Steroid Hormone Production in Normal and Abnormal Human Adrenocortical Tissue

Whitehouse, B. J.; Vinson, G. P.

doi:10.1515/9783111447001-012

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“…Honn and Chavin (17) found that a maximally stimulatory concentration of 3 nmol/L ACTH stimulated cortisol output to levels 4-5 times higher than control values. Most previous studies with human adrenal glands obtained from patients with Cushing's syndrome showed that (partial) autonomy of the adrenal gland in vivo is generally also reflected by the functions of cells or tissues incubated in vitro, in that they become less responsive to ACTH than normal tissue (1)(2)(3)(4)(5). However, in one previous study a tumor causing Cushing's syndrome, which was apparently not suppressible by dexamethasone or stimulated by ACTH in vivo, responded to ACTH in vitro (7).…”

Section: Discussionmentioning

confidence: 99%

“…3) By comparing the preoperative dynamic tests of the pituitary-adrenal axis, the plasma ACTH concentration, the morphology of the adrenal glands, and their in vitro responsiveness, a gradual transition from pituitary to (partial) adrenal autonomy could be recognized in several patients. (J Clin Endocrinol Metab 70: 192, 1990) P REVIOUS studies with adrenal glands obtained from patients with Cushing's syndrome have shown that evidence of autonomy of the adrenal gland in the dynamic tests in vivo is in most cases reflected by a lowered responsiveness of the cells to ACTH in vitro (1)(2)(3)(4)(5). However, both from in vivo tests with ACTH administration and from in vitro investigations it has been shown that adrenal adenomas often retain a sensitivity to the stimulatory effect of ACTH (6)(7)(8).…”

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Characterization of Adrenal Autonomy in Cushing's Syndrome: A Comparison betweenin Vivoandin VitroResponsiveness of the Adrenal Gland

Lamberts¹,

Zuiderwijk²,

Uitterlinden³

et al. 1990

The Journal of Clinical Endocrinology & Metabolism

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We measured cortisol and precursor steroid production in response to ACTH, cholera toxin, and forskolin by the dispersed adrenocortical cells prepared from the adrenal glands of 10 patients with different forms of Cushing's syndrome. The cells prepared from the hyperplastic adrenal glands from 4 patients with Cushing's disease responded in a dose-dependent manner to ACTH, cholera toxin, and forskolin. The adrenal cells prepared from 4 encapsulated adrenal adenomas showed no (n = 2), a lowered (n = 1), or a clear (n = 1) response of cortisol release to ACTH. The cells prepared from the adrenal glands of 1 patient with dysplastic micronodular adrenal glands showed a limited response to ACTH, while the cells from an adrenocortical carcinoma, which secreted very little cortisol per cell, were unresponsive to ACTH, cholera toxin, and forskolin. The reaction of the dispersed adrenal cells from these 10 patients to ACTH, cholera toxin, and forskolin showed a close correlation (P less than 0.001 in all instances). This suggests that the defect in autonomous glands is not located at the level of the ACTH receptor, but, rather, involves the adenylate cyclase complex as a whole or its coupling to cAMP-dependent protein kinase. The release into the medium of the cortisol precursors deoxycortisol, 17-hydroxyprogesterone, and progesterone showed that the four autonomous nodules were characterized by a significantly higher deoxycortisol/cortisol ratio in the medium (P less than 0.01), suggesting a relative blockade of 11 beta-hydroxylase in these adrenal adenomas. This was further substantiated in cells from several adrenals by a significant increase in the release of these precursors in response to ACTH in the absence of a cortisol response. We conclude the following. 1) Adrenal adenoma formation in patients with Cushing's syndrome is accompanied by a parallel decrease in the stimulation of the release of steroid hormones in response to ACTH, cholera toxin, and forskolin. This points to a defect in the adenoma cells beyond the ACTH receptor. 2) Adrenal adenoma formation in patients with Cushing's syndrome is accompanied by a relative blockade of 11 beta-hydroxylase activity. 3) By comparing the preoperative dynamic tests of the pituitary-adrenal axis, the plasma ACTH concentration, the morphology of the adrenal glands, and their in vitro responsiveness, a gradual transition from pituitary to (partial) adrenal autonomy could be recognized in several patients.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Characterization of Adrenal Autonomy in Cushing's Syndrome: A Comparison betweenin Vivoandin VitroResponsiveness of the Adrenal Gland

Lamberts¹,

Zuiderwijk²,

Uitterlinden³

et al. 1990

The Journal of Clinical Endocrinology & Metabolism

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Different Sensitivity to Adrenocorticotropin of Dispersed Adrenocortical Cells from Patients with Cushing's Disease with Macronodular and Diffuse Adrenal Hyperplasia*

Lamberts

Bons

Bruining

1984

The Journal of Clinical Endocrinology & Metabolism

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A patient with Cushing's syndrome and low plasma ACTH levels had a unilateral adrenal mass (diameter, 3 cm), which proved to consist of adenomatous hyperplasia. Dispersed adrenocortical cells prepared from this mass responded to ACTH with a maximal increment in cortisol release of more than 400%. Five months after operation Cushing's syndrome recurred. Computed tomography scanning showed an enlarged macronodular adrenal gland on the other side. The cells prepared from this adrenal gland were stimulated by ACTH by more than 600%. In adrenal glands from eight other patients with Cushing's disease cells from macroscopic nodules in hyperplastic adrenocortical tissue had increased responsiveness to ACTH in vitro, in comparison to cells from macroscopically diffuse hyperplastic adrenal tissue. The stimulability of the pituitary-adrenal axis (by metyrapone) and its suppressibility (by high dose dexamethasone) did not differ between the two groups of patients. These observations suggest that in the presence of adenomatous or macronodular adrenal hyperplasia lower circulating ACTH levels may sustain hypercortisolism than in diffuse adrenal hyperplasia. The presence of a unilateral adrenal mass and low normal plasma ACTH levels in patients with Cushing's syndrome, therefore, does not unequivocally indicate the presence of an autonomous adrenal adenoma. Tests with metyrapone and dexamethasone should still be carried out in order to make a secure differential diagnosis.

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Glucocorticoid response and adrenal lipid peroxidation in rats submitted to chronic hypobaric hypoxia

Martín

Aguirre

Grosman

et al. 1993

Archives Internationales de Physiologie, de Biochimie et de Bio

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The well known physiological changes that occur in adaptation to chronic hypobaric hypoxia (CHH) prevent the fall in arterial blood oxygen pressure below normal limits but neither the ventilatory nor the circulatory adaptation are able to maintain a normal capillary blood pO2. We report here our findings on adrenal histology, function, and lipid peroxidation in intact and castrated rats of both sexes submitted to twelve weeks of adaptation to 4,400 m simulated altitude. In the CHH rats hematocrit was increased; adrenal weight was increased in males and decreased in castrated females. Adrenal histology and histochemistry were normal. Corticosterone level and uric acid were unchanged except in castrated animals: corticosterone was decreased in males and increased in females. Uric acid was increased in castrated males, the only group in which adrenal lipid peroxidation was unaffected by castration. In the remaining groups, it was diminished compared to their intact controls. Intact normoxic males showed a significant direct correlation between plasmatic lipoperoxidation products (TBA-reactive substances) and uric acid (r = 0.961), which disappeared under hypoxia or with castration. Sex related differences were found in hematocrit and adrenal weight responses. The presence of androgens was involved in the adaptative response of cortical and reticular histometry, lipid peroxidation, and corticosterone level. These results do not support Selye's hypothesis of exhausted adrenal glands in chronic stages of adaptation and suggest that a proper relation between adrenal and gonadal steroids hormones is essential for systemic and tissular responses to diminished oxygen supply.

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Steroid Hormone Production in Normal and Abnormal Human Adrenocortical Tissue

Cited by 3 publications

References 0 publications

Characterization of Adrenal Autonomy in Cushing's Syndrome: A Comparison betweenin Vivoandin VitroResponsiveness of the Adrenal Gland

Characterization of Adrenal Autonomy in Cushing's Syndrome: A Comparison betweenin Vivoandin VitroResponsiveness of the Adrenal Gland

Different Sensitivity to Adrenocorticotropin of Dispersed Adrenocortical Cells from Patients with Cushing's Disease with Macronodular and Diffuse Adrenal Hyperplasia*

Glucocorticoid response and adrenal lipid peroxidation in rats submitted to chronic hypobaric hypoxia

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