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Intracavernous sinus ectopic adrenocorticotropin-secreting tumours causing therapeutic failure in transsphenoidal surgery for Cushing's disease.

BACKGROUND: The major cause of surgical failure in the treatment of Cushing's disease lies in unsuccessful identification of adenomas. In the present study, we investigated the pathogenesis of negative exploration in transsphenoidal surgery for Cushing's disease by analyzing neuro-imaging studies, endocrinological examination and selective venous sampling. METHODS: Thirty patients with ACTH-dependent Cushing's syndrome that met the endocrinological criteria for Cushing's disease were treated by transsphenoidal microsurgery. Depending on positive or negative identification of adenomas during the surgery, selective adenomectomy, partial hypophysectomy or subtotal hypophysectomy was performed. FINDINGS: All nine patients who underwent selective adenomectomy showed endocrinological remission and did not need any hormone replacement therapy. Of the 12 patients who underwent partial hypophysectomy, 11 showed normalization of hypercortisolism but seven needed permanent replacement of hydrocortisone. Four patients underwent subtotal hypophysectomy because no adenoma could be identified in spite of detailed exploration, and three of them showed remission but with permanent requirements of hydrocortisone and other pituitary hormones. Five patients, whose hypercortisolism persisted after initial surgery, underwent total hypophysectomy as secondary transsphenoidal surgery, and only one of them showed endocrinological remission. Of the six patients with surgical failure, four were thought to be rare cases in whom the ACTH-secreting tumours may have occurred ectopically in the cavernous sinus without direct contact with the pituitary gland. Endocrinologically, these four patients showed a low or no response to corticotropin releasing hormone (CRH) stimulation, and for three of them, radiation therapy to the sellar region including the cavernous sinus was effective for persistent hypercortisolemia. INTERPRETATION: Recognition of an ectopic intracavernous sinus ACTH-secreting tumour as a pathological entity for Cushing's disease may not only enhance the diagnostic accuracy but also be important for determining the optimal surgical mode for persistent Cushing's disease.

Adenoma↗

Genetic information in the diagnosis and treatment of hypertension.

Advancement in cardiovascular science should be measured by a number of new diagnostic and therapeutic options applied in clinical practice as a result of translational research. Hypertension genetics is a good example of such a successful transfer of knowledge from bench to bedside. There are genetic methods currently used as diagnostic tools in patients presenting with secondary forms of hypertension, including primary hyperaldosteronism, Cushing's syndrome, pheochromocytoma, and chronic kidney disease. Directed treatment that corrects pathophysiologic abnormalities is available for several monogenic forms of hypertension as a result of uncovering their underlying genetic mechanisms. Progress in hypertension pharmacogenetics and pharmacogenomics brings closer a perspective of personalized antihypertensive treatment and gene transfer strategies, which, although still considered as innovative approaches, may soon become options to treat, control, and, possibly, cure hypertension.

Adrenocortical Hyperfunction↗

Primary aldosteronism. A study in contrasts.

Two patient with primary aldosteronism, one with a solitary adrenal adenoma and the other with bilateral nodular hyperplasia, are described. Both patients showed the classic features of primary aldosteronism in electrolyte and hormone patterns, but there were important differences in the biochemistry of their excised adrenal tissue. In addition, the injection of plasma from the patient with bilateral adrenal hyperplasia into the sheep's transplanted adrenal gland elicited a definite aldosterone secretory response, but there was no aldosterone response to the injection of plasma from the patient with a solitary adrenal adenoma. The findings support the hypothesis that an extra-adrenal stimulus may contribute to the pathogenesis of bilateral adrenal hyperplasia.

Adenoma↗

Maternal and amniotic fluid 17 alpha-hydroxyprogesterone levels during pregnancy: diagnosis of congenital adrenal hyperplasia in utero.

17 alpha-Hdroxyprogesterone levels (17 alpha-OHP) were measured in 70 samples of amniotic fluid and 30 samples of maternal serum obtained at different stages of normal pregnancy and in samples of maternal serum and amniotic fluid from a pregnancy with the fetus affected with congenital adrenal hyperplasia. The mean level of 17 alpha-hydroxyprogesterone in the amniotic fluid from control pregnancies was 133.9 +/- 7.6 ng. per 100 ml. (range, 25.1 to 266.6 ng. per 100 ml). The levels were significantly higher in midpregnancy (157.4 +/- 8.4 ng. per 100 ml.) than in late pregnancy (79.2 +/- 6.8 ng. per 100 ml.) (p less than 0.01). Amniotic fluid 17 alpha-OHP levels in the affected pregnancy were significantly higher than the control levels. Mean maternal 17 alpha-OHP level during early pregnancy and midpregnancy was 259.5 +/- 22 ng. per 100 ml. and there was a two-to three-fold increase after 37 weeks (672.2 +/- 61 ng. per 100 ml.) The maternal 17 alpha-OHP levels in the affected pregnancy were significantly higher than the control levels after 34 weeks, but before 34 weeks, the level was within the range seen in control pregnancies. Measurement of 17 alpha-OHP levels in the amniotic fluid before 24 weeks and maternal serum after 34 weeks can be utilized for the prenatal diagnosis of congenital adrenal hyperplasia.

Adrenal Hyperplasia, Congenital↗

Maternal and amniotic fluid steroids throughout human pregnancy.

Concentrations of testosterone, dihydrotestosterone, androstenedione, progesterone, 17 alpha-hydroxyprogesterone, and estradiol were measured by radioimmunoassay in the amniotic fluid and maternal peripheral blood obtained from normal pregnancies between 14 and 40 weeks of gestation. There was a sex difference in the levels of all the androgenic steroids in the amniotic fluid before 20 weeks with higher levels in pregnancies with male fetuses. Amniotic fluid 17 alpha-hydroxyprogesterone levels were significantly elevated in a pregnancy with the fetus affected with congenital adrenal hyperplasia. The levels of all the steroids in the amniotic fluid were significantly elevated in the pregnancy with molar degeneration of the placenta. There was a sex difference in the levels of dihydrotestosterone in the maternal peripheral blood before 20 weeks with higher levels in pregnancies with male fetuses. There was no correlation between the steroid levels in the maternal serum and amniotic fluid even though most of the samples of maternal serum were drawn at the same time as amniocentesis.

Adrenocortical Hyperfunction↗