Infertility risk assessment with ultrasound in congenital adrenal hyperplasia male patients.

Testicular adrenal rest tumor (TART) is a prevalent complication associated with congenital adrenal hyperplasia (CAH), culminating in gonadal dysfunction and infertility. Early hormonal intervention is preventive, but excessive glucocorticoid poses risks. Developing reliable methods for early TART diagnosis and monitoring is crucial. The present study aims to formulate a scoring system to identify high-risk infertility through analysis of TART ultrasound features. Grayscale and power Doppler ultrasound were employed in this retrospective study to evaluate testicular lesions in male CAH patients. Lesion assessment encompassed parameters such as range, echogenicity, and blood flow, and these were subsequently correlated with semen parameters. Results of 49 semen analyzes from 35 patients demonstrated a notable inverse correlation between lesion scores and both sperm concentration (rs = - 0.83, P < 0.001) and progressive motility (rs = - 0.56, P < 0.001). The ROC curve areas for evaluating oligospermia and asthenozoospermia were calculated as 0.94 and 0.72, respectively. Establishing a lesion score threshold of 6 revealed a sensitivity of 75.00% and specificity of 93.94% for oligospermia and a sensitivity of 53.85% and specificity of 100.00% for asthenozoospermia. These findings underscore the potential utility of incorporating ultrasound into routine CAH patient management, facilitating timely interventions to preserve male fertility.

Ovarian adrenal rest tumor in congenital adrenal hyperplasia: Is medical treatment the first line option?

SUMMARY Ovarian adrenal rest tumors (OARTs) are very rare. We describe a case of a young woman with uncontrolled classical congenital adrenal hyperplasia (CCAH), presenting with bilateral OARTs, successfully treated with steroid replacement. A 20-year-old woman, known to have 21OH-CCAH, presented with severe abdominal pain, vomiting, diarrhea, and fever. As a result of poor compliance, 6 months before her admission hirsutism worsened and amenorrhea, hyperpigmentation, and weakness developed. ACTH levels were 278 < pmol/L and 17OHP 91.3 nmol/L. She was admitted for parenteral antibiotics and high-dose hydrocortisone treatment. CT revealed bilateral juxta-ovarian masses (6.2 x 3.6 x 7.4 cm left and 5 x 2.2 x 3.2 cm right) that on MRI were iso-intense in T1 and hypointense in T2, with early enhancement and rapid washout. One week of high-dose hydrocortisone resulted in significant clinical and laboratory improvement and the patient was discharged with 2 mg dexamethasone/day. One month later US revealed shrinkage of the masses and dexamethasone dose was decreased. At three months from discharge, she has resumed regular menses, and a repeated MRI revealed the para-ovarian masses have shrunk. One year after the diagnosis, the para-ovarian masses have shrunk more to 2.8 x 1.9 x 4.3 on the left and 2.1 x 0.9 x 1.2 on the right with less contrast enhancement in comparison to previous test possibly due to fibrotic changes of the tissue. OARTs are rare tumors with a poorly known natural history, and surgery has been the first option in the few reported cases. We demonstrate that medical treatment is a good alternative, leading to significant tumor shrinkage over a short period.

Ovarian adrenal rest tumor in congenital adrenal hyperplasia: Is medical treatment the first line option?

Ovarian adrenal rest tumors (OARTs) are very rare. We describe a case of a young woman with uncontrolled classical congenital adrenal hyperplasia (CCAH), presenting with bilateral OARTs, successfully treated with steroid replacement. A 20-year-old woman, known to have 21OH-CCAH, presented with severe abdominal pain, vomiting, diarrhea, and fever. As a result of poor compliance, 6 months before her admission hirsutism worsened and amenorrhea, hyperpigmentation, and weakness developed. ACTH levels were 278 < pmol/L and 17OHP 91.3 nmol/L. She was admitted for parenteral antibiotics and high-dose hydrocortisone treatment. CT revealed bilateral juxta-ovarian masses (6.2 × 3.6 × 7.4 cm left and 5 × 2.2 × 3.2 cm right) that on MRI were iso-intense in T1 and hypointense in T2, with early enhancement and rapid washout. One week of high-dose hydrocortisone resulted in significant clinical and laboratory improvement and the patient was discharged with 2 mg dexamethasone/day. One month later US revealed shrinkage of the masses and dexamethasone dose was decreased. At three months from discharge, she has resumed regular menses, and a repeated MRI revealed the para-ovarian masses have shrunk. One year after the diagnosis, the para-ovarian masses have shrunk more to 2.8 × 1.9 × 4.3 on the left and 2.1 × 0.9 × 1.2 on the right with less contrast enhancement in comparison to previous test possibly due to fibrotic changes of the tissue. OARTs are rare tumors with a poorly known natural history, and surgery has been the first option in the few reported cases. We demonstrate that medical treatment is a good alternative, leading to significant tumor shrinkage over a short period.

Testicular adrenal rest tumors in children with congenital adrenal hyperplasia.

OBJECTIVES: To identify testicular adrenal rest tumors (TARTs) prevalence among children with congenital adrenal hyperplasia (CAH) and to assess hormonal control role as a contributing factor for TART development. Testicular adrenal rest tumors are benign tumors complicating CAH. It affects adult males with CAH commonly, with a reported prevalence of 40% on average, and up to 94%. There is insufficient data regarding their prevalence in children aged above 4 years and adolescents. METHODS: This descriptive study included 21 children and adolescents with CAH (17 salt wasting type, 4 non salt wasting type) aged 4-20 years who were screened for TARTs by routine testicular ultrasonography from October 2012 to December 2020 at King Abdulaziz University Hospital, Jeddah, Kingdom of Saudi Arabia. Serum adrenocorticotropic hormone, 17-hydroxy progesterone, testosterone, dehydroepiandrosterone, and luteinizing hormone levels were measured. RESULTS: Testicular adrenal rest tumors were detected in 6 (28%) patients (median age: 12.5 years). The youngest affected child was 8 years old. All patients with TARTs were asymptomatic with impalpable testicular masses at the time of detection. Bilateral involvement was observed in 5 patients, while one patient had unilateral involvement. All patients with TARTs had poor hormonal control, and 4 patients had advanced bone age. CONCLUSION: Testicular adrenal rest tumors development has been shown to correlate with poor hormonal control. Annual screening of young children with CAH for TART development is crucial, even for asymptomatic or with impalpable testicular masses.

Sonographic features of the testicular adrenal rests tumors in patients with congenital adrenal hyperplasia: a single-center experience and literature review.

PURPOSE: Testicular adrenal rests tumor (TART) is a rare kind of benign tumor in the testis. It usually occurred secondary to congenital adrenal hyperplasia (CAH), a hormonal disorder caused by hydroxylase deficiency. As the first-line examination method, ultrasound provides crucial diagnostic information for TART, although misdiagnosis to malignancy is quite common because of its rare prevalence. We aimed to summarize the sonographic manifestations of TART to improve the diagnostic accuracy and specificity. METHODS: Eight CAH patients with TART identified by ultrasound in our medical center were retrospectively reviewed. Clinical and hormonal profile, semen analysis and treatment choices were collected. Sonographic examinations were performed at the first evaluation and interpreted by experienced radiologists individually. All patients received regular follow-up, and 5 patients undertook repeated scrotal ultrasound. A literature review of TART in CAH patients was conducted, with 123 patients from 23 articles since 1990 included. RESULTS: A total of 8 patients aged between 4 to 27 years old were enrolled. 7 of 8 (87.5%) patients exhibited bilateral testicular lesions. The sizes of the testicular lesions were between 0.18 ml to 5.68 ml, and all showed a clear boundary. 10/15 (66.7%) lesions were homogenously hypoechoic, 4/15 (26.7%) were heterogeneously iso-hypoechoic, and 1/15 (6.7%) were homogenously isoechoic. 10/15 (66.7%) lesions were hyper-vascular. The longitudinal follow-up of 5 patients showed testicular lesions changed in terms of size, echogenicity, and vascularity after steroid treatment. A potential correlation may exist between ACTH levels and tumor size (p = 0.066). From the literature review, 100/123 (81%) patients got bilateral lesions, and 95% of them were located near the mediastinum. 80/103 (78%) lesions exhibited a clear boundary, and predominant lesions (74%) were hypoechogenic. Vascularity was with great diversity. Seventy-nine lesions of 44 patients were followed-up by scrotal ultrasound, among which 29 (37%) remained unchanged, 29(37%) shrank, and 21(27%) disappeared. CONCLUSIONS: Key sonographic characteristics of TART are: resembled lesions on both testes, located near the mediastinum, clear boundary, and changed in size or echogenicity after steroid treatment. These features can help radiologists to make an accurate diagnosis of TART.

Testicular adrenal rest tumors in patients with congenital adrenal hyperplasia: 6 years of follow-up.

Background Testicular adrenal rest tumors (TARTs) leading to primary gonadal failure are the main etiology of infertility in congenital adrenal hyperplasia (CAH). We aimed at identifying the evolution of TART and related findings in young CAH patients. Methods Twelve male patients (3-23 years old) with 21-hydroxilase deficiency (11 with classic salt-wasting form) were included. Testicular ultrasonography (US) was performed in two moments, by a single blinded specialist in pediatric diagnostic imaging. Tumor progression was classified according to the Response Evaluation Criteria in Solid Tumors (RECIST). The clinical and laboratory data were retrieved from medical records. Serum 17-OH-progesterone (17OHP) and androstenedione concentrations were evaluated during the whole period of follow-up, from the CAH diagnosis. A logistic regression model with repeated measures was developed for the analysis. Results The prevalence of TART was 41.6% (n = 5) in the initial US evaluation and 66.6% (n = 8) after 6 years of follow-up. Tumor progression was detected in 4 of the 5 patients, and 1 presented with a stable tumor. Three patients presented with new tumors in the second evaluation. Most of the patients (n = 11) were pubertal, including a 7-year-old child with TART who presented with central precocious puberty. At regression analysis, it was observed that an inadequate hormonal control led to a 16 times greater chance of a patient to present with TART (OR = 16.08; confidence interval [CI] 95% = 2.38-108.81; p = 0.004). Conclusions We found a high prevalence of progressive TART in young pubertal subjects. US testicular screening should help in improving therapeutic optimization in CAH patients to reduce future impairment in fertility.

Case series of testicular adrenal rest tumours in boys with congenital adrenal hyperplasia: A single centre experience.

Testicular adrenal rest tumours (TART) are aberrant adrenal tissue within the testes (1). Although benign, they can lead to obstruction of the seminiferous tubules and infertility in patients with congenital adrenal hyperplasia (CAH). We report six boys who developed TART, a complication of CAH. Diagnosis was confirmed by ultrasound and testicular vein sampling of elevated 17-hydroxyprogesterone (17-OHP) levels. Glucocorticoids dosages were increased 1½-2 folds to suppress size of the aberrant adrenal tissues. Despite reductions in 17-OHP, the lesions remained unchanged. Three patients had testis-sparing surgery to excise the TART and to preserve normal testicular tissues.

Computed tomography findings of testicular adrenal rest tumors resulted from 21-hydroxylase deficiency.

21-hydroxylase deficiency is a rare kind of autosomal recessive disorders, which can result in congenital adrenal hyperplasia and/or testicular adrenal rest tumors. 21-hydroxylase deficiency with TARTs is prone to be misdiagnosed as Leydig cell tumors. Although the sonographic characteristics of TARTs have been summarized in previous reports, its features in computed tomography images were rarely reported. In this study, we presented and summarized the clinical and imaging data of a special case suffering this disease, aiming to improve the imaging diagnosis performance.

Para-ovarian adrenal rest tumors: gynecologic manifestations of untreated congenital adrenal hyperplasia.

Congenital adrenal hyperplasia (CAH) is an inherited disorder of adrenal steroidogenesis often diagnosed in infancy. Gynecologists may encounter adult patients with CAH due to the clinical effects of increased androgens, e.g. hirsutism, clitoromegaly, oligomenorrhea, or, rarely, pelvic masses. This case report reviews the association of para-ovarian adrenal rest tumors with CAH, and the role of gynecologists in their evaluation and treatment. A 23-year-old woman with CAH (21-hydroxyase deficiency) untreated for the past 5 years presented with a pelvic mass and elevated serum testosterone (1433 ng/dL) and plasma ACTH (1117 pg/mL). Intraoperative findings revealed multiple retroperitoneal masses. Final pathology demonstrated adrenal rest tissue. Para-ovarian and ovarian adrenal rest tumors may present as a rare gynecologic manifestation in patients with untreated CAH.

Testicular adrenal rest tumor screening and fertility counseling among males with congenital adrenal hyperplasia.

BACKGROUND: Reduced fertility is a common potential problem among males with congenital adrenal hyperplasia (CAH), with nearly half experiencing impaired sperm production. The major cause of oligo/azoospermia in CAH is testicular adrenal rest tumors (TARTs). Studies indicate that ultrasound screening for TARTs should begin during childhood, yet it remains unclear whether boys with CAH are routinely screened for TARTs and/or counseled about infertility risk and potential interventions such as fertility testing and/or preservation. OBJECTIVE: The purpose of this study was to examine TART screening and fertility counseling practices among boys with CAH. STUDY DESIGN: An IRB-approved retrospective chart review was conducted of all males with ICD-9/10 codes for CAH (2007-2016) at a large pediatric academic center to examine: age and indication for diagnosis; age at first and last documented pediatric endocrinology and urology visit; history of ultrasound examinations; and documentation of fertility counseling. RESULTS: Forty-six patients were included, of whom 38 had 21-hydroxylase deficiency. Median age at diagnosis was 2 weeks (range 7 days-10 years). Median age at the most recent pediatric endocrinology clinic visit was 14 years (range 2-42 years). Twenty-nine patients were >11 years old (63% of the sample) at the time of the study and 14 of these were >18 years old (30% of the sample). Seven patients (15%) had a screening ultrasound at some point in their care, of whom three had TARTs. Fertility was mentioned in the records of six subjects (13% of the sample). Six of the subjects (13%) had any mention of fertility in their records. None of the patients had biochemical testing or semen analysis to assess gonadal function, and none were offered fertility preservation. Only one patient was seen by a pediatric urologist. DISCUSSION: Despite the limitations of a single-center retrospective design, our findings highlight that TART screening and fertility counseling remain underutilized in boys with CAH. There is a need for increased awareness and development of practice guidelines within pediatric urology and endocrinology to address this common and understudied problem. CONCLUSION: In addition to a screening ultrasound in puberty and consideration of semen analysis after puberty, these boys may benefit from seeing a pediatric urologist independently or in an interdisciplinary program. Boys with CAH and their families should be educated about infertility risk and potential interventions, with the goal of improving reproductive outcomes in this population.

Chemical Shift MR Imaging of the Adrenal Gland: Principles, Pitfalls, and Applications.

Adrenal lesions are a common imaging finding. The vast majority of adrenal lesions are adenomas, which contain intracytoplasmic (microscopic) fat. It is important to distinguish between adenomas and malignant tumors, and chemical shift magnetic resonance (MR) imaging can be used to accomplish this distinction by depicting the fat in adenomas. Chemical shift imaging is based on the difference in precession frequencies of water and fat molecules, which causes them to be in different relative phases during the acquisition sequence and allows in-phase and opposed-phase images to be obtained. It is important to acquire these images by using the earliest possible echo times, with the opposed-phase echo before the in-phase echo, and by using a single breath hold to preserve diagnostic accuracy. Intracytoplasmic fat is depicted as signal drop on opposed-phase images when compared with in-phase images. Both qualitative and quantitative methods for assessing signal drop are detailed. The appearances of adrenal adenomas and other adrenal tumors on chemical shift MR images are described, and discriminatory ability at chemical shift MR imaging compared with that at adrenal computed tomography (CT) is explained. Other adrenal-related conditions in which chemical shift MR imaging is helpful are also discussed. Chemical shift MR imaging is a robust tool for evaluating adrenal lesions that are indeterminate at nonenhanced CT. However, it is important to know the advantages and disadvantages, including several potential imaging pitfalls. The characterization of adrenal lesions by using chemical shift MR imaging and adrenal CT should always occur in the appropriate clinical setting.

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

OBJECTIVE: 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). DESIGN: Retrospective analysis of men attending an adult CAH clinic in a tertiary centre. PATIENTS: Fifty men with CAH due to 21 hydroxylase deficiency were identified of whom 35 were salt wasting and 15 were non-salt-wasting. MEASUREMENTS: 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. RESULTS: 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. CONCLUSIONS: 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.

Diagnosis of Testicular Adrenal Rest Tumors on Ultrasound: A Retrospective Study of 15 Cases Report.

The aim of this study was to evaluate the imaging features of testicular adrenal rest tumors (TARTs) on baseline ultrasound (BUS).The imaging features of 30 TART lesions pathologically or clinically confirmed in 15 patients who had undergone BUS were evaluated, and the sonographic characteristics of the lesions were analyzed.All 15 cases were bilateral and located near the testicular mediastinum. Approximately 56.7% (17/30) of the TART lesions exhibited homogeneous hypoechogenicity, 36.7% (11/30) of the lesions exhibited heterogeneous hypoechogenicity, and 6.6% (2/30) of the lesions exhibited heterogeneous isoechogenicity. In addition, 76.7% (23/30) of the lesions exhibited a rich blood supply, whereas 23.3% (7/30) of the lesions exhibited a scarce blood supply.The sonographic characteristics of the TARTs were bilateral growth, location adjacent to the testicular mediastinum, hypoechogenicity, and rich blood supply, which may play important roles in early clinical diagnosis.

Clinical Outcome, Hormonal Status, Gonadotrope Axis, and Testicular Function in 219 Adult Men Born With Classic 21-Hydroxylase Deficiency. A French National Survey.

CONTEXT: Outcomes of congenital adrenal hyperplasia due to classic 21-hydroxylase deficiency (21OHD) have been widely studied in children and women, but less so in men. OBJECTIVE: The objective was to analyze data from a network of metropolitan French teaching hospitals on the clinical outcome of classic 21OHD in a large sample of congenital adrenal hyperplasia/21OHD-genotyped adult men, and particularly the impact of 21OHD on the gonadotrope axis, testicular function, and fertility. METHODS: From April 2011 to June 2014, tertiary endocrinology departments provided data for 219 men with 21OHD (ages, 18-70 y; 73.6% salt wasters, 26.4% simple virilizers). Testicular sonography was performed in 164 men, and sperm analysis was performed in 71 men. RESULTS: Mean final height was 7.8 cm lower than in a reference population. Obesity was more common, and mean blood pressure was lower than in the reference population. None of the patients were diabetic, and lipid status was generally normal. Blood electrolyte status was normal in the vast majority of men, despite markedly elevated ACTH and renin levels. Serum progesterone, 17-hydroxyprogesterone, and androstenedione levels were above normal in the vast majority of cases. Hormonal profiling variously showed a normal gonadotrope-testicular axis, gonadotropin deficiency, or primary testicular insufficiency. Testicular sonography revealed testicular adrenal rest tumors (TARTs) in 34% of 164 men. Serum inhibin B and FSH levels were significantly lower and higher, respectively, in patients with TARTs. Severe oligospermia or azoospermia was found in 42% of patients and was significantly more prevalent in men with TARTs (70%) than in men with normal testes (3.6%; P < .0001). Among men living with female partners, TARTs were significantly more prevalent in those who had not fathered children. CONCLUSION: We report the spectrum of testicular/gonadotrope axis impairment in the largest cohort of 21OHD men studied to date. Our results suggest that French men with 21OHD managed in specialized centers frequently have impaired exocrine testicular function but that its reproductive implications are often overlooked.

Increased prevalence of testicular adrenal rest tumours during adolescence in congenital adrenal hyperplasia.

UNLABELLED: Testicular adrenal rest tumours (TART) are one of the most important causes of infertility in adult male patients with congenital adrenal hyperplasia (CAH). These benign tumours are already detected in children, but screening of TART is not routinely performed. OBJECTIVE: To define retrospectively the prevalence of TART in 41 paediatric male CAH patients aged 0-19 years regularly followed by high-frequency (Fcentral 12-MHz) ultrasound techniques. RESULTS: Above the age of 10 years, there was a clear increase in the prevalence of TART: 10-12 years, 28% (2 of 7 patients), 13-14 years, 50% (4/8), and 15-16 years, 75% (3/4). Above the age of 16 years, TART were detected in 100% of the patients (7/7). The tumours were not detectable by palpation. CONCLUSION: TART is already present in childhood with an increasing prevalence after onset of puberty. We recommend regular ultrasound from the onset of puberty in all boys with classic CAH.

Testicular adrenal rest tumors develop independently of long-term disease control: a longitudinal analysis of 50 adult men with congenital adrenal hyperplasia due to classic 21-hydroxylase deficiency.

CONTEXT: Testicular adrenal rest tumors (TARTs) and hypogonadotropic hypogonadism are the two most common causes for male infertility in classic 21-hydroxylase deficiency. Current hypotheses suggest the quality of disease control to be one of the main pathogenic factors for TART development. OBJECTIVE: The aim was to study long-term predictors for TART development in a retrospective longitudinal study. DESIGN: Fifty men with classic 21-hydroxylase deficiency (31 salt wasting, 19 simple virilizing) were investigated. Testicular ultrasound at a median age at investigation of 27 years detected TARTs in 28 of 50 subjects (19 salt wasting, 9 simple virilizing). TART presence was correlated with long-term parameters of disease control during childhood and adolescence obtained from patients' charts: 24-hour urine pregnanetriol, serum 17-hydroxyprogesterone, onset and stage of pubic hair development, testicular growth, and bone age in relation to chronological age. RESULTS: There was no difference in pregnanetriol excretion over lifetime between patients with and without TARTs. Similarly, neither development of pubic hair and testicular volume (Tanner) nor bone age in relation to chronological age differed between the two groups. Furthermore, the two groups had the same body mass index and the same impairment of final height in relation to midparental target height. CONCLUSION: Our longitudinal analysis demonstrates no association between TART presence and parameters of disease control. These data, therefore, argue for other mechanisms more relevant for TART induction including those occurring during fetal development.

Testicular adrenal rest tumors in boys with congenital adrenal hyperplasia: 3D US and elastography--do we get more information for diagnosis and monitoring?

BACKGROUND: Testicular adrenal rest tumors (TART) are the nodular testicular lesions deriving from the adrenal remnant tissue reported in boys and men with congenital adrenal hyperplasia. Until now, the diagnostics of TART have been based on a combination of clinical features, imaging methods (primarily two dimensional ultrasound--2D US), response of the foci to glycocorticosteroid (GCS) therapy and exclusion of the neoplastic process. Application of 2D US supplies however a limited range of information about the volume, demarcation, structure and vascularization of the lesions. OBJECTIVE: To define whether the use of 3D US, power Doppler and elastography changes the algorithm of the diagnostics and monitoring or treatment of TART. MATERIAL AND METHODS: In this study, modern ultrasound techniques such as 3D US and elastography were introduced in two boys with TART. RESULTS: The 3D power Doppler option gives the opportunity for accurate assessment of the volume of testes and adrenal tissue foci and their vascularization. Sonographic elastography allows the assessment of stiffness of adrenal tissue areas compared to normal testis parenchyma. CONCLUSION: The use of these modern techniques enables more adequate and advanced diagnostics, and more precise monitoring of the effects of treatment in patients with TART.