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An Atlas of Lumps and Bumps, Part 34: Premature Thelarche

Alexander K.C. Leung, MD1,2, Benjamin Barankin, MD3, Joseph M. Lam, MD4, Andrew A. H. Leung, BSc5, Alex H. C. Wong6

Premature Thelarche

Premature thelarche denotes isolated breast development in girls 8 years of age or younger who do not manifest any other signs of pubertal development.1-4 Signs of pubertal development include a growth spurt, pubic and/or axillary hair development, and menarche.5 The peak prevalence is between 12 and 17 months of age.6 In one study of 318 girls between 12 and 48 months of age seen in a large midwestern city in the United States, the overall prevalence of premature thelarche was 4.7%.6 The peak prevalence by race and ethnicity was 4.2% among White non-Hispanics, 4.6% among Blacks, and 6.5% among white Hispanics.6 In a cross-sectional study of 2978 girls aged 2 to 7 years across nine cities in Zhejiang province in China, 143 girls were diagnosed with premature thelarche for a prevalence of 4.8%.7 Of the 143 girls, 100 (70%) were diagnosed with premature thelarche before the age of 2 years.7

Premature thelarche may result from an "overactivation" of the hypothalamic-pituitary axis in early childhood secondary to altered sensitivity to steroids of the hypothalamic receptors that control sexual maturation. This causes transient estrogen secretion by the follicular cysts of the ovaries and increased production of adrenal androgens from the zona reticularis.1-4 The increased adrenal androgens may serve as precursors for the peripheral conversion to estrogens. Also, increased sensitivity of breast tissue to estrogen can lead to premature thelarche.1-3,8,9

Exposure to exogenous estrogens either indirectly through the breastfeeding mother or directly through estrogen-contaminated foods, drugs, herbs, cosmetics or pesticides, may cause premature thelarche.1-3,7,8,10,11Non-estrogen-containing drugs associated with premature thelarche include spironolactone, digitalis, cimetidine, risperidone, marijuana, and phenothiazines.1-3,12 There have been conflicting reports regarding the potential of lavender essential oil and tea tree essential oil to exhibit estrogen-like or anti-androgen activities that may result in premature thelarche.13-17 However, a systematic review of 11 case reports showed that lavender essential oil does not have an estrogenic effect and that exposure to lavender essential oil or tea tree essential oil would not lead to premature thelarche.18 Other risk factors include body mass index standard deviation scores above one and early onset of menarche in the mother.7,19 Although premature thelarche is usually sporadic, a number of familial cases have been reported.1-3 Some girls with premature thelarche may have an activating mutation in the GNAS gene, which codes for a subunit of G-stimulating protein.1-3,20

The enlargement may involve only one breast, one breast asymmetrically, or both breasts symmetrically. (Fig. 1)1-3,5

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Figure 1. Enlargement may involve only one breast, one breast asymmetrically, or both breasts symmetrically.

Typically, breast hypertrophy does not proceed beyond Tanner stage III and in a unilateral case, it does not proceed beyond Tanner stage II.5,8 No significant changes of the nipples or areolae should occur.1-3 The breast size may fluctuate cyclically.1-4,19-21 The enlarged breast tissue may be tender, but this is usually transient. The vulva, labia majora, labia minora, and vagina remain infantile. No pubic or axillary hair should develop. The size of the uterus should remain consistent with the child's chronological age.1-3 Body habitus is childlike and does not show mature contours and affected children are of average height and weight. Growth and osseous maturation, the onset of puberty and menarche, and the pattern of adolescent sexual development should be normal.7,22

With few exceptions, total serum estrone and estradiol concentrations in children with premature thelarche are within the normal range for prepubertal girls. Laboratory tests are seldom indicated.

The condition is benign. And although no therapy is necessary, repeated parental reassurance is essential. Because breast enlargement may be the first sign of pseudoprecocious puberty or true puberty, a prolonged observation period monitoring other pubertal events and linear growth is indicated in all instances. Although an increase in growth velocity increases the risk of true puberty, the clinical use of increased growth velocity to differentiate premature thelarche from true puberty is still an open-ended question.23

Breast development may regress (32%), persist unchanged (57%), or progress (11%).1-3 The age of onset does not predict whether breast tissue will regress, persist, or progress.8,24 Still, overall, the prognosis is good.


AFFILIATIONS:
1Clinical Professor of Pediatrics, the University of Calgary, Calgary, Alberta, Canada
2Pediatric Consultant, the Alberta Children’s Hospital, Calgary, Alberta, Canada
3Dermatologist, Medical Director and Founder, the Toronto Dermatology Centre, Toronto, Ontario, Canada
4Associate Clinical Professor of Pediatrics, Dermatology and Skin Sciences, the University of British Columbia, Vancouver, British Columbia, Canada
5Faculty of Medicine, St. George’s University, Grenada
6Department of Family Medicine, The University of Calgary, Calgary, Alberta, Canada

CITATION:
Leung AKC, Barankin B, Lam JM, Leong KF. An Atlas of Lumps and Bumps, Part 34: premature thelarche. Consultant. 2023;63(12):e5. doi:10.25270/con.2023.12.000003

CORRESPONDENCE:
Alexander K. C. Leung, MD, #200, 233 16th Ave NW, Calgary, AB T2M 0H5, Canada (aleung@ucalgary.ca)

EDITOR’S NOTE:
This article is part of a series describing and differentiating dermatologic lumps and bumps. To access previously published articles in the series, visit: https://www.consultant360.com/resource-center/atlas-lumps-and-bumps.


REFERENCES

1. Leung AKC. Premature thelarche. In: Leung AK, ed. Common Problems in Ambulatory Pediatrics: Symptoms and Signs. New York: Nova Science Publishers, Inc; 2011:273-276.

2. Leung AKC. Premature thelarche. In: Lang F, ed. The Encyclopedia of Molecular Mechanism of Disease. Berlin: Springer-Verlag; 2009:1716-1717.

3. Leung AKC. Hormone-related disorders: 2 types of abnormal breast enlargement. Consultant for Pediatricians. 2012;8:225-226.

4. Codner E, Román R. Premature thelarche from phenotype to genotype. Pediatr Endocrinol Rev. 2008;5(3):760-765.

5. Xu Y, Li Y, Liang S, Li G. Differential analysis of nutrient intake, insulin resistance and lipid profiles between healthy and premature thelarche Chinese girls. Ital J Pediatr. 2019;45(1):166. doi:10.1186/s13052-019-0758-z.

6. Curfman AL, Reljanovic SM, McNelis KM, et al. Premature thelarche in infants and toddlers: prevalence, natural history and environmental determinants. J Pediatr Adolesc Gynecol. 2011;24(6):338-341. doi:10.1016/j.jpag.2011.01.003.

7. Zhang J, Xu J, Liu L, Xu X, Shu X, Yang Z, et al. The prevalence of premature thelarche in girls and gynecomastia in boys and the associated factors in children in Southern China. BMC Pediatr. 2019;19(1):107. doi:10.1186/s12887-019-1426-6.

8. Khokhar A, Mojica A. Premature thelarche. Pediatr Ann. 2018;47(1):e12-e15. doi:10.3928/19382359-20171214-01.

9. Uçar A, Saka N, Baş F, Bundak R, Günöz H, Darendeliler F. Is premature thelarche in the first two years of life transient? J Clin Res Pediatr Endocrinol. 2012;4(3):140-145. doi: 0.4274/Jcrpe.709.

10. Coppola L, Tait S, Ciferri L, et al. Integrated approach to evaluate the association between exposure to pesticides and idiopathic premature thelarche in girls: The PEACH project. Int J Mol Sci. 2020;21(9):3282. doi:10.3390/ijms21093282.

11. Okdemir D, Hatipoglu N, Kurtoglu S, Akın L, Kendirci M. Premature thelarche related to fennel tea consumption? J Pediatr Endocrinol Metab. 2014;27(1-2):175-179. doi:10.1515/jpem-2013-0308.

12. White AM, Singh R, Rais T, Coffey BJ. Premature thelarche in an 8-year-old girl following prolonged use of risperidone. J Child Adolesc Psychopharmacol. 2014;24(4):228-230. doi:10.1089/cap.2014.2442.

13. Giroux JM, Orjubin M. Letter to the editor: "Lavender products associated with premature thelarche and prepubertal gynecomastia: Case reports and endocrine-disrupting chemical activities". J Clin Endocrinol Metab. 2020;105(7):e2677-2678. doi:10.1210/clinem/dgaa226.

14. Larkman T. Letter to the editor: "Lavender products associated with premature thelarche and 1 prepubertal gynecomastia: Case reports and endocrine-disrupting chemical activities". J Clin Endocrinol Metab. 2020;105(9):dgaa392. doi:10.1210/clinem/dgaa392.

15. Linklater A, Hewitt JK. Premature thelarche in the setting of high lavender oil exposure. J Paediatr Child Health. 2015 Feb;51(2):235. doi:10.1111/jpc.12837.

16. Ramsey JT, Li Y, Arao Y, et al. Lavender products associated with premature thelarche and prepubertal gynecomastia: Case reports and endocrine-disrupting chemical activities. J Clin Endocrinol Metab. 2019;104(11):5393-5405. doi:10.1210/jc.2018-01880.

17. Tyler Ramsey J, Diaz A, Korach KS. Response to Letter to the Editor: "Lavender products associated with premature thelarche and prepubertal gynecomastia: Case reports and EDC activities". J Clin Endocrinol Metab. 2020;105(7):e2692-2693. doi:10.1210/clinem/dgaa227.

18. Hawkins J, Hires C, Dunne E, Baker C. The relationship between lavender and tea tree essential oils and pediatric endocrine disorders: A systematic review of the literature. Complement Ther Med. 2020;49:102288. doi:10.1016/j.ctim.2019.102288.

19. 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;101 (2) :e71-e75. doi:10.1111/j.1651-2227.2011.02444.x.

20. Román R, Johnson MC, Codner E, Boric MA, áVila A, Cassorla F. Activating GNAS1 gene mutations in patients with premature thelarche. J Pediatr. 2004;145(2):218-222. doi:10.1016/j.jpeds.2004.05.025.

21. Diamantopoulos S, Bao Y. Gynecomastia and premature thelarche: a guide for practitioner. Pediatr Rev. 2007;28(9):e57-68. doi:10.1542/pir.28-9-e57.

22. Çatlı G, Erdem P, Anık A, Abacı A, Böber E. Clinical and laboratory findings in the differential diagnosis of central precocious puberty and premature thelarche. Turk Pediatri Ars. 2015;50(1):20-26. doi10.5152/tpa.2015.2281.

23. Varimo T, Huttunen H, Miettinen PJ, et al. Precocious puberty or premature thelarche: Analysis of a large patient series in a single tertiary center with special emphasis on 6- to 8-year-old girls. Front Endocrinol (Lausanne). 2017;8:213. doi:10.3389/fendo.2017.00213.

24. 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;156(3):466-471. doi:10.1016/j.jpeds.2009.09.071.


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