Basal Serum Luteinising Hormone Cut-Off, and Its Utility and Cost-Effectiveness for Aiding the Diagnosis of the Onset of Puberty in Girls With Early Stages of Breast Development

Somboon Wankanit; Pat Mahachoklertwattana; Oraluck Pattanaprateep; Preamrudee Poomthavorn

Disclosures

Clin Endocrinol. 2020;91(1):46-54. 

In This Article

Abstract and Introduction

Abstract

Objective: To determine basal and gonadotrophin-releasing hormone analogue (GnRHa)-stimulated peak luteinising hormone (LH) cut-offs to diagnose onset of early or normal puberty in girls with each Tanner stage of breast (II and III).

Design, Patients and Measurements: A retrospective study of 601 girls with breast onset before 8 years of age who underwent GnRHa test was conducted. Patients were categorized as CPP and premature thelarche. Each group was divided into two subgroups; Tanner II and III. Cost-effectiveness analysis was performed.

Results: In comparison with basal LH cut-off of 0.3 IU/L, basal LH cut-off of 0.2 IU/L had comparable specificity (Tanner II: 98.0% vs 94.8%, Tanner III: 98.8% vs 93.8%), but greater sensitivity (Tanner II: 28.3% vs 41.7%, Tanner III: 45.2% vs 59.3%). Specificity of basal LH cut-off of 0.2 IU/L was not inferior to that of the traditionally used peak LH of 5 IU/L. Using basal LH cut-off of 0.2 IU/L followed by GnRHa test in girls with negative basal LH was more cost-saving when compared with using the cut-off of 0.3 IU/L. Moreover, using basal LH cut-off of 0.2 IU/L followed by GnRHa test provided a cost reduction when compared with performing GnRHa test in all patients.

Conclusions: Basal serum LH cut-off of 0.2 IU/L could be a simple and cost-saving tool for initial diagnosis of onset of early or normal puberty in girls with Tanner II and III before proceeding to GnRH testing.

Introduction

Central precocious puberty (CPP) in girls is defined as having breast development before 8 years of age. Some girls who have breast development before 8 years of age may not have progression of the puberty, so-called premature thelarche (PT). Progressive CPP is characterized by progressive breast development and increased height velocity during the follow-up periods with advanced bone age. Serum gonadotrophins especially luteinising hormone (LH) are central to the diagnosis.[1,2] Gonadotrophin-releasing hormone (GnRH) test with serum gonadotrophin level measurements is the gold standard for the CPP diagnosis. Basal or random serum LH concentration of girls with early phase of CPP is often in the prepubertal range; therefore, GnRH test is required to demonstrate pubertal peak LH level and thus provides the diagnosis of CPP. However, GnRH is unavailable worldwide, so subcutaneous GnRH analogue (GnRHa) has been used as an alternative and its diagnostic accuracy has been proven to be acceptable.[3–5]

Previous studies have demonstrated that basal and peak LH levels in normal girls increased with advanced stages of breast development.[6–8] In girls with Tanner stages IV-V breasts, basal LH level is usually clearly elevated. In contrast, basal LH levels of girls with early phase of puberty (Tanner stages II-III) often overlap with those of prepubertal girls (Tanner stage I), rendering GnRH or GnRHa test requirement for defining the onset of early or normal puberty. GnRH or GnRHa test is costly and labour intensive because serial blood samples are required. Therefore, the diagnostic accuracy of basal LH cut-off should be defined in girls with Tanner stages II and III breasts to minimize the GnRH test requirement.

Among studies using either GnRH or GnRHa test for diagnosing girls with CPP, basal LH cut-offs of 0.1–0.6 IU/L have provided sensitivity of 35%-76% and specificity of 80%-100% while peak LH cut-offs of 5.0–6.9 IU/L showed sensitivity and specificity of 78%-93% and 91%-100%, respectively.[4,5,8–10] However, those studies included CPP girls with both early and advanced stages of breast development. None of those studies evaluated the accuracy of the cut-offs for each breast stage especially CPP girls with early stage of breast development. In addition, there have been no studies evaluating the cost-effectiveness of performing basal LH followed by GnRHa test in patients with negative basal LH and performing GnRHa test in all patients. Therefore, this study aimed to determine the basal LH cut-offs to diagnose the onset of early or normal puberty in girls with Tanner stages II and III breasts and to evaluate the cost-effectiveness of basal LH followed by GnRHa test in patients with negative basal LH in comparison with performing GnRHa test in all patients for diagnosing CPP.

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