Adrenalectomy for treatment of Cushing syndrome: results in 122 patients and long-term follow-up studies

Patients with Cushing syndrome (n = 122) who underwent adrenalectomy from 1957 through 1993 were reviewed for survival and complications. Of the 122 patients, 70 had adrenocortical adenoma, 30 Cushing's disease, 6 primary pigmented nodular adrenocortical disease (PPNAD), 7 other types of primary nodular hyperplasia, 5 adrenocortical carcinoma, and 4 ectopic ACTH syndrome. Sixty-five patients with adrenocortical adenoma are alive, and the survival rate was equal to the age-matched control population, when patients who died of the postoperative complication were excluded. Of the patients with Cushing's disease, 20 are alive; and 10 of 16 patients (63%) who were followed-up and evaluated had skin pigmentation. Four of sixteen patients (25%) developed Nelson's syndrome. Four PPNAD patients and five with other types of nodular hyperplasia are alive. Most of these patients underwent bilateral total adrenalectomy, but some patients remitted after unilateral adrenalectomy. All of five adrenocortical carcinoma patients and four with ectopic ACTH syndrome died within 2 years after operation. The prognosis for patients with adrenocortical adenoma after unilateral adrenalectomy is excellent, though it is important to avoid operative complications. The rapid cure of signs and symptoms of glucocorticoid excess after total adrenalectomy is ensured, and prognosis is satisfactory under careful glucocorticoid replacement, making total adrenalectomy an alternative treatment for Cushing's disease.     

Incidence of Nelson's syndrome after adrenalectomy for Cushing's disease in children: results of a nationwide survey

To establish the incidence of Nelson's syndrome in children treated with total bilateral adrenalectomy (TBA) for Cushing's disease, a survey was made of members of The Lawson Wilkins Pediatric Endocrine Society. Thirty-one patients aged 10 months to 16 years had been treated with TBA for Cushing's disease; one had been treated with ortho para prime isomer of dichlorodiphenyldichloroethane alone. Postadrenalectomy hyperpigmentation was reported in 18 patients. Sella enlargement was detected in eight patients (25%) after 1 to 5.5 years (mean, three years) post-TBA. Five of these patients have had documented pituitary adenomas to date. This incidence is higher than the adult figure of 10% to 16%.     

Is gastric lymphoma an infectious disease?

In a 10-year-old ovariohysterectomized standard Schnauzer, the finding of dexamethasone-resistant hypersecretion of cortisol, the results of computed tomography, and elevated plasma concentrations of ACTH suggested the presence of both adrenocortical tumour and pituitary-dependent hyperadrenocorticism. The dog made an uneventful recovery after bilateral adrenalectomy and remained in good health for 31/2 years with substitution for the induced hypoadrenocorticism. Then the enlarged pituitary caused neurological signs and eventually euthanasia was performed. The surgically excised right adrenal contained a well-circumscribed tumour of differentiated adrenocortical tissue and in the left adrenal there were two adrenocortical tumours and a pheochromocytoma. The unaffected parts of the adrenal cortices were well developed and without regressive transformation. At necropsy there were no metastatic lesions. The cells of the pituitary tumour were immunopositive for ACTH and had characteristics of malignancy. The present combination of corticotrophic tumour, adrenocortical tumours, and pheochromocytoma may be called 'multiple endocrine neoplasia' (MEN), but does not correspond to the inherited combinations of diseases known in humans as the MEN-1 and the MEN-2 syndromes. It is suggested that the co-existence of hyperadrenocorticism and pheochromocytoma may be related to the vascular supply of the adrenals. Some chromaffin cells of the adrenal medulla are directly exposed to cortical venous blood, and intra-adrenal cortisol is known to stimulate catecholamine synthesis and may promote adrenal medullary hyperplasia or neoplasia.     

Aminoglutethimide in the treatment of Cushing's syndrome

The efficacy and tolerability of aminoglutethimide for the treatment of Cushing's syndrome was assessed in 66 cases three of which are described in the present paper. Aminoglutethimide provided palliation from the signs and symptoms of hypercorticism in 13 of 21 patients with metastatic adrenocortical carcinoma and four of six patients with ectopic ACTH production due to metastatic carcinomas. All six of the patients with adrenal adenomas showed clinical and biochemical improvement, while 14 of the 33 patients with bilateral adrenal hyperplasia of pituitary origin improved. Adverse reactions attributed to aminoglutethimide such as drowsiness, rash, and nausea occurred in 58 per cent of cases. These data suggest that aminoglutethimide has a place in controlling the signs and symptoms of adrenocorticoid excess in patients with Cushing's syndrome due to malignancy and is effective preoperative therapy for patients with adrenal adenomas and bilateral hyperplasia.     

Laparoscopic surgery of adrenal glands: indications and limits

Over the last four years it has been demonstrated that laparoscopy can be used successfully for adrenalectomy, providing certain advantages over conventional open surgery. The aim of this study was to determine the indications for laparoscopic approach in adrenal surgery. From June 1994 to June 1996 laparoscopic transabdominal flank approaches were proposed in patients with a unilateral 8 cm or less, non-malignant tumors of the adrenal gland. For tumors under 4 cm in diameter only secreting tumors were removed. Among 77 patients requiring ablation of the adrenal gland, 50 (65%) underwent a laparoscopic procedure: 29 Conn adenomas, 10 Cushing adenomas, 6 Pheochromocytomas, 4 incidentalomas. One patient had Cushing's disease and underwent bilateral resection. Mean tumor size was 26 mm (7-75 mm). Malignancy was demonstrated in 2 tumors: one cortisone secreting tumor and one leiomyosarcoma. Conversion was required in 4 cases (8%). Mean operative time for unilateral adrenalectomies was 147 minutes (50-300'). There were no deaths. Morbidity included: one hemorrhage via the trocar orifice requiring reoperation, one infarction of the spleen which regressed spontaneously, one parietal hematoma, and one case of phebitis of the lower limb. The endocrinopathy was successfully cured in all patients with secreting tumors. The 27 other patients underwent open adrenalectomy. Laparoscopic approach was not proposed due to suspected malignancy in 13 cases, previous surgery in 8 cases and multiple, bilateral and/or extra adrenal tumors in 6 cases. Laparoscopic approach to the adrenal gland is the procedure of choice in patients with Conn adenomas, Cushing adenomas and in most cases of pheochromocytomas. It is not indicated for malignant and large tumor (> 8 cm). Currently two-thirds of our patients requiring and adrenalectomy are operated laparoscopically.     

Initial experience with laparoscopic adrenalectomy

We present the first experience with laparoscopic adrenalectomy, which was in Slovakia introduced to the surgical practice on March 3, 1996. We analyse first seven patients who underwent completed laparoscopic adrenalectomy (five leftsided, two right-sided). Four patients had cortex adenoma (clinically 2 incidentalomas and 2 Cishing syndroma), three patients had cortex hyperplasia (clinically Conn syndroma). Average duration of operation was 120 minutes, there were no postoperative complications. Average postoperative hospital stay was 5 days. Our initial experiences are comparable with that of surgical departments which has more than two-years experiences. Laparoscopic adrenalectomy is a perfect method for the small adrenal tumors and it is better than traditional transabdominal approach.     

Laparoscopic unilateral and bilateral adrenalectomy for Cushing's syndrome. Transperitoneal and retroperitoneal approaches

OBJECTIVE: This prospective randomized study compares the safety and efficacy of transperitoneal laparoscopic adrenalectomy (TLPA) and retroperitoneal approach (RLPA) in obese patients with Cushing's syndrome. SUMMARY BACKGROUND DATA: Recently, a retroperitoneal laparoscopic approach has been described with benefits of avoiding the respiratory and hemodynamic effects of carbon dioxide (CO2) pneumoperitoneum and giving direct access without the need to mobilize abdominal organs. METHODS: Twenty-one adrenalectomies were performed in 9 patients (2 men, 7 women; mean age, 46.33 +/- 19.41 years old; range, 16 to 74 years old) with Cushing's adenoma and in 6 women (mean age, 41.83 +/- 9.97 years old; range, 34 to 62 years old) with Cushing's disease. Randomization gave 10 TLPA and 11 RLPA. Arterial blood gas samples, mean arterial pressure, heart rate, and clinical parameters were evaluated. RESULTS: The partial pressure of carbon dioxide (PaCO2) increased in both retroperitoneal and transperitoneal CO2 insufflation compared with basal values (p < 0.01), and the TLPA showed a greater rise in the PaCO2 level compared with the RLPA at 30 minutes (p < 0.05); simultaneously, a significant increase (p < 0.05) of mean arterial pressure was observed in the TLPA compared with RLPA. No significant changes in heart rate were observed in both groups. The operative time with the TLPA and RLPA in patients with adenoma was 88.75 versus 105 minutes, respectively (p = not significant [NS]), and in patients with bilateral hyperplasia was 271.66 versus 305 minutes, respectively (p = NS). No patients required blood transfusions. The number of doses of analgesic with TLPA and RLPA in patients with adenoma was 3.25 versus 3.5, respectively (p = NS), and in patients with bilateral hyperplasia was 7.66 versus 7.33, respectively (p = NS). The hospital stay with TLPA and RLPA in patients with adenoma was 3.0 versus 2.75 days, respectively (p = NS), and in patients with bilateral hyperplasia was 6.0 versus 6.66 days, respectively (p = NS). The days to return to normal activity with TLPA and RLPA in patients with adenoma were 12.5 versus 12.25, respectively (p = NS), and in patients with bilateral hyperplasia were 19.66 versus 19.33, respectively (p = NS). Two patients with bilateral hyperplasia and TLPA had urinary infection. CONCLUSIONS: Transperitoneal laparoscopic adrenalectomy and RLPA may become the techniques of choice for surgical removal of the adrenal lesions in Cushing's syndrome. The retroperitoneoscopic approach might be a better option in patients with previous abdominal surgery and in patients with pre-existing cardiorespiratory disease.     

New etiopathogenic, clinical and therapeutic findings in multiple endocrine neoplasia type 1

Multiple Endocrine Neoplasia type 1 (MEN 1) syndrome comprises tumors or hyperplasia of different glands, including parathyroid, pituitary, adrenal cortex and the gastroenteropancreatic system. The vast majority of MEN 1 are found in familial clusters, although a few cases are sporadic. Hypercalcemia and/or nephrocalcinosis are the first and most common clinical manifestation in familial MEN 1 syndrome, followed by islet cell tumors (especially those secreting gastrin or insulin) and pituitary dysfunction due to either functioning or non-functioning microadenomas. Genetic studies indicate that familial MEN 1 syndrome is inherited through a dominant gene with incomplete penetrance and variable expression. The diagnosis of MEN 1 syndrome is mainly based on the careful assessment of the clinical history, symptoms physical evaluation along with the assay of serum electrolytes (i.e., calcium, phosphorus, etc.) and hormonal substances (i.e., gastrin, insulin, pancreatic polypeptide, prolactin, adrenocorticotropic hormone, etc.). In addition, several provocative tests have been used to identify endocrine tumors (particularly those of the gastroenteropancreatic system) and imaging techniques play a crucial role for the diagnostic approach in MEN 1 syndrome. Even though in the long term, the prognosis of MEN 1 syndrome is unfavourable. Recently, however, many therapeutic strategies, including both surgical and pharmacological options, have been developed to reduce the size of the neoplasm and control symptoms associated with hormone oversecretion.     

Laparoscopic adrenalectomy

Between June and September 1993, laparoscopic adrenalectomy was indicated in five patients (three women, two men; aged 25-50 years). Three had a phaeochromocytoma, two had an adenoma (Conn's syndrome). Four of the five tumours were localized to the right adrenal gland, one to the left. Tumour diameter ranged from 3 to 5 cm. The laparoscopic procedure was successful in four of the patients (three right, one left). In the fifth case the operations had to be completed by conventional surgery, because of non-controllable haemorrhage. Duration of operation ranged between 165 and 360 min for right adrenalectomy and was 135 min for the left one. Rapid convalescence, lower dose of pain-killing drug required, short hospital stay and good cosmetic results characterized the postoperative course after the laparoscopic procedure. This technique thus opens up new perspectives for adrenal surgery.     

The localization of aldosterone-producing adenoma on computed tomography--a comparative study with adrenal scintigraphy and plasma aldosterone concentration in the adrenal or renal vein

The evaluation of computed tomography (CT) for detecting aldosterone-producing adenoma in primary aldosteronism was performed by comparison with adrenal scintiscan; determination of aldosterone in adrenal or renal veins, retroperitoneal pneumography and adrenal venography was reliable for diagnosis of adrenal tumors in pheochromocytoma or Cushing's syndrome, but not so effective for small adenoma of primary aldosteronism. An abdominal CT scan was performed on six patients with primary aldosteronism, one with idiopathic hyperaldosteronism and one with glucocorticoid responsive hyperaldosteronism; in an attempt to evaluate the utility of this noninvasive procedure. Diagnosis of hyperaldosteronism was made by demonstrating the elevated plasma aldosterone concentration and aldosterone secretion rate, normal excretion rate of urinary 17-OHCS and 17-KS, and low plasma renin activity. The CT scan correctly predicted unilateral adrenal adenoma in all the patients with primary aldosteronism of which the findings were identical to those demonstrated by surgery. The diameter of these tumors ranged from 10 X 7 X 6 to 19 X 17 X 14 mm. Also the CT scan in idiopathic hyperaldosteronism and glucocorticoid responsive hyperaldosteronism showed bilateral adrenal hyperplasia and bilateral normal adrenal glands, respectively. The pathological findings in these two cases disclosed the adrenal hyperplasia of zona glomerulosa and adrenal hyperplasia of zona subglomerulosa accompanied by a normal thickness of the adrenal gland, respectively. The precision of the CT scan, adrenal scintigraphy and determination of plasma aldosterone in the adrenal or renal veins were almost equal to the diagnosis of the localization of adrenal adenoma. It is concluded that the CT scan is a noninvasive and most useful method for the localization of aldosterone-producing adenoma and helpful in distinguishing adrenal adenoma from adrenal hyperplasia.     

Long-term survival after bilateral adrenalectomy for metastatic lung cancer: a case report

Selected patients with solitary metastases from non-small cell lung cancer can benefit from an aggressive treatment approach that includes resection of the metastases. This approach has been used for solitary adrenal metastases, but successful long-term treatment of bilateral adrenal metastases has not been previously reported. This is the report of a patient with bilateral adrenal metastases from lung cancer who is disease-free 9 years after bilateral adrenalectomy and chemotherapy. From this evidence, one may hypothesize that adrenal metastases are occasionally lymphatic in origin and that metastases with this route of spread are more amenable to aggressive curative treatment than adrenal metastases of hematogenous origin.     

Retroperitoneal adrenalectomy: open or endoscopic?

Conventional adrenalectomy requires relatively large incisions. To assess the value of retroperitoneal endoscopic adrenalectomy, a case-control study was performed comparing the endoscopic technique to conventional posterior adrenalectomy. All patients had adrenal tumors less than 7 cm in diameter. Endoscopic retroperitoneal adrenalectomy required more operative time (90 vs. 60 minutes, p < 0.0001) than the open approach but was associated with less blood loss (20 vs. 125 ml, p < 0.0001). Endoscopic adrenalectomy caused less pain postoperatively (p = 0.0005) and was associated with fewer complications (p = 0.035). The hospital stay was shorter after endoscopic adrenalectomy than after open adrenalectomy (p < 0.0001). In conclusion, we advocate endoscopic retroperitoneal adrenalectomy in patients with small adrenal tumors.     

Medical management after pituitary surgery

Although the majority of patients with pituitary tumor, undergoing transsphenoidal microsurgery, have a low incidence of hormonal deficiency after surgery, the endocrinological evaluations should be carefully done before and after surgery. Glucocorticoid replacement is necessary in patients with Cushing's disease during and after surgery as well as those with adrenal insufficiency. Repeated CRF test is useful to assess the secondary adrenal insufficiency of Cushing's disease after surgery. Patients with impaired secretion of both ACTH and TSH should receive glucocorticoid replacement before thyroid hormone replacement in order to avoid adrenal crisis. A combination of CRF, GRF, TRH and GnRH is a safer and more reliable test to evaluate pituitary function than the conventional triple test consisting of insulin, TRH and GnRH, especially in patients predicted to have pituitary-adrenal insufficiency. Diabetes insipidus(DI), immediately after pituitary surgery, should be treated with subcutaneous injection of Pitressin. Even if patients seem to have recovered from DI several days after surgery, they must be monitored closely because of the incidence of triphasic DI. Less attention has been given to replacement for GH deficiency in adults. Recent reports revealed that GH replacement in adults with GH deficiency decreases visceral fat tissue and increases plasma calcium, phosphorus, osteocalcin and procollagen III levels. GH replacement will become more popular even in adults. Many options and technological advantages in the diagnosis and treatment of pituitary tumors have developed in a decade. In the near future, post-operative patients with pituitary tumors must be cared for in view of the "quality of life".     

Risk indicators for malnutrition are associated inversely with quality of life for participants in meal programs for older adults

OBJECTIVE: To investigate the feasibility, safety and results of laparoscopic transperitoneal adrenalectomies performed with the patient supine, in patients affected by secreting and silent adrenal lesions. METHODS: Exclusion criteria were suspected adrenal primary malignancies. Fifty patients (33 women and 17 men; mean age 49.6 years, range 19-75 years) underwent 51 laparoscopic adrenalectomies (one bilateral). After complete endocrinological evaluation, computed tomography or magnetic resonance imaging, or a combination thereof, 14 non-secreting adenomas, 13 aldosterone-producing adenomas, 13 cortisol-producing adenomas, eight phaeochromocytomas (one bilateral), one androgen-secreting adenoma, and two metastases were considered eligible for adrenalectomy. In five patients, associated procedures were performed during surgery. RESULTS: The lesions ranged in size from 1.5 to 10 cm. There were no intraoperative complications and no blood transfusions were required. The postoperative course was uneventful and painless in all patients. Mean postoperative hospital stay was 2.5 days. In all hypertensive patients, significant improvement or cure of hypertension was observed at follow-up (mean 18 months). In patients with secreting adenomas, normalization of hormone concentrations was obtained after removal of the tumour. In six patients with incidentaloma, the exaggerated 17-hydroxyprogesterone response to ACTH disappeared after surgery. CONCLUSIONS: Secreting and non-secreting adrenal lesions were treated safely by laparoscopy. Relatively small incidentalomas and subclinical hormonally active tumours can be removed by laparoscopy. Early diagnosis enhances prevention and treatment.     

Direct anti-atherosclerosis-related effects of garlic

Leydig cell tumors are very rarely seen testicular tumors and can be difficult to distinguish from testicular tumors of the adrenogenital syndrome. Testicular tumors of the adrenogenital syndrome are confined to patients with congenital adrenal hyperplasia. The authors report a case of a patient with malignant Leydig cell tumor and a history of congenital adrenal hyperplasia (adrenogenital syndrome). To the authors' knowledge, this has not been reported previously.     

The dexamethasone-modified adrenal scintiscan in hyporeninemic aldosteronism (tumor versus hyperplasia). A comparison with adrenal venography and adrenal venous aldosterone

The dexamethasone-modified adrenal scintiscan, a noninvasive procedure, is described for the preoperative distinction between primary aldosteronism (aldosterone-producing ademona) and idiopathic aldosteronism (bilateral hyperplasia) and for the preoperative localization of aldostersone-producing adenomas. This procedure has been carried out on 17 subsequently proved cases of primary aldosteronism and nine cases (four unexplored) of idiopathic aldosteronism. In the tumor cases, it indicated correctly the side of the tumor in 88 per cent. It was correct in predicting the existence of bilateral hyperplasia in all of the five cases explored. It produced the same response in four more cases believed to have bilateral hyperplasia, in which surgical exploration has not been carried out. Many of the same patients had, in addition, standard adrenal scintiscans (SS), adrenal venography, and determinations of aldosterone in adrenal venous blood. These results are compared with those of the dexamethasone scintiscan (DS). In tumor localization, the 88 per cent figure for the DS was only moderately better than that of the other three (71 per cent, SS; 80 per cent, venography; 80 per cent, adrenal venous aldosterone levels). However, in predicting bilateral hyperplasia, the DS was 100 per cent correct, as were the levels of aldosterone in adrenal venous blood. The SS and adrenal venography failed in bilateral hyperplasia and gave many false-positive results indicating tumor. The DS, a relatively simple outpatient procedure, appears to be at least as effective, both in lateralizing tumors and distinguishing between tumor and bilateral hyperplasia, as the more difficult, expensive, and sometimes hazardous invasive procedure of bilateral adrenal vein catheterization.     

Adrenal incidentaloma: proposal for a correct treatment

BACKGROUND: The incidence of unsuspected adrenal masses (incidentalomas) based on CT-scan results to be higher than in the past. The aim for our study was to establish some guidelines for an appropriate management. METHODS: From 1986 to 1995, 61 patients with no history or clinical findings suggestive of adrenal mass or adrenal hyperfunction were discovered by radiologic examination to have an incidentaloma larger than 1 cm. In each patient basal biochemical evaluations were obtained to exclude the presence of adrenal cortical or medullary dysfunction. There were 28 men and 33 (54.1%) women, with a mean age of 53 years (range 16-74). 19 patients underwent CT-guided fine-needle biopsy to exclude metastatic tumors. Furthermore in 29 patients 75-Se-selenomethyl-norcholesterol was performed and 17 were studied by MRI. RESULTS: At CT-scan mean lesion diameter was 5.48 +/- 3.76 cm (range 2-23); 32 adrenal masses were right sided and 3 (4.9%) were bilateral. 17 patients had concordant scintigraphic imaging pattern, 6 bilateral uptake and 6 had discordant imaging. CT-guided FNAB showed malignancy in 9. Adrenalectomy was performed in 45 patients according to a score calculated by 4 parameters: age of the patients, size of the mass, scintigraphic pattern, MR imaging. Twenty-four had a score greater than 9 and in the remaining 21 patients in spite of a score lower than 10 adrenalectomy was performed based on: 1) increased size at CT scan follow-up (15 pts); 2) either suspected primitive malignant neoplasm at CT-guided FNAB or history of malignancy (6 pts); 3) elevated 24-hour dopamine (4 pts). In 12 (26.7%) patients a malignant tumor was found. There were not any statistically significant differences (p > 0.05) between the age of the patients with malignant neoplasms and those with benign masses, and between the size of the masses, which were 7.58 +/- 5.93 cm (range 2-23) and 5.03 +/- 2.81 cm (range 3-17) respectively. The difference in scores between the patients with malignant masses (12.17 +/- 2.95) and those with benign ones (9.09 +/- 1.33) was statistically significant (p < 0.01). CONCLUSIONS: Since adrenal incidentaloma have a malignancy rate higher than the other adrenal tumors, it is crucial to outlinesome criteria to sort out the patients at risk for whom adrenalectomy is to be warranted. Based on our results we believe that patients with a score > 9 should undergo adrenalectomy.     

Sixth congress of the European Genetic Therapy Group

PURPOSE: Course and pathophysiology of a typical syndrome after irradiation of the cauda equina were studied. PATIENTS AND MATERIALS: 7 patients with irradiation damage of the cauda equina were examined clinically and neurophysiologically. RESULTS: After a mean delay of 5 years and 6 months all patients developed an ascending lower motor neuron weakness of the legs without pain, in part accompanied with mild sensory and sphincter symptoms. Electromyography, evoked potentials and neurography were important for the differential diagnosis to tumor infiltration. The course was progredient. DISCUSSION: For a long time, the underlaying damage was thought to be in the anterior horn cell body. The course of the studied patients with additional sensory and vegetative symptoms implies for a direct bilateral damage of the cauda equina. A better term for the syndrome is "post-irradiation cauda-equina-syndrome".     

Hypergastrinaemia in Cushing's syndrome: pituitary origin or glucocorticoid-induced?

OBJECTIVES: Several reports have shown an increase in serum gastrin levels in patients with Cushing's syndrome (CS). However, the actual origin of this hypergastrinaemia is not known. Two hypotheses have been proposed: concomitant ACTH and gastrin secretion by corticotrophic pituitary adenomas or hypergastrinaemia induced by hypercortisolism. DESIGN AND PATIENTS: We performed simultaneous, bilateral inferior petrosal sinus (IPS) sampling in nine patients with Cushing's disease (CD), proven by histological studies. In all of them, blood samples were taken from both IPS and a peripheral vein to measure plasma ACTH and serum gastrin. In addition, we measured peripheral serum gastrin levels after an overnight fast in 10 patients with CS (seven with pituitary tumours and three with adrenal tumours) before and after surgical treatment. RESULTS: Petrosal-peripheral and interpetrosal gradients of ACTH were higher than 2.0 and 1.4, respectively, confirming the pituitary origin of ACTH. Mean serum gastrin levels were 149.1 +/- 53.6 ng/l in peripheral vein, 183.4 +/- 71.7 ng/l in dominant IPS and 181.4 +/- 68.9 ng/l in non-dominant IPS. No significant differences in gastrin concentrations in these locations were found. Mean preoperative gastrin level in patients with CD was 194.6 +/- 47.9 ng/l, whereas in patients with adrenal tumours it was 247.3 +/- 125.9 ng/l. After surgical treatment, the gastrin levels decreased to 62.1 +/- 13.2 ng/l (P < 0.05) and 90.3 +/- 50.3 ng/l (NS), respectively. CONCLUSIONS: These results suggest that hypergastrinaemia is a common finding in patients with Cushing's syndrome. The lack of significant petrosal-peripheral gradient in individuals with Cushing's disease and the reduction in gastrin level following adrenal tumour resection argues against the hypothesis of a predominantly pituitary source of gastrin, suggesting a glucocorticoid related mechanism as an explanation for the hypergastrinaemia.     

Adrenocortical overexpression of gastric inhibitory polypeptide receptor underlies food-dependent Cushing's syndrome

Abnormal responsiveness of adrenocortical cells to gastric inhibitory polypeptide (GIP) in food-dependent Cushing's syndrome suggested that adrenal expression of ectopic, overexpressed, or mutated GIP receptor (GIPR) underlies this syndrome. The expression of GIPR was studied by RT-PCR in human adrenal tissues from two patients with GIP-dependent Cushing's syndrome (adenoma, bilateral hyperplasia), five fetal or adult controls, one patient with Cushing's disease, and four patients with non-food-dependent cortisol-secreting adenomas or bilateral hyperplasias and compared to that in normal pancreas. Hybridization of the RT-PCR-amplified ribonucleic acids with the human GIPR complementary DNA showed an overexpression of GIPR in the adrenals of the two GIP-dependent Cushing's syndrome patients compared to that in normal adrenal tissues (2-3 orders of magnitude) or pancreas (10-fold); no signal could be seen in adrenal adenomas or macronodular hyperplasia from cases of non-food-dependent Cushing's syndrome. No mutation of the GIPR was identified by sequencing the full-length receptor in GIP-dependent adrenal tissue. New alternative spliced isoforms of the GIPR were found, but are identical in GIP-dependent and normal adrenal tissues. Incubation of adrenal cells with GIP stimulates cortisol secretion in GIP-dependent, but not in normal fetal, adult, or non-food-dependent Cushing's syndrome, adrenals. We conclude that the GIPR overexpression and its coupling to steroidogenesis underlie GIP-dependent Cushing's syndrome.