Headaches, palpitations, and diaphoresis are the classic triad of pheochromocytoma, but not all patients with pheochromocytoma are symptomatic.
Pheochromocytoma crisis can occur spontaneously or be precipitated by medications, including β-adrenergic receptor blockers and sympathomimetics.
Pheochromocytomas may lead to Takotsubo and reverse Takotsubo cardiomyopathies.
Pheochromocytoma-induced hypertension should be treated with α-adrenergic blockade before β-adrenergic blockade to prevent severe hypertensive episodes.
A 66-year-old woman presented to the emergency department with a 1-week history of productive cough and malaise. She had a history of type 2 diabetes and hypothyroidism, and no history of hypertension. Her medications were metformin, gliclazide, and levothyroxine. Two days before presentation, her family doctor had prescribed oral amoxicillin for a respiratory tract infection, and she had started taking an over-the-counter nasal decongestant spray containing pseudoephedrine. She described an unexplained 20-pound weight loss over the last year and intermittent palpitations. She did not smoke and used alcohol infrequently. Her mother had passed away from colon cancer and her half sister had lung cancer; she reported no endocrinopathies in first-degree relatives.
The patient’s heart rate was 150 beats per minute, blood pressure 144/99 mm Hg, and oxygen saturation above 95% on room air. She was afebrile. She appeared diaphoretic, hypovolemic (dry mucous membranes, low jugular venous pressure), and had no signs of respiratory distress such as tachypnea or accessory respiratory muscle use. Laboratory investigations showed a leukocyte count of 14.0 (normal range 4.0–11.0) × 109/L, with neutrophilia of 12.4 (normal range 2.0–7.5) × 109/L. Her creatinine level was 110 μmol/L; the only previous result available was 70 μmol/L 4 years earlier, and lactate was 2.4 (normal range 0.5– 2.2) mmol/L. Her initial high-sensitivity troponin level was 32 (normal ≤ 16 ng/L) and the result of a repeat test 4 hours later was unchanged. Her glucose level was elevated, at 19.3 (normal range 3.6–7.7) mmol/L, and thyroid-stimulating hormone level was 2.9 (normal range 0.35–4.94) mIU/L. An electrocardiogram showed sinus tachycardia. We ordered a computed tomography (CT) pulmonary angiogram to assess for pulmonary embolism, which showed right upper and left lower lobe ground-glass opacities, suggesting community-acquired pneumonia with no findings of pulmonary embolism. A mass in the left upper abdomen was also seen.
Initially, we ordered 1 g of ceftriaxone intravenously (IV) to treat community-acquired pneumonia and infused 3 L of Ringer’s lactate IV over 5 hours. We managed the patient’s hyperglycemia with sliding-scale insulin and requested a CT scan of her abdomen to characterize the mass.
The next morning, about 15 hours after the patient’s initial presentation, her hypovolemia had resolved (jugular venous pressure, lactate, and creatinine levels had normalized) but her tachycardia persisted. We ordered an echocardiogram, which showed normal biventricular function. That night, the patient’s heart rate remained elevated at 140 beats per minute, and her systolic blood pressure rose to 150 mm Hg. In consultation with the cardiology team, the on-call physician ordered 25 mg of oral metoprolol to treat palpitations and hypertension, as well as the ongoing sinus tachycardia. Her heart rate decreased to 120 beats per minute, but blood pressure remained elevated. The abdominal CT that evening showed an 8-cm left retroperitoneal mass with cystic and solid features, possibly adrenal in origin, without extra-adrenal disease (Figure 1). We requested 24-hour urine cortisol, plasma renin and aldosterone levels, and serum and urine metanephrines.
<a href="https://www.cmaj.ca/content/cmaj/196/13/E441/F1.large.jpg?width=800&height=600&carousel=1" title="Computed tomography scan with contrast of the abdomen of a 66-year-old woman with a possible adrenal mass in the left upper quadrant, concerning for pheochromocytoma (blue arrow)." class="highwire-fragment fragment-images colorbox-load" rel="gallery-fragment-images-2045425408" data-figure-caption="
Computed tomography scan with contrast of the abdomen of a 66-year-old woman with a possible adrenal mass in the left upper quadrant, concerning for pheochromocytoma (blue arrow).
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Figure 1:
Computed tomography scan with contrast of the abdomen of a 66-year-old woman with a possible adrenal mass in the left upper quadrant, concerning for pheochromocytoma (blue arrow).
Five hours after receiving metoprolol, the patient’s blood pressure increased to 173/125 mm Hg, she developed tachypnea, and her oxygen requirements increased. Her troponin level increased to 10 160 ng/L and her electrocardiogram showed new anterior ST depression. A repeat echocardiogram revealed a hyperdynamic apex with global akinesis, concerning for reverse Takotsubo cardiomyopathy (TCM) (Figure 2; 2 supplementary videos are available at Appendix 1, at www.cmaj.ca/lookup/doi/10.1503/cmaj.231575/tab-related-content).
<a href="https://www.cmaj.ca/content/cmaj/196/13/E441/F2.large.jpg?width=800&height=600&carousel=1" title="Echocardiogram showing akinesis of basal segments (blue markings) and a hyperdynamic apex (red markings) suggesting reverse Takotsubo cardiomyopathy. Images include apical 4-chamber view in end-systole (A) and end-diastole (B), as well as parasternal long axis view in end-systole (C) and end-diastole (D)." class="highwire-fragment fragment-images colorbox-load" rel="gallery-fragment-images-2045425408" data-figure-caption="
Echocardiogram showing akinesis of basal segments (blue markings) and a hyperdynamic apex (red markings) suggesting reverse Takotsubo cardiomyopathy. Images include apical 4-chamber view in end-systole (A) and end-diastole (B), as well as parasternal long axis view in end-systole (C) and end-diastole (D).
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Figure 2:
Echocardiogram showing akinesis of basal segments (blue markings) and a hyperdynamic apex (red markings) suggesting reverse Takotsubo cardiomyopathy. Images include apical 4-chamber view in end-systole (A) and end-diastole (B), as well as parasternal long axis view in end-systole (C) and end-diastole (D).
We transferred the patient to the intensive care unit (ICU) and inserted an endotracheal tube. Three hours after intubation, she developed severe hypotension, with systolic blood pressure of 70 mm Hg. She developed cardiogenic shock and, despite multiple vasopressors, required veno-arterial extracorporeal membrane oxygenation (ECMO). Cardiac CT showed no coronary artery atherosclerosis.
The results of the patient’s endocrine investigations showed elevated levels of metanephrines of 221.13 (normal 0–0.50) nmol/L, normetanephrines of 121.71 (normal 0–0.90) nmol/L, and 24-hour urine metanephrines of 4053 (normal 0–170) nmol/d, confirming a diagnosis of pheochromocytoma. Her 24-hour urine cortisol and plasma renin-aldosterone ratio were normal.
The patient’s hemodynamic instability improved and ECMO was discontinued 3 days after it was started. In the ICU, physicians prescribed doxazosin at a dose of 2 mg/d, titrated up by 2 mg increments per day to 16 mg/d. Four days after initiating doxazosin, we started the patient on metoprolol to treat persistent tachycardia, at a dose of 12.5 mg twice daily, and titrated to 25 mg twice daily as her blood pressure tolerated. On these medications, her average blood pressure was less than 130/80 mm Hg, heart rate less than 80 beats per minute, and we discharged her home. To expand plasma volume, we advised liberal fluid intake (2–3 L/d) and salt intake (5–10 g/d).
Forty-six days after discharge, the patient underwent complete surgical removal of the adrenal mass. Pathology results confirmed the diagnosis of pheochromocytoma. Her immediate postoperative blood pressure was 99/62 mm Hg, and a few weeks later, it was 99/57 mm Hg without medications. Her postoperative plasma metanephrines level was 0.07. Genetic screening for familial disorders associated with pheochromocytoma — including succinate dehydrogenase disorders, neurofibromatosis 1, von Hippel–Lindau syndrome, and multiple endocrine dysplasia 2 — was negative.
Discussion
Pheochromocytoma is a rare tumour arising from chromaffin cells in the adrenal medulla, leading to uncontrolled catecholamine synthesis and secretion. Pheochromocytomas are the underlying cause of hypertension in 0.2%–0.4% of patients, with 2–8 cases detected annually per million people.1 Headaches, palpitations, and diaphoresis are the classic triad of pheochromocytoma, but patients may experience other signs and symptoms including nausea, vomiting, tremors, anxiety, and chest pain (Table 1).2 Hypertension can be paroxysmal or sustained. About 5%–8% of patients with pheochromocytoma are asymptomatic. Asymptomatic pheochromocytoma is usually associated with large cystic tumours or familial syndromes including von Hippel–Lindau syndrome, multiple endocrine dysplasia 2, succinate dehydrogenase disorders, and neurofibromatosis 1.1,3 Because the symptoms associated with hypersecretion of catecholamines can mimic several other medical conditions, time until diagnosis may be delayed. Early recognition and diagnosis is key before the development of severe, and in some cases fatal, cardiovascular complications. About 10%–17% of adrenal pheochromocytomas are malignant.4
View this table:
Table 1:
Signs and symptoms of pheochromocytoma and pooled sensitivities2
Diagnosing pheochromocytoma requires biochemical confirmation of excessive catecholamine release and imaging to localize the tumour. Elevated plasma-free metanephrines and 24-hour urine fractionated metanephrines have the highest sensitivity, of 98% and 93%, respectively, with a specificity of 94% for both.5 In adults, CT is the preferred imaging modality for diagnosis because its spatial resolution is superior to that of magnetic resonance imaging.4 Functional imaging studies such as meta-iodobenzylguanidine (MIBG) or positron emission tomography–CT scans may also be used.
Hypertension and tachycardia in patients with pheochromocytoma must be managed before surgery. α-Adrenergic blockers should be prescribed first and then dose titrated until blood pressure is no longer elevated. β-Blockers should be started only after successful α-adrenergic blockade, to mitigate the risk of life-threatening hypertension and cardiopulmonary decompensation from unopposed α-adrenergic stimulation. α-Adrenergic blockade can be achieved with the nonselective agent phenoxybenzamine or selective agents such as prazosin, terazosin, or doxazosin. Phenoxybenzamine, an irreversible α-blocker, is more effective in preventing intraoperative hemodynamic instability but is not readily available.6 According to retrospective data, a target blood pressure of less than 130/80 mm Hg while seated and greater than 90 mm Hg systolic while standing, with a target heart rate of 60–70 beats per minute seated and 70–80 beats per minute standing, is desired before surgical resection of the tumour, usually 7–14 days after medical optimization.4
A life-threatening complication of pheochromocytoma is a pheochromocytoma crisis, which can lead to hemodynamic instability and end-organ dysfunction. It can occur spontaneously, due to trauma, or be triggered by medications, including β-adrenergic receptor blockers, sympathomimetics (e.g., pseudoephedrine, ephedrine), dopamine receptor antagonists, opioid analgesics, neurotransmitter reuptake blockers, and peptide and steroid hormones (e.g., glucagon, adrenocorticotrophic hormone, corticosteroids). 4,7 The clinical presentation of a pheochromocytoma crisis ranges from severe hypertension to circulatory failure and shock.
Pheochromocytoma has uncommonly been associated with TCM or reverse TCM.8 Takotsubo cardiomyopathy, popularly known as “broken heart syndrome,” is characterized by transient regional systolic dysfunction with normal coronary oxygen supply, usually in the setting of extreme emotional or physical stress associated with high endogenous catecholamine activity. Typical TCM is characterized by transient hypokinesis of the left ventricular apex. Generally, it affects females older than 55 years and resolves within a week of presentation. Although the pathogenesis is not well understood, the association with physical or emotional stress suggests it may be caused by catecholamine-induced coronary microvascular vasoconstriction or spasm leading to myocardial stunning.9 Other potential causes of TCM include myocarditis or direct catecholamine-associated myocardial toxicity.9 Reverse TCM is a rare variant of TCM, featuring apical hyperkinesis and basal or inferior wall hypokinesis. Case studies have reported that ECMO can be used to successfully manage pheochromocytoma-induced TCM or cardiogenic shock, as shown in our patient.10
This patient experienced an uncommon occurrence of reverse TCM triggered by a pheochromocytoma crisis, which was likely provoked by the administration of metoprolol before adequate α-blockade. Additionally, the patient’s use of a nasal decongestant spray containing pseudoephredine before presentation likely exacerbated her initial tachycardia. The absence of hypertension and classic symptoms of pheochromocytoma made the diagnosis especially challenging.
The section Cases presents brief case reports that convey clear, practical lessons. Preference is given to common presentations of important rare conditions, and important unusual presentations of common problems. Articles start with a case presentation (500 words maximum), and a discussion of the underlying condition follows (1000 words maximum). Visual elements (e.g., tables of the differential diagnosis, clinical features or diagnostic approach) are encouraged. Consent from patients for publication of their story is a necessity. See information for authors at www.cmaj.ca
Contributors: All of the authors contributed to the conception and design of the work, drafted the manuscript, revised it critically for important intellectual content, gave final approval of the version to be published and agreed to be accountable for all aspects of the work.
This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY-NC-ND 4.0) licence, which permits use, distribution and reproduction in any medium, provided that the original publication is properly cited, the use is noncommercial (i.e., research or educational use), and no modifications or adaptations are made. See: https://creativecommons.org/licenses/by-nc-nd/4.0/
Skinstitut Holiday Gift Kits take the stress out of gifting
Toronto, October 31, 2024 – Beauty gifts are at the top of holiday wish lists this year, and Laser Clinics Canada, a leader in advanced beauty treatments and skincare, is taking the pressure out of seasonal shopping. Today, Laser Clincs Canada announces the arrival of its 2024 Holiday Gift Kits, courtesy of Skinstitut, the exclusive skincare line of Laser Clinics Group.
In time for the busy shopping season, the limited-edition Holiday Gifts Kits are available in Laser Clinics locations in the GTA and Ottawa. Clinics are conveniently located in popular shopping centers, including Hillcrest Mall, Square One, CF Sherway Gardens, Scarborough Town Centre, Rideau Centre, Union Station and CF Markville. These limited-edition Kits are available on a first come, first served basis.
“These kits combine our best-selling products, bundled to address the most relevant skin concerns we’re seeing among our clients,” says Christina Ho, Senior Brand & LAM Manager at Laser Clinics Canada. “With several price points available, the kits offer excellent value and suit a variety of gift-giving needs, from those new to cosmeceuticals to those looking to level up their skincare routine. What’s more, these kits are priced with a savings of up to 33 per cent so gift givers can save during the holiday season.
There are two kits to select from, each designed to address key skin concerns and each with a unique theme — Brightening Basics and Hydration Heroes.
Brightening Basics is a mix of everyday essentials for glowing skin for all skin types. The bundle comes in a sleek pink, reusable case and includes three full-sized products: 200ml gentle cleanser, 50ml Moisture Defence (normal skin) and 30ml1% Hyaluronic Complex Serum. The Brightening Basics kit is available at $129, a saving of 33 per cent.
Hydration Heroes is a mix of hydration essentials and active heroes that cater to a wide variety of clients. A perfect stocking stuffer, this bundle includes four deluxe products: Moisture 15 15 ml Defence for normal skin, 10 ml 1% Hyaluronic Complex Serum, 10 ml Retinol Serum and 50 ml Expert Squalane Cleansing Oil. The kit retails at $59.
In addition to the 2024 Holiday Gifts Kits, gift givers can easily add a Laser Clinic Canada gift card to the mix. Offering flexibility, recipients can choose from a wide range of treatments offered by Laser Clinics Canada, or they can expand their collection of exclusive Skinstitut products.
Brightening Basics 2024 Holiday Gift Kit by Skinstitut, available exclusively at Laser Clincs Canada clinics and online at skinstitut.ca.
Hydration Heroes 2024 Holiday Gift Kit by Skinstitut – available exclusively at Laser Clincs Canada clinics and online at skinstitut.ca.
LONDON (AP) — Most people have accumulated a pile of data — selfies, emails, videos and more — on their social media and digital accounts over their lifetimes. What happens to it when we die?
It’s wise to draft a will spelling out who inherits your physical assets after you’re gone, but don’t forget to take care of your digital estate too. Friends and family might treasure files and posts you’ve left behind, but they could get lost in digital purgatory after you pass away unless you take some simple steps.
Here’s how you can prepare your digital life for your survivors:
Apple
The iPhone maker lets you nominate a “ legacy contact ” who can access your Apple account’s data after you die. The company says it’s a secure way to give trusted people access to photos, files and messages. To set it up you’ll need an Apple device with a fairly recent operating system — iPhones and iPads need iOS or iPadOS 15.2 and MacBooks needs macOS Monterey 12.1.
For iPhones, go to settings, tap Sign-in & Security and then Legacy Contact. You can name one or more people, and they don’t need an Apple ID or device.
You’ll have to share an access key with your contact. It can be a digital version sent electronically, or you can print a copy or save it as a screenshot or PDF.
Take note that there are some types of files you won’t be able to pass on — including digital rights-protected music, movies and passwords stored in Apple’s password manager. Legacy contacts can only access a deceased user’s account for three years before Apple deletes the account.
Google
Google takes a different approach with its Inactive Account Manager, which allows you to share your data with someone if it notices that you’ve stopped using your account.
When setting it up, you need to decide how long Google should wait — from three to 18 months — before considering your account inactive. Once that time is up, Google can notify up to 10 people.
You can write a message informing them you’ve stopped using the account, and, optionally, include a link to download your data. You can choose what types of data they can access — including emails, photos, calendar entries and YouTube videos.
There’s also an option to automatically delete your account after three months of inactivity, so your contacts will have to download any data before that deadline.
Facebook and Instagram
Some social media platforms can preserve accounts for people who have died so that friends and family can honor their memories.
When users of Facebook or Instagram die, parent company Meta says it can memorialize the account if it gets a “valid request” from a friend or family member. Requests can be submitted through an online form.
The social media company strongly recommends Facebook users add a legacy contact to look after their memorial accounts. Legacy contacts can do things like respond to new friend requests and update pinned posts, but they can’t read private messages or remove or alter previous posts. You can only choose one person, who also has to have a Facebook account.
You can also ask Facebook or Instagram to delete a deceased user’s account if you’re a close family member or an executor. You’ll need to send in documents like a death certificate.
TikTok
The video-sharing platform says that if a user has died, people can submit a request to memorialize the account through the settings menu. Go to the Report a Problem section, then Account and profile, then Manage account, where you can report a deceased user.
Once an account has been memorialized, it will be labeled “Remembering.” No one will be able to log into the account, which prevents anyone from editing the profile or using the account to post new content or send messages.
X
It’s not possible to nominate a legacy contact on Elon Musk’s social media site. But family members or an authorized person can submit a request to deactivate a deceased user’s account.
Passwords
Besides the major online services, you’ll probably have dozens if not hundreds of other digital accounts that your survivors might need to access. You could just write all your login credentials down in a notebook and put it somewhere safe. But making a physical copy presents its own vulnerabilities. What if you lose track of it? What if someone finds it?
Instead, consider a password manager that has an emergency access feature. Password managers are digital vaults that you can use to store all your credentials. Some, like Keeper,Bitwarden and NordPass, allow users to nominate one or more trusted contacts who can access their keys in case of an emergency such as a death.
But there are a few catches: Those contacts also need to use the same password manager and you might have to pay for the service.
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Is there a tech challenge you need help figuring out? Write to us at onetechtip@ap.org with your questions.
The Canadian Paediatric Society says doctors should regularly screen children for reading difficulties and dyslexia, calling low literacy a “serious public health concern” that can increase the risk of other problems including anxiety, low self-esteem and behavioural issues, with lifelong consequences.
New guidance issued Wednesday says family doctors, nurses, pediatricians and other medical professionals who care for school-aged kids are in a unique position to help struggling readers access educational and specialty supports, noting that identifying problems early couldhelp kids sooner — when it’s more effective — as well as reveal other possible learning or developmental issues.
The 10 recommendations include regular screening for kids aged four to seven, especially if they belong to groups at higher risk of low literacy, including newcomers to Canada, racialized Canadians and Indigenous Peoples. The society says this can be done in a two-to-three-minute office-based assessment.
Other tips encourage doctors to look for conditions often seen among poor readers such as attention-deficit hyperactivity disorder; to advocate for early literacy training for pediatric and family medicine residents; to liaise with schools on behalf of families seeking help; and to push provincial and territorial education ministries to integrate evidence-based phonics instruction into curriculums, starting in kindergarten.
Dr. Scott McLeod, one of the authors and chair of the society’s mental health and developmental disabilities committee, said a key goal is to catch kids who may be falling through the cracks and to better connect families to resources, including quicker targeted help from schools.
“Collaboration in this area is so key because we need to move away from the silos of: everything educational must exist within the educational portfolio,” McLeod said in an interview from Calgary, where he is a developmental pediatrician at Alberta Children’s Hospital.
“Reading, yes, it’s education, but it’s also health because we know that literacy impacts health. So I think that a statement like this opens the window to say: Yes, parents can come to their health-care provider to get advice, get recommendations, hopefully start a collaboration with school teachers.”
McLeod noted that pediatricians already look for signs of low literacy in young children by way of a commonly used tool known as the Rourke Baby Record, which offers a checklist of key topics, such as nutrition and developmental benchmarks, to cover in a well-child appointment.
But he said questions about reading could be “a standing item” in checkups and he hoped the society’s statement to medical professionals who care for children “enhances their confidence in being a strong advocate for the child” while spurring partnerships with others involved in a child’s life such as teachers and psychologists.
The guidance said pediatricians also play a key role in detecting and monitoring conditions that often coexist with difficulty reading such as attention-deficit hyperactivity disorder, but McLeod noted that getting such specific diagnoses typically involves a referral to a specialist, during which time a child continues to struggle.
He also acknowledged that some schools can be slow to act without a specific diagnosis from a specialist, and even then a child may end up on a wait list for school interventions.
“Evidence-based reading instruction shouldn’t have to wait for some of that access to specialized assessments to occur,” he said.
“My hope is that (by) having an existing statement or document written by the Canadian Paediatric Society … we’re able to skip a few steps or have some of the early interventions present,” he said.
McLeod added that obtaining specific assessments from medical specialists is “definitely beneficial and advantageous” to know where a child is at, “but having that sort of clear, thorough assessment shouldn’t be a barrier to intervention starting.”
McLeod said the society was partly spurred to act by 2022’s “Right to Read Inquiry Report” from the Ontario Human Rights Commission, which made 157 recommendations to address inequities related to reading instruction in that province.
He called the new guidelines “a big reminder” to pediatric providers, family doctors, school teachers and psychologists of the importance of literacy.
“Early identification of reading difficulty can truly change the trajectory of a child’s life.”
This report by The Canadian Press was first published Oct. 23, 2024.
