The occurrence of malignant thyroid lesions in patients after radioiodine treatment due to benign thyroid diseases

Wstęp: Leczenie radiojodem (RT, radioiodine treatment) chorób łagodnych tarczycy jest uznaną, bezpieczną i skuteczną metodą. W grupie chorych po RT, pozostających pod wieloletnią obserwacją autorów pracy, czasami zdarzały się przypadki zmian nowotworowych w tarczycy. Postanowiono ocenić jak często, mimo wykluczenia zmian złośliwych w tarczycy przed leczeniem, może się to zdarzyć w dłuższym okresie obserwacji. Materiał i metody: Grupa 4314 chorych (7438 osobolat) po RT pozostawała następnie pod obserwacją od 1-8 lat (śr. 20,69 miesięcy). W trakcie badań kontrolnych, oprócz oceny czynności tarczycy, wykonywano między innymi biopsję aspiracyjną cienkoigłową (BAC) zmian ogniskowych w tarczycy lub zmian na szyi, do której kwalifikowano ultrasonograficznie lub klinicznie (pojawienie się zmiany palpacyjnej). Pacjentów z nieprawidłowym BAC analizowano i weryfikowano histopatologicznie. Wyniki: U 12 z 4314 (0,27%) chorych stwierdzono w BAC zmiany podejrzane. Zmiany w tarczycy znaleziono u 9 osób (8 K, 1 M) w wieku 46-73 lat (śr. wieku 56 lat), 3-57 miesięcy po RT. Raka brodawkowatego stwierdzono u dwóch osób, guz z komórek Hürthle’a u jednej osoby, cytologicznie podejrzane komórki u dwóch osób (histopatologicznie zmiany łagodne). Dwie chore nie zgodziły się na leczenie operacyjne: jedna z podejrzeniem raka brodawkowatego, a druga z komórkami cytologicznie podejrzanymi w BAC. Guzek pęcherzykowy był podejrzany u 2 chorych: o jednej z nich nie ma danych, drugi chory został zdyskwalifikowany do leczenia operacyjnego tarczycy z powodu współistniejącego rozpoznania raka płuca. U pozostałych 3 osób stwierdzono zmiany przerzutowe w okolicznych węzłach chłonnych z powodu innych nowotworów. Wnioski: Zmiany nowotworowe w tarczycy u pacjentów po RT z powodu zmian łagodnych zdarzają się sporadycznie, ale wskazana jest okresowa ocena kliniczna i ultrasonograficzna tych chorych. (Endokrynol Pol 2010; 61 (5): 454-457)Introduction: Radioiodine treatment (RT) of benign thyroid diseases is a well-known, safe, and effective treatment. In a group of patients after RT, who remained in long-term follow-up, sporadic cases of malignant thyroid lesions occurred. The aim of the study was to estimate how often it happened despite the exclusion of malignancy before RT. Material and method: A group of 4314 patients (7438 person-years) underwent RT and subsequently were followed-up for 1-8 years (mean 20.69 months). Apart from thyroid function estimation, if needed, fine needle aspiration biopsy (FNAB) of the thyroid or neck focal lesions was performed based on ultrasonographic or clinical examination. Patients with pathological FNAB were analyzed and histopathologically verified. Results: In 12 out of 4314 cases (0.27%) suspicious FNAB results were found. Suspicious thyroid lesion results were found in 9 patients (8 F, 1 M), aged 46-73 (average 56 years) followed up for 3-57 months after RT: papillary cancer in two patients, Hürthle cell tumour in one patient, and suspicious cells in two patients (with benign lesions on postoperative histopathology). Two patients refused surgery (a suspicion of papillary cancer in one case and suspicious cells in FNAB in the second case). A follicular tumour in FNAB was suspected in two cases (no data about the first, and the second with lung cancer was not operable). In the remaining 3 cases FNAB revealed lymph node metastases due to other cancers. Conclusions: Malignant thyroid lesions in patients after RT due to benign thyroid diseases are seldom detected. However, periodical clinical and ultrasonographic evaluation is recommended. (Pol J Endocrinol 2010; 61 (5): 454-457

The diagnostic value of dual-phase SPECT/CT scintigraphy based on transport kinetics of 99mTc-sestamibi confirmed with histopathological findings in patients with secondary hyperparathyroidism — practical consideration

BACKGROUND: Dual phase 99mTc-sestamibi SPECT/CT preoperative parathyroid scintigraphy (PPS) is seldom discussedin terms of the transport kinetics of the tracer.Objectives: To assess the relationship between the characteristic type of tracer transport in particular PPS and histopathologicalfindings in patients with secondary hyperparathyroidism (sHPT).MATERIAL AND METHODS: The study comprised 27 patients (13 females and 14 males) with sHPT. Based on tracer accumulationin early phase (EP) and delayed phase (DP), the following types of accumulation for PPS(+) lesions were identified: EP(–)/DP(+) (type I), EP(+)/DP(+) (type II), EP(+)/DP(–) (type III). EP(–)/DP(–) (type IV) lesions constituted PPS(–) group invisible inSPECT/CT. Overall, 69 lesions 59 PPS(+) and 10 PPS(–) were evaluated histopathologically.RESULTS: Among SPECT/CT PPS(+), types I, II and III occurred in 9 (15%), 49 (83%), and 1 (2%) lesions, respectively. Thefrequency of histopathological diagnosis of normal and abnormal (APG — adenoma or hyperplasia) parathyroid gland, as wellas non-parathyroid (thyroid, lymph nodes, or fat) lesions differed significantly between type I, II, and III lesions (p = 0.036).APG histopathological diagnosis was significantly more frequent in lesions with type II uptake than in lesions with type I uptake(76% vs. 33%, p = 0.0197). Type II lesions had significantly higher odds for histopathological diagnosis of APG or NPG thantype IV, PPS(–) lesions [odds ratio = 13.1 (95% CI: 2.75 to 63.27)].CONCLUSIONS: For SHP patients evaluated with SPECT/CT PPS accumulation type I is a weak premise for surgeon to findparathyroid pathology. Only persistent 99mTc-sestamibi accumulation in both phases - equivocal with accumulation type II— effectively differentiates parathyroid and non-parathyroid lesions as well as indicates with high probability the presence ofadenoma or hyperplasia. Type III consistent with washout pattern is rare in sHPT

Occurrence of malignant lesions in patients referred to 131I therapy due to benign thyroid diseases

Wstęp: Leczenie 131I łagodnych chorób tarczycy można stosować po wykluczeniu występowania patologii wymagającej zabiegu operacyjnego - jest to najczęściej nowotwór lub jego podejrzenie. Celem pracy była analiza częstości współwystępowania nowotworów tarczycy u pacjentów kierowanych do leczenia 131I z powodu nadczynności w przebiegu łagodnych chorób tarczycy. Materiał i metody: W latach 2000-2005 3663 pacjentów skierowano do leczenia 131I. Przed leczeniem 131I u wszystkich pacjentów wykonano: ocenę czynności tarczycy, jodochwytność, scyntygram, USG, a u 505 (13,8%) biopsję aspiracyjną cienkoigłową (BAC) z badaniem cytologicznym. Dawkę leczniczą 131I podano 3083 (84,2%) pacjentom. Wyniki: U 8 (0,22% całości i 1,6% spośród tych, którym wykonano BAC) pacjentek w trakcie badań wstępnych stwierdzono zmianę nowotworową lub jej podejrzenie. Wszystkie chore, z wyjątkiem jednej, nie były wcześniej badane cytologicznie, a średnica zmian wynosiła 6-28 mm. W badaniu cytologicznym stwierdzono: u 3 chorych raka brodawkowatego, u 3 - guza pęcherzykowego, u 1 - guz z komórek Hürthle’a, a w jednym przypadku, ze względu na obecność podejrzanych komórek, zalecono weryfikację histopatologiczną. U 6 pacjentek chorobą podstawową było wole wieloguzkowe nadczynne, a u 2 - choroba Gravesa-Basedowa. Wnioski: 1. Powyższe dane wskazują na konieczność dużej czujności onkologicznej medyków nuklearnych mimo wstępnej już selekcji chorych wykonanej przez lekarzy kierujących do leczenia 131I. 2. Wykonywanie BAC jest bardzo ważnym elementem kwalifikacji do leczenia radiojodem. 3. Scyntygrafia tarczycy jest pomocna przy wyborze miejsca do BAC.Introduction: 131I therapy should be performed after exclusion of any morphological pathology that needs surgery - usually malignancy or its suspicion. The aim of the study was to evaluate the range of this problem in patients considered for radioiodine therapy due to benign thyroid diseases. Material and methods: In 2000-2005 year 3663 patients with hyperthyreosis were referred to 131I therapy. All patients were subjected to routine procedure which comprised of thyroid function assesment, radioiodine uptake, thyroid scan, ultrasound examination. In 505 (13.8%) patients according to indications fine needle biopsy (FNAB) with cytological examination was performed. 131I therapy dose was given to 3083 (84.2%) patients. Results: Eight patients (1.6%) were positive or with suspicion of malignancy on FNAB. All but one had no cytological examination before referral. The diameter of the lesions ranged from 6 to 28 mm. Cytological diagnosis was: in 3 patients - ca papillare, in 3 - follicular tumour, in 1 - Hürthle’a cell tumour, and in one patient histopathological examination was required without definitive cytological diagnosis. In six patients primary diagnosis was toxic nodular goiter, in three patients Graves’ disease. Conclusion: 1. Obtained data underline the need for bigger malignancy alert of nuclear medicine physicians during qualification of patients for 131I treatment despite of patients preselection by referring doctors. 2. Performing FNAB is a very important part of qualification to radioiodine treatment. 3. Thyroid scan is supportive in choosing a proper place for FNAB

The application of SPECT/CT scintigraphy with MIBI-Tc99m in the diagnosis of thyroid nodules - a preliminary report

Wstęp: Niediagnostyczne badania cytologiczne (FNAB, fine needle aspiration biopsy) guzków tarczycy lub inne przyczyny utrudniające podjęcie decyzji o leczeniu operacyjnym tarczycy, takie jak wiek pacjenta lub zawansowanie choroby towarzyszące, stanowią poważną przyczynę w ostatecznym wyborze posterowania, szczególnie jeżeli nie ma jednoznacznych danych wskazujących na obecność zmiany nowotworowej. Dodatkowym sposobem wyjaśnienia charakteru zmiany jest badanie radioizotopowe z MIBI-Tc99m. Gromadzenie MIBI jest interpretowane jako sygnał zwiększający ryzyko złośliwości, zwłaszcza gdy utrzymuje się przez dłuższy czas. W pracy postanowiono ocenić przydatność badania scyntygraficznego SPECT/CT z MIBI-Tc99m metodą wymywania w relacji do wyników badania histopatologicznego. Materiał i metody: W 2009 roku wykonano u 12 chorych w wieku 54-75 (śr. 63,5) lat badania scyntygraficzne tarczycy planarne oraz SPECT/CT z MIBI-Tc99m, poprzedzone o badanie wymywania. Wyliczono wskaźniki wymywania i wskaźniki guz/tło w obrazach wczesnych i późnych. Chorzy ze wzmożonym wychwytem znacznika byli operowani i badani histopatologicznie. Wyniki: Wzmożone gromadzenie MIBI-Tc99m obserwowano u 8 pacjentów (10 zmian), a brak gromadzenia (prawidłowy wynik) u 4 (5 zmian). Na 15 badań w 13 przypadkach zaobserwowano wymywanie się radiofarmaceutyku ze zmiany, które sugeruje łagodny charakter zmiany. Operowano trzech chorych ze zmianami gromadzącymi MIBI-Tc99m w badaniu scyntygraficznym, niemniej wynik badania histopatologicznego był we wszystkich przypadkach prawidłowy. Zaobserwowano, że interpretacja obrazów tarczycy SPECT/CT z MIBI-Tc99m uzyskiwanych metodą wymywania jest łatwiejsza i czytelniejsza niż w badaniu planarnym. U 3 z pozostałych 5 chorych dane kliniczne nie zwiększają obecnie podejrzenia raka, u 2 nie kontynuowano obserwacji. Wnioski: Ocena scyntygraficzna tarczycy wykonywana z zastosowaniem SPECT/CT z MIBI-Tc99m metodą wymywania może być pomocna w diagnostyce różnicowej guzków tarczycy. (Endokrynol Pol 2010; 61 (5): 422-426)Introduction: Thyroid cancer diagnosis is based mainly on fine needle aspiration biopsy (FNAB) performed under ultrasonography guidance. Questions arise in cases of an inconclusive FNAB result - when there is no clear evidential data to support the existence of a malignant lesion or when there are any other reasons which make the decision process difficult, such as the patient’s age or coexisting diseases. To clarify this issue the patient should be encouraged to undergo surgery treatment or to be followed up. Thyroid scintigraphy with an oncophilic tracer such as MIBI-Tc99m may be helpful. Material and methods: The study comprised a group of 12 patients, aged 54-75 (av. 63.5) years, who, in 2009, underwent planar and SPECT/CT thyroid scintigraphy with MIBI-Tc99m using washout method. The tumour/background ratio in early and delayed images was calculated and the wash-out ratio was estimated. Patients with increased focal lesion uptake were operated on and the lesions were histopathologically verified. Results: Abnormal scintigraphy results were obtained in 8 patients (10 lesions) and normal results in 4 patients (5 lesions). Out of 15 studies, in 13 cases the washout from the lesion was observed within 2 hours. It was noticed that the images obtained with SPECT/CT washout method were clearer and easier to read in comparison to planar studies. Three patients with an abnormal results underwent surgery and had benign histopathology results after the operation, in 3 patients the observation is being confirmed without any increase in malignancy suspicions, and 2 were lost for observation. Conclusions: Our preliminary results do support the use of MIBI-Tc99m in the evaluation of indeterminate thyroid nodules. To validate the hypothesis that MIBI-Tc99m may be used to exclude malignancy in lesions indeterminate by FNAB we propose to use SPECT-CT derived images and standardized evaluation criteria. (Pol J Endocrinol 2010; 61 (5): 422-426

Secretion of beta-human chorionic gonadotropin by non-small cell lung cancer: a case report

<p>Abstract</p> <p>Introduction</p> <p>We describe a case of non-small cell lung cancer that was found to stain positive for beta-human chorionic gonadotropin on immunohistochemistry. Only a few case reports have described lung cancers that secrete beta-human chorionic gonadotropin.</p> <p>Case presentation</p> <p>A 68-year-old Caucasian man presented with symptoms of weakness, fatigue and weight loss for the past two months. On examination, he was found to have generalized lymphadenopathy, and radiologic workup revealed numerous metastases in the lungs, liver and kidneys. Biopsy of the supraclavicular lymph node revealed metastatic large cell lung cancer with beta-human chorionic gonadotropin hormone positivity. The serum beta-human chorionic gonadotropin level was 11,286 mIU/ml (upper limit of normal, 0.5 mIU/ml in non-pregnant females). He was diagnosed with stage 4 lung non-small cell lung cancer. The patient refused chemotherapy. He was discharged home with hospice care.</p> <p>Conclusion</p> <p>The markedly elevated serum values of beta-human chorionic gonadotropin initially prompted the medical team to investigate germinal tumors. In the presence of a negative testicular ultrasound, workup was performed to find an extratesticular source of the tumor. Finally, the diagnosis was made with a tissue biopsy. This case illustrates that atypical markers can be seen in many cancers, emphasizing the role of immunohistochemistry and tissue biopsy in establishing the diagnosis.</p

Insulin-Like Growth Factor (IGF) Binding Protein-2, Independently of IGF-1, Induces GLUT-4 Translocation and Glucose Uptake in 3T3-L1 Adipocytes

Insulin-like growth factor binding protein-2 (IGFBP-2) is the predominant IGF binding protein produced during adipogenesis and is known to increase the insulin-stimulated glucose uptake (GU) in myotubes. We investigated the IGFBP-2-induced changes in basal and insulin-stimulated GU in adipocytes and the underlying mechanisms. We further determined the role of insulin and IGF-1 receptors in mediating the IGFBP-2 and the impact of IGFBP-2 on the IGF-1-induced GU. Fully differentiated 3T3-L1 adipocytes were treated with IGFBP-2 in the presence and absence of insulin and IGF-1. Insulin, IGF-1, and IGFBP-2 induced a dose-dependent increase in GU. IGFBP-2 increased the insulin-induced GU after long-term incubation. The IGFBP-2-induced impact on GU was neither affected by insulin or IGF-1 receptor blockage nor by insulin receptor knockdown. IGFBP-2 significantly increased the phosphorylation of PI3K, Akt, AMPK, TBC1D1, and PKCζ/λ and induced GLUT-4 translocation. Moreover, inhibition of PI3K and AMPK significantly reduced IGFBP-2-stimulated GU. In conclusion, IGFBP-2 stimulates GU in 3T3-L1 adipocytes through activation of PI3K/Akt, AMPK/TBC1D1, and PI3K/PKCζ/λ/GLUT-4 signaling. The stimulatory effect of IGFBP-2 on GU is independent of its binding to IGF-1 and is possibly not mediated through the insulin or IGF-1 receptor. This study highlights the potential role of IGFBP-2 in glucose metabolism

Gallbladder adenocarcinoma with human chorionic gonadotropin: a case report and review of literature

<p>Abstract</p> <p>Background</p> <p>The case of adenocarcinoma with human chorionic gonadtropin (HCG), primary in the male gallbladder, is extremely rare. A Medline search has shown only a few similar cases reported.</p> <p>Methods</p> <p>We herein describe a case of primary gallbladder adenocarcinoma associated by ectopic HCG positive tumor cells in a 79-year-old male.</p> <p>Results</p> <p>Pathological examination showed a mixture of moderately and poorly differentiated adenocarcinoma with ectopic HCG and placental alkaline phosphatase (PlAP) in tumor cells, though the increase of serum or urinary HCG secretion was not confirmed. The literatures were also reviewed.</p> <p>Conclusions</p> <p>A case of gallbladder cancer with ectopic HCG production is quite rare in the literature, though many similar cases in other site, especially in GI tract, are reported. Embryological consideration suggests the increased frequency of similar cases more than being thought now.</p

Practical recommendations for the management of diabetes in patients with COVID-19

Diabetes is one of the most important comorbidities linked to the severity of all three known human pathogenic coronavirus infections, including severe acute respiratory syndrome coronavirus 2. Patients with diabetes have an increased risk of severe complications including Adult Respiratory Distress Syndrome and multi-organ failure. Depending on the global region, 20-50% of patients in the coronavirus disease 2019 (COVID-19) pandemic had diabetes. Given the importance of the link between COVID-19 and diabetes, we have formed an international panel of experts in the field of diabetes and endocrinology to provide some guidance and practical recommendations for the management of diabetes during the pandemic. We aim to briefly provide insight into potential mechanistic links between the novel coronavirus infection and diabetes, present practical management recommendations, and elaborate on the differential needs of several patient groups

Early detection of diabetic kidney disease by urinary proteomics and subsequent intervention with spironolactone to delay progression (PRIORITY): a prospective observational study and embedded randomised placebo-controlled trial

Background: Microalbuminuria is an early sign of kidney disease in people with diabetes and indicates increased risk of cardiovascular disease. We tested whether a urinary proteomic risk classifier (CKD273) score was associated with development of microalbuminuria and whether progression to microalbuminuria could be prevented with the mineralocorticoid receptor antagonist spironolactone. Methods: In this multicentre, prospective, observational study with embedded randomised controlled trial (PRIORITY), we recruited people with type 2 diabetes, normal urinary albumin excretion, and preserved renal function from 15 specialist centres in ten European countries. All participants (observational cohort) were tested with the CKD273 classifier and classified as high risk (CKD273 classifier score &gt;0·154) or low risk (≤0·154). Participants who were classified as high risk were entered into a randomised controlled trial and randomly assigned (1:1), by use of an interactive web-response system, to receive spironolactone 25 mg once daily or matched placebo (trial cohort). The primary endpoint was development of confirmed microalbuminuria in all individuals with available data (observational cohort). Secondary endpoints included reduction in incidence of microalbuminuria with spironolactone (trial cohort, intention-to-treat population) and association between CKD273 risk score and measures of impaired renal function based on estimated glomerular filtration rate (eGFR; observational cohort). Adverse events (particularly gynaecomastia and hyperkalaemia) and serious adverse events were recorded for the intention-to-treat population (trial cohort). This study is registered with the EU Clinical Trials Register (EudraCT 20120-004523-4) and ClinicalTrials.gov (NCT02040441) and is completed. Findings: Between March 25, 2014, and Sept 30, 2018, we enrolled and followed-up 1775 participants (observational cohort), 1559 (88%) of 1775 participants had a low-risk urinary proteomic pattern and 216 (12%) had a high-risk pattern, of whom 209 were included in the trial cohort and assigned to spironolactone (n=102) or placebo (n=107). The overall median follow-up time was 2·51 years (IQR 2·0–3·0). Progression to microalbuminuria was seen in 61 (28%) of 216 high-risk participants and 139 (9%) of 1559 low-risk participants (hazard ratio [HR] 2·48, 95% CI 1·80–3·42; p&lt;0·0001, after adjustment for baseline variables of age, sex, HbA1c, systolic blood pressure, retinopathy, urine albumin-to-creatinine ratio [UACR], and eGFR). Development of impaired renal function (eGFR &lt;60 mL/min per 1·73 m2) was seen in 48 (26%) of 184 high-risk participants and 119 (8%) of 1423 low-risk participants (HR 3·50; 95% CI 2·50–4·90, after adjustment for baseline variables). A 30% decrease in eGFR from baseline (post-hoc endpoint) was seen in 42 (19%) of 216 high-risk participants and 62 (4%) of 1559 low-risk participants (HR 5·15, 95% CI 3·41–7·76; p&lt;0·0001, after adjustment for basline eGFR and UACR). In the intention-to-treat trial cohort, development of microalbuminuria was seen in 35 (33%) of 107 in the placebo group and 26 (25%) of 102 in the spironolactone group (HR 0·81, 95% CI 0·49–1·34; p=0·41). In the safety analysis (intention-to-treat trial cohort), events of plasma potassium concentrations of more than 5·5 mmol/L were seen in 13 (13%) of 102 participants in the spironolactone group and four (4%) of 107 participants in the placebo group, and gynaecomastia was seen in three (3%) participants in the spironolactone group and none in the placebo group. One patient died in the placebo group due to a cardiac event (considered possibly related to study drug) and one patient died in the spironolactone group due to cancer, deemed unrelated to study drug. Interpretation: In people with type 2 diabetes and normoalbuminuria, a high-risk score from the urinary proteomic classifier CKD273 was associated with an increased risk of progression to microalbuminuria over a median of 2·5 years, independent of clinical characteristics. However, spironolactone did not prevent progression to microalbuminuria in high-risk patients. Funding: European Union Seventh Framework Programme