Preclinical Cushing's Syndrome Research Articles

Do the diagnostic criteria for subclinical hypercortisolism exist?

“Subclinical hypercortisolism” (SH) refers to a condition associated with a mild chronic increase in cortisol secretion. By definition, patients with SH do not exhibit specific symptoms of overt Cushing's syndrome (such as purple striae, easy bruising, proximal muscle weakness), SH has been preferred to “subclinical Cushing's syndrome”, a semantic ambiguity since Cushing's syndrome is, by definition, a set of symptoms; and to the term “preclinical Cushing syndrome” because the progression toward overt clinical hypercortisolism is very rare. However, SH still is misnomer as a number of studies suggest that this condition may induce long-term non-specific adverse conditions related to the mild cortisol excess (i.e. diabetes, hypertension, obesity, and osteoporosis). Various attempts have been made to define SH that remains a matter of controversies and uncertainties.

Towards a universally accepted definition of subclinical Cushing's syndrome - subclinical autonomous hypercortisolism.

The concept of subclinical cortisol excess and importantly its relevance remains a controversial issue in Endocrinology 1, 2. Preclinical Cushing's syndrome 3, subclinical Cushing's syndrome or subclinical hypercortisolism 2, recently rebadged in the European Society of Endocrinology Guidelines as “autonomous cortisol secretion” 4, is an example where a universally agreed upon definition (and name) has proven to be elusive. It has even been suggested that the syndrome is often an artefact of currently available tests of hypothalamic-pituitary-adrenal axis function 5, 6. This article is protected by copyright. All rights reserved.

Laparoscopic adrenalectomy for adrenal tumors: A 21-year single-institution experience

We have performed laparoscopic adrenalectomy including retroperitoneoscopic adrenalectomy via a single large port (RASLP) and conventional laparoscopic adrenalectomy (CLA) for adrenal tumors since 1992, and report our experience to date. The study population consisted of 134 patients who underwent laparoscopic adrenalectomy from 1992 to 2012. Fifty-eight patients (18 aldosterone-producing adenomas, 13 adenomas with Cushing's syndrome, 1 adenoma with preclinical Cushing's syndrome, and 26 nonfunctioning tumors) were treated using RASLP, and 76 patients (33 aldosterone-producing adenomas, 17 adenomas with Cushing's syndrome, 6 adenomas with preclinical Cushing's syndrome, 17 pheochromocytomas, and 3 nonfunctioning tumors) were treated using CLA. Complications were graded according to the modified Clavien system. The majority of RASLPs were performed during the 1990s, whereas all patients underwent CLA after 2000. The mean operation times (166 vs. 205minutes, p<0.01) and intraoperative estimated blood loss (85 vs. 247mL, p<0.01) were significantly lower in the CLA group. Conversion to open surgery was required in three patients (5%) in the RASLP group and five patients (7%) in the CLA group (p=0.73). Postoperative complications were grade 1 in three patients and grades 4 and 5 in one patient each in the RASLP group, whereas grade 2 in one patient was observed in the CLA group (p=0.085). Although this study included biases such as different eras and indications, CLA resulted in decreased operative times, blood loss, and postoperative complications compared with RASLP. CLA has so far become our preferred procedure for patients with adrenal tumor in our experience.

A Decrease in the Dose of Pegvisomant was Needed for the Treatment of Acromegaly after Adrenalectomy in a Patient with Coexisting Preclinical Cushing's Syndrome

We herein describe the case of a 47-year-old woman with pre-clinical Cushing's syndrome caused by a left adrenal adenoma, which was diagnosed 6 years after trans-sphenoidal selective removal of a pituitary adenoma for acromegaly at age 35. The patient was started on bromocriptine and then somatostatin analogues after the surgery; however, since her serum insulin-like growth factor-1 (IGF-1) values remained above the age-adjusted normal range, the treatment for acromegaly was switched from somatostatin analogues to pegvisomant (10 mg daily), before a left laparoscopic adrenalectomy. After the subsequent adrenalectomy, the dose of pegvisomant could be reduced gradually to once every 4 days without any increase in the serum IGF-1 values. This is the first report describing the need for a different dose of pegvisomant for the treatment of acromegaly before and after adrenalectomy for pre-clinical Cushing's syndrome.

Synaptophysin immunoreactivity in adrenocortical adenomas: a correlation between synaptophysin and CYP17A1 expression

The adrenal cortex is not considered to be an intrinsic part of the diffuse neuroendocrine system, but adrenocortical neoplasms possess neuroendocrine properties. In this study, we examined synaptophysin (SYP) and neural cell adhesion molecule (NCAM) expression in adrenocortical adenomas in relation to adrenal function. Immunohistochemical analysis showed that 50.7 and 98.6% of the cortical adenomas showed SYP and NCAM immunoreactivities respectively. There was no apparent difference in NCAM immunoreactivity among the adenomas. However, the immunostaining for SYP was significantly stronger in cortisol-producing adenomas (CPA) than in aldosterone-producing adenomas (APA), nonfunctioning adenomas (NFA), showing no clinical or endocrinological abnormality, or adenomas associated with preclinical Cushing's syndrome (preCS). Western blotting and real-time PCR demonstrated that the expression level of SYP protein and mRNA was significantly higher in CPA than in APA or NFA. Additionally, the SYP mRNA level showed a positive correlation with CYP17A1 mRNA. In addition to the plasma membrane, mitochondria, and smooth endoplasmic reticulum, SYP immunoreactivity was detected in the Golgi area, which is known to be involved in the regulation of mitochondrial cholesterol and the transport of steroid intermediates. It was unexpected that the ratio of positive cells for SYP in preCS was less than that in APA and NFA. However, further examination is required, because the number of preCS cases we investigated was very small. We propose that SYP expression in adrenocortical cells may be involved in some aspect of adrenal function such as transport or secretion of glucocorticoids.

Síndrome de Cushing: situaciones especiales

The present article reviews: Corticotrophin (ACTH) independent bilateral macronodular adrenal hyperplasia, which is characterized by aberrant adrenal receptors due to either ectopic expression or to overexpression (eutopic expression). Micronodular adrenal hyperplasia, which provokes small pigmented nodules in the adrenal gland with atrophy of the internodal tissue. These nodules may not be visible on imaging tests. The term subclinical Cushing's syndrome, coined in 1981, should be used in patients with clinically non-functioning adrenal adenomas but who show autonomous cortisol production that is insufficient to generate overt Cushing's syndrome. This entity must be distinguished from preclinical Cushing's syndrome, given that the subclinical form does not necessarily herald the development of symptoms of hypercortisolism. Cushing's syndrome is uncommon in children and adolescents. Regarding the general incidence of the disease, only 10% of cases are diagnosed in this age group. The most common cause of endogenous Cushing's disease in children older than 7 years is ACTH-dependent Cushing's disease (85%). The association of Cushing's syndrome and pregnancy is highly uncommon, since hypercortisolism usually causes amenorrhea, oligomenorrhea and infertility due to inhibition of gonadotropin secretion. One hundred thirty-six pregnancies have been described in 122 women, with a gestational age at diagnosis of 18.4+/-1 weeks.

プレクリニカルクッシング症候群術後のステロイド補充に関する臨床的検討

Diagnostic criteria for preclinical Cushing's syndrome (PCS) were reported in 1996. However, requirement of postoperative steroid hormone replacement is still controversial issue. In this study, we observed recent surgical cases retrospectively and evaluate the use of postoperative steroid hormone replacement. Eighteen patients with PCS underwent surgery from 1997 to 2007 in Jikei University Hospital. Thirteen of them received postoperative steroid hormone replacement. We investigated preoperative hormone activity by 131I-adosterol scintigraphy and suppression of ACTH and evaluated the requirement of postoperative steroid hormone replacement. Preoperative serum cortisol was normal range in all patients. Serum ACTH was suppressed in 10 of them (56%). In 131I-adosterol scintigraphy, accumulation in ipsilateral side was observed in all patients. Accumulation in contralateral side was observed in 13 patients whose serum ACTH had tendency to be suppressed. Mean period of steroid hormone replacement was 19.8 weeks. Patients with lower preoperative ACTH tended to require longer period until withdrawal of steroid hormone replacement. In addition, patients received steroid hormone replacement with higher starting dose significantly required longer period. Three of them had complications during tapering of steroid hormone. Postoperative adrenal insufficiency is important issue as postoperative management of PCS patients whose function of contralateral adrenal or pituitary gland is suppressed. 131I-adosterol scintigraphy and preoperative serum ACTH were important factors to evaluate the requirement of postoperative steroid hormone replacement. Especially, patients with low preoperative serum ACTH tended to require long duration of postoperative steroid hormone replacement. On the other hand, patients with accumulation of contralateral side in 131I-adosterol scintigraphy and without suppression of serum ACTH may not require steroid hormone replacement. Decrease starting dose of steroid hormone replacement for appropriate patients could shorten the period of steroid hormone replacement safely.

Phaeochromocytoma comb?ned with subclinical Cushing's syndrome and pituitary microadenoma

Phaeochromocytoma (PHEO) occasionally associates with pathological lesions of the adrenal cortex. The coexistence of PHEO and pre-clinical Cushing's syndrome (PCS) of the same adrenal gland has rarely been reported. We report a case of PHEO and PCS originating from the same adrenal gland and discuss the peculiar diagnostic aspects of this entity. A 64 yr old man was hospitalized to evaluate the right adrenal mass which was discovered incidentally by ultrasonography. He had a history of type 2 diabetes mellitus and hyperlipidemia. Blood pressure measurements were all normal during his hospital stay. Laboratory examination showed: urinary catecholamines were markedly increased. HbA1C of 14.3 %, midnight cortisol of 11(microg/dL), cortisol was not suppressed after the overnight 1 mg oral dexamethasone suppression test (DST): 3.42(microg/dL), 24 hr free cortisol in the urine : 213 microg/day (10-100), cortisol levels were suppressed more than 50% with 8 mg of dexamethasone. CT scan of the adrenal glands showed a 6 cm well encapsulated right adrenal mass together with a clearly normal left adrenal gland. MRI investigation of the sella turcica revealed a pituitary microadenoma on the right side of the adenohypophysis He was treated with alpha and subsequent beta blockers after the diagnosis of PHEO and PCS was made. Right adrenalectomy was performed. The pathology showed typical PHEO with adrenocortical hyperplasia. VMA, metanefrin and free cortisol levels were normalized one month after surgery. The present report is a rare case of PHEO combined with PCS in the same adrenal gland.

A Case of Primary Aldosteronism Associated with Renal Artery Stenosis and Preclinical Cushing's Syndrome

We identified a left adrenal tumor, left renal atrophy, and left renal artery stenosis (RAS) in a 52-year-old man by MRI/magnetic resonance angiography (MRA) during evaluation of hypertension. Laboratory tests revealed hypokalemia, a high plasma aldosterone concentration (PAC), low plasma renin activity (PRA), and normal plasma cortisol. An excessive response of aldosterone and cortisol to adorenocorticotrophic hormone (ACTH) was found upon selective sampling of the left adrenal vein. Selective renal venous sampling showed a left/right renal venous PRA ratio of 1.7. A dexamethasone (8 mg) suppression test showed insufficient suppression of cortisol. We diagnosed this patient as having aldosterone-producing adrenal adenoma (APA) associated with renovascular hypertension (RVH) and preclinical Cushing's syndrome. As an initial treatment, percutaneous transluminal renal angioplasty was performed. Postoperatively, the patient's blood pressure decreased. One month later, the tumor was removed by complete laparoscopic left adrenalectomy. Postoperatively, blood pressure decreased further and both PAC and PRA were normalized. However, antihypertensive therapy could not be completely stopped. The renal dysfuntion that occurred prior to treatment seemed to prevent complete normalization of blood pressure.

Preclinical Cushing's Syndrome Resulting from Adrenal Black Adenoma Diagnosed with Diabetic Ketoacidosis

A right adrenal tumor was incidentally discovered on abdominal computed tomography performed on a 53-year-old Japanese man, who had been hospitalized with diabetic ketoacidosis. Normal values were obtained for adrenal hormones in the morning after an overnight fast and urinary cortisol excretion after treatment of diabetic ketoacidosis with insulin. However, overnight dexamethasone administration with 1 mg or 8 mg did not completely suppress serum cortisol levels. There were no remarkable physical findings related to Cushing's syndrome. The patient was diagnosed as having preclinical Cushing's syndrome (PCS). Histological examination of the adrenalectomy specimen demonstrated adrenal black adenoma. Blood glucose levels subsequently improved after adrenalectomy, and the patient never developed adrenal insufficiency after hydrocortisone withdrawal. The patient was treated with diet therapy alone, and maintained good glycemic control. However, the patient still showed a diabetic pattern in an oral glucose tolerance test. It seems that the existence of PCS in addition to the underlying type 2 diabetes mellitus contributed to aggravation of blood glucose levels. Although there are many aspects of the natural course of PCS that have not been thoroughly elucidated, it is necessary to remain aware that a PCS patient with abnormal glucose metabolism may develop diabetic ketoacidosis by environmental agents.

Possibly Simultaneous Primary Aldosteronism and Preclinical Cushing's Syndrome in a Patient with Double Adenomas of Right Adrenal Gland

We reported a rare case of simultaneous primary aldosteronism and preclinical Cushing's syndrome due to unilateral double adrenocortical adenomas in a 57 year-old woman who had had hypertension for the last 10 years. Abdominal computed tomography showed double tumors in her right adrenal gland. Physical findings revealed simple obesity and hypertension, but no other abnormal findings were detected. Laboratory findings demonstrated that serum potassium was 3.8 mmol/l; plasma renin activity, 0.3 ng/ml/h; plasma aldosterone, 100 pg/ml, and aldosterone renin ratio (ARR), 33. Serum cortisol was 15.7 microg/dl. There was no circadian rhythm of serum cortisol, and no suppression of serum cortisol in response to exogenous dexamethasone administration. Right adrenalectomy was performed under laparoscopy. Two well-circumscribed tumors, whose sizes were 21 and 19 mm in greatest diameter, were detected. They were macroscopically composed of a golden-yellow portion admixed with a brown portion, which corresponded to clear cells and compact cells, respectively. Immunohistochemical staining for steroidogenic enzymes demonstrated the presence of all the enzymes involved in corticosteroidogenesis in these two adenomas, indicating that the two adenomas produced both cortisol and mineralocorticoid. Specifically, one adenoma mainly caused excessive production of cortisol as compared to the other one. These findings indicate that overproduction of both cortisol and mineralocorticoid was evident in the two adenomas of the right adrenal gland in immunohistochemical study for steroidogenic enzymes, whereas there was less clinical manifestation of primary aldosteronism and Cushing's syndrome in the present patient.

A Case of Preclinical Cushing's Syndrome Resulting from Black Adrenal Adenoma Incidentally Discovered during Evaluation of Diabetic Nephropathy

A Case of Preclinical Cushing's Syndrome Resulting from Black Adrenal Adenoma Incidentally Discovered during Evaluation of Diabetic Nephropathy

Coexistence of three distinct adrenal tumors in the same adrenal gland in a patient with primary aldosteronism and preclinical Cushing's syndrome

A 62-year-old woman was admitted to our hospital because of hypokalemia. Physical examination revealed no signs of excessive adrenocortical steroid production, as are found in Cushing's syndrome. Her plasma renin activity (PRA) was suppressed (0.10 ng/ml per h), and her serum aldosterone level was high (30.0 ng/dl). PRA was not increased after a renin-releasing test. Her plasma adrenocorticotropic hormone (ACTH) level was low (<5 pg/ml), but her serum cortisol level was normal (21.0 microg/dl). Administration of 8 mg dexamethasone did not suppress her plasma cortisol level. Finally, she was diagnosed with clinical primary aldosteronism associated with preclinical Cushing's syndrome. Magnetic resonance image revealed three sequential nodular masses (each 15 mm x 15 mm) in the right adrenal gland. A right adrenalectomy was performed by endoscopy. The three removed tumors appeared to have different characteristics. Microscopic examination revealed that the upper and lower tumors were adrenocortical adenomas, and the middle tumor was a black adenoma. Immunohistochemical staining for the enzymes involved in cortisol biosynthesis suggested that the upper tumor secreted aldosterone, whereas either or both of the two other tumors secreted cortisol. Surprisingly, at 33 years of age, she had been diagnosed with Cushing's syndrome, due to a cortisol-producing adrenocortical adenoma, and she had received a left adrenalectomy. Clinically and pathophysiologically, this was a very rare case.

A Case of Preclinical Cushing's Syndrome Associated with Diurnal Rhythms of ACTH and Cortisol in Blood: Correlation with Histological Findings

We describe a case of adrenocortical adenoma with preclinical Cushing's syndrome demonstrating diurnal rhythms of ACTH and cortisol in blood. A 50-year-old man was admitted to the hospital for the evaluation of incidental right adrenal mass with hyperglycemia and hypertension. On admission, there were no signs of clinical manifestation of hypercortisolism. The basal levels of cortisol (9.3 microg/dl) and ACTH (9.4 pg/ml) at 0800 h were not elevated and these diurnal rhythms were maintained. One or 8 mg of dexamethasone given orally overnight suppressed the plasma ACTH but not serum cortisol. Ultrasonogram, CT and scintiscan of (131)I adosterol all demonstrated an enlarged adrenal mass in the right adrenal gland. The right adrenal gland was subsequently resected by laparoscopic surgery. Histopathological findings of resected adrenal tumor were consistent with adrenocortical adenoma. Adjacent non-neoplastic adrenal tissue demonstrated adrenocortical atrophy but DHEA-sulfotransferase immunoreactivity in the zona reticularis was detected.

Pheochromocytoma combined with pre-clinical Cushing’s syndrome in the same adrenal gland

Pheochromocytoma (PHEO) occasionally associates with pathological lesions of the adrenal cortex. In most of them, ectopic adrenocorticotropic hormone (ACTH) produced by PHEO resulted in bilateral adrenocortical hyperplasia. The coexistence of PHEO and pre-clinical Cushing's syndrome (PCS) of the same adrenal gland has rarely been reported. We report on a patient and discuss the peculiar diagnostic aspects of this entity. A 52-yr-old Turkish woman was hospitalized at Farabi Hospital for further examinations of a right adrenal mass that was incidentally discovered by abdominal ultrasonography during examinations for abdominal bloating and "gas" in other hospital. The patient had a history of palpitations, nervousness, sweating and heat intolerance. On admission, her blood pressure was 140/90 mmHg. A physical examination revealed no signs of an excessive production of adrenocortical steroids such as in CS. Tension Holter monitoring revealed paroximal hypertension attacks (183/105 mmHg). Urinary catecholamines were markedly increased. Her serum cortisol concentrations ranged from 5 to 17 microg/dl, whereas ACTH levels were undetectable. Cortisol was not suppressed on the overnight 1 mg oral dexamethasone suppression test (DST), 2-day low-dose dexamethasone suppression test (DST). Abdominal computed tomography and magnetic resonance imaging studies revealed a solid round tumor approximately 4 cm in diameter, located in the right adrenal gland. A 131 lodine-metaiodobenzylguanidine (131 I-MIBG) scan revealed uptake within tumor in the right adrenal gland. Right adrenalectomy was performed; the surgical specimen revealed PHEO and adrenocortical hyperplasia. To our knowledge, the present report is a rare case of PHEO combined with PCS in the same adrenal gland.

Conduite à tenir face à un incidentalome surrénalien associé à une hypertension artérielle

Hypertension (HTA) is a very common disease but its origin is well knowed only in 1 to 5% of the cases. HTA is present in half of the patients who have an adrenal incidentaloma. Clinical data, hormonal sampling, computed tomography and adrenal scintigraphies are necessary to identify hyperfunctioning adrenal tumors. Adrenalectomy is indicated in case of potential malignant tumors and hyperfunctioning tumors. If HTA seems to be not in relation with the adrenal mass, it is recommanded to recognize a congenital enzymatic block in order to ovoid an unnecessary adrenalectomy and to search for a pre clinical Cushing's syndrome. The last one is associated with HTA in 91% of the cases, and with a morbid obesity, mellitus diabetes or dyslipidemia in 50% of the cases. The removal of the adrenal mass improves the HTA for half of the patients. If the adrenocortical tumor is nonfunctioning, patients have to be followed during a long time. HTA will be considered as “essential” after a new comprehensive analysis performed 3 years later.

Primary Aldosteronism Combined With Preclinical Cushing's Syndrome in an Elderly Patient

Pre-clinical Cushing's syndrome (pre-CS) is sometimes seen with adrenal cortical tumors. An 80-year-old woman had severe hypertension and hypokalemia, the typical clinical features of primary aldosteronism, but detailed hormonal examinations revealed the accompanying pre-CS. After adrenalectomy by laparoscopy, her blood pressure was remarkably reduced and the hypokalemia also recovered. The tumor consisted of mostly light clear cells and scattered dark compact cells resembling islands. Abundant expression of cytochrome P450 aldosterone synthase in the clear cells and cytochrome P450 11beta-hydroxylase in the dark cells was detected by immunohistochemical studies, which confirmed that clear cells can produce aldosterone and compact cells can produce cortisol.

Discrepancies in Results of Low-and High-dose Dexamethasone Suppression Tests for Diagnosing Preclinical Cushing's Syndrome

According to the diagnostic criteria for adrenal preclinical Cushing's syndrome (PreCS) established by a group headed by the Ministry of Health, Labor and Welfare (MHLW), low- and high-dose dexamethasone suppression tests (DSTs) must be performed to prove autonomous cortisol secretion, i.e., > or =3 microg/dL serum cortisol following 1-mg DST administration, and > or =1 microg/dL serum cortisol following 8-mg DST administration. However, discrepancies have been documented in the results of low-and high-dose DSTs. We therefore investigated the validity of the DST for diagnosing PreCS by performing 1-mg and 8-mg DSTs in 39 patients with adrenal incidentaloma, but no characteristic Cushingoid symptoms. In about half of these patients (20/39, 51.3%), high-dose DST was positive but low-dose was negative, and one or more of the other abnormalities of hypothalamus-pituitary-adrenal axis dysfunction was seen in 75% of these patients. Furthermore, no significant difference in incidence of glucose intolerance and hypertension was noted in patients with positive high-dose DST and negative low-dose DST compared with patients with positive low- and high-dose DST. Under the current MHLW diagnostic criteria, patients with positive high-dose DST and negative low-dose DST are not diagnosed with PreCS, but some of these patients should be. Discrepancies in the results of low- and high-dose DSTs appear attributable to the current cutoff values, and further investigations are necessary to resolve these discrepancies.

Subclinical Cushing's Syndrome

Clinically inapparent adrenal masses, or adrenal incidentalomas, are discovered inadvertently in the course of workup or treatment of unrelated disorders. Cortical adenoma is the most frequent type of adrenal incidentaloma accounting for approximately 50% of cases in surgical series and even greater shares in medical series. Incidentally discovered adrenal adenomas may secrete cortisol in an autonomous manner, that is not fully restrained by pituitary feed-back, in 5 to 20% of cases depending on study protocols and diagnostic criteria. A number of different alterations in the endocrine tests aimed to assess the function of the hypothalamic-pituitary-adrenal axis has been demonstrated in such patients. This heterogeneous condition has been termed as subclinical Cushing's syndrome, a definition that is more accurate than preclinical Cushing's syndrome since the evolution towards clinically overt hypercortisolism does occur rarely, if ever. The criteria for qualifying subclinical cortisol excess are controversial and we presently do not have sufficient evidence to define a gold standard for the diagnosis of subclinical Cushing's syndrome. An increased frequency of hypertension, central obesity, impaired glucose tolerance, diabetes and hyperlipoproteinemia has been described in patients with subclinical Cushing's syndrome; however, there is not evidence-based demonstration of its long-term complications and, consequently, the management of this condition is largely empirical. Either adrenalectomy or careful observation associated with treatment of metabolic syndrome has been suggested as treatment options because data are insufficient to indicate the superiority of a surgical or nonsurgical approach to manage patients with subclinical hyperfunctioning adrenal cortical adenomas.

Clinical characteristics of 16 patients suspected preclinical Cushing's syndrome

In 1996, Japanese guidelines for the diagnosis of preclinical adrenal Cushing's syndrome were proposed. However, several patients with preclinical Cushing's syndrome (PCS) didn't clearly show that these diagnostic guidelines were universally applicable. The aim of the present study was to evaluate the validity of these diagnostic guidelines on the basis of our clinical experience. We performed adrenalectomy for adrenal incidentaloma in 16 patients with suspected PCS at our university hospital from 1990 through 2002. Eight patients met the Japanese criteria for the diagnosis of PCS (PC group) and 8 did not (dexamethasone [DXM] suppression group). Clinical characteristics and pathology profiles were compared between the groups. No patients in the DXM suppression group showed responses of serum cortisol levels on a 1-mg overnight dexamethasone suppression test. Twenty-four-hour urinary levels of 17-hydroxycorticosteroids were significantly higher in the PC group than in the DXM suppression group. In all patients of both groups, adrenal scintigraphy showed marked accumulation of radioisotope in the adhesive, atrophic adrenal cortex. One patient of the DXM suppression group had severe adrenal symptoms after adrenalectomy. Several patients in the DMX suppression group showed clinical improvement after adrenalectomy, as well as did several patients in the PC group. Endocrine activity may have been higher in the PC group than in the DXM suppression group. However, because patients who failed a 1-mg DXM suppression test may in fact have autonomous cortisol secretion, adrenalectomy may still be indicated. Autonomous cortisol secretion might not be documented with the 1-mg overnight DXM suppression test; therefore, the results must be interpreted carefully.