Autoimmune Polyglandular Syndrome Type Research Articles

Autoimmune polyglandular syndrome type 2: a clinical case of a rare combination of primary adrenal insufficiency and latent autoimmune diabetes in adults

Autoimmune polyglandular syndrome type 2: a clinical case of a rare combination of primary adrenal insufficiency and latent autoimmune diabetes in adults

A patient diagnosed with new-onset type 1 diabetes and Addison's disease at initial presentation.

A previously healthy 17-year-old female presented to the emergency department with complaints of vomiting, shortness of breath, and tachycardia. She was found to have an elevated blood glucose and was admitted for presumed new onset type 1 diabetes mellitus (T1DM). During the admission, she was noted to have frequent episodes of hypoglycemia despite conservative insulin dosing and high urine output with glucosuria, which seemed out of proportion to her glucose levels and fluid status. She also had persistent hyponatremia despite normalization of blood glucose. Further work-up was initiated to investigate alternative or additional diagnoses to explain these atypical findings. Adrenocorticotropic hormone (ACTH) level was elevated, consistent with the diagnosis of Addison's disease, which led to the subsequent diagnosis of autoimmune polyglandular syndrome type II (APS-2). This is one of the first reports in the literature of concurrent diagnosis of T1DM and Addison's disease at initial presentation and demonstrates the importance of not anchoring to one diagnosis. This case shows the importance of considering multiple diagnoses and investigating atypical signs and symptoms. This case highlights the importance of a thorough history including review of systems. Hyponatremia and recurrent hypoglycemia in a person with type 1 diabetes should raise suspicion for adrenal insufficiency. This case makes us consider the screening for Addison's disease in a person with new onset type 1 diabetes in addition to autoimmune thyroid disease and celiac disease. People with an autoimmune disease should be monitored for other autoimmune diseases in the future.

Clinical case of autoimmune polyglandular syndrome type II

The peculiarities of clinical symptoms and the difficulties of diagnosing have been considered on the clinical example of manifestations of autoimmune polyglandular syndrome type II in a young woman. Autoimmune polyglandular syndrome type II is a rather rare pathology, its prevalence is 1 : 20.000 cases of the population. The diagnosis of this disease is determined by the presence of insufficiency of at least two endocrine glands with mandatory adrenal insufficiency. The second component of the disease can be any autoimmune thyroid disease or type 1 diabetes mellitus, which is also autoimmune in nature, or both conditions. Adrenal insufficiency is the initial manifestation of this syndrome in approximately 50% of patients, occurs simultaneously with autoimmune thyroiditis or type 1 diabetes in 20% of patients, the remaining 30% of patients may have a different sequence of manifest components of autoimmune polyglandular syndrome type II. In this article, special attention is paid to the importance of careful monitoring of patients with at least one autoimmune disorder of endocrine organ. The data presents in detail a history of patient who had only type 1 diabetes and autoimmune thyroiditis for 7 years, and the manifestation of adrenal insufficiency was registered 7 years after the manifestation of the primary components of autoimmune polyglandular syndrome type II. The authors highlighted diagnostically significant changes in laboratory methods. The analysis has been performed for the literature data, related to the disease. The necessary to observe patients regularly for quick diagnosis and to reduce the risk of developing both immediate and delayed complications has been emphasized. Special attention should be paid to the examination of relatives of the first line of kinship among patients with the established diagnosis of autoimmune polyglandular syndrome type II for the presence of possible heredity.

Primary Adrenal Insufficiency in Autoimmune Polyglandular Syndrome Type 1 - A Case Report and Literature Review

Primary Adrenal Insufficiency in Autoimmune Polyglandular Syndrome Type 1 - A Case Report and Literature Review

Cutaneous Manifestations in Autoimmune Polyendocrinopathy-Candidiasis-Ectodermal Dystrophy (APECED): A Comprehensive Review.

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), or polyglandular autoimmune syndrome type 1 (PAS-1/APS-1), is a rare autosomal recessive disorder linked to mutations in the autoimmune regulator (AIRE) gene. This review provides a detailed analysis of cutaneous manifestations in APECED, focusing on chronic mucocutaneous candidiasis (CMC), alopecia areata (AA), and vitiligo. The classic triad of hypoparathyroidism, adrenal insufficiency, and CMC serves as a diagnostic cornerstone. However, the varied clinical spectrum of APECED, particularly its cutaneous presentations, poses a diagnostic challenge. CMC, often an early sign, varies in prevalence across populations, including Finnish (100%), Irish (100%), Saudi Arabian (80%), Italian (60-74.7%), North American (51-86%), and Croatian (57.1%) populations. Similarly, AA prevalence varies in different populations. Vitiligo also exhibits variable prevalence across regions. The review synthesizes the current knowledge arising from a narrative analysis of 14 significant human studies published in English up to October 2023. Moreover, this paper underscores the importance of early detection and monitoring, emphasizing cutaneous manifestations as key diagnostic indicators. Ongoing research and clinical vigilance are crucial for unraveling the complexities of this rare autoimmune syndrome and enhancing patient care.

Autoimmune polyglandular syndrome type 2 in the form of Carpenter syndrome in a 16.5-year-old girl

Autoimmune polyglandular syndrome type 2 in the form of Carpenter syndrome in a 16.5-year-old girl

Late manifestation of autoimmune polyglandular syndrome type 1 with hypoparathyroidism and autoimmune thyroiditis

Autoimmune polyglandular syndrome type 1 (APS 1) is a rare genetic disorder caused by a mutation in the autoimmune regulator AIRE gene. The diagnosis is usually based on the combination of at least two components of the classic triad: mucocutaneous candidiasis, hypoparathyroidism, and primary adrenal insufficiency. Other autoimmune disorders, including thyroid diseases, also occur and may manifest before the primary components. The disease is more likely to manifest during infancy, but some components may develop in adult patients. As the components of the syndrome do not occur simultaneously, verification of the diagnosis is often delayed. A significant challenge in the management of patients with APS 1 is the selection of optimal drug doses due to polypragmasy and the frequent presence of autoimmune disorders and/or candidiasis of the gastrointestinal tract. We present a clinical case of a patient with an atypical course of APS 1, in whom the first endocrine components (hypoparathyroidism and hypothyroidism) were diagnosed in adulthood. This case highlights the phenotypic diversity of APS 1, and the difficulties in selecting therapy when several autoimmune endocrine diseases are combined.

The content of regulatory B-lymphocytes in autoimmune adrenal insufficiency

Introduction: Currently, the need to expand knowledge about the mechanisms of impaired immune tolerance in autoimmune adrenal insufficiency (AAI) remains relevant. It is not excluded that in AAI there are disturbances in the system of regulatory B-lymphocytes (Breg).Objective: To assess the state of the B-regulatory cells system of immunity in AAI.Material and methods: the content of Breg was evaluated in patients with AAI, including isolated AAI and AAI as part of autoimmune polyglandular syndrome type 2 (APS-2) and as part of APS-1, in patients with primary adrenal insufficiency (1-AI) of non-autoimmune genesis, conditionally healthy individuals without AI and autoimmune diseases.Results: A decrease in the content of Breg in vivo was revealed in patients with isolated AAI and AAI in the composition of APS-2 compared with conditionally healthy participants. The content of Breg in vivo in patients with 1-AI of non-autoimmune genesis did not statistically differ from the indicators of conditionally healthy participants.Conclusion: for the first time in the world, a tendency to a decrease in the content of Breg in AAI, caused by a disturbance of peripheral immune tolerance, was found. Thus, these cells can be considered as promising markers for the prognosis, early diagnosis, and differential diagnosis of AAI.

A novel missense mutation in the AIRE gene underlying autoimmune polyglandular syndrome type 1.

The immune regulator gene AIRE plays an essential role in the establishment of immune tolerance and the prevention of autoimmunity. This transcription factor plays a critical role in promoting self-tolerance in the thymus by regulating the expression of a large number of self-antigens that share the common feature of being tissue-restricted in their expression pattern in the periphery. Dysfunction of AIRE in humans causes a rare disease, autoimmune polyglandular syndrome type 1 (APS1), characterized by an autoimmune response against peripheral tissues, particularly endocrine tissues. Although a few dominant mutations have been described, the inactivation of AIRE is usually caused by recessive mutations. Recent data suggests that alterations in AIRE function contribute not only to APS1 but also to more common forms of autoimmune disease. Here, we present a previously unreported missense mutation (NM_000383.2:c.260T > C) in exon 2 of the AIRE gene, predicted to cause the substitution (p.(Leu87Pro)) in the CARD domain of the AIRE protein. When inherited in conjunction with another dysfunctional AIRE allele, this mutation was associated with immune dysregulation in a pediatric patient. The presence of hypergammaglobulinemia, malabsorption syndrome, ectodermal dysplasia, mucocutaneous candidiasis, vitiligo, and hypothyroidism as well as the presence of multiple autoantibodies allowed us to confirm an APS1 diagnosis.

First case recognized as autoimmune polyglandular syndrome type 2 with double seronegative myasthenia gravis - A case report-from Pakistan

First case recognized as autoimmune polyglandular syndrome type 2 with double seronegative myasthenia gravis - A case report-from Pakistan

Autoimmune polyglandular syndrome type 4: experience from a single reference center.

To characterize patients with APS type 4 among those affected by APS diagnosed and monitored at our local Reference Center for Autoimmune Polyglandular Syndromes. Monocentric observational retrospective study enrolling patients affected by APS diagnosed and monitored in a Reference Center. Clinical records were retrieved and analyzed. 111 subjects (51 males) were affected by APS type 4, mean age at the onset was 23.1 ± 15.1 years. In 15 patients the diagnosis of APS was performed during the first clinical evaluation, in the other 96 after a latency of 11 years (range 1-46). The most frequent diseases were type I diabetes mellitus and celiac disease, equally distributed among sexes. The prevalence of APS type 4 is 9:100,000 people. Type I diabetes mellitus was the leading indicator of APS type 4 in 78% subjects and in 9% permitted the diagnosis occurring as second manifestation of the syndrome. Our data, showing that 50% of patients developed APS type 4 within the first ten years, don't suggest any particular follow-up time and, more importantly, don't specify any particular disease. It is important to emphasize that 5% of women developed premature ovarian failure.

FRI209 Psychiatric Illness Masking Autoimmune Polyglandular Syndrome In A Middle-aged Woman

Abstract Disclosure: L. Esper: None. A. Ibrahim: None. S. Sen: None. Introduction: Autoimmune polyglandular syndrome type 2 (APS-2) or Schmidt's syndrome, is a rare disorder characterized by the coexistence of autoimmune adrenal and thyroid disease and/or type 1 diabetes mellitus. Clinical case: A 51-year-old woman with past medical history of depression and bipolar disorder presented to the hospital with weakness and dizziness. The patient reported increased dizziness and weakness over several months that progressed and limited her level of daily activities. She had been experiencing decreased energy, poor appetite and occasional nausea but denied vomiting or abdominal pain. She also denied any changes in her weight. She suffered from constipation but that was her baseline for many years. She was diagnosed with bipolar disorder with depression in her 20s and required multiple admissions for severe depression. She had been following up with her psychiatrist and assumed to have worsening depression. Her mood stabilizers and antidepressant medications were adjusted over several months without improvement. In the Emergency Department, her blood pressure was 98/58. Her heart rate was 57. Labs revealed Na: 115, K: 5.3 and Cr:0.87. The patient was admitted to the general medical floor for treatment of symptomatic hyponatremia. Hyponatremia was initially thought to be due to depression and decreased oral intake. She was started on fluid with slight improvement in sodium levels without significant improvement in symptoms. Further work up for the etiology of her hyponatremia and weakness elicited 2 endocrinopathies. She had a morning cortisol of 4. Cosyntropin stimulation test did not elicit a proper response. At baseline, cortisol was 4.2 and then 4.5 and 4.3 at 30 and 60 minutes, respectively. She was also found to have hypothyroidism (TSH 10, FT4: 0.4). Patient was started on hydrocortisone and fludrocortisone initially and subsequently thyroid hormone replacement was added with resolution of symptoms and hyponatremia. She reported being postmenopausal since age 41. Given that the patient had at least two endocrinopathies, 21 hydroxylase antibody testing was ordered and found to be positive. Addison's disease diagnosis is often delayed. A cross-sectional study in 2013 showed that less than 50% of patients with adrenal insufficiency were correctly diagnosed within the first half year after symptoms appeared. It however took more than 5 years until the condition was diagnosed for 20% patients. (1) The delay was primarily attributed to concomitant presence of psychiatric and gastroenterological conditions. Conclusion: Poly endocrinopathies often present with vague symptoms that need to be worked up to prevent the life-threatening effects of APS2 including adrenal crisis. We present an uncommon case of middle-aged woman with Tri-glandular syndrome with delayed diagnosis due to underlying psychiatric disease. (1) Meyer et al. Horm Metab 2013; 45:92-95 Presentation: Friday, June 16, 2023

FRI271 A Case Of Autoimmune Polyglandular Syndrome Type 2 Presenting With Cardiac Symptoms

Abstract Disclosure: J. Lin: None. C. Lee: None. A.R. Crawford: None. C. Taub: None. Autoimmune polyglandular syndrome type 2 (APS 2) is characterized by the combination of autoimmune adrenal insufficiency with autoimmune primary hypothyroidism, and/or type 1 diabetes mellitus, as well as other autoimmune conditions. The estimated prevalence is reported to be 1.4-4.5 cases per 100,000 persons. Presenting symptoms are often nonspecific, leading to delayed diagnosis; however, manifestations can sometimes become rapidly life-threatening. Cardiac symptoms, rare but clinically significant, can be the first presentation for APS 2. 34 year old male with history of asthma presents with nausea and chest pain, found to have pericarditis that was complicated by pericardial tamponade and cardiogenic shock requiring emergent pericardiocentesis and mechanical support with veno-arterial extracorporeal membrane oxygenation. Stress dose steroids were given due to concern for fulminant myocarditis. His condition improved with glucocorticoid treatment, but the etiology of his acute decompensation was unclear. He completed the prednisone taper before discharge and was started on amiodarone for atrial flutter. He presented with recurrent symptoms a week later. Cardiac MRI showed pericarditis without myocarditis. PET scan showed pericardial inflammation without evidence of malignancy or vasculitis. Broad infectious workup including viral studies was negative. An extensive biochemical workup showed low serum aldosterone and high renin activity while on prednisone. Autoimmune workup was positive for 21-hydroxylase antibody, thyroid peroxidase antibody, and homozygous for celiac HLA DQ8, suggestive of APS 2. Patient was started on levothyroxine for subclinical hypothyroidism with TSH >20. Interleukin blockade with anakinra was initiated, and patient was discharged with 25mg of daily prednisone pending insurance authorization for anakinra. A month later, patient re-presented with pericarditis. Patient received stress dose steroids, and was started on fludrocortisone. Levothyroxine was stopped because of amiodarone induced thyrotoxicosis. Patient was discharged on a prednisone taper regimen, and anakinra was approved a month later. Few case reports have described the association between APS 2 with pericardial tamponade. In healthy patients presenting with unexplained pericarditis, autoimmunity should be considered as a differential diagnosis as it can rapidly become life-threatening requiring urgent intervention. It is important to recognize for these patients, they are at risk for recurrent pericarditis and cardiac tamponade. Presentation: Friday, June 16, 2023

SAT317 Adrenal Insufficiency Diagnosed During Pregnancy

Abstract Disclosure: A. Rosado-Burgos: None. L.N. Madera Marin: None. M.A. Ortiz-Rivera: None. L. El Musa Penna: None. W. Medina-Torres: None. L.R. Sepulveda-Garcia: None. M. Alvarado: None. L.A. Gonzalez-Rodriguez: None. M. Ramirez: None. Introduction: Primary adrenal insufficiency (AI) that is a potentially life-threatening condition and commonly associated to destruction of adrenal cortex by autoantibodies. AI predominantly affects women of reproductive age and can affect the outcome and course of pregnancy, causing reduced parity, risk of preterm birth, and low birth weight. Symptoms of AI are nonspecific and can result in a challenging diagnosis. Clinical case: 25 year-old pregnant female G1P0A0 at 12 weeks gestational age (WGA) with long standing history of Type 1 Diabetes Mellitus (DMT1) and Hypothyroidism. She was evaluated while hospitalized for metabolic control during pregnancy. The patient had been previously admitted at 7 WGA with hyperglycemic episodes requiring insulin dosing adjustments. Now, 5 weeks later, was found with numerous hypoglycemic episodes even after omitting pre-prandial insulins. Additionally, she had persistent fatigue, general malaise, nausea, vomits, anorexia, and difficulty concentrating. Laboratory workup showed a TSH of 22.96 uIU/mL (nl 0.4-4.0), FreeT4 0.91 (nl 0.89-1.74), that had been within normal limits 6 weeks prior. She reported taking pre-natal vitamins only one hour after LT4, therefore malabsorption was suspected. Insulin requirements were decreased by 50%. Vitals signs without evidence of hemodynamic instability and laboratory workup without electrolyte nor acid base disturbances. However, due to clinical presentation and history of other autoimmune diseases, AI was suspected. Severe hypothyroidism, AI and hyperemesis gravidarum can mimic several features of each other’s clinical presentation. Midmorning cortisol level was found at 7.8 ug/dl (nl for pregnancy >19) but no ACTH levels taken prior to replacement. Considering acuteness and severity of symptoms it was decided to administer IV LT4 equivalent dose which can increase cortisol metabolism precipitating adrenal crisis. For this reason, stress dose hydrocortisone (HC) was empirically administered. Rapid clinical improvement was observed after LT4 and corticosteroid replacement therapy with resolution of nausea, vomits, anorexia as well as hypoglycemic episodes and was discharge home with her usual LT4 PO dose and corticosteroid replacement therapy. Twenty-one-alpha hydroxylase antibodies were positive, making the diagnosis of primary adrenal insufficiency highly suspected. Conclusion: Presentation was consistent with Polyglandular Autoimmune Syndrome Type 2. Diagnosis of AI during pregnancy is rare as it is considered a hypercortisolemic state. Changes in cortisol levels during pregnancy make the diagnosis of AI even more challenging. Dynamic testing can be considered, however, most of these studies have not been validated in pregnancy. In this case patient continues with HC replacement therapy while in her 3rd trimester of pregnancy without any maternal of fetal complications. Presentation: Saturday, June 17, 2023

FRI255 Polyglandular Autoimmune Syndrome Type 2 Presenting With Severe Hyponatremia

Abstract Disclosure: A. West: None. A.N. Davis: None. A. Warner: None. S. Salcin: None. Introduction: Polyglandular autoimmune syndrome type 2 (PAS-2) is a polygenic autoimmune syndrome which presents with two or more specific autoimmune manifestations. The combination of Addison’s disease and Hashimoto’s thyroiditis has been referred to as Schmidt Syndrome. Treatment of hypothyroidism without recognition of concomitant adrenal insufficiency may result in exacerbation of adrenal insufficiency (AI). We present a case of PAS-2 presenting with severe hyponatremia. Case: A 28-year-old male presented to an outside hospital with fatigue and weakness. His sodium was 121mEq/L and TSH >356mcIU/mL, and he was admitted for management of hyponatremia. He was started on oral levothyroxine, urea tablets, and fluid restriction. In the weeks following discharge, the patient had worsening fatigue, weakness, dizziness, nausea, and weight loss, and he presented to our ED. His vital signs were stable without tachycardia or hypotension. He was lethargic but fully oriented. Hyperpigmented areas of the tongue and nose were noted. Laboratory evaluation revealed sodium 111mEq/L, potassium 4.5mEq/L, TSH 43.56 (0.4-4.7mcIU/mL), and free T4 of 1.12 (0.58-1.76ng/dL). He was admitted to the medical intensive care unit for management of severe hyponatremia. Repeat sodium was 112mEq/L with serum cortisol 4.57mcg/dL. Hypertonic saline was given without improvement in hyponatremia. Cortisol level was determined to be inappropriately normal in the setting of severe hyponatremia. Cosyntropin stimulation test was performed with baseline, 30 minute, and 60 minute cortisol levels of 5.31, 6.17, and 6.26, respectively, consistent with AI. ACTH level was not obtained due to the blood sample being hemolyzed. Other results include positive 21-hydroxylase antibody, TPO antibody >900 IU/mL, and undetectable GAD 65 antibody. He received IV stress dose steroids with resolution of his symptoms and his hyponatremia. Oral hydrocortisone replacement therapy was started prior to discharge. Discussion: Patients with one autoimmune endocrinopathy are at risk of developing a second one. Our patient’s hyponatremia was initially attributed to his hypothyroidism without recognition of concomitant AI. Early diagnosis of AI is important prior to initiation of levothyroxine, as treatment of hypothyroidism may exacerbate AI. The sodium level in our patient worsened from 121mEq/L at the previous admission to 111mEq/L when he presented to our hospital, related to worsening of his AI while being treated for his hypothyroidism. Timely diagnosis of associated AI requires high index of suspicion in such patients, particularly in patients with signs or symptoms which may overlap with hypothyroidism, such as hyponatremia in our patient. AI should be considered in any patient who presents with hyponatremia, even those who lack other classic features such as hypotension, hyperkalemia, and hypoglycemia. Presentation: Friday, June 16, 2023

FRI244 Autoimmune Polyglandular Syndrome Type 2 And Peripartum Cardiomyopathy: A Case Report

Abstract Disclosure: A.G. Jimenez: None. J.D. Christensen: None. P. Surampudi: None. S. Phatak: None. J. Yoon: None. Background: Peripartum cardiomyopathy (PPCM) is a diagnosis of exclusion with evolving understanding of pathophysiology. There is limited consideration of the autoimmune processes contributing to PPCM. Case Presentation: A 20-year-old female had a recent delivery complicated by placenta previa, hemorrhage requiring transfusion, and pelvic infection. She presented 2 weeks postpartum with altered mental status and abdominal pain, found to be in septic shock, acute respiratory failure, acute liver injury initially thought to be secondary to retained products of conception. Subsequently, she was diagnosed with moderate-to-severe PPCM as she developed signs of heart failure, low ejection fraction <35%, mild ventricular dilatation, cardiogenic shock, hemorrhagic pericardial effusion with tamponade. She had no other prior cardiovascular history. She was briefly started on bromocriptine for treatment of suspected prolactin-mediated PPCM, in addition to digoxin, as her blood pressure was unable to sustain other treatments for PPCM. However, she hemodynamically decompensated and required persistent pressor support, leading to evaluation for other causes. Due to her prior history of hypothyroidism, an adrenal evaluation with a cosyntropin stimulation test was done. It demonstrated an undetectable cortisol at 0, 30, 60 minutes, with an elevated ACTH (1256, n=7-63 ng/dL), consistent with primary adrenal insufficiency (PAI). Workup for PAI did not reveal any infectious, infiltrative, vascular, pharmacological, or neoplastic etiology. Lab workup for concomitant hypophysitis was significant for low IGF-1 (Z-score -5.8, n= -2.0 to +2.0), but otherwise had expected elevated prolactin (121 ng/mL, n=5.2-26.5 ng/mL), suppressed LH (0.3 mIU/mL) and FSH (2.4 mIU/mL), and normal TSH (3.87 mIU/mL, n=0.27-4.20 mIU/mL) on levothyroxine 100 mcg. She had normal parathyroid hormone and hemoglobin A1c levels with no history of chronic candidiasis. Further workup showed positive antibodies to adrenal 21-hydroxylase enzyme, thyroid peroxidase, and glutamic acid decarboxylase 65, suggestive of autoimmune polyglandular syndrome (APS) type 2. She was started on glucocorticoids and mineralocorticoids for adrenal insufficiency resulting in a significant clinical improvement. She was subsequently discharged in stable condition. Conclusion: Due to increased rates of mortality in PPCM (4-11%), thought should be given to nontraditional etiologies of cardiac failure. Although rare, adrenal insufficiency must be considered in those with moderate-to-severe PPCM who continue to decompensate despite treatments. Untreated adrenal insufficiency can result in fatal consequences if not immediately treated. APS type 2 should be considered even in those without any confirmed family history of autoimmune disease. Those with autoimmune tendencies may be at higher risk of PPCM. Presentation: Friday, June 16, 2023

FRI269 Two Cases Of Familial Polyglandular Autoimmune Syndrome Type II Presenting With Adrenal Insufficiency Precipitated By SARS-CoV-2 Infection

Abstract Disclosure: J. Sassic: None. N. Hosein: None. G. Jackson: None. Introduction: Polyglandular autoimmune syndrome (PGA) type II is characterized primarily by autoimmune adrenal disease and thyroid disease. Additionally, about 50% of patients will experience autoimmune diabetes mellitus. The incidence of PGA type II is around 1:20,000 but shows strong familial clustering, and predominantly affects women in a 3:1 ratio. Here we report a case of two patients, a woman and her son, who were diagnosed 6 months apart with type II PGA who presented with adrenal insufficiency acutely affected by SARS-CoV-2 infection. Clinical Case: Patient 1 is a 59 year-old female with history significant for previously-diagnosed autoimmune thyroiditis who presented with complaint of generalized fatigue and weight loss for months following a SARS-CoV-2 infection, who was found to have severe hyponatremia with serum sodium of 106 mmol/L (137-145 mmol/L) and was admitted to the intensive care unit. There, she received cosyntropin testing which revealed severe adrenal insufficiency, with post-cosyntropin cortisol level at 1.2 mcg/dL (>14 mcg/dL). Anti-21-hydroxylase antibodies were positive. Her A1c was found to be 5.8% (<5.7%), indicating prediabetes in a patient with BMI of 18.5 kg/m2. Glutamic acid decarboxylase antibodies were tested and were also positive. Patient’s sodium was repleted and she was tapered from stress-dose to physiologic steroid dosing and was discharged on hydrocortisone and fludrocortisone. About 6 months later, Patient 2, a 25-year-old male and the son of Patient 1 presented to the emergency department with complaint of a week of nausea and vomiting, and three months of generalized fatigue. He was found to be SARS-CoV-2 positive and was also hyponatremic with serum sodium of 122 mmol/L. He also received cosyntropin testing which was revealed undetectably low cortisol levels both pre- and post-cosyntropin administration. Anti-21-hydroxylase antibodies and anti-thyroid peroxidase antibodies were positive, the latter at 243.3 IU/mL (<5.61 IU/mL). Patient responded well to stress-dose steroids and normal saline to normalize his sodium levels. Due to his mother’s positive antibodies, glutamic acid decarboxylase, anti-islet, and anti-insulin antibodies were also tested, which were negative. Patient was discharged on physiologic hydrocortisone and fludrocortisone. Conclusion: Polyglandular autoimmune syndrome is a relatively uncommon disease but with strong polygenic inheritance. This case was an interesting presentation where SARS-CoV-2 infection likely precipitated the symptoms and acute effects of adrenal insufficiency. Additionally, knowledge of the patient’s family history resulted in rapid diagnosis and management of the patient’s underlying pathophysiology. Presentation: Friday, June 16, 2023

SAT318 Autoimmune Polyglandular Syndrome II In A Young Female With Severe Weight Loss, DKA, And Psychiatric Features

Abstract Disclosure: G. Wintermyer: None. C. Arcilla: None. E. Villanueva: None. Autoimmune polyglandular syndrome type II (APS II) is a rare combination of multiple endocrine diseases. The most common associated diseases are diabetes type I, Hashimoto thyroiditis, and Addison’s disease. Most patients present with nonspecific symptoms, typically in adulthood. Here we describe a 19-year-old female with APS II:A 19-year-old female with history of depression presented to hospital with severe nausea, vomiting and chest pain. She was diagnosed with pneumomediastinum secondary to hyperemesis. The symptoms were assumed secondary to ziprasidone that she was then taking.Patient experienced 20-pound weight loss in a very short period. Patient went to ED again for excessive weight loss. She was diagnosed with DKA for the first time and was admitted to ICU (Glucose level above 500 mg/dL and A1C 7.1%). After discharge, patient came to the endocrinology clinic for management of type 1 diabetes. Her BMI was 17 kg/m2. Vital signs were normal. Since the start of insulin therapy, patient gained weight and her BMI increased to 18.5 kg/m2.Patient was clinically well for about 1 year. She had periodic complete blood tests, including TSH, A1C and CMP, all of which remained normal with A1C’s of 6.3% and 6.8%. Approximately 1 year later, her TSH was 8.230 uIU/mL and free T4 was 0.92 ng/dL with subsequent TPO of 27 IU/mL. Diagnosis of Hashimoto’s hypothyroidism was made, and she was started on levothyroxine.Even though patient was on treatment for hypothyroidism, she complained of fatigue. CMP showed sodium 133 mEq/l and bicarbonate 17 mEq/l. Celiac antibodies presented negative. Cortisol AM and ANA were ordered. Before patient had the lab tests done, she was admitted to psychiatric hospital due to psychosis and bizarre behavior. Shortly after, patient was transferred to medical hospital for nausea and vomiting. Her labs were as follow: Sodium 100 mEq/l, Potassium 6.5 mEq/l, Bicarbonate 12 mEq/l, anion gap 19, Glucose 157 mg/dl. Stat cortisol and ACTH were 1.3 mg/dL and 332 pg/mL, respectively.Patient was admitted to ICU with adrenal crisis. She was started on Fludrocortisone and IV Hydrocortisone and IV fluid for hyponatremia. She was discharged from hospital with resolution of her psychiatric features. Her final diagnosis was APS II. She was started on Fludrocortisone 0.1, Hydrocortisone 20 mg in the morning and 10 mg at night.Clinicians should keep this disease in mind when assessing a patient who has presented with other autoimmune endocrinologic diseases, especially diabetes type I or adrenal insufficiency. Frequent visits, vital checks, CMP, and antibody screening tests including GAD antibodies, anti-adrenal antibodies, and TPO antibodies help in diagnosing this syndrome earlier.Clinicians also should be mindful of psychiatric features in a patient. They should try to rule out medical causes before diagnosing a patient with psychiatric disease as profound hyponatremia can cause acute psychosis. Presentation: Saturday, June 17, 2023

SAT224 Nonsurgical Hypoparathyroidism: 40 Years After Diagnosis

Abstract Disclosure: L.I. Kaplan: None. A. Yuen: None. P.D. Greenberg: None. Background: The majority of cases of hypoparathyroidism occur after neck surgery. The most common nonsurgical cause is autoimmune, either in isolation or part of Autoimmune Polyglandular Syndrome Type 1. Hypomagnesemia is a functional cause. Hypoparathyroidism can occur as part of genetic syndromes that include congenital anomalies, short stature and developmental delay. Non-syndromic genetic etiologies including Autosomal Dominant Hypocalcemia type 1 (ADH1), a gain of function mutation in the calcium sensing receptor (CaSR) that can present in infancy, childhood or adulthood with hypocalcemia (50% symptomatic), hypercalcuria (10%) and basal ganglia calcification (35%). For ADH1, targeted therapies are being developed. Clinical Case: A 90-year-old male was diagnosed with hypoparathyroidism at age 50 when he presented with hand cramping and was found to have hypocalcemia with low PTH. He was started on calcitriol and calcium supplementation. Many years later he started following at our endocrine clinic. Past medical history includes prostate cancer treated with radiation and androgen deprivation therapy, HTN, and pre-diabetes. He has no history of neck surgery, other endocrinopathies, candidiasis, vitiligo or congenital anomalies. He has no family history of hypocalcemia and has two children without calcium abnormalities. His DEXA shows stable +T scores in LS spine and bilateral hips. He has not had brain imaging. Nephrocalcinosis was not reported on renal ultrasound. More than 10 years ago, he presented with severe hypercalcemia, acute renal failure (Ca 13.5 mg/dl, Cr 6.0mg/dl, Phos 5.5mg/dl) and ureteral stones after taking over the counter calcium supplements in excess. He underwent stone removal with return to baseline renal function. Subsequently, he underwent knee replacement surgeries and required IV calcium until he was able to swallow pills. Since this time, he has been managed on calcitriol, calcium carbonate, vitamin D3, and chlorthalidone with close follow up for adjustment of regimen to target Ca 8.0-8.5 mg/dl. He has not had a recurrence of severe hypercalcemia, hyperphosphatemia or nephrolithiasis. He feels well and lives at home with his wife. Lab values over the past 10 years are as follows: Ca 8.1-10.6 mg/dl (8.5-10.5), Alb 4.0-4.6 g/dl (3.5-5.4), Phos 4.3-5.5 mg/dl (2.8-4.5), Mg 1.7-1.9 mg/dl (1.3-2.1), K 3.7-4.4 mEq/L (3.6-5.2), Cr 1.0-1.5 mg/dl (0.5-1.3), PTH 0.00-1.4 pg/ml (10-55), 25 OH Vit D 18-58 ng/ml (32-100), 1,25 OH Vit D3 25.5-37.2 pg/ml (19.9-79.3), 24hr Urine Ca 162- 384 mg/24 hrs (50-400). Clinical lessons: Chronic hypoparathyroidism can be well managed with close follow up and frequent lab monitoring. This patient should be referred for genetic testing, particularly to look for ADH1 mutation in the CaSR gene as targeted treatments are being developed. His children should be tested for any mutations found in him. Presentation: Saturday, June 17, 2023

FRI697 Severe Hypocalcemia Due To Idiopathic Hypoparathyroidism In An Elderly Female

Abstract Disclosure: K.A. Chopra: None. Most cases of acquired hypoparathyroidism in adulthood occur after neck surgery or radiation. However, idiopathic cases, although rare, do occur in elderly patients and should be a diagnosis of exclusion after thorough investigation. 76-year-old female with a history of chronic kidney disease, anemia of chronic disease, and hypertension presented with fatigue. Labs showed calcium (Ca) 5.7(RR 8.4-10.2 mg/dL), albumin 3.5(RR 3.5-5 g/dL), magnesium 2(RR 1.6-2.5 mg/dL), phosphorus 7.8(RR 2.5-4.4 mg/dL), parathyroid hormone 9(RR 15-75 pg/mL), 25-hydroxyvitamin D 32(RR 12-99 ng/mL). Patient denied history of neck surgery or radiation. Patient denied nephrolithiasis, perioral numbness, paresthesias, family history of hypoparathyroidism. Physical exam notable for positive Chvostek sign. Neck ultrasound unremarkable, no evidence of infiltrative disease. Urine Ca was low at 6 mg/24 hour(RR 100-300 mg/24hr). ACE level 10 nmol/ml/min(RR<40 nmol/ml/min) and 1,25 dihydroxyvitamin D level 12(RR 18-78 pg/mL) making sarcoidosis or granulomatous disease unlikely. HIV screen negative and interferon gamma response to mycobacterium tuberculosis antigens was not detected. Ferritin elevated at 300(RR 12-150 ng/mL) but transferrin saturation was 15%(RR 15-55%), not consistent with hemochromatosis. Antiparathyroid antibodies were negative. Patient denied mucocutaneous candidiasis, however testing for underlying autoimmune polyglandular syndrome type 1 (APS type 1) and adrenal insufficiency was completed with cosyntropin stimulation test. Patient had normal response to cosyntropin with baseline cortisol 20.1 (RR 6-18.4 ug/dL) and ACTH 37.7(RR<52 pg/mL), 30 minute cortisol 27(RR 6-18.4 ug/dL) and 60 minute cortisol 37(RR 6-18.4 ug/dL). Patient was treated with Ca gluconate infusion (100 ml of 10% Ca gluconate in 1000 mL of normal saline) at 30 ml/hr and Ca level gradually improved. Once Ca level was greater than 8.0(RR 8.4-10.2 mg/dL), Ca drip was discontinued. Due to patient’s lack of prior neck surgery history, lack of evidence of infiltrative conditions, negative antiparathyroid antibodies, normal adrenal function (unlikely APS type 1), lack of family history, and low urine Ca (unlikely activating mutation of Ca sensing receptor), patient’s hypoparathyroidism was considered idiopathic. Patient was discharged on oral Ca carbonate, Ca acetate, and calcitriol tablets. On follow up, patient had Ca 8.5(RR 8.4-10.2 mg/dL) with symptom improvement. Although hypocalcemia is commonly encountered, it is rare to see severe hypocalcemia in an elderly patient due to hypoparathyroidism without a history of neck surgery or radiation. Therefore, it is vitally important to conduct a thorough investigation to rule out underlying causes before diagnosing idiopathic hypoparathyroidism as highlighted in our case to guide future treatment and optimize patient health. Presentation: Friday, June 16, 2023