Prevalence and long‐term follow‐up outcomes of testicular adrenal rest tumours in children and adolescent males with congenital adrenal hyperplasia

Aycan, Zehra; Baş, Veysel Nijat; Çeti̇nkaya, Semra; Ağladıoğlu, Sebahat Yılmaz; Tiryaki, Tugùrul

doi:10.1111/cen.12033

Cited by 73 publications

(81 citation statements)

References 29 publications

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“…Two case series and one case report describe patients with 11βOHD and TARTs [144][145][146]. One of these series was a follow-up study of 60 boys and adolescent males with CAH of which five had 11βOHD.…”

Section: Testicular Adrenal Rest Tumorsmentioning

confidence: 99%

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Clinical perspectives in congenital adrenal hyperplasia due to 11β-hydroxylase deficiency

2016

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Congenital adrenal hyperplasia due to 11 beta-hydroxylase deficiency is a rare autosomal recessive genetic disorder. It is caused by reduced or absent activity of 11β-hydroxylase (CYP11B1) enzyme and the resultant defects in adrenal steroidogenesis. The most common clinical features of 11 beta-hydroxylase deficiency are ambiguous genitalia, accelerated skeletal maturation and resultant short stature, peripheral precocious puberty and hyporeninemic hypokalemic hypertension. The biochemical diagnosis is based on raised serum 11-deoxycortisol and 11-deoxycorticosterone levels together with increased adrenal androgens. More than 100 mutations in CYP11B1 gene have been reported to date. The level of in-vivo activity of CYP11B1 relates to the degree of severity of 11 beta-hydroxylase deficiency. Clinical management of 11 beta-hydroxylase deficiency can pose a challenge to maintain adequate glucocorticoid dosing to suppress adrenal androgen excess while avoiding glucocorticoid-induced side effects. The long-term outcomes of clinical and surgical management are not well studied. This review article aims to collate the current available data about 11 beta-hydroxylase deficiency and its management.

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Section: Testicular Adrenal Rest Tumorsmentioning

confidence: 99%

“…One of these series was a follow-up study of 60 boys and adolescent males with CAH of which five had 11βOHD. Three of five boys (60%) were identified to have TART based on ultrasonography [145]. All three cases had poor biochemical control and were diagnosed with TARTs at ages 14, 16 and 17 years.…”

Section: Testicular Adrenal Rest Tumorsmentioning

confidence: 99%

Clinical perspectives in congenital adrenal hyperplasia due to 11β-hydroxylase deficiency

2016

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“…CYP21A2, CYP11B1 and NR0B1/DAX1 mutations), the malignancy risk for the testis is estimated as being low (37,38,39). 46,XY patients with 21-hydroxylase deficiency and 11b-hydroxylase deficiency may develop TARTs, which can compromise fertility and sometimes be mistaken for Leydig cell malignancy; but TARTs are benign (37,40) and can be controlled by proper treatment (41). Importantly, testosterone overproduction as seen in some of these defects seems not to be associated with increased germ cell cancer risk (15,37).…”

Section: European Journal Of Endocrinologymentioning

confidence: 99%

Human 3β-hydroxysteroid dehydrogenase deficiency seems to affect fertility but may not harbor a tumor risk: lesson from an experiment of nature

Burckhardt

Udhane

Marti

et al. 2015

European Journal of Endocrinology

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Context: 3b-hydroxysteroid dehydrogenase deficiency (3bHSD) is a rare disorder of sexual development and steroidogenesis. There are two isozymes of 3bHSD, HSD3B1 and HSD3B2. Human mutations are known for the HSD3B2 gene which is expressed in the gonads and the adrenals. Little is known about testis histology, fertility and malignancy risk. Objective: To describe the molecular genetics, the steroid biochemistry, the (immuno-)histochemistry and the clinical implications of a loss-of-function HSD3B2 mutation. Methods: Biochemical, genetic and immunohistochemical investigations on human biomaterials. Results: A 46,XY boy presented at birth with severe undervirilization of the external genitalia. Steroid profiling showed low steroid production for mineralocorticoids, glucocorticoids and sex steroids with typical precursor metabolites for HSD3B2 deficiency. The genetic analysis of the HSD3B2 gene revealed a homozygous c.687del27 deletion. At pubertal age, he showed some virilization of the external genitalia and some sex steroid metabolites appeared likely through conversion of precursors secreted by the testis and converted by unaffected HSD3B1 in peripheral tissues. However, he also developed enlarged breasts through production of estrogens in the periphery. Testis histology in late puberty revealed primarily a Sertoli-cell-only pattern and only few tubules with arrested spermatogenesis, presence of few Leydig cells in stroma, but no neoplastic changes. Conclusions: The testis with HSD3B2 deficiency due to the c.687del27 deletion does not express the defective protein. This patient is unlikely to be fertile and his risk for gonadal malignancy is low. Further studies are needed to obtain firm knowledge on malignancy risk for gonads harboring defects of androgen biosynthesis.

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“…However, if high gonadotropin levels are found, they can be indicative of a testicular failure (22,30). Whereas some investigators found that TARTs regressed and spermatogenesis was reactivated when glucocorticoid therapy was instituted or intensified (11,31), others report that patients remain azoospermic (27,32). The use of dexamethasone (0.25-0.5 mg p.o.…”

Section: Hormonal Treatment and Outcomementioning

confidence: 99%

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

Tüttelmann

Mallidis

Nieschlag

et al. 2014

European Journal of Endocrinology

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Context: Classical congenital adrenal hyperplasia (CAH), a genetic disorder characterized by 21-hydroxylase deficiency, impairs male fertility, if insufficiently treated. Patient: A 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/COG (IVS2-13A/COG) in CYP21A2. Hydrocortisone (24 mg/m 2 ) 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.Results: Normalization of testosterone levels and a stable low sperm concentration (0.5 mill/ml) with good sperm motility (85% ACB 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. Conclusions: TARTs 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.

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Prevalence and long‐term follow‐up outcomes of testicular adrenal rest tumours in children and adolescent males with congenital adrenal hyperplasia

Abstract: Objective There are a few studies regarding the prevalence of testicular adrenal rest tumours (TARTs) in boys and adolescent males with congenital adrenal hyperplasia (CAH), and there is little information regarding the treatment outcomes in patients with TARTs.

Cited by 73 publications

References 29 publications

Clinical perspectives in congenital adrenal hyperplasia due to 11β-hydroxylase deficiency

Clinical perspectives in congenital adrenal hyperplasia due to 11β-hydroxylase deficiency

Human 3β-hydroxysteroid dehydrogenase deficiency seems to affect fertility but may not harbor a tumor risk: lesson from an experiment of nature

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

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