Posterior pituitary tumors are rare nonneuroendocrine neoplasms originating in the neurohypophysis that lack hormonal secretory capacity. Surprisingly, these tumors are relatively frequently ...associated with adenohypophyseal syndromes of hormonal hypersecretion such as Cushing’s disease and acromegaly. Fifteen cases of posterior pituitary tumor associated with hypercortisolism have been reported to date, 13 of them were pituicytomas (Pi) and 2 were granular cell tumors (GCT). Six patients with posterior pituitary tumor associated with acromegaly have been reported (4 Pi and 2 GCT). The main forms of clinical presentation and the possible pathophysiological mechanisms of this association are reviewed.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
In 2017, the World Health Organization established that pituicytoma, granular cell tumor (GCT), spindle cell oncocytoma (SCO) and sellar ependymomas (SE) are posterior pituitary tumors (PPT). They ...probably arise from the pituicytes and may constitute a unique histopathological entity. We carried out a systematic review using PubMed’s database. A total of 266 patients with pathological diagnosis of PPT (135 pituicytomas, 69 GCT, 47 SCO, 8 SE and 7 mixed histology tumors) were analyzed. Gender distribution was identical and median age at diagnosis was 48 ± 21.8 years. Main presentation symptoms were visual disorders (
n
= 142; 58.1%), headache (
n
= 99; 40.5%), hypopituitarism (
n
= 84; 34.4%), hypercortisolism (
n
= 10; 4.1%), polyuriapolydipsia (
n
= 6; 2.4%) and acromegaly features (
n
= 5; 2.0%). On MRI, 122 (47.6%) patients showed sellar with suprasellar extension masses, 67 (23.1%) were suprasellar and 63 (24.6%) exclusively sellar. Median tumor size was 22.0 ± 14.2 mm. Two hundred sixty four patients underwent surgery, transphenoidal access was selected in 132 (64.4%) and craniotomy in 58 (28.3%). Complications were hypopituitarism (
n
= 70; 42.1%), diabetes insipidus (
n
= 55; 33.1%) and hemorrhage (
n
= 50; 30.1%). Tumor persisted in 93 patients (45.6%) and recurred in 13 (6.4%). Regarding comparison between main types of PPT, SCO patients were diagnosed later (60.0 vs 47.0 vs 47.0 years,
p
= 0.023), the tumor was larger 25.0 mm 10.8 vs 20.0 mm 14.2 vs 2.0 mm 15.0 and they were frequently sellar with suprasellar extension tumors (71.7% vs 46.2% vs 32.8%,
p
= 0.003) compared to pituicytoma and GCT. In conclusion, PPT are rare tumors and have been misdiagnosed mainly as non-functioning pituitary adenomas. Different types of PPT share similar epidemiology, clinical manifestations and surgical outcomes. Surgery is the only curative option but complications and subtotal resection are common.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Coexistence of pituitary adenoma, intracranial meningioma and cerebral aneurysm has never been described. We report on a patient with GH-secreting pituitary macroadenoma associated with a right ...frontal meningioma and with two intracavernous asymptomatic aneurisms. A 61-year-old woman was referred to our Endocrine Unit 13 years after a right frontal craniotomy for a pituitary tumour. Endocrine investigation showed high levels of IGF-1 (560 ng/ml) and increased basal serum GH (56 ng/ml) levels, not suppressed after OGTT. MRI showed persistence of a homogeneously enhancing intra- and suprasellar lesion, compressing the visual pathways, with bilateral intracavernous invasion and simultaneous coexistence of a right intracavernous internal carotid artery (ICA) aneurysm in direct contact with the pituitary tumour. Somatostatin analog treatment normalized GH and IGF-1 levels. Eight months later, the patient underwent a balloon ICA occlusion with disappearance of the right ICA aneurysm. One year later, a new MRI confirmed the presence of the pituitary mass showing also a right intracranial frontal meningioma and a new ICA aneurysm on the left side. Previous studies have suggested that prolonged GH hypersecretion could play a role in the genesis of intracranial aneurysms, inducing atherosclerotic and/or degenerative modification of the arterial walls. Other aetiological factors include a mechanical effect due to a direct contact between adenoma and aneurysm. Coexistence of pituitary adenoma and intracranial meningioma is a rare event, but also for this association it has been suggested that GH or other growth factors could play a role in appearance or in growth of meningioma. In our case, meningioma appeared and grew, despite the effective treatment of acromegaly. PUBLICATION ABSTRACT
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Pharmacologic treatment of acromegaly is currently based upon assay-error strategy, the first-generation somatostatin receptor ligands (SRL) being the first-line treatment. However, about 50% of ...patients do not respond adequately to SRL. Our objective was to evaluate the potential usefulness of different molecular markers as predictors of response to SRL. We used somatotropinoma tissue obtained after surgery from a national cohort of 100 acromegalic patients. Seventy-one patients were treated with SRL during at least 6 months under maximal therapeutic doses according to IGF1 values. We analyzed the expression of SSTR2, SSTR5, AIP, CDH1 (E-cadherin), MKI67 (Ki-67), KLK10, DRD2, ARRB1, GHRL, In1-Ghrelin, PLAGL1 and PEBP1 (RKIP) by RT-qPCR and mutations in GNAS gene by Sanger sequencing. The response to SRL was categorized as complete response (CR), partial (PR) or non-response (NR) if IGF1 was normal, between >2<3 SDS or >3 SDS IGF1 at 6 months of follow-up, respectively. From the 71 patients treated, there were 27 CR (38%), 18 PR (25%) and 26 NR (37%). SSTR2, Ki-67 and E-cadherin were associated with SRL response (P < 0.03, P < 0.01 and P < 0.003, respectively). E-cadherin was the best discriminator for response prediction (AUC = 0.74, P < 0.02, PPV of 83.7%, NPV of 72.6%), which was validated at protein level. SSTR5 expression was higher in patients pre-treated with SRL before surgery. We conclude that somatotropinomas showed heterogeneity in the expression of genes associated with SRL response. E-cadherin was the best molecular predictor of response to SRL. Thus, the inclusion of E-cadherin in subsequent treatment-decision after surgical failure may be useful in acromegaly.
Knowledge of ectopic Cushing’s syndrome (CS) due to thymic neuroendocrine tumours (NETs) comes from short series or single cases. Our aim is to perform a systematic review using PubMed, Embase, ...Scopus, Ovid Medline and Biosis Previews of all cases with ectopic CS due to thymic NETs reported in the last 40 years and describe one illustrative patient attended in our institution. Search of literature: From 162 patients, 58.6% were male and mean age was 34.6 ± 13.9 years-old. Median of symptoms until diagnosis was 6 2–24 months and 62% had aggressive CS. Imaging was positive in 93.7% (chest X-ray), 97.8% (computed tomography), 80.7% (somatostatin receptor scintigraphy) and median tumour size was 47 25–68.5 mm. At presentation, 18% had localized disease, 26.2% locally invasive and 55.7% advanced. Eighty-eight present underwent surgery and histological subtypes were atypical (46.7%), typical (30.4%) and carcinoma (21.7%). Tumour persisted or recurred in 70.1%, 63% received radiotherapy and 45.2% chemotherapy. Follow-up median was 26.6 14.5–57.5 months and mortality was reported in 35.8% with median survival of 38 19–60 months. MEN-1 mutation was referred in 3.1%. Comparatively, carcinomas had aggressive CS more frequently while atypical showed advanced disease more often. In conclusion, thymic NETs causing ectopic CS are presented as aggressive hypercortisolism in the middle aged population. The disease is commonly extended at diagnosis and persists or recurs after surgery in most patients with a short term high mortality.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Predicting which acromegaly patients could benefit from somatostatin receptor ligands (SRL) is a must for personalized medicine. Although many biomarkers linked to SRL response have been identified, ...there is no consensus criterion on how to assign this pharmacologic treatment according to biomarker levels. Our aim is to provide better predictive tools for an accurate acromegaly patient stratification regarding the ability to respond to SRL. We took advantage of a multicenter study of 71 acromegaly patients and we used advanced mathematical modelling to predict SRL response combining molecular and clinical information. Different models of patient stratification were obtained, with a much higher accuracy when the studied cohort is fragmented according to relevant clinical characteristics. Considering all the models, a patient stratification based on the extrasellar growth of the tumor, sex, age and the expression of E-cadherin, GHRL, IN1-GHRL, DRD2, SSTR5 and PEBP1 is proposed, with accuracies that stand between 71 to 95%. In conclusion, the use of data mining could be very useful for implementation of personalized medicine in acromegaly through an interdisciplinary work between computer science, mathematics, biology and medicine. This new methodology opens a door to more precise and personalized medicine for acromegaly patients.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Knowledge of xanthogranuloma (XG) of the sellar region comes from short series or single cases. We performed a systematic review, using the PubMed, Web of Science, Embase, Scopus, eLibrary, and ...BIOSIS Preview databases, of all cases reported from 2000 to the present. We also describe one unreported patient treated in our institution. A search of the literature revealed that of 71 patients 50.7% were male and that mean age at diagnosis was 34.7 ± 19.2 years old. Median time from clinical onset until diagnosis was 7 (3-21) months. Hypopituitarism (70.4%), visual disorders (64.7%), headache (53.5%), and polyuria-polydipsia (28.2%) were the most common symptoms. On MRI, median tumor size was 20 (16-29) mm, while 71.8% were sellar/suprasellar and less frequently exclusively suprasellar (15.5%) or sellar (12.7%). On T1-weighted imaging, XG was hyperintense in 76.3% of patients, while it showed variable appearance on T2-weighted imaging. The tumor showed cystic features in 50.7%, gadolinium enhancement in 45.1%, and calcification in 22.5% of patients. All patients underwent surgery (77.4% transphenoidal approach and 18.3% craniotomy), with hypopituitarism (56.4%), diabetes insipidus (34.5%), and visual defects (7.3%) being the most common complications. Total/subtotal resection was achieved in 93.5%, while the tumor was partially removed in 6.6%. Median follow-up was 24 (6-55) months and no tumor recurrence or remnant growth was reported in 97.5% of cases. In conclusion, XG affects the younger population, manifested by hormonal deficit and mass effect symptoms. Surgery is safe and offers excellent outcomes, though hypopituitarism is frequent post-surgery. Tumor recurrence or remnant growth is rare and radiological surveillance is a good option for patients with remnant lesions.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Purpose and methods
Sarcomas of the sellar region are uncommon and unexpected tumors. Here, we review the cases reported in literature via a systematic search.
Results
Ninety-four patients, 58.5% ...male with mean age of 39.2 ± 17.2 years were included. Fifty-seven (62%) had soft tissue sarcomas (STS) and 35 (38%) bone sarcomas (BS). Sarcoma was a primary tumor in 66%, developed after radiotherapy in 31.9% and 7.4% were metastatic. Median time between radiotherapy and sarcoma development was 10.5 (11) years. Main presentation symptoms were visual disorders (87.9%), headache (61.5%) and III cranial nerve palsy (24.1%). After surgery, sarcoma persisted or recurred in 82.3% and overall mortality reported was 44.6% with 6.5 (14) months of median survival. Tumor appeared earlier in BS compared to STS (34.4 ± 15.1 vs. 42.6 ± 17.6 years),
p
= 0.034 and complete tumor resection was achieved more often (41.3% vs. 4.4%),
p
= < 0.001. Condrosarcoma and rhabdomyosarcoma were more frequent subtypes among primary tumors while fibrosarcoma was among post-radiation sarcomas. Tumor size was larger in radiation associated sarcomas (mean maximum diameter 46.3 ± 9.3 vs. 29.1 ± 8.0 mm,
p
= 0.004) and persistency/recurrence was similar in both groups (70.1 vs. 73.3%,
p
= 0.259).
Conclusion
Sarcomas appear as mass effect symptoms in the middle aged population, mainly as primary tumors, but one third is associated with radiotherapy. Surgery is commonly not curative, mortality rate is high and death ensues shortly after diagnosis.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Background: Antithyroid drug-induced agranulocytosis (AIA) (neutrophils <500/µL) is a rare but serious complication in the treatment of hyperthyroidism. Methodology: Adult patients with AIA who were ...followed up at 12 hospitals in Spain were retrospectively studied. A total of 29 patients were studied. The etiology of hyperthyroidism was distributed as follows: Graves’ disease (n = 21), amiodarone-induced thyrotoxicosis (n = 7), and hyperfunctioning multinodular goiter (n = 1). Twenty-one patients were treated with methimazole, as well as six patients with carbimazole and two patients with propylthiouracil. Results: The median (IQR) time to development of agranulocytosis was 6.0 (4.0–11.5) weeks. The most common presenting sign was fever accompanied by odynophagia. All of the patients required admission, reverse isolation, and broad-spectrum antibiotics; moreover, G-CSF was administered to 26 patients (89.7%). Twenty-one patients received definitive treatment, thirteen patients received surgery, nine patients received radioiodine, and one of the patients required both treatments. Spontaneous normalization of thyroid hormone values occurred in six patients (four patients with amiodarone-induced thyrotoxicosis and two patients with Graves’ disease), and two patients died of septic shock secondary to AIA. Conclusions: AIA is a potentially lethal complication that usually appears around 6 weeks after the initiation of antithyroid therapy. Multiple drugs are required to control hyperthyroidism before definitive treatment; additionally, in a significant percentage of patients (mainly in those treated with amiodarone), hyperthyroidism resolved spontaneously.
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