Incidentally found adrenocortical carcinoma. A study of 21 patients.

The frequency of adrenocortical carcinoma was studied in a group of 311 incidentally discovered adrenal tumours. Clinical characteristics were also analysed. Ultrasound scan and computed tomography were the main imaging techniques used. Hormonal examinations were also carried out. The patients with an adrenal tumour diameter greater than or equal to 4.0 cm, and those with excess steroid production were recommended for surgery. Of 131 patients treated with surgery, adrenocortical carcinoma was diagnosed in 21 cases. The diameter of these tumours ranged between 3.2 and 20.0 cm. The majority of these were hormonally inactive, but, in some cases increased corticosteroid secretion was noted. In 17/21 patients, mitotane was administered following surgery, with a good response in 13 cases. These 21 cases were compared with a group of 51 patients with clinically overt adrenocortical carcinoma.

Incidentally discovered adrenal mass (incidentaloma): investigation and management of 208 patients.

OBJECTIVE: Incidentally discovered adrenal masses are fairly common, although there are some controversies concerning the results of hormonal investigation (especially DHEAS values) and the methods of management. We summarize our experience in diagnosis, pathological findings and treatment of a large group of patients with incidentally found adrenal tumours. DESIGN AND PATIENTS: Our study included patients referred to the Department of Endocrinology of the Centre of Post-graduate Medical Education (Warsaw, Poland) during the last 10 years because of an adrenal tumour incidentally found on ultrasound scan. In all cases this was confirmed by computed tomography. There were 208 patients (148 female and 60 male), 14-76 years old. Unilateral adrenal masses were found in 172 patients (right 106, left 66), while bilateral masses were demonstrated in 36 patients. The size of the tumours ranged between 0.8 and 21.0 cm. The most common clinical abnormalities were hypertension (36 cases), obesity (23 cases), diabetes (8 cases), Addison's disease (6 cases). MEASUREMENTS: Endocrine tests evaluating pituitary-adrenal function (urinary excretion of 17-hydroxycorticosteroids, 17-ketosteroids and catecholamines, plasma concentrations of ACTH, cortisol, DHEAS, androstendione and testosterone, dexamethasone suppression test and corticotrophin-releasing hormone stimulation test). RESULTS: Cortisol hypersecretion was noted in two patients with coexisting Cushing's disease and high normal 17-OHCS values with lack of dexamethasone suppressibility were found in six other patients with pre-clinical Cushing's syndrome. More common were subtle hormonal abnormalities: low ACTH levels (in 33 out of 98 investigated patients), diminished dexamethasone suppressibility and lack of ACTH response in the CRH test (in two out of 12 patients). Urinary catecholamine excretion was elevated in nine patients. In the group of 85 patients treated by surgery the most frequent pathological findings were: adrenocortical adenoma (21), carcinoma (17), phaeochromocytoma (13), metastatic masses (12) and myelolipoma (10). The size of carcinomas ranged from 3.2 to 20.0 cm, while the size of non-malignant tumours ranged from 1.5 to 21.0 cm. CONCLUSIONS: Every patient with an incidentally discovered adrenal mass has to be investigated to detect malignancy and subtle hormonal overproduction, to select the cases for surgical treatment. Most of the adrenocortical carcinomas were > 7.0 cm in diameter. For prophylactic purposes, adrenal incidentalomas > 4.0 cm should be treated by surgery, while the smaller ones could be followed-up (with special care for those between 3.0 and 4.0 cm).

MRI versus CT in the diagnosis of Nelson's syndrome.

The purpose of the study was to evaluate the utility of MRI and CT in the diagnosis of Nelson's syndrome, i. e. pituitary tumours in patients bilaterally adrenalectomized for Cushing's disease. Thirteen patients, followed up for 5-29 years after adrenalectomy, were studied. In 6 of them CT and MRI revealed no changes in the pituitary gland. In the remaining 7 patients only three CT scans were suggestive of a pituitary adenoma. MRI studies with administration of gadodiamide confirmed the CT diagnosis of Nelson's tumour in 3 patients and disclosed microadenomas in a further 4 patients. Neurosurgical treatment in 4 patients confirmed the MRI findings. Additionally CT and MRI examinations were performed in 5 patients suspected of a recurrent Nelson's tumour 3-11 years after neurosurgery. MRI visualized recurrent adenomas in 3 patients that were not well seen by CT scans. In our experience MRI was more effective than CT in the diagnosis of Nelson's syndrome.

Early diagnosis of Nelson's syndrome.

Nelson's syndrome is a specific form of Cushing's disease treated by bilateral adrenalectomy, presenting with a deep hyperpigmentation caused by a pituitary adenoma (corticotropinoma). These ACTH-secreting tumors are frequently aggressive, so early diagnosis is of prime importance. We have studied 33 patients with Nelson's syndrome, 28 women and 5 men, aged 14-56 yr at the time of adrenalectomy and 16-58 yr at the time of Nelson's syndrome diagnosis (observed for 5-32 yr). Methods of examination included simultaneous adrenocorticotropic hormone (ACTH) and cortisol measurements during routine hydrocortisone replacement therapy, computed tomography (CT), pituitary magnetic resonance imaging (MRI), and visual field examination. The results obtained in a group of six patients diagnosed in the last 3 yr were compared with those obtained in a group of 27 patients examined before 1992. High plasma ACTH levels accompanied by normal serum cortisol concentration were characteristic for a late stage of the disease. Absolute temporal scotomas were an early finding. MRI, especially with the gadolinium enhancement, was superior to CT in demonstrating pituitary microadenomas in Nelson's syndrome. Thus, MRI diagnosis allowed for an early neurosurgical treatment of the patients with Nelson's tumors.

Adrenocortical carcinoma. A clinical study and treatment results of 52 patients.

BACKGROUND: Adrenocortical carcinoma is a rare tumor with a poor prognosis. This work was aimed at analyzing the clinical outlook and treatment results of 52 patients with this disease. METHODS: This study included patients with adrenocortical carcinoma referred to the Department of Endocrinology at the Center of Postgraduate Medical Education (Warsaw, Poland) during the last 30 years. In 11 patients, the adrenal tumor was found incidentally by ultrasonographic scan. Hormonal examinations made it possible to define the endocrine activity of the tumors, whereas imaging techniques helped to determine their staging. Forty-eight patients underwent surgery, and 36 of them received mitotane. This drug was administered to 26 patients for a range of 10 months to 10 years; 13 patients received mitotane immediately after the operation, and 13 others after a delay. The patients with severe hypercorticism were pretreated before surgery with aminoglutethimide and mitotane. RESULTS: The study comprised 10 men and 42 women; hormonally active tumors were diagnosed in 39 of them. Cushing's syndrome was the most frequent entity. At diagnosis, 17 cases were classified as localized disease, 15 as regional disease, and 20 as distant disease. Pretreatment with the inhibitors of steroidogenesis improved the survival perspectives in the early postoperative period. As of this writing, there were 12 survivors in the group of 26 patients treated by surgery and long term mitotane therapy and only 2 survivors of 7 patients treated with surgery only. CONCLUSIONS: Surgery with immediate adjuvant long term mitotane administration was the most effective form of therapy for patients with adrenocortical carcinoma.

Ectopic ACTH syndrome due to bilateral ovarian androblastoma with double, gynandroblastic differentiation in one ovary.

A case of fulminant Cushing's syndrome due to an ectopic ACTH secretion in a patient with bilateral ovarian sex-cord stromal tumour is reported. Surgical resection of the ovaries as well as the inhibitors of steroid synthesis and cytostatics caused only transient improvement because the widespread neoplastic dissemination progressed very quickly.

[Effect of aminoglutethimide on ACTH plasma levels in Cushing's disease and Nelson syndrome]. / Wplyw aminoglutetymidu na stezenie ACTH w osoczu w chorobie Cushinga i zespole Nelsona.

Out of all steroidogenesis inhibitors aminoglutethimide is most frequently used agent for so-called chemical adrenalectomy, especially in oncological cases. The present studies aimed at assessing an effect of the inhibition of cortisol synthesis on plasma ACTH in patients treated with aminoglutethimide. According to the rules of negative feedback, an increase in plasma ACTH should be expected. Aminoglutethimide has been administered to 24 patients with Cushing's disease for 1-6 months. Plasma ACTH did not increase but statistically significantly decreased despite a decrease in blood cortisol. It indicates that aminoglutethimide directly inhibits ACTH secretion. No return of the normal circadian rhythm of cortisol and ACTH release suggests that the drug exerts an effect on ACTH release regulating mechanisms. No definite results were achieved in patients with Nelson syndrome treated with aminoglutethimide for a short period of time. Plasma ACTH levels tend to decrease but no statistical significance was observed in comparison with placebo. It may depend on markedly increased corticotrophin secretion in Nelson tumors.

A correlative study between cortisol and ACTH in Cushing's disease following bilateral adrenalectomy and in Nelson's syndrome.

Correlation analysis was used to investigate the interrelation between plasma ACTH and serum cortisol concentrations determined at 8:00, 12:00, 16:00 and 22:00 h in 48 patients bilaterally adrenalectomized for Cushing's disease, including 23 patients with a pituitary adenoma (Nelson's syndrome). In the patients without evidence of a pituitary adenoma a significant inverse correlation was found at 8:00, 16:00, 22:00 h and additionally when all the pairs of estimations were analyzed. In a full-blown Nelson's syndrome an inverse correlation was not proved (p = 0.05). During remission in Nelson's syndrome an inverse correlation between cortisol and ACTH concentrations was stated at 8:00 h and after the evaluation of all the pairs of estimations. The results of our studies have shown that exogenous cortisol exerts a partial inhibitory action on ACTH secretion in patients bilaterally adrenalectomized for Cushing's disease. In active Nelson's syndrome this influence is questionable, it comes however into prominence during remission.

Incidentally found adrenal tumours: results of investigation of the pituitary-adrenal axis.

In the last 7 years 64 patients (48 women, 16 men, aged 25-75 yrs) with incidentally found asymptomatic adrenal tumours have been observed in the Department of Endocrinology. In 11 patients a routine clinical investigations revealed metastatic tumours at the adrenal glands. In the remaining 53 patients the diameter of the adrenal tumours was < or = 3 cm. Only two of them were treated surgically; the rest has been observed regularly and ultrasonographic examinations have been repeated every 3 to 6 months. Twenty three patients with adrenal tumours < 3 cm of diameter were treated by surgery. The macroscopical examination revealed adrenal cortical adenoma in 11 cases, adrenocortical carcinoma in seven, and pheochromocytoma in 5 patients. The investigation of the pituitary-adrenal system (urinary excretion of 17-OHCS before and during dexamethasone administration, 17-KS, "free" corticosteroids, plasma ACTH, cortisol and S-DHA levels) did not reveal any abnormality except that in 10 patients the plasma ACTH concentration was low, especially in the morning. These values were significantly lower as compared with the remaining patients and with control group. One of the possible interpretations is a pituitary suppression by only periodically increased concentrations of the corticosteroids.

Association of Addison's disease with autoimmune disorders--a long-term observation of 180 patients.

This study aimed at evaluating the frequency of autoimmune disorders in Addison's disease. We have observed 180 patients (113 females, 67 males, aged 9-74 years) for 1 to 26 years. Tuberculosis was noted in 54 patients. Autoimmune disorders were found in 80 patients (44%); however, 125 (69%) patients were believed to have an autoimmune origin of adrenocortical insufficiency. In 20 patients two or more autoimmune disorders were found to coexist with Addison's disease.

[Multiple adenoma of the adrenal cortex with the clinical picture of Cushing's syndrome]. / Mnogie gruczolaki kory nadnerczy z klinicznym obrazem zespolu Cushinga.

The paper sums up the experience of the clinic in diagnosing and therapy of the Cushing syndrome due to multiple autonomous adrenal cortical adenomas. The observation was carried out in a group of 5 women between 15-44 years of age (31.7 on an average). In the clinical material including 225 cases of the Cushing syndrome, they amounted to 2.2 per cent. All the five patients had typical somatic symptoms, myasthenia, ++amenorrhea. In hormonal examinations the content of 17-OHCS in the 24-hour urine was only periodically increased, 17-KS was within the normal range. There was no inhibiting action of dexamethasone on the excretion of cortisol, even when the initial values of corticosteroids++ were normal. The concentration of ACTH in the blood (determined in 3 cases) was around low normal range. Three patients underwent computer tomography; in one case adrenal glands were of normal size, in the second case--the two glands were enlarged, in the third case--the right gland was much larger than the left one. Microscopic examinations showed the atrophy of adrenal cortex beyond the adenomas. In case of multiple adenomas of the left gland surgery was confined to unilateral adrenalectomy. Among the remaining 4 patients, 3 underwent simultaneous resection of the two glands. All the patients showed the regression of symptoms of the disease, except for the changes in bones. One patient did not turn up for further therapy after unilateral adrenalectomy because of partial improvement.

The effect of magnesium valproate on plasma ACTH concentrations in Nelson's syndrome.

Sodium valproate, a gamma-aminobutyric acid (GABA) agonist, was found to decrease plasma ACTH concentration in some cases of Cushing's disease and Nelson's syndrome. In this study we have investigated the influence of magnesium valproate (MV), a newly introduced salt of valproic acid, on plasma ACTH levels in 8 patients with Nelson's syndrome. The daily dose, 1200 mg of MV, significantly decreased plasma ACTH level at 10 p.m. compared with placebo. A single dose of 400 mg of MV, led to a reduction in plasma ACTH concentration only in two out of seven patients during a four-hour observation. The fall in plasma ACTH level in the same patients at 10 p.m., after the next two doses of this drug, suggests that single dose may be insufficient for introducing GABA-dependent reduction in ACTH release. During a long-term therapy with MV, in all three patients investigated a marked decrease in plasma ACTH was observed. Our results suggest that magnesium valproate may be useful during chronic therapy in some patients with ACTH hypersecretion.