Cushing's disease coexisting with a single macronodule simulating adenoma of the adrenal cortex

Leiba, S; Shindel, Bella; Weinberger, I; Fuchs, Jacobs; Rotenberg, Z; C, Mor; Kaufman, H.

doi:10.1530/acta.0.1120323

Cited by 17 publications

(15 citation statements)

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“…Our studies shed some further light on the different forms of autonomy at the adrenal level and the possible transition from pituitary to adrenal autonomy, as they have been hypothesized in a number of patients with different forms of Cushing's syndrome (9)(10)(11)(12)(13)(14). In this respect the in vivo and in vitro data of patient 4 are helpful.…”

Section: Discussionsupporting

confidence: 55%

“…During the course of the disease such an adrenal nodule may become autonomous, which eventually will result in suppression of pituitary ACTH release and of the uninvolved adrenal cortex (28,29). Thus, the solitary macronodules in the patients previously described (9,11,12,14,28) may have represented an intermediary stage in the transition between diffuse adrenal hyperplasia and the appearance of an autonomous adrenocortical adenoma, while the single encapsulated adenoma of patient 4, which was unresponsive in vitro to ACTH, might even represent another further step in the process of this transition, just before autonomous cortisol release by this adenoma (completely) suppresses pituitary ACTH release and eventually also suppresses the activity of the surrounding and contralateral adrenal gland. The final and last step of this transition might be represented by patient 8.…”

Section: Discussionmentioning

confidence: 93%

“…This patient differed from the previously described patients with Cushing's disease with a coexisting single macronodule of the adrenal cortex (9-14, 28, 29) in that these nodules always consisted of hyperplastic tissue and were not surrounded by a capsule, while in vitro studies (as carried out in three cases) showed a normal or a hyperresponse of cortisol to ACTH compared with that of the surrounding diffuse hyperplastic adrenal tissue. A dual control with various degrees of autonomy of the adrenal in some cases and the predominance of pituitary control in others has been hypothesized (12,14,29,30). During the course of the disease such an adrenal nodule may become autonomous, which eventually will result in suppression of pituitary ACTH release and of the uninvolved adrenal cortex (28,29).…”

Section: Discussionmentioning

confidence: 99%

“…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). In recent years a number of patients with supposedly pituitary-dependent Cushing's disease have been described in whom a single adrenal adenoma was also detected (9)(10)(11)(12)(13)(14). These patients might represent different stages of the transition from pituitary to adrenal-dependent Cushing's syndrome.…”

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confidence: 99%

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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: Discussionsupporting

confidence: 55%

Section: Discussionmentioning

confidence: 93%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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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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“…A rare case of Cushing's disease coexisting with a single macronodule simulating the adenoma of the adrenal cortex has been reported [10]. Endocrinologic tests indicated Cushing's disease, whereas the radiological findings suggested a left adrenal adenoma.…”

Section: Discussionmentioning

confidence: 98%

Adrenal Tuberculosis in Cushing's Disease with Bilateral Macronodular Adrenocortical Hyperplasia

et al. 2006

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Abstract. Cushing's disease is a disorder of hypercortisolism caused by a pituitary micro-or macro-adenoma. Most patients with Cushing's disease have a bilateral adrenal enlargement, which depends on the duration of the disease, as a result of the long standing ACTH stimulation of both adrenal glands. However, in macronodular adrenocortical hyperplasia (MNH) that is caused by Cushing's disease, if the MNH gains autonomy, a bilateral adrenalectomy, as well as the removal of pituitary adenoma, is often essential. We encountered a patient diagnosed with Cushing's disease with bilateral adrenal tuberculosis simulating MNH. She had taken anti-tuberculosis medications one year prior to admission due to spinal tuberculosis. Sellar MRI revealed a pituitary macroadenoma, but adrenal CT showed enlargement in both adrenal glands that appeared to be MNH. A hormonal study and bilateral inferior petrosal sinus sampling revealed Cushing's disease. Therefore, she underwent trans-sphenoidal surgery of the pituitary mass. The pituitary surgery was successful and the serum cortisol returned to normal range. However, the adrenal mass rapidly enlarged after removing the pituitary tumor without showing evidence of a recurrence or adrenal autonomy of hypercortisolism. Accordingly, a laparoscopic left adrenalectomy was performed to examine the nature of the mass. The resected left adrenal gland was pathologically determined to have a lesion of tuberculosis with some part of the intact cortex. So we assumed that the cause of rapid adrenal enlargement might be due to adrenal tuberculosis. In summary, to the best of our knowledge, this is the first case of Cushing's disease coexisting with both adrenal tuberculosis simulating a bilateral MNH.

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A patient with recurrent hypercortisolism after removal of an ACTH-secreting pituitary adenoma due to an adrenal macronodule

Timmers

Ginneken

Wesseling

et al. 2006

J Endocrinol Invest

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A 41-yr-old female was referred for signs and symptoms of Cushing's syndrome. Cortisol was not suppressed by 1 mg dexamethasone (0.41 micromol/l). Midnight cortisol and ACTH were 0.44 micromol/l and 18 pmol/l, respectively. Urinary cortisol excretion was 250 nmol/24 h (normal between 30 and 150 nmol/24 h). A magnetic resonance imaging (MRI) revealed a pituitary lesion of 7 mm. ACTH and cortisol levels were unaltered by administration of human CRH and high-dose dexamethasone. Inferior sinus petrosus sampling showed CRH-stimulated ACTH levels of 128.4 (left sinus) vs a peripheral level of 19.2 pmol/l, indicating Cushing's disease. After 4 months of pre-treatment with metyrapone and dexamethasone, endoscopic transsphenoidal resection of an ACTH-positive pituitary adenoma was performed. ACTH levels decreased to 2.6 pmol/l and fasting cortisol was 0.35 micromol/l. Despite clinical regression of Cushing's syndrome and normalization of urinary cortisol, cortisol was not suppressed by 1 mg dexamethasone (0.30 micromol/l). Ten months post-operatively, signs and symptoms of Cushing's syndrome reoccurred. A high dose dexamethasone test according to Liddle resulted in undetectable ACTH, but no suppression of cortisol levels, pointing towards adrenal-dependent Cushing's syndrome. Computed tomography (CT)-scanning showed a left-sided adrenal macronodule. Laparoscopic left adrenalectomy revealed a cortical macronodule (3.5 cm) surrounded by micronodular hyperplasia. Fasting cortisol had decreased to 0.02 micromol/l. Glucocorticoid suppletion was started and tapered over 12 months. Symptoms and signs of hypercortisolism gradually disappeared. This case illustrates, that longstanding ACTH stimulation by a pituitary adenoma can induce unilateral macronodular adrenal hyperplasia with autonomous cortisol production.

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Cushing's disease coexisting with a single macronodule simulating adenoma of the adrenal cortex

Cited by 17 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

Adrenal Tuberculosis in Cushing's Disease with Bilateral Macronodular Adrenocortical Hyperplasia

A patient with recurrent hypercortisolism after removal of an ACTH-secreting pituitary adenoma due to an adrenal macronodule

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