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CASE REPORT
Year : 2017  |  Volume : 44  |  Issue : 2  |  Page : 114-116

Isolated premature thelarche: A normal growth variant


1 Department of Pediatrics, Jawaharlal Nehru Medical College, KLE University, Belagavi, Karnataka, India
2 Department of Endocrinology, Jawaharlal Nehru Medical College, KLE University, Belagavi, Karnataka, India

Date of Web Publication11-Oct-2017

Correspondence Address:
Prithi R Inamdar
A14/2, JNMC Quaters, Nehru Nagar, Belagavi - 590 010, Karnataka
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jss.JSS_5_17

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  Abstract 

Premature thelarche is frequently considered to be a normal variant of growth and development as it shows spontaneous remission in majority of cases. However, progression to precocious puberty is seen in up to 13% of cases. We present a case of 11-month-old female child with a history of progressive breast enlargement. Investigations revealed normal bone age and hormonal evaluation. This case emphasizes the importance of simple baseline investigations to differentiate precocious puberty and premature thelarche, thus ameliorating the parental anxiety.

Keywords: Bone age, precocious puberty, premature thelarche


How to cite this article:
Inamdar PR, Bellad RM, Herekar VR, Sarvi MR, Ghatnatti VB, Shah HA. Isolated premature thelarche: A normal growth variant. J Sci Soc 2017;44:114-6

How to cite this URL:
Inamdar PR, Bellad RM, Herekar VR, Sarvi MR, Ghatnatti VB, Shah HA. Isolated premature thelarche: A normal growth variant. J Sci Soc [serial online] 2017 [cited 2020 Sep 18];44:114-6. Available from: http://www.jscisociety.com/text.asp?2017/44/2/114/216502


  Introduction Top


Precocious puberty is the premature activation of the hypothalamic-pituitary-gonadal (HPG) axis at an inappropriate chronological age before 8 years in girls and 9 years in boys.[1] Precocious puberty is classified as central where the development of secondary sexual character is due to premature activation of HPG axis and peripheral, which is due to exogenous excess of hormones outside the HPG aixs.[2] Thelarche is a first sign of puberty in females.

Isolated premature thelarche is seen in 4.7% of female children and in up to 14% of all patients referred to endocrinology clinic for evaluation of precocious puberty.[3],[4] In premature thelarche, bone age corresponds with the chronological age and other signs of puberty such as pubarche and menarche are absent as against precocious puberty where there is an advanced bone age with pubertal developments.[1] Premature thelarche is frequently considered to be a normal variant of growth and development as it shows spontaneous remission in majority of cases. However, progression to precocious puberty is seen in up to 13% of cases.[3]

We present this case to emphasize the importance of simple baseline investigations to differentiate precocious puberty and premature thelarche, thus ameliorating the parental anxiety.


  Case Report Top


An 11-month-old female child presented to us with bilateral, progressive, symmetrical enlargement of breast noticed by her mother for the past 3 months. There was no associated pubic or axillary hair growth or per vaginal bleed. She was first born to parents of nonconsanguineous marriage. The antenatal period was unremarkable. She was full term at birth but being small for gestational age (birth weight of 1.7 kg). Immediate postnatal life was uneventful. Child was exclusively breast fed for 6 months and at present was on breast feeding plus age appropriate complementary feeding. Mother was not on any contraceptive hormonal medications. There was no history of any other source of exposure to hormonal medications.

At presentation, child had normal vital parameters and was normotensive. Physical examination revealed pallor. Her anterior fontanel was 1 cm × 1 cm open and level, eye examination was normal without any evidence of papilledema. There was bilateral nontender enlargement of breast buds with elevated breast tissue which extended beyond the borders of the areola. [Figure 1] shows Areola which was well defined but in contour with surrounding breast corresponding to stage 3 of Tanners classification. There was no pubic and axillary hair. External genitalia were normal female structure. Her present weight was 6.8 kg and length was 75 cm (both being normal according to the WHO growth charts). Past records of height were not available to assess the height velocity.
Figure 1: Lateral view of child with thelarche stage 3 by tanners with absent axillary hair

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Investigations revealed low hemoglobin of 7% g with microcytic hypochromic picture on peripheral smear. Electrolytes were normal (Na - 144 mEq/l and K - 5.01 mEq/l). Her early morning levels of estradiol (E2) were 5 pg/ml (reference range of undetectable 20 pg/ml), luteinizing hormone (LH) was 0.1 mIU/ml (0.1–3.3 mIU/ml), follicle-stimulating hormone (FSH) was 1.19 mIU/ml (0.1–7.1 mIU/ml), and prolactin was 9.26 ng/ml (3.2–20 ng/mL). Ultrasound abdomen demonstrated normal uterus and ovary. [Figure 2] shows normal bone age with two carpal bones corresponding with the chronological age.
Figure 2: X-ray wrist with two carpal bones, corresponding with the chronological age

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In the absence of other signs of puberty and since bone age was normal, a diagnosis of isolated premature thelarche was made and the patient was advised to follow-up subsequently.


  Discussion Top


Premature thelarche is defined as isolated breast development in girls under 8 years of age.[5] Although the etiology of premature thelarche is unclear, various postulated mechanisms are increased sensitivity of breast tissue to estradiol (E2), transient E2 secretion from ovarian cysts, dietary estrogen intake, and transient activation of the HPG axis.[6] It is frequently seen in girls below 2 years of age.[7] Early age of onset of thelarche is generally associated with spontaneous regression. Onset of thelarche latter at 5–7 years is more likely to progress to central precocious puberty.[8] Our child presented at 11 months suggesting a strong possibility of regression of thelarche.

Precocious puberty can cause rapid bone maturation thus reducing the final height, inappropriate body appearance, and psychological behavioral abnormalities, thus warranting early diagnosis and intervention. Hence, it is imperative to be able to identify precocious puberty from the all cases of premature thelarche.

The prime investigation to be done is the estimation of the bone age. In our case, bone age determined by wrist X-ray was corresponding to chronological age. Advancement of bone age of more than 1 year or greater than two standard deviation is considered as on indicator of precocious puberty.[9] However, in girls below 2 years, growth velocity has higher sensitivity for systemic estrogen effects.[6] The gold standard test for differentiating precocious puberty from premature thelarche is a gonadotropin-releasing hormone (GnRH)-stimulated LH response demonstrating an increased basal and stimulated LH response and an increased basal and stimulated LH/FSH ratio.[10] However, it accounts for significant cost and repeated venepunctures. Studies have demonstrated a single basal LH >0.3 IU/L, a significant indicator of progression of puberty.[6] A rational approach is to reserve GnRH stimulation test for girls with an advanced bone age, growth velocity of more than 1 standard deviation, and basal LH of more than 0.3 IU/L. Our child had a LH level of 0.1 IU/L. We deferred GnRH stimulation test, as basal LH was low. For others, the test would be indicated only if they demonstrate advancement of signs of puberty.[6] Newer markers identified for the differential diagnosis of premature thelarche and precocious puberty are serum kisspeptin, leptin, and neurokinin B.[11] Their utility in clinical setting needs to be identified.

Although it is presumed that onset of thelarche <2 years of age undergo spontaneous remission, large studies have demonstrated resolution in only 60% of the patients with onset <2 years of age with 18.4% patients developing central precocious puberty.[12] Our child is being followed up for any progression of thelarche.

We conclude that premature thelarche should prompt the clinician to do a careful baseline evaluation and judicious reassurance of the parents who tend to be highly anxious regarding thelarche. At the same time, it warrants careful follow-up for nonregression or progression to puberty.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
  References Top

1.
Latronico AC, Brito VN, Carel JC. Causes, diagnosis, and treatment of central precocious puberty. Lancet Diabetes Endocrinol 2016;4:265-74.  Back to cited text no. 1
[PUBMED]    
2.
Kletter GB, Klein KO, Wong YY. A pediatrician's guide to central precocious puberty. Clin Pediatr (Phila) 2015;54:414-24.  Back to cited text no. 2
[PUBMED]    
3.
Pasquino AM, Pucarelli I, Passeri F, Segni M, Mancini MA, Municchi G, et al. Progression of premature thelarche to central precocious puberty. J Pediatr 1995;126:11-4.  Back to cited text no. 3
    
4.
Atta I, Laghari TM, Khan YN, Lone SW, Ibrahim M, Raza J. Precocious puberty in children. J Coll Physicians Surg Pak 2015;25:124-8.  Back to cited text no. 4
    
5.
Apter D, Bützow TL, Laughlin GA, Yen SS. Gonadotropin-releasing hormone pulse generator activity during pubertal transition in girls: Pulsatile and diurnal patterns of circulating gonadotropins. J Clin Endocrinol Metab 1993;76:940-9.  Back to cited text no. 5
    
6.
Uçar A, Saka N, Baş F, Bundak R, Günöz H, Darendeliler F, et al. Is premature thelarche in the first two years of life transient? J Clin Res Pediatr Endocrinol 2012;4:140-5.  Back to cited text no. 6
    
7.
Berberoğlu M. Precocious puberty and normal variant puberty: Definition, etiology, diagnosis and current management. J Clin Res Pediatr Endocrinol 2009;1:164-74.  Back to cited text no. 7
    
8.
Takakuwa S. Premature thelarche in later childhood demonstrates a pubertal response to GnRH stimulation test at one year after breast development. Clin Pediatr Endocrinol 2011;20:81-7.  Back to cited text no. 8
    
9.
Greulich WW, Pyle SI. Radiographic Atlas of Skeletal Development of the Hand and Wrist. Stanford: Stanford University Press; 1959.  Back to cited text no. 9
    
10.
Neely EK, Hintz RL, Wilson DM, Lee PA, Gautier T, Argente J, et al. Normal ranges for immunochemiluminometric gonadotropin assays. J Pediatr 1995;127:40-6.  Back to cited text no. 10
    
11.
Abacı A, Çatlı G, Anık A, Küme T, Çalan ÖG, Dündar BN, et al. Significance of serum neurokinin B and kisspeptin levels in the differential diagnosis of premature thelarche and idiopathic central precocious puberty. Peptides 2015;64:29-33.  Back to cited text no. 11
    
12.
Volta C, Bernasconi S, Cisternino M, Buzi F, Ferzetti A, Street ME, et al. Isolated premature thelarche and thelarche variant: Clinical and auxological follow-up of 119 girls. J Endocrinol Invest 1998;21:180-3.  Back to cited text no. 12
    


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