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Open access

Shamaila Zaman, Bijal Patel, Paul Glynne, Mark Vanderpump, Ali Alsafi, Sairah Khan, Rashpal Flora, Fausto Palazzo and Florian Wernig

Summary

Ectopic adrenocorticotropic hormone (ACTH) production is an uncommon cause of Cushing’s syndrome and, rarely, the source can be a phaeochromocytoma. A 55-year-old man presented following an episode of presumed gastroenteritis with vomiting and general malaise. Further episodes of diarrhoea, joint pains and palpitations followed. On examination, he was hypertensive with no clinical features to suggest hypercortisolaemia. He was subsequently found to have raised plasma normetanephrines of 3.98 nmol/L (NR <0.71) and metanephrines of 0.69 nmol/L (NR <0.36). An adrenal CT showed a 3.8 cm right adrenal nodule, which was not MIBG-avid but was clinically and biochemically consistent with a phaeochromocytoma. He was started on alpha blockade and referred for right adrenalectomy. Four weeks later, on the day of admission for adrenalectomy, profound hypokalaemia was noted (serum potassium 2.0 mmol/L) with non-specific ST-segment ECG changes. He was also diagnosed with new-onset diabetes mellitus (capillary blood glucose of 28 mmol/L). He reported to have gained weight and his skin had become darker over the course of the last 4 weeks. Given these findings, he underwent overnight dexamethasone suppression testing, which showed a non-suppressed serum cortisol of 1099 nmol/L. Baseline serum ACTH was 273 ng/L. A preliminary diagnosis of ectopic ACTH secretion from the known right-sided phaeochromocytoma was made and he was started on metyrapone and insulin. Surgery was postponed for 4 weeks. Following uncomplicated laparoscopic adrenalectomy, the patient recovered with full resolution of symptoms.

Learning points:

  • Phaeochromocytomas are a rare source of ectopic ACTH secretion. A high clinical index of suspicion is therefore required to make the diagnosis.
  • Ectopic ACTH secretion from a phaeochromocytoma can rapidly progress to severe Cushing’s syndrome, thus complicating tumour removal.
  • Removal of the primary tumour often leads to full recovery.
  • The limited literature suggests that the presence of ectopic Cushing’s syndrome does not appear to have any long-term prognostic implications.
Open access

Anna Popławska-Kita, Marta Wielogórska, Łukasz Poplawski, Katarzyna Siewko, Agnieszka Adamska, Piotr Szumowski, Piotr Myśliwiec, Janusz Myśliwiec, Joanna Reszeć, Grzegorz Kamiński, Janusz Dzięcioł, Dorota Tobiaszewska, Małgorzata Szelachowska and Adam Jacek Krętowski

Summary

Papillary thyroid gland carcinoma is the most common type of malignancy of the endocrine system. Metastases to the pituitary gland have been described as a complication of papillary thyroid cancer in few reported cases since 1965. We report the case of a 68-year-old female patient with a well-differentiated form of thyroid gland cancer. Despite it being the most common malignant cancer of the endocrine system, with its papillary form being one of the two most frequently diagnosed thyroid cancers, the case we present is extremely rare. Sudden cardiac arrest during ventricular fibrillation occurred during hospitalization. Autopsy of the patient revealed papillary carcinoma of the thyroid, follicular variant, with metastasis to the sella turcica, and concomitant sarcoidosis of heart, lung, and mediastinal and hilar lymph nodes. Not only does atypical metastasis make our patient’s case most remarkable, but also the postmortem diagnosis of sarcoidosis makes her case particularly unusual.

Learning points:

  • The goal of presenting this case is to raise awareness of the clinical heterogeneity of papillary cancer and promote early diagnosis of unexpected metastasis and coexisting diseases to improve clinical outcomes.
  • Clinicians must be skeptical. They should not fall into the trap of diagnostic momentum or accept diagnostic labels at face value. Regardless of the potential mechanisms, clinicians should be aware of the possibility of the coexistence of thyroid cancer and sarcoidosis as a differential diagnosis of lymphadenopathy.
  • This case highlights the importance of the diagnostic and therapeutic planning process and raises awareness of the fact that one uncommon disease could be masked by another extremely rare disorder.
Open access

Kaja Grønning, Archana Sharma, Maria Adele Mastroianni, Bo Daniel Karlsson, Eystein S Husebye, Kristian Løvås and Ingrid Nermoen

Summary

Primary adrenal lymphoma (PAL) is a rare cause of adrenal insufficiency. More than 90% is of B-cell origin. The condition is bilateral in up to 75% of cases, with adrenal insufficiency in two of three patients. We report two cases of adrenal insufficiency presenting at the age of 70 and 79 years, respectively. Both patients had negative 21-hydroxylase antibodies with bilateral adrenal lesions on CT. Biopsy showed B-cell lymphoma. One of the patients experienced intermittent disease regression on replacement dosage of glucocorticoids.

Learning points:

  • Primary adrenal lymphoma (PAL) is a rare cause of adrenal insufficiency.
  • Bilateral adrenal masses of unknown origin or in individuals with suspected extra-adrenal malignancy should be biopsied quickly when pheochromocytoma is excluded biochemically.
  • Steroid treatment before biopsy may affect diagnosis.
  • Adrenal insufficiency with negative 21-hydroxylase antibodies should be evaluated radiologically.
Open access

Isabella Lupi, Alessandro Brancatella, Mirco Cosottini, Nicola Viola, Giulia Lanzolla, Daniele Sgrò, Giulia Di Dalmazi, Francesco Latrofa, Patrizio Caturegli and Claudio Marcocci

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
Open access

Sarah W Y Poon, Karen K Y Leung and Joanna Y L Tung

Summary

Severe hypertriglyceridemia is an endocrine emergency and is associated with acute pancreatitis and hyperviscosity syndrome. We describe an infant with lipoprotein lipase deficiency with severe hypertriglyceridemia who presented with acute pancreatitis. She was managed acutely with fasting and intravenous insulin infusion, followed by low-fat diet with no pharmacological agent. Subsequent follow-up until the age of 5 years showed satisfactory lipid profile and she has normal growth and development.

Learning points:

  • Hypertriglyceridemia-induced acute pancreatitis has significant morbidity and mortality, and prompt treatment is imperative.
  • When no secondary causes are readily identified, genetic evaluation should be pursued in hypertriglyceridemia in children.
  • Intravenous insulin is a safe and effective acute treatment for hypertriglyceridemia in children, even in infants.
  • Long-term management with dietary modifications alone could be effective for primary hypertriglyceridemia due to lipoprotein lipase deficiency, at least in early childhood phase.
Open access

Huilin Koh, Manish Kaushik, Julian Kenrick Loh and Chiaw Ling Chng

Summary

Thyroid storm with multi-organ failure limits the use of conventional treatment. A 44-year-old male presented with thyroid storm and experienced cardiovascular collapse after beta-blocker administration, with resultant fulminant multi-organ failure requiring inotropic support, mechanical ventilation, extracorporeal membrane oxygenation (ECMO) and continuous renal replacement therapy. Hepatic and renal failure precluded the use of conventional thyroid storm treatment and early plasma exchange was instituted. The patient underwent emergency thyroidectomy after four effective exchanges, with subsequent rapid reversal of multi-organ failure. The challenges of institution of plasma exchanges with ongoing ECMO support, dialysis and timing of thyroidectomy are discussed. This case highlights the important role of early therapeutic plasma exchange (TPE) as an effective salvage therapy for lowering circulating hormones and stabilization of patients in preparation for emergency thyroidectomy in patients with thyroid storm and fulminant multi-organ failure.

Learning points:

  • Administration of beta-blockers in thyroid storm presenting with congestive cardiac failure may precipitate cardiovascular collapse due to inhibition of thyroid-induced hyperadrenergic compensation which maintains cardiac output.
  • TPE can be an effective bridging therapy to emergency total thyroidectomy when conventional thyroid storm treatment is contraindicated.
  • End-organ support using ECMO and CRRT can be combined with TPE effectively in the management of critically ill cases of thyroid storm.
  • The effectiveness of plasma exchange in lowering thyroid hormones appears to wane after 44–48 h of therapy in this case, highlighting the importance early thyroidectomy.
Open access

Jose León Mengíbar, Ismael Capel, Teresa Bonfill, Isabel Mazarico, Laia Casamitjana Espuña, Assumpta Caixàs and Mercedes Rigla

Summary

Durvalumab, a human immunoglobulin G1 kappa monoclonal antibody that blocks the interaction of programmed cell death ligand 1 (PD-L1) with the PD-1 and CD80 (B7.1) molecules, is increasingly used in advanced neoplasias. Durvalumab use is associated with increased immune-related adverse events. We report a case of a 55-year-old man who presented to our emergency room with hyperglycaemia after receiving durvalumab for urothelial high-grade non-muscle-invasive bladder cancer. On presentation, he had polyuria, polyphagia, nausea and vomiting, and laboratory test revealed diabetic ketoacidosis (DKA). Other than durvalumab, no precipitating factors were identified. Pre-durvalumab blood glucose was normal. The patient responded to treatment with intravenous fluids, insulin and electrolyte replacement. Simultaneously, he presented a thyroid hormone pattern that evolved in 10 weeks from subclinical hyperthyroidism (initially attributed to iodinated contrast used in a previous computerised tomography) to overt hyperthyroidism and then to severe primary hypothyroidism (TSH: 34.40 µU/mL, free thyroxine (FT4): <0.23 ng/dL and free tri-iodothyronine (FT3): 0.57 pg/mL). Replacement therapy with levothyroxine was initiated. Finally, he was tested positive for anti-glutamic acid decarboxylase (GAD65), anti-thyroglobulin (Tg) and antithyroid peroxidase (TPO) antibodies (Abs) and diagnosed with type 1 diabetes mellitus (DM) and silent thyroiditis caused by durvalumab. When durvalumab was stopped, he maintained the treatment of multiple daily insulin doses and levothyroxine. Clinicians need to be alerted about the development of endocrinopathies, such as DM, DKA and primary hypothyroidism in the patients receiving durvalumab.

Learning points:

  • Patients treated with anti-PD-L1 should be screened for the most common immune-related adverse events (irAEs).
  • Glucose levels and thyroid function should be monitored before and during the treatment.
  • Durvalumab is mainly associated with thyroid and endocrine pancreas dysfunction.
  • In the patients with significant autoimmune background, risk–benefit balance of antineoplastic immunotherapy should be accurately assessed.
Open access

A Chinoy, N B Wright, M Bone and R Padidela

Summary

Hypokalaemia at presentation of diabetic ketoacidosis is uncommon as insulin deficiency and metabolic acidosis shifts potassium extracellularly. However, hypokalaemia is a recognised complication of the management of diabetic ketoacidosis as insulin administration and correction of metabolic acidosis shifts potassium intracellularly. We describe the case of a 9-year-old girl with newly diagnosed type 1 diabetes mellitus presenting in diabetic ketoacidosis, with severe hypokalaemia at presentation due to severe and prolonged emesis. After commencing management for her diabetic ketoacidosis, her serum sodium and osmolality increased rapidly. However, despite maximal potassium concentrations running through peripheral access, and multiple intravenous potassium ‘corrections’, her hypokalaemia persisted. Seventy two hours after presentation, she became drowsy and confused, with imaging demonstrating central pontine myelinolysis – a rare entity seldom seen in diabetic ketoacidosis management in children despite rapid shifts in serum sodium and osmolality. We review the literature associating central pontine myelinolysis with hypokalaemia and hypothesise as to how the hypokalaemia may have contributed to the development of central pontine myelinolysis. We also recommend an approach to the management of a child in diabetic ketoacidosis with hypokalaemia at presentation.

Learning points:

  • Hypokalaemia is a recognised complication of treatment of paediatric diabetic ketoacidosis that should be aggressively managed to prevent acute complications.
  • Central pontine myelinolysis is rare in children, and usually observed in the presence of rapid correction of hyponatraemia. However, there is observational evidence of an association between hypokalaemia and central pontine myelinolysis, potentially by priming the endothelial cell membrane to injury by lesser fluctuations in osmotic pressure.
  • Consider central pontine myelinolysis as a complication of the management of paediatric diabetic ketoacidosis in the presence of relevant symptoms with profound hypokalaemia and/or fluctuations in serum sodium levels.
  • We have suggested an approach to the management strategies of hypokalaemia in paediatric diabetic ketoacidosis which includes oral potassium supplements if tolerated, minimising the duration and the rate of insulin infusion and increasing the concentration of potassium intravenously (via central line if necessary).
Open access

Aisling McCarthy, Sophie Howarth, Serena Khoo, Julia Hale, Sue Oddy, David Halsall, Brian Fish, Sashi Mariathasan, Katrina Andrews, Samson O Oyibo, Manjula Samyraju, Katarzyna Gajewska-Knapik, Soo-Mi Park, Diana Wood, Carla Moran and Ruth T Casey

Summary

Primary hyperparathyroidism (PHPT) is characterised by the overproduction of parathyroid hormone (PTH) due to parathyroid hyperplasia, adenoma or carcinoma and results in hypercalcaemia and a raised or inappropriately normal PTH. Symptoms of hypercalcaemia occur in 20% of patients and include fatigue, nausea, constipation, depression, renal impairment and cardiac arrythmias. In the most severe cases, uraemia, coma or cardiac arrest can result. Primary hyperparathyroidism in pregnancy is rare, with a reported incidence of 1%. Maternal and fetal/neonatal complications are estimated to occur in 67 and 80% of untreated cases respectively. Maternal complications include nephrolithiasis, pancreatitis, hyperemesis gravidarum, pre-eclampsia and hypercalcemic crises. Fetal complications include intrauterine growth restriction; preterm delivery and a three to five-fold increased risk of miscarriage. There is a direct relationship between the degree of severity of hypercalcaemia and miscarriage risk, with miscarriage being more common in those patients with a serum calcium greater than 2.85 mmol/L. Neonatal complications include hypocalcemia. Herein, we present a case series of three women who were diagnosed with primary hyperparathyroidism in pregnancy. Case 1 was diagnosed with multiple endocrine neoplasia type 1 (MEN1) in pregnancy and required a bilateral neck exploration and subtotal parathyroidectomy in the second trimester of her pregnancy due to symptomatic severe hypercalcaemia. Both case 2 and case 3 were diagnosed with primary hyperparathyroidism due to a parathyroid adenoma and required a unilateral parathyroidectomy in the second trimester. This case series highlights the work-up and the tailored management approach to patients with primary hyperparathyroidism in pregnancy.

Learning points:

  • Primary hyperparathyroidism in pregnancy is associated with a high incidence of associated maternal fetal and neonatal complications directly proportionate to degree of maternal serum calcium levels.
  • Parathyroidectomy is the definitive treatment for primary hyperparathyroidism in pregnancy and was used in the management of all three cases in this series. It is recommended when serum calcium is persistently greater than 2.75 mmol/L and or for the management of maternal or fetal complications of hypercalcaemia. Surgical management, when necessary is ideally performed in the second trimester.
  • Primary hyperparathyroidism is genetically determined in ~10% of cases, where the likelihood is increased in those under 40 years, where there is relevant family history and those with other related endocrinopathies. Genetic testing is a useful diagnostic adjunct and can guide treatment and management options for patients diagnosed with primary hyperparathyroidism in pregnancy, as described in case 1 in this series, who was diagnosed with MEN1 syndrome.
  • Women of reproductive age with primary hyperparathyroidism need to be informed of the risks and complications associated with primary hyperparathyroidism in pregnancy and pregnancy should be deferred and or avoided until curative surgery has been performed and calcium levels have normalised.
Open access

Ana Gonçalves Ferreira, Tiago Nunes da Silva, Sofia Alegria, Maria Carlos Cordeiro and Jorge Portugal

Summary

Pheochromocytoma/paraganglioma (PPGL) are neuroendocrine tumors that can secrete catecholamines. The authors describe a challenging case who presented as stress cardiomyopathy and myocardial infarction (MI). A 76-year-old man, with a medical history of Parkinson’s disease, type 2 diabetes mellitus, hypertension, dyslipidaemia and a previous inferior MI in 2001, presented to the emergency department due to chest pain, headaches and vomiting. He also reported worsening blood glucose levels and increasing constipation over the preceding weeks. BP was 185/89 mmHg (no other relevant findings). EKG had ST segment depression in leads V2-V6, T troponin was 600 ng/L (<14) and the echocardiogram showed left ventricular hypokinesia with mildly compromised systolic function. Nevertheless, he rapidly progressed to severe biventricular dysfunction. Coronary angiogram showed a 90% anterior descendent coronary artery occlusion (already present in 2001), which was treated with angioplasty/stenting. In the following days, a very labile BP profile and unexplained sinus tachycardia episodes were observed. Because of sustained severe constipation, the patient underwent an abdominal CT that revealed a retroperitoneal, heterogeneous, hypervascular mass on the right (62 × 35 mm), most likely a paraganglioma. Urinary metanephrines were increased several fold. 68Ga-DOTANOC PET-CT scan showed increased uptake in the abdominal mass (no evidence of disease elsewhere). He was started on a calcium-channel blocker and alpha blockade and underwent surgery with no major complications. Eight months after surgery, the patient has no evidence of disease. Genetic testing was negative for known germline mutations. This was a challenging diagnosis, but it was essential for adequate cardiovascular stabilization and to reduce further morbidity.

Learning points:

  • PPGL frequently produces catecholamines and can manifest with several cardiovascular syndromes, including stress cardiomyopathy and myocardial infarction.
  • Even in the presence of coronary artery disease (CAD), PPGL should be suspected if signs or symptoms attributed to catecholamine excess are present (in this case, high blood pressure, worsening hyperglycaemia and constipation).
  • Establishing the correct diagnosis is important for adequate treatment choice.
  • Inodilators and mechanical support might be preferable options (if available) for cardiovascular stabilization prior to alpha blockade and surgery.
  • Laboratory interference should be suspected irrespective of metanephrine levels, especially in the context of treated Parkinson’s disease.