Serum Androgens as a Continuing Index of Adequacy of Treatment of Congenital Adrenal Hyperplasia

Korth-Schütz, Sigrun; Virdis, R; Saenger, Paul; Levine, Lenore S.; New, Maria I.

doi:10.1203/00006450-197704000-00349

Cited by 22 publications

(31 citation statements)

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“…A introdução das técnicas de radioimunoensaio para dosagens hormonais, incluindo esteróides, trouxe uma verdadeira revolução em pesquisa e diagnóstico de patologias endócrinas (29)(30)(31). Os métodos em geral incluíam um processo de extração em solvente orgâni-co seguido, ou não, de cromatografia.…”

Section: Discussionunclassified

Dosagem de cortisol e cortisona livres urinários empregando cromatografia líquida associada a espectrometria de massa em tandem (LC-MS/MS)

Vieira

Nakamura

Carvalho

2005

Arq Bras Endocrinol Metab

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A dosagem de cortisol livre na urina (CLU) é um método útil na triagem de pacientes suspeitos de síndrome de Cushing. Os imunoensaios atuais apresentam limitações que dificultam sua aplicação e a comparação de resultados por diferentes ensaios. No presente método para dosagem de cortisol e cortisona livres urinários, baseado em cromatografia líquida com detecção por espectrômetro de massa em tandem (LC-MS/MS), uma alíquota de urina 24h (200µL) é misturada com solução contendo quantidade conhecida de cortisol deuterado e extraída on-line em fase sólida (C 18 ). O eluato é transferido para uma segunda coluna C 18 (Phenomenex Luna, 3µ, de 50 x 2mm), e o eluato obtido em modo isocrático é aplicado diretamente no MS/MS modelo Quattro Micro, operando no modo positivo de ionização química a pressão atmosférica (APCI). Todo o processo é automatizado e a quantificação é feita por diluição isotópica com base nas razões das áreas dos picos dos analitos e do padrão interno deuterado. O estudo de especificidade mostrou que nenhum esteróide testado apresenta reatividade cruzada superior a 1% com cortisol ou cortisona. A sensibilidade funcional é <1µg/L para os dois esteróides, e o CV interensaio <8%. Os estudos de recuperação e de linearidade foram satisfatórios, e a comparação entre os resultados obtidos para cortisol em 98 amostras de rotina, pelo ensaio em estudo e por um RIE, mostraram correlação de r= 0,838, sendo os valores obtidos por LC-MS/MS significativamente mais baixos (medianas de 22,0 e 49,4µg/24h, respectivamente) (P<0,0001). Os valores de referência para cortisol foram definidos entre 11 e 43µg/24h, compatíveis com métodos semelhantes recentemente descritos. A dosagem concomitante de cortisona livre urinária permite o estudo da atividade da enzima 11β-HSD2 e a pesquisa da síndrome do excesso aparente de mineralocorticóides. O método descrito representa a primeira descrição, em nosso meio, de uma nova geração de métodos para a medida de esteróides hormonais, baseados em processos preparativos automatizados e leitura por espectrometria de massa em tandem. Free urinary cortisol (UFF) measurement is one of the most useful screening tests for Cushing's syndrome. Immunoassays employed today by most clinical laboratories present limitations, specially concerning specificity. These limitations restrain a widespread application of the method, as well as the comparison of results obtained by the use of different methods. We present the development and characterization of a UFF and cortisone method based on liquid chromatography and tandem mass spectrometry (LC-MS/MS). A 200µL aliquot from a 24h urine sample

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Section: Discussionunclassified

Dosagem de cortisol e cortisona livres urinários empregando cromatografia líquida associada a espectrometria de massa em tandem (LC-MS/MS)

Vieira

Nakamura

Carvalho

2005

Arq Bras Endocrinol Metab

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“…A concentration that is extremely high (Ͼ40 nmol/L) indicates undertreatment. Third, androstenedione concentrations correlate best with 24-h urine 17-KS (27)(28)(29), but single values are difficult to interpret and do not necessarily reflect clinical control, with overlap between values in well-controlled and poorly controlled individuals (29 ). Fourth, it is extremely difficult to assess overtreatment from a single serum value of any of these hormones, because values within the "normal range" may reflect either good control or overtreatment (26 ).…”

Section: Serum Monitoringmentioning

confidence: 99%

“…In general, one should not attempt to normalize 17OHP concentrations, because this will certainly lead to overtreatment. Fifth, testosterone concentrations are not useful markers in male infants or pubertal males owing to testicular production of testosterone under the influence of gonadotropins (27)(28)(29)(30). Finally, if one does wish to use serum concentrations to assess control, they should be obtained at a standardized time before the administration of the morning glucocorticoid dose.…”

Section: Serum Monitoringmentioning

confidence: 99%

Monitoring of Therapy in Congenital Adrenal Hyperplasia

Dauber¹,

Kellogg

Majzoub³

2010

Clinical Chemistry

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BACKGROUND:Congenital adrenal hyperplasia is a group of disorders caused by defects in the adrenal steroidogenic pathways. In its most common form, 21-hydroxylase deficiency, patients develop varying degrees of glucocorticoid and mineralocorticoid deficiency as well as androgen excess. Therapy is guided by monitoring clinical parameters as well as adrenal hormone and metabolite concentrations. CONTENT:We review the evidence for clinical and biochemical parameters used in monitoring therapy for congenital adrenal hyperplasia. We discuss the utility of 24-h urine collections for pregnanetriol and 17-ketosteroids as well as serum measurements of 17-hydroxyprogesterone, androstenedione, and testosterone. In addition, we examine the added value of daily hormonal profiles obtained from salivary or bloodspot samples and discuss the limitations of the various assays.

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“…Korth-Schutz et al (16) and Anderson (2) found low levels of serum dehydroepiandrosterone in both optimally and poorly controlled patients with CAH and concluded that dehydroepiandrosterone is not a good index of control in this condition. In another study of 21 patients who were treated for CAH (18), pregnenolone and 17-hydroxypregnenolone increased only after repeated injections of repository ACTH, but not after short term synthetic ACTH stimulation.…”

Section: Resultsmentioning

confidence: 99%

Disproportionate Supression of Dehydroepiandrosterone Sulfate (DHEAS) in Treated Patients with Congenital Adrenal Hyperplasia due to 21-Hydroxylase Deficiency

et al. 1983

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SummarySerum concentrations of dehydroepiandrosterone sulfate (DHEAS) were measured in 28 patients (18 females, 10 males) with congenital adrenal hyperplasia due to 21-hydroxylase deficiency who were treated with oral hydrocortisone (non-salt losers) or hydrocortisone and 9-a-fluorohydrocortisone (salt-losers). Adequacy of therapy was assessed by clinical findings, determination of bone age, urinary excretion of 17-ketosteroids, and serum concentration of 17-hydroxyprogesterone. These allowed the separation of patients into three groups: poorly controlled, adequately controlled and overtreated. Individual values for serum levels of DHEAS were compared to mean normal values for age. In the adequately controlled and overtreated patients, mean serum concentrations of DHEAS were significantly lower than normal values for age ( P < 0.05). In the poorly treated patients, the mean serum concentration of DHEAS was not significantly different from normal values for age ( P = 0.50).These data indicate that the serum concentration of DHEAS is overly suppressed in treated patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency. This finding suggests that measurement of the serum levels of DHEAS has limited value in assessing the adequacy of therapy in this disease. Abbreviations CAH, congenital adrenal hyperplasia due to 21-hydroxylase deficiency DHEAS, dehydroepiandrosterone sulfate 17-OHP, 17-hydroxyprogesterone SDS, standard deviation score A major goal in long term management of patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency (CAH) is to suppress the effects of excessive adrenal androgens. The adequacy of suppression has been traditionally monitored by periodic measurement of 24-h urinary excretion of 17-ketosteroids and pregnanetriol. The reliability of these assays, however, is hampered by inaccuracies in collection of 24-h urine specimens. A suitable compound that can be measured in blood, therefore, has been searched for by several investigators. Dehydroepiandrosterone sulfate (DHEAS), the most abundant adrenal androgen, seems to be a likely candidate for this purpose because it is almost exclusively synthesized by the adrenal glands (17,19). Moreover, as DHEAS has a long half-life (24, 26), its concentration in serum is less susceptible to diurnal variations (25).Recent studies have demonstrated that serum levels of DHEAS are increased in patients with untreated CAH (1 1, 15,23); however, data on the serum concentration of the hormone during therapy are very limited. Serum levels of DHEAS did not increase in six patients with CAH when therapy was discontinued for 3 days (33). Golden et al. (1 1) found elevated levels of serum DHEAS in patients with CAH only when they were overtly undertreated, but values for serum levels of DHEAS were not correlated with the age of the patients. Because secretion of DHEAS is age dependent (8,15,23), its role in the management of patients with CAH cannot be quantitated unless appropriate age-matched control values are applied. The ...

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Serum Androgens as a Continuing Index of Adequacy of Treatment of Congenital Adrenal Hyperplasia

Cited by 22 publications

References 0 publications

Dosagem de cortisol e cortisona livres urinários empregando cromatografia líquida associada a espectrometria de massa em tandem (LC-MS/MS)

Dosagem de cortisol e cortisona livres urinários empregando cromatografia líquida associada a espectrometria de massa em tandem (LC-MS/MS)

Monitoring of Therapy in Congenital Adrenal Hyperplasia

Disproportionate Supression of Dehydroepiandrosterone Sulfate (DHEAS) in Treated Patients with Congenital Adrenal Hyperplasia due to 21-Hydroxylase Deficiency

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