Autoimmune Adrenalitis Research Articles

Coexistence of 21 Hydroxylase Deficiency and Autoimmune Adrenalitis: A Case Report

Abstract21-Hydroxylase deficiency (21 OHD) is the most common cause of congenital adrenal hyperplasia (CAH). Despite its relative frequency, many aspects of this disease are understudied. The aim of our case report was to highlight the association between nonclassic CAH (NCCAH) and autoimmunity, and to encourage future research to explore the possible cause-and-effect relationship between CAH and tumorigenesis. Here, we report the case of a 41-year-old woman with a history of nonclassic 21 OHD, who demonstrated typical signs of acute adrenal insufficiency. As it is well known, this is an unusual presentation of NCCAH and therefore a panel of laboratory and radiological exams were conducted in order to determine the associated etiology of the adrenal insufficiency, which revealed to be autoimmune adrenalitis. Another striking particularity of our case is the coexistence of NCCAH and cutaneous T lymphoma in our patient, which to our knowledge has never been reported in literature. This case illustrates the need to scrutiny for the etiology of adrenocortical crisis in the setting of NCCAH. It also emphasizes the possible associations between NCCAH and autoimmunity in one hand and neoplasms on the other hand.

Miliary Tuberculosis Causing Presumed Primary Adrenal Insufficiency and Addisonian Crisis: A Case Report from Rural Kenya

Miliary Tuberculosis Causing Presumed Primary Adrenal Insufficiency and Addisonian Crisis: A Case Report from Rural Kenya

Schmidt's Syndrome: An Uncommon Cause of Spontaneous Hypoglycemia

AbstractSchmidt's syndrome, or autoimmune polyendocrine syndrome type 2 (APS-2), is an uncommon disorder characterized by the co-occurrence of autoimmune thyroiditis and adrenalitis. APS-2 is defined as a combination of Addison's disease, autoimmune thyroid disease, and/or type 1 diabetes mellitus. It is an autosomal dominantly inherited polygenic disorder with incomplete penetrance; the candidate genes include but are not limited to HLA-DR3, HLA-DR4, CTLA-4, PTPN22, and CD25-IL-2. Autoimmune thyroiditis, often Hashimoto's disease, results in hypothyroidism. Primary adrenal failure results in enhanced secretion of adrenocorticotrophic hormone melanocyte and co-secretion of melanocyte-stimulating hormone, contributing to hyperpigmentation. Mineralocorticoid deficiency results in salt wasting, fatigue and cramps, postural hypotension, and hyperkalemia. Cortisol, an insulin counter-regulatory hormone, plays a pivotal role in maintaining euglycemia; deficiency predisposes to the development of hypoglycemia. We here report a rare presentation of Schmidt's syndrome as hypoinsulinemic hypoglycemia in a middle-aged male patient. Management includes treatment of acute hypoglycemic episodes with glucose or glucagon, long-term glucocorticoids and mineralocorticoids for adrenal insufficiency, and thyroid hormone supplements for hypothyroidism. This case report and brief overview aim to contribute to the scientific understanding of Schmidt's syndrome/APS-2. Additionally, here we briefly outline the diagnostic challenges in hypoglycemia evaluation, including the utilization of Whipple's triad and the gold standard supervised 72-hour fast and evaluation for primary adrenal and thyroid insufficiencies.

ASSOCIATION OF INFLAMMATORY BOWEL DISEASE AND AUTOIMMUNE PRIMARY ADRENAL INSUFFICIENCY

Abstract AIMS To assess the prevalence and association of inflammatory bowel disease (IBD) with autoimmune primary adrenal insufficiency (APAI). BACKGROUND Patients with inflammatory bowel disease are at risk for developing other immune mediated diseases (IMD). There is a paucity of data on the association of IBD with autoimmune primary adrenal insufficiency/ autoimmune adrenalitis. To date, only small series have been published in the literature and well-designed population-based studies have not yet examined this association. METHODS We identified patients from the Healthcare Cost and Utilization Project - National Inpatient Sample between the years 2016 to 2020. Our cohort included IBD patients of all ages, and our control group consisted of non-IBD patients. The study's primary outcome was to evaluate the association of APAI in the study group compared to the control group. Secondary outcomes included demographics of IBD patients with APAI. ICD-10 diagnostic codes were used to identify patients. RESULTS During the study period, a total of 1,652,070 IBD patients were identified. Of these, 3,699 had a concurrent diagnosis of APAI, yielding an overall prevalence rate of 0.22%. In the non-IBD cohort, the total number of patients were 173,000,000 and the prevalence of APAI was 0.06%. Patients with IBD who had APAI were 70% females, and 90% were of white ethnic background. Among IBD patients, Crohn’s disease had a higher prevalence of APAI than Ulcerative Colitis, 0.27% vs. 0.14 %, respectively (p<0.001). Patients with IBD-APAI also had other coexisting IMDs, with asthma having the highest prevalence (13.11%), followed by rheumatoid arthritis (10.41%) and type-1 diabetes mellitus (2.57%). On multivariable logistic regression analysis, patients with IBD had 3.04 times higher odds of having a concurrent APAI diagnosis than patients without IBD (OR 3.046, CI: 2.796- 3.318, P<0.001). Women were 1.59 times more likely to have APAI than men (OR 1.590, CI: 1.539 - 1.643, p<0.001). On subgroup analysis, patients with CD had 1.9 times higher odds of having APAI than UC (OR: 1.901 CI: 1.579 - 2.290, p<0.001). CONCLUSIONS Patients with IBD, especially women of white ethnic background, have a higher association of APAI than non-IBD patients. CD patients are more likely to develop APAI than UC. Further studies are needed to understand the association and overlapping pathologic mechanisms between IMDs which may help further understand IBD-related comorbidities. Figure Table

Long-diagnosed primary adrenal insufficiency in the setting of Werlhof’s disease. A clinical case report

Chronic adrenal insufficiency is an endocrine disease caused by insufficient secretion of adrenal hormones due to dysfunction of one or more links of the hypothalamic-pituitary-adrenal axis. The highest prevalence has been documented in Scandinavian countries: 15–22 people per 100,000 population, while other European countries report 10 cases per 100,000 population. Autoimmune adrenalitis is the most common cause of primary adrenal insufficiency in adults, and it can be either alone (40 %) or a component of autoimmune polyglandular syndromes (60 %). The etiologic factors of primary adrenal insufficiency include tuberculosis or AIDS. These causes of adrenal cortical insufficiency are particularly relevant in Ukraine. The article describes a clinical case of a patient with both primary adrenal insufficiency and Werlhof’s disease. The prevalence of adrenal insufficiency and etiologic factors of primary adrenal insufficiency are highlighted. A detailed differential diagnosis of primary adrenal insufficiency with other diseases that could cause clinical symptoms such as hypoglycemic states, severe weight loss, hypotension, severe muscle weakness, hyponatremia, hyperkalemia is performed. The basic principles of diagnosis, treatment, and prognosis in primary adrenal insufficiency are discussed. Despite typical, specific manifestations of adrenal insufficiency, diagnosis in real clinical practice is difficult. Awareness and vigilance of doctors regarding the symptoms of adrenal insufficiency is necessary. Late detection of chronic adrenal insufficiency can lead to complications. Timely diagnosis and treatment of chronic adrenal insufficiency improves disease prognosis and quality of life.

SAT280 Burden Of Disease and Quality Of Life In Patients After Bilateral Adrenalectomy Versus Autoimmune Adrenalitis: A Cross-sectional Survey Study

Abstract Disclosure: R. Gregg Garcia: None. I. Bancos: None. Background: Bilateral adrenalectomy (BLA) is a procedure with limited indications, such as bilateral pheochromocytomas and certain cases of Cushing syndrome. Impaired quality of life (QoL) has been reported in patients with primary adrenal insufficiency (PAI) due to autoimmune adrenalitis (AA). We hypothesized that, when compared to AA, patients post-BLA experience worse QoL due to sequelae of Cushing syndrome or pheochromocytoma. Objective: To compare the QoL and burden of disease in patients with PAI due to BLA versus AA. Methods: A cross-sectional study of adults with PAI due to BLA or AA, August 15 - November 26, 2022. Patients were excluded if PAI was diagnosed within one year from the enrollment date or if active malignancy was present. Participants completed a questionnaire about symptoms, burden of disease, adrenal crisis, and QoL (AddiQoL). Results: Of 120 patients with PAI, 49 (41%) had BLA, and 71 (59%) had AA. Median age was 52 years (range 23-80), without subgroup differences, but a higher proportion of women in the post-BLA vs the AA group (86% vs 69%, p=0.04). Reasons for BLA were Cushing syndrome (44, 90%) and bilateral pheochromocytomas (5, 10%). Duration of PAI was higher in patients with AA (median 12 vs 7 years post-BLA, p=0.02). The majority of patients reported wearing a medical bracelet (82%), having injectable glucocorticoid (90%), and comfort injecting (61%), without subgroup differences. Total daily hydrocortisone dose was higher in patients with AA vs patients post-BLA (mean of 23 mg vs 20 mg, p=0.03). A total of 26 (22%) patients reported at least one adrenal crisis within the last year, with a greater proportion in the post-BLA group (33% vs 14% in AA, p=0.02). No subgroup differences were noted in risk factors for adrenal crisis development, such as hydrocortisone equivalent dose, type of glucocorticoid therapy, duration of PAI, having a medic alert bracelet and injectable glucocorticoids, comfort injecting, or physical activity. Compared to AA, patients post-BLA had a similar QoL (median AddiQoL score 86 vs 84, p-value 0.72). Duration of PAI was not associated with QoL. Physical activity ≥3 times/week was associated with a better QoL (median AddiQoL score 90 vs 80 in those with lower level of physical activity, p=0.001); no subgroup differences in physical activity ≥3 times/week were found (57% in BLA vs 62% in AA, p=0.59). Since the initial diagnosis of PAI, more patients with AA reported that PAI was “harder” to manage (23% vs 6% post-BLA, p-value 0.04), with most patients reporting that management was easier (52% in AA and 63% in BLA) or not different (25% in AA and 31% in BLA). Conclusions: Despite a higher prevalence of adrenal crisis, more patients with BLA vs AA found PAI easier to manage. Moreover, patients with BLA and AA had a similar level of comfort and education managing PAI, similar QoL, and engaged in similar levels of physical activity, despite history of Cushing syndrome. Presentation: Saturday, June 17, 2023

FRI235 Primary Adrenal Insufficiency As Presenting Symptom Of Disseminated Histoplasmosis And Cryptococcus Co-Infection In Immunocompetent Patient

Abstract Disclosure: A. Thompson: None. Background: Autoimmune adrenalitis remains the most common cause of primary adrenal insufficiency in the United States. Infectious etiologies from fungal sources are much less commonly seen. Below we discuss a case of disseminated histoplasmosis and cryptococcus that initially presented with primary adrenal insufficiency. Case: A 74 y/o F with history of Type 2 DM presented to the hospital with 3 months of fatigue and weight loss. She was initially found to be in DKA and shock requiring vasopressor support. Following the resolution of DKA, she remained hypotensive without obvious cause. A random cortisol was found to be 8.2 [6-25 ug/dL]. She then underwent an ACTH stimulation test and her cortisol level at 30 minutes was 5.9 ug/dL and at 60 minutes was 4.2 ug/dL. An ACTH level was obtained and found to be elevated at 69 [7.2-63 pg/mL]. She was subsequently started on Hydrocortisone and her shock resolved. CT adrenal glands were notable for bilateral adrenal masses measuring 4.5 cm on the right and 4.6 cm on the left with HU of 27. No other suspicious lesions were noted on imaging. An infectious work up was initiated, which was notable for fungal serologies positive of Histoplasmosis with titer of 1:8 (<1:8). Histoplasmosis urine antigen was positive as well. She was tested for Cryptococcus, which was positive with a titer of 1:8 (<1:8). She started treatment with Amphotericin B for 4 weeks followed by Itraconazole for maintenance therapy. Discussion: Primary adrenal insufficiency from invasive fungal infection remains uncommon and is found in less than 10% of cases. Disseminated fungal infections are identified as causes like histoplasmosis and paracoccidiomycosis. Disseminated cryptococcus is an exceedingly rare cause of adrenal insufficiency. These invasive infections can lead to bilateral enlargement of the adrenal glands and calcifications are seen on radiographic imaging. Such cases can also lead to perivasculitis and cause thrombosis and subsequent infarction of the adrenal glands. Disseminated fungal infections are more commonly seen in patients with underlying immunodeficiency such as HIV or those receiving immunosuppressant therapy. This case highlights that these infections can still be seen in those without a compromised immune system. Diagnosis can be challenging given the vague symptoms of adrenal insufficiency but should be considered in patients with electrolyte disturbances, hypoglycemia, and hypotension. There is potential for adrenal recovery following treatment with antifungal therapy. Conclusion: Although autoimmune adrenalitis is the most common cause of primary adrenal insufficiency in the US, this case highlights the importance of evaluating for other potential causes such as infectious sources, which can be treated and potentially have adrenal recovery. Presentation: Friday, June 16, 2023

FRI210 Rare Clobetasol Induced Adrenal Insufficiency In A Patient With Chronic Psoriasis

Abstract Disclosure: H. Maldonado Rivera: None. A. Subtain: None. S. Pastori: None. J.A. Gonzalez: None. S.R. Vallepu: None. N. Shahid: None. E. Angueira: None. N. Shaaban: None. A 38-year man with PMH of severe plaque psoriasis presented to the ED with complaints of right leg weakness. Patient denied nausea, vomiting, headache, chest pain, shortness of breath, and tremors. His skin psoriasis has been affecting him since childhood but got worse at age 24. The patient has been using clobetasol creams to reduce the itchiness and scaly skin that is formed throughout his body. Patient had morning cortisol level of 2.0 mcg/dL (n >15 mcg/dL). Patient’s cortisol level increased to 13.6 mcg/dL in the first 30 minutes and 17.0 mcg/dL at 60 minutes of corticotropin stimulation test. Based on the result, patient is diagnosed with adrenal insufficiency due to values of cortisol being <18.0mcg/dL. ACTH levels measured at the start were 22.1 pg/mL (n 6-76 pg/mL). This patient’s adrenal insufficiency is potentially multifactorial. The patient may have secondary adrenal insufficiency due to chronic use of clobetasol, a medium-potency topical steroid which has been associated with adrenal insufficiency with prolonged use. This is the most probable diagnosis in the presence of stable blood pressure and in the absence of nausea, vomiting, hyponatremia, hyperkalemia, hypercalcemia, and eosinophilia. However, the patient’s lack of gaining weight and hyperpigmentation seen in the lips and tongue as well as psoriasis, autoimmune skin disease condition may predispose the patient to develop primary adrenal insufficiency. In that case, the patient would need lifelong treatment with PO steroids, especially needing stress dosing if he becomes severely ill. This patient may be developing a primary adrenal insufficiency due to a potential autoimmune adrenalitis. Currently, patient has adequate blood pressure and electrolytes, which suggest he may develop disease later and is currently not in need of fludrocortisone. Patient’s anti-adrenal antibodies, anti-21-hydroxylase antibodies were negative. Patient was started on a medium stress dose of prednisone 20 mg PO in AM and 10 mg in PM. Patient was discharged with prednisone 10 mg PO in AM and 5 mg in PM (this is the equivalent of 40mg of hydrocortisone in AM and 20mg of Hydrocortisone in PM due to moderate illness). Eventually, patient’s prednisone dose was tapered to 5 mg in AM and 2.5mg in PM. Conclusion: This is a very rare case of clobetasol, a medium potency topical steroid used to treat severe plaque psoriasis causing secondary adrenal insufficiency due to negative feedback inhibition of hypothalamus-pituitary-adrenal axis. Reference: Ohman EM, Rogers S, Meenan FO, McKenna TJ. Adrenal Suppression following Low-Dose Topical Clobetasol Propionate. Journal of the Royal Society of Medicine. 1987;80(7):422-424.doi:10.1177/014107688708000709 Presentation: Friday, June 16, 2023

FRI258 A Diagnostic Journey To Autoimmune Polyendocrine Syndrome Type 2

Abstract Disclosure: S. Amankwah: None. H.K. Driscoll: None. C. Muojieje: None. M. Sanati: None. Background: Approximately 50-65% of patients with autoimmune adrenal insufficiency have one or more autoimmune endocrine disorders. This case demonstrates the importance of considering autoimmune polyendocrine syndrome (APS) when a patient presents with more than one autoimmune endocrine disorder. Case: A 29-year-old woman with history of idiopathic intracranial hypertension, hypothyroidism on levothyroxine 50 mcg daily, endometriosis, and chronic migraines complained of fatigue, word finding difficulty, misspeaking of words, and staring spells. An MRI of the brain w+wo IV contrast revealed hypo-enhancing appearance of the pituitary gland. The patient was referred to endocrinology by neurology. Hormonal work up was performed checking for prolactin, ACTH, morning cortisol, TSH, Free T4, FSH, LH, IGF-1 and a serum chemistry panel. Thyroid antibodies were also ordered to help understand the etiology of her hypothyroidism. Pituitary hormones were normal except elevated TSH and borderline low serum cortisol. Subsequently a co-syntropin stimulation test resulted in inadequate cortisol rise. ACTH level measured inappropriately low normal. The patient then started steroid replacement therapy. Thereafter, 21-hydroxylase antibodies, serum renin and aldosterone were checked to screen for Addison Disease. Her 21-hydroxylase antibody was positive, aldosterone level low, and renin elevated pointing to autoimmune adrenalitis etiology. Her thyroid antibodies were also positive indicating autoimmune thyroid disease. Considering these results, the condition of APS came into question. Hence, the patient was screened for type 1 diabetes mellitus which was positive for glutamic acid decarboxylase 65 antibody but negative for insulin and pancreatic islet cell antibodies. Her hemoglobin A1c was 5.0%. Due to her history of gluten intolerance, she was screened for celiac disease which was negative for t-Transglutaminase antibody. The patient’s fatigue improved on steroid replacement therapy. She became euthyroid after increasing her levothyroxine dose to 75 mcg daily, and repeated MRI a year later did not show pituitary abnormalities. Discussion: APS type 2 is a polygenic inherited disorder associated with HLA-DR3 and DR4 that affects adult females more than males. The syndrome is characterized by type 1 diabetes mellitus, autoimmune thyroid disease and Addison disease. Associated nonendocrine autoimmune syndromes include celiac disease, pernicious anemia, and atrophic gastritis. These characteristics overlap with APS type 1 except for autoimmune thyroid disease that presents with type 2. It should be noted that thyroxine therapy can precipitate a life-threatening Addison crisis in a patient with untreated adrenal insufficiency and hypothyroidism. Therefore, it is necessary to evaluate adrenal function in all hypothyroid patients in whom APS is suspected. Presentation: Friday, June 16, 2023

Autoimmune adrenal insufficiency in children: a hint for polyglandular syndrome type 2?

BackgroundPrimary adrenal insufficiency (PAI) in childhood is a life-threatening disease most commonly due to impaired steroidogenesis. Differently from adulthood, autoimmune adrenalitis is a rare condition amongst PAI’s main aetiologies and could present as an isolated disorder or as a component of polyglandular syndromes, particularly type 2. As a matter of fact, autoimmune polyglandular syndrome (APS) type 2 consists of the association between autoimmune Addison’s disease, type 1 diabetes mellitus and/or Hashimoto’s disease.Case presentationWe report the case of an 8-year-old girl who presented Addison’s disease and autoimmune thyroiditis at an early stage of life. The initial course of the disease was characterized by numerous crises of adrenal insufficiency, subsequently the treatment was adjusted in a tertiary hospital with improvement of disease control.ConclusionsAPS type 2 is a rare condition during childhood, probably because it may remain latent for long periods before resulting in the overt disease. We recommend an early detection of APS type 2 and an adequate treatment of adrenal insufficiency in a tertiary hospital. Moreover, we underline the importance of a regular follow-up in patients with autoimmune diseases, since unrevealed and incomplete forms are frequent, especially in childhood.

Pre-clinical Autoimmune Adrenalitis, biochemically diagnosed; Treat or Not?

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

A detailed pituitary profile always matters

Abstract 29-year-old female with known hypothyroidism and positive thyroid auto antibodies, followed up throughout pregnancy for adjusted doses of thyroid replacement therapy, presented 2 months post-partum with gradually increasing fatigue, repeated pre-syncope experience, inability to cope with daily home and family needs and headache. Adequacy of thyroid replacement therapy was questioned, TSH has been performed: 0.18 mIU/ml. Checking the blood pressure in lying and standing position has showed Postural hypotension. An urgent measurement of Cortisol (am) showed a result of1.06 ug/dl. Preliminary Differential Diagnoses have been suggested; Pituitary apoplexy, Pituitary adenoma, Autoimmune adrenalitis (Autoimmune Polyglandular Syndrome) or Others. On further detailed history, the patient affirmed dizziness and fainting liability on standing from lying position, bitemporal headache more in the morning. However, she denied frequent urination throughout the day, neither repeated times at night. In addition, she confirmed efficient breast feeding. Continued Lab investigations: ACTH (am) (Low); FT4 (Low; on replacement therapy); IGF1 (Normal) Serum osmolality (Normal); Urine osmolality (Normal); E2 / LH / FSH (normal physiological levels) Prolactin (normal for breast feeding) MRI pituitary and sella: Diffuse isointense enlargement of anterior pituitary gland. Homogenous and strong diffuse pituitary enhancement with gadolinium contrast. History and investigations were not fully matching with any of the previously proposed differential diagnoses, especially in regards of selective corticotroph and thyrotroph affection, sparing other pituitary cell types. Moreover, the autoimmune predisposition, the nature of the clinical presentation and its timing during early postpartum period, together with the laboratory and imaging investigations were all matching with the diagnosis of Lymphocytic Hypophysitis. The Patient got pregnant again 14 months post-partum, reflecting spared gonadotroph function and highlighting the importance to identify this uncommon diagnosis and to notify the patient about normal gonadal function and the normal possibility of pregnancy. However, she remained on hydrocortisone and thyroxine replacement. Finally, it is important that this condition should not be misdiagnosed in the first place as postpartum thyroid disturbance and TSH results, especially during and after pregnancy, shall always be interpreted in the clinical context and with the overall thyroid profile.

Bilateral Adrenal Masses with Different Aetiologies Presenting as Addisonian Crisis with Acute Kidney Injury: A Case Series

An Addisonian Crisis (AC) is an endocrinological emergency associated with high mortality, resulting from an acute deficit of hormones from the adrenal glands. It can occur either in a patient with known Adrenal Insufficiency (AI) or as the initial presentation of the disease. Primary Adrenal Insufficiency (PAI), which can be caused by autoimmune adrenalitis or tubercular adrenalitis, is the most common cause worldwide and particularly prevalent in developing countries like India. Other causes of PAI include infiltrative pathology, drugs, haemorrhage, or, rarely, malignancy. Secondary Adrenal Insufficiency (SAI) often occurs due to abrupt steroid withdrawal or defects at the level of the pituitary or hypothalamus. The present case series highlights three cases (three male patients) in which patients presented with adrenal crisis despite no prior history of AI. Subsequently, they were diagnosed with bilateral adrenal masses of different aetiologies, including primary adrenal malignancy and granulomatous infiltration of the adrenals due to Tuberculosis (TB). One case involved bilateral primary adrenal malignancy with left perirenal and pararenal space infiltration, while the other two patients were diagnosed with disseminated TB with adrenal gland infiltration. The presentation of all three cases was characterised by non specific symptoms. Initial management for all three patients involved mineralocorticoid and glucocorticoid replacement, and they were discharged with corticosteroid supplements. However, the patient with bilateral adrenal malignancy was referred to the surgery and oncology department for further evaluation and management, whereas the remaining two patients were started on Antitubercular (ATT) drugs for definite treatment.

PSAT037 The Unlikely Suspect - A New Diagnosis of Autoimmune Addison's Disease in an 80-year old Lady

Abstract Introduction Hyponatremia is a common cause of hospitalization in older adults. Addison's disease (AD), an uncommon cause of hyponatremia, is primary adrenal insufficiency (AI) caused by autoimmune adrenalitis, infections, adrenal hemorrhage, or infiltration. Autoimmune adrenalitis is an uncommon cause of AD after age 60 years. We report an 80 year old patient with hyponatremia who was ultimately diagnosed with autoimmune AD. Case report An 80 year-old lady with steroid-controlled asthma, presented to the ER with weakness, imbalance, nausea and vomiting two weeks after a urinary tract infection. Her blood pressure was 96/64 mm Hg with otherwise normal vital signs and unremarkable general examination. Laboratory evaluation revealed hyponatremia (Na 120 mmol/L), hyperkalemia (K 5.7 mmol/L) and acute kidney injury (creatinine 1.2 mg/dl, GFR 43 ml/min/m). Hyperkalemia resolved with intravenous fluids, insulin and dextrose therapy (K 4.7 mmol/L). However, hyponatremia persisted (Na 120-123 mmol/L) despite fluid restriction, normal saline, and salt tablets. Additionally, patient remained hypotensive with blood pressure between 90/40-120/60 mm Hg. Due to concern for AI from prior steroid use, morning cortisol was measured and was low (4.63 mcg/dl). Concurrent ACTH level was elevated (252 pg/ml, range 7.2-63.3 pg/ml). Cosyntropin stimulation test done during hospitalization was abnormal (4.5 mcg/d→6.7 mcg/dl→8 mcg/dl) confirming AD. At outpatient consultation with endocrinology, patient reported nausea and vomiting for 18 months prior to hospitalization, 50 lbs weight loss, weakness, short-term memory loss, and dizziness attributed to vertigo. Symptoms worsened a month prior to patient's hospitalization. Repeat cosyntropin stimulation test remained abnormal (8.5 mcg/dl→9.6 mcg/dl→10 mcg/dl). CAT scan of the abdomen with adrenal protocol was unremarkable for adrenal masses, hemorrhage, infiltration, or metastasis. Surprisingly, 21-hydroxylase antibody testing was positive confirming autoimmune AD. The patient has been on hydrocortisone 15 mg in AM + 5 mg in PM and fludrocortisone 0.1 mg daily for one year now with improvement in symptoms. Discussion Medications, poor diet, and diabetes are common causes of hyponatremia in the elderly. AD, an uncommon cause of hyponatremia, should be considered in a hospitalized hyponatremic elderly patient. Non-specificity of AD symptoms makes the diagnosis in this age group difficult, often causing delay in appropriate management. Autoimmune AD is characterized by the presence of 21-hydroxylase antibodies. Data on autoimmune AD incidence in the elderly is limited due to rarity. Our patient's autoimmune AD was likely masked due to steroid use for asthma. During COVID-19 pandemic, masking, and social distancing decreased the patient's steroid needs and unmasked AD after the UTI. Our case highlights the importance of considering autoimmune AD as a cause of AI even in the elderly. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

PSAT034 A Case of Adrenal Crisis in Association With a Febrile Response to the bnt162b2 mRNA COVID-19 (Pfizer) Vaccine Heralding a Diagnosis of Primary Adrenal Insufficiency.

Abstract Background In the face of the COVID-19 pandemic, messenger RNA (mRNA) vaccines were approved for the first time for use in the general population. Vaccination can trigger a febrile flu-like response that is self-limited in healthy individuals. Febrile illness is a classic trigger of acute adrenal insufficiency in patients who are cortisol deficient, but recognizing this clinical scenario is challenging in patients with undiagnosed adrenal insufficiency. Case Presentation A 24-year-old male presented to an acute care community hospital with fatigue, fever, and vomiting 12 hours after receiving the second dose of the BNT162b2 mRNA Covid-19 (Pfizer) vaccine. He was 6 feet tall, and his weight was 175 pounds. He had a temperature of 103 F, a blood pressure of 88/42 mmHg, and a heart rate of 100 bmp on admission. Hypotension persisted despite aggressive fluid resuscitation and broad-spectrum antibiotics. CT of the chest and CT angiogram of the abdomen and Pelvis did not identify an etiology for his presentation. Over a period of hours, he became obtunded, disoriented, and required vasopressor support. He received 100 mg of IV hydrocortisone followed by 50 mg every 6 hours for treatment of presumed sepsis and was transferred to an intensive care unit. Within 24 hours of starting glucocorticoid therapy, he was awake and oriented, defervesced, and became normotensive. This rapid improvement led to suspicion of adrenal insufficiency as an underlying diagnosis. Further questioning revealed a 4-month history of recurrent nausea, vomiting, severe fatigue, to the point where he had trouble climbing a flight of stairs, and a 40-pound unintentional weight loss. He visited an emergency department 3 times over this period and had outpatient evaluations by gastroenterology and cardiology without identifying a cause. Inpatient evaluation revealed a morning Cortisol of 1.4 ug/dL (n 4.8-19.5 ug/dL), aldosterone <3 ng/dL (n <16 ng/dL), and ACTH 1071 pg/mL (n 7.2-63.3 pg/mL) leading to the diagnosis of primary adrenal insufficiency. He was started on physiologic doses of adrenal replacement hormones and discharged home in stable condition 4 days after his admission date. Conclusions A severe post-vaccination reaction should elicit physicians to look for an alternative diagnosis. Autoimmune adrenalitis is the most common cause of primary adrenal insufficiency and is uniquely associated with a long lag to diagnosis. The diagnosis is often made in the setting of an intervening illness or physiologic stressor when a patient's condition acutely deteriorates. Patients with known adrenal insufficiency should be reminded to address post-vaccination febrile reactions with an increase in glucocorticoid doses. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

ODP030 Autoimmune Adrenalitis Following mRNA Covid- 19 Immunization In A Patient Without A Known Diagnosis Of Adrenal Insufficiency.

Abstract A 45-year-old female with a past medical history of Hashimoto thyroiditis and celiac disease presented after a syncopal episode that resulted in a motor vehicle accident. The patient had symptoms of fatigue, nausea, and anorexia for three weeks following the second dose of the Pfizer-BioNTech COVID-19 Vaccine. Initial laboratory tests revealed hyponatremia with serum sodium (Na) of 123mEq/L that worsened to 111mEq/L after receiving the normal saline infusion. Serum potassium was 3.4mEq/l, Thyroid-stimulating hormone level was 6.350mIU/l, free thyroxine level was 1.1 ng/dl and glucose were 85mg/dl. The PCR test for COVID-19 was negative. Vitals were unremarkable except for a low blood pressure of 90/60. On physical examination, the patient was alert and communicative and there was no hyperpigmentation of the skin. The patient denied personal and family history of adrenal insufficiency. She denied prior use of any steroid medications. Her prior outpatient serum Na levels were normal (138-140 mEq/L). The patient was admitted to the ICU for severe hyponatremia, where she was treated with fluid restriction and hypertonic saline. However, she remained hypotensive, and serum sodium failed to improve above 118mEq/l. Serum cortisol at 8: 00 am and 10: 00 am were 4.5 and 5.8 mcg/dl, respectively. She was started on stress doses of hydrocortisone 100 mg intravenous (IV) followed by hydrocortisone 50 mg IV every 8 hours and serum Na improved to 130m Eq/l. Steroids were tapered gradually to physiological doses. The levothyroxine dose was also increased from the home dose of 75mcg to 88 mcg daily due to the elevated TSH. Hormonal workup showed aldosterone of 0.3ng/dl, plasma renin activity of 20, and adrenocorticotropic hormone(ACTH) levels of >1250pg/ml. Gonadotropins, insulin-like growth factor-1, and prolactin were within normal limits. Cosyntropin stimulation test after holding steroids for 24 hours was abnormal, with pre-cosyntropin cortisol level 7. 0mcg/dl, and the 60-minute post-cosyntropin cortisol level 7.1mcg/dl. The diagnosis of autoimmune adrenalitis was confirmed with a positive 21-hydroxylase antibody test. The patient had an uneventful recovery and was discharged on oral hydrocortisone. Presentation: No date and time listed

LBODP012 A Case of Addison's Disease Presented With Rhabdomyolysis And Psychosis

Abstract Background Addison's disease is a disorder of deficiencies in glucocorticoids and mineralocorticoids, mostly resulting from destruction of the adrenal cortex. Rhabdomyolysis and psychosis can be symptoms presented in cases of adrenal crisis. Clinical Case A 42-year-old male was hospitalized for rhabdomyolysis (CK 5200 U/L), hyponatremia (Na 117 mmol/L), hyperkalemia (K 6.4 mmol/dL) and acute renal failure (Creatinine 4.4 mg/dL). Past medical history was significant for a similar episode of rhabdomyolysis: negative EMG, muscle biopsy nonconclusive, diagnosed with autoimmune hypothyroidism and started on levothyroxine 50 mcg daily five years ago. Renal function improved and electrolyte abnormality was resolved with IV hydration. ACTH was elevated (580 pg/mL), cortisol and aldosterone were undetectable; patient was discharged on hydrocortisone 10 mg bid from outside hospital. His mood and personality changed significantly after he started hydrocortisone. One week later he was admitted to a psychiatry unit due to mania and psychosis, and was started on risperidone and divalproex sodium. Cosyntropin stimulation test confirmed primary adrenal insufficiency, likely autoimmune adrenalitis with positive 21-hydroxylase antibody. Hydrocortisone was replaced with prednisone 5mg daily and fludrocortisone 0.2 mg daily. Psychiatric symptoms completely resolved in two months; patient was taken off psychiatric medications. Clinical condition was stable in follow-up visits. Electrolytes and blood pressure continued to stay in normal range. This case of Addison's disease initially presented with rhabdomyolysis as a first symptom, manifested by acute psychosis in the course of treatment with hydrocortisone. The association between adrenal insufficiency and rhabdomyolysis has been reported, but the underlying mechanism is not clear. Several theories have been proposed to explain neuropsychiatric manifestations secondary to adrenal insufficiency (1); there is no definite answer yet. Conclusion Adrenal insufficiency should be evaluated in patients with rhabdomyolysis. Mental disturbances triggered by adrenal crisis and treatment should be considered by both endocrinologist and psychiatrist. Reference: (1) Farah, J., et al. Severe Psychotic Disorder as the Main Manifestation of Adrenal Insufficiency. Case Rep Psychiatry. 2015; 2015: 512430. Presentation: No date and time listed

Autoimmune Primary Adrenal Insufficiency in Children

Objective:Primary adrenal insufficiency (PAI) is a rare condition in children, and is potentially life-threatening. The most common cause is congenital adrenal hyperplasia, and autoimmune etiology is the most frequent acquired cause in this age group. Symptoms are usually non-specific and, when suspected, investigation should include adrenocorticotropin hormone (ACTH) and morning serum cortisol measurement and, in some cases, a cosyntropin test to confirm the diagnosis. Prompt treatment is essential to prevent an adverse outcome.Methods:We retrospectively collected clinical and laboratory data from adrenal insufficiency due to autoimmune adrenalitis, observed from 2015 to 2020 in a pediatric endocrinology department of a tertiary care hospital.Results:Eight patients were identified, seven males and one female, with age at diagnosis between 14 and 17 years. The symptoms at presentation ranged from non-specific symptoms, such as chronic fatigue and weight loss, to a severe presentation, with altered mental status and seizures. The median duration of symptoms was 4.5 months. The diagnosis was confirmed by serum cortisol and plasma ACTH measurement and all were confirmed to have autoimmune etiology (positive anti-adrenal antibodies). At diagnosis, the most common laboratory abnormality was hyponatremia. All patients were treated with hydrocortisone and fludrocortisone. One patient presented with evidence of type 2 autoimmune polyglandular syndrome.Conclusion:PAI is a rare condition in the pediatric age group. Due to non-specific symptoms, a high index of suspicion is necessary to establish a prompt diagnosis. Once an autoimmune etiology is confirmed, it is important to initiate the appropriate treatment and search for signs and symptoms of other autoimmune diseases during follow-up.

Adrenal insufficiency due to autoimmune adrenalitis in pediatric age

Adrenal insufficiency due to autoimmune adrenalitis in pediatric age

The Diagnosis and Management of Endocrine Side Effects of Immune Checkpoint Inhibitors.

The immunologically mediated side effects of immune checkpoint inhibitors (CPI) often involve the endocrine system as well, and they can even be fatal, as in the case of unrecognized hypophysitis. Distinguishing such side effects from tumor-related changes is often difficult, because their clinical features can be nonspecific. This review is based on publications retrieved by a selective search in PubMed, with special attention to international recommendations. Depending on their target molecules, the CPI now in use differ from one another in the incidence of side effects such as autoimmune thyroid disease (4-16%), hypophysitis (0.1- 18%), adrenalitis (0.7-8%), and autoimmune diabetes mellitus (0.5-2%). The typical clinical warning signs and laboratory constellations of hypophysitis include exhaustion, hyponatremia, and headache. Hypo- and hyperthyroidism and primary adrenocortical insufficiency likewise have nonspecific manifestations. Autoimmune diabetes mellitus often takes a fulminant course. Patients being treated with CPI should be monitored at close intervals, at least as frequently as the administration of the drug, so that endocrine side effects can be recognized in time. In case of doubt, glucocorticoid supplementation should be given whenever hypocortisolism is suspected, even before endocrine evaluation is completed and the results are available. Interrupting or discontinuing CPI treatment is rarely indicated. With the increasing number of patients being treated with CPI, more and more physicians from a wide variety of specialties, not necessarily working in specialized centers, now have to consider immunologically mediated endocrine side effects in the differential diagnosis, and treat them properly when they arise. These things should be done in collaboration with endocrinologists. The ongoing study of such side effects of the CPI now in use, and of those that will be introduced in the future, is important and will lead to improved understanding.