appearance of secondary sexual signs before the age of 8 years. Early puberty is diagnosed if pubertal signs appear between the age of 8 and 9 years. We found a positive association between the levels of organochloride pesticides (p,p'-DDE) in precocious puberty in girls adopted from developing countries and significantly higher levels than in native Belgian girls with the same condition.We have compared the serum levels of eight p,p'- DDE in 56 Macedonian girls with PSD and a control group of 24 normal, age-matched girls, using a gas chromatographic analyzer coupled to a tandem mass spectrometer detector. Of the 56 girls with PSD, 42 had premature thelarche, five had early puberty, and nine had precocious puberty of idiopathic (n = 8) or organic (n = 1) origin. We found traces of p,p'- DDE in nine girls (16%) and negative results in 41 (73%), while the remaining six (10%) had a mean level of 1.17 ± 0.7 μg/L. In the control group, traces were found in one girl (4%) and negative results in 18 (75%), while the remaining five (20%) had a mean level of 1.18 ± 0.6 μg/L. We found elevated levels of lindane in the girls with PSD (mean value 1.2 ± 0.8) and significantly higher levels in the control group (1.4 ± 0.8) (p <0.05). We concluded that Macedonian girls with PSD do not have higher levels of p,p'-DDE in their serum than the normal controls. However, the elevated levels of lindane in this population should be further investigated.

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Toward More Targeted and Cost-Effective Gonadotropin-Releasing Hormone Analog Treatment in Girls with Central Precocious Puberty

Hormone Research in Paediatrics ◽

10.1159/000491103 ◽

2018 ◽

Vol 90 (1) ◽

pp. 1-7 ◽

Cited By ~ 8

Author(s):

Paul B. Kaplowitz ◽

Philippe F. Backeljauw ◽

David B. Allen

Keyword(s):

Precocious Puberty ◽

Cost Effective ◽

Central Precocious Puberty ◽

Gonadotropin Releasing Hormone ◽

Healthy Children ◽

Defined Benefit ◽

Early Puberty ◽

Releasing Hormone ◽

Early Maturation ◽

Puberty Onset

The use of gonadotropin-releasing hormone analogs (GnRHa) for the treatment of central precocious puberty (CPP), especially in girls, has increased rapidly in recent years. In the context of a secular trend towards earlier puberty onset, many girls now treated for CPP are healthy children experiencing puberty onset within the early end of the normal range. Justifications for GnRHa treatment include the preservation of adult height (AH) potential and the alleviation of presumed distress of early maturation and menarche. With a case of a family requesting treatment for an 8-year-old girl in early puberty as a background, studies of the effect of untreated CPP and of GnRHa treatment of CPP on AH are reviewed. In addition, the limited evidence relating CPP to significant psychological distress – in part due to early menses, and for the amelioration of such distress by GnRHa treatment – is discussed. Taken together, current information suggests that for girls with mildly early onset of puberty (ages 7–9 years), an informed assent discussion with the family should include the consideration of reassurance and observation for many girls who might otherwise receive 2–4 years of GnRHa treatment for a poorly defined benefit and at a cost of at least $20–30,000 per year.

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An Approach to the Evaluation and Management of the Obese Child with Early Puberty

Journal of the Endocrine Society ◽

10.1210/jendso/bvab173 ◽

2021 ◽

Author(s):

Christine B Tenedero ◽

Krista Oei ◽

Mark R Palmert

Keyword(s):

Precocious Puberty ◽

Weight Status ◽

Adult Height ◽

Age At Onset ◽

False Negative ◽

Central Precocious Puberty ◽

Bone Age ◽

Breast Development ◽

Early Puberty ◽

Line Test

Abstract With the decline in age at onset of puberty and increasing prevalence of childhood obesity, early breast development in young, obese girls has become a more frequent occurrence. Here, we examine available literature to answer a series of questions regarding how obesity impacts the evaluation and management of precocious puberty. We focus on girls as the literature is more robust, but include boys where literature permits.Suggestions include: (1) Age cut-offs for evaluation of precocious puberty should not differ substantially from those used for non-obese children. Obese girls with confirmed thelarche should be evaluated for gonadotropin-dependent, central precocious puberty (CPP) to determine if further investigation or treatment is warranted. (2) Basal luteinizing hormone (LH) levels remain a recommended first-line test. However, if stimulation testing is utilized, there is a theoretical possibility that the lower peak LH responses seen in obesity could lead to a false negative result. (3) Advanced bone age (BA) is common among obese girls even without early puberty; hence its diagnostic utility is limited. (4) Obesity does not eliminate the need for MRI in girls with true CPP. Age and clinical features should determine who warrants neuroimaging. (5) BA can be used to predict adult height in obese girls with CPP to inform counselling around treatment. (6) Use of gonadotropin-releasing hormone analogues (GnRHa) leads to increased adult height in obese girls. (7) Obesity should not limit GnRHa use as these agents do not worsen weight status in obese girls with CPP.

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The Regulatory Mechanism of Water Activities on Aflatoxins Biosynthesis and Conidia Development, and Transcription Factor AtfB Is Involved in This Regulation

Toxins ◽

10.3390/toxins13060431 ◽

2021 ◽

Vol 13 (6) ◽

pp. 431

Author(s):

Longxue Ma ◽

Xu Li ◽

Xiaoyun Ma ◽

Qiang Yu ◽

Xiaohua Yu ◽

...

Keyword(s):

Transcription Factor ◽

Transcription Factors ◽

Environmental Factors ◽

Health Risks ◽

Sexual Development ◽

Regulatory Mechanism ◽

Food Storage ◽

Economic Losses ◽

Transcriptional Level ◽

Conidia Production

Peanuts are frequently infected by Aspergillus strains and then contaminated by aflatoxins (AF), which brings out economic losses and health risks. AF production is affected by diverse environmental factors, especially water activity (aw). In this study, A. flavus was inoculated into peanuts with different aw (0.90, 0.95, and 0.99). Both AFB1 yield and conidia production showed the highest level in aw 0.90 treatment. Transcriptional level analyses indicated that AF biosynthesis genes, especially the middle- and later-stage genes, were significantly up-regulated in aw 0.90 than aw 0.95 and 0.99. AtfB could be the pivotal regulator response to aw variations, and could further regulate downstream genes, especially AF biosynthesis genes. The expressions of conidia genes and relevant regulators were also more up-regulated at aw 0.90 than aw 0.95 and 0.99, suggesting that the relative lower aw could increase A. flavus conidia development. Furthermore, transcription factors involved in sexual development and nitrogen metabolism were also modulated by different aw. This research partly clarified the regulatory mechanism of aw on AF biosynthesis and A. flavus development and it would supply some advice for AF prevention in food storage.

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PELVIC ULTRASONOGRAPHY IN PREMATURE THELARCHE (PT), PREMATURE ADRENARCHE (PA), PRECOCIOUS PUBERTY (PP), EARLY PUBERTY (EP) AND OTHER ENDOCRINE ABNORMALITIES

Pediatric Research ◽

10.1203/00006450-198801000-00163 ◽

1988 ◽

Vol 23 (1) ◽

pp. 128-128

Author(s):

S Salardi ◽

L F Orsini ◽

A Reggiani ◽

S Partesotti ◽

E Frejaville ◽

...

Keyword(s):

Precocious Puberty ◽

Early Puberty ◽

Premature Thelarche ◽

Premature Adrenarche ◽

Pelvic Ultrasonography

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Hypothyroidism and Precocious Sexual Development: Another Case

PEDIATRICS ◽

10.1542/peds.52.1.149 ◽

1973 ◽

Vol 52 (1) ◽

pp. 149-150

Author(s):

Adolfo Perez Comas

Keyword(s):

Weight Gain ◽

Short Stature ◽

Growth Retardation ◽

Sexual Development ◽

Similar Case ◽

Pubic Hair ◽

Breast Development ◽

Attention Span ◽

Admission Data ◽

Irregular Menses

Recently, an article in Pediatrics by Costin et al.1 described two new cases of hypothyroidism and precocious sexual development. I would like to report another similar case with our available data. M.L.M., a 13-year-old girl was first seen by us at age 12-4/12 for short stature. Her history included growth retardation, diminution of attention span, somnolence, anorexia with weight gain, and constipation beginning between ages 4 to 6. At 9½ years of age irregular menses began, breast development was first noticed at 10 years, and pubic hair at 11½ years. Her initial admission data are in Table I.

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Inequity in Child Health as a Global Issue

PEDIATRICS ◽

10.1542/peds.112.s3.739 ◽

2003 ◽

Vol 112 (Supplement_3) ◽

pp. 739-741

Author(s):

Tony Waterston

Keyword(s):

Health Care ◽

Developing Countries ◽

Child Health ◽

Environmental Factors ◽

Clean Water ◽

Annual Income ◽

Dietary Energy ◽

Refugee Status ◽

Global Issue ◽

The Social

The Issue. Poverty, violence, lack of education, abuse and exploitation, and refugee status are among the primary determinants of the health of children worldwide. There are 1.3 billion people living on less than US $1 per day. Half the world’s population, 3 billion people, live on less than US $1.30 per day. Of the 4.4 billion people who live in developing countries, 60% lack access to sanitation, 33% lack clean water, 20% have no health care, and 20% do not have enough dietary energy and protein.1 The world’s 225 richest people have a combined wealth equivalent to the annual income of the poorest 2.5 billion people, nearly half of the world’s population.1 This article describes a number of the social, political, and environmental factors impacting children in the developing (southern hemisphere) world and how these are affected by actions taken in the developed (northern hemisphere) world.

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