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PubMed1998

Ectopic ACTH Cushing's syndrome: V3 vasopressin receptor but not CRH receptor gene expression in a pulmonary carcinoid tumor.

In the etiological diagnosis of ACTH-dependent Cushing's syndrome, it may be difficult to distinguish pituitary disease from ectopic ACTH production, specially when this is due to a benign neuroendocrine tumor. We describe a patient with partial dexamethasone suppression consistent with Cushing's disease, an absent response to CRH suggesting ectopic ACTH production and an atypical, apparent circadian rhythm. Bilateral cavernous sinus catheterization suggested a nonpituitary source of ACTH and, in the search of an ectopic tumor, somatostatin receptor scintigraphy, abdominal CT scan, and duodenopancreatic endoscopic echography were performed and failed to reveal any abnormality. Thoracic CT scan disclosed a tiny right lung nodule that showed a definite tracer uptake on MIBG scintigraphy. After resection, the nodule proved to be an 8-mm typical pulmonary carcinoid, with positive immunostaining for the classical neuroendocrine markers and for ACTH, and showing tissue expression of the POMC gene. However, the CRH receptor gene was not expressed, explaining the absent CRH response in vivo, whereas the V3 vasopressin receptor gene was expressed in the tumor tissue. The latter feature appears to be characteristic of benign carcinoids and may contribute to explaining the CRH-independent circadian rhythm observed in this case.

ACTH Syndrome, Ectopic↗
PubMed1993

Abnormal embryogenesis in the etiology of ectopic pregnancy.

Flow cytometric measurements of DNA using paraffin-embedded retrospective material were performed on 42 samples of ectopic conceptuses to see whether there were any aberrations from normal DNA. It was found that DNA aneuploidy was associated with tubal implantation in 14 (33%) cases. The range of DNA indices of the DNA aneuploid peaks was from 1.14 to 2.17. Near-diploid karyotype changes were seen in 8 (19%) cases. Six cases were found to be tetraploid. In 18 abortions with known cytogenetic status, all 3 cytogenetically normal cases showed DNA diploidy in flow cytometry. It was also found that 3 out of 10 cases of trisomy 21 were DNA aneuploid. Flow cytometric DNA reflects only chromosomal changes where a significant number of cells have either lost or acquired several chromosomes. DNA aneuploidy of ectopic pregnancies suggests a grave chromosomal aberration in one third of the cases. Abnormal embryogenesis may contribute significantly to the occurrence of ectopic implantation.

Aneuploidy↗
PubMed1983

Scanning electron microscopy of human Fallopian tube in ectopic pregnancy.

The scanning electron microscopy by virtue of its high resolution topographic reproduction of epithelial surfaces lining the female genital tract, provides unique information toward understanding the anatomy and physiology of the female reproductive system. The human Fallopian ectopic pregnancy is an urgent gynecologic event, which was and still is a diagnostic challenge. There is an increase in the incidence of ectopic pregnancy in recent years. With the purpose of exploring the etiology of tubal ectopic pregnancy from the ultrastructure point of view, we examined 7 cases of tubal pregnancy and compared them to a similar number of normal tubes. We do not find evidence to the pathophysiology of tubal pregnancy by examination of the ultrastructure of the human tube with scanning electron microscopy.

Epithelium↗
PubMed1987

Bedside application of an ultrasensitive urine test for HCG in patients with suspected ectopic pregnancy.

One hundred and seven patients with suspected ectopic pregnancy were tested for HCG at the bedside using the Tandem Icon. The test was performed by ward doctors with no formal laboratory experience. The patients were managed conservatively or by surgery as dictated by the clinical picture and the Icon test result. Retrospective categorisation of the 107 patients by laboratory analysis and clinical outcome showed that 21 were pregnant (17 ectopic, 4 intrauterine) and 86 non-pregnant. At the bedside the Icon was reported as negative in one pregnant patient and three patients who were not pregnant were found to give Icon-positive results. In the laboratory the Icon correctly categorised all patients. Three of the four discrepant results were found to be a direct result of the operator's inexperience in analytical procedure and interpretation. The Tandem Icon HCG urine assay can reliably be used at the bedside of patients with suspected ectopic pregnancy provided that the operator has had sufficient experience in its use.

Chorionic Gonadotropin↗
PubMed1992

Cushing's syndrome associated with ectopic corticotropin production and small-cell lung cancer.

PURPOSE: This study was undertaken to review the clinical and laboratory features and response to treatment of patients with Cushing's syndrome associated with ectopic corticotropin (adrenocorticotropic hormone; ACTH) production and small-cell lung cancer (SCLC). PATIENTS AND METHODS: We undertook a retrospective chart review of 545 patients with SCLC seen at Toronto General Hospital between 1980 and 1990 and identified 23 patients (4.5%) with Cushing's syndrome and ectopic ACTH production. RESULTS: There were 17 male and six female patients, with a median age of 60 years. The syndrome was diagnosed at the time of initial presentation of SCLC in 13 patients and at relapse in 10 patients. Seven patients had limited disease and 16 had extensive disease at their initial diagnosis of SCLC, but 20 of 23 had extensive disease at the time of diagnosis of Cushing's syndrome. Ten patients had bone marrow involvement. The most frequent physical findings included edema (83%) and proximal myopathy (61%). All patients had elevated plasma and urinary free cortisol levels; 22 had a hypokalemic alkalosis, and 13 had hyperglycemia. Only one patient had a normal ACTH level. The response rate (complete plus partial) to chemotherapy for patients who had the syndrome diagnosed at initial presentation of SCLC was only 46%, and their median survival was only 3.57 months. Only two patients achieved complete normalization of all hormone parameters, and neither experienced hormone relapse at the time of SCLC relapse. Complications of therapy included gastrointestinal (GI) ulceration (six patients), GI bleeding (four), perforation of a duodenal ulcer (one), pneumonia (10), septic shock (three), and fungal infections (five). CONCLUSION: Ectopic ACTH production is associated with a low response to chemotherapy, short survival, and a high rate of complication to therapy.

ACTH Syndrome, Ectopic↗
PubMed1986

Cushing's syndrome secondary to ectopic corticotropin-releasing hormone-adrenocorticotropin secretion.

A 47-yr-old woman with severe Cushing's syndrome had a bronchial carcinoid secreting ACTH and corticotropin-releasing hormone (CRH) and associated pituitary corticotroph hyperplasia. While the clinical picture was consistent with the ectopic ACTH syndrome, the biochemical pattern was that of pituitary ACTH-dependent hypercortisolism. Both plasma ACTH and CRH levels were high. However, while plasma ACTH increased during metyrapone administration and decreased during administration of high dose of dexamethasone, plasma CRH levels did not change, suggesting a direct pituitary response to these testing maneuvers. Immunoperoxidase staining of the tumor tissue confirmed the presence of ACTH and CRH, and the finding of an ACTH and a CRH concentration gradient across the tumor bed indicated that the tumor was actively secreting these two hormones. Cytochemical heterogeneity was seen in the tumor, in which two distinct populations of cells, one secreting ACTH and beta-endorphin and the other secreting CRH, were identified. This patient, thus, had an unusual syndrome of ectopic ACTH and ectopic CRH secretion.

ACTH Syndrome, Ectopic↗
PubMed1999

Lack of utility of (111)In-pentetreotide scintigraphy in localizing ectopic ACTH producing tumors: follow-up of 18 patients.

Octreotide scintigraphy has been advocated as the principal imaging modality for localizing ectopic ACTH-secreting tumors in Cushing's syndrome. To assess its usefulness we reviewed the course of 18 consecutive patients with ectopic ACTH-producing tumor. Imaging included (111)In-pentetreotide scintigraphy, computed tomography (CT), and/or magnetic resonance imaging (MRI). Tumor was detected initially in 7/18 patients, and in 3/18 during follow-up. No ACTH-secreting tumor was detected by octreotide scintigraphy when CT/ MRI were negative. Seventeen of forty octreotide scintigrams were abnormal. CT and/or MRI confirmed tumors in 10, but demonstrated nonendocrine lesions in association with 6 false positive octreotide scintigrams. Hepatic venous sampling for ACTH refuted one lesion detected by octreotide and CT scans. Twenty-three of forty octreotide scintigrams were normal. Of these, 8 were false negative, as CT and/or MRI detected tumor; 10 agreed with negative CT and MRI, and 5 correctly refuted false positive CT and/or MRI scans. Repeated CT/ MR, but not octreotide scintigraphy, led to tumor resection in 2 patients. We conclude that octreotide scintigraphy does not offer greater sensitivity than CT/MRI and that false positive scans are common. Although octreotide scintigraphy may be helpful in selected cases, it is not a significant advance over conventional imaging for ectopic ACTH-secreting tumors.

ACTH Syndrome, Ectopic↗
PubMed1999

Usefulness of somatostatin receptor scintigraphy in patients with occult ectopic adrenocorticotropin syndrome.

SRIF receptor scintigraphy (SRS) has been proposed for the localization of ectopic ACTH-secreting tumors responsible for Cushing's syndrome. However, in most cases reported, the tumors were also visible using conventional imaging. Therefore, the usefulness of SRS in localizing truly occult ectopic ACTH-secreting tumors remains unknown. We report the results of SRS in 12 patients with ectopic ACTH syndrome (EAS) and in whom the source of ACTH was occult at presentation despite carefully performed conventional imaging. The diagnosis of EAS was made by identification of an ACTH-secreting tumor during follow-up in 5 patients or given a pituitary-to-peripheral ACTH ratio of 1.9 or less during petrosal sinus sampling combined with CRH injection and a negative pituitary magnetic resonance imaging (MRI). Whole-body planar SRS, using (111)In-pentetreotide, was performed 19 times in the 12 patients during initial workup and/or follow-up. Axial tomography imaging (single-photon emission-computed tomography) was performed in 7 of these. Conventional imaging was performed within a month of SRS, allowing comparison of the two approaches for the localization of the ACTH-secreting tumors. In addition, the response of plasma cortisol, after a single injection of 200 microg octreotide, was studied in 6 patients. Five patients had negative SRS and conventional imaging studies. The source of ACTH secretion remains occult despite 10-55 months of follow-up in four of these, whereas a 2-cm ileal carcinoid tumor, with liver micrometastases, was found at laparotomy in one patient, 14 months after presentation. SRS was positive in 4 of 12 patients. It was false-positive in 1 patient with follicular thyroid adenoma. Nineteen months after presentation, SRS identified liver metastasis that was also visible using MRI in one patient, but the primary tumor remains occult. SRS identified a 10-mm pancreatic tumor that became detectable, using computed tomography (CT) scanning 9 months later, in 1 patient; and 2 mediastinal lymph nodes of 10 mm, previously ignored by MRI, in another patient, whereas no tumor was detectable within the parenchymal lung. SRS had little influence on therapeutic options in these 2 patients, in whom no final diagnosis could be made. Repetition of SRS during the follow-up of patients with previously negative scintiscans was useless. Conventional imaging was positive in 6 of 12 patients. In the 2 patients with pancreatic tumor and isolated mediastinal lymph nodes, conventional imaging studies were interpreted as positive only after the results of SRS. One patient had liver metastasis that was also visible using SRS. Thin-section CT scanning visualized ACTH-secreting bronchial tumors and metastatic mediastinal lymph nodes of 10-15 mm in diameter in 3 patients after 14-72 months of follow-up, whereas SRS was negative. There was no evident relationship between the endocrine status (hyper- or eucortisolism) and the results of SRS. The in vivo response of plasma cortisol to octreotide correlated to the results of SRS in 4 of 6 cases. In conclusion, both imaging procedures had a low diagnostic yield in this series. However, the sensitivity of SRS for the detection of bronchial carcinoids was lower than that of thin-section CT scanning. We therefore advocate the use of conventional imaging, including thin-section CT scanning of the chest, analyzed by experienced radiologists, as the first-line investigation in patients with occult EAS. SRS should not be repeated during the follow-up in patients with a previously negative scintigram.

ACTH Syndrome, Ectopic↗
PubMed1988

Episodic ectopic ACTH syndrome associated with pulmonary infarctions.

The etiology of the ectopic ACTH syndrome, associated with certain tumors, is unclear. The ectopic ACTH syndrome was diagnosed in our patient by the characteristic clinical and laboratory findings. Shortly after admission, pulmonary infarctions were documented by lung scans and computed tomography. After treatment with anticoagulants, his plasma ACTH level and its suppressibility became normal. There was no evidence of a tumor. The ectopic ACTH syndrome recurred one year later in conjunction with another episode of pulmonary infarctions. During anticoagulant therapy his infarctions cleared and his plasma ACTH level normalized. In the five years since the onset, no tumor has been found, and plasma ACTH level remains normal and suppressible. We propose that our patient's pulmonary infarctions stimulated pulmonary ACTH production, leading to Cushing's syndrome.

ACTH Syndrome, Ectopic↗
PubMed1985

Ectopic eruption of the maxillary permanent first molar: the effect of increased mesial angulation on arch length.

Fifty-four cases of ectopically erupted maxillary permanent first molars were studied with a method using the measurements obtained from photographs of the study casts. The amount of relative loss of anteroposterior arch length of the right and left sides was shown to correlate with the increased mesial angulation of the maxillary permanent first molar. The bilateral ectopic group has a significantly larger mesial angulation of the permanent first molar on a maxilla with shorter anteroposterior arch length. The relative loss of arch length with ectopic eruption of the permanent first molar limits the use of unilateral appliances for treatment. The use of an appliance with bilateral arch support seems preferable.

Cephalometry↗
PubMed1994

A case of ectopic ACTH syndrome associated with Zollinger-Ellison syndrome: long-term survival with chemical adrenalectomy.

The female patient in this report was suffering from a pancreatic islet cell tumor which exhibited ectopic ACTH syndrome associated with Zollinger-Ellison syndrome. When this combined syndrome was diagnosed, there were already multiple metastasis to the liver. Zollinger-Ellison syndrome was treated with a histamine-H2-receptor blocker, and ectopic ACTH syndrome was controlled with trilostane, metyrapone and o,p'-DDD. She survived more than 6 years after the diagnosis, mostly as an outpatient. During treatment she became cachexic. After she died, an autopsy was done. Immunohistochemical staining established that tumor cells contained ACTH- and gastrin-like immunoreactivity. Our treatment suggested the efficacy of chemical adrenalectomy in managing ectopic ACTH syndrome associated with Zollinger-Ellison syndrome.

ACTH Syndrome, Ectopic↗
PubMed2001

An ectopic ACTH-producing carcinoid tumor localized by the measurement of ACTH in the bronchial lavage.

We report a case of an ectopic ACTH-producing carcinoid in the lung. Typical Cushingoid appearance, elevated plasma ACTH and serum cortisol, bilateral enlargement of the adrenal glands, absence of pituitary adenoma and negativity in petrosus sinus venous sampling indicated the ectopic ACTH syndrome. Venous samplings from a lung tumor which was detected by the chest X-ray, did not show any step-up of ACTH. However, ACTH concentration in the bronchoscopic lavage was as high as that in the peripheral blood. Removal of the tumor, which was an ACTH producing carcinoid, resulted in normalization of ACTH and cortisol concentrations. Measurement of ACTH in the bronchoscopic lavage was useful for the diagnosis of ectopic ACTH-producing tumor.

ACTH Syndrome, Ectopic↗
PubMed1980

A case of oat cell carcinoma of the lung associated with ectopic production of ADH, neurophysin and ACTH.

A woman with oat cell carcinoma of the lung showed the typical findings of the syndrome of inappropriate secretion of ADH initially during her hospital course. Ectopic production of ADH was indicated. The presence of ectopic production of ACTH was then suggested after the appearance of the elevation of plasma cortisol and ACTH which was not suppressed by dexamethasone administration. The laboratory findings of metabolic alkalosis and hypokalemia were also consistent with hyperadrenocorticism. In tumor tissue obtained by biopsy, ACTH and ADH were proven to be present by radioimmunoassay as well as nicotine-stimulated-neurophysin and estrogen-stimulated-neurophysin. This was a rare case in which the simultaneous production of ADH and ACTH was clinically diagnosed. It is suggested that the elevation of neurophysins in plasma is of value in the diagnosis of ectopic production of ADH.

ACTH Syndrome, Ectopic↗
PubMed1978

Ectopic pregnancy: criteria and accuracy of ultrasonic diagnosis.

Of 26 ectopic pregnancies, a correct positive ultrasonic diagnosis was made in 77%, while a false negative diagnosis was made in 23%. Most commonly, the ectopic pregnancy appeared as a complex adnexal mass immediately adjacent to an enlarged "empty" uterus. Ultrasonic identification of an extrauterine gestational sac, allowing a definitive diagnosis of ectopic pregnancy, was uncommon.

Diagnostic Errors↗
PubMed1980

Diagnostic ultrasound in threatened abortion and suspected ectopic pregnancy.

200 women threatened with abortion during the first 16 weeks of pregnancy were examined with diagnostic ultrasound to determine whether there were signs of intrauterine life. Of the 90 who showed positive signs, 8 aborted spontaneously later, the other 82 continued their pregnancy. The ultrasound investigation revealed no signs of intrauterine life in 110 patients. Of these, spontaneous abortion or later evacuation because of missed abortion 101 (histopathological examination showed degenerated villi in 98), not pregnant 4, mola hydatidosa 3, extrauterine pregnancies 2. An ultrasound examination was performed to ascertain whether 136 women with suspected ectopic pregnancy had intrauterine pregnancies. 61 of them had an intrauterine gestational sac, confirmed at clinical follow-up. One of the 61 was operated on with laparoscopy because of pain; no abnormalities were found. In 36 of the other 75, laparoscopy was performed. Ectopic pregnancy 21, ovarian or parovarian cyst 11, adhesions 2, salpingitis 1, and normal 1. Diagnostic ultrasound is excellent for accurate prognosis in threatened abortion. Unnecessary operations avoided; hospitalization in suspected ectopic pregnancies reduced.

Abortion, Threatened↗
PubMed1980

Freeze microscopy of the endometrium in ectopic pregnancy.

A series of 60 patients with suspected ectopic pregnancy was reviewed in order to assess the diagnostic value of freeze microscopy of endometrial curettings. By this procedure the correct diagnosis has been make in 82 per cent of patients, i.e. it established whether the patient was pregnant and whether the pregnancy was intra- or extrauterine. Eighteen patients had an ectopic pregnancy. 13 of them were detected primarily on microscopy of frozen sections, while the remaining 5 were erroneously classified as non-pregnant. The diagnostic sensitivity of freeze microscopy proved to be equal to microscopy of the subsequent paraffin sections. A diagnostic and therapeutic schedule can be set up for patients with suspected ectopic pregnancy when the histological appearances of the frozen sections and the result of the HCG reaction are known.

Endometrium↗
PubMed1982

Diagnostic value of ultrasound scanning and curettage in ectopic pregnancy. A prospective controlled trial.

The object of this study was to assess the diagnostic value of ultrasonic scanning alone and of ultrasonic scanning combined with histological examination of endometrial tissue on suspicion of subacute ectopic pregnancy. For the 93 patients comprising the study, ectopic pregnancy was diagnosed in 21 cases. The diagnostic sensitivity of ultrasound scanning alone proved high, there being 97% correct, negative diagnosis, while a correct positive diagnosis was made in 79%. Ultrasound scanning combined with histological examination of endometrial tissue did not improve the diagnostic accuracy. It is concluded that on suspicion of ectopic pregnancy, ultrasound scanning is a valuable screening method for the exclusion of this condition.

Adult↗
PubMed1984

Pseudogestational sac in ectopic pregnancy.

A case of tubal pregnancy demonstrated by sonography is presented. In addition to the true ectopic gestational sac, an intra-uterine structure closely resembling a gestational sac was detected simultaneously. Such a finding of a pseudogestational sac in the uterine cavity may mislead to the diagnosis of an intra-uterine gestation. Thus, this sonographic finding is not sufficient to exclude the diagnosis of ectopic pregnancy. Clinicians should be aware of the possible finding of a pseudogestational sac in cases of ectopic pregnancy and the pathophysiological basis of this phenomenon is discussed.

Adult↗