One-Year Long-Term Follow up for Post-Acute Sequelae of Covid-19 Pots Patients

Background: Persistence of orthostatic tachycardia, palpitations, and fatigue beyond 4 weeks of an acute COVID-19 infection has been termed Post-Acute Sequelae of COVID-19 (PASC) POTS. We have previously reported 6-month outcomes of PASC POTS. Long-term management and outcomes of these patients is unknown. Objective(s): To examine the long-term management and outcomes of PASC POTS patients. Method(s): We conducted a retrospective study of all patients who were diagnosed with POTS at Cardiology, Neurology, and Rehabilitation Post-COVID clinic after a COVID-19 infection between March 1, 2020, and November 1, 2022, at the University of Texas Health San Antonio. We examined COVID history, POTS diagnosis, management, and one-year outcomes of post-COVID POTS patients. Result(s): In 42 patients that were diagnosed with PASC POTS, 33 had a one-year follow-up. 100% were female, 60.6% were Caucasian. Average age was 40.6 + 11 years while the average BMI was 31.9 + 10.4 kg/m2. The most common symptoms were fatigue (87.9%), palpitations (75.7%), brain fog (72.7%), orthostatic tachycardia, exercise intolerance, and dyspnea (70%). The mean heart rate change with 10-minute standing test was 42.68 + 26.73 beats per minute. At 12-months follow-up, the most common symptom was still fatigue (66.7%), palpitations (45.5%), orthostatic tachycardia, and orthostatic intolerance (42.4%). All patients were managed with increased salt and fluid intake, lower compression stockings and rehabilitation. Fifty five percent of patients were treated with Enhanced External Counter Pulsation (EECP), 42% were treated with beta blockers, 18% with fludrocortisone, 15% with midodrine, and 15% with Pyridostigmine. At 1 year follow-up, 33% of patients reported improvement in their symptoms, 33% reported worsening of symptoms, 24% reported stable symptoms, and 9% had resolution. Conclusion(s): PASC POTS patients continue to experience adverse symptoms even at one year. Physical therapy and rehabilitation and pharmacological therapy appear improve symptoms in a minority of patients.Copyright © 2023

Successful matched unrelated donor hematopoietic stem cell transplantation for infantile Wolman disease

Introduction: Wolman disease is a rare genetic disorder with an autosomal recessive inheritance. A mutation in the LIPA gene causes lysosomal acid lipase (LAL) deficiency results in lipid storage and adrenal insufficiency. Death in early infancy is due to liver failure. Patients and methods: We describe the clinical course of a three-month-old infant diagnosed with Wolman disease. A rapid mutational analysis confirmed a LIPA gene defect. Results: He underwent matched unrelated donor peripheral blood stem cell hematopoietic stem cell transplantation (HSCT) at 3 months of age, with a treosulfan-based conditioning, which resulted in engraftment with donor-derived hematopoietic cells. He required supportive care for sinusoidal obstruction syndrome and mucositis. He was administered low dose prednisolone for grade I skin graft versus host disease, and a complete donor chimerism was documented on several occasions. At one year post HSCT, his growth and development were optimal, and there was no hepatosplenomegaly. He is maintained on glucocorticoid and mineralocorticoid supplements for primary hypoaldosteronism. Conclusion: The case emphasizes the timely diagnosis and the potential for successful treatment of Wolman disease by HSCT. © 2022 Pediatric Hematology Oncology Chapter of Indian Academy of Pediatrics

Hyponatremia in Empty Sella Syndrome: Is it a Covid Sequelae?

The symptoms associated with empty sella syndrome (ESS) include headache, giddiness, vomiting, visual field deficits, and endocrine problems, as well as the radiological appearance of an enlarged sella turcica. This case report highlights a 45-year-old female who had a COVID-19 infection 2 months back and presented with chronic headache, giddiness, and lethargy having persistent hyponatremia later diagnosed as empty sella syndrome on brain magnetic resonance imaging. In this case, we tried to correlate all of these clinical and radiological features as COVID-19 sequelae due to post-Covid hypothalamic-pituitary axis dysfunction.Copyright © 2023 Authors. All rights reserved.

THE UNPREDICTABILITY OF LABILE BP: AFFERENT BAROREFLEX FAILURE IN A CRITICAL PATIENT WITH MULTIPLE THYROID SURGERIES AND COVID-19 INFECTION

SESSION TITLE: Cardiovascular Critical Care Cases SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/19/2022 12:45 pm - 1:45 pm INTRODUCTION: The carotid sinus-arterial baroreflex is essential in maintaining blood pressure (BP) regulation. Afferent baroreflex failure (ABF) can present with labile changes in BP within seconds and can be secondary to neck surgery or radiation (RT). The prevalence and etiology of this condition remain unknown, and management of BP can be challenging. We present here the first case, to our knowledge, of ABF precipitated by thyroidectomy, in a patient (pt) with active COVID-19 pneumonia (PNA), causing difficult control of severely labile BP in a critical care unit. CASE PRESENTATION: A 74-year-old female with a history of COPD and a thyroid mass s/p an open left hemithyroidectomy & isthmusectomy, partial right thyroidectomy with drain placement who presented with dyspnea and hypoxia with COVID-19 PNA and superimposed bacterial PNA. She was immediately intubated and admitted to the ICU. Due to improved alertness and breathing, an extubation trial was done on day 2 but was unsuccessful due to a neck mass compressing the trachea, and during extubation, the pt began to develop stridor, desaturate, and was reintubated. CT head and neck showed a markedly enlarged thyroid with left tracheal deviation and the pt underwent complete thyroidectomy the following day. On the 4th day following surgery, the pt desaturated on PRVC and CXR showed new consolidation, and the PNA panel was positive for K. pneumoniae. The pt's BP began to fluctuate from the 80's/40's - 260's/190's. Titrating pressors were not effective in controlling her volatile BP. Clonidine was started to control hypertensive urgencies, but severe subsequent hypotensive episodes made it difficult to continue. A trial of Fentanyl drip did not add a benefit either. Adequate BP control was finally achieved through administering Clonidine only when SBP reached above 180mmHg and Midodrine when SBP reached below 80mmHg. DISCUSSION: Blood pressure changes can be sensed by carotid sinus stretch receptors. ABF can manifest secondary to carotid sinus nerve damage following neck surgery or radiation. The diagnosis of ABF remains ill-defined;with limited research available to guide definitive management. Critically ill patients with poor prognosis have demonstrated higher ACTH levels with a longer cortisol release, with elevated IL-8 and IL-6 concentrations, concluding potential destructive pituitary-adrenal axis response in the setting of inflammation. IL-6 in particular can manifest following hypoxic conditions. In certain cases of POTS and AD in COVID-19, there has been an improvement of symptoms with the use of B-blockers, fludrocortisone, midodrine, methyldopa, and clonidine. CONCLUSIONS: Additional research with a multidisciplinary approach is warranted to fully optimize the treatment of ABF in patients with neck surgery and or inflammatory conditions such as COVID-19. Reference #1: Biaggioni I, Shibao CA, Jordan J. Evaluation and Diagnosis of Afferent Baroreflex Failure. Hypertension. 2022 Jan;79(1):57-9. Reference #2: Dimopoulou I, Alevizopoulou P, Dafni U, Orfanos S, Livaditi O, Tzanela M, Kotanidou A, Souvatzoglou E, Kopterides P, Mavrou I, Thalassinos N. Pituitary-adrenal responses to human corticotropin-releasing hormone in critically ill patients. Intensive care medicine. 2007 Mar;33(3):454-9. Reference #3: Dani M, Dirksen A, Taraborrelli P, Torocastro M, Panagopoulos D, Sutton R, Lim PB. Autonomic dysfunction in 'long COVID': rationale, physiology and management strategies. Clinical Medicine. 2021 Jan;21(1):e63. DISCLOSURES: No relevant relationships by Wadah Akroush No relevant relationships by Shady Geris No relevant relationships by Brooke Kania No relevant relationships by Anas Mahmoud No relevant relationships by Rajapriya Manickam

COVID-19-INDUCED POSTURAL ORTHOSTATIC TACHYCARDIA SYNDROME

SESSION TITLE: Extraordinary Cardiovascular Reports SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/18/2022 01:35 pm - 02:35 pm INTRODUCTION: Postural orthostatic tachycardia syndrome (POTS) is one of the most common autonomic disorders (1). POTS is diagnosed by increasing heart rate by 30 bpm on more, within the first 10 minutes of standing, without orthostatic hypotension (2). Associated debilitating symptoms are lightheadedness, fainting, tremor, orthostatic intolerance, and tachycardia (2). Viral infections such as HIV, hepatitis C, mumps, Epstein bar virus, and influenza have been commonly reported with POTS syndrome (3 ). We are presenting a rare case of COVID-19 induced POTS. CASE PRESENTATION: 38-year-old presented to the hospital with the chief complaint of shortness of breath chest tightness. Her past medical history was significant for COVID-19 infection two weeks before presentation. On arrival patient's vitals were within normal limits. Her physical examination was unremarkable. Laboratory investigations, including complete blood count, thyroid function test, and comprehensive metabolic profile, were unremarkable. Chest x-ray, CT angiogram, and echocardiogram were unremarkable for any consolidation, pulmonary embolism, and congestive heart failure. Orthostatic vitals were obtained, showing that the patient's heart rate increased from 90 beats/minute to 140 beats/minute, from supine to standing. This patient was diagnosed with COVID-19 induced POTS, given she was meeting the criteria of POTS and no other reason was found for postural orthostatic tachycardia. She was managed conservatively with hydration, and the patient was also instructed about yoga therapy. She was discharged home with a cardiology follow-up. DISCUSSION: COVID-19 induced POTS is a relatively new entity that most commonly affect female, and the estimated prevalence is around is 17 per 100,000 patients (3). It has been reported that 10% of the patient who tests positive for COVID-19 infection remains unwell beyond three weeks after recovery from the infection (2). For some of those patients, POTS may be the cause of their symptoms. The exact pathophysiology for COVID-19 induced POTS is poorly understood and may includes peripheral neuropathy, baroreceptor dysfunction, hypovolemia, and increased serum norepinephrine (2). Nonpharmacological treatment includes increasing fluid consumption of 2 to 3 L of water per day, lower limb compression stockings, and regular exercise (2). The commonly off-label pharmacological treatment include ivabradine, fludrocortisone, midodrine, and beta-blockers (2). CONCLUSIONS: POTS is a new and under-recognized entity. The clinician should have a high suspicion of POTS syndrome in a patient with a history of recent or remote COVID-19 infection presenting with orthostatic symptoms. Timely diagnosis is essential to prevent the morbidity associated with debilitating symptoms. Reference #1: Blitshteyn S & Whitelaw S. Postural Orthostatic Tachycardia Syndrome (POTS) and Other Autonomic Disorders After COVID-19 Infection: A Case Series of 20 Patients. Immunol Res. 2021;69(2):205-11. Reference #2: Jenna Stephanie O'Sullivan, Andrew Lyne, Carl J Vaughan. COVID-19-Induced Postural Orthostatic Tachycardia Syndrome Treated with Ivabradine. BMJ Case Reports CP. 2021;14(6):e243585. Reference #3: Sujana Reddy, Satvik Reddy, Manish Arora. A Case of Postural Orthostatic Tachycardia Syndrome Secondary to the Messenger RNA COVID-19 Vaccine. Cureus. 2021;13(5). DISCLOSURES: No relevant relationships by Arshan Khan

Review of Integrative Therapies for Management of Post-COVID Dysautonomia

Methods: We reviewed reports of post COVID dysautonomia and management strategies pursued to understand best practices and provide a primer for clinicians to guide patient management. We reviewed the literature for case reports of post COVID dysautonomia and compiled the cases into a table. Treatment approaches and outcomes were aggregated into an algorithm for management guidance. Results: Ten studies regarding post COVID dysautonomia were reviewed. Strategies included conservative approaches such as fluids, salt consumption, compression stockings, abdominal binders and head of bed elevation as well as strength building such as yoga, resistance exercise, and recumbent physical activity. Moreover, psychosocial support including cognitive behavioral therapy, biofeedback, and support groups were emphasized along with pharmacologic remedies such as midodrine, ivabradine, fludrocortisone, intravenous immunoglobulin, gabapentin, and topical lidocaine in additoin to interventions such as enhanced external counterpulsation. Primary and secondary outcomes included self-report surveys, autonomic laboratory testing, hand grip strength and heart rate variability. Background: Growing numbers of cases of dysautonomia after acute COVID-19 infection are being reported involving previously healthy patients. This post-COVID dysautonomia is predominantly characterized by lingering neurologic and cardiovascular dysfunction including tachycardia, orthostatic intolerance, migraine, exercise intolerance, fatigue, and cognitive impairment. Anxiety, insomnia, and uncertainty surrounding the COVID-19 pandemic present additional risk factors for sympathetic overdrive and deconditioning. Best management strategies and practice guidelines for this patient population remains unknown. Conclusion: Our review suggests consideration of an integrative, multimodal treatment approach involving physical activity, mental well-being, nutrition, stress management, and medication. These primarily facilitate management of dysautonomia, but rarely lead to complete symptom resolution. Despite the uncertainty associated with post-COVID dysautonomia, patient validation, education, and lifestyle approaches provide the cornerstone of management. Since post-COVID dysautonomia will comprise an increasing number of care consultations, clinician awareness, prompt diagnosis, and personalized management are essential.

Primary Adrenal Insufficiency after COVID-19 Infection

Introduction: The clinical presentation of SARS-CoV-2 ranges greatly from asymptomatic disease to critical illness. The multisystemic effect of COVID-19 is becoming increasingly apparent, but its impact on the endocrine system, in particular, the hypothalamic adrenal axis has yet to be defined. Case Description: A 64-year-old woman with hypothyroidism and type 2 diabetes mellitus presented to the emergency room with a 1-week history of abdominal pain, nausea, and vomiting. The patient experienced an asymptomatic COVID-19 infection 5 months prior and reported an unintentional 30-lb weight loss since. She had been admitted several times at an outside hospital for hyponatremia where she never received exogenous steroids. Physical exam was notable for hypotension, epigastric tenderness, and hyperpigmentation of oral mucosa. Chemistry was significant for hyponatremia 117 mmol/L (135-145). Hyponatremia workup revealed a TSH of 0.33 mcIU/ml (0.35-4.00), free T4 1.4 ng/dl (0.6-1.7), serum osmoles 253 mOsm/kg (279-300), urine osmoles 324 mOsm/kg (300-900) and urine sodium 104 mmol/l consistent with hypotonic hyponatremia. Fluid restriction and salt tablets were initiated. Morning 8 AM cortisol returned low (2.6 μg/dl (ref: >18). A high-dose 250 mcg ACTH stimulation test followed;cortisol levels returned 2.3, 2.9, and 2.6 μg/dl (ref: >18) at baseline, 30, and 60 minutes, respectively. ACTH level was elevated to 1944 pg/ml (7.2-63.3), aldosterone was undetectable < 3.0 ng/dl (upright: 4.0-31.0), anti-21-hydroxylase antibody were positive (ref: neg). CT scan of the abdomen returned unremarkable for any adrenal pathologies. Fluid restriction and salt tablets were discontinued. Hypotension and hyponatremia resolved after initiation of Hydrocortisone IV 25 mg q8h. She was discharged on Hydrocortisone 30 mg daily and Fludrocortisone 0.05 mg daily. Discussion: This patient presented with hyponatremia and biochemical evidence of adrenal insufficiency confirmed by an abnormal stress cortisol response to a high-dose ACTH stimulation test. The markedly elevated ACTH level, inappropriately low aldosterone level, and the presence of anti-21-hydroxylase antibodies support the diagnosis of Addison's disease. Primary adrenal insufficiency (AI) after COVID-19 due to adrenal infarcts and hemorrhage have been documented, but the normal CT suggested that the etiology of AI, in this case, was not due to the aforementioned. This case is the first to suggest the onset of Addison’s disease in the COVID-19 sequelae.

Ectopic ACTH by Carcinoid Tumor Mimicking Nelson Syndrome in a Patient with Bilateral Adrenalectomy

Introduction: Nelson syndrome has been reported in up to 25% of adults after bilateral adrenalectomy (BLA) for Cushing’s disease (CD). It usually manifests as an expanding pituitary mass, rising adrenocorticotropic (ACTH) hormone levels and, in many patients, the development of hyperpigmentation. We review the clinical course of a patient with rising ACTH levels after BLA for presumed CD. Although the diagnosis of Nelson syndrome was considered, he was found 9 years after BLA to have an ectopic ACTH secreting bronchial carcinoid tumor as a cause for the elevated ACTH levels. Case Description: A 35 year old male was evaluated at another institution in 2010 after he presented with weight gain, new onset hypertension, muscle weakness with multiple falls, depression, irritability and emotional lability. He was diagnosed with CD and was referred to a university center where he underwent trans-sphenoidal pituitary surgery in May 2011. An adenoma was seen on frozen section but not on the final pathology. He developed transient symptoms of adrenal insufficiency on the second post-operative day. Because of persistent hypercortisolism he underwent BLA in November 2011. We started following him in 2012 and signs of hypercortisolism gradually resolved. He appeared euadrenal on hydrocortisone 10 mg am, 5 mg 12 noon and 5 mg 6 pm and fludrocortisone 0.05 mg daily. ACTH levels increased from 54 pg/ml (6-50) in 2012 to 1024 pg/ml in 2019. He had no hyperpigmentation and MRI of the pituitary from 2014-20 did not show a pituitary mass. During an evaluation for COVID-19 infection in May 2020, a chest x ray revealed a right lower lobe lung mass measuring 3.3 x 2.0 cm. He underwent right lower lobe lung lobectomy in July 2020 and pathology revealed a carcinoid tumor-spindle cell pattern which stained strongly positive for ACTH and weakly positive for chromogranin. ACTH levels after the surgery decreased to 16.3 pg/ml. Discussion: Some authors have suggested that Nelson syndrome be considered in patients with BLA who have one of the following: an expanding pituitary mass or ACTH levels >500 p/ml at 3 different time points after surgery. This case highlights the need to consider ectopic ACTH syndrome as another cause for rising ACTH levels after BLA for CD especially in those patients who are not found to have a discreet adenoma after pituitary surgery.

Adrenal crisis in elderly patients with adrenal insufficiency following COVID-19 vaccination

Introduction: Adrenal insufficiency (AI) is a life-threatening disorder requiring life-long glucocorticoid (GC) replacement therapy. There is no systematic evidence if COVID-19 vaccination can precipitate an adrenal crisis (AC) in patients with known AI. Case Description: Case 1 75-year-old (yo) man with a history of (h/o) optimally controlled hypothyroidism and primary AI since 2006 on levothyroxine 150 mcg, prednisone 4 mg, and fludrocortisone 0.1 mg daily developed a subjective fever, nausea, fatigue, and weakness following 2nd dose of Moderna vaccine. Clinical and biochemical evaluation in a local medical center demonstrated the presence of dehydration, hypotension, moderate hyponatremia, and cortisol level of 0.1 mcg/dl suggesting that he was in adrenal crisis. Following the admission, he was treated with stress dose steroids and intravenous fluids for 3 days and was discharged home in stable condition. Case 2 76-yo man with a h/o panhypopituitarism since 2003 on levothyroxine 150 mcg, hydrocortisone 20 mg in am and 10 mg in pm, and testosterone replacement therapy sought medical attention in the emergency department 1 day after he received 2nd dose of Moderna vaccine complaining of fatigue, generalized weakness, and chills. His blood pressure was 84/47 mmHg, heart rate was 130 bpm suggesting he was in adrenal crisis. Following the admission, he was treated with stress dose steroids and intravenous fluids for 4 days and was discharged home in stable condition. Discussion: COVID-19 vaccination may cause various side effects including pain at the injection site, fatigue, headache, myalgias, arthralgias, chills, and fever which may place AI patients at risk for adrenal crisis as seen in our cases. In general, AI patients are instructed to increase the GC dose 2-3 times for several days during stressful situations. There is no evidence or clear recommendations if such advice should be offered to the AI patients receiving COVID-19 vaccination The survey of clinicians conducted by the Pituitary Society showed that most clinicians plan to maintain the current GC dose with vaccine administration with consideration of increasing GC dose in case of fever, arthralgias and/or myalgias. The UK Society of Endocrinology recommends that there is no need to routinely increase GC dose at the time of COVID 19 vaccination. We suggest that AI patients should be instructed to immediately implement the sick day rule and increase their GC dose if they develop any constitutional symptoms following the COVID-19 vaccination. It is unknown if the prophylactic increase in GC dose should be advised as we have no information on the potential impact of excessive GC on the immune response to the vaccination.

Low-dose corticosteroid therapy for cardiogenic shock in adults (COCCA): study protocol for a randomized controlled trial.

BACKGROUND: Cardiogenic shock (CS) is a life-threatening condition characterized by circulatory insufficiency caused by an acute dysfunction of the heart pump. The pathophysiological approach to CS has recently been enriched by the tissue consequences of low flow, including inflammation, endothelial dysfunction, and alteration of the hypothalamic-pituitary-adrenal axis. The aim of the present trial is to evaluate the impact of early low-dose corticosteroid therapy on shock reversal in adults with CS. METHOD/DESIGN: This is a multicentered randomized, double-blind, placebo-controlled trial with two parallel arms in adult patients with CS recruited from medical, cardiac, and polyvalent intensive care units (ICU) in France. Patients will be randomly allocated into the treatment or control group (1:1 ratio), and we will recruit 380 patients (190 per group). For the treatment group, hydrocortisone (50 mg intravenous bolus every 6 h) and fludrocortisone (50 µg once a day enterally) will be administered for 7 days or until discharge from the ICU. The primary endpoint is catecholamine-free days at day 7. Secondary endpoints include morbidity and all-cause mortality at 28 and 90 days post-randomization. Pre-defined subgroups analyses are planned, including: postcardiotomy, myocardial infarction, etomidate use, vasopressor use, and adrenal profiles according the short corticotropin stimulation test. Each patient will be followed for 90 days. All analyses will be conducted on an intention-to-treat basis. DISCUSSION: This trial will provide valuable evidence about the effectiveness of low dose of corticosteroid therapy for CS. If effective, this therapy might improve outcome and become a therapeutic adjunct for patients with CS. TRIAL REGISTRATION: ClinicalTrials.gov , NCT03773822 . Registered on 12 December 2018.