scholarly journals MON-273 Retrospective Analysis of Gonadotropin-Mediated Pubertal Induction in Male Patients with Congenital Hypogonadotropic Hypogonadism (CHH)

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Biagio Cangiano ◽  
Giovanni Goggi ◽  
Fabiana Guizzardi ◽  
Valeria Vezzoli ◽  
Paolo Duminuco ◽  
...  
Keyword(s):  
Retrospective Analysis ◽  
Multiple Regression ◽  
Semen Analysis ◽  
Final Height ◽  
Pubertal Development ◽  
Hypogonadotropic Hypogonadism ◽  
Bone Age ◽  
Testicular Development ◽  
Testosterone Replacement Therapy ◽  
Male Patients

Abstract CHH is a rare disease characterized by a failure to enter (complete forms) or to complete (partial forms) pubertal development. It has a strong genetic background and it needs a treatment to allow the puberty to complete. In male this goal could be achieved either by the classic testosterone replacement therapy or by the exogenous gonadotropins (Gn) administration which allows both the endogenous testosterone production and the testicular development. So far, only few studies have explored this latter therapeutic approach in inducing the CHH pubertal development and no internationally recognized protocols are available. Aim of this retrospective analysis is to (i) investigate clinical and biochemical predictors of testicular response to Gn-induced puberty in CHH; (ii) study the non-reproductive outcomes of this treatment (height, body proportions) and their determinants. A total of 19 CHH male patients, undergoing two years of Gn-mediated (FSH and hCG) puberty induction started between the ages of 14 and 23 years, were retrospectively evaluated. For each patient clinical history, physical examination, hormonal evaluation, and genetic analysis using Targeted Next Generation Sequencing for CHH genes was performed; 8 patients accepted to perform a semen analysis (SA) at the end of their treatment.Mann Whitney test and multiple regression analysis showed testicular volume after 24 months of Gn-mediated pubertal induction, to be significantly associated with: (i) the presence of cryptorchidism; (ii) the presence of a completely definable genetic cause for the disease; (iii) the presence of a complete CHH form. No significant association was found with the cumulative dose of hCG administered in 24 months. The statistical analyses regarding SA could not find the same associations. Multiple regression analyses investigating the eunuchoid habitus and a measure of the difference of subject’s final height from his target (deltaSDSth), showed a significant association with: (i) age at the beginning of the induction; (ii) the duration of growth during induction; (iii) and (for deltaSDSth) bone age before the induction. Duration of growth during induction resulted to be associated with previous testosterone priming and with partial CHH.In summary, our study confirms cryptorchidism and complete genetic forms of CHH as negative predictors of testicular response probably because they usually affect early phases of life with a complete GnRH deficiency. We also found that the eunuchoid habitus and deltaSDSth are associated not only with delayed treatment, but also with the duration of stature growth during the induction, apparently related to earlier androgenization.

scholarly journals Predictors of reproductive and non-reproductive outcomes of gonadotropin mediated pubertal induction in male patients with congenital hypogonadotropic hypogonadism (CHH)

2021 ◽  
Author(s):  
B. Cangiano ◽  
G. Goggi ◽  
S. Federici ◽  
C. Bresesti ◽  
L. Cotellessa ◽  
...  
Keyword(s):  
Genetic Background ◽  
Semen Analysis ◽  
Hypogonadotropic Hypogonadism ◽  
Bone Age ◽  
Reproductive Outcomes ◽  
Targeted Next Generation Sequencing ◽  
Congenital Hypogonadotropic Hypogonadism ◽  
Gonadotropin Stimulation ◽  
Complete Form ◽  
Male Patients

Abstract Purpose To investigate predictors of testicular response and non-reproductive outcomes (height, body proportions) after gonadotropin-induced puberty in congenital hypogonadotropic hypogonadism (CHH). Design A retrospective analysis of the puberty induction in CHH male patients, undergoing an off-label administration of combined gonadotropin (FSH and hCG). Methods Clinical and hormonal evaluations before and during gonadotropin stimulation in 19 CHH patients genotyped by Targeted Next Generation Sequencing for CHH genes; 16 patients underwent also semen analysis after gonadotropins. Results A lesser increase in testicular volume after 24 months of induction was significantly associated with: (I) cryptorchidism; (II) a positive genetic background; (III) a complete form of CHH. We found no significant correlation with the cumulative dose of hCG administered in 24 months. We found no association with the results of semen analyses, probably due to the low numerosity. Measures of body disproportion (eunuchoid habitus and difference between adult and target height: deltaSDSth), were significantly related to the: (I) age at the beginning of puberty induction; (II) duration of growth during the induction; (III) initial bone age. The duration of growth during induction was associated with previous testosterone priming and to partial forms of CHH. Conclusions This study shows that a strong genetic background and cryptorchidism, as indicators of a complete GnRH deficiency since intrauterine life, are negative predictors of testicular response to gonadotropin stimulation in CHH. Body disproportion is associated with a delay in treatment and duration of growth during the induction, which is apparently inversely related to previous androgenization.

scholarly journals Testosterone Therapy and Its Monitoring in Adolescent Boys with Hypogonadism: Results of an International Survey from the I-DSD Registry

2021 ◽  
pp. 1-8
Author(s):  
Marianna R. Stancampiano ◽  
Angela K. Lucas-Herald ◽  
Jillian Bryce ◽  
Gianni Russo ◽  
Graziano Barera ◽  
...  
Keyword(s):  
Hypogonadotropic Hypogonadism ◽  
Bone Age ◽  
Gonadal Development ◽  
Testosterone Replacement Therapy ◽  
Adolescent Boys ◽  
Mineral Density ◽  
Androgen Synthesis ◽  
Monitoring Therapy ◽  
Bone Age Assessment ◽  
Contemporary Practice

It is unclear whether testosterone replacement therapy (TRT) in adolescent boys, affected by a range of endocrine diseases that may be associated with hypogonadism, is particularly common. The aim of this study was to assess the contemporary practice of TRT in boys included in the I-DSD Registry. All participating centres in the I-DSD Registry that had boys between 10 and 18 years of age and with a condition that could be associated with hypogonadism were invited to provide further information in 2019. Information on 162 boys was collected from 15 centres that had a median (range) number of 6 boys per centre (1.35). Of these, 30 (19%) from 9 centres were receiving TRT and the median (range) age at the start was 12.6 years (10.8–16.2), with 6 boys (20%) starting at <12 years. Median (range) age of boys not on TRT was 11.7 years (10.7–17.7), and 69 out of 132 (52%) were <12 years. TRT had been initiated in 20 of 71 (28%) boys with a disorder of gonadal development, 3 of 14 (21%) with a disorder of androgen synthesis, and all 7 (100%) boys with hypogonadotropic hypogonadism. The remainder who did not have TRT included 15 boys with partial androgen insensitivity, 52 with non-specific XY DSD, and 3 with persistent Müllerian duct syndrome. Before starting TRT, liver function and blood count were checked in 19 (68%) and 18 boys (64%), respectively, a bone age assessment was performed in 23 (82%) and bone mineral density assessment in 12 boys (43%). This snapshot of contemporary practice reveals that TRT in boys included in the I-DSD Registry is not very common, whilst the variation in starting and monitoring therapy is quite marked. Standardisation of practice may lead to more effective assessment of treatment outcomes.

scholarly journals Hypogonadotropic hypogonadism in human immunodeficiency virus-infected men: uncommonly low testosterone levels

2017 ◽  
Vol 2017 ◽  
Author(s):  
Ana Coelho Gomes ◽  
José Maria Aragüés ◽  
Sílvia Guerra ◽  
Joana Fernandes ◽  
Mário Rui Mascarenhas
Keyword(s):  
Antiretroviral Therapy ◽  
Highly Active Antiretroviral Therapy ◽  
Pubertal Development ◽  
Hypogonadotropic Hypogonadism ◽  
Severe Illness ◽  
Testosterone Replacement Therapy ◽  
List Type ◽  
Testosterone Levels ◽  
Pituitary Dysfunction ◽  
Low Testosterone

Summary Hypogonadotropic hypogonadism (HH) is common and occurs prematurely in HIV-infected men. However, HH with very low testosterone has not been described. Three men with normal pubertal development and HIV1 diagnosis at the ages of 22, 34 and 35 years. All complained of decreased libido, anejaculation and erectile dysfunction thirteen years, six months and one year after HIV diagnosis, respectively. Two had depressive syndrome and two were treated with antiretroviral therapy. Laboratory tests revealed isolated HH in all. Sellar and head CT scans were normal and all had normal CD4 count. They started testosterone replacement therapy, with symptoms improvement. Causes of HH in HIV-infected men include undernutrition, severe illness, drugs, pituitary dysfunction and comorbidities. Despite having none of these conditions (except two that were treated with low-dose psychotropics), our patients had HH with uncommonly low testosterone. This suggests that a different mechanism contributes to severe HH in HIV-infected men. Learning points: The pathogenesis of hypogonadotropic hypogonadism in HIV-infected men is multifactorial and androgen deficiency is more often a consequence of secondary hypogonadism than primary hypogonadism. Causes of hypogonadotropic hypogonadism in HIV-infected men include undernutrition, severe illness, drugs (psychotropics, opiates, megestrol acetate or steroids), pituitary dysfunction (tumor, hyperprolactinemia), an AIDS-related lesion (very rarely) and comorbid conditions, such as antibody to hepatitis C virus seropositivity and injection drug use. Highly active antiretroviral therapy (HAART), particularly protease inhibitor therapy has been associated with sexual dysfunction in men, but the causal nature of this relation has not been clearly established. Hypogonadotropic hypogonadism with uncommonly low testosterone levels are not usually associated with the conditions referred and this suggests that a different mechanism could contribute to severe hypogonadotropic hypogonadism in HIV-infected men. Screening for hypogonadism in all HIV-infected men might help to understand its etiology.

Gonadotropin- and Adrenocorticotropic Hormone-Independent Precocious Puberty of Gonadal Origin in a Patient with Adrenal Hypoplasia Congenita Due to DAX1 Gene Mutation – A Case Report and Review of the Literature: Implications for the Pathomechanism

2018 ◽  
Vol 91 (5) ◽  
pp. 336-345 ◽  
Author(s):  
Stella A. Nagel ◽  
Michaela F. Hartmann ◽  
Felix G. Riepe ◽  
Stefan A. Wudy ◽  
Martin Wabitsch
Keyword(s):  
Gene Mutation ◽  
Precocious Puberty ◽  
Adrenocorticotropic Hormone ◽  
Pubertal Development ◽  
Hypogonadotropic Hypogonadism ◽  
Bone Age ◽  
Pubic Hair ◽  
Adrenal Hypoplasia Congenita ◽  
Body Odour ◽  
Adrenal Hypoplasia

Background/Aims: Mutations in the DAX1 gene cause X-linked adrenal hypoplasia congenita (AHC) classically associated with hypogonadotropic hypogonadism. Unexpectedly, precocious puberty (PP) has been reported in some cases, its mechanism remaining unclear. Methods: We longitudinally studied a boy with AHC due to DAX1 gene mutation who developed peripheral PP at age 4.5 years. Initially he presented pubic hair, penile enlargement, advanced bone age and elevated testosterone levels. PP progressed with acne, body odour and ejaculations. In addition, we summarized reported findings of patients with DAX1 mutations and PP in the literature in a structured manner providing a basis to discuss possible pathomechanisms of PP in DAX1 patients. Results: In our patient, hydrocortisone treatment was increased to 20 mg/m2/day as suggested in similar published cases. However, despite the suppression of adrenocorticotropic hormone (ACTH), this remained without clinical effect or change in laboratory results. The progression of symptoms of pubertal development was well suppressed under cyproterone acetate treatment. Twenty-four-hour steroid urine excretion rate measurements excluded an effect of adrenal androgens and showed a prepubertal rise of excreted testosterone. Testes size remained small. GnRH testing showed peripheral PP. Conclusion: We hypothesize that an intrinsic, gonadotropin- and ACTH-independent activation of steroidogenesis in the DAX1 deficient testes leads to PP in AHC patients with DAX1 mutations.

scholarly journals Hypogonadotropic Hypogonadism in Non-Functioning Pituitary Adenomas: Impact of Intervention

2017 ◽  
Vol 125 (06) ◽  
pp. 368-376 ◽  
Author(s):  
Diana Monteiro ◽  
Paula Freitas ◽  
Romana Vieira ◽  
Davide Carvalho
Keyword(s):  
Pituitary Adenomas ◽  
Hypogonadotropic Hypogonadism ◽  
Testosterone Replacement Therapy ◽  
Retrospective Evaluation ◽  
Surgery Outcome ◽  
Post Surgery ◽  
Male Patients ◽  
The Impact ◽  
Older Males ◽  
Non Functioning Pituitary Adenomas

Abstract To determine the prevalence of hypogonadotropic hypogonadism (HH) among patients with non-functioning pituitary adenomas (NFPA) and the post-surgery outcome on pituitary gonadotropins secretion (PGS); to determine the prevalence of erectile dysfunction (ED) on male patients with NFPA, to evaluate the impact of testosterone replacement therapy (TRT) in those with HH. Retrospective evaluation of gonadal function in 109 NFPA patients (45 males), with a mean age of 51.8 years, diagnosed on the last 10 years. ED questionnaire applied to 34 male patients. Male patients with NFPA were significantly older (males 58.1±15.8 vs. females 47.4±16.94; p=0.001). Most patients had macroadenomas (67%; p=0.001) and only a minority were incidentalomas (19%; p<0.001). Prevalence of HH was 40% (60% on males, 25% on females; p<0.001). Surgery was performed in 54% of all patients (71% of males, 42% of females; p<0.003). After intervention, 14% became HH, 69% maintained previous function and 17% improved. On the questionnaire, 76% reported having ED, 54% of which had HH and 21% were under TRT. Of the patients under TRT, 79% still had ED. Median age of patients with ED was significantly higher [with ED 65 vs. without 49 years; p=0.012). There was no BMI difference between patients with or without TRT (28.0 vs. 27.4 Kg/m2). NFPA was more frequent in older rather than younger patients. Males were older, had more HH and surgery. There was no significant improvement of pituitary function with surgery (17%) and 13% became iatrogenic HH. TRT had a low efficacy to improve ED in these patients.

scholarly journals A Clinical Experience of Pubertal Induction in Female Patients With Congenital Hypogonadotropic Hypogonadism (CHH) From an Endo-ERN Referral Center

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A665-A665
Author(s):  
Silvia Federici ◽  
Biagio Cangiano ◽  
Giovanni Goggi ◽  
Luca Persani ◽  
Marco Bonomi
Keyword(s):  
Clinical Experience ◽  
Case Reports ◽  
Final Height ◽  
Pubertal Development ◽  
Hypogonadotropic Hypogonadism ◽  
Night Time ◽  
Average Growth ◽  
Congenital Hypogonadotropic Hypogonadism ◽  
First Choice ◽  
Transdermal Estradiol

Abstract Female congenital hypogonadotropic hypogonadism (CHH) is a rare condition, with a strong genetic background, characterized by absent or incomplete pubertal development, for which inductive treatment with sex-hormone is required. Although the available data, mostly coming from studies in patients with Turner syndrome, indicate transdermal estradiol (TDE) as the first-choice formulation, no internationally validated therapeutic schemes are currently available. Furthermore, data on CHH patients are certainly lacking and there is no standard of care for pubertal induction in this specific population. The aim of our work was the retrospective analysis of the data from a collection of case reports of pubertal induction in CHH patients referred to our Center. Six patients underwent induction with transdermal estradiol (TDE) at the starting dose of 0.1µg/kg/day (night-time for the first 4-6 months), increased every 4-6 months up to the adult dose, for a mean period of 2.86 ± 0.45 ys. Micronized progesterone (200 mcg) was introduced at reaching of 50µg dose or if breakthrough bleeding occurred. Treatment was monitored through clinical and anthropometric evaluations at each dose modification. The average age of induction was 17.25 ± 1.41 ys, with each bone age&gt; 13 ys. Three out of six patients already had a Tanner B2 stage at diagnosis. The mean times of pubertal advancement were respectively 1.3 ± 0.46 ys for the achievement of B3, 2.13 ± 0.29 ys for the B4 and 2.35 ± 0.77 ys for menarche; all the patients reached an adult breast conformation (B5) in 2.81 ± 0.28 ys. These data are consistent with physiological pubertal progress. All of them achieved adequate uterine development (medium longitudinal diameter 72.2 ± 3.37mm), except one patient with suboptimal development (54mm). The final height (FH) was adequate in all patients, with SDS FH +1.6 (-0.43 - +3.38), in spite of an average growth of 4.11 cm (2.5-6) ​​during the induction period and a growth rate &gt; 2cm/year only in 50% of patients. No side effects were reported, and individual compliance and satisfaction were quite high. This clinical experience suggests that the adopted regimen, consistent with current literature, guarantees excellent efficacy and safety. However, further studies are needed to identify the optimal treatment in adolescents with CHH, taking into account their higher age at the start of induction, the modest impact on growth and final stature, to focus on the specific clinical objectives in these patients

scholarly journals Individualised vs fixed dose of oral 17β-oestradiol for induction of puberty in girls with Turner syndrome: an open-randomised parallel trial

2012 ◽  
Vol 167 (4) ◽  
pp. 523-529 ◽  
Author(s):  
José I Labarta ◽  
Maria L Moreno ◽  
Juan P López-Siguero ◽  
Cristina Luzuriaga ◽  
Itxaso Rica ◽  
...  
Keyword(s):  
Turner Syndrome ◽  
Final Height ◽  
Pubertal Development ◽  
Well Being ◽  
Bone Age ◽  
Fixed Dose ◽  
Promoting Effect ◽  
Open Label ◽  
Tanner Staging ◽  
Dose Oral

ContextOestrogen induction of pubertal changes in Turner girls may reinforce their psychological well-being and may also optimise final height; however, oestrogen type, dose, and route are not well established.ObjectiveTo induce normal pubertal development in Turner girls and ovarian insufficiency with oral 17β-oestradiol (E2), either as individualised dose (ID) or as fixed dose (FD), and to determine whether growth is affected.DesignOpen-label randomised, parallel groups, multicentre clinical trial in 48 GH-treated Turner girls. Oral E2was given in tablets, either as an ID of 5–15 μg/kg per day during 2 years or as a FD of 0.2 mg daily during the first year followed by 0.5 mg daily during the second year. Main outcome measures were the event of attaining a Tanner breast staging ≥4 (primary), FSH, and auxological variables (secondary).ResultsShorter median time to Tanner staging ≥ B4 in the FD group (733 days) compared with the ID group (818 days) (P=0.046). Higher proportion of girls with Tanner staging ≥ B4 (65%) in the FD group compared with the ID group (42%) (P=0.068). Bone age did not show inadequate acceleration and adult height prediction was maintained in both groups. No oestrogen-related adverse events were reported.ConclusionsTwo-year treatment with oral E2can progressively induce normal pubertal development in Turner syndrome. Low-dose oral E2given as a FD produces a satisfactory pubertal development not inferior to ID. Treatment was well tolerated and did not interfere with the growth-promoting effect of GH.

Growth and development in girls with Turner's syndrome during early therapy with low doses of estradiol

1986 ◽  
Vol 113 (4_Suppl) ◽  
pp. S157-S163 ◽  
Author(s):  
K.W. KASTRUP ◽  
_ _
Keyword(s):  
Growth Velocity ◽  
Final Height ◽  
Bone Age ◽  
Growth Spurt ◽  
First Year ◽  
Turner's Syndrome ◽  
Turner’S Syndrome ◽  
Early Therapy ◽  
Group I ◽  
Group Ii

Abstract Early therapy with a low dose of estrogen (estradiol-17β) was given to 33 girls with Turner's syndrome (T.s.) for a period of 4 years. The dose (0.25-2 mg/day) was adjusted every 3 months to maintain plasma estradiol in the normal concentration range for bone age. Growth velocity was compared with that of untreated girls with T.s. All girls were above age 10 years. Bone age was below 10 years in 11 girls (group I) and above 10 years in 22 girls (group II). Growth velocity in the first year of treatment in group I 7.5 ± 1.3 cm (SD) with mean SD score (SDS) of +4.3 and in group II 4.9 ± 1.3 with mean SDS of +3.5. Growth velocity decreased in the following years to 1.6 ± 1.0 cm, SDS -1.44 in group I and 0.9 ± 0.6cm, SDS -2.34 in group II during the fourth year. Withdrawal bleeding occurred in 16 girls of group II after the mean of 23 (range 15-33) months and in 3 girls of group I after 15 to 51 months of treatment. The treatment did not cause an inappropriate acceleration of pubertal development. Breast development appeared in most girls by 3 months of treatment. Pubic hair appeared by 12 months of treatment in group I; it was present in most girls in group II at start of treatment. Final height is known for 12 girls of group II; it was 144.2 ± 4.5 cm. The final height as predicted at the start of therapy was 142.2 ± 5.3 cm. Bone age advanced in the first year of treatment by 2 years. Early treatment with small doses of estrogens induces a growth spurt and normalizes the events of puberty. This will presumably decrease the psychological risks associated with abnormally delayed development.

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