Activation of Testicular Adrenal Rest Tissue by Prolonged Excessive ACTH Production

Hamwi, George J.; Gwinup, Grant; Mostow, Jack H.; Besch, Paige K.

doi:10.1210/jcem-23-9-861

Cited by 77 publications

(28 citation statements)

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“…In contrast to the high incidence of TART in adult male CAH patients (up to 94%) (12,13), ovarian adrenal rest tumours in female CAH patients are very rare (14) and other locations of adrenal rest tumours in adult CAH patients have never been reported. Here, we report on an adult patient with CAH due to 3b-hydroxysteroid dehydrogenase (HSD) deficiency with bilateral TART and additionally a large perirenal adrenal rest tumour.…”

Section: Introductionmentioning

confidence: 83%

An adrenal rest tumour in the perirenal region in a patient with congenital adrenal hyperplasia due to congenital 3β-hydroxysteroid dehydrogenase deficiency

Grinten¹,

Duthoi²,

Otten³

et al. 2008

European Journal of Endocrinology

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Background: In contrast to the high incidence of testicular adrenal rest tumours (TART) in adult male patients with congenital adrenal hyperplasia (CAH), ovarian adrenal rest tumours in female CAH patients are very rare and other locations of adrenal rest tumours have never been reported. Here, we report on an adult patient with CAH due to 3b-hydroxysteroid dehydrogenase (HSD) deficiency with bilateral TART and additionally a large perirenal adrenal rest tumour. Case report: The patient was known with CAH due to 3b-HSD deficiency and treated with hydrocortisone and fludrocortisone since the neonatal period. In puberty, there was lack of compliance with consequently high POMC concentrations. At the age of 16 years, bilateral TART were detected by scrotal ultrasound. Intensifying glucocorticoid medication did not result in decrease in POMC concentrations and shrinkage of size of the tumours. At the age of 23 years, abdominal ultrasound was performed because of abdominal complaints, showing a round inhomogeneous structure with a diameter of 4 cm near the left renal hilus. A computer tomography scan showed a multinodular lesion in the retroperitoneal region beside the left kidney. Histological investigation after removal of the tumour showed sheets of large polygonal cells with abundant eosinophilic cytoplasm, separated by dense fibrous tissue strands. The histological and immunohistochemical profile resulted in a diagnosis of an adrenal rest tumour. Conclusion: In adult CAH patients, ectopic adrenal rest tumours can be present outside the testicular region. Further investigations are necessary to determine whether regularly screening for these tumours is useful.

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Section: Introductionmentioning

confidence: 83%

An adrenal rest tumour in the perirenal region in a patient with congenital adrenal hyperplasia due to congenital 3β-hydroxysteroid dehydrogenase deficiency

Grinten¹,

Duthoi²,

Otten³

et al. 2008

European Journal of Endocrinology

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“…TAR have also been reported sporadically in situations of high circulating ACTH other than CAH, e.g. Nelson's syndrome (2) and Cushing's disease (3). In addition to being ACTH-dependent, TAR secrete 17-hydroxyprogesterone (17-OH P) and cortisol (1).…”

Section: Introductionmentioning

confidence: 99%

Testicular adrenal rests: evidence for luteinizing hormone receptors and for distinct types of testicular nodules differing for their autonomization

Benvenga

Smedile²,

Giudice³

et al. 1999

European Journal of Endocrinology

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We report one patient with 21-hydroxylase deficiency and associated bilateral macro-orchidism caused by nodular hyperplasia of testicular adrenal rests (TAR). The boy, referred to us when 10 years old, was born with bilateral cryptorchidism that was treated unsuccessfully with i.m. injections of human chorionic gonadotropin (hCG) and later on with orchidopexy. He was treated with oral dexamethasone (0.625 mg per day) for the following 13 years.After one year, there was a marked reduction in steroid hormone levels (17-hydroxyprogesterone (17-OH P) from 27.2 to 1.2 nmol/l, testosterone from >104 to 4.8 nmol/l, estradiol (E 2 ) from 481 to 33 pmol/l). After the same period of time, both testicular volume and nodularity decreased: from 45 to 18 ml and from numerous to four nodules in the right testis, and from 40 to 13 ml and from numerous to three nodules in the left testis. At the third year, there were transient increases in serum gonadotropins, testicular volume (right testis = 25 ml, left testis = 20 ml) and steroid hormones, including cortisol (serum ACTH and dehydroepiandrosterone sulfate remained suppressed). At the fourth year of follow-up, there were still four nodules in the right testis and three in the left testis. The LH-dependency (which implies possession of LH/hCG receptors) of these nodules was also substantiated by their steroidogenic response to an acute i.m. hCG test. An exogenous ACTH stimulation test increased serum 17-OH P and cortisol. Since these nodules, unlike the majority of those present initially, were not suppressed by the corticosteroid therapy and since they were not detected when the patient returned for control at 23 years of age, they had partial autonomy from ACTH. At 23 years of age, the patient had a single nodule in the right testis (right testis volume = 13 ml, left testis volume = 10 ml), which should have accounted for the consistent difference in size between the two gonads. Serum LH was about 7 mU/l and FSH about 23 mU/l. The responsiveness of plasma steroid hormones to hCG had changed quantitatively and qualitatively. Secretion of cortisol was absent, secretion of 17-OH P and testosterone was reduced, and secretion of E 2 was much increased. The ACTH stimulation test showed that serum cortisol did not respond, while the other steroids responded in the order of 17-OH P > E 2 > testosterone.We conclude that there were three different groups of TAR when the patient was already 10 years old: (i) ACTH-sensitive (the majority), (ii) partially ACTH-insensitive but LH/hCG-sensitive (three nodules in the left testis and three in the right testis), (iii) almost entirely ACTH-insensitive and partially hCG-insensitive (a single nodule in the right testis). Probably, the never suppressed gonadotropin levels (presumably due to the bilateral testicular damage subsequent to the cryptorchid state) and the hCG therapy were major etiological factors for the appearance of the second and third population of TAR.

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“…The numbers in brackets refer to the numbering system of steroid standards given in Table I. thesis and of steroid hormone synthesis ( 14). It (16)(17)(18)(19). The question of whether these tumors arise from regular testicular tissue (20) or from adrenal remnants within the testes (21) is as yet unsettled (19), but prolonged exposure to markedly elevated concentrations of ACTH has generally been implied in their pathogenesis (17).…”

Section: Discussionmentioning

confidence: 99%

“…It (16)(17)(18)(19). The question of whether these tumors arise from regular testicular tissue (20) or from adrenal remnants within the testes (21) is as yet unsettled (19), but prolonged exposure to markedly elevated concentrations of ACTH has generally been implied in their pathogenesis (17). Thus, during prolonged overexposure to ACTH, the human gonad is capable of producing 1 1-hydroxylated steroids.…”

Section: Discussionmentioning

confidence: 99%

Stimulation of gonadal steroid synthesis by chronic excess of adrenocorticotropin in patients with adrenocortical insufficiency.

Vierhapper¹,

Nowotny²,

Waldhäusl³

1986

J. Clin. Invest.

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Analysis of 24-h urinary steroid excretion was performed by capillary gas chromatography in six patients (five men, one woman) with adrenocortical insufficiency. Ten healthy subjects (five men, five women) served as controls. A complete absence of all 21-hydroxylated steroid metabolites was seen in patients with adrenocortical insufficiency, whereas the excretion of several steroids lacking hydroxylation in the 21-position (pregnenolone, pregnenetriol, and 11-ketoandrosterone) was markedly increased. In addition, the presence of 1 1j-hydroxyandrosterone was confirmed by mass-spectrometry in the urine of three patients. This pattern of steroid excretion was unchanged in patients with adrenocortical insufficiency, both after stimulation by 1-24 adrenocorticotropin (ACTH) and after short-term (3-d) suppression with dexamethasone. We conclude that patients with adrenocortical insufficiency present a pattern of steroid excretion characterized by the absence of 21-hydroxylated metabolites. In the absence of functional adrenocortical tissue, long-term pathologically elevated concentrations of ACTH apparently stimulate early steps of steroid synthesis, most likely in the gonads. In addition, the presence of 11-hydroxylated steroid metabolites(1 1-ketoandrosterone, 1 1 fl-hydroxyandrosterone) in the urine of patients with adrenocortical insufficiency demonstrates that chronic AC1TH excess in this disorder may induce some activity of 11,6-hydroxylase, an enzyme not found in the gonads under physiological conditions.

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Activation of Testicular Adrenal Rest Tissue by Prolonged Excessive ACTH Production

Cited by 77 publications

References 0 publications

An adrenal rest tumour in the perirenal region in a patient with congenital adrenal hyperplasia due to congenital 3β-hydroxysteroid dehydrogenase deficiency

An adrenal rest tumour in the perirenal region in a patient with congenital adrenal hyperplasia due to congenital 3β-hydroxysteroid dehydrogenase deficiency

Testicular adrenal rests: evidence for luteinizing hormone receptors and for distinct types of testicular nodules differing for their autonomization

Stimulation of gonadal steroid synthesis by chronic excess of adrenocorticotropin in patients with adrenocortical insufficiency.

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