Related Disciplines > Oncology
You are looking at 61 - 70 of 138 items
Diabetes and Metabolism, Garvan Institute of Medical Research, Sydney, New South Wales, Australia
Search for other papers by Shivani Patel in
Google Scholar
PubMed
St Vincent’s Clinical School, UNSW Sydney, Darlinghurst, New South Wales, Australia
Search for other papers by Venessa Chin in
Google Scholar
PubMed
Diabetes and Metabolism, Garvan Institute of Medical Research, Sydney, New South Wales, Australia
St Vincent’s Clinical School, UNSW Sydney, Darlinghurst, New South Wales, Australia
Search for other papers by Jerry R Greenfield in
Google Scholar
PubMed
Summary
Durvalumab is a programmed cell death ligand 1 inhibitor, which is now approved in Australia for use in non-small-cell lung and urothelial cancers. Autoimmune diabetes is a rare immune-related adverse effect associated with the use of immune checkpoint inhibitor therapy. It is now being increasingly described reflecting the wider use of immune checkpoint inhibitor therapy. We report the case of a 49-year-old female who presented with polyuria, polydipsia and weight loss, 3 months following the commencement of durvalumab. On admission, she was in severe diabetic ketoacidosis with venous glucose: 20.1 mmol/L, pH: 7.14, bicarbonate 11.2 mmol/L and serum beta hydroxybutyrate: >8.0 mmol/L. She had no personal or family history of diabetes or autoimmune disease. Her HbA1c was 7.8% and her glutamic acid decarboxylase (GAD) antibodies were mildly elevated at 2.2 mU/L (reference range: <2 mU/L) with negative zinc transporter 8 (ZnT8) and islet cell (ICA) antibodies. Her fasting C-peptide was low at 86 pmol/L (reference range: 200–1200) with a corresponding serum glucose of 21.9 mmol/L. She was promptly stabilised with an insulin infusion in intensive care and discharged on basal bolus insulin. Durvalumab was recommenced once her glycaemic control had stabilised. Thyroid function tests at the time of admission were within normal limits with negative thyroid autoantibodies. Four weeks post discharge, repeat thyroid function tests revealed hypothyroidism, with an elevated thyroid-stimulating hormone (TSH) at 6.39 mIU/L (reference range: 0.40–4.80) and low free T4: 5.9 pmol/L (reference range: 8.0–16.0). These findings persisted with repeat testing despite an absence of clinical symptoms. Treatment with levothyroxine was commenced after excluding adrenal insufficiency (early morning cortisol: 339 nmol/L) and hypophysitis (normal pituitary on MRI).
Learning points:
-
Durvalumab use is rarely associated with fulminant autoimmune diabetes, presenting with severe DKA.
-
Multiple endocrinopathies can co-exist with the use of a single immune checkpoint inhibitors; thus, patients should be regularly monitored.
-
Regular blood glucose levels should be performed on routine pathology on all patients on immune checkpoint inhibitor.
-
Clinician awareness of immunotherapy-related diabetes needs to increase in an attempt to detect hyperglycaemia early and prevent DKA.
Unit of Endocrinology, Department of Medical Specialties, Azienda Ospedaliero-Universitaria di Modena, Ospedale Civile di Baggiovara, Modena, Italy
Search for other papers by C Greco in
Google Scholar
PubMed
Unit of Endocrinology, Department of Medical Specialties, Azienda Ospedaliero-Universitaria di Modena, Ospedale Civile di Baggiovara, Modena, Italy
Search for other papers by G Brigante in
Google Scholar
PubMed
Search for other papers by E Taliani in
Google Scholar
PubMed
Search for other papers by S Corrado in
Google Scholar
PubMed
Unit of Endocrinology, Department of Medical Specialties, Azienda Ospedaliero-Universitaria di Modena, Ospedale Civile di Baggiovara, Modena, Italy
Search for other papers by M Simoni in
Google Scholar
PubMed
Search for other papers by B Madeo in
Google Scholar
PubMed
Summary
A 74-year-old man was referred to the Endocrinology Unit because of multinodular goiter. The dominant nodule (1.7 × 1.9 × 2.4 cm), at the medium-superior third of the left lobe, was inhomogeneously hypoechoic, with irregular margins, macrocalcifications and intranodular vascularization. Fine-needle aspiration biopsy (FNAB) was performed. The cytological diagnosis was TIR 2, benign, according to the 2013 Italian thyroid cytology classification system. Moderately high serum calcitonin (s-Ct) (61.5 pg/mL, n.r. 0–7.5) and normal CEA were detected. The Ct level in FNAB wash-out fluid (Ct-FNAB) was 1450 pg/mL. Based on s-Ct and Ct-FNAB levels, patient underwent total thyroidectomy. Macroscopically, a dominant circumscribed nodule of 2 ecm was described; the histological and immunohistochemical features identified medullary thyroid carcinoma (MTC) with paraganglioma (PG)-like pattern positive for Ct, CEA and chromogranin and negative for S-100 sustentacular cells (SC). Moreover, papillary carcinoma of 3 mm in the right lobe was also associated. No areas of hyperaccumulation of the tracer were documented at Ga68 PET/CT. No RET-proto-oncogene mutations were found. Post-surgery s-Ct levels were within normal range (4 pg/mL). Two years after thyroidectomy, the patient is still disease-free. We reported a case of sporadic and rare variant of MTC: this is the ninth described case of PG-like MTC. In this case, cytologically benign, the clinical suspicion arose from high Ct values at FNAB wash-out fluid. Even if clinical behavior of this variant seems indolent, additional studies are necessary to understand prognoses and predictive factors.
Learning points:
-
Several unusual histological variants of medullary thyroid carcinoma (MTC) have been described such as spindle cell, giant cell, clear cell, melanotic, squamous, angiosarcoma-like variants; even rarer is the paraganglioma (PG)-like pattern.
-
We here describe a case of medullary PG-like thyroid carcinoma in a 74-year-old man. This is a rare histological variant of MTC hardly diagnosed by cytology, since immunohistochemical investigations are necessary.
-
Measurement of calcitonin both in serum and in wash-out fluid from fine-needle aspiration could be an additional tool for an early and non-invasive identification of these variants.
Search for other papers by Karen Decaestecker in
Google Scholar
PubMed
Search for other papers by Veerle Wijtvliet in
Google Scholar
PubMed
Search for other papers by Peter Coremans in
Google Scholar
PubMed
Search for other papers by Nike Van Doninck in
Google Scholar
PubMed
Summary
ACTH-dependent hypercortisolism is caused by an ectopic ACTH syndrome (EAS) in 20% of cases. We report a rare cause of EAS in a 41-year-old woman, presenting with clinical features of Cushing’s syndrome which developed over several months. Biochemical tests revealed hypokalemic metabolic alkalosis and high morning cortisol and ACTH levels. Further testing, including 24-hour urine analysis, late-night saliva and low-dose dexamethasone suppression test, confirmed hypercortisolism. An MRI of the pituitary gland was normal. Inferior petrosal sinus sampling (IPSS) revealed inconsistent results, with a raised basal gradient but no rise after CRH stimulation. Additional PET-CT showed intense metabolic activity in the left nasal vault. Biopsy of this lesion revealed an unsuspected cause of Cushing’s syndrome: an olfactory neuroblastoma (ONB) with positive immunostaining for ACTH. Our patient underwent transnasal resection of the tumour mass, followed by adjuvant radiotherapy. Normalisation of cortisol and ACTH levels was seen immediately after surgery. Hydrocortisone substitution was started to prevent withdrawal symptoms. As the hypothalamic–pituitary–axis slowly recovered, daily hydrocortisone doses were tapered and stopped 4 months after surgery. Clinical Cushing’s stigmata improved gradually.
Learning points:
-
Ectopic ACTH syndrome can originate from tumours outside the thoracoabdominal region, like the sinonasal cavity.
-
The diagnostic accuracy of IPSS is not 100%: both false positives and false negatives may occur and might be due to a sinonasal tumour with ectopic ACTH secretion.
-
Olfactory neuroblastoma (syn. esthesioneuroblastoma), named because of its sensory (olfactory) and neuroectodermal origin in the upper nasal cavity, is a rare malignant neoplasm. It should not be confused with neuroblastoma, a tumour of the sympathetic nervous system typically occurring in children.
-
If one criticises MRI of the pituitary gland because of ACTH-dependent hypercortisolism, one should take a close look at the sinonasal field as well.
Search for other papers by Isabella Lupi in
Google Scholar
PubMed
Search for other papers by Alessandro Brancatella in
Google Scholar
PubMed
Search for other papers by Mirco Cosottini in
Google Scholar
PubMed
Search for other papers by Nicola Viola in
Google Scholar
PubMed
Search for other papers by Giulia Lanzolla in
Google Scholar
PubMed
Search for other papers by Daniele Sgrò in
Google Scholar
PubMed
Search for other papers by Giulia Di Dalmazi in
Google Scholar
PubMed
Search for other papers by Francesco Latrofa in
Google Scholar
PubMed
Search for other papers by Patrizio Caturegli in
Google Scholar
PubMed
Search for other papers by Claudio Marcocci in
Google Scholar
PubMed
Summary
Programmed cell death protein 1/programmed cell death protein ligand 1 (PD-1/PD-L1) and cytotoxic T-lymphocyte antigen 4/B7 (CTLA-4/B7) pathways are key regulators in T-cell activation and tolerance. Nivolumab, pembrolizumab (PD-1 inhibitors), atezolizumab (PD-L1 inhibitor) and ipilimumab (CTLA-4 inhibitor) are monoclonal antibodies approved for treatment of several advanced cancers. Immune checkpoint inhibitors (ICIs)-related hypophysitis is described more frequently in patients treated with anti-CTLA-4; however, recent studies reported an increasing prevalence of anti-PD-1/PD-L1-induced hypophysitis which also exhibits slightly different clinical features. We report our experience on hypophysitis induced by anti-PD-1/anti-PD-L1 treatment. We present four cases, diagnosed in the past 12 months, of hypophysitis occurring in two patients receiving anti-PD-1, in one patient receiving anti-PD-1 and anti-CTLA-4 combined therapy and in one patient receiving anti-PD-L1. In this case series, timing, clinical presentation and association with other immune-related adverse events appeared to be extremely variable; central hypoadrenalism and hyponatremia were constantly detected although sellar magnetic resonance imaging did not reveal specific signs of pituitary inflammation. These differences highlight the complexity of ICI-related hypophysitis and the existence of different mechanisms of action leading to heterogeneity of clinical presentation in patients receiving immunotherapy.
Learning points:
-
PD-1/PD-L1 blockade can induce hypophysitis with a different clinical presentation when compared to CTLA-4 blockade.
-
Diagnosis of PD-1/PD-L1 induced hypophysitis is mainly made on clinical grounds and sellar MRI does not show radiological abnormalities.
-
Hyponatremia due to acute secondary adrenal insufficiency is often the principal sign of PD-1/PD-L1-induced hypophysitis and can be masked by other symptoms due to oncologic disease.
-
PD-1/PD-L1-induced hypophysitis can present as an isolated manifestation of irAEs or be in association with other autoimmune diseases
Search for other papers by Wei Yang in
Google Scholar
PubMed
Search for other papers by David Pham in
Google Scholar
PubMed
Search for other papers by Aren T Vierra in
Google Scholar
PubMed
Search for other papers by Sarah Azam in
Google Scholar
PubMed
Search for other papers by Dorina Gui in
Google Scholar
PubMed
Search for other papers by John C Yoon in
Google Scholar
PubMed
Summary
Ectopic ACTH-secreting pulmonary neuroendocrine tumors are rare and account for less than 5% of endogenous Cushing’s syndrome cases. We describe an unusual case of metastatic bronchial carcinoid tumor in a young woman presenting with unprovoked pulmonary emboli, which initially prevented the detection of the primary tumor on imaging. The source of ectopic ACTH was ultimately localized by a Gallium-DOTATATE scan, which demonstrated increased tracer uptake in a right middle lobe lung nodule and multiple liver nodules. The histological diagnosis was established based on a core biopsy of a hepatic lesion and the patient was started on a glucocorticoid receptor antagonist and a somatostatin analog. This case illustrates that hypercogulability can further aggravate the diagnostic challenges in ectopic ACTH syndrome. We discuss the literature on the current diagnosis and management strategies for ectopic ACTH syndrome.
Learning points:
-
In a young patient with concurrent hypokalemia and uncontrolled hypertension on multiple antihypertensive agents, secondary causes of hypertension should be evaluated.
-
Patients with Cushing’s syndrome can develop an acquired hypercoagulable state leading to spontaneous and postoperative venous thromboembolism.
-
Pulmonary emboli may complicate the imaging of the bronchial carcinoid tumor in ectopic ACTH syndrome.
-
Imaging with Gallium-68 DOTATATE PET/CT scan has the highest sensitivity and specificity in detecting ectopic ACTH-secreting tumors.
-
A combination of various noninvasive biochemical tests can enhance the diagnostic accuracy in differentiating Cushing’s disease from ectopic ACTH syndrome provided they have concordant results. Bilateral inferior petrosal sinus sampling remains the gold standard.
Search for other papers by Teresa M Canteros in
Google Scholar
PubMed
Search for other papers by Valeria De Miguel in
Google Scholar
PubMed
Search for other papers by Patricia Fainstein-Day in
Google Scholar
PubMed
Summary
Severe Cushing syndrome (SCS) is considered an emergency that requires immediate treatment to lower serum cortisol levels. Fluconazole may be considered an alternative treatment in Cushing syndrome when ketoconazole is not tolerated or unavailable. We report a 39-year-old woman with a history of partial pancreaticoduodenectomy due to a periampullary neuroendocrine tumor with locoregional extension. Three years after surgery, she developed liver metastases and was started on 120 mg of lanreotide/month, despite which, liver metastases progressed in the following 6 months. The patient showed extreme fatigue, muscle weakness, delirium, moon face, hirsutism and severe proximal weakness. Laboratory tests showed anemia, hyperglycemia and severe hypokalemia. 24-h urinary free cortisol: 2152 nmol/day (reference range (RR): <276), morning serum cortisol 4883.4 nmol/L (RR: 138–690), ACTH 127.3 pmol/L (RR: 2.2–10). She was diagnosed with ectopic ACTH syndrome (EAS). On admission, she presented with acute upper gastrointestinal tract bleeding and hemodynamic instability. Intravenous fluconazole 400 mg/day was started. After 48 h, her mental state improved and morning cortisol decreased by 25%. The dose was titrated to 600 mg/day which resulted in a 55% decrease in cortisol levels in 1 week, but then had to be decreased to 400 mg/day because transaminase levels increased over 3 times the upper normal level. After 18 days of treatment, hemodynamic stability, lower cortisol levels and better overall clinical status enabled successful bilateral adrenalectomy. This case report shows that intravenous fluconazole effectively decreased cortisol levels in SCS due to EAS.
Learning points:
-
Severe Cushing syndrome can be effectively treated with fluconazole to achieve a significant improvement of hypercortisolism prior to bilateral adrenalectomy.
-
Intravenous fluconazole is an alternative treatment when ketoconazole is not tolerated and etomidate is not available.
-
Fluconazole is well tolerated with mild side effects. Hepatotoxicity is usually mild and resolves after drug discontinuation.
Search for other papers by Tejhmal Rehman in
Google Scholar
PubMed
Search for other papers by Ali Hameed in
Google Scholar
PubMed
Search for other papers by Nigel Beharry in
Google Scholar
PubMed
Search for other papers by J Du Parcq in
Google Scholar
PubMed
Search for other papers by Gul Bano in
Google Scholar
PubMed
Summary
Beta-human chorionic gonadotropin (βhCG) is normally produced by syncytiotrophoblasts of the placenta during pregnancy and aids embryo implantation. However, it is also secreted in varying amounts in non-pregnant conditions commonly heralding a neoplastic process. We present a case of 50-year-old man, who presented with bilateral gynaecomastia with elevated testosterone, oestradiol, suppressed gonadotropins with progressively increasing levels of human chorionic gonadotropin (hCG). Biochemical and radiological investigations including ultrasonography of testes, breast tissue, MRI pituitary and CT scan full body did not identify the source of hCG. FDG PET scan revealed a large mediastinal mass with lung metastasis. Immunostaining and histological analysis confirmed the diagnosis of primary choriocarcinoma of the mediastinum. It is highly aggressive and malignant tumor with poor prognosis. Early diagnosis and management are essential for the best outcome.
Learning points:
-
High βhCG in a male patient or a non-pregnant female suggests a paraneoplastic syndrome.
-
In the case of persistently positive serum hCG, exclude immunoassay interference by doing the urine hCG as heterophilic antibodies are not present in the urine.
-
Non-gestational choriocarcinoma is an extremely rare trophoblastic tumor and should be considered in young men presenting with gynaecomastia and high concentration of hCG with normal gonads.
-
A high index of suspicion and extensive investigations are required to establish an early diagnosis of extra-gonadal choriocarcinoma.
-
Early diagnosis is crucial to formulate optimal management strategy and to minimize widespread metastasis for best clinical outcome.
Search for other papers by Haruhiko Yamazaki in
Google Scholar
PubMed
Search for other papers by Hiroyuki Iwasaki in
Google Scholar
PubMed
Search for other papers by Yoichiro Okubo in
Google Scholar
PubMed
Search for other papers by Nobuyasu Suganuma in
Google Scholar
PubMed
Search for other papers by Katsuhiko Masudo in
Google Scholar
PubMed
Search for other papers by Hirotaka Nakayama in
Google Scholar
PubMed
Search for other papers by Yasushi Rino in
Google Scholar
PubMed
Search for other papers by Munetaka Masuda in
Google Scholar
PubMed
Summary
The objective this study is to report two cases of thyroid gland invasion by upper mediastinal carcinoma. Mediastinal tumors are uncommon and represent 3% of the tumors seen within the chest. In reports on mediastinal masses, the incidence of malignant lesions ranged from 25 to 49%. The thyroid gland can be directly invaded by surrounding organ cancers. We report these cases contrasting them to the case of a thyroid cancer with mediastinal lesions. Case 1 was a 73-year-old woman who was diagnosed with papillary thyroid carcinoma, and she underwent surgery and postoperative radioactive iodine. Case 2 was a 74-year-old man who was diagnosed with non-small-cell lung carcinoma, favor squamous cell carcinoma, and he underwent chemoradiotherapy. Case 3 was a 77-year-old man who was diagnosed a thymic carcinoma based on pathological findings and referred the patient to thoracic surgeons for surgical management. The images of the three cases were similar, and the differential diagnoses were difficult and required pathological examination. Primary thyroid carcinoma and invading carcinoma originating from the adjacent organs need to be distinguished because their prognoses and treatment strategies are different. It is important to properly diagnose them by images and pathological findings.
Learning points:
-
The thyroid gland in the anterior neck can be directly invaded by surrounding organ cancers.
-
Primary thyroid carcinoma and invading carcinoma originating from the adjacent organs need to be distinguished because their prognoses and treatment strategies are different.
-
It is important to properly diagnose by images and pathological findings.
Search for other papers by Zaina Adnan in
Google Scholar
PubMed
Search for other papers by David Nikomarov in
Google Scholar
PubMed
Search for other papers by Michal Weiler-Sagie in
Google Scholar
PubMed
Search for other papers by Noga Roguin Maor in
Google Scholar
PubMed
Summary
Phosphaturic mesenchymal tumor (PMT) represents a rare cause of osteomalacia. The clinical signs and symptoms are vague and these lead to diagnosis delay. In the presence of hypophosphatemia and relatively high urine phosphate excretion, this entity should be taken into consideration in the deferential diagnosis of osteomalacia. In the present article, we report 81-year-old man presented to our clinic for evaluation due to osteopenia. His laboratory results disclosed hypophosphatemia, relatively increased urine phosphate excretion and increased level of intact fibroblast growth factor 23 (FGF23). A 68Gallium DOTATATE PET/CT revealed pathological uptake in the upper aspect of the left shoulder adjacent to the coracoid process. For suspected PMT a wide resection of the tumor was performed and pathological findings were consistent for PMT. Laboratory tests were normalized postoperatively. Reviewing the literature, we had identified 33 reported cases of PMTs among elderly patients age ≥70 years. Unlike previously reported data, where tumors predominantly localized in the lower extremities and pelvis, our search disclosed a high rate of tumor localization (10 cases – 33.3%) in the head with equal number of tumors (14 cases – 42.4%) localized in the head and upper extremity as well as in pelvis and lower extremity. The present case describes unique tumor localization in an elderly patient and our literature search demonstrated for the first time a high rate of tumor localization in the head among this group of patients.
Learning points:
-
PMTs represent a rare entity that should be considered in the differential diagnosis of elderly patients presented with persistent hypophosphatemia.
-
Unlike previously reported data, head and neck tumor localization is frequent among elderly patients.
-
68Gallium-conjugated somatostatin peptide analogs, such as 68Ga-DOTATATE PET/CT demonstrated the greatest sensitivity and specificity for tumor localization in patients with phosphaturic mesenchymal tumors (PMTs).
-
Wide tumor resection using intraoperative ultrasound is of major importance in order to ensure long-term cure.
Centre for Endocrinology, Diabetes and Metabolism, Birmingham Health Partners, Birmingham, UK
Departments of Endocrinology, University Hospital Birmingham NHS Foundation Trust, Birmingham, UK
Search for other papers by Vasileios Chortis in
Google Scholar
PubMed
Search for other papers by Christine J H May in
Google Scholar
PubMed
Departments of Cellular Pathology, University Hospital Birmingham NHS Foundation Trust, Birmingham, UK
Search for other papers by Kassiani Skordilis in
Google Scholar
PubMed
Departments of Endocrinology, University Hospital Birmingham NHS Foundation Trust, Birmingham, UK
Search for other papers by John Ayuk in
Google Scholar
PubMed
Centre for Endocrinology, Diabetes and Metabolism, Birmingham Health Partners, Birmingham, UK
Departments of Endocrinology, University Hospital Birmingham NHS Foundation Trust, Birmingham, UK
Search for other papers by Wiebke Arlt in
Google Scholar
PubMed
Search for other papers by Rachel K Crowley in
Google Scholar
PubMed
Summary
Context
Adrenal incidentalomas (AI) represent an increasingly common problem in modern endocrine practice. The diagnostic approach to AIs can be challenging and occasionally reveals surprising features. Here we describe two rare cases of complex adrenal lesions consisting of phaeochromocytomas with synchronous metastases from extra-adrenal primaries.
Case descriptions
Patient 1 – a 65-year-old gentleman with a newly diagnosed malignant melanoma was found to harbour an adrenal lesion with suspicious radiographic characteristics. Percutaneous adrenal biopsy was consistent with adrenocortical adenoma. After excision of the skin melanoma and regional lymphatic metastases, he was followed up without imaging. Three years later, he presented with abdominal discomfort and enlargement of his adrenal lesion, associated with high plasma metanephrines. Adrenalectomy revealed a mixed tumour consisting of a large phaeochromocytoma with an embedded melanoma metastasis in its core. Patient 2 – a 63-year-old lady with a history of NF-1-related phaeochromocytoma 20 years ago and previous breast cancer presented with a new adrenal lesion on the contralateral side. Plasma normetanephrine was markedly elevated. Elective adrenalectomy revealed an adrenal tumour consisting of chromaffin cells intermixed with breast carcinoma cells.
Conclusions
Adrenal incidentalomas require careful evaluation to exclude metastatic disease, especially in the context of a history of previous malignancy. Adrenal biopsy provides limited and potentially misleading information. Phaeochromocytomas are highly vascularised tumours that may function as a sieve, extracting and retaining irregularly shaped cancer cells, thereby yielding adrenal masses with intriguing dual pathology.
Learning points:
-
Adrenal incidentalomas require careful evaluation focused on exclusion of underlying hormone excess and malignant pathology.
-
Adrenal biopsy can be misleading and should only be considered in select cases.
-
Phaeochromocytomas harbouring intratumoural metastases from other, extra-adrenal primary malignancies represent rare pathological entities that highlight the complexities that can be presented by adrenal tumours.