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Purpose: To compare thalamic volume and cognitive functions of patients with mild autonomous cortisol secretion (MACS) with control subjects and patients with overt Cushing's syndrome (CS)., Methods: In this cross-sectional study, volumes of regions of interest were assessed using 3 T magnetic resonance imaging and a voxel-based morphometry approach in 23 patients with MACS, 21 patients with active CS, 27 patients with CS in remission, and 21 control subjects. Cognitive functions were assessed using validated questionnaires., Results: Patients with MACS had smaller left thalamic (F = 3.8, p = 0.023), left posterior thalamic (F = 4.9, p = 0.01), left medial thalamic (F = 4.7, p = 0.028), and right lateral thalamic (F = 4.1, p = 0.025) volumes than control subjects. Patients with active CS also had smaller left thalamic (F = 3.8, p = 0.044), left posterior thalamic (F = 4.9, p = 0.007), left medial thalamic (F = 4.7, p = 0.006), and right lateral thalamic (F = 4.1, p = 0.042) volumes compared to controls. Patients with CS in remission had smaller left medial (F = 4.7, p = 0.030) and right lateral thalamic (F = 4.1, p = 0.028) volumes than controls. Neuropsychological tests showed no difference between the groups., Conclusion: MACS may decrease thalamic volume., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Adrenal cortical carcinoma is a rare diagnosis and may present with hormone secretion. A histological differentiation between an adrenal cortical adenoma and carcinoma can be very difficult. However, a fast diagnosis including staging and complete surgical resection is pivotal for the prognosis of an adrenal cortical carcinoma. Metastasing adrenal cortical carcinoma should be treated with a mitotane based chemotherapy, and inclusion in the "firm-act study" is highly recommended. The present case report demonstrates the diagnostic pitfalls in a female patients with Cushing's syndrome who suffered from metastasing adrenal cortical carcinoma.

ACTH-independent macronodular bilateral adrenal hyperplasia (AIMAH) is a rare cause of endogenous Cushing's syndrome. Here, massive bilateral adrenal enlargement is accompanied by ACTH-independent hypercortisolism. The detection of ectopic hormone receptors which, according to a new concept, control the cortisol production in AIMAH, offers the opportunity of normalizing the hypercortisolism by pharmacologically influencing the receptor or its ligand. We here present the case of a 46 year old male patient. Using clinical and pharmacological tests we found evidence of ectopic receptors in the AIMAH. After suspicion was erroneously raised that a malignant lesion could be inside of the right adrenal mass, the decision was made to resect both adrenals instead of trying to treat the hypercortisolism by pharmacological means. This surgical approach (bilateral adrenalectomy) has been the standard way of treatment for AIMAH until the new concept of the ectopic receptors was developed.

Adrenocortical tumours have to be differentiated from cortical hyperplasias, medullary tumours and extra-adrenal tumours or metastases. These diagnoses are mostly possible using routine paraffin sections. In some cases, immunostaining for differing cortical and medullary tumours and metastases are necessary. Adrenal hyperplasias can be congenital or acquired. They are diffuse, micronodular or macronodular and may be inactive or induce a cortical hyperfunction. Very rarely, macronodular hyperplasias may transform into autonomous adenomas. Primary, pigmented adrenocortical disease is a rare, special type of primary adrenal Cushing's syndrome, showing many small tumours with pleomorphic cells and an atrophic surrounding cortical tissue. Adrenal adenomas are mostly unilateral and solitary tumours weighing less than 50 g. Adrenal cortical carcinomas are mostly larger. Like the adenomas, they may be inactive and may induce a hypercortisolism, a hyperandrogenism or (very rarely in carcinomas) a hyperaldosteronism. Differentiating cortical adenomas and carcinomas is difficult in some cases but is possible using a diagnostic algorithm. Myelolipomas are benign, inactive tumours composed of mature fat cells and bone marrow cells. They have to be differentiated from adenomas with myelolipomatous metaplasia. Further, rare primary cortical tumours are mentioned.

Fifty patients with adrenal tumors (18 men and 32 women, average age 51.8 years) underwent laparoscopic adrenalectomy from February 1992 to October 1995. Clinical diagnosis included pheochromocytoma in 3 patients, primary aldosteronism (including 1 with a 11-OH-corticosterone-producing tumor) in 15, Cushing's syndrome (including 7 with pre-Cushing's syndrome) in 13, non-functioning tumors in 17, 1 metastatic adrenal carcinoma, and 1 adrenal tuberculosis. Transperitoneal laparoscopic adrenalectomy was performed by the method reported previously. Extraperitoneal laparoscopic adrenalectomy was performed with the patient under general anesthesia in the lateral position. A working space was created by inserting a balloon dissector through a small skin incision. A total of four trocars were inserted. Three of the 50 patients were switched to open surgery, including 1 with metastatic adrenal carcinoma and 1 with adrenal tuberculosis. Laparoscopic tumor removal was successful in the other 47 patients. The average operating time and blood loss were 209 min and 177 ml, respectively. Blood loss was greater in the patients with pheochromocytoma. In patients with Cushing's syndrome, postoperative recovery tended to take longer. Postoperative complications occurred in 40% of the patients in this group, but all complications were minor and successfully treated without any surgical procedures. In the 10 patients undergoing retroperitoneal laparoscopic adrenalectomy, operative courses were excellent, excluding 1 patient with adrenal tuberculosis. Although laparoscopic adrenalectomy is considered to be appropriate for patients with pheochromocytoma and Cushing's syndrome, it appears unsuitable for the removal of malignant and inflammatory lesions.

The case histories of two young ladies with Cushing's disease are described. Both patients were treated first with Gamma Knife radiosurgery and subsequently by microsurgery. The radiosurgery caused a marked reduction in tumour volume but only a partial relief of the endocrinopathy. Comparison of the histological findings with the radiological findings following radiosurgery indicates that confluent necrosis is not a prerequisite for a reduction in tumour volume. It seems more likely that the reduction in tumour volume is related to changes in cellular dynamics.

98 biopsies of the paraadenomatous adenohypophysis in acromegaly, galactorrhea combined acromegaly, isolated galactorrhea, hypothalamic-hypopphysial Cushing's disease. Nelson's syndrome, and in nonfunctional adenomas were studied by light microscopic methods in order to find evidence for a possible hyperplasiogenic origin of the different types of adenomas. It was hoped that the numerical relations and structures of hypophysial cells might provide significant information. Nodular ACTH cell-hyperplasia was found frequently apart from ACTH cell-tumors in Cushing's disease and Nelson's syndrome and on this basis we suggest that the adenomas in both diseases arise from hyperplasia. During their further development these adenomas seem to become autonomous, since the number of paraadenomatous ACTH cells decreased in bigger tumors. Some of the cases with isolated galactorrhea showed hyperplasia of acidophil and chromophobe cells in the paraadenomatous adenohypophysis. It can thus be assumed that porlactin cell-tumors also develop from prolactin cell-hyperplasia. Both the adenomas and the nonfunctional tumors in acromegaly seem to grow autonomously from the beginning, since paraadenomatous hyperplasia is seldom seen.

The main ultrastructural feature of human adrenal cortices following administration of aminoglutethimide (Elipten CIBA), a steroid biosynthesis blocking agent, is a striking intracellular accumulation of lipids, also seen in the light microscopy. The lipids accumulate in the adrenocortical cells but are also stored in the cytoplasm of pericapillary histiocytes. The lipids are present in the adrenocortical cells mostly as rounded liposomes of variable size, whereas those in the histiocytes usually show up as an amorphous debris with abundant myelin figures and cholesterol crystals. In some areas of the adrenal cortex activated histiocytes changing into lipophages may become the prevalent cell. They also take the place of destroyed adrenocortical cells and can form compact cell aggregates of variable size or even columnar strands between neighbouring capillaries, thus resembling columns of adrenocortical cells. In some of the adrenocortical cells focal cytoplasmic degradation, turning into coagulation necrosis, was observed. In others initial cytolysis was found. In contrast with earlier findings in experimental animals, mitochondrial changes in humans were not a prominent feature. The only changes occasionally observed were a focal disappearance of the vesicular cristae and a concomitant fibrillary loosening of the mitochondrial matrix.

Adenomata taken from nine patients with Cushing's syndrome were observed by electron microscopy. Agranular endoplasmic reticulum was prominently developed in all cases, occasionally fine dotty granules were observed in the tubules of agranular endoplasmic reticulum. Mitochondria showed a wide variety of changes in size, shape and internal structure, and somtimes contained electron dense droplets in their matrix. Mitochondria resembling those in the normal zona fasciculata intermingled with pathologically altered ones, suggesting that the adenomata which caused Cushing's syndrome were derived from the zona fasciculata. Fibrous structures were seen in the cytoplasm in one case. It is proposed that all of the changes in cellular organelles of the adenoma cells are correlated with increased secretory activity.

A case of a feminizing adrenocortical tumor associated with Cushing's syndrome in a 29 year old male is presented. The ultrastructural features are compared with adrenal tumors secreting aldosterone, glucocorticoids of androgens. As in adrenal carcinomas, this tumor demonstrates nuclear pleomorphism with enlarged nucleoli and nuclear pseudoinclusions. The cytoplasmic organelles show some parallels between feminizing and androgen-secreting adrenal tumors. Different types of mitochondria occur with varying amounts of smooth endoplasmic reticulum. Numerous microbodies are present. Histological and ultrastructural signs indicating probably malignancy are discussed and it is noted that most of the feminizing adrenal tumors are carcinomata. Neither local recurrence nor distant metastases have yet been detected in this case, two years after excision of the tumor.

Chronic excess of glucocorticoids results in Cushing's syndrome in humans. A common cause of excess cortisol secretion is the presence of an adrenocorticotropin secreting pituitary tumor which stimulates the adrenal cortex to produce excess glucocorticoids. ACTH-secreting AtT-20 mouse pituitary cells transplanted subcutaneously in oestrogenized athymic nude mice form tumors rapidly. Six weeks after receiving the tumor transplants, the mice weighed 45% more than normal mice due to the increase in body fat. The tumor-bearing mice exhibit the familial "buffalo hump" appeaance due to the abnormal distribution of body fat. The adrenal glands of the tumor-bearing animals are enlarged due to hypertrophy of the zona fasciculata. The foamy looking fasciculata cells in normal mice were converted to dense, eosinophilic cells in the tumor-bearing mice. Transplantation of normal pituitary glands to athymic nude mice with or without oestrogen treatment did not produce these morphological changes. The experimental model described here may be useful for future studies of Cushing's syndrome.