Testicular Adrenal Rest Tumors Research Articles

MANAGEMENT OF ENDOCRINE DISEASE: Gonadal dysfunction in congenital adrenal hyperplasia.

Gonadal dysfunction is an adverse outcome in patients with congenital adrenal hyperplasia (CAH), which may become apparent already during puberty. Clinical consequences of gonadal dysfunction include menstrual disturbances in females and hypogonadism and impaired fertility in males and females. In males, gonadal dysfunction can be caused by primary gonadal failure due to testicular adrenal rest tumours (TART), and by secondary gonadal failure due to poor hormonal control. In females, gonadal dysfunction can result from an overproduction of adrenal androgens including 11-oxygenated C-19 androgens and progestins, and rarely from ovarian adrenal rest tumours. In all patients with CAH, optimal hormonal control is the key for adequate gonadal function. Therefore, regular measurements of adrenal steroids and/or their metabolites should be performed. In addition, markers of the hypothalamus-pituitary-gonadal axis need to be assessed. In females, the regularity of the menstrual cycle should be evaluated. In males, regular evaluation for TART using ultrasonography is recommended from the start of puberty or even earlier when poor hormonal control is present. When TART is present, counselling on cryopreservation of semen should be offered.

Testicular adrenal rest tumor (TART) in congenital adrenal hyperplasia misdiagnosed as Leydig cell tumor

Testicular adrenal rest tumor (TART) in congenital adrenal hyperplasia misdiagnosed as Leydig cell tumor

Ovarian adrenal rest tumor in a patient with salt-wasting form of congenital adrenal hyperplasia

The article describes the clinical case of diagnosing and choosing the tactics for treating ovarian adrenal rest tumors (OART) in a patient with a salt-wasting form of congenital adrenal hyperplasia (CAH). There are only several clinical cases descriptions of OART in the world literature. At present, the tactics of observation and treatment of the ovarian adrenal rest tumors has not been developed. In each case, individual tactics are chosen. The main predisposing factor to the occurrence of OART is considered to be long periods of decompensation of CAH. ACTH stimulates the hyperplasia and hypertrophy of the residual adrenal tissue in the ovaries and secondary tumors develop. The instrumental methods that allow to diagnose OART include ultrasound, MRI of the pelvic organs, PET with 18FDG. The tactics of treating OART, in contrast to the testicular adrenal rest tumors in men (TART), according to world literature are mainly surgical. Organ-preserving operations were performed, as well as the removal of tumors along with the ovary. Cases of a combination of adenocarcinoma and CAH are also described. Each new case of OART is unique and with the accumulation of international experience, a consensus will be developed.

Clinical characteristics of testicular adrenal rest tumor and factors associated with its occurrence in 21-hydroxylase deficiency patients

Objective: To analyze the occurrence and clinical characteristics of testicular adrenal rest tumor (TART) in 21-hydroxylase deficiency (21-OHD) patients, and further explore the possible factors related to the occurrence of TART. Methods: Twenty-seven male 21-OHD patients who visited Peking Union Medical College Hospital from January to December 2018 were enrolled and their clinical and biochemical data were collected. The CYP21A2 mutations were identified by Sanger sequencing and multiple ligation probe amplification (MLPA). Patients were divided into different subgroups according to the residual activity of 21-hydroxylase: Null (residual enzymatic activity 0, 3 cases), group A (0-<1%, 9 cases), group B (1%-5%, 7 cases), group C (20%-50%, 2 cases) and group D (6 cases). The ultrasound of testis was used to detect whether there was TART and its morphological characteristics. Results: Among 27 patients with 21-OHD [average age (17.4±9.3) years], 55.6% (15/27) had TART lesions, most of them were adolescents, and the youngest was only 4 years old. The lesions were mostly bilateral and hypoechoic. The levels of 17α-hydroxyprogesterone (17-OHP) and progesterone in patients with TART were higher than those in patients without TART [17-OHP: 199.6 (62.1, 232.7) nmol/L vs 7.4 (3.2, 105.0) nmol/L, P=0.003; progesterone: 97.1 (42.0, 126.8) nmol/L vs 5.4 (0.7, 20.0) nmol/L, P=0.004]. There was a correlation between the occurrence of TART and genotype of CYP21A2. Patients with Null and A genotypes were more likely to have TART than those with B and C genotypes (8/12 vs 4/9, P=0.021). Conclusions: TART is common in 21-OHD male patients, which is related to 17-OHP and CYP21A2 genotype. It is of great significance for the early screening of TART in 21-OHD patients.

Testicular Adrenal Rest Tumour (TART) or Testicular Malignancy: A Clinical Dilemma.

Testicular adrenal rest tumour (TART) is a known entity in patients with congenital adrenal hyperplasia. An adult patient presenting with testicular enlargement raises a concern for malignancy and this creates a diagnostic dilemma between non-malignant conditions such as TART versus testicular malignancy. We describe a case where the patient underwent orchiectomy due to clinical concern for malignancy but, retrospectively, this outcome could have been prevented by medical treatment. This case emphasises the need to learn from errors. There is a need to increase awareness of the condition among medical professionals to reduce the chances of unnecessary surgical intervention.LEARNING POINTSTo recognize testicular adrenal rest tumour (TART) as cause of testicular enlargement in adult patients with congenital adrenal hyperplasia.To differentiate TART from other types of testicular malignancy.Consider medical treatment with exogenous glucocorticoid and mineralocorticoid replacement to prevent unnecessary surgical intervention.

MON-171 Characterization of the Adrenal Gland and Adrenal Rest Tissues in Congenital Adrenal Hyperplasia

Background: Adrenonodular hyperplasia and tumor formation are common long-term complications of congenital adrenal hyperplasia (CAH) driven by chronic ACTH elevation. Clinical studies indicate that the majority of males with classic CAH have testicular adrenal rest tumors (TART). Ovarian adrenal rest tumors (OART) are less commonly observed. Little is known about the pathophysiology of adrenal rest, however both adrenal cortex and Leydig cell markers have been described in TART, suggesting a pluripotent embryological cell origin. Objective: To characterize adrenals and adrenal rest tissues of patients with CAH in comparison with normal tissues. Materials and Methods: Using immunohistochemistry (IHC) and, real-time qRT-PCR we investigated CAH-affected adrenals (n=5), adrenal rest tissues (n=2; 1 testicular, 1 ovarian), controls [normal adrenal (n=2), testis (n=1), and ovary (n=1)]. Tissue sections prepared from paraffin embedded tissue blocks were immunostained with adrenal [melanocortin 2 receptor (MC2R), delta-like homolog 1 (DLK-1), steroidogenic factor 1 (SF-1), steroidogenic acute regulatory protein (StAR) and other cytochrome P450 genes], inflammatory [interleukin 2 receptor (IL-2R), B-lymphocyte antigen (CD20), cluster of differentiation 3 (CD3), tumor necrosis factor alpha (TNFα), interleukin 6 (IL6)], and gonadal markers [progesterone receptor (PR), androgen receptor (AR), insulin-like 3 (INSL3)]. RNA was isolated and gene expression studies were performed. High-throughput RNA sequencing technology was used to analyze the differential transcriptome profiles between the CAH adrenals, adrenal rest and normal tissues.Results:In contrast to the controls, CAH adrenals and adrenal rest tissues showed the following:(i) IHC studies revealed 95% of tissue positive for adrenal zona-reticularis; (ii) significant nodular lymphocytic infiltration with a predominance of B and T lymphocytes and overexpression of lymphocyte markers IL-2R, CD20, CD3, and inflammatory cytokines TNFα and IL6; (iii) increased expression of adrenocortical specific genes MC2R, DLK1. Conclusion: CAH-affected adrenals and adrenal rest tissue have similar predominance of zona reticularis and demonstrate lymphocytic infiltration. Active inflammation may play a role in the abnormal development of adrenal and adrenal rest tissue in CAH patients.

Glucocorticoid replacement regimens for treating congenital adrenal hyperplasia.

Glucocorticoid replacement regimens for treating congenital adrenal hyperplasia.

Congenital adrenal hyperplasia with an ovarian adrenal rest tumor: a case report

Adrenal rest tumors (ART) are extra-adrenal findings of adrenal tissue. Testicular adrenal rest tumors (TART) are widespread in males with congenital adrenal hyperplasia (CAH). Ovarian adrenal rest tumours (OART), which form in females with CAH, are less commonly seen. Reports in literature of OART are extemely rare. The case is here presented of a 43-year-old female who was diagnosed at the age of 15 years with CAH and underwent bilateral adrenalectomy at the age of 37. On presentation at our clinic, 4×2 cm mass was determined on the right adnexa in the advanced tests and a right-side salpingo-oopherectomy was performed. The pathology examination reported heterotopic adrenal cortical tissue. Routine ovarian imaging in females with CAH is not indicated. Although OART are rarely seen, they should be kept in mind and these patients should be evaluated radiologically together with laboratory tests.

Testicular Adrenal Rest Tumors in Patients with Congenital Adrenal Hyperplasia: A Case Series

Objective: Testicular adrenal rest tumors (TARTs) are the main etiology of infertility in congenital adrenal hyperplasia (CAH). The aim of this study is to determine the patients diagnosed with TART and to evaluate the risk factors associated with the development of the disease. Methods: Clinical characteristics of 31 patients with CAH including 19 male, and 12 female patients who were followed up in our clinic were retrospectively reviewed regarding the presence of TART. Differences between clinical and laboratory findings of patients with and without TART were examined. Six male patients with TART were included in the study. Clinical characteristics such as pubertal stage, treatment doses, laboratory findings were evaluated. Changes in size of TARTs were examined with ultrasound follow-ups at six month- intervals. Results: The prevalence of TARTs was 31.5 % (6/19 male). Precocious puberty was higher in patients with TART than without TART. The mean age of the patients was 9.1±2.4 (range: 5.2-12.4) years at the time of diagnosis with TART. Five patients with TART were inadequately controlled. Four patients had a history of precocious puberty. Tumor progression was detected in 4 of 6 patients. In three patients with tumor progression, serum 17-hydroxy progesterone (17-OHP) values increased during follow-up, probably due to non-compliance with treatment. Conclusion: Scrotal ultrasound monitoring should be performed in all male patients with CAH in early childhood irrespective of disease control.

Testicular adrenal rest tumors diagnosed on ultrasound with a history of congenital adrenal hyperplasia and medication non-compliance.

Testicular adrenal rest tumors diagnosed on ultrasound with a history of congenital adrenal hyperplasia and medication non-compliance.

Absence of Testicular Adrenal Rest Tumors in Newborns, Infants, and Toddlers with Classical Congenital Adrenal Hyperplasia

Introduction: Testicular adrenal rest tumors (TART) are a known consequence for males with classical congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency. TART are associated with potential infertility in adults. However, little is known about TART in very young males with CAH. Objective: We assessed the presence of TART in newborn, infant, and toddler males with classical CAH via scrotal ultrasound. Methods: Males with CAH had scrotal ultrasounds during the first 4 years of life, evaluating testes for morphology, blood flow, and presence of TART. Newborn screen 17-hydroxyprogesterone (17-OHP) and serum 17-OHP at the time of ultrasound were recorded. Bone ages were considered very advanced if ≥2 SD above chronological age. Results: Thirty-one ultrasounds in 16 males were performed. An initial ultrasound was obtained in four newborns at diagnosis (6.8 ± 2.1 days), six infants (2.2 ± 0.9 months), and six toddlers (2.4 ± 0.9 years). Eleven males had at least one repeat ultrasound. A large proportion (11/16) were in poor hormonal control with an elevated 17-OHP (325 ± 298 nmol/L). One infant was in very poor hormonal control (17-OHP 447 nmol/L) at initial ultrasound, and two toddlers had advanced bone ages (+3.2 and +4.5 SD) representing exposure to postnatal androgens. However, no TART were detected in any subjects. Conclusions: TART were not found by scrotal ultrasound in males up to 4 years of age with classical CAH despite settings with expected high ACTH drive. Further research into the occurrence of TART in CAH may elucidate factors that contribute to the detection and individual predisposition to TART.

The High Prevalence of Testicular Adrenal Rest Tumors in Adult Men With Congenital Adrenal Hyperplasia Is Correlated With ACTH Levels.

Introduction: The aims of this study were to determine the prevalence of testicular-adrenal rest tumors (T-ARTs) in patients with congenital adrenal hyperplasia (CAH) and to evaluate the related ultrasound (US) features, hormonal profiles, and semen parameters. Therefore, we attempted to understand the potential impact of adrenocorticotropic hormone (ACTH) on the persistence or disappearance of T-ART.Methods: We conducted a longitudinal cohort study including patients with CAH who were undergoing treatment with cortisone and, when indicated, fludrocortisone replacement therapy. We performed andrological examinations, US of the testis, hormone profiling, and semen analysis.Results: Of the 25 patients (mean ± SD age, 32.2 ± 7.5 years), T-ARTs were detected by US in 14 (56.0%) patients. The mean ± SD diameter of the lesions was 13.2 ± 6.8 mm. Among 3 (21.4%) patients, the lesions were observed in one testis, whereas both testes were affected in the remaining 11 (78.6%) patients. The lesions were hypoechoic in 12 (85.7%) patients and hyperechoic in 2 (14.3%). Plasma ACTH and 17-hydroxyprogesterone (17-OHP) levels were significantly higher in patients with T-ART than in patients without lesions (319.4 ± 307.0 pg/ml and 12.4 ± 2.7 ng/ml vs. 33.5 ± 10.7 pg/ml and 8.2 ± 1.8 ng/ml, respectively; p < 0.01). The mean values of sperm concentration and motility were significantly lower in patients with T-ART than in patients without lesions (12.1 ± 12.4 × 106 cells/ml and 18.4 ± 11.1% vs. 41.5 ± 23.2 × 106 cells/ml and 30.8 ± 15.4%, respectively; p < 0.05). Logistic regression analysis showed ACTH level as a significant predictor of T-ART (p < 0.05). In patients with T-ART, the dose of hydrocortisone was increased by ~25–30%, while the fludrocortisone treatment remained unchanged. After 6 months of steroid treatment, patients underwent US and hormonal evaluation. Disappearance and a reduction in T-ART were observed in 6 (42.9%) and 5 (35.7%) patients, respectively; a reduction in ACTH levels (from 319.4 ± 307.0 to 48.1 ± 5.1 pg/ml; p < 0.01) was reported. A significant correlation between ACTH level reduction and T-ART diameter reduction was observed (p < 0.5; r = 0.55).Conclusions: T-ARTs were detected in 56% of patients with CAH and were associated with impaired semen parameters. However, these lesions are potentially reversible, as demonstrated by the disappearance/reduction after adjustment of cortisone therapy and by the reduction in plasma ACTH level. Our study supports the importance of periodic US evaluation and maintenance of plasma ACTH levels within the normal range in men with CAH.

An evaluation of the risk factors for orchidism and the efficacy of intensive corticosteroids therapy for the complicating testicular adrenal rest tumors in the patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency during the childhood and pubescent stages

Objective To explore the risk factors for orchidism and the curative efficacy of intensive corticosteroids therapy for the testicular adrenal rest tumors (TART) in the patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency (21OHD) during childhood and pubescent periods. Methods A total 12 cases (27 case-times) with TART were adopted in intensive corticosteroids therapy, 7 cases (7case-times) as control group without intensive therapy. Retrospective analysis following parameters: (1) The testicular volume and the echogenic characteristics of TART by B-mode ultrasound. (2) Serum levels of FSH, LH, testosterone, 17-hydroxyprogesterone, androstendion, and inhibin-B were measured. (3) Orchidism was defined by one of following events: serum level of inhibin-B≤3rd % for normal, and(or) serum level of testosterone<1.42 ng/ml for the individual which is already in Tanner Ⅳ stage. (4) The relationship between regression of TART and intensive therapy project. Results The prevalence of TART in 21-OHD was 28.18% during 2-18 years old, and the youngest age with TART was 2.48 year of old. The regression rate of TART by intensive therapy was higher than that of the control significantly, 20/30 and 1/11(tumor-times) respectively(P=0.004). When the dose of dexamethasone ≥30% of total doses of corticosteroids, the regression rate of TART was higher than those less than 30% ones, or adopted hydrocortisone alone, were both respectively 16/20 and 4/10(P=0.045). The risk factors for orchidism related to early diagnosis: The TARTs stages in diagnosis (≥stages III; P=0.003), the tumor in size, hyperechogenicity in B ultrasound of the tumors(P=0.003). Inhibin-B is the earliest displayed biochemical warker for orchidism. Conclusions The TART could regress when got early diagnosis and adopted intensive corticosteroids therapy on time. Delayed diagnosis was the main risk factor for orchidism. For early diagnosis of TART, we suggest to conduct the scrotal ultrasound regularly started from 2 years of age. Key words: Congenital adrenal hyperplasia; 21-hydroxylase deficiency; Childhood and pubescent; Testicular adrenal rest tumors; Intensive corticosteroids therapy; Orchidism

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.

SUN-371 Successful Induction of Fertility with Low-Dose Dexamethasone in a Patient with Congenital Adrenal Hyperplasia and Testicular Adrenal Rest Tumor

Background Testicular adrenal rest tumors (TARTs) have been described in men with classic congenital adrenal hyperplasia (CAH) at a prevalence up to 90% and are a common cause of infertility in men with CAH. These tumors are located in the rete testis and because of their central location, can lead to mechanical obstruction, impaired blood flow and functional impairment of seminiferous tubules. TARTs have characteristics of adrenocortical cells and ACTH has been implicated in tumor growth. Previous reports have described restoration of fertility in patients with classic CAH and TARTs with administration of dexamethasone at relatively high doses of 750-1000 mcg daily (1, 2). We describe restoration of fertility in a male with classic CAH and TART with the use of lower dose dexamethasone. Case description A 28-year old male with classic CAH due to 21-hydroxylase deficiency presented to us for a follow-up visit after having been lost to follow-up for over a decade with concerns of impaired fertility. He had known bilateral TARTs, first noted at age 18. He and his wife had discontinued all forms of contraception 6 months prior to seeking care and reported a minimal coital frequency of 2-3 times/ week. His biochemical evaluation showed poor CAH control despite reported compliance with Prednisone 5 mg every morning and Fludrocortisone 50 mcg twice daily{(0800h evaluation prior to medication: 17-hydroxyprogesterone (17-OHP): 13060 ng/dL (reference: 13- 120); androstenedione (A4) 1025 ng/dl (reference: 26- 125), ACTH 866 pg/ml (reference: 5-46), plasma renin activity (PRA) 7.1 ng/ ml/h (reference: 0.6-4.3), FSH 1.7 U/L (reference: 1-11), LH 1.3 U/L (reference: 1-8 U/L) and total testosterone 473 ng/ dL (reference: 240-950). A semen analysis showed azoospermia (sperm count =0). Testicular ultrasonography (U/S) showed marked progression of total TART volume to approximately 16% of his total testicular volume (5.01 cc of 32.30 cc). Patient was switched to dexamethasone (250 mcg at bedtime) to suppress the nocturnal surge of ACTH to help decrease TART size. A follow-up U/S performed 5 months later showed a significant decrease in tumor size bilaterally. His total TART volume decreased by 90% (0.48 cc from a previous volume of 5.01 cc). Repeat semen analysis showed a sperm count of 131. In conjunction, biochemical control of CAH showed improvement with 0800h evaluation prior to medication: 17-OHP 66 ng/dL, A4 16 ng/ dL, ACTH 13.5 pg/ml, PRA 11 ng/ ml/h, FSH 5.4 U/L, LH 1 U/L and T 287 ng/dL. The patient’s wife was confirmed to be pregnant nine months after the initiation of dexamethasone and delivered a healthy full-term baby girl. Conclusion This case demonstrates that use of a long-acting glucocorticoid such as dexamethasone at doses as low as 250 mcg daily can decrease TART size and reverse male infertility. Acknowledgements This research was supported by the Intramural Research Program of the NIH.

SUN-398 A Case of Bilateral Testicular Adrenal Rest Tumors in a Patient with Congenital Adrenal Hyperplasia Due to 21 Hydroxylase Deficiency

Case study: This is a 28-year-old male, who was diagnosed since childhood with classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency. He is a product of consanguineous marriage and one of his sister is suffering from the same problem. He was maintained on hydrocortisone tablets twice a day “10 mg and 15 mg”, in addition to fludrocortisone 0.1 mg once daily. His current problem stared since two years. He was not compliant to his medicine, because of depression. Then, he noticed darkening of his skin. Additionally, he was suffering from fatigue and erectile dysfunction as well as primary infertility. Clinically, he was hyperpigmented, and there was a testicular mass felt in each testis. He had an MRI Abdomen which showed the left adrenal gland contained a large lobulated mass filled with macroscopic fat measuring 3.7*2.9 cm and the right adrenal gland had another fat rich lobulated mass of 1.6*1.1 cm. Ultrasound testes revealed bilateral irregular hypoechoic lesion close to the rete testis. The right testicular measured 2.6*0.7 cm and the left one measured 2.6*0.5 cm. Pertaining laboratory results showed ACTH 26.4 pmol/L (1.6 - 13.9), 17-hydroxyprogesterone 855 nmol/L ( 1.8-10.3), the repeated result was 974 nmol/L , FSH <0.1 , and total testosterone 2.75 nmol/L ( 8.64 - 29). The patient was started on night dose of long acting steroid dexamethasone 0.5 mg once daily, in addition to fludrocortisone 0.1 mg once daily. He was evaluated regularly over two years. The skin hyper pigmentation has got better. His sexual function and sperm count improve with time, but he is still seeking for fertility. The repeated laboratory results showed ACTH dropped to 1.5 pmol/L (1.6 - 13.9), 17-hydroxyprogesterone 0.66 nmol/L (1.8-10.3).The latest MRI adrenals had shown reduction in the size of both adrenal masses to less than 1 cm. The ultrasound testes showed the left mass has reduced in size from 2.6*0.5 cm to 1.4*0.3 cm and the right testicular adrenal rest tumor has resolved completely. Discussion: Congenital adrenal hyperplasia is a rare inherited disease. Inappropriate management might result in rare complications such as testicular adrenal rest tumor. The use of a long acting glucocorticoid to suppress ACTH might result in regression of testicular adrenal rest tumor or complete. In conclusion: Testicular adrenal rest tumor is a benign condition which might occurs in patient with congenital adrenal hyperplasia. The tumor might regress or even disappear with proper ACTH suppression.

CAH presenting as premature puberty with associated testicular adrenal rest tumors (TART)

CAH presenting as premature puberty with associated testicular adrenal rest tumors (TART)

Three Cases of Testicular Adrenal Rest Tumors in Congenital Adrenal Hyperplasia—A Diagnostic and Therapeutic Challenge

Three Cases of Testicular Adrenal Rest Tumors in Congenital Adrenal Hyperplasia—A Diagnostic and Therapeutic Challenge

Testicular Adrenal Rest Tumors: Current Insights on Prevalence, Characteristics, Origin, and Treatment.

This review provides the reader with current insights on testicular adrenal rest tumors (TARTs), a complication in male patients with congenital adrenal hyperplasia (CAH). In recent studies, an overall TART prevalence of 40% (range, 14% to 89%) in classic patients with CAH is found. Reported differences are mainly caused by the method of detection and the selected patient population. Biochemically, histologically, and molecularly, TARTs exhibit particular adrenal characteristics and were therefore thought to originate from aberrant adrenal cells. More recently, TARTs have been found to also exhibit testicular characteristics. This has led to the hypothesis of pluripotent cells as the origin of TARTs. High concentrations of ACTH could cause hyperplasia of these pluripotent cells, as TARTs appear to be associated with poor hormonal control with concomitant elevated ACTH. Unfortunately, as yet there are no methods to prevent the development of TARTs, nor are there guidelines to treat patients with TARTs. Intensified glucocorticoid treatment could improve fertility status in some cases, although studies report contradicting results. TARTs can also lead to irreversible testicular damage, and therefore semen cryopreservation could be offered to patients with TARTs. Further research should focus on the etiology and pharmacological treatment to prevent TART development or to treat TARTs and improve the fertility status of patients with TARTs.

Typical characteristics of children with congenital adrenal hyperplasia due to 11β-hydroxylase deficiency: a single-centre experience and review of the literature.

Background 11β-hydroxylase deficiency (11βOHD) is a rare disease representing the second most common cause of congenital adrenal hyperplasia (CAH) (5-8%) with an incidence of about 1:100,000. In contrast to 21-hydroxylase deficiency (21OHD), 11βOHD is not included in neonatal screening programmes. The objective of this study was to demonstrate the typical features of male patients with 11βOHD. Methods Clinical, biochemical and radiological data of patients with 11βOHD were analysed in this retrospective single-centre analysis. Results Six male patients of four unrelated families with 11βOHD were identified (0.1-13.5 years of chronological age [CA] at diagnosis). The predominant symptoms were arterial hypertension, tall stature and precocious pseudopuberty. Bone ages (BAs) were remarkably advanced at diagnosis in four index patients (median difference BA-CA: 5.5 years, range 1.5-9.2 years). Homozygous mutations were identified in exon 7 (c.1179_1180dupGA [p.Asn394Argfs*37]) and exon 8 (c.1398+2T>C) of the CYP11B1 gene leading both to a complete loss of function. The latter mutation has not yet been described in databases. 11βOHD was identified by the measurement of 11-deoxycortisol in a newborn screening card of one patient retrospectively. Testicular adrenal rest tumours (TARTs) were detected in three patients at 3.7 years, 11 years and 14.4 years. Conclusion The diagnosis of CAH due to 11βOHD is delayed and should be suspected in children with arterial hypertension, tall stature and precocious pseudopuberty. Patients may develop TARTs as early as infancy. 11βOHD should be included in newborn screening programmes, at least in newborns of index families, to allow early diagnosis and the start of treatment to reduce morbidity.