Testicular Adrenal Rest Tissue Research Articles

Experience in optimizing fertility outcomes in men with congenital adrenal hyperplasia due to 21 hydroxylase deficiency.

Men with congenital adrenal hyperplasia (CAH) have impaired fertility. We aimed to assess fertility outcomes and the importance of hypogonadotropic hypogonadism, testicular failure and the presence of testicular adrenal rest tumours (TART). Retrospective analysis of men attending an adult CAH clinic in a tertiary centre. Fifty men with CAH due to 21 hydroxylase deficiency were identified of whom 35 were salt wasting and 15 were non-salt-wasting. Review of fertility history and parameters including luteinizing hormone (LH), follicle-stimulating hormone (FSH), androstenedione, 17-hydroxyprogesterone (17-OHP), semen analysis and the presence of testicular adrenal rest tissue (TART) on ultrasound. TART were detected by ultrasound in 21 (47%), and their presence was associated with an elevated FSH (P = 0·01). Severe oligospermia was present in 11 of 23 (48%), and this was associated with an elevated FSH (P = 0·02), suppressed LH (P < 0·01) and TART (P = 0·03) when compared to those with a sperm count >5 × 10(6) per ml. Of those that desired fertility, 10 of 17 (59%) required treatment intensification and four underwent in vitro fertilization. Intensification resulted in a rise in median LH (0·6-4·3 IU/l; P = 0·01). Live birth rate was 15 of 17 (88%) with a median (range) time to conception of 8 (0-38) months. Suppressed LH is a marker for subfertility and is often reversible. Testicular failure is closely associated with TART formation. If TART are detected, sperm cryopreservation should be offered given the risk of progression to irreversible testicular failure. Male fertility in CAH can be improved by intensified treatment and assisted reproductive technology.

The state of the Sertoli cells in the children and adolescents presenting with congenital adrenal hyperplasia due to 21-hydroxylase deficiency

Introduction. Compromised fertility is one of the main health-related problems encountered by men suffering from 21-hydroxylase deficient congenital adrenal hyperplasia (CAH). This condition can be attributed either to the disease itself or to the presence of the testicular adrenal rest tissue (TART). The dysfunction of the reproductive system can be diagnosed as early as the childhood and adolescence based on the reduced levels of anti-müllerian hormone (AMH) and inhibin B, i.e. the specific markers of Sertoli cell activity. Materials and methods. We have examined 53 patients at the age varying from 1 to 19 years presenting with the confirmed diagnosis of 21-hydroxylase deficient congenital adrenal hyperplasia and 21 children aged from 6 to 17 years free from endocrine pathology (the control group). Special attention was given to the elucidation of the relationship between the inhibin B and AMH levels, the clinical form of the disease, and the presence of TART. Results. The level of inhibin B in the patients with congenital adrenal hyperplasia at the onset of puberty turned out to be lower compared with that in the control group, regardless of the form of the disease. The presence of TART was documented in 9 patients (30%) with salt-wasting CAH (SW CAH) and in 1 patient (4.3%) having the simple virilizing form of CAH (SV CAH). The patients with TART had a lower level of inhibin B but not AMH. Conclusion. The excessive production of androgens does not exert a negative influence on the activity of the Sertoli cells in the boys suffering from congenital adrenal hyperplasia prior to puberty. The lowered level of inhibin B during the pubertal period, in the absence of reduction of the AMH level, suggests dysfunction of the Sertoli cells. The dysfunction during puberty is especially well apparent in the presence of TART.

The development of ectopic testicular adrenal rest tissue (TART) in the children and adolescents presenting with congenital adrenal cortical dysfunction

We have evaluated the prevalence of the ectopic testicular adrenal rest tissue (TART) among 71 patients at the age varying from 1 to 19 years and compared the visualization techniques (ultrasound examination, MRI) employed to diagnose TART. This condition was revealed in 14.1% of the patients (10/71). One of them presented with the simple virile (SV) form of the disease and 9 with the salt-wasting one. Most cases of TART (9 of the ten) were diagnosed with the help of the ultrasound technique whereas MRI allowed to determine the size of the neoplasms. The study has demonstrated the relationship between TART and 17-OH and PRA (plasma rennin activity) levels at the time of their measurement. Moreover, the relationship between the number of measurements and the PRA level during the last year has been documented. It is concluded that TART most frequently develops in the children given the poorly controlled treatment; the insufficiency of both gluco- and mineralocorticoids is a predetermining but not the sole risk factor of the condition being considered.

Doppler ultrasonography and magnetic resonance imaging findings of testicular adrenal rest tissue in a patient with 11 β hydroxylase deficiency. Case report.

Benign intratesticular lesions are rare; thus, radiological diagnosis is important to avoid unnecessary surgical intervention. Testicular adrenal rest tumors (TART) are the nodular testicular lesions deriving from the adrenal remnant tissue reported in patients with congenital adrenal hyperplasia. We present ultrasonographic (US) and magnetic resonance imaging (MRI) findings of intratesticular adrenal rests in a 16-year-old patient with 11 β hydroxilase deficiency. Scrotal ultrasonography demonstrated bilateral heterogenous hypoechoic lesions located around mediastinum testis and highly vascularized on powerDoppler US. On MRI the lesions were hyperintense on T1-weighted and hypointense on T2-weighted images and enhanced brightly on post-contrast images.

Testicular adrenal rest tissue in a patient with classical congenital adrenal hyperplasia: color Doppler findings

Congenital adrenal hyperplasia (also known as congenital adrenogenital syndromes) refers to a group of autosomal recessive diseases characterized by altered cortisol production, which may be associated with aldosterone deficiency. The absence of cortisol synthesis stimulates corticotropin production by the adrenal cells and the accumulation of cortisol precursors, which will be diverted for the production of sex hormones. In affected males, ectopic adrenal tissue frequently develops, usually at the testicular level. This tissue is absolutely identical to that of the adrenal gland itself, and its functionality can be stimulated by ACTH and suppressed with glucocorticoid therapy. The authors report the case of a male patient with classic congenital adrenal hyperplasia, who was referred to our staff for evaluation of bilateral testicular tenderness and enlargement. Color Doppler sonography revealed mild enlargement of both gonads, widespread disruption of the testicular echostructure, and hypervascularization. Two months later, when the underlying disease had been controlled, repeat color Doppler ultrasonography revealed markedly decreased vascularity, although no change was noted on the B-mode examination. The color Doppler findings thus represent an early indicator of response to treatment.

Adrenal rest tissue in gonads of patients with classical congenital adrenal hyperplasia: Multicenter study of 45 French male patients

ObjectivesSeveral cases of testicular adrenal rest tumours have been reported in men with congenital adrenal hyperplasia (CAH) due to the classical form of 21-hydroxylase deficiency but the prevalence has not been established. The aims of this report were to evaluate the frequency of testicular adrenal rest tissue in this population in a retrospective multicentre study involving eight endocrinology centres, and to determine whether treatment or genetic background had an impact on the occurrence of adrenal rest tissue. Material and methodsTesticular adrenal rest tissue (TART) was sought clinically and with ultrasound examination in forty-five males with CAH due to the classical form of 21-hydroxylase deficiency. When the diagnosis of testicular adrenal rest tumours was sought, good observance of treatment was judged on biological concentrations of 17-hydroxyprogesterone (17OHP), delta4-androstenedione, active renin and testosterone. The results of affected and non-affected subjects were compared. ResultsTART was detected in none of the 18 subjects aged 1 to 15years but was detected in 14 of the 27 subjects aged more than 15years. Five patients with an abnormal echography result had no clinical signs. Therapeutic control evaluated at diagnosis of TART seemed less effective when diagnosis was made in patients with adrenal rest tissue compared to TART-free subjects. Various genotypes were observed in patients with or without TART. ConclusionDue to the high prevalence of TART in classical CAH and the delayed clinical diagnosis, testicular ultrasonography must be performed before puberty and thereafter regularly during adulthood even if the clinical examination is normal.

Phenotypic profiling of parents with cryptic nonclassic congenital adrenal hyperplasia: findings in 145 unrelated families

To comprehensively phenotype parents identified with nonclassic congenital adrenal hyperplasia (NCCAH) by family genetic studies, termed here as cryptic NCCAH and to define the incidence of cryptic NCCAH in the parents of a large cohort of patients with 21-hydroxylase deficiency. Genotyping was performed on 249 parents of 145 unrelated congenital adrenal hyperplasia (CAH) patients. Parents with two CYP21A2 mutations underwent extensive evaluation. Of the 249 parents, ten (4%; seven females and three males) were identified as having cryptic NCCAH. The majority was of ethnicities previously reported to have a higher incidence of NCCAH. Cosyntropin stimulation performed in eight parents provided biochemical confirmation (17-hydroxyprogesterone range 56-364 nmol/l) and cortisol response was ≤500 nmol/l in three parents (38%). Of the seven women (27-54 years) with cryptic NCCAH, four had prior infertility, two reported irregular menses, two had treatment for hirsutism, one had androgenic alopecia. Men were asymptomatic. All cryptic NCCAH parents reported normal puberty and had normal height. Adrenal hypertrophy and a small adrenal myelolipoma were observed in two parents; testicular adrenal rest tissue was not found. Parents diagnosed with NCCAH by genetic testing are mostly asymptomatic. Temporary female infertility and suboptimal cortisol response were commonly observed. Ongoing glucocorticoid therapy is not indicated in adults with CAH identified by family genotype studies unless symptomatic, but glucocorticoid stress coverage should be considered in select cases. Parents of a child with CAH have a 1:25 risk of having NCCAH; if the mother of a child with CAH has infertility, evaluation for NCCAH is indicated.

Prevalence of Testicular Adrenal Rest Tissue in Neonates

Prevalence of Testicular Adrenal Rest Tissue in Neonates

Prevalence of Testicular Adrenal Rest Tissue in Neonates

Background: Infertility is a serious complication among male congenital adrenal hyperplasia (CAH) patients which is often caused by testicular adrenal rest tumors (TART). TART are already present in childhood and early infancy in CAH patients. The incidence of TART in neonates without CAH has not yet been described in detail before. Objective: To study the prevalence of testicular adrenal rests in non-CAH neonates. Design: Descriptive study. Setting: Radboud University Nijmegen Medical Centre, The Netherlands. Patients and Methods: 115 testis samples of 89 male infants without CAH who died within the neonatal period were histologically examined. Main Outcome Measures: Prevalence of adrenal rest tissue in the neonatal testes. Results: Adrenal rests were found in 4 samples (3.5%). These adrenal nodules were all located within the epididymis; only in 1 sample a nodule was found close to the rete testis but still within the caput of the epididymis. No nodules were found within the testes. Of the 4 children with adrenal rests, 3 had urological malformations. Conclusion: The incidence of testicular adrenal rests in non-CAH neonates is low. Further studies are necessary to study the incidence of TART in CAH infants and detect typical risk factors in this patient group.

Clinical and Pathological Features Associated With the Testicular Tumor of the Adrenogenital Syndrome

Testicular tumor of the adrenogenital syndrome is a rare clinical entity found in young men with endocrine disorders. Histologically it resembles Leydig cell tumor. We 1) reviewed the clinical features of testicular tumor of the adrenogenital syndrome and 2) determined if special histopathological features of the tumor and synaptophysin reactivity could distinguish testicular tumor of the adrenogenital syndrome from Leydig cell tumor. We reviewed the medical and pathological records for all patients with testicular tumor of the adrenogenital syndrome seen at our institution from 1978 to 2004. These tumors were examined by histological and immunophenotypic methods for comparison to Leydig cell tumor. A total of 14 males with an endocrine disorder had pathological evidence of testicular tumor of the adrenogenital syndrome. These tumors were often bilateral (93% or 13 of 14 cases), associated with pain (92% or 12 of 13) and refractory to medical management with high dose exogenous steroids (93% or 13 of 14). Testicular tumor of the adrenogenital syndrome was managed by tumor enucleation in 7 patients (54%) and by radical orchiectomy in 6 (46%). All patients had resolution of pain at 3-month followup. Upon histological review features found to be more common to testicular tumor of the adrenogenital syndrome compared with Leydig cell tumor were nuclear pleiomorphism, low mitotic activity, extensive fibrosis, lymphoid aggregates, adipose metaplasia and prominent lipochrome pigment. Synaptophysin (ICN, Costa Mesa, California) reactivity was strong in testicular tumor of the adrenogenital syndrome but rarely observed in Leydig cell tumor. In our series medical treatment failed in patients with testicular tumor of the adrenogenital syndrome and conservative surgical therapy was possible in select individuals. We identified special histopathological and immunophenotypic features, including synaptophysin staining, which distinguish testicular tumor of the adrenogenital syndrome from Leydig cell tumor.

Nonclassical 21-Hydroxylase Deficiency

Nonclassical congenital adrenal hyperplasia (CAH) owing to steroid 21-hydroxylase deficiency (NC21OHD) is the most frequent of all autosomal recessive genetic diseases, occurring in one in 100 persons in the heterogeneous New York City population. NC21OHD occurs with increased frequency in certain ethnic groups, such as Ashkenazi Jews, in whom one in 27 express the disease. NC21OHD is underdiagnosed in both male and female patients with hyperandrogenic symptoms because hormonal abnormalities in NC21OHD are only mild to moderate, not severe as in the classical form of CAH. Unlike classical CAH, NC21OHD is not associated with ambiguous genitalia of the newborn female. The hyperandrogenic symptoms include advanced bone age, early pubic hair, precocious puberty, tall stature, and early arrest of growth in children; infertility, cystic acne, and short stature in both adult males and females; hirsutism, frontal balding, polycystic ovaries, and irregular menstrual periods in females; and testicular adrenal rest tissue in males. The signs and symptoms of hyperandrogenism are reversed with dexamethasone treatment.

Testicular adrenal rest tissue in congenital adrenal hyperplasia: serial sonographic and clinical findings.

The purpose of this study was to describe the serial sonographic findings and clinical and laboratory data obtained during follow-up of patients with congenital adrenal hyperplasia in whom testicular adrenal rest tissue develops. We retrospectively reviewed testicular sonography and laboratory data for 12 patients with congenital adrenal hyperplasia who also had intratesticular masses consistent with adrenal rest tissue. The studies were done during follow-up that ranged from 7 months to 10 years. During follow-up of 11 of the 12 patients after the initial sonographic diagnosis, the testicular adrenal rest tissue either remained stable in size (n = 1), grew larger or smaller (n = 9), disappeared (n = 4), or reappeared after disappearing (n = 3). In one patient, the testicular adrenal rest tissue grew very rapidly in a 1-month interval. Discordant changes in the testicular adrenal rest tissue were noted in 10 patients with bilateral masses. We found no relationship between the change in size of the masses and clinical control (based on 17-hydroxyprogesterone level) at the time of sonography. In patients with congenital adrenal hyperplasia who have testicular masses detected sonographically, testicular adrenal rest tissue is the most likely diagnosis. Testicular adrenal rest tissue may remain stable in size, grow larger or smaller, or disappear during sonographic follow-up. The change in size may be marked, may occur very rapidly, and, in our study cohort, was not related to short-term clinical control based on 17-hydroxyprogesterone level at the time of sonography.

Testicular adrenal rest tissue in congenital adrenal hyperplasia: findings at Gray-scale and color Doppler US.

To study the ultrasound (US) features of scrotal adrenal rest tissue in congenital adrenal hyperplasia (CAH). Gray-scale and color Doppler US examinations were performed of scrotal masses in eight patients. The masses were evaluated for size, location, echogenicity, sound attenuation, and vascularity. Seventeen intratesticular masses and one extratesticular mass were examined. All were hypoechoic except for one intratesticular mass that contained hyperechoic areas. Six masses demonstrated sound attenuation. The mediastinum testis was found in the center of 11 of the 17 intratesticular masses. At color Doppler US, six masses were hypervascular, seven were isovascular, and five were hypovascular relative to the normal testicle. All intratesticular masses contained vascular structures that entered them from the normal testis without change in course or caliber. Eleven masses showed a spoke-like pattern of converging vessels. The US features of scrotal adrenal rests assist diagnosis of CAH.

ACTIVATION OF TESTICULAR ADRENAL REST TISSUE BY PROLONGED EXCESSIVE ACTH PRODUCTION.

The concept that continuous excessive ACTH production can cause tumorous hyperplasia of “adrenal rest” cells within the testis is supported by studies in the patient reported here, who appears to represent the first reported instance of a cortisol4-producing testicular tumor in recurrent Cushing's disease. A 14-year-old boy who had had a subtotal adrenalectomy and subtotal resection of a pituitary tumor presented with signs of recurrent glucocorticoid excess associated with the development of a testicular tumor. Urinary 17-ketosteroids, 17-hydroxysteroids and plasma ACTH levels were elevated. ACTH stimulation and dexamethasone suppression suggested an autonomous steroidproducing tumor. Removal of the testicular tumor produced symptomatic improvement, with a reversion to normal of the urinary steroids in spite of persistence of pigmentation. Histologically, the tumor was reported to be either an interstitial tumor of testicular origin or an adrenal rest tumor. Incubation studies of the tumor with C14-label...