Role of Gonadotropin-releasing Hormone Stimulation Test in Diagnosing Gonadotropin Deficiency in Both Males and Females with Delayed Puberty

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Abstract

Background:

Delayed puberty can result either from constitutional delay of growth and puberty (CDP) or idiopathic hypogonadotropic hypogonadism (IHH). Gonadotropin-releasing hormone (GnRH) stimulation test has been generally accepted as a current method for diagnosing delayed puberty. The objective of this research was to assess the cut-off values and the efficacy of GnRH stimulation test in the diagnosis of delayed puberty in both males and females.

Methods:

A study of 91 IHH, 27 CDP patients, 6 prepubertal children, and 20 pubertal adults was undertaken. Blood samples were obtained at 0, 30, 60, and 120 min after GnRH administration and the levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were measured. For each parameter, the sensitivities and specificities were estimated, and the receiver operating characteristic (ROC) curves were constructed.

Results:

The ROC curves indicated that a serum basal LH <0.6 IU/L or peak LH <9.74 IU/L resulted in moderate sensitivity (73.8% or 80.0%) and specificity (90.9% or 86.4%) in the diagnosis of HH in males. Serum basal LH <0.85 IU/L or basal FSH <2.43 IU/L resulted in moderate sensitivity (80.0% or 100.0%) and specificity (75.0% or 50.0%) in the diagnosis of HH in females.

Conclusions:

Our data suggest that isolated use of the gonadorelin stimulation test is almost sufficient to discriminate between HH and CDP in males, but unnecessary in females. The most useful predictor is serum basal or peak LH to differentiate these two disorders in males, but serum basal LH or FSH in females.

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Most cited references 15

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Understanding diagnostic tests 3: Receiver operating characteristic curves.

Anthony K. Akobeng (2007)

The results of many clinical tests are quantitative and are provided on a continuous scale. To help decide the presence or absence of disease, a cut-off point for 'normal' or 'abnormal' is chosen. The sensitivity and specificity of a test vary according to the level that is chosen as the cut-off point. The receiver operating characteristic (ROC) curve, a graphical technique for describing and comparing the accuracy of diagnostic tests, is obtained by plotting the sensitivity of a test on the y axis against 1-specificity on the x axis. Two methods commonly used to establish the optimal cut-off point include the point on the ROC curve closest to (0, 1) and the Youden index. The area under the ROC curve provides a measure of the overall performance of a diagnostic test. In this paper, the author explains how the ROC curve can be used to select optimal cut-off points for a test result, to assess the diagnostic accuracy of a test, and to compare the usefulness of tests. The ROC curve is obtained by calculating the sensitivity and specificity of a test at every possible cut-off point, and plotting sensitivity against 1-specificity. The curve may be used to select optimal cut-off values for a test result, to assess the diagnostic accuracy of a test, and to compare the usefulness of different tests.

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Delayed puberty: analysis of a large case series from an academic center.

Ines L Sedlmeyer, Mark Palmert (2002)

Despite the clinical importance of delayed puberty, the understanding of this condition is hampered by the lack of studies evaluating etiologies and predisposing factors among large case series. We performed a retrospective study of clinical and laboratory data from adolescents ( or =1 SD beyond the mean), or diagnostic of delay (development > or =2 SD beyond the mean). The most common cause of delayed puberty was constitutional delay of growth and maturation (CD), which affected 53% of the subjects (63% of males and 30% of females). The remaining subjects could be divided into four categories: those with an underlying condition associated with delayed, but spontaneous, pubertal development [functional hypogonadotropic hypogonadism (FHH)], 19% of subjects; those with permanent hypogonadotropic hypogonadism, 12% of subjects; those with permanent hypergonadotropic hypogonadism, 13% of subjects; and those without clearly classified disorders, 3% of subjects. Like CD, FHH was male predominant, whereas the other categories either affected both genders equally or were predominantly female. In total, 50 different etiologies led to pubertal delay within our case series. Data permitted classification of family histories of pubertal timing among primary relatives in 95 of 122 of the CD and in 25 of 45 of the FHH cases. Analysis revealed at least a tendency to pubertal delay in 77% of the CD and in 64% of the FHH families and a diagnosis of delay in 38% of the CD and 44% of the FHH families. Both parents contributed to the positive family histories. The rates of positive family histories among the CD and FHH groups were approximately twice those seen among the other subjects in our case series. Among all subjects, those with FHH had the most marked growth delay, and girls had the greater bone age delay. Among the boys and at comparable chronological ages, CD and FHH were characterized by greater delays in pubic hair development and bone age than in the other diagnostic groups. Although CD is typically associated with leanness, 22% of our subjects had a BMI SD score at the 85th percentile or above for chronological age. These overweight subjects differed from the rest of the CD group: bone age was less delayed, and height was less affected. Finally, our analysis suggested a possible association between attention deficit disorder with or without hyperactivity and pubertal delay in our CD and FHH subjects. Our study provides valuable data regarding the variety and frequency of diagnoses that lead to delayed puberty. The results underscore the importance of performing a thorough evaluation and family history in adolescents with delayed puberty. Moreover, the data from our case series provide clues for unraveling the mechanism(s) of idiopathic pubertal delay and lead to the hypothesis that the pubertal delay seen among some subjects with FHH and CD may stem in part from similar underlying physiology.

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Assessment of basal and gonadotropin-releasing hormone-stimulated gonadotropins by immunochemiluminometric and immunofluorometric assays in normal children.

Paola B Lara, Tiago B Ferreira, Samuel A R Pereira … (2007)

Recently, new methodologies have been applied to commercial immunofluorometric (IFMA) and immunochemiluminometric (ICMA) LH and FSH assays. The objective of the study was to use ICMA to establish basal and GnRH-stimulated LH and FSH reference values in normal subjects of different ages and sexual development, compared with IFMA. We established basal and GnRH-stimulated LH and FSH levels of 315 prepubertal and pubertal children (170 males and 145 females) divided into five groups according to Tanner stage. Of these, 106 subjects (59 males and 47 females) were submitted to GnRH test. The prepubertal upper limit of normal for basal LH, determined by the 95th percentiles of the prepubertal population, were 0.2 IU/liter (ICMA) and 0.6 IU/liter (IFMA) in both genders. No overlap of basal LH levels determined by ICMA was observed between prepubertal and pubertal males, but basal LH determined by IFMA overlapped in 11.8% of subjects. In girls, both methods yielded overlapping values (10.4%, ICMA; and 84.6%, IFMA). The LH peak after GnRH stimulation that defined puberty was 4.1 IU/liter (ICMA) and 3.3 IU/liter (IFMA) in boys and 3.3 IU/liter (ICMA) and 4.2 IU/liter (IFMA) in girls. After GnRH stimulation, values determined by the two methods overlapped in both genders. We conclude that ICMA is more sensitive and precise than IFMA, permitting differentiation of pubertal and prepubertal stage in boys under basal conditions. However, in girls the overlap of basal values was marked, indicating the need for the GnRH test to establish maturity of the hypothalamus-pituitary-gonadal axis.

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Author and article information

Journal

Journal ID (nlm-ta): Chin Med J (Engl)

Journal ID (iso-abbrev): Chin. Med. J

Journal ID (publisher-id): CMJ

Title: Chinese Medical Journal

Publisher: Medknow Publications & Media Pvt Ltd (India )

ISSN (Print): 0366-6999

Publication date (Print): 20 September 2015

Volume: 128

Issue: 18

Pages: 2439-2443

Affiliations

[1 ]Department of Endocrinology, Chinese PLA General Hospital, Beijing 100853, China

[2 ]Department of Internal Medicine, Fushun Hospital of Traditional Chinese Medicine, Fushun, Liaoning 113008, China

[3 ]School of Medicine, Nankai University, Tianjin 300071, China

[4 ]Department of Endocrinology, Shanxi Dayi Hospital, Taiyuan, Shanxi 030032, China

Author notes

Address for correspondence: Prof. Yi-Ming Mu, Department of Endocrinology, Chinese PLA General Hospital, Beijing 100853, China E-Mail: muyiming@ 123456301hospital.com.cn

Article

Publisher ID: CMJ-128-2439

DOI: 10.4103/0366-6999.164926

PMC ID: 4725567

PubMed ID: 26365959

SO-VID: b9ef2e64-d309-49c0-a163-8399c4b1bd8b

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This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.

Role of Gonadotropin-releasing Hormone Stimulation Test in Diagnosing Gonadotropin Deficiency in Both Males and Females with Delayed Puberty

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Abstract

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Results:

Conclusions:

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Karger: Endocrinology

Most cited references 15

Understanding diagnostic tests 3: Receiver operating characteristic curves.

Delayed puberty: analysis of a large case series from an academic center.

Assessment of basal and gonadotropin-releasing hormone-stimulated gonadotropins by immunochemiluminometric and immunofluorometric assays in normal children.

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