Wszystko co świeci w PET nie jest nowotworem złośliwym! Wychwyt 18F-deoksyglukozy a biologia nowotworu: incidentaloma przysadki mózgowej u chorego, który przebył dwie niezwiązane choroby nowotworowe

    Introduction: 18F-deoxy-glucose positron emission tomography combined with computed tomography (18F-FDG PET/CT) is routinely used in the detection of malignant disease based on the property of malignant cells to fuel their growth and replication by increased glucose uptake. Malignant lesions are rare in the sellar region, while pituitary adenomas are the most common pathology. These are benign neoplasms with insidious onset and low proliferation activity, and therefore are only exceptionally detected by 18F-FDG PET/CT. Studies that compare the biology of pituitary adenomas and their radiological properties using PET/CT are still lacking. Case report: We investigate and discuss tumour biology in light of increased 18F-FDG avidity in a symptom-free, 70-year-old male patient, previously treated for two different malignancies (lung and rectal). Increased tracer accumulation in the sellar region was incidentally detected on a follow-up 18F-FDG PET/CT scan. Additional MRI disclosed pituitary adenoma. Normal hormonal status was found, consistent with the diagnosis of non-functioning pituitary adenoma. Analysis of tumour tissue after pituitary surgery confirmed a silent gonadotroph adenoma with low proliferation index. Low expression of oncogene-induced senescence markers did not support senescence as the explanation for the tumour’s low proliferative activity although it was in consonance with the hormonal activity. Conclusions: Pituitary adenomas can manifest as hypermetabolic foci on 18F-FDG PET/CT imaging with increased tracer uptake even in indolent, clinically silent pituitary adenomas with low mitotic activity. Special attention should be paid to evaluation of 18F-FDG avid pituitary adenomas in patients with multiple malignancies, bearing in mind that avidity does not always mirror its biological behaviour.Wstęp: Pozytonowa tomografia emisyjna sprzężona z tomografią komputerową przy użyciu 18F-deoksy-glukozy (18F-FDG PET/CT) to metoda stosowana rutynowo do wykrywania nowotworów złośliwych, opierająca się na właściwościach komórek nowotworowych, których wzrost i replikacja wiąże się ze zwiększeniem wychwytu glukozy. Zmiany złośliwe występują rzadko w okolicy siodła tureckiego, natomiast do najczęstszych patologii należą gruczolaki przysadki mózgowej. Są to łagodne nowotwory z podstępnym początkiem choroby i małą aktywnością proliferacyjną, dlatego też są wykrywane wyjątkowa rzadko za pomocą badania 18F-FDG PET/CT. Nie przeprowadzono dotychczas badania porównującego cechy biologiczne gruczolaków przysadki mózgowej i ich właściwości radiologiczne z zastosowaniem techniki PET/CT. Opis przypadku: Autorzy zbadali i omówili biologię nowotworu w aspekcie zwiększonego wychwytu 18F-FDG u 70-letniego chorego bez objawów, leczonego wcześniej z powodu dwóch różnych nowotworów (płuca i odbytnicy). Zwiększony wychwyt znacznika w okolicy siodła tureckiego wykryto przypadkowo podczas kontrolnego badania 18F-FDG PET/CT. Wykonane dodatkowo badanie MRI ujawniło gruczolaka przysadki mózgowej. Stężenia hormonów u chorego były w normie, co było zgodne z rozpoznaniem nieczynnego gruczolaka przysadki mózgowej. Badanie tkanki guza po resekcji chirurgicznej potwierdziło diagnozę niemego klinicznie gruczolaka gonadotropowego o niskim wskaźniku proliferacji. Niska ekspresja markerów starzenia się indukowanego onkogenami nie potwierdziła hipotezy, że starzenie się może tłumaczyć małą aktywność proliferacyjną nowotworu, natomiast była zgodna z aktywnością hormonalną. Wnioski: Gruczolaki przysadki mózgowej mogą być widoczne w badaniu 18F-FDG PET/CT jako ogniska hipermetaboliczne o zwiększonym wychwycie znacznika nawet w przypadku nieczynnych, niemych klinicznie guzów przysadki o małej aktywności mitotycznej. Należy zwrócić szczególną uwagę na ocenę 18F-FDG-awidnych gruczolaków przysadki u chorych z wieloma nowotworami, pamiętając, że intensywność wychwytu znacznika nie zawsze odzwierciedla biologię nowotworu

Clinical case seminar - familial intracranial germinoma

Background: Intracranial germinomas (ICG) are uncommon brain neoplasms with extremely rare familial occurrence. Because ICG invades the hypothalamus and/or pituitary, endocrine dysfunction is one of the common determinants of these tumours. We present two brothers with a history of ICG. Patient 1 is a 25-year-old male who suffered from weakness of the right half of his body at the age of 18 years. Cranial MRI revealed a mass lesion in the left thalamus. He underwent neurosurgery, and the tumour was removed completely. Histopathological (HP) and immunohistochemical analyses verified the diagnosis of pure germinoma. He experienced complete remission of the tumour after radiation therapy. At the age of 22 years a diagnosis of isolated growth hormone deficiency (IGHD) was established and GH replacement was initiated. Molecular genetic analysis of the tumour tissue detected the mutation within exon 2 in KRAS gene. Patient 2 is a 20-year-old man who presented with diabetes insipidus at the age of 12 years. MRI detected tumour in the third ventricle and pineal region. After endoscopic tumour biopsy the HP diagnosis was pure germinoma. He received chemotherapy followed by radiotherapy and was treated with GH during childhood. At the age of 18 years GH replacement was reintroduced. A six-month follow-up during the subsequent two years in both brothers demonstrated the IGF1 normalisation with no MRI signs of tumour recurrence. Conclusion: To the best of our knowledge, so far only six reports have been published related to familial ICG. The presented two brothers are the first report of familial ICG case outside Japan. They have been treated successfully with GH therapy in adulthood

Traumatic brain injury: neuropathological, neurocognitive and neurobehavioral sequelae

Traumatic brain injury (TBI) causes substantial neurological disabilities and mental distress. Annual TBI incidence is in magnitude of millions, making it a global health challenge. Categorization of TBI into severe, moderate and mild by scores on the Glasgow coma scale (GCS) is based on clinical grounds and standard brain imaging (CT). Recent research focusedon repeated mild TBI (sport and non-sport concussions) suggests that a considerable number of patients have long-term disabling neurocognitive and neurobehavioral sequelae. These relate to subtle neuronal injury (diffuse axonal injury) visible only by using advanced neuroimaging distinguishing microstructural tissue damage. With advanced MRI protocols better characterization of TBI is achievable. Diffusion tensor imaging (DTI) visualizes white matter pathology, susceptibility weight imaging (SWI) detects microscopic bleeding while functional magnetic resonance imaging (fMRI) provides closer understanding of cognitive disorders etc. However, advanced imaging is still not integrated in the clinical care of patients with TBI. Patients with chronic TBI may experience many somatic disorders, cognitive disturbances and mental complaints. The underlying pathophysiological mechanisms occurring in TBI are complex, brain injuries are highly heterogeneous and include neuroendocrine dysfunctions. Post-traumatic neuroendocrine dysfunctions received attention since the year 2000. Occurrence of TBI-related hypopituitarism does not correlate to severity of the GCS scores. Complete or partial hypopituitarism (isolated growth hormone (GH) deficiency as most frequent) may occur after mild TBI equally as after moderate-to-severe TBI. Many symptoms of hypopituitarism overlap with symptoms occurring in patients with chronic TBI, i.e. they have lower scores on neuropsychological examinations (cognitive disability) and have more symptoms of mental distress (depression and fatigue). The great challenges for the endocrinologist are: (1) detection of hypopituitarism in patients with TBI prospectively (in the acute phase and months to years after TBI), (2) assessment of the extent of cognitive impairment at baseline, and (3) monitoring of treatment effects (alteration of cognitive functioning and mental distress with hormone replacement therapy). Only few studies recently suggest that with growth hormone (rhGH) replacement in patients with chronic TBI and with abnormal GH secretion, cognitive performance may not change while symptoms related to depression and fatigue improve. Stagnation in post-TBI rehabilitation progress is recommended as a signal for clinical suspicion of neuroendocrine dysfunction. This remains a challenging area for more research

Glucoregulation in normal weight schizophrenia patients treated by first generation antipsychotics

Introduction Schizophrenia patients are at greater risk of obesity, diabetes mellitus (DM), lipid abnormalities and cardiovascular disorders. The metabolic complications in patients are associated with several risk factors: family history of DM, lifestyle, smoking, dietary habits, physical inactivity, but also with antipsychotic medication. In literature, most publications have been focused on the effects of the second generation antipsychotics (SGA) on glucose metabolism. However, less attention has been paid to abnormality in glucoregulation, patients with schizophrenia treated with the first generation antipsychotics (FGA). Objective The present study evaluated glucose metabolism in normal weight schizophrenia patients treated with FGA. METHOD The cross-sectional study included 18 patients (FGA treated) and 20 healthy controls with neither group differences in sex distribution, age, nor in BMI. Inclusion criteria were normal BMI (20-25 kg/m2). The glucose levels, insulin levels and growth hormone levels during oral glucose tolerance test (OGTT) were measured. Results Fasting glucose and insulin levels did not differ significantly between groups. Groups differed in OGTT glucose and insulin peak and area under curve (AUC), level of significance p<0.05 (patients vs. controls: glucose peak 8.3±0.4 vs.6.9±0.5 mmol/l, glucose AUC 758±28 vs. 640±36 mU/l/120 min; insulin peak in patients 92.7±15.6 mU/l; insulin AUC 6060±1016 mU/l/120 min, insulin peak in controls 47.9±6.5 mU/l; insulin AUC 2597±256 mU/l/120 min). Conclusion Patients with schizophrenia, although with normal body mass index, are at high risk of abnormal glucose regulation. Not only SGA increase the risk of impaired glucoregulation and metabolic syndrome, but this may also be due to FGA or schizophrenia per se.

The influence of hyperprolactinemia on coagulation parameters in females with prolactinomas

Introduction. Currently there is little information on the effects of prolactin (PRL) on the coagulation and fibrinolytic systems. Objective. The aim of this study was to evaluate the effects of hypeprolactinemia on the parameters of the hemostatic system and activation of the coagulation system. Methods. We studied PRL levels, body mass index (BMI), values of activated partial thromboplastin time (aPTT), prothrombin time (PT), thrombin time (TT), D-dimer level, von Willebrand factor antigen (vWFAg) and fibrinogen in 15 young female patients with microprolactinomas before and after therapy and in 15 healthy female controls. Results. As expected, pretreatment PRL levels were significantly higher in patients than in controls (140.90±42.87 vs. 12.53±4.05 ng/ml; p<0.001). PT, although still in the normal range, was prolonged in patients with hyperprolactinemia as compared to the control group (13.53±1.39 vs. 12.65±0.53 s; p=0.03) and normalized after therapy (12.69±0.65 vs. 12.65±0.53 s; p=0.88). TT, although in normal range, was significantly shorter in the hypeprolactinemic patients than in the controls (14.34±4.52 vs. 17.21±1.35 s; p<0.025) and after treatment remained significantly shorter than in the controls (15.17±1.55 vs. 17.21±1.35 s; p<0.0001). D-dimer values before treatment in the patients with hyperproplactinemia were above the normal range (239.47±107.93 vs. 131.27±50.64 ng/ml, p=0.002) and decreased to normal values after therapy (239.47±107.93 vs. 146.60±39.15 ng/ml; p<0.001). D-dimer levels correlated with PRL (r=0.30) and the change in serum D-dimer values significantly correlated with the change in PRL levels during therapy (r=0.62). aPTT, vWFAg and fibrinogen were similar in patients and controls. Conclusion. In our study, increased thrombin generation that resulted in elevated D-dimer levels may be one of the contributing factors to the prethrombotic state in patients with hyperprolactinemia. [Projekat Ministarstva nauke Republike Srbije, br. 175033 i br. 174016

Hypopituitarism in five PROP1 mutation siblings: long-lasting natural course and the effects of growth hormone replacement introduction in middle adulthood

Twenty years after the first description of combined hypopituitarism (CPHD) caused by PROP1 mutations, the phenotype of affected subjects is still challenging for clinicians. These patients suffer from pituitary hormone deficits ranging from IGHD to panhypopituitarism. ACTH deficiency usually develops later in life. Pituitary size is variable. PROP1 mutation is the most frequent in familial congenital hypopituitarism (CH). Reports on initiation of hormonal replacement including growth hormone (GH) in adults with CH are scarce. We identified 5 adult siblings with CPHD due to PROP1 mutation (301-302delAG), aged 36-51 years (4 females), never treated for hormone deficiencies. They presented with short stature (SD from - 3.7 to - 4.7), infantile sexual characteristic, moderate abdominal obesity and low bone mineral density in 3 of them. Complete hypopituituitarism was confirmed in three siblings, while two remaining demonstrated GH, TSH, FSH and LH deficiencies. Required hormonal replacement including rhGH was initiated in all patients. After several months necessity for hydrocortisone replacement developed in all patients. After 2 years of continual replacement therapy, BMD and body composition (measured by DXA-dual X-ray absorptiometry) improved in all subjects, most prominently in two younger females and the male sibling. Besides rhGH therapy, these three patients have received sex hormones contributing to the favorable effect. The male sibling was diagnosed with brain glioblastoma two years following complete hormonal replacement. This report provides important experience regarding hormonal replacement, particularly rhGH treatment, in adults with long-term untreated CH. Beneficial effect of such therapy are widely acknowledged, yet these subjects could be susceptible to certain risks of hormonal treatment initiated in adulthood. Careful and continual clinical follow-up is thus strongly advised