The management of nivolumab-induced endocrine immune-related adverse events

Immune-mediated endocrine adverse events induced by nivolumab therapy are related to the activation of the immunological system, and often they affect the pituitary, thyroid, and pancreas leading to hypophysitis, thyroiditis, and diabetes mellitus. The exact pathomechanism of nivolumab-induced endocrinopathy usually remains unknown. The endocrine adverse events are unique when compared to other immune-mediated adverse events because the manifestations are often irreversible and require a life-long hormonal replacement and careful monitoring. Endocrinopathies in patients with disseminated neoplastic disease, often present with non-specific symptoms, making them difficult to diagnose. The cooperation of a clinical oncologist and endocrinologist is crucial for making a correct diagnosis and for inducing appropriate hormone replacement therapy. This attitude may improve prognosis in oncological patients with endocrine complications of immunotherapy. In this article, we present the current data regarding the clinical management of immune-mediated endocrinopathies, including hypophysitis, thyroiditis, and diabetes mellitus.Immune-mediated endocrine adverse events induced by nivolumab therapy are related to the activation of the immunological system, and often they affect the pituitary, thyroid, and pancreas leading to hypophysitis, thyroiditis, and diabetes mellitus. The exact pathomechanism of nivolumab-induced endocrinopathy usually remains unknown. The endocrine adverse events are unique when compared to other immune-mediated adverse events because the manifestations are often irreversible and require a life-long hormonal replacement and careful monitoring. Endocrinopathies in patients with disseminated neoplastic disease, often present with non-specific symptoms, making them difficult to diagnose. The cooperation of a clinical oncologist and endocrinologist is crucial for making a correct diagnosis and for inducing appropriate hormone replacement therapy. This attitude may improve prognosis in oncological patients with endocrine complications of immunotherapy. In this article, we present the current data regarding the clinical management of immune-mediated endocrinopathies, including hypophysitis, thyroiditis, and diabetes mellitus

Hypophysitis, panhypopituitarism, and hypothalamitis in a Scottish terrier dog

A 6-year old male neutered Scottish Terrier was referred with a 1 week history of progressive lethargy and anorexia. Neurological examination localized a lesion to the forebrain and hormonal testing showed panhypopituitarism. Magnetic resonance imaging (MRI) of the brain revealed a rounded, well-defined, suprasellar central mass. The mass was slightly hyperintense to the cortical grey matter on T2-weighted (T2W), hypointense on T1-weighted (T1W) images and without T2* signal void. There was a central fusiform enhancement of the mass after contrast administration which raised the suspicion of a pituitary neoplasm. Rapid deterioration of the dog prevented further clinical investigations. Histopathologic examination revealed a lymphocytic panhypophysitis of unknown origin suspected autoimmune involving the hypothalamus (hypothalamitis). This is a unique case report of a dog presenting with inflammatory hypophysitis and hypothalamitis of suspected autoimmune origin with detailed clinical, MRI, histology and immunohistochemistry findings

Zaburzenia gospodarki węglowodanowej w akromegalii. Czy częstość ich występowania zależy od aktywności choroby oraz czasu trwania objawów?

Introduction: Acromegaly is characterized not only by disabling symptoms, but also by relevant co-morbidities. Insulin resistance, leading to glucose intolerance is one of the most important contributory factors to the cardiovascular mortality in acromegaly. Material and methods: We analysed the records of 220 na&#239;ve patients with acromegaly diagnosed at our Department in the years 1995-2007. Diagnosis of active acromegaly was established on the basis of widely recognized criteria. In each patient glucose and insulin concentrations were assessed when fasting and during the 75 g OGTT. Results: Normoglycaemia existed in 46% of acromegalic patients. Among glucose tolerance abnormalities we found impaired fasting glucose in 19%, impaired glucose tolerance in 15% and overt diabetes mellitus in 20%. There was no statistically significant differences in gender, duration of the disease, basal plasma GH, IGF-1 or fasting insulin concentrations between normoglycaemic patients and those with impairments in glucose tolerance. The groups showed statistically significant differences with respect to age at diagnosis (p < 0.01). There was no significant correlation between GH, IGF-1 concentrations and fasting plasma glucose. There was no correlation between the duration of the disease and fasting plasma glucose. We found a statistically significant correlation between plasma GH, IGF-1 concentrations and HOMA, QUICKI and insulinAUC. Conclusions: The prevalence of diabetes mellitus among acromegalics is much higher than in the general population. The occurrence of glucose tolerance impairments does not depend on the duration of the disease. In patients with acromegaly insulin resistance and hyperinsulinemia are positively correlated with the level of activity of the disease.Wstęp: Akromegalia charakteryzuje się występowaniem nie tylko typowych objawów klinicznych, ale też licznych powikłań prowadzących do przedwczesnej śmierci. Insulinooporność, prowadząca do zaburzeń tolerancji glukozy, uznana jest za istotny czynnik ryzyka występowania incydentów sercowo-naczyniowych u chorych na akromegalię. Materiał i metody: Badaniem retrospektywnym objęto 220 chorych z akromegalią diagnozowanych w Klinice Endokrynologii CMKP w Warszawie w latach 1995-2007. Rozpoznanie akromegalii zostało potwierdzone na podstawie powszechnie uznanych kryteriów. U każdego pacjenta oznaczono glukozę i insulinę na czczo oraz w OGTT. Wyniki: Prawidłową glikemię stwierdzono u 46% pacjentów. U większości, w momencie rozpoznania choroby, występowały zaburzenia gospodarki węglowodanowej: u 19% nieprawidłowa glikemia na czczo, u 15% nieprawidłowa tolerancja glukozy, a u 20% cukrzyca. Pacjenci z normoglikemią oraz z zaburzeniami tolerancji glukozy nie różnili się pod względem płci, czasu trwania objawów, stężeń GH, IGF-1 i insuliny na czczo. Stwierdzono natomiast różnicę pod względem wieku chorych (p < 0.01). Nie wykazano korelacji między stężeniem GH ani IGF-1 a glikemią na czczo. Nie wykazano zależności pomiędzy czasem trwania choroby a glikemią na czczo. Stwierdzono natomiast istotną statystycznie zależność pomiędzy stężeniem GH oraz IGF-1 a wskaźnikami HOMA i QUICKI oraz polem powierzchni pod krzywą dla insuliny. Wnioski: Częstość występowania cukrzycy u chorych z akromegalią jest znacznie wyższa niż w populacji ogólnej. Nie stwierdzono zależności między czasem trwania choroby a nasileniem zaburzeń gospodarki węglowodanowej. U chorych z akromegalią insulinooporność i hiperinsulinemia dodatnio korelują z aktywnością choroby

The Role of Stress in Assessing Life Satisfaction and Self-Efficacy Among Prison Officers

Stress is a major public health concern. It can be observed in all aspects of life, in everyday family life and work life. The focus of this article is work-related stress. Work stress can be observed in any work environment and in all professions. As a complex condition it affects different people in different ways. The study presented in this article was done on a sample of 59 prison officers who volunteered to participate. Among those 59 participants 34 were males and 25 were females aged between 25 to 52. Each participant received a survey to collect general information about the person and included three questionnaires: The Questionnaire of Stress in the Prison Service (KSSW), Generalized Self-Efficacy Scale (GSES), and Satisfaction with Life Scale (SWLS). The questionnaire took approximately 45 minutes. Results turned out to be rather surprising. Findings showedthat job stress of prison officers is not significantly correlated with the amount of time they spend among prisoners. The results also showed that being married or having a partner is not a protective factor against job stress for that sample. Results also showed that negative significant correlation between job stress and life satisfaction and job stress and self-efficacy were only found for particular subscales of KSSW not for the overall levels of stress.Further analysis of the results suggests that the very core of prison officers’ job is the most stressful factor. This is an interesting finding that may be a basis for further research for specific stressors and coping strategies that may help the officers

Postępowanie w przypadku wystąpienia endokrynologicznych działań niepożądanych przy stosowaniu leku niwolumab

Powikłania endokrynne występujące w trakcie immunoterapii nowotworów niwolumabem są związane z aktywacją układu immunologicznego i dotyczą najczęściej gruczołów wydzielania wewnętrznego, takich jak przysadka, tarczyca i trzustka. Dokładny patomechanizm leżący u podstaw endokrynopatii indukowanych niwolumabem pozostaje w większości nieznany. Powikłania endokrynne są wyjątkowe w porównaniu z innymi immunologicznymi działaniami niepożądanymi immunoterapii ze względu na to, że są najczęściej nieodwracalne. Zaburzenia te prowadzą do niedoczynności danego gruczołu, dlatego wymagają u chorego przewlekłej substytucji hormonalnej i systematycznej kontroli laboratoryjnej. Objawy zaburzeń czynności układu endokrynnego u pacjenta z rozsianym procesem nowotworowym bywają niespecyficzne i sprawiają tym samym trudność onkologom w postawieniu właściwego rozpoznania. Współpraca między onkologiem klinicznym a endokrynologiem jest niezbędna zarówno do postawienia właściwego rozpoznania, jak i do wdrożenia odpowiedniej substytucji hormonalnej. Może się przyczynić do poprawy rokowania pacjentów onkologicznych, u których wystąpią powikłania endokrynne immunoterapii. W niniejszym artykule zostanie opisane postępowanie w przypadku najczęstszych endokrynopatii występujących podczas leczenia niwolumabem, do których zalicza się zapalenie przysadki, zapalenie tarczycy i cukrzycę typu 1

Corticotropinoma as the underlying cause of intermittent Cushing’s syndrome in a patient previously diagnosed with primary pigmented nodular adrenocortical disease

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Macro-GH - a clinical entity causing a diagnostic challenge - a case report.

AIM: Presentation of a new case of a patient with macro-GH, that may interfere with different GH assays leading to false-positive results in serum samples. CASE PRESENTATION: A 61-year-old female was referred with a pituitary macroadenoma and elevated growth hormone levels The laboratory tests showed increased fasting GH level, measured by a sandwich chemiluminescence immunoassay (LIAISON® XL) without suppression on oral glucose tolerance test and normal IGF-1. The patient did not have the typical signs and symptoms of acromegaly. The patient underwent a transsphenoidal resection of a pituitary tumor, showing only α-subunit immunostaining. Postoperative GH levels remained elevated. An interference in the determination of GH level was suspected. GH was analyzed by three different immunoassays, UniCel DxI 600, Cobas e411 and hGH-IRMA. Heterophilic antibodies and rheumatoid factor were not detected in serum sample. GH recovery after precipitation with 25% polyethylene glycol (PEG) was 12%. Size-exclusion chromatography confirmed the presence of macro-GH in serum sample. CONCLUSION: If results of laboratory tests are not consistent with the clinical findings, the presence of an interference within immunochemical assays could be suspected. To identify interference caused by the macro-GH, the PEG method and size-exclusion chromatography should be used

Subclinical left ventricular systolic dysfunction in patients with naive acromegaly — assessment with two-dimensional speckle-tracking echocardiography: retrospective study

Introduction: The aim of the study was to evaluate global longitudinal strain (GLS) in patients with naive acromegaly with normal left ventricular (LV) ejection fraction (EF). Material and methods: Forty-three consecutive patients with naive acromegaly with normal LV systolic function as measured by EF, examined from 2008 to 2016, and 52 patients of a control group matched for age and sex underwent two-dimensional speckle-tracking echocardiography to assess GLS. Results: The median GLS was significantly lower in the acromegaly group than in the control group (in %, –16.6 vs. –20.7; p &lt; 0.01). The majority of acromegalic patients (n = 26; 60.5%) had abnormal GLS. Patients with impairment in GLS had a longer median duration of acromegaly symptoms (in years, 10.0 vs. 5.0; p &lt; 0.05) and greater LV thickness (posterior wall in mm, 12.5 vs. 12.0; p &lt; 0.05) compared to those with normal GLS. Patients with abnormal GLS had higher IGF-1 concentration, but without statistical significance. Diabetes mellitus and arterial hypertension, which are more common in acromegaly, were not significant determinants of abnormal GLS. The mean left ventricular mass index (LVMI) was increased in the acromegaly group compared to controls (in g/m2, 136 vs. 97; p &lt; 0.01). There wasa significant negative correlation between LVMI and GLS (R = –0.47; p &lt; 0.01). Conclusions: Naive acromegalic patients presented abnormal GLS, which indicates subclinical systolic dysfunction in these patients. It has not been proven that arterial hypertension and diabetes mellitus are significant determinants of abnormal GLS