Pituitary Disease Management And Patient Care Recommendations During The Covid-19 Pandemic

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the viral strain that has caused the coronavirus disease 2019 (COVID-19) pandemic, has presented healthcare systems around the world with an unprecedented challenge. In locations with significant rates of viral transmission, social distancing measures and enforced ‘lockdowns’ are the new ‘norm’ as governments try to prevent healthcare services from being overwhelmed. However, with these measures have come important challenges for the delivery of existing services for other diseases and conditions. The clinical care of patients with pituitary disorders typically involves a multidisciplinary team, working in concert to deliver timely, often complex, disease investigation and management, including pituitary surgery. COVID-19 has brought about major disruption to such services, limiting access to care and opportunities for testing (both laboratory and radiological), and dramatically reducing the ability to safely undertake transsphenoidal surgery. In the absence of clinical trials to guide management of patients with pituitary disease during the COVID-19 pandemic, herein the Professional Education Committee of the Pituitary Society proposes guidance for continued safe management and care of this population.

Introduction

In many centers worldwide, the evaluation and treatment of pituitary disorders has already been substantially impacted by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the viral strain that has caused the coronavirus disease 2019 (COVID-19) pandemic. With reduced access to routine clinical services, patients with suspected or confirmed pituitary disease face the prospect of delays in diagnosis and implementation of effective treatment plans. Furthermore, patients undergoing surgery may be at increased risk from COVID-19, whilst the risk of infection to healthcare providers during pituitary surgery is of particular concern.

Herein, we discuss several clinical scenarios where clinical care can be adjusted temporarily without compromising patient outcomes. For this expert guidance, The Pituitary Society Professional Education Committee, which includes neuroendocrinologists and neurosurgeons from four continents, held an online video conference call with subsequent discussions conducted through email communications. The suggestions are not evidence-based due to the novelty and timing of the pandemic; furthermore, re-evaluation every few months in light of emerging data, is recommended. The approach will also likely vary from country to country depending on the risk of viral infection, local rules for “lockdown”, and the capabilities of individual health care systems.

Pituitary surgery challenges during the COVID-19 pandemic

The significant challenges to pituitary surgery presented by COVID-19 can be considered in terms of the phase of the pandemic, the patient, the surgeon, and the healthcare institution (Table 1).

Table 1 Pituitary surgery challenges and recommendations during COVID-19 pandemic

The World Health Organization (WHO) recognizes several phases of a pandemic wave [1]. When the pandemic is in progress (WHO pandemic phase descriptions; Phase 6) [2] there is a high prevalence of active cases. In the immediate post-peak period, the pandemic activity appears to wane, but active cases remain, and additional waves may follow. Previous pandemics have had many such waves, each separated by several months (www.cdc.gov). The corollary is that there will remain a significant possibility of patients and surgeons contracting COVID-19 until a vaccine is developed or herd immunity is achieved by other means.

The patient requiring pituitary surgery may be especially vulnerable to COVID-19 due to age and/or comorbidities. This is particularly true of patients with functioning pituitary adenomas such as those with Cushing’s disease (CD), where cortisol excess results in immunosuppression, hypercoagulability, diabetes mellitus and hypertension, and acromegaly which is also frequently complicated by diabetes mellitus and hypertension. Moreover, the risk for patients undergoing surgery that develop COVID-19 in the perioperative period appears to be very high. In a retrospective analysis of 34 patients who underwent elective—non pituitary—surgeries during the incubation period of COVID-19, 15 (44.1%) patients required admission to the intensive care unit, and 7 (20.5%) died [3]. Although this study included cases of variable technical difficulty, complexity and risk—from excision of breast lump to total hip replacement—we would suggest that patients undergoing pituitary surgery that develop COVID-19 are likely to be at similar or greater risk. These risks must be balanced carefully against the natural history of pituitary disease and, in particular, whether undue delay may result in irreversible morbidity such as visual loss in patients with pituitary apoplexy.

The surgeon remains in direct contact with the patient throughout their operation and is therefore at risk of contracting COVID-19 if the patient has an active infection. Iorio-Morin et al. [4] suggest that surgeons performing transsphenoidal pituitary surgery (TSS) may be at the greatest risk, because such surgery is performed under general anesthesia, requiring intubation and extubation, exposes the colonized nasal mucosa, and usually involves sphenoid drilling, which can result in aerosolization of contaminated tissues.

The healthcare institution will invariably divert resources from elective services to support the care of patients with COVID-19, with a knock-on effect on the capacity to manage patients with pituitary disease (Table 1). Bernstein et al. [5] suggest that surgery is particularly affected in such reorganization, because of both the need for redeployment of anesthesiologists able to manage patient airways, and availability of protective physical resources such as masks, gowns, and gloves (personal protective equipment; PPE). Furthermore, in areas with high number of infections, several operating rooms (OR)s were converted into intensive care units (ICU) to treat patients with COVID-19, thus limiting patients’ access to elective surgery even more.

Recommendations for pituitary surgery

When the viral risk is decreasing in a specific geographic area, we would advocate a stepwise, but flexible normalization of activity, addressing each of the aforementioned factors.

Burke et al. [6] proposed a staged volume limiting approach to scheduling surgical cases depending on the number of community cases and inpatients with COVID-19, and staffing shortages. In extreme cases, where significant assistance is required from outside institutions, only emergent cases can proceed.

Until further data become available, all patients undergoing pituitary surgery should undergo screening for COVID-19, until a vaccine is developed or herd immunity is achieved by other means. At the least, we recommend screening patients for cough, fever, or other recognized symptoms of infection with SARS-CoV-2, and taking swab samples for testing if there is any clinical suspicion. Depending on the level of COVID-19 activity in the community, and available resources, a more exhaustive strategy may be appropriate, including isolation of patients for up to 2 weeks before surgery, paired swabs and/or serological tests for all patients irrespective of symptoms, and routine chest X-ray or chest computed tomography (CT), depending on local guidance. In patients with COVID-19 in whom surgery is indicated, in general we recommend delaying surgery if possible, ideally until patients no longer have symptoms and have a negative swab test result.

The nature of the patient’s pituitary disease is an important consideration, and we propose stratifying cases as emergent, urgent, or elective. We recommend that patients continue to be operated on in an emergent fashion if they present with pituitary apoplexy, acute severe visual loss, or other significant mass effect, or if there is concern regarding malignant pathology. Selected patients with slowly progressive visual loss, functioning tumors with aggressive clinical features, and those with an unclear diagnosis, may also benefit from urgent (but not emergent) surgery, with decisions made on a case-by-case basis. Patients with incidental and asymptomatic tumors, known nonfunctioning adenomas [7] or functioning tumors, which are well controlled with medical therapy, can be scheduled as elective cases.

In most cases, TSS remains the safest, most effective, and most efficient approach to pituitary tumors. In a series of 9 consecutive patients without COVID-19 undergoing pituitary and skull base surgery during the pandemic, Kolias et al. [8] reported that none of the patients or staff contracted COVID-19 following adoption of a standardized risk-mitigation strategy. In the rare instances where a patient with COVID-19 requires emergent surgery that cannot be deferred, alternative transcranial approaches may be considered (avoiding nasal mucosa). To replace high-speed drilling, the use of non-powered tools such as rongeurs and chisels has been recommended. If this is not possible large suction tubes can be used to aspirate as much particulate matter as possible [9]. In such cases, the availability and use of PPE, and in particular filtering facepiece (FFP3) respirators, is mandated. Depending on the level of COVID-19 activity in the community, and the availability and effectiveness of testing, PPE may be appropriate in all cases.

At an institutional level, there must remain flexibility in anticipation of further waves of COVID-19. This necessitates a reduction in capacity, particularly in available ICU beds, that must be recognized when scheduling challenging surgical cases. In the long term, resumption of full elective workloads depends on wider national and international factors, including widespread testing, and widespread immunity through vaccination or other means.

Pituitary diseases diagnosis and management

Acromegaly

Acromegaly, a condition that arises from growth hormone (GH) excess, generally occurs as a result of autonomous GH secretion from a somatotroph pituitary adenoma [1011], is associated with substantial morbidity and excess mortality, which can be mitigated by prompt and adequate treatment [12]. Diagnosis is often delayed because of the low prevalence of the disease, the frequently non-specific nature of presenting symptoms, and the typically subtle progression of clinical features [1011]. During the COVID-19 pandemic many outpatient clinics have closed or limited work hours. Patients are often reluctant to seek care out of fear of possible exposure to the coronavirus. Therefore, even longer diagnostic delays are anticipated. In addition, patients who present with vision loss and larger tumors encroaching upon the optic apparatus are at risk for experiencing persistent visual compromise unless the optic chiasm and nerves are promptly decompressed.

To improve patient access to care and minimize potentially deleterious delays in diagnosis and treatment, clinicians may conduct virtual visits (VV) using secure, internet-based electronic medical record platforms. A detailed history can be obtained and a limited physical examination is possible, including inspection of the face, skin and extremities.

Diagnosis

Establishing the diagnosis of acromegaly requires testing of serum insulin-like growth factor-I (IGF-I) levels [11] (Box 1). Access to accurate IGF-I assays is critical in light of the substantial analytical and post-analytical problems that have plagued several IGF-I immunoassays. While the oral glucose tolerance test (OGTT) is considered the diagnostic “gold standard”, this test is not essential in many patients, including those with a clear-cut clinical picture and an unequivocally elevated serum IGF-I level. Deferring the lengthy (2-h) OGTT may minimize the risk of potential exposure to infectious agents.

Given the over-representation of macroadenomas in patients with acromegaly, pituitary imaging is indicated, preferably by a pituitary-specific magnetic resonance imaging (MRI) protocol, although CT may be performed to rule out a large tumor if MRI is not feasible. Obtaining imaging at satellite sites detached from major hospitals may also decrease the risk of infection exposure.

Management

Transsphenoidal pituitary surgery remains the treatment of choice for most patients with acromegaly [1011], and patients with visual compromise as a result of a pituitary adenoma compressing the optic apparatus should still undergo pituitary surgery promptly. Other patients could be treated medically until the pandemic subsides. Medical treatment options are somatostatin receptor ligands (SRLs), octreotide long-acting release (LAR), lanreotide depot and pasireotide LAR, pegvisomant and cabergoline (used off-label) [13]. Medical therapies can be effective in providing symptomatic relief, control GH excess or action, and potentially reduce tumor size (except pegvisomant, which does not have direct antiproliferative effects). Preoperative medical therapy has been reported to improve surgical outcomes in some, but not all studies. Pasireotide, which potentially can induce QTc prolongation, should be used with caution in patients who are taking, either as prophylaxis or treatment, medications for COVID-19 (azithromycin, hydroxychloroquine), which can also have an effect on QTc interval. Furthermore, as hyperglycemia is very frequent in patients treated with pasireotide and needs close monitoring at start of the treatment, this treatment should be reserved for truly resistant cases, with large tumors and who cannot have surgery yet. Notably, lanreotide depot, cabergoline or pegvisomant can be administered by the patient or a family member and therefore an in-person visit to a clinic is not required. If SRLs that require health care professional administration are required, raising the dose may allow the interval between injections to be extended beyond 4 weeks while maintaining disease control. Virtual visits can be implemented to monitor the patient’s course and response to medical therapy during the pandemic. Careful management of comorbidities associated with acromegaly remains an essential part of patient care [1415].

Prolactinomas

Hyperprolactinemia may be physiological in origin or arise because of an underlying pathophysiologic cause, medication use or laboratory artifact. Therefore, an initial evaluation for hyperprolactinemia should include a comprehensive medication history, a thorough evaluation for secondary causes, including primary hypothyroidism, and a careful assessment for clinical features of hyperprolactinemia, including hypogonadism and galactorrhea. Unless a secondary cause of hyperprolactinemia can be established definitively, further investigation is indicated to evaluate the etiology of hyperprolactinemia.

Diagnosis

The diagnosis of a lactotroph adenoma can be inferred in most patients based on the presence of a pituitary adenoma and an elevated prolactin level, which is typically proportionate in magnitude to adenoma size. Pituitary imaging (MRI or CT) is therefore a key step in the investigation of hyperprolactinemia. Evaluation for hypopituitarism is also necessary.

Management

Although observation and routine follow-up with serial prolactin levels and imaging is acceptable for patients who are asymptomatic and who have a microadenoma, most patients diagnosed with a prolactinoma will require treatment. Dopamine-agonists (DA) can normalize prolactin levels and lead to reduction in size of the lactotroph adenoma [16]. In patients who have a microadenoma and who are not seeking fertility, hormone-replacement therapy may also be appropriate if serum prolactin is routinely followed and imaging performed as necessary.

Medical therapy can be managed effectively and efficiently via VVs coupled with laboratory/imaging studies as needed. However, in all patients in whom a DA will be initiated, it is critical that a comprehensive psychiatric history is obtained prior to commencing treatment. Patients may not readily volunteer their psychiatric history and may not appreciate the relevance of such information. For example, until specifically questioned about their psychiatric history, the patient described in the illustrative case (Box 2) did not report a history of severe depression, suicide attempt and prolonged psychiatric hospitalization 8 months prior to presentation with hyperprolactinemia. At the time of the visit, he was not taking any psychiatric medications and was not under the care of a mental health team. Given this patient’s significant psychiatric history, lack of ongoing psychiatric care, and the well-recognized adverse effects of DA therapy, including increased impulsivity, depression and psychosis [17], a DA was not initiated. Counseling on potential DA side-effects is crucial, as they may also present in individuals with no prior psychiatric history [17]. Furthermore, during the COVID-19 pandemic when there is reduced access to routine medical and mental health care, patients who develop symptoms of severe depression may not have ready access to mental health services, or may not seek care. Therefore, it is particularly important to make patients aware of these potential side effects and the critical importance of reporting them.

In the small number of patients for whom medical therapy is not possible and where surveillance is not appropriate (e.g., macroprolactinoma with visual loss) the risks and benefits of surgical intervention will need to be carefully weighed.

Cushing’s disease

Left untreated, CD has significant morbidity and mortality, and delays in diagnosis (from a few months to even years) are common. Clinical presentation is also very variable with some patients having subtle symptoms while others present with more striking/classical features. Severe hypercortisolemia induces immunosuppression, which may place patients with untreated CD at particular risk from COVID-19.

New patients referred for endocrinology evaluation with clinical suspicion of Cushing’s

Diagnosis

Screening for, and confirmation of Cushing’s syndrome (CS) and, furthermore, localization for CD is laborious and requires serial visits and testing procedures [1819]. If initial laboratory abnormalities are consistent with hypercortisolemia, a VV should allow for an estimate of the severity of clinical presentation and facilitate planning for further testing and treatment. Careful questioning for potential causes of exogenous CS (including, but not limited to, history of high-dose oral corticosteroids, intraarticular injections or topical preparations) is an important first step. Subsequently, establishing the likelihood and pretest probability of CS is more important than ever now, when testing may be delayed. While presentation varies significantly between patients, some features, although not all highly sensitive, are more specific, e.g. easy bruising, facial plethora, large wide > 1 cm violaceous striae, proximal weakness and hypokalemia. Diagnosis of CS is often challenging even under normal circumstances, however, a diagnosis by VV is more nuanced and difficult. Conversely, if a patient has a high likelihood of CS, we recommend limited laboratory evaluation (urinary free cortisol (UFC), adrenocorticotropic hormone (ACTH), liver panel, basic metabolic panel), preferably at a smaller local laboratory rather than a Pituitary Center, to reduce viral risk exposure. Salivary cortisol samples could represent a hazard for laboratory staff and they are prohibited in some countries [1819]. In the US, laboratories have continued to process salivary cortisol samples and salivary cortisol has higher sensitivity compared with UFC and has the convenience of mailing multiple specimens at a time, without travel [1819]. Though usually we strongly recommend sequential laboratory testing under normal circumstances, limiting trips to a laboratory is preferred during COVID-19.

If preliminary assessment confirms ACTH-dependent CS [1819] and no visual symptoms are reported, imaging may be delayed. However, in the presence of any visual symptoms, and recognizing the challenges of undertaking a formal visual field assessment, proceeding directly with MRI or CT (shorter exam time and easier machine access) imaging, will allow confirmation or exclusion of a large pituitary adenoma compressing the optic chiasm. If the latter is confirmed, the patient will need to be evaluated by a neurosurgeon. In contrast, a small pituitary adenoma may not be visible on CT, but in such cases MRI may be deferred for a few months until COVID-19 restrictions limiting access to care are lifted.

Another VV will help to decide, in conjunction with patient’s preference, the best next step, which in cases of more severe clinical Cushing’s, and in the absence of a large pituitary adenoma, would be medical therapy. The magnitude of 24 h-UFC elevation could also represent a criterion for primary therapy, since higher values have been associated with increased risk of infection.

In parallel, it is also important to address comorbidities including diabetes mellitus, hypertension and hyperlipidemia. In light of the increased risk of venous thromboembolism, in discussion with primary care providers, plans for regular mobilization/exercise as permitted (including at home when orders to stay in are in place) and/or prophylactic low weight molecular heparin should be considered.

Management

First line medical therapy options vary, depending on country availability, regulatory approval and patient comorbidities. Ideally, an oral medication, which is easier to administer is preferred; options include ketoconazole, osilodrostat or metyrapone [2021]. Cabergoline therapy, which has lesser efficacy [2021] compared with adrenal steroidogenesis inhibitors, can be also attempted in very mild cases. The initial laboratory profile should be reviewed to exclude significant abnormalities of renal and/or liver function prior to commencing treatment. Starting doses of all medications should be the lowest possible to avoid adrenal insufficiency (AI) and up titration should be slow, with VVs weekly if possible. All patients with CS on any type of medical therapy should have prescribed glucocorticoids (GC) both in oral and injectable forms available at home and information regarding AI should be provided during a VV when starting therapy for CS. Down titration of other medications for diabetes and hypertension may also be needed over time. Pasireotide (both subcutaneous and LAR preparations) would be a second line option, reflecting higher risk of significant hyperglycemia that would require treatment [22].

If the clinical features of CS are mild and longstanding, with no acute deterioration, another possibility is to aggressively treat the associated comorbidities for a few months; depending on local circumstances, this may actually be less risky for the patient by avoiding the risk of AI/crisis and the need for an emergency department (ED) visit and/or admission.

For patients with Cushing’s disease with endocrinology chronic care

Patients in remission after surgery with adrenal insufficiency on glucocorticoid replacement

These patients are likely to remain at slightly higher risk of COVID-19 infection due to immunosuppression from previous hypercortisolemia. Furthermore, GC doses should be adjusted to prevent adrenal crisis and visits to an ED. Lower GC daily doses (10–15 mg hydrocortisone/day) are now frequently used for replacement and virtual and/or phone visits are encouraged to evaluate an appropriate regimen and sufficient supplies of medication and injectable GC (at home) should be prescribed. Patients with potential symptoms of under replacement may require an increase in daily dose, while balancing any risk of GC over replacement and possible consequent immunosuppression.

Patients in non-remission treated with medical therapy (dependent on country availability)

Doses may need to be adjusted to reduce the risk of AI/crisis and reduce the need for serial laboratory work. Monthly or bimonthly VVs are appropriate for clinical evaluation and up titration should be slower than usual. Patients with CD on medical therapy need to have at home prescriptions for oral and injectable GC and instruction on AI surveillance. Patients should also be advised, that if they develop a fever, to stop Cushing’s medication for few days; if they develop AI symptoms, GC administration will be required. In some countries, block and replace regimens are also employed to avoid risk of AI. Of note, for mifepristone, a glucocorticoid receptor (GR) antagonist, patients will require much higher doses of GC to reverse the blockade (1 mg of dexamethasone approximately per 400 mg of mifepristone) and for several days, as drug metabolites also have GR antagonist effects.

Furthermore, for all patients who have made dose changes or discontinued medications for Cushing’s, it is essential to follow very closely and consider adjustments in the doses of concomitant medications, especially insulin, other antidiabetic and antihypertensive medications, and potassium supplements.

If patients have history of radiotherapy and are still on medications for CD, a VV every few months should be performed to determine if anti-Cushing’s treatment can be slowly down-titrated (to avoid AI). A morning serum cortisol would be ideal to rule out AI off medications, however, if laboratory testing cannot be undertaken safely, clinical evaluation by serial VVs can be helpful. While head-to-head data will never be available, in COVID-19 hotspots, given the higher risk of infection with laboratory testing or face to face visits, mild hypercortisolemia might be “better” than adrenal crisis, especially in the short term!

Patients with CD have increased rates of depression, anxiety and can have decreased quality of life (QoL) even when in long-term remission, thus in the challenging circumstances of the current pandemic it is it even more important to focus on psychological evaluation during virtual endocrinology visits, with referral to virtual counseling as needed.

From https://link.springer.com/article/10.1007/s11102-020-01059-7?utm_source=newsletter_370

Medical ID Jewelry Often Lacks Clear Instructions For Adrenal Insufficiency

Rushworth RL, et al. Clin Endocrinol. 2019;doi:10.1111/cen.13985.

Only 4.8% of patients with adrenal insufficiency who use medical identification jewelry clearly indicate on their emblem the need for urgent parenteral hydrocortisone in the event of an adrenal crisis, potentially jeopardizing the ability to receive proper assistance in an emergency, according to a cross-sectional analysis published in Clinical Endocrinology.

“Although the use of medical identification jewelry is recommended for patients with adrenal insufficiency to assist in the prevention and treatment of an adrenal crisis, the results of this study indicate that this advice is taken up by only a modest proportion of patients,” R. Louise Rushworth, MBBS, PhD, FAFPHM, an adjunct professor and medical epidemiologist at the School of Medicine, Sydney, and the University of Notre Dame Australia, told Endocrine Today. “Patients with secondary adrenal insufficiency have a lower uptake than those with primary adrenal insufficiency despite their risk of an adrenal crisis approaching that people with primary adrenal insufficiency.”

In a cross-sectional analysis, Rushworth and colleagues analyzed data from 1,955 patients with adrenal insufficiency aged at least 20 years with an active subscription to a large medical jewelry provider (MedicAlert) as of September 2018. The researchers calculated subscription rates by adrenal insufficiency subtype, geographic area, age and sex using relevant population data.

The overall subscription rate was 105.79 per million, representing approximately one-third of the estimated 300 per million patients with adrenal insufficiency in the population, according to researchers. Among subscribers, 57.4% had primary adrenal insufficiency and 15.1% had a diagnosis of congenital adrenal hyperplasia. The overall subscription rate for patients with primary adrenal insufficiency was 61.72 per million, or 61.7% of the approximately 100 per million patients with primary adrenal insufficiency in the Australian population, according to researchers.

Researchers observed considerable differences in subscription rates based on geographic region, patient age and sex. Western Australia had an overall subscription rate (247 per million) that was more than four times higher than Victoria, the state with the lowest subscription rate (60.87 per million; P < .0001). Patients aged 60 to 69 years had the highest subscription rate (165.15 per million), whereas patients aged 30 to 39 years had the lowest rate (47.23 per million; P < .001). Additionally, most subscribers reporting primary adrenal insufficiency were women (69%).

The researchers found that hydrocortisone was the most common replacement therapy (41.6%), followed by cortisone acetate (25.6%) and prednisone (16.3%). They noted that few patients — only 4.8% — clearly mentioned the need for urgent parenteral hydrocortisone in the event of severe illness.

Rushworth said most patients who used medical identification jewelry did not have clear emergency instructions inscribed on the emblem, and that this may lead to delays in administration of hydrocortisone in an emergency.

“Guidelines recommend that patients with adrenal insufficiency who are at risk for adrenal crisis should wear medical identification jewelry as a form of nonverbal communication in an emergency,” Rushworth said. “These should be recommended by the treating doctor, and adherence should be encouraged and reviewed regularly. The jewelry should be inscribed with clear instructions for emergency treatment, for example: ‘Adrenal insufficiency. Give IM 100 mg hydrocortisone.’” – by Regina Schaffer

From https://www.healio.com/endocrinology/adrenal/news/online/%7Be7eef183-09a5-46aa-96e1-1feb7c8f1e05%7D/medical-id-jewelry-often-lacks-clear-instructions-for-adrenal-insufficiency?page=2

Cortisol Pumps May Be Viable Option to Reduce Adrenal Crisis in Severe Adrenal Insufficiency

The use of an insulin pump to deliver continuous pulsatile cortisol may be a viable treatment option in patients with severe adrenal insufficiency who are unresponsive to oral corticosteroids, according to study results presented at the 28th Annual Congress of the American Association of Clinical Endocrinologists, held April 24 to 28, 2019, in Los Angeles, California.

According to the investigators, increasing oral steroid doses may be required to prevent adrenal crisis in patients with adrenal insufficiency. However, in light of the associated side effects of long-term use of steroids, an alternative treatment method is needed. Insulin pumps, typically used to treat patients with diabetes, can be used to deliver steroids and may provide symptom control, prevent adrenal crisis, and lower required corticosteroid dose.

The current study enrolled patients with adrenal insufficiency who could not absorb oral corticosteroid treatment or were not responding to treatment. Of 118 patients with adrenal insufficiency, 6 patients were switched to pump treatment.

The results indicated that the use of cortisol pumps was associated with a 78.5% risk reduction for adrenal crisis compared with oral corticosteroids. As hydrocortisone dose was gradually tapered using the cortisol pump, there was a mean dose reduction of 62.77 mg compared with oral corticosteroid therapy.

The researchers noted that in addition to reducing the number of adrenal crises, use of a cortisol pump was found to be associated with better symptom control and quality of life.

“Continuous pulsatile cortisol replacement via pump is an option for management of severe adrenal insufficiency in patients unresponsive to oral therapy,” concluded the researchers.

Reference

Khalil A, Ahmed F, Alzohaili O. Insulin pump for adrenal insufficiency, a novel approach to the use of insulin pumps to deliver corticosteroids in patients with poor cortisol absorption. Presented at: American Association of Clinical Endocrinologists 28th Annual Scientific & Clinical Congress; April 24-28, 2019; Los Angeles, CA.

From https://www.endocrinologyadvisor.com/home/conference-highlights/aace-2019/cortisol-pumps-may-be-viable-option-to-reduce-adrenal-crisis-in-severe-adrenal-insufficiency/

Health Alert: Adrenal Crisis Causes Death in Some People Who Were Treated with hGH

Doctors conducting the follow-up study of individuals treated with hGH looked at causes of death among recipients and found some disturbing news. Many more people have died from a treatable condition called adrenal crisis than from CJD (MaryO’Note: Creutzfeldt-Jakob Disease). This risk does not affect every recipient. It can affect those who lack other hormones in addition to growth hormone. Please read on to find out if this risk applies to you. Death from adrenal crisis can be prevented.

Adrenal crisis is a serious condition that can cause death in people who lack the pituitary hormone ACTH. ACTH is responsible for regulating the adrenal gland. Often, people are unaware that they lack this hormone and therefore do not know about their risk of adrenal crisis.

Most people who were treated with hGH did not make enough of their own growth hormone. Some of them lacked growth hormone because they had birth defects, tumors or other diseases that cause the pituitary gland to malfunction or shut down. People with those problems frequently lack other key hormones made by the pituitary gland, such as ACTH, which directs the adrenal gland to make cortisol, a hormone necessary for life. Having too little cortisol can be fatal if not properly treated.

Treatment with hGH does not cause adrenal crisis, but because a number of people lacking growth hormone also lack ACTH, adrenal crisis has occurred in some people who were treated with hGH. In earlier updates we have talked about how adrenal crisis can be prevented, but people continue to die from adrenal crisis, which is brought on by lack of cortisol. These deaths can be prevented. Please talk to your doctor about whether you are at risk for adrenal crisis.

  • Why should people treated with hGH know about adrenal crisis? Among the people who received hGH, those who had birth defects, tumors, and other diseases affecting the brain lacked hGH and often, other hormones made by the pituitary gland. A shortage of the hormones that regulate the adrenal glands can cause many health problems. It can also lead to death from adrenal crisis. This tragedy can be prevented.
  • What are adrenal hormones? The pituitary gland makes many hormones, including growth hormone and ACTH, a hormone which signals the adrenal glands to make cortisol, a hormone needed for life. If the adrenal gland doesn’t make enough cortisol, replacement medications must be taken. The most common medicines used for cortisol replacement are:
    • Hydrocortisone
    • Prednisone
    • Dexamethasone
  • What is adrenal crisis? Adrenal hormones are needed for life. The system that pumps blood through the body cannot work during times of physical stress, such as illness or injury, if there is a severe lack of cortisol (or its replacement). People who lack cortisol must take their cortisol replacement medication on a regular basis, and when they are sick or injured, they must take extra cortisol replacement to prevent adrenal crisis. When there is not enough cortisol, adrenal crisis can occur and may rapidly lead to death.
  • What are the symptoms of lack of adrenal hormones? If you don’t have enough cortisol or its replacement, you may have some of these problems:
    • feeling weak
    • feeling tired all the time
    • feeling sick to your stomach
    • vomiting
    • no appetite
    • weight loss

    When someone with adrenal gland problems has weakness, nausea, or vomiting, that person needs immediate emergency treatment to prevent adrenal crisis and possible death.

  • Why are adrenal hormones so important? Cortisol (or its replacement) helps the body respond to stress from infection, injury, or surgery. The normal adrenal gland responds to serious illness by making up to 10 times more cortisol than it usually makes. It automatically makes as much as the body needs. If you are taking a cortisol replacement drug because your body cannot make these hormones, you must increase the cortisol replacement drugs during times of illness, injury, or surgery. Some people make enough cortisol for times when they feel well, but not enough to meet greater needs when they are ill or injured. Those people might not need cortisol replacement every day but may need to take cortisol replacement medication when their body is under stress. Adrenal crisis is extremely serious and can cause death if not treated promptly. Discuss this problem with your doctor to help decide whether you need more medication or other treatment to protect your health.
  • How is adrenal crisis treated? People with adrenal crisis need immediate treatment. Any delay can cause death. When people with adrenal crisis are vomiting or unconscious and cannot take medicine, the hormones can be given as an injection. Getting an injection of adrenal hormones can save your life if you are in adrenal crisis. If you lack the ability to make cortisol naturally, you should carry a medical ID card and wear a Medic-Alert bracelet to tell emergency workers that you lack adrenal hormones and need treatment. This precaution can save your life if you are sick or injured.
  • How can I prevent adrenal crisis?
    • If you are always tired, feel weak, and have lost weight, ask your doctor if you might have a shortage of adrenal hormones.
    • If you take hydrocortisone, prednisone, or dexamethasone, learn how to increase the dose when you become ill.
    • If you are very ill, especially if you are vomiting and cannot take pills, seek emergency medical care immediately. Make sure you have a hydrocortisone injection with you at all times, and make sure that you and those around you (in case you’re not conscious) know how and when to administer the injection.
    • Carry a medical ID card and wear a bracelet telling emergency workers that you have adrenal insufficiency and need cortisol. This way, they can treat you right away if you are injured.

Remember: Some people who lacked growth hormone may also lack cortisol, a hormone necessary for life. Lack of cortisol can cause adrenal crisis, a preventable condition that can cause death if treated improperly. Deaths from adrenal crisis can be prevented if patients and their families recognize the condition and are careful to treat it right away. Adrenal crisis is a medical emergency. Know the symptoms and how to adjust your medication when you are ill. Taking these precautions can save your life.

From https://www.niddk.nih.gov/health-information/endocrine-diseases/national-hormone-pituitary-program/health-alert-adrenal-crisis-causes-death-people-treated-hgh

Yes, You Need a Medical Alert Bracelet!

Shared with permission from https://aiunited.org/medicalbracelets/

Advice from a Volunteer Firefighter with Adrenal Insufficiency

My name is Jeannie, and I have been diagnosed with Secondary AI since March of 2015. To make a long story short, I was diagnosed with a pituitary adenoma in Feb of 2015. It was apron 8mm x 10mm at the time wit was found. On April 25th, 2015 I was getting ready for work in the early morning hours.. I passed out in my bathroom and was immediately rushed to the hospital by my husband. They did a secondary MRI and found that the tumor had tripled in size to 23mm x almost 41mm. My Cortisol was also so low it was undetectable by the lab. I was taken by ambulance to Emory University hospital in Atlanta where the Neurosurgeon I had been in consult with was. I arrived there on Sunday and was in Surgery Wednesday Morning. The surgery took 9 hours and recovery was close to 6.

Prior to this all taking place I was a volunteer firefighter, and had worked EMS for almost 16 years. I have been in nearly every situation possible. I see so many people that have our condition asking about Medic Alert bracelets, What kind they should have, what it should say on it, etc. So I have put together a short list to help out a little bit. This is coming from both someone who has this extremely rare disease, and also from the Emergency Medical Side of me. Knowing what We as medics look for in the field, How quickly things move, what we ask or need to know, etc.

Please know that this IS NOT Professional Medical advice, But this is advice coming from someone who can shed some light on how to potentially save your life if you should ever be alone, or without anyone who knows your condition and you fall unconscious or are unable to the the responders what your condition is.

First off if you are looking for a medic alert bracelet or wondering if you should get one.

**The answer is yes, If you have been diagnosed ANY TYPE of adrenal insufficient or are on replacement medication.. YES. you need one.**

Here are some of those reasons and some pointers on what they should look like / what they should say.

#1– If you are found unconscious, and there are not bystanders around to tell emergency crews what is wrong with you, You will go longer without your steroids. If we see on your bracelet that you are steroid dependent, it dissolves the ENTIRE guessing game of why you’re unconscious.

#2– It should have on there your emergency contact and a GOOD telephone number. That way if nothing else. We can call them. NOT EVERY EMS AGENCY HAS ACCESS TO THE “CLOUD” BASED SYSTEMS THAT STORE YOUR INFO. Please be sure that if your emergency contacts number changes.. You change it on your bracelet. There is nothing worse than wasted time calling a number that doesn’t belong to the person we NEED to talk to.

#3– DO NOT MAKE IT “PRETTY” OR “NOT SO OBVIOUS”. I can not stress this enough. Ladies I know that you want the cute ones that look like normal bracelets, and have pretty charms, etc on them… THE ENTIRE point of a medical alert bracelet is that someone needs to see it and know that they should look at it. If it looks like a regular bracelet or regular necklace and it isn’t obvious within the first 3 seconds once we get to you and look in the obvious places (neck/wrist). it will NOT get seen. I promise you, we are too busy trying to play the guessing game of why you are not responding, than to take a look at every single piece of regular jewelry and see if it might have a really small inscribing of what is wrong with you. Once again. Make it noticeable. We will see that we need to look at it. Once we do. The guessing game is more than likely OVER. and we can begin to treat you appropriately.

#4– Most EMT’s and Paramedics Don’t Understand or know about Addisons or the treatment involved. If nothing else, carry a letter from your doctor explaining what is wrong with you, etc. It is very rare, and NOT covered in most Paramedic courses. So please, for those of you that put “ADRENAL INSUFFICIENT” on your bracelet and NOT “STEROID DEPENDENT” please keep in mind that you may end up with the Paramedic that just graduated, is nervous, and will mistake adrenal insufficiency for Adrenaline insufficiency.. and try to give you epinephrine. Please understand that I have seen this almost happen. It is something that is easily misunderstood in the heat of the moment.

#5– If you have an emergency injection that you carry with you all the time, on your person, or somewhere close. PUT ON THERE THAT YOU HAVE IT! MOST ems agencies have standing protocol that they can assist with emergency medications (Don’t jump in here if you are one of those states that doesn’t allow it.. I said most) That way if we find you down, and look at your bracelet, AND see that you have emergency meds with you… guess what now, not only is the guessing game over, You’re ALSO getting the RIGHT EMERGENCY MEDS, instead of us having to either give you what we carry, or you having to wait until you get to the ER and the ER doc has to go through your file and figure out that you need the medication that’s been in your pocketbook the ENTIRE TIME.If you are unsure if your state allows this, or if you Local EMS agency can do this. Contact their local medical control and ask. If they do, Please offer to give a small talk on what the disease is and how to use the emergency kit. Most will know once they see the acto-vial, but if they do not, Please educate them. Explain to them that it can be the only thing that could save your life.

Please take the time and make sure that you have correct information on your bracelet. Secondary or Primary, the treatment in an Emergency situation is the same. So there is NO need for you to spell out if you are secondary or primary. Both get the emergency injection in case of a crisis. Both get fluid bolus, heart and blood pressure monitoring. Nothing is different when it comes to an emergency situation. If you have any questions on the wording or what to get on it. Be sure you at least have an emergency contact, That you are steroid dependent, and where your emergency injection is located.

IF you know that your local EMS agency uses the “cloud” for stored emergency info, you can spend the money to get it. But I worked for service that covered a county with over 100 sq miles, and we didn’t use it. It is unreliable and takes too much time to log in to the system, try to read the small number on your band, type it in, etc. When you can simply put the information on the band itself.

If you have any other further questions, You can refer to AIU’s emergency page.

%d bloggers like this: