Гиперандрогения

[Melnichenko]

Алекс , спасибо за прекрасную ссылку , но в СВОБОДНОМ тестостероне , помимо теоретического большого вопроса , есть практический вопрос - имеющиеся в нашей стране \ в мире в целом наборы для определения СВОБОДНОГО тестостерона весьма несовершенны ( т.е это отнюдь не ситуация со свободным тироксином , куда хуже ) связано это с этапом разделения свободных \ связанных форм . А при беременности именно последних и станет больше , даже со свободным Т4 в третьем триместре маемся ...
Существует довольно много работ на эту тему ( в нашей стране это публикации Н.П. Гончарова и С.Ю . Калинченко ) , убедительно говорящих о необходимости отказа от использовнаия закупаемых наборов и использования коэффициента общий тестостерон\ секс-связывающий глобулин для оценки биологически активного тестостерона .
НО я внимательно посмотрю еще раз ссылку - указаны ли там виды наборово , которыми рекомендуется определять св. тестостерон ..

[AlexT]

Современное состояние по тестостерону и методам его определения хорошо изложено здесь:

[Ссылки доступны только зарегистрированным пользователям ]

Интересные тексты по эндокринологии беременности:

[Ссылки доступны только зарегистрированным пользователям ]

[yakov]

Я тоже позволю себе привести цитаты по обсуждаемым вопросам из "Normal and Problem Pregnancies", 4th ed, 2002:

The diagnosis is based on the clinical picture and high serum 17-hydroxyprogesterone (17-OHP) levels. In addition, serum testosterone, progesterone, and DHEA-S levels are also elevated. In the salt-wasting type, low aldosterone and high renin levels are typically found. In patients with the nonclassic form or late-onset disease, serum 17-OHP levels are over 200 ng/dl in the basal state during the follicular phase of the menstrual cycle, and have an exaggerated response to the administration of ACTH, with values over 1,500 ng/dl.

The goal of treatment is to prevent adrenal insufficiency, to provide salt-retaining corticosteroids in cases of the salt-losing variety, to suppress androgen secretion to prevent virilization, and to normalize growth and later reproductive function. This is achieved with doses of hydrocortisone between 25 and 75 mg/day or 10 to 25 mg/m2 /day, divided in two or three doses.[225] Dexamethasone with a longer half-life is preferred by some authors in doses of 0.25 to 0.75 mg/day.[226] Parameters of adequate glucocorticoid dosage are assessed by the determination of plasma 17-OHP, androstenedione (A), and testosterone (T); growth curve velocity; and the rate of skeletal maturation. Adult patients with the salt-losing variety also require mineralocorticoid therapy in the form of Florinef (fludrocortisone) 0.05 to 0.3 mg/day. The dose is adjusted to normalize plasma renin activity. The pediatric dose is 70 μ/m2 /day. No adjustment is needed in pregnancy.[227] A free testosterone determination is the best test to assess glucocorticoid therapy during gestation. [227] However, the techniques for the determination of free testosterone have not been universally refined at the present time. The fetal outcome may be normal. In spite of the lack of suppression of maternal androgens, placental aromatase activity has a protective effect not only on the fetal genitalia but also in preventing the effect of androgens on the fetal brain.

Chorionic villus biopsy at 8 to 10 weeks' gestation allows the earliest and most accurate prenatal diagnosis.[219] Early treatment, as soon as pregnancy is recognized, may prevent the development of masculinization of external genitalia in the affected female fetus. Dexamethasone is the drug of choice, since it crosses the placenta most readily and suppresses fetal adrenal androgen synthesis, reducing masculinization. Potentially affected mothers should be treated until fetal sex is known. Overall, this treatment is effective in about two thirds of patients.[234] The dose of dexamethasone is between 1.0 and 1.5 mg daily from early in pregnancy until delivery (20 μg/kg maternal weight). Maternal estriol levels are an accurate index of fetal adrenal function and genital development,[235] while amniotic fluid steroid levels have shown an inconsistent correlation with fetal masculinization. Pang et al.[236] reported maternal side effects of this therapy including cushingoid facial features; facial hirsutism; excessive weight gain; and permanent striae, hypertension, and gestational diabetes. The authors recommend that patients be made aware of potential side effects, that women receiving this treatment be closely monitored, and that the dose of dexamethasone be reduced during the second half of pregnancy, to reduce side effects.

на мой взгляд, есть интересные данные по поводу назначения ГКС и постнатального развития детей. Сразу обращаю внимание, что ГК при риске преждевременных родов назначаются кратковременно и в иной дозе, чем, например, необходимо при ВДКН. Кроме того, есть сообщения о более высоком АД у детей, матери которых получали ГК, и риске развития гипертонии в молодом возрасте. К сожалению, данных по отдаленным результатам очень мало.

Am J Obstet Gynecol. 1999 Jan;180(1 Pt 1):114-21

Repeated antenatal corticosteroids: size at birth and subsequent development.

French NP, Hagan R, Evans SF, Godfrey M, Newnham JP.

Department of Neonatal Paediatrics, King Edward Memorial Hospital, Perth, Australia.

OBJECTIVE: The objective was to study the effects of repeated antenatal corticosteroids on birth size, growth, and development in preterm infants. STUDY DESIGN: This observational study followed up for 3 years a prospective geographic cohort in the state of Western Australia of 477 singleton infants born at <33 weeks' gestation. RESULTS: Birth weight ratio decreased with increasing number of corticosteroid courses (P =.001), and multivariate analyses confirmed a reduction in birth weight of as much as 9% (P =.014) and a reduction in head circumference of as much as 4% (P =.0024). There were no additional benefits in mortality or respiratory outcomes, and there was a trend toward more severe chronic lung disease. At age 3 years growth and severe disability outcomes did not appear to be related to increasing number of corticosteroid courses. CONCLUSIONS: In this cohort study repeated corticosteroid courses were associated with adverse effects on size at birth without apparent benefits. These changes have the potential to affect later development.


Как только ракета запущена, кто отвечает за то, где она приземлится?
"Это не входит в мою сферу деятельности", -
сказал Вернер фон Браун.

[AlexT]

Обратил сегодня внимание на интерпретацию в руководстве ААСЕ дексаметазоновой пробы:

Interpretations

If the high level of testosterone is suppressed more than 40% and dehydroepiandrosterone sulfate is suppressed more than 60% after administration of dexamethasone, the source of the increased androgen is most likely the adrenal glands.

If the testosterone level fails to be suppressed but dehydroepiandrosterone sulfate and cortisol respond, the source of testosterone is primarily the ovaries.

If testosterone suppression is less than 40%, a combined ovarian and adrenal contribution is responsible for the excessive testosterone secretion.

If lack of androgen suppression is associated with a lack of cortisol suppression, the patient most likely has adrenal hyperfunction (for example, Cushing’s disorder or adrenal cancer) or the patient may have failed to take the dexamethasone tablets as directed. Appropriate steps must be taken to determine which of these two possibilities is the likely explanation.

Получается , если не делать все 3 гормона - тестостерон, кортизол и ДГАЭС, можно сделать грубую ошибку.

Например, если делать только ДГАЭС (или 17КС!!!) , то подавление их дексаметазоном может ошибочно быть интерпретировано как надпочечниковая гиперандрогения, хотя уровень тестостерона (который не исследовался) может остаться повышенным...

Ситуация при поликистозе с его распространенностью очень вероятная - вот один из путей гипердиагностики ВГКН...