scholarly journals Elevated 11-oxygenated androgens are not a major contributor to HPG-axis disturbances in adults with congenital adrenal hyperplasia due to 21-hydroxylase deficiency

2021 ◽  
Author(s):  
Matthias K. Auer ◽  
Luisa Paizoni ◽  
Meike Neuner ◽  
Christian Lottspeich ◽  
Heinrich Schmidt ◽  
...  
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Hypogonadotropic Hypogonadism ◽  
Hormonal Contraceptives ◽  
Adrenal Hyperplasia ◽  
Hpg Axis ◽  
Testosterone Levels ◽  
Regular Cycle ◽  
Adrenal Rest ◽  
21 Hydroxylase Deficiency ◽  
Testicular Adrenal Rest

AbstractContextHypothalamus-pituitary-gonadal (HPG)-axis disturbances are a common phenomenon in patients with classic congenital adrenal hyperplasia (CAH). 11-oxygenated androgens have been suggested to play a role in this context.DesignCross-sectional single center study including 89 patients (N=42 men, N=55 women) with classic CAH.Main Outcome MeasuresIndependent predictors for hypogonadism in men and secondary amenorrhea in women with CAH with a special focus on 11-ketotestosterone (11KT) and 11β-hydroxyandrostenedione (11OHA4).ResultsHypogonadotropic hypogonadism was present in 23% of men and 61% of those women currently not on contraceptives suffered from irregular menstrual cycles or amenorrhea. Testicular adrenal rest tumor (TART) was documented in 28% of men. While 11KT (3.5x) and 11OHA4 (5.7x) among other adrenal steroids were significantly elevated in men with hypogonadism, in stepwise logistic regression, the only significant independent predictor for hypogonadism were elevated 17-OHP levels (B = 0.006; p = 0.039). Although 11KT (5.2x) and 11OHA4 (3.7x) levels were also significantly higher in women with amenorrhea in comparison to those with a regular cycle, the only significant predictor for amenorrhea were elevated total testosterone levels (B = 1.806; p = 0.040). 11-oxygenated androgens were not different in those with TART and those without. Of note, there were no significant differences in 11OHA4 or 11KT between those with a regular cycle and those currently on hormonal contraceptives.Conclusions11-oxygenated androgens do not seem to add additional information for explaining menstrual disturbances and hypogonadism in patients with CAH in comparison to established marker of disease control.HighlightsThe 11-oxygenated androgens 11-ketotestosterone and 11β-hydroxyandrostenedione are significantly elevated in men with CAH with hypogonadotropic hypogonadism and women with amenorrhea.Elevated 17-OHP levels in male patients and elevated testosterone levels in female patients are however the dominant predictor of HPG-axis disturbances.11-oxygenated androgens are not predictive for testicular adrenal rest tumors in men with CAH11-ketotestosterone and 11β-hydroxyandrostenedione levels do not seem to be influenced by intake of oral contraceptives.

scholarly journals Restoration of fertility by gonadotropin replacement in a man with hypogonadotropic azoospermia and testicular adrenal rest tumors due to untreated simple virilizing congenital adrenal hyperplasia

2014 ◽  
Vol 170 (4) ◽  
pp. K11-K17 ◽  
Author(s):  
Julia Rohayem ◽  
Frank Tüttelmann ◽  
Con Mallidis ◽  
Eberhard Nieschlag ◽  
Sabine Kliesch ◽  
...  
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Adrenal Hyperplasia ◽  
Hydroxylase Deficiency ◽  
Testosterone Levels ◽  
Testosterone Production ◽  
Testicular Adrenal Rest Tumors ◽  
Simple Virilizing ◽  
Adrenal Rest ◽  
21 Hydroxylase Deficiency ◽  
Testicular Adrenal Rest

ContextClassical congenital adrenal hyperplasia (CAH), a genetic disorder characterized by 21-hydroxylase deficiency, impairs male fertility, if insufficiently treated.PatientA 30-year-old male was referred to our clinic for endocrine and fertility assessment after undergoing unilateral orchiectomy for a suspected testicular tumor. Histopathological evaluation of the removed testis revealed atrophy and testicular adrenal rest tumors (TARTs) and raised the suspicion of underlying CAH. The remaining testis was also atrophic (5 ml) with minor TARTs. Serum 17-hydroxyprogesterone levels were elevated, cortisol levels were at the lower limit of normal range, and gonadotropins at prepubertal levels, but serum testosterone levels were within the normal adult range. Semen analysis revealed azoospermia. CAH was confirmed by a homozygous mutation g.655A/C>G (IVS2-13A/C>G) inCYP21A2. Hydrocortisone (24 mg/m2) administered to suppress ACTH and adrenal androgen overproduction unmasked deficient testicular testosterone production. As azoospermia persisted due to sustained hypogonadotropic hypogonadism, a combined s.c. gonadotropin replacement with human chorionic gonadotropin (hCG) (1500 IU twice weekly) and FSH (human menopausal gondadotropin (hMG) 150 IU three times weekly) was initiated.ResultsNormalization of testosterone levels and a stable low sperm concentration (0.5 mill/ml) with good sperm motility (85% A+B progressive) were achieved within 21 months of treatment. Despite persisting TARTs, while receiving treatment, the patient successfully impregnated his wife twice, the latter impregnation leading to the birth of a healthy girl.ConclusionsTARTs in unrecognized (simple virilizing) CAH may lead to unnecessary orchiectomy. In hypogonadotropic, azoospermic CAH, a combined treatment with oral corticosteroids and subcutaneously administered hCG and FSH can successfully restore testicular testosterone production and fertility, even if only one hypoplastic and atrophic testis with adrenal rest tumors is present.

scholarly journals Fertility, sexuality and testicular adrenal rest tumors in adult males with congenital adrenal hyperplasia

2012 ◽  
Vol 166 (3) ◽  
pp. 441-449 ◽  
Author(s):  
Henrik Falhammar ◽  
Helena Filipsson Nyström ◽  
Urban Ekström ◽  
Seth Granberg ◽  
Anna Wedell ◽  
...  
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Fat Mass ◽  
Sperm Concentration ◽  
Inhibin B ◽  
Adrenal Hyperplasia ◽  
Hydroxylase Deficiency ◽  
Testicular Adrenal Rest Tumors ◽  
Adrenal Rest ◽  
21 Hydroxylase Deficiency ◽  
Testicular Adrenal Rest

ObjectiveFertility in males with congenital adrenal hyperplasia (CAH) is reported from normal to severely impaired. Therefore, we investigated fertility/fecundity, social/sexual situation, and pituitary–gonadal function in CAH males.Subjects and methodsThe patient cohort comprised 30 males, aged 19–67 years, with 21-hydroxylase deficiency. Their fertility was compared with age-matched national population data. For the evaluation of social/sexual factors and hormone status, age-matched controls were recruited (n=32). Subgroups of different ages (<30 years and older) and CYP21A2 genotypes (null (severe salt-wasting (SW)), I2splice (milder SW), and I172N (simple virilizing)) were also studied. Patients underwent testicular ultrasound examination (n=21) and semen analysis (n=14).ResultsFertility was impaired in CAH males compared with national data (0.9±1.3 vs 1.8±0.5 children/father, P<0.001). There were no major differences in social and sexual factors between patients and controls apart from more fecundity problems, particularly in the I172N group. The patients had lower testosterone/estradiol (E2) ratio and inhibin B, and higher FSH. The semen samples were pathological in 43% (6/14) of patients and sperm concentration correlated with inhibin B and FSH. Testicular adrenal rest tumors (TARTs) were found in 86% (18/21). Functional testicular volume correlated positively with the testosterone/E2 ratio, sperm concentration, and inhibin B. Patients with pathological semen had increased fat mass and indications of increased cardiometabolic risk.ConclusionsFertility/fecundity was impaired in CAH males. The frequent occurrence of TARTs resulting in testicular insufficiency appears to be the major cause, but other factors such as elevated fat mass may contribute to a low semen quality.

scholarly journals Testicular adrenal rest tumor in infertile man with congenital adrenal hyperplasia: case report and literature review

2011 ◽  
Vol 129 (5) ◽  
pp. 346-351 ◽  
Author(s):  
Giovanni Scala Marchini ◽  
Marcello Cocuzza ◽  
Rodrigo Pagani ◽  
Fábio César Torricelli ◽  
Jorge Hallak ◽  
...  
Keyword(s):  
Case Report ◽  
Congenital Adrenal Hyperplasia ◽  
Tumor Resection ◽  
Testicular Tumor ◽  
Seminiferous Tubules ◽  
Adrenal Hyperplasia ◽  
Hydroxylase Deficiency ◽  
Adrenal Rest ◽  
21 Hydroxylase Deficiency ◽  
Testicular Adrenal Rest

CONTEXT: Synthesis of cortisol and aldosterone is impaired in patients with congenital adrenal hyperplasia (CAH) because of 21-hydroxylase deficiency. Men with CAH have low fertility rates compared with the normal population, and this is related to testicular adrenal rest tumors. Findings of azoospermia in combination with a testicular tumor on ultrasound are likely to have a mechanical cause, especially when in the testicular mediastinum. The preferred treatment method consists of intensive corticoid therapy. However, when the tumor is unresponsive to steroid therapy, surgical treatment should be considered. CASE REPORT: We present the case of a male patient with CAH due to 21-hydroxylase deficiency who presented a testicular tumor and azoospermia. Treatment with low daily corticoid doses had previously been started by an endocrinologist, but after 12 months, no significant change in sperm count was found. Although the adrenocorticotrophic hormone and 17-hydroxyprogesterone levels returned to normal values, the follicle-stimulating hormone (FSH), luteinizing hormone and testosterone levels remained unchanged. Ultrasound examination confirmed that the testicles were small and heterogenous bilaterally, and revealed a mosaic area at the projection of the testis network bilaterally. Magnetic resonance imaging confirmed the finding. Testicular biopsy revealed the presence of preserved spermatogenesis and spermiogenesis in 20% of the seminiferous tubules in the right testicle. The patient underwent testis-sparing tumor resection. After 12 months of follow-up, there was no tumor recurrence but the patient still presented azoospermia and joined an intracytoplasmic sperm injection program.

scholarly journals Case Report:clinical experience of bilateral giant pediatric Testicular adrenal rest tumors with 3 Beta-Hydroxysteroid Dehydrogenase-2 family history

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Lingyun Yu ◽  
Pengyu Chen ◽  
Wenbin Zhu ◽  
Junjie Sun ◽  
Shoulin Li
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Tumor Size ◽  
Hydroxysteroid Dehydrogenase ◽  
Endocrine Treatment ◽  
Adrenal Hyperplasia ◽  
Hydroxylase Deficiency ◽  
Testicular Adrenal Rest Tumors ◽  
Adrenal Rest ◽  
21 Hydroxylase Deficiency ◽  
Testicular Adrenal Rest

Abstract Background We reported a patient with Testicular adrenal rest tumors(TARTs) caused by congenital adrenal hyperplasia(CAH). TARTs occur frequently in CAH population with 21-hydroxylase deficiency(21-OHD). There are few reports of TARTs with 3β-hydroxysteroid dehydrogenase deficiency-2 (3β-2HSD).Furthermore,gaint TARTs are rarely mentioned in reported cases involving affected siblings. Case presentation A 14-year-old male patient was admitted by congenital adrenal hyperplasia with progressively increasing bilateral testicular masses.The Patient and his elder brother had been performed mutational and chromosome analysis and biopsy. Hormonal and anthropometric measurements were performed during endocrine treatments. We successfully performed surgery and excised two 83mm×46mm×44mm and 74mm×49mm×31mm tumors. Our pathology and immunochemistry tests have proven TARTs in patient. At first, both siblings received regular doses of hydrocortisone and fludrocortisones and tumor size regressed. During the one-year irregular intake due to Covid-19 pandemic, endocrine treatment became insensitive and tumor size slowly increased. The gene analysis reported two novel mutations C.776 C>T and C.674 T>A. The C.776 C>T is from father and has been reported. The C.674 T>A inherited from mother and cannot found in gene library and may related to TARTs. Conclusions This case illustrates inadequate hormone therapy could cause tumor enlargement. It is essential to seek for ultrasound examination once suspected scrotal mass occurred.It is necessary to adjust endocrine medicine or adopt surgery in refractory gaint TARTs. And presence of tunica vaginalis cavity may indicate the severity of TARTs in surgery.

scholarly journals Prevalence of testicular adrenal rest tumours in male children with congenital adrenal hyperplasia due to 21-hydroxylase deficiency

2007 ◽  
Vol 157 (3) ◽  
pp. 339-344 ◽  
Author(s):  
Hedi L Claahsen-van der Grinten ◽  
Fred C G J Sweep ◽  
Johan G Blickman ◽  
Ad R M M Hermus ◽  
Barto J Otten
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Tumour Size ◽  
Inhibin B ◽  
Seminiferous Tubules ◽  
Adrenal Hyperplasia ◽  
Hydroxylase Deficiency ◽  
Gonadal Dysfunction ◽  
Adrenal Rest ◽  
21 Hydroxylase Deficiency ◽  
Testicular Adrenal Rest

Objective: Testicular adrenal rest tumours (TART) are a well-known complication in adult male patients with congenital adrenal hyperplasia (CAH), with a reported prevalence of up to 94%. In adulthood, the tumours are associated with gonadal dysfunction most probably due to longstanding obstruction of the seminiferous tubules. The aim of our study was to determine the presence of TART and their influence on gonadal function in childhood. Design: Retrospective study. Patients and methods: Scrotal ultrasound was performed in 34 children with CAH due to 21-hydroxylase deficiency who were between 2 and 18 years old. FSH, LH, testosterone and inhibin B concentrations were measured in serum of 27 patients. Results: TART were detected by ultrasound in 8 out of 34 (24%) children. In two of them, bilateral tumours were found. All lesions were located in the rete testis. Seven patients had the salt-wasting type of CAH; one patient had the simple virilising type of CAH. Mean tumour size was 4.1 mm (range 2–8 mm). In none of the patients were the tumours palpable. Two children with TART were between 5 and 10 years old, the other six children were above 10 years old. In all children with TART, LH, FSH, testosterone and inhibin B levels were similar to the patients without TART. Conclusion: TART can be found in CAH children before the age of 10 years. The absence of gonadal dysfunction in our group of children suggests that gonadal dysfunction as frequently reported in adult CAH patients with TART develops after childhood.

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