Near-fatal pheochromocytoma crisis after beta-blocker and tumour haemorrhage.

Pheochromocytomas are rare neuroendocrine tumors characterised by the secretion of catecholamines and their metabolites. While some patients may be asymptomatic, they can also present with various symptoms including hypertensive crisis, headaches, palpitations, diaphoresis or other signs of catecholamine toxicity. Adrenal haemorrhage, though rare, is a potentially fatal complication that is often diagnosed during autopsy. In all patients with suspected pheochromocytoma, regardless of whether haemorrhagic conversion has occurred, prompt diagnosis is imperative. Early identification allows for the timely initiation of treatment, preventing potentially life-threatening complications. This case report details the haemorrhagic conversion of an undiagnosed pheochromocytoma in a female patient in her 30s.

The interpretation of immunometric, chromatographic and mass spectrometric data for steroids in diagnosis of endocrine disorders.

The analysis of steroids for endocrine disorders is in transition from immunoassay of individual steroids to more specific chromatographic and mass spectrometric methods with simultaneous determination of several steroids. Gas chromatography (GC) and liquid chromatography (LC) coupled with mass spectrometry (MS) offer unrivalled analytical capability for steroid analysis. These specialist techniques were often judged to be valuable only in a research laboratory but this is no longer the case. In a urinary steroid profile up to 30 steroids are identified with concentrations and excretion rates reported in a number of ways. The assays must accommodate the wide range in steroid concentrations in biological fluids from micromolar for dehydroepiandrosterone sulphate (DHEAS) to picomolar for oestradiol and aldosterone. For plasma concentrations, panels of 5-20 steroids are reported. The profile results are complex and interpretation is a real challenge in order to inform clinicians of likely implications. Although artificial intelligence and machine learning will in time generate reports from the analysis this is a way off being adopted into clinical practice. This review offers guidance on current interpretation of the data from steroid determinations in clinical practice. Using this approach more laboratories can use the techniques to answer clinical questions and offer broader interpretation of the results so that the clinician can understand the conclusion for the steroid defect, and can be advised to program further tests if necessary and instigate treatment. The biochemistry is part of the patient workup and a clinician led multidisciplinary team discussion of the results will be required for challenging patients. The laboratory will have to consider cost implications, bearing in mind that staff costs are the highest component. GC-MS and LC-MS/MS analysis of steroids are the choices. Steroid profiling has enormous potential to improve diagnosis of adrenal disorders and should be adopted in more laboratories in favour of the cheap, non-specific immunological methods.

Study protocol for a prospective, multicentre study of hypercortisolism in patients with difficult-to-control type 2 diabetes (CATALYST): prevalence and treatment with mifepristone.

INTRODUCTION: Even with recent treatment advances, type 2 diabetes (T2D) remains poorly controlled for many patients, despite the best efforts to adhere to therapies and lifestyle modifications. Although estimates vary, studies indicate that in >10% of individuals with difficult-to-control T2D, hypercortisolism may be an underlying contributing cause. To better understand the prevalence of hypercortisolism and the impact of its treatment on T2D and associated comorbidities, we describe the two-part Hyper c ortisolism in P at ients with Difficult to Control Type 2 Di a betes Despite Receiving Standard-of-Care Therapies: Preva l ence and Treatment with Korl y m® (Mifepri st one) (CATALYST) trial. METHODS AND ANALYSIS: In part 1, approximately 1000 participants with difficult-to-control T2D (haemoglobin A1c (HbA1c) 7.5%-11.5% despite multiple therapies) are screened with a 1 mg dexamethasone suppression test (DST). Those with post-DST cortisol >1.8 µg/dL and dexamethasone level ≥140 ng/dL are identified to have hypercortisolism (part 1 primary endpoint), have morning adrenocorticotropic hormone (ACTH) and dehydroepiandrosterone sulfate (DHEAS) measured and undergo a non-contrast adrenal CT scan. Those requiring evaluation for elevated ACTH are referred for care outside the study; those with ACTH and DHEAS in the range may advance to part 2, a randomised, double-blind, placebo-controlled trial to evaluate the impact of treating hypercortisolism with the competitive glucocorticoid receptor antagonist mifepristone (Korlym®). Participants are randomised 2:1 to mifepristone or placebo for 24 weeks, stratified by the presence/absence of an abnormal adrenal CT scan. Mifepristone is dosed at 300 mg once daily for 4 weeks, then 600 mg daily based on tolerability and clinical improvement, with an option to increase to 900 mg. The primary endpoint of part 2 assesses changes in HbA1c in participants with hypercortisolism with or without abnormal adrenal CT scan. Secondary endpoints include changes in antidiabetes medications, cortisol-related comorbidities and quality of life. ETHICS AND DISSEMINATION: The study has been approved by Cleveland Clinic IRB (Cleveland, Ohio, USA) and Advarra IRB (Columbia, Maryland, USA). Findings will be presented at scientific meetings and published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT05772169.

Management of a giant adrenal schwannoma.

In this case report, we present a man in his 60s who presented with an incidentally discovered right adrenal mass, which turned out to be an adrenal schwannoma. This is a very rare tumour that originates from Schwann cells and involves the peripheral nerves. The tumour was removed by open adrenalectomy, and this 15-cm adrenal schwannoma is one of the largest reported in the literature, with none >16 cm having ever been reported. This case highlights the importance of keeping an open mind about the cause of an incidentally discovered adrenal mass, which is an increasingly common way for adrenal tumours to present given the increased access to cross-sectional imaging. As well as presenting the case and the pathological basis behind adrenal schwannomas, we include a review of the literature and a general discussion about incidentally discovered adrenal masses.

Perioperative management of phaeochromocytoma with stress cardiomyopathy and aberrant vascular drainage.

The following case discusses the surgical considerations for a patient presenting with cardiogenic shock secondary to a phaeochromocytoma crisis with stress cardiomyopathy. The patient underwent an interval laparoscopic adrenalectomy. Pneumoperitoneum insufflation was performed at lower pressures; manipulation of the adrenal tumour was minimised, and the adrenal vein was ligated early. However, as intraoperative blood pressure (BP) remained elevated and rising, further gentle dissection revealed an aberrant inferior phrenic vein draining the adrenal nodule. BP was finally reduced following ligation of the inferior phrenic vein, demonstrating the clinical significance of an unusual dual venous drainage from the adrenal nodule in this patient.

Oncocytic adrenal cortical adenoma: a benign lesion mimicking malignancy.

Adrenocortical tumours are rare in children and account for only 0.3%-0.4% of all neoplasms in childhood. They present with variable signs and symptoms, depending on the type of hormonal hypersecretion. The majority of the adrenocortical tumours in children are functional (90%) and malignant (88%). Here, we describe a functional plurihormonal oncocytic adrenal cortical adenoma in a young girl, that mimicked a malignant adrenal lesion, clinically as well as on imaging and biochemical features. This report bears the objective of being aware of the atypical biochemical as well as imaging characteristics of oncocytic adrenal tumours.

Elevated IL-6 levels in a patient with pheochromocytoma.

Pheochromocytoma is a chromaffin cell-derived adrenal medullary tumour and usually presents with paroxysms of hypertension, palpitations, sweating and headache due to excessive catecholamine release. These tumours can also secrete a variety of bioactive neuropeptides and hormones other than catecholamines, resulting in unusual clinical manifestations. We report a female in her mid-30s who presented with fever, anaemia, thrombocytosis and markedly elevated inflammatory markers. The fever profile, including cultures, was negative. Contrast-enhanced CT of abdomen showed a large solid-cystic right adrenal lesion with elevated plasma-free normetanephrine levels suggestive of pheochromocytoma. The fever persisted despite empirical antibiotics and antipyretics. Interleukin-6 (IL-6) levels were elevated (41.2 pg/mL (3-4 pg/mL)). She was initiated on naproxen (NPX) at a dose of 250 mg two times per day. The patient responded to NPX, and after stabilisation, she underwent an adrenalectomy. There was a complete resolution of fever with normalisation of IL-6 levels postoperatively.

Anastomosing haemangioma of adrenal gland: an unusual vascular tumour.

With only 15 reported cases, anastomosing haemangioma of adrenal is a rare entity and usually presents as adrenal incidentaloma. A hypertensive, diabetic, non-smoker man in his late 60s presented with irritative voiding symptoms. On evaluation, he was found to have a urinary bladder mass and left adrenal incidentaloma measuring 8 cm. Metabolic evaluation confirmed it to be non-functional.The patient underwent transurethral resection of bladder tumour with left laparoscopic adrenalectomy. Intraoperatively, the adrenal tumour was highly vascular with multiple feeder vessels. Grossly it was soft, encapsulated with focal grey-brown areas. Microscopically, most of adrenal gland was replaced by anastomosing proliferating capillary vessels within framework of non-endothelial supporting cells reminiscent of splenic sinusoids. The tumour was positive for CD-31, CD-34, Glut-1 and SMA.Anastomosing haemangioma is a benign entity but it must be differentiated from angiosarcoma. Characteristic imaging features are not yet defined and is, therefore, difficult to diagnose preoperatively.

Cushing's syndrome diagnosed incidentally on CT imaging.

In this case report, we describe an uncommon presentation of Cushing's syndrome in a patient in their 60s who presented to the emergency department with left-sided chest pain. The initial workup for the patient was unremarkable except for an elevated blood pressure and elevated fasting plasma glucose. A CT scan of the chest, abdomen and pelvis was performed, demonstrating a splenic artery thrombus with multiple splenic infarcts, in addition to a combination of macronodular adrenal hyperplasia, bilateral gynecomastia, centripetal fat distribution and suspected mild bone demineralisation. Adrenocorticotropic hormone-independent macronodular adrenal hyperplasia, a rare aetiology responsible for Cushing's syndrome, was raised as a potential unifying diagnosis for the patient's hypercoagulable status, which was subsequently confirmed on an endocrinological investigation. The case report underscores the importance of communicating clinically relevant details to the imaging specialist in combination with considering a broad differential, including endocrine disorders, when evaluating an undifferentiated patient with atypical imaging findings.

Rare and aggressive metastatic pheochromocytoma recurrence in a patient with MEN 2A syndrome.

An adult male in his early 30s diagnosed with multiple endocrine neoplasia type 2A syndrome, confirmed through genetic testing, presented as bilateral pheochromocytoma in a metachronous fashion, primary hyperparathyroidism and medullary thyroid carcinoma. Left and right adrenalectomy was done 9 years and 3 years ago, respectively. He was also subjected to total thyroidectomy with neck dissection and left inferior parathyroidectomy. During surveillance monitoring, 24-hour total urine metanephrines were elevated 13.977 mg (Normal value 0-1 mg) 1 year after right adrenalectomy. Adrenal CT scan demonstrated a 2.1 cm ovoid focus in the right suprarenal region, and functional imaging (131I meta-iodobenzylguanidine (MIBG scan) showed an avid uptake on the right frontal bone. Excision of the right adrenal bed and the right frontal bone tumour was performed, and metastatic pheochromocytoma was confirmed histologically. The patient achieved clinical and biochemical remission postoperatively and is currently receiving steroid and thyroxine replacement.

Triad of cluster-like headaches, hypertension and hypercoagulability a pointer to pheochromocytoma.

We report the case of a middle-aged hypertensive woman presenting to the neurology department with short-lasting episodic headaches for 4 years. She was initially diagnosed and treated with cluster headaches for one year. Following this, she presented with right lower limb arterial claudication. Arterial Doppler of lower limbs showed thrombosis of the bilateral common femoral arteries. Further computed tomography (CT) angiogram of the lower limbs confirmed extensive arterial thrombosis in bilateral lower limbs. The CT angiogram incidentally detected a left adrenal lesion. She had elevated urinary vanillylmandelic Acid and 24-hour metanephrines suggesting the presence of a pheochromocytoma. She was initially medically managed and later underwent left open adrenalectomy. Histopathology examination of the sections proved pheochromocytoma. Postsurgery, the patient's symptoms improved remarkably. This case highlights the importance of diagnosing pheochromocytoma when you encounter a patient with refractory short-lasting headaches, hypertension and hypercoagulability.

Immunoassay interferences: laboratory pitfall in the diagnosis of adrenocortical carcinoma.

A woman in her late 50s with recent onset of hypertension, diabetes, lumbar pain and unintentional weight loss was diagnosed with a cortisol and androgen-producing adrenal mass. Despite this, serum adrenocorticotropic hormone (ACTH) concentration was inappropriately elevated, which was investigated thoroughly. Investigations included a brain magnetic resonance imaging to exclude concomitant pituitary adenoma, a corticotropin-releasing hormone stimulation test and a gallium-68 DOTATATE and 18F-FDOPA PET scan, both excluding ectopic ACTH production. Considering the disparity between clinical presentation and biochemical results, the ACTH was reanalysed using the Cobas immunoassay (Roche, Switzerland), ultimately unveiling the cause for ACTH elevation. ACTH levels had previously been measured with ACTH Immulite (Siemens, Germany), a two-site immunoassay which is prone to interferences causing falsely elevated ACTH concentrations. Inaccurate laboratory levels can lead to diagnosis delay and unnecessary diagnostic procedures and a close communication between the physicians and laboratorians is of utmost importance.

True mesothelial cyst of the adrenal gland: its clinical profile and management.

The incidence of adrenal cysts is 0.06% and only 9% of these are true mesothelial cysts. Here, we present a case of a true mesothelial cyst together with a review of the literature. A female in her 30s presented to the surgical outpatient department complaining of right flank pain. Her contrast-enhanced CT scan revealed a 7.5×6.5×4.5 cm right adrenal gland cyst. The patient underwent a laparoscopic right adrenalectomy. Immunohistopathology revealed the cyst to be mesothelial in nature. The majority of true mesothelial adrenal cysts are benign, unilateral and more common in women. Any adrenal cyst diagnosed as a functional lesion or one that may be malignant or with a diameter of 5 cm or greater requires surgical care whereas smaller lesions can be managed conservatively. Laparoscopic adrenalectomy for an adrenal cyst of diameter greater than 6 cm is a safe and feasible procedure in expert hands if there is no invasion of surrounding tissue.

Asymptomatic trigger of adrenal crisis in a patient with Sheehan syndrome: importance of timely recognition and intervention.

Our patient is a female in her 70s who initially presented following an episode of bowel and bladder incontinence, as well as unresponsiveness. Her family denied any preceding illness or sick symptoms. During her workup, it was noted that she was wearing a medical bracelet, which listed prednisone as one of her daily medications, raising concern for an acute adrenal crisis (AC). Ultimately, our patient's condition improved with high-dose intravenous steroids before being tapered to her home regimen. Current literature highlights the pathophysiological complexity of an AC but fails to identify clear risk factors that trigger such events, especially in asymptomatic patients. Accordingly, our case highlights this gap, arguing the importance of appropriate patient education and timely intervention for such clinically ambiguous yet life-threatening presentations.

Sulfasalazine as a cause of false-positive elevation of urinary normetanephrine in patients with adrenal mass and suspected phaeochromocytoma: a diagnostic challenge.

In patients with suspected phaeochromocytoma, biochemical screening of urine or blood for excess secretion catecholamines and/or their metabolites is performed. Elevated levels of catecholamines and metanephrines help in establishing the diagnosis of phaeochromocytoma. In two patients with adrenal lesions who were subjected to biochemical testing significantly elevated urinary normetanephrines appeared to establish the diagnosis of phaeochromocytoma. However, on subsequent investigations, this was demonstrated to be a 'false positive' finding. Both these patients were on sulfasalazine, an anti-inflammatory drug used in inflammatory bowel disease, rheumatoid arthritis and ankylosing spondylitis. Sulfasalazine can cause analytical interference in some assays for urinary normetanephrine and result in spuriously elevated levels, leading to misdiagnosis of phaeochromocytoma. In this report, one patient underwent adrenalectomy and another had conservative management.Although this has been previously reported, increased awareness of the possibility of false-positive results on urinary metanephrines testing is important to reduce the potential for misdiagnosis and unnecessary treatment.

Metastatic paraganglioma presenting with spinal cord compression requiring urgent surgery.

We report a rare case of a functional bladder paraganglioma diagnosed in a young man who presented with acute compressive thoracic myelopathy secondary to vertebral metastasis. A histological diagnosis of a metastatic paraganglioma was made following biopsy of a rib lesion. CT revealed a lesion in the inferior wall of the bladder, which demonstrated avid uptake on 68Ga-DOTATATE PET/CT. Serum metanephrine levels were more than 40 times the upper limit of normal. The patient was hypertensive and treatment with doxazosin was initiated. In view of neurological deterioration, he required urgent spinal decompression to preserve neurological function and prevent permanent paraplegia. Despite inadequate alpha-blockade, surgery was successful, and the perioperative course was uneventful. Alpha-blockade was subsequently optimised. Treatment with cyclophosphamide, vincristine and dacarbazine was started but, in view of disease progression, treatment was subsequently changed to sunitinib.

Castleman disease masquerading as a paraganglioma showing uptake on DOTATATE PET.

A man in his 50s presented with shortness of breath and was found to have a large paracaval mass, which on further evaluation with CT, showed a large heterogeneously enhancing mass lesion adjacent to right renal hilum. His 24-hour urinary metanephrines and nor-metanephrines were normal. In view of location and features on CT, paraganglioma was considered as a possibility. A 68Ga-DOTATATE positron emission tomography/CT demonstrated avidity in the lesion with maximum standardised uptake value of 16.5. He underwent right laparoscopic converted to open mass excision along with nephrectomy. Histopathological examination was suggestive of hyaline vascular Castleman disease.

ARMC5-negative primary bilateral macronodular adrenal hyperplasia.

A woman in her 60s with chronic fatigue, depressed mood and proximal muscle weakness was referred to our endocrinology department. Physical examination revealed facial plethora, atrophic skin and ankle oedema. Adjuvant blood and urine analyses indicated endogenous ACTH-independent Cushing syndrome. Abdominal imaging showed bilateral macronodular adrenals, measuring 58.9 × 29.7 mm on the right and 55.6 × 42.6 mm on the left. Primary bilateral macronodular adrenal hyperplasia was confirmed by pathology after bilateral adrenalectomy. Gradual mental and physical recovery was observed in the months following surgery. Genetic sequencing failed to reveal mutations in the ARMC5 gene.Cushing syndrome is a rare entity that should be suspected when typical clinical signs, including skin atrophy with ecchymosis, muscle weakness or coloured stretch marks, are present. Primary bilateral macronodular adrenal hyperplasia is an uncommon cause of endogenous Cushing syndrome. It is a benign condition characterised by adrenal macronodules exceeding 1 cm and hypercorticism.

Therapeutic outcomes with surgical and medical management for primary aldosteronism: protocol for a systematic review and meta-analysis.

INTRODUCTION: Treatment strategies for primary aldosteronism (PA) include unilateral adrenalectomy and medical treatment with mineralocorticoid receptor (MR) antagonists. Whether these two different treatment strategies are comparable in mitigating the detrimental effect of PA on outcomes is still debated. OBJECTIVES: The primary aim of this systematic review is to identify, appraise and synthesise existing literature comparing clinical outcomes after treatment in patients with PA. METHODS AND ANALYSIS: A systematic and comprehensive search will be performed using PubMed, Web of Science and EMBASE, for studies published until December 2022. Observational and interventional studies will be eligible for inclusion. The quality of observational studies will be assessed using the Newcastle-Ottawa Scale, while interventional studies will be assessed using the Cochrane Effective Practice Organization of Care tool. The collected evidence will be narratively synthesised. We will perform meta-analysis to pool estimates from studies considered to be homogeneous. Reporting of the systematic review and meta-analysis will be in accordance with the Meta-analysis of Observational Studies in Epidemiology Preferred Reporting Items for Systematic reviews and Meta-Analysis guidelines. ETHICS AND DISSEMINATION: As this study is based solely on the published literature, no ethics approval is required. This review will aim to provide some estimates on outcomes, including survival, rates of clinical and biochemical control, cardiovascular and cerebrovascular events, as well as data on quality of life and renal function, in patients with PA treated surgically or with MR antagonists. The study findings will be presented at scientific meetings and will be published in an international peer-reviewed scientific journal. PROSPERO REGISTRATION NUMBER: CRD42022362506.