scholarly journals The differential diagnosis of constitutional delay of puberty and hypogonadotropic hypogonadism in boys

2020 ◽  
Author(s):  
Oleg Yurevich Latyshev ◽  
Lubov Borisovna Brzhezinskaya ◽  
Goar Feliksovna Okminyan ◽  
Elena Valentinovna Kiseleva ◽  
Mikhail Ivanovich Pykov ◽  
...  
Keyword(s):  
Differential Diagnosis ◽  
Gnrh Agonist ◽  
Hypogonadotropic Hypogonadism ◽  
Bone Age ◽  
Testicular Volume ◽  
Delayed Puberty ◽  
Constitutional Delay ◽  
Genetic Mechanisms ◽  
Somatic Diseases ◽  
Hcg Test

Backgraund: The problem of differential diagnosis of constitutional delay of puberty/CPD and hypogonadotropic hypogonadism/HH in boys is discussed, as boys have similar genetic mechanisms and appearance. Aims: to determine accuracy of the criteria for the differential diagnosis of CDP and HH. Materials: The study included 56 boys14,40,7 years old with delayed puberty (G1P1-3/testicular volume 3сm3). We excluded patients with hypergonadotropic hypogonadism, treated with sex steroids or gonadotropins for 12 months, with endocrine/somatic diseases affecting puberty. At the first visit, we evaluated anthropometric data, bone age, testicular volume, hormones and the results of the gonadotropin-releasing hormone test/GnRH agonist test and the human chorionic gonadotropin test/hCG test. The HH was defined by a testicular volume 3сm3 after 2 years follow-up. The patients were divided into two groups: the first group with CDP and testicles 3cm3 (n=50) and the second group with HH and testicles 3cm3 (n=6). Results: At the first visit in boys with CDP corrected target height was less (Me SDS -1,8 vs -0,4, р=0,02), bone age was less (Ме SDS -2,5 vs - 0,2 р=0,03), testicular volume was more (Ме 1,9 vs 0,5, p=0,0003), hormones were significantly higher, such as, LH (Ме 1,1 vs 0,1mIU/ml, p=0,0002), FSH (Ме 1,9 vs 0,2IU/l, p=0,00007), inhibinB (Ме 142,3 vs 31,3pg/ml, p=0,00009), maxLH (Ме 18,9 vs 0,6mIU/ml, p=0,00007), maxLH/FSH (Ме 2,3 vs 0,4, p=0,0002) on the GnRH agonist test and testosterone (Ме 14,4 vs 1,1nmol/l, p=0,0001) on the hCG test than in boys with HH. The LH 0,3 mIU/ml had 86% sensitivity, 100% specificity; maxLH/FSH1- 92% sensitivity, 100% specificity; testosterone 2,7 nmol/l on the hCG test - 98% sensitivity, 100% specificity for differential diagnosis of CDP and HH in boys. However, maxLH 3,5 mIU/ml on the GnRH agonist test, FSH 0,5 IU/l, inhibinB 58 pg/ml had 100% sensitivity and specificity for diagnosis of CDP. Conclusions: The inhibinB 58 pg/ml, LH 0,3 mIU/ml, FSH 0,5 IU/l or maxLH 3,5 mIU/ml, maxLH/FSH 1,0 on the GnRH agonist test, testosterone 2,7 nmol/l on the hCG test have an excellent accuracy for the differential diagnosis of CDP and HH in prepubertal boys with delayed puberty.

Delayed Puberty

2020 ◽  
Author(s):  
Amanda French
Keyword(s):  
Pubertal Timing ◽  
Hormone Replacement ◽  
Hypogonadotropic Hypogonadism ◽  
Disease Process ◽  
Optimal Growth ◽  
Underlying Disease ◽  
Delayed Puberty ◽  
Hypergonadotropic Hypogonadism ◽  
Pubertal Delay ◽  
Constitutional Delay

Although common, delayed puberty can be distressing to patients and families.   Careful assessment is necessary to ensure appropriate physical and social development in patients that require intervention to reach pubertal milestones and achieve optimal growth.  Most pubertal delay is from lack of activation of the hypothalamic-pituitary-gonadal axis which then results in a functional or physiologic GnRH deficiency.  The delay may be temporary or permanent.  Constitutional delay (CDGP), also referred to as self-limited delayed puberty (DP), describes children on the extreme end of normal pubertal timing and is the most common cause of delayed puberty, representing about one third of cases.  Hypergonadotropic hypogonadism (primary hypogonadism) results from a failure of the gonad itself, and hypogonadotropic hypogonadism (secondary hypogonadism) results from a failure of the hypothalamic-pituitary axis, which is usually caused by another process, often systemic.  Diagnosis is based on history and examination.  Treatment is based on the underlying cause of pubertal delay and may include hormone replacement.  Involving a pediatric endocrinologist should be considered.  Appropriate counseling and ongoing support are important for all patients and families, regardless of underlying disease process.   This review contains 4 figures, 4 tables, and 32 references. Keywords: puberty, delayed puberty, hypogonadism, hypogonadotropic hypogonadism, hypergonadotropic hypogonadism, menarche, thelarche, constitutional delay and growth in puberty, Turner syndrome

scholarly journals The human chorionic gonadotropin test is more powerful than the gonadotropin-releasing hormone agonist test to discriminate male isolated hypogonadotropic hypogonadism from constitutional delayed puberty

2003 ◽  
pp. 23-29 ◽  
Author(s):  
V Degros ◽  
C Cortet-Rudelli ◽  
B Soudan ◽  
D Dewailly
Keyword(s):  
Chorionic Gonadotropin ◽  
Human Chorionic Gonadotropin ◽  
Testosterone Level ◽  
Pubertal Development ◽  
Hypogonadotropic Hypogonadism ◽  
Serum Testosterone ◽  
Serum Testosterone Level ◽  
Delayed Puberty ◽  
Hcg Test

OBJECTIVE: The effectiveness of biological investigations aiming at discriminating isolated hypogonadotropic hypogonadism (IHH) from constitutional delayed puberty (CDP) in male patients is still controversial. We revisited the diagnostic power of the basal serum testosterone level, the Triptorelin test and the human chorionic gonadotropin (hCG) test in a cohort of 33 boys with delayed puberty. DESIGN: Boys were aged 14.2 to 26.2 Years at referral. A 5-Year-long clinical follow-up after the initial study allowed confirmation of the diagnosis. At the end of the follow-up period, IHH was found in 13 patients while the other 20 had normal spontaneous pubertal development (CDP). RESULTS: At referral, a basal morning testosterone level >1.7 nmol/l was observed in 55% of patients with CDP exclusively (predictive positive value (PPV)=100%; predictive negative value (PNV)=59%). For CDP, the PPV of the LH peak 3 h after Triptorelin was 100% by setting the upper threshold at 14 IU/l and the PNV was 72%. However, no lower threshold could discriminate IHH from CDP in the remaining patients with an LH peak 3 h after Triptorelin <14 IU/l. In CDP patients, the PPV of the serum testosterone increment after hCG stimulation (deltaT/hCG) was 100% for values >9 nmol/l (PNV=72%). In IHH patients, the PPV of deltaT/hCG was 100% for values <3 nmol/l (PNV=82%). Only 29% of the studied population had a deltaT/hCG between these lower and upper thresholds and therefore could not have been classified initially. CONCLUSIONS: (i) Dynamic testing for the diagnosis of delayed puberty is useful only when the basal testosterone level is lower than 1.7 nmol/l; (ii) in that case, the hCG test has better discriminating power than the Triptorelin test and appears as the best cost-effective investigation. It prevents useless and expensive investigations in about one-half of CDP patients with a basal morning testosterone level lower than 1.7 nmol/l.

Longitudinal Increases in Serum Insulin-like Factor 3 and Testosterone Determined by LC-MS/MS in Pubertal Danish Boys

2020 ◽  
Vol 105 (10) ◽  
pp. 3173-3178 ◽  
Author(s):  
Jakob Albrethsen ◽  
Marie Lindhardt Ljubicic ◽  
Anders Juul
Keyword(s):  
Serum Insulin ◽  
Hypogonadotropic Hypogonadism ◽  
Peptide Hormone ◽  
Delayed Puberty ◽  
Serum Concentrations ◽  
Serum Lh ◽  
Constitutional Delay ◽  
Diagnostic Role

Abstract Background Serum concentrations of the peptide hormone insulin-like factor 3 (INSL3) is a candidate marker for improved distinction between constitutional delay of growth and puberty (CDGP) and permanent hypogonadotropic hypogonadism (HH) in boys. Aim To assess the possible diagnostic role of LC-MS/MS-based INSL3 measurements as a marker of imminent puberty by comparison with testosterone (T) and luteinizing hormone (LH) levels in serum longitudinally collected from 18 healthy boys throughout puberty. Results The first increase in serum LH was detected on average 4 months earlier, as compared with the first observed increases in INSL3 and T. When comparing the 2 testicular hormones only, we found that in 22% (4 of 18) of the boys the first increase in serum INSL3 was observed prior to the first observed increase in T, whereas in 44% (8 of 18) the first increase in T was observed before the first observed increase in INSL3. In the remaining 6 boys, the 2 testicular hormones showed the first increase at the same examination. Conclusion In some boys with delayed puberty, the first indication of testicular maturation may be detectable by observing serum INSL3. Further studies of LC-MS/MS determination of serum INSL3 in patients with CDGP and HH are warranted.

scholarly journals Genetic Evaluation Supports Differential Diagnosis in Adolescent Patients with Delayed Puberty

2021 ◽  
Author(s):  
Tansit Saengkaew ◽  
Heena R Patel ◽  
Kausik Banerjee ◽  
Gary Butler ◽  
Mehul Tulsidas Dattani ◽  
...  
Keyword(s):  
Differential Diagnosis ◽  
Exome Sequencing ◽  
Clinical Diagnosis ◽  
Hypogonadotropic Hypogonadism ◽  
Genetic Evaluation ◽  
Delayed Puberty ◽  
Diagnostic Challenge ◽  
Panel Testing ◽  
Gene Panel Testing ◽  
Pubertal Delay

Context: Pubertal delay can be the clinical presentation of both idiopathic hypogonadotropic hypogonadism (IHH) and self-limited delayed puberty (SLDP). Distinction between these conditions is a common but important diagnostic challenge in adolescents. Objective: To assess whether gene panel testing can assist with clinical differential diagnosis, to allow accurate and timely management of delayed puberty patients. Design: Retrospective study Methods: Patients presenting with delayed puberty to UK Paediatric services, followed up to final diagnosis, were included. Whole-exome sequencing was analysed using a virtual panel of genes previously reported to cause either IHH or SLDP to identify rare, predicted deleterious variants. Deleterious variants were verified by in silico prediction tools. The correlation between clinical and genotype diagnosis was analysed. Results: Forty-six patients were included, 54% with a final clinical diagnosis of SLDP and 46% with IHH. Red flags signs of IHH were present in only 3 patients. Fifteen predicted deleterious variants in 12 genes were identified in 33% of the cohort, with most inherited in a heterozygous manner. A fair correlation between final clinical diagnosis and genotypic diagnosis was found. Panel testing was able to confirm a diagnosis of IHH in patients with pubertal delay. Genetic analysis identified three patients with IHH that had been previously diagnosed as SLDP. Conclusion:This study supports the use of targeted exome sequencing in the clinical setting to aid the differential diagnosis between IHH and SLDP in adolescents presenting with pubertal delay. Genetic evaluation thus facilitates earlier and more precise diagnosis, allowing clinicians to direct treatment appropriately.

Delayed Puberty

2020 ◽  
Author(s):  
Amanda French
Keyword(s):  
Pubertal Timing ◽  
Hormone Replacement ◽  
Hypogonadotropic Hypogonadism ◽  
Disease Process ◽  
Optimal Growth ◽  
Underlying Disease ◽  
Delayed Puberty ◽  
Hypergonadotropic Hypogonadism ◽  
Pubertal Delay ◽  
Constitutional Delay

Although common, delayed puberty can be distressing to patients and families.   Careful assessment is necessary to ensure appropriate physical and social development in patients that require intervention to reach pubertal milestones and achieve optimal growth.  Most pubertal delay is from lack of activation of the hypothalamic-pituitary-gonadal axis which then results in a functional or physiologic GnRH deficiency.  The delay may be temporary or permanent.  Constitutional delay (CDGP), also referred to as self-limited delayed puberty (DP), describes children on the extreme end of normal pubertal timing and is the most common cause of delayed puberty, representing about one third of cases.  Hypergonadotropic hypogonadism (primary hypogonadism) results from a failure of the gonad itself, and hypogonadotropic hypogonadism (secondary hypogonadism) results from a failure of the hypothalamic-pituitary axis, which is usually caused by another process, often systemic.  Diagnosis is based on history and examination.  Treatment is based on the underlying cause of pubertal delay and may include hormone replacement.  Involving a pediatric endocrinologist should be considered.  Appropriate counseling and ongoing support are important for all patients and families, regardless of underlying disease process.   This review contains 4 figures, 4 tables, and 32 references. Keywords: puberty, delayed puberty, hypogonadism, hypogonadotropic hypogonadism, hypergonadotropic hypogonadism, menarche, thelarche, constitutional delay and growth in puberty, Turner syndrome

scholarly journals Reversible Kallmann syndrome: report of the first case with a KAL1 mutation and literature review

2007 ◽  
Vol 156 (3) ◽  
pp. 285-290 ◽  
Author(s):  
Rogerio Silicani Ribeiro ◽  
Teresa Cristina Vieira ◽  
Julio Abucham
Keyword(s):  
Single Case ◽  
Hypogonadotropic Hypogonadism ◽  
Growth Factor Receptor ◽  
Serum Testosterone ◽  
Bone Age ◽  
Kallmann Syndrome ◽  
Testosterone Replacement ◽  
Delayed Puberty ◽  
Exon 2 ◽  
First Case

Kallmann syndrome (KS) describes the association of isolated hypogonadotropic hypogonadism with hypo/anosmia. A few KS patients may reverse hypogonadism after testosterone withdrawal, a variant known as reversible KS. Herein, we describe the first mutation in KAL1 in a patient with reversible KS and review the literature. The proband was first seen at 22 years complaining of anosmia and lack of puberty. His brother had puberty at 30 years and a maternal granduncle had anosmia and delayed puberty. On physical examination, he was P2G1, testes were 3 ml and bone age was 14 years. During 20 years of irregular testosterone replacement, he developed secondary sexual characteristics and testicular enlargement. At the age of 41 years, after stopping testosterone replacement for 5 months, his testes were 15 ml, serum testosterone, LH, and FSH responses to GnRH were normal, and his wife was pregnant. The molecular study revealed a cytosine insertion in exon 2 of KAL1, generating a frameshift at codon 75 and a premature stop at codon 85. The expected gene product is a truncated peptide with 85 of the 610 amino acids present in the wild-type protein. Fourteen cases of reversible KS have been described but the genotype was only studied in a single case showing a heterozygous fibroblast growth factor receptor type 1 (FGFR1) mutation. Considering the low prevalence of mutations in KAL1 or FGFR1 in KS, it is possible that these genotypes are more prevalent in reversible KS than in other KS patients, but additional studies are necessary to confirm this hypothesis.

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