MACROGENITOSOMIA PRECOX ASSOCIATED WITH HYPERPLASIA OF THE ANDROGENIC TISSUE OF THE ADRENAL AND DEATH FROM CORTICOADRENAL INSUFFICIENCY CASE REPORT<sup>1</sup>

Wilkins, Lawson; Fleischmann, Walter; Howard, John Eager

doi:10.1210/endo-26-3-385

Cited by 175 publications

(62 citation statements)

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“…Heterotopic masses of the adrenal cortex in patients with CAH may be present not only in the mediastinum * * * * * * testis, but also in the spermatic cord and within the epididymis (13,14). These tumors are characterized as TARTs, developing due to chronic ACTH stimulation (15,16).…”

Section: Testicular Adrenal Rest Tumorsmentioning

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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Section: Testicular Adrenal Rest Tumorsmentioning

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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“…The prepubertal increase in circulating adrenal androgens (the term used here, as it often is, to denote dehydroepiandrosterone (DHEA) and its sulfo-conjugate (DHEAS) despite their lack of androgenic biopotency) is now the most commonly used definition of adrenarche, an event thought to have evolved in humans and some great apes but not in Old World monkeys (Arlt et al 2002). The innermost zone of the adrenal cortex, the zona reticularis (ZR), is the site of adrenal androgen biosynthesis and secretion in humans (Wilkins et al 1940, Blackman 1946, Wieland et al 1965, Endoh et al 1996, Gell et al 1998 and in rhesus macaque (Macaca mulatta; Mapes et al 1999), and adrenarche coincides with the differentiation and maturation of the ZR (Suzuki et al 2000, Rainey et al 2001, Hui et al 2009). In general, however, evidence on adrenarche in NHP is scant, almost completely lacking with respect to the development of the functional morphology of the adrenal ZR in any species except the rhesus macaque .…”

Section: Introductionmentioning

confidence: 99%

Adrenarche in nonhuman primates: the evidence for it and the need to redefine it

Conley¹,

Bernstein²,

Nguyen³

2012

Journal of Endocrinology

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Adrenarche is most commonly defined as a prepubertal increase in circulating adrenal androgens, dehydroepiandrosterone (DHEA) and its sulfo-conjugate (DHEAS). This event is thought to have evolved in humans and some great apes but not in Old World monkeys, perhaps to promote brain development. Whether adrenarche represents a shared, derived developmental event in humans and our closest relatives, adrenal androgen secretion (and its regulation) is of considerable clinical interest. Specifically, adrenal androgens play a significant role in the pathophysiology of polycystic ovarian disease and breast and prostate cancers. Understanding the development of androgen secretion by the human adrenal cortex and identifying a suitable model for its study are therefore of central importance for clinical and evolutionary concerns. This review will examine the evidence for adrenarche in nonhuman primates (NHP) and suggest that a broader definition of this developmental event is needed, including morphological, biochemical, and endocrine criteria. Using such a definition, evidence from recent studies suggests that adrenarche evolved in Old World primates but spans a relatively brief period early in development compared with humans and some great apes. This emphasizes the need for frequent longitudinal sampling in evaluating developmental changes in adrenal androgen secretion as well as the tenuous nature of existing evidence of adrenarche in some species among the great apes. Central to an understanding of the regulation of adrenal androgen production in humans is the recognition of the complex nature of adrenarche and the need for more carefully conducted comparative studies and a broader definition in order to promote investigation among NHP in particular.

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“…The subjects were five healthy female volunteers, aged [19][20][21][22][23][24][25][26][27] yr, who had not taken oral contraceptives for at least 6 mo, and five healthy male volunteers, aged [21][22][23][24][25][26][27][28] yr. All subjects were within ± 10% oftheir ideal body weight (according to Metropolitan Life Insurance Tables). The aim and potential risks of the investigation were explained to each subject and written consent was obtained in each case.…”

Section: Methodsmentioning

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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MACROGENITOSOMIA PRECOX ASSOCIATED WITH HYPERPLASIA OF THE ANDROGENIC TISSUE OF THE ADRENAL AND DEATH FROM CORTICOADRENAL INSUFFICIENCY CASE REPORT¹

Cited by 175 publications

References 0 publications

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

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

Adrenarche in nonhuman primates: the evidence for it and the need to redefine it

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

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MACROGENITOSOMIA PRECOX ASSOCIATED WITH HYPERPLASIA OF THE ANDROGENIC TISSUE OF THE ADRENAL AND DEATH FROM CORTICOADRENAL INSUFFICIENCY CASE REPORT1

Cited by 175 publications

References 0 publications

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

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

Adrenarche in nonhuman primates: the evidence for it and the need to redefine it

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

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MACROGENITOSOMIA PRECOX ASSOCIATED WITH HYPERPLASIA OF THE ANDROGENIC TISSUE OF THE ADRENAL AND DEATH FROM CORTICOADRENAL INSUFFICIENCY CASE REPORT¹