Unusual Imaging Findings Associated with Germ Cell Tumors.

Germ cell tumors, because they contain immature and mature elements, can differentiate into different tissue types. They can exhibit unusual imaging features or manifest in a syndromic fashion. The authors describe these features and assign them to one of the following categories: (a) unusual manifestations of metastatic disease (growing teratoma syndrome, choriocarcinoma syndrome, ossified metastases, and gliomatosis peritonei); (b) autoimmune manifestations (sarcoidlike reaction and paraneoplastic syndromes); (c) endocrine syndromes (sex hormone production, struma ovarii, and struma carcinoid); or (d) miscellaneous conditions (ruptured dermoid cyst, squamous cell carcinoma arising from a mature teratoma, Currarino triad, fetus in fetu, pseudo-Meigs syndrome, and pancreatitis). Rare conditions associated with germ cell tumors demonstrate characteristic imaging findings that can help lead to the appropriate diagnosis and management recommendations. When evaluating for potential metastatic disease, alternative benign diagnoses should be considered (eg, growing teratoma syndrome, ossified metastases, ruptured dermoid cyst, gliomatosis peritonei, and sarcoidlike reaction), which may impact management. Germ cell tumors may also lead to life-threatening complications such as extensive hemorrhage from choriocarcinoma metastases or the rupture of mature teratomas, cases in which timely diagnosis is crucial. Autoimmune and endocrine manifestations such as paraneoplastic encephalitis, autoimmune hemolytic anemia, and hyperthyroidism may occur owing to the presence of germ cell tumors and can create a diagnostic dilemma for clinicians. Knowledge of the syndromic and unusual imaging findings associated with germ cell tumors helps guide appropriate management. ©RSNA, 2019.

Less frequent requests for In-111 pentreotide and its brothers of endocrinological interest.

The somatostatin receptor scintigraphy (SRS), using octreotide radiolabelled with 111In (octreoscan, OCTs), is a consolidated diagnostic procedure in patients with neuroendocrine tumors. A higher accuracy has been demonstrated with single photon emission computed tomography-CT, while a further improvement has been obtained with positron emission tomography (PET)-CT, using somatostatin analogues radiolabeled with 68Ga, significantly increasing the number of detected lesions. Although the well-known presence of an OCTs uptake in many benign diseases, when in an active phase, the application of SRS in these patients did not find any clinical relevance yet. In this paper we discuss two fields of endocrinological interest where SRS could play a clinical role. In patients with Graves exophtalmos, the capability to differentiate between active and non-active disease can be helpful in define prognosis and therapeutic strategies. In patients with endocrine paraneoplastic syndromes (PNS), SRS can help in finding the underlying neoplasm, contributing to its characterization as premise to a therapeutic choice. The possible role of a surgery guided by OCTs is also explained and suggested. The incremental value of PET-CT with Ga-68 peptides is hypothesized to reduce the number of unknown neoplastic lesions frequently present in patients with PNS.

Scintigraphic evaluation of primary congenital hypothyroidism: results of the Greek screening program.

The Greek screening program for primary congenital hypothyroidism was initiated in 1979. By early 2000, thyrotropin measurements had been performed in 1,976,719 newborns, using dried blood spots obtained by heel prick. Among these children, 584 were diagnosed with congenital hypothyroidism (incidence: 1/3,384 births) and were given L-thyroxine (L-T4) replacement therapy. In order to further evaluate and classify the children as having either an aplastic (AT) or an ectopic thyroid gland (ET) or as showing thyroidal dyshormonogenesis (DN, with a nomotopic gland), scintigraphic studies were performed at the age of 2-3 years. In 413 children of this age group (including 24 subsequently diagnosed as having had transient hypothyroidism, in whom L-T4 therapy was not resumed), thyroid hormones were measured and scintigraphic studies were done after withdrawal of L-T4 replacement treatment for 3 weeks. Given the long duration of the study, we used various scintigraphic modalities. In 96 children (group A), scintigraphy was performed using technetium-99m pertechnetate (99mTcO4-; 18.5 MBq given i.v.) and a rectilinear scanner. Seventy-three children (group B) were studied with 99mTcO4- (18.5 MBq given i.v.) and a gamma camera equipped with a pinhole collimator. In these groups, atropine was administered 30 min prior to the study (0.02 mg/kg i.v. or i.m.) in order to reduce the secretion of saliva from the salivary glands. Finally, in the remaining 220 children (group C) iodine-123 sodium iodide (123I-Na) (0.74-1.85 MBq i.v.) and the same gamma camera were used. Between-group comparisons of scintigraphic findings were done with the chi square test. In 191 children from group C, thyroglobulin (Tg) was measured and in 49 children ultrasound (US) was performed (categorising the gland as AT or ET/DN). Comparison of these modalities was done with the kappa statistic. In group A, 61.5% of children had AT, 26.0% had ET and 12.5% had DN; in group B, 28.8% of children had AT, 52.0% had ET and 19.2% had DN; in group C, 23.2% of children had AT, 63.2% had ET and 13.6% had DN. Statistically significant differences in group A versus groups B and C were noted for AT and ET. The implementation of newer scintigraphic modalities, and especially the use of 123I-Na, indicates that the commonest finding in congenital hypothyroidism is ET. Scintigraphy was more concordant with Tg measurements (though at a moderate level) than with US. The latter was even less concordant with Tg values. These results show that the most appropriate approach for the evaluation and classification of congenital hypothyroidism is 123I-Na scanning.

Transcatheter adrenal arterial embolization of cortisol-producing tumors. Two cases of Cushing's syndrome.

Transcatheter arterial embolization (TAE) was performed in 2 patients with Cushing's syndrome caused by adrenal adenoma by using a mixture of absolute ethanol and iohexol. In 1 patient successful suppression of the hypersecretion of cortisol has continued for 9 months after TAE without complications. However, in the other patient, TAE was discontinued due to marked hypertension and tachycardia induced by a massive release of catecholamines from the embolized "normal" part of the tumor-bearing adrenal gland during the procedure. These results suggest that it is important to perform TAE of only the arterial branches feeding the tumor.

MIB1 immunopositivity is associated with rapid regrowth of pituitary adenomas.

Pituitary adenomas are generally regarded as benign tumours, but they may recur. We identified eight patients with pituitary adenomas that showed rapid regrowth within 2 years of initial surgery. We estimated the percentage of cells in each specimen that showed positive immunostaining for MIB1 (a novel anti-Ki-67) and compared the values to those of 40 adenomas that showed no regrowth. The mean MIB1 index for 40 adenomas that showed no evidence of regrowth was 0.19 +/- 0.06%. This was significantly (p < 0.0001) lower than that for adenomas that showed rapid regrowth (1.27 +/- 0.31%), based on the initial resected specimens. Immediately after detection of rapid regrowth and in adenomas that were resistant to bromocriptine or irradiation, the MIB1 index was always greater than 1.0%. Most patients with rapidly regrowing adenomas were well controlled by radiation therapy. Our results suggest that a MIB1 index greater than 1.0% may be a useful predictor of rapid regrowth of pituitary adenomas and may be useful for planning of therapy.

Somatostatin receptor scintigraphy in patients with pituitary adenoma.

Presence of high-affinity somatostatin (SST) receptors in most endocrine tumor cells allow in vivo scintigraphic visualization of these neoplasms after intravenous administration of a radionuclide-labeled somatostatin analog. 111In-octreotide is at present the most often used substance for imaging of the SST receptor expression in vivo. The aim of this study is to investigate the correlation between presence of in vivo scintigraphically detectable SST receptors in pituitary tumors and clinical parameters such as patients' age, tumor size, hormonal hypersecretion, and response to octreotide therapy. Forty-two-consecutive patients were enrolled in this trial. Twenty-five of them had nonsecreting pituitary tumors, 11 were acromegalic, and 6 had macro- or microprolactinoma. Scintigraphic images of the head were obtained at 10 min and 24 hours after injection of the radionuclide. In 23 patients, no specific binding of 111In-octreotide was found. Five patients showed a weak positive, 5 had a positive, and 9 a strong positive signal in the region of interest. Uptake of octreotide was significantly correlated with tumor size and age (p < 0.01). Small-size pituitary adenomas were most likely to be scintigraphically receptor-negative, while large suprasellar tumors tended to exhibit a rather strong receptor positivity. Statistical analysis of the data could not confirm the hypothesized correlation between endocrine activity of the pituitary tumors and the scintigraphically proven SST receptor expression in vivo. A positive Octreoscan was not predictive for the result of octreotide therapy.

[Somatostatin receptor scintigraphy. Methodology, indications, results]. / Somatostatinrezeptor-szintigraphie. Methodik, indikationen, ergebnisse.

Somatostatin-receptor scintigraphy has been in clinical use for several years. Most of the experience with somatostatin tumor scintigraphy has been obtained with gastro-enteropathic (GEP) tumors and carcinoids. Clinical applications of somatostatin imaging have been reported in small-cell lung carcinomas, malignant lymphomas, renal-cell carcinomas, breast cancers and medullary thyroid cancers. Somatostatin analogues were initially applicable in larger medical institutions because of the necessity for radioactive labeling with iodine (octreotide to [123I-Tyr3]-octreotide); however, the clinical results with iodinated analogues were worse than the relatively new analogue [111In-DTPA-D-Phe1]octreotide, now available as Octreoscan. This review describes the current status of the clinical application of somatostatin receptor imaging, together with our own experience in carcinoids, GEP tumors and medullary thyroid carcinomas.

Normogonadotropic primary amenorrhea in a growth hormone-deficient woman with ectopic posterior pituitary: gonadotropin pulsatility and follicle-stimulating hormone bioactivity.

We studied the gonadotropic function in a 25-year-old woman suffering from congenital GH deficiency, complaining of primary amenorrhea and wishing to become pregnant. She disclosed a hypoplasic anterior pituitary within a small sella turcica and an ectopic posterior pituitary lobe located below the median eminence. Immunoreactive LH and FSH plasma levels were normal, basal and in response to a GnRH iv bolus but estradiol was low. LH pulse frequency was elevated and FSH bioactivity was low in a granulosa cell aromatase bioassay. Pulsatile administration of iv GnRH at a slower, normal pace, failed to induce ovulation or to increase FSH bioactivity, with or without concomitant GH replacement. However treatment with exogenous im gonadotropins, when preceeded by GH replacement, succeeded in inducing mature oocytes and pregnancy. We concluded that the hypogonadism observed in this patient was due to rapid GnRH pulsatility and poor biological activity of endogenous FSH.

Adrenal nonhyperfunctioning adenoma and nonadenoma: CT attenuation value as discriminative index.

BACKGROUND: When an asymptomatic adrenal mass is incidentally discovered on abdominal CT scans, the distinction between a nonhyperfunctioning adenoma and a nonadenoma would be important. METHODS: We evaluated the CT findings of 36 adrenal masses (14 nonhyperfunctioning adenomas, 22 nonadenomas) in 34 patients with no evidence of hormonal hypersecretion. CT attenuation values of adrenal masses on CT scans were calculated by setting a circular region of interest as large as possible in the center of each adrenal mass. RESULTS: Below 20 HU in CT attenuation values, all adrenal masses, except one case of ganglioneuroma with myxomatous change, were nonhyperfunctioning adenomas. With an arbitrary threshold of 20 HU, the sensitivity of CT attenuation values in distinguishing nonhyperfunctioning adenomas from nonadenomas was 64%, the specificity was 95%, and the accuracy was 83%. When decreasing the threshold to 15 HU, the sensitivity was 64%, the specificity was 100%, and the accuracy was 86%. The CT attenuation value on noncontrast CT was more useful for making this distinction than the size and interior homogeneity. CONCLUSIONS: Our data suggest that an asymptomatic adrenal mass with homogeneous low attenuation (< or = 15 HU) and less than or equal to 4 cm indicates a nonhyperfunctioning adenoma, and no further examinations are necessary. CT attenuation value on non-contrast CT is the most important discriminatory factor.

[Somatostatin receptor scintigraphy in preoperative diagnosis of the site of endocrine gastrointestinal tumors]. / Die Somatostatinreceptor-Szintigraphie in der präoperativen Lokalisationsdiagnostik endokriner gastrointestinaler Tumoren.

To determine the value of somatostatin-receptor scintigraphy in the localization of various endocrine gastrointestinal tumors, we compared the results obtained with this new technique with the results obtained with computed tomography and sonography. We could not find an overall advantage of somatostatin-receptor scintigraphy as compared to computed tomography or sonography in the localization of intestinal carcinoids (n = 13), gastrinomas (n = 12), functionally non-active endocrine pancreatic tumors (n = 8) and various other endocrine pancreatic tumors (n = 4). In 2 patients with endocrine pancreatic tumors however, the tumors were localized preoperatively only by somatostatin-receptor scintigraphy. Somatostatin-receptor scintigraphy may occasionally be helpful in the localization of gastrointestinal endocrine tumors if these tumors are not localized by conventional imaging studies. Somatostatin-receptor scintigraphy does not solve the problem to localize small endocrine tumors.

111In-pentetreotide (somatostatin analogue) scintigraphy as an imaging procedure for endocrine gastro-entero-pancreatic tumors.

It was the aim of the present study to examine whether 111In-pentetreotide, a somatostatin analogue with predominantly renal excretion, is a suitable receptor agonist for scintigraphic imaging of endocrine gastro-entero-pancreatic (GEP) tumors, and to evaluate the contribution of the usual imaging times 4 and 24 h p.i. In 36 patients, planar scintigrams obtained 4 h, and 24 h after i.v. injection of 111 or 222 MBq 111In-pentetreotide were compared to the results of other imaging procedures and of surgery. Single photon emission computed tomography (SPECT) was also performed 24 h p.i. Positive scintigraphies were obtained in 32 out of 36 patients (18/19 patients with carcinoid syndrome, 8/9 with non hormone-producing endocrine GEP tumors, 2/4 with gastrinomas, 1/1 with glucagonoma, 1/1 with a VIPoma, 2/2 with paragangliomas). In 9 patients tumor manifestations previously not detected by conventional imaging procedures were disclosed by 111In-pentetreotide scintigraphy. 24-h images yielded significantly more true positive findings than 4-h images. In 4 patients liver metastases missed on planar scans were detected by SPECT. A discrepancy between patient-based and organ-based analysis of the results was encountered thus indicating a possible intraindividual heterogeneity in somatostatin receptor expression. In conclusion, 111In-pentetreotide is a suitable somatostatin analogue for scintigraphic in vivo demonstration of somatostatin receptors and for imaging of most tumor manifestations in patients with endocrine GEP tumors. Further studies will have to evaluate whether or not a positive receptor scintigraphy predicts response to treatment with long-acting somatostatin analogues.

[Ultrasound of incidental tumors of the adrenal gland and endocrine hypertension]. / Sonographische Inzidentalome der Nebenniere und endokrine Hypertonie.

We report on a retrospective analysis of 1,500 hypertensive patients who underwent a sonographic examination of the abdomen. 8 'incidentalomas' of the adrenal gland (0.6%) were thereby found. Endocrinological analysis showed that only 1 of the incidentalomas was active (pheochromocytoma). The other tumors had no endocrine activity. On the other side, 7 patients without any sonographic abnormality had hyperaldosteronism, 1 patient suffered from an adrenomedullary hyperplasia. Those patients had been thought to have endocrine hypertension from clinical suspicion. We conclude that a thorough sonographic examination of the adrenal area is an important part of the diagnostic workup in hypertensive patients, although most of the incidentally discovered tumors are endocrinologically inactive. Adrenocortical and adrenomedullary hyperplasias and adrenocortical adenomas are detected clinically while they are still not visible by ultrasound.

Incidentally discovered adrenal tumors.

The introduction of computed tomography has dramatically increased the detection and in turn the incidence of incidentally identified adrenal abnormalities; the current incidence rate is approximated at 2%. Improvements in technology can be expected to increase the reported incidence even further and magnify the clinical problem these abnormalities pose. Although most clinicians would agree that surgery is indicated in patients with primary adrenal malignancy and those with significant endocrine function, strategies for the management of patients with incidentally identified lesions remain controversial. One approach is to base the risk of primary adrenal malignancy on lesion size and undertake biochemical evaluation only for patients who, on clinical grounds, are likely to have endocrinopathy. Another approach is to assess endocrine function (biochemically and radiographically) in all patients and recommend surgery or additional evaluation (eg, needle biopsy) for those found to have abnormalities. Recent studies of patients with benign, incidentally discovered adrenal lesions suggest that these common lesions are almost all hormonally functional to some extent. The natural history of subclinical but functioning adrenal adenomas is not known.

Treatment with Sandostatin and in vivo localization of tumors with radiolabeled somatostatin analogs.

The presence of high numbers of somatostatin receptors seems to be the basis for the successful control by Sandostatin of hormonal hypersecretion by most growth hormone-secreting pituitary adenomas, endocrine pancreatic tumors, and carcinoids. In this report, we present preliminary data on in vivo somatostatin receptor imaging with a 123I-coupled somatostatin analog (204-090) in patients with these types of tumors.

[Computerized tomography findings in hormonally inactive adrenal gland tumors]. / Computertomographische Befunde hormonell inaktiver Nebennierentumoren.

CT examinations of 6 years served as basis for the incidence of hormonally inactive space-occupying masses at the adrenal. Of a total of 25,000 patients, 313 (1.3%) suffered from disease of the adrenals, and of these 261 patients had a hormonally inactive adrenal tumour. Adenomas were the most frequent space-occupying growths (101 patients), followed by metastases of the adrenals (77 patients), whereas adrenal carcinomas (4 patients), myelolipomas (3 patients), ganglioneuromas (3 patients) adrenal cysts (3 patients) and adrenal haemorrhages (2 patients) were rare findings.

CT of cerebral abnormalities in precocious puberty.

True precocious puberty occurs as a result of the premature release of luteinizing hormone-releasing hormone from the hypothalamus, which stimulates the secretion of the pituitary gonadotropins, which in turn stimulate the gonadal sex steroids. The differential diagnosis of true precocious puberty includes cerebral and idiopathic categories. This differentiation, which cannot be made endocrinologically due to similarities in pituitary gonadotropin and sex steroid levels, may be facilitated by high-resolution CT. A CT study of 90 children (73 girls and 17 boys) with true precocious puberty was performed at the NIH to detect cerebral causes of their precocious puberty. Thirty-four cerebral abnormalities were demonstrated in 32 children, 16 boys and 16 girls. These included hypothalamic hamartomas (17), hypothalamic astrocytoma (one), optic chiasm lesions (six), ventricular abnormalities (eight), arachnoid cyst (one), and teratoma (one). The CT appearance of these cerebral abnormalities is discussed and related to the endocrinologic findings and natural history of true precocious puberty. A practical neuroradiologic approach to the evaluation of children with precocious puberty is presented.

ACTH-producing apudoma metastatic to the liver.

A young man presented with combative psychosis and elevated levels of plasma adrenocorticotropic hormone (ACTH). A solitary vascular pancreatic mass and diffuse vascular hepatic nodules were demonstrated on selective splenic and hepatic arteriograms. These classic angiographic findings are used to emphasize the role of angiography in initial radiographic evaluation and to summarize the angiographic appearance of functioning pancreatic adenomas. Even though this is an aggressive tumor, early diagnosis and intensive treatment may allow prolonged remission, if not cure.