Diagnosis Of Primary Adrenal Insufficiency Research Articles

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.

On Primary Adrenal Insufficiency with Normal Concentrations of Cortisol - Early Manifestation of Addison's Disease.

Primary adrenal insufficiency (AI) is an endocrine disorder in which hormones of the adrenal cortex are produced to an insufficient extent. Since receptors for adrenal steroids have a wide distribution, initial symptoms may be nonspecific. In particular, the lack of glucocorticoids can quickly lead to a life-threatening adrenal crisis. Therefore, current guidelines suggest applying a low threshold for testing and to rule out AI not before serum cortisol concentrations are higher than 500 nmol/l (18 μg/dl). To ease the diagnostic, determination of morning cortisol concentrations is increasingly used for making a diagnosis whereby values of>350 nmol/l are considered to safely rule out Addison's disease. Also, elevated corticotropin concentrations (>300 pg/ml) are indicative of primary AI when cortisol levels are below 140 nmol/l (5 μg/dl). However, approximately 10 percent of our patients with the final diagnosis of primary adrenal insufficiency would clearly have been missed for they presented with normal cortisol concentrations. Here, we present five such cases to support the view that normal to high basal concentrations of cortisol in the presence of clearly elevated corticotropin are indicative of primary adrenal insufficiency when the case history is suggestive of Addison's disease. In all cases, treatment with hydrocortisone had been started, after which the symptoms improved. Moreover, autoantibodies to the adrenal cortex had been present and all patients underwent a structured national education program to ensure that self-monitored dose adjustments could be made as needed.

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

SAT315 A Case Of PAI "Do Not Miss This Rare Cause"

Abstract Disclosure: R. Alshantti: None. C. Musurakis: None. U. Rafat: None. W. Akhter: None. J.L. Gilden: None. A. Moid: None. Background: Adrenoleukodystrophy (ALD) is an X-linked disorder caused by a mutation in the ABCD1 gene, located at Xq28. This impairs beta-oxidation and breakdown of very long chain fatty acids (VLCFAs) which then accumulate in the CNS, adrenal cortex, and Leydig cells of the testes, leading to three main phenotypes of X-ALD: childhood cerebral ALD, adrenomyeloneuropathy AMN, and adrenal insufficiency (AI). AI presents in 47% of X-ALD cases by age 10 years. X-ALD represents a spectrum of phenotypes that vary in age of onset, severity, and clinical characteristic. AI may predate, occur simultaneously with, or follow the onset of the neurologic deterioration. While in the majority, it is inherited in an X-linked manner, at least 4.1% of individuals with X-ALD have a de novo pathogenic variant of ABCD1. Case Description: A 30-year-old male, previously healthy, was found to have adrenal nodule on CT renal during the evaluation of a transient episode of acute abdominal pain. Further evaluation of the adrenal nodule with a CT adrenal protocol showed a 1.5 cm x 1.0 cm right adrenal nodule, HU 22, washout of 66.7% consistent with an adrenal adenoma. Evaluation of adrenal hormones failed to show abnormal hypersecretion, but rather suggested insufficiency. Lab tests: RENIN FRZ PLS 45.76 ng/mL/h (0.25 - 5.82), ALDOSTERONE <1 ng/dL, ACTH >1250 pg/mL (0 - 47), SALIV CORT 0.06 mcg/dL, DHEAS 28.19 ug/dL (34.5 - 568.9). The patient was referred to endocrinology. Only reported symptom was poor exercise tolerance. Diagnosis of primary adrenal insufficiency was confirmed by low AM cortisol of 7.91 ug/dL, and very high ACTH of >1250 H pg/mL. He was started on glucocorticoid & mineralocorticoid replacements. An evaluation to determine the etiology of PAI was conducted. The patient was not taking any medications or drugs. Family history was noncontributory. 21 OH Ab was negative. Quantiferron was negative. Our patient had no risk factors or clinical manifestations to suggest TB or fungal infections. No bleeding disorders. CT adrenal findings did not suggest infiltrative, infectious, hemorrhage, or malignant etiologies. Blood tests for VLCFAs showed elevations in phytanic, C22:0, C24:0, C26:0, C24/C22, & C26/C22. These are consistent with X-linked adrenomyeloneuropathy. Genetic testing has confirmed the diagnosis; POSITIVE for a hemizygous pathogenic variant in ABCD1, consistent with a diagnosis of X-linked adrenoleukodystrophy/adrenomyeloneuropathy (ALD/AMN). Conclusion: Our case highlights the importance of a comprehensive evaluation to determine the cause of PAI. When autoimmunity and infectious etiologies are ruled out in male patients, it is crucial to consider X- ALD regardless of age at presentation, family history, or presence/absence of neurologic symptoms. This diagnosis is particularly important not to miss, since X-ALD can have devastating implications not only for the patient but also the family. Presentation: Saturday, June 17, 2023

FRI236 Primary Adrenal Insufficiency Due To Coccidiomycosis

Abstract Disclosure: T. Duro: None. Introduction: Primary adrenal insufficiency due to infectious adrenalitis is not common in the United States. When it occurs, the most common culprits are tuberculosis, histoplasmosis, and HIV-related manifestations. We present a rare case of disseminated coccidiomycosis presenting with hypercalcemia, adrenal insufficiency, and a right adrenal mass. Case Report: A 73-year-old Hispanic man living in New Mexico with history of paraesophageal hernia and a thoracic aortic aneurysm was admitted in the hospital during a COVID-19 infection due to severe weakness, poor oral intake, and abdominal pain. His labs on admission showed: mild eosinophilia, serum calcium corrected for albumin 13.8 mg/dL (n 8.4 - 10.4 mg/dL), PTH <6 pg/mL(n 18 - 84 pg/mL), PTH-rp 4.4 pmol/L (n 0.0 - 2.3 pmol/L), Vitamin D25-OH 18 ng/mL (n >29 ng/mL), Calcitriol 8.1 ng/mL (n 19.9 - 73.9 ng/mL), serum kappa/lambda light chain ratio 2.09 (n 0.29 - 1.65), SPEP and UPEP no M-spike, normal pattern, 8AM serum cortisol 0.9 ug/dL (n5.27 - 22.45 ug/dL), ACTH >1250 pg/mL (n 0 - 46 pg/mL), DHEA-S 20ug/dL (n 80 - 560 ug/dL), plasma normetanephrine 3.29 nmol/L (n 0.00 -0.89 nmol/L), plasma metanephrine <0.10 nmol/L (n 0.00 - 0.49 nmol/L). Abdominal CT scan showed a right hypodense adrenal mass measuring4.8 x 2.4 x 3.7 cm, with small areas of calcification. His left adrenal gland showed thickening and nodularity. Primary adrenal insufficiency was diagnosed based on labs above. He was given high dose IV hydrocortisone which was tapered to PO Hydrocortisone 15mg QAM and 5mg QPM. Fludrocortisone 0.1mg PO daily was also added. His presenting symptoms resolved. Work up for HIV, tuberculosis, and syphilis was negative. His hypercalcemia was thought to be due to acute adrenal insufficiency and less likely related to malignancy or other causes. His mildly elevated PTH-rp was thought to be due to his renal dysfunction, and his mildly elevated kappa/lambda ratio was thought to be non-specific by the oncology consultants after the patient had a negative nuclear bone scan. He was treated with IV fluids and his hypercalcemia resolved. Due to elevated plasma normetanephrines a pheochromocytoma could not be excluded. CT adrenal protocol imaging showed a 4.2 cm right adrenal mass with unenhanced attenuation: 40.6 HU. Absolute washout: 4.0 %, suggestive of hemorrhage. The left adrenal gland was unremarkable on this scan.Alpha and beta blockade were instituted, and the patient underwent aright adrenalectomy. Pathology showed: Necrotizing granulomatous inflammation and coccidioides-like organisms on GMS stain. His coccidioides serum antibodies were positive. He was referred to infectious diseases and was started on fluconazole 400mg daily. He is doing well. Clinical Lessons: Disseminated coccidiomycosis is a rare cause of infectious adrenalitis, but it should remain on the differential diagnosis of primary adrenal insufficiency, especially in endemic areas. Presentation: Friday, June 16, 2023

FRI268 Late Onset Polyglandular Autoimmune Syndrome Type 2

Abstract Disclosure: M.S. Nicholson: None. A. Barnett: None. A 66-year old white female was admitted for weakness, acute kidney injury, and hypotension. This is her 3rd hospital or ER visit in the last 12 months for similar complaints. She has a 25 year history of type 2 diabetes on insulin and oral therapy and 30 year history of hypothyroidism on levothyroxine 75 mcg daily. She was on oral estrogen replacement therapy for post-menopausal symptoms with a hysterectomy in her early 50s. She has a sister with type 2 diabetes on oral meds and hypothyroidism. She has a brother with type 1 diabetes. Her serum sodium was 135 mmol/L (135-145), potassium was 5.4 mEq/L (3.5 -5.1), and calcium was 9.2 (8.5-10.1). Her Creatinine was 1.2 with a GFR of 48. A random cortisol in the ED was 9.2 (no ref range). Blood pressure was low and she was tachycardic and her weight was 68 kg. She was a well developed female with a a tanned complexion. Areas of vitiligo were noted on her arms. A cosyntropin stimulation test was done midday with a baseline, 30, and 60 minute cortisol levels of 9.2, 8.8, and 9.3 respectively. Baseline ACTH was 877.6 pg/mL (7.2-63.6). Her TSH was 4.09 mIU/mL (0.358-3.74) and free T4 was 1.29 ng/dL (0.76-1.46). DHEA-S was 14 mcg/dL (13-130). She was started on stress dose steroids with rapid improvement in BP, hyponatremia, and symptoms. GAD-65 antibodies were above 250 IU/mL and 21-hydroxylase antibodies were positive. Her TPO antibodies were negative. Non-insulin diabetes medications were stopped and she was discharged home after stabilization on prednisone 5 mg daily and fludrocortisone 0.1 mg daily. This patient has an atypical presentation of polyglandular autoimmune syndrome type 2 (PAS2). She presented with an Addisons crisis at the age of 66. She was already diagnosed with hypothyroidism and insulin requiring diabetes and evidence of vitiligo. A majority of patients with PAS2 are female and present in their 20s to 40s with primary adrenal insufficiency and primary hypothyroidism. Her initial manifestation was hypothyroidism and then diabetes and vitiligo with adrenal insufficiency many years later. Her random cortisol was not suppressed and this lead to a delay in her diagnosis. This was likely due to oral estrogen therapy raising cortisol-binding globulin. Her elevated baseline ACTH and lack of response to ACTH stimulation confirmed her diagnosis of primary adrenal insufficiency. An ACTH stimulation test was repeated as an outpatient with similar response. This case highlights the importance of provocative testing for adrenal disorders and testing for autoimmune causes of endocrine disorders when patients are not responding as expected. Presentation: Friday, June 16, 2023

Approach to the Patient: Diagnosis of Primary Adrenal Insufficiency in Adults.

Approach to the Patient: Diagnosis of Primary Adrenal Insufficiency in Adults.

Radiation of bilateral adrenal metastases is associated with a high risk of primary adrenal insufficiency.

Adrenal metastasis is the most common adrenal malignancy and can be bilateral in up to 43% of patients. Radiotherapy (RT) is one option available to treat adrenal metastases. The risk of primary adrenal insufficiency (PAI) after adrenal RT is unclear. Determine the incidence and the timeline of PAI in patients undergoing adrenal RT. Single-centre longitudinal retrospective cohort study of adult patients with adrenal metastases treated with RT between 2010 and 2021. Of 56 patients with adrenal metastases treated with adrenal RT, eight (14.3%) patients developed PAI at a median of 6.1 months (interquartile range [IQR]: 3.9-13.8) after RT All patients developing PAI had either unilateral RT in the setting of contralateral adrenalectomy or bilateral adrenal RT. Patients who developed PAI received a median RT dose of 50 Gy (IQR: 44-50 Gy), administered in a median of five fractions (IQR: 5-6). Treated metastases decreased in size and/or metabolic activity on positron emission tomography in seven patients (87.5%). Patients were initiated on hydrocortisone (median daily dose of 20 mg, IQR: 18-40) and fludrocortisone (median daily dose of 0.05 mg, IQR: 0.05-0.05 mg). At the end of the study period, five patients died, all due to extra-adrenal malignancy, at a median time of 19.7 months (IQR: 16-21.1 months) since RT and median time of 7.7 months (IQR: 2.9-12.5 months) since the diagnosis of PAI. Patients receiving unilateral adrenal RT with two intact adrenal glands have a low risk of PAI. Patients receiving bilateral adrenal RT have a high risk of PAI and require close monitoring.

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.

PSUN26 Radiation For Adrenal Metastases: Should Patients be Monitored For Primary Adrenal Insufficiency?

Abstract Background Adrenal metastasis is the most common adrenal malignancy and can be bilateral in up to 43% of patients. Risk of primary adrenal insufficiency (PAI) in bilateral metastases is 12%. Adrenal radiation is one of the options available to treat adrenal metastases. The risk of PAI after bilateral adrenal radiation is unclear. Objective We aimed to determine the incidence and the timeline of PAI in patients undergoing adrenal radiation for bilateral metastases. Design, Setting, and Participants: Single center retrospective study of adult patients with adrenal metastases treated with adrenal radiation between 2010 and 2021. Results Of 55 patients with adrenal metastases treated with adrenal radiation, 7 (12.7%) had bilateral therapy, of whom 5 (all with lung adenocarcinoma) developed PAI. Another patient with history of unilateral adrenal radiation and previous contralateral adrenalectomy also developed PAI. Following the radiation therapy (median dose 50 Gy [range 20-65 Gy]), administered in a median of 5 fractions (range 5-18 fractions) in 6 patients who developed PAI, all treated metastases either decreased in size during imaging follow up or demonstrated a decrease in SUV uptake on PET scan. PAI developed at a median time of 6.1 months after radiation (range 0.5-20.4 months). PAI was diagnosed based on laboratory monitoring in 3 patients and based on treating endocrinologist's discretion (e.g., symptoms, clinical context) in the other 3 patients. Patients were initiated on hydrocortisone (median daily dose of 20 mg, range 15-80 mg) and fludrocortisone (median dose of 0.05 mg, range 0.05-0.1 mg) At the end of the study period, daily replacement dose was higher for both for hydrocortisone (median of 35 mg, range 15-160 mg) and for fludrocortisone (median of 0.0625 mg, range 0.05-0.1 mg). All but one patient with PAI had passed away at the end of the study, at a median time of 19.7 months (range 6.1-55.8 months) since radiation and median time of 7.7 months (range 1.2-55.3 months) since the diagnosis of PAI. In the two patients with bilateral adrenal radiation who did not develop PAI, the follow up was short: 1 patient passed away six-months post-radiation and another patient had only 4 months of follow up. Conclusion Adrenal radiation is an effective therapy for patients with adrenal metastases. Risk of PAI is very high when bilateral adrenal radiation is administered, and patients need to be counseled about it. We observed that daily glucocorticoid replacement dose was excessive in some patients possibly reflecting the use of stress dosing due to underlying sickness. Both clinical and biochemical monitoring every 3-6 months should be instituted in patients undergoing bilateral adrenal radiation. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.

PSUN24 Adrenal Metastases Treated with Radiotherapy: Development of Adrenal Insufficiency

Abstract Introduction Adrenal metastases are the second most common neoplasms of the adrenal cortex. Adrenal insufficiency (AI) develops when more than 90% of the cortex is destroyed. In patients with adrenal metastases requiring local treatment, stereotactic ablative radiation therapy (SAbR) has been shown to be well tolerated. Yet, data on the development of AI following adrenal SAbR are scarce. Therefore, we aimed to assess the incidence, timing, and factors associated with the development of AI in patients undergoing SAbR for the treatment of adrenal metastases. Utilizing an IRB approved registry protocol, we conducted a retrospective longitudinal follow-up study to characterize 66 patients (73% men; median age 61 years) with adrenal metastases who underwent SabR, followed for median 3.8 years from the initial cancer diagnosis and 11.5 months from SAbR. The diagnosis of primary AI was based on low morning serum cortisol levels (<5 μg/dL) with >2-fold elevated plasma ACTH, or peak cortisol <18 μg/dL post cosyntropin. Primary carcinomas included renal cell (41%), lung (38%), colorectal (9%), melanoma (5%), and others (7%). Twenty-four (38%) patients had bilateral adrenal metastases. At the time of SAbR, 41 (62.1%) patients had uninvolved contralateral adrenal glands, 16 (24.2%) had bilateral adrenal metastases, and 9 (13.6%) had contralateral adrenalectomy prior to SAbR. Nine patients had bilateral SAbR and 9 had SAbR to one adrenal gland in the setting of contralateral adrenalectomy. Most patients (66.7%) underwent 5 SAbR fractions, with a median dose of 800 cGy/fraction. In our cohort, 39/66 (59%) patients underwent comprehensive assessment of adrenal function. Overall, 7 (10.6%) patients developed post-SAbR AI at median time of 4.3 months (range, 0.7-20.2). The incidence of post-SAbR AI was 22.2% (2/9) in patients with prior contralateral adrenalectomy, 18.8% (3/16) with bilateral adrenal metastases, and 0% (0/41) with normal contralateral adrenal gland. A 6-month-AI-free survival rate was 72.7% (95% CI, 37.0-90.3) in patients with bilateral metastases and 64.8% (1.6-73.7) in patients with contralateral adrenalectomy. Post-SAbR median progression-free survival (local disease) was 3.0 years, with 6-month and 1-year survival rates of 82.4% and 75.0%, respectively. Conclusions Our study shows thatpatients with a normal contralateral adrenal gland are unlikely to develop post-SAbR AI. In contrast, AI occurred in ∼ 20% of patients with prior contralateral adrenalectomy or bilateral adrenal metastases. In this high-risk cohort, only 60% of patients underwent assessment of adrenal function. It is crucial to monitor adrenal function in patients undergoing SAbR for adrenal metastasis, especially in those with affected or surgically absent contralateral gland. This study reinforces the importance of a team-based approach to the management of patients with adrenal metastasis to improve patient outcomes. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.

ODP273 Schmidt Syndrome Causing Multiorgan Failure

Abstract Introduction To our knowledge there has not been a case report published on the acute presentation of Schmidt syndrome (Polyglandular Autoimmune Syndrome Type 2) in which all three manifestations of type 1 diabetes mellitus (T1DM), primary adrenal insufficiency, and hypothyroidism were found and diagnosed at the same time. Case Description A 32-year-old male with suspected alcohol abuse presented to the hospital with nausea, vomiting, and weakness of two weeks duration after sustaining a fall. He was admitted for Diabetic Ketoacidosis (DKA) and shock requiring three pressors with unclear etiology. Labs were significant for severe hyponatremia of 113 mmol/L (136-145), elevated anion gap of 22, glucose 206 mg/dL (70-100), bicarbonate 11mmol/L (21-31), beta hydroxybutyrate 5.90 mmol/L (0. 0-0.42), and pH 7.22 (7.35-7.45) with Hemoglobin A1c 14.5% (<5.7). An insulin drip was instituted for DKA and the hyponatremia persisted. Cortisol was found to be suppressed at 3. 0 ug/dL (3.1-22.4) with significantly elevated ACTH 220.4 pg/mL (7.2-63.3) suggesting a new diagnosis of primary adrenal insufficiency. IV hydrocortisone 100 mg q8H was started on day 2 of hospitalization. Thyroid labs showed elevated TSH 10.10 uIU/mL (0.36-3.74) confirming hypothyroidism, prompting initiation of IV levothyroxine. His hospital course was complicated by cardiac arrest and acute respiratory failure requiring intubation. Cardiac work up was negative except for severe non-ischemic cardiomyopathy with significantly reduced ejection fraction of 20-25%. Bronchoscopy was performed and showed no evidence of obstructing pulmonary etiologies. SARS Coronavirus PCR was negative. He also had shock liver along with Disseminated intravascular coagulation (DIC). His kidney function worsened requiring continuous kidney replacement therapy (CRRT). Urine microscopy showed granular casts consistent with acute tubular necrosis. TPO antibodies, adrenal antibodies, GAD antibodies, and Zinc Transporter 8 antibodies all came back positive along with an undetectable C- peptide confirming the diagnosis of Hashimotos hypothyroidism, primary adrenal insufficiency, and T1DM respectively. He was eventually discharged on basal bolus insulin regimen, levothyroxine 75 mcg po daily, fludrocortisone 0. 05 mg po daily, and prednisone 5 mg po daily. The patient had multifactorial shock from an acute presentation of DKA, primary adrenal insufficiency, and hypothyroidism all presenting simultaneously. Conclusion This case illustrates the severe impact of having three endocrine organs affected all at once. The prevalence of Schmidt syndrome is very low at 1: 20,000 in the general population and can be associated with other non-endocrine autoimmune disorders. Prevalence of autoimmune thyroid disease is 70%, T1DM 50%, and Addison's disease is almost 100%. Due to the low prevalence, one needs a high clinical suspicion with the correct lab findings to diagnose this disease. Incorrect diagnoses or a late diagnosis can lead to life threatening consequences to the patient. The mainstay of treatment is hormone replacement, with corticosteroids given before thyroid replacement. Presentation: No date and time listed

Cortisol Deficiency in Lenvatinib Treatment of Thyroid Cancer: An Underestimated Common Adverse Event.

Background: Lenvatinib treatment has shown a significant improvement in progression-free survival in patients with metastatic, progressive, radioiodine-refractory differentiated thyroid cancer, although its use is associated with considerable toxicity. Fatigue is one of the most frequent adverse events (AEs). It has been reported that adrenal insufficiency (AI) may be involved in lenvatinib-related fatigue. In our study, we assessed the pituitary/adrenal axis before and during treatment, and the possible involvement of AI in lenvatinib-related fatigue. This was done to clarify the incidence, development, and time course of AI during lenvatinib treatment.Methods: We studied 13 patients who were selected for lenvatinib therapy. Adrenal function was evaluated by measuring cortisol and adrenocorticotropic hormone (ACTH) levels and through the ACTH (250 μg) stimulation test.Results: During treatment, seven patients (54%) developed AI. High levels of ACTH were observed in accordance with the diagnosis of primary AI (PAI). By evaluating the first ACTH test, before starting lenvatinib treatment, we found that patients with <646.6 nmol/L cortisol peak had an increased risk of developing PAI during lenvatinib treatment. Fatigue was observed in 11 patients (84.6%) during lenvatinib treatment. Cortisone acetate treatment induced an improvement in fatigue in six of seven patients (85.7%) in the PAI group, without the need to change the lenvatinib dosage.Conclusions: PAI may be considered one of the most common AEs associated with lenvatinib. Our data strongly suggest that PAI could be involved in lenvatinib-associated fatigue, particularly in patients with extreme fatigue. In this context, early diagnosis of PAI is essential, especially since glucocorticoid replacement therapy can induce a significant improvement in fatigue, without the need to reduce the dosage of lenvatinib. However, further studies are required to confirm these preliminary findings.

Genetic Diagnosis of Primary Adrenal Insufficiency in Children: A Paradigm Change

Genetic Diagnosis of Primary Adrenal Insufficiency in Children: A Paradigm Change

Careful Evaluation of Cosyntropin Dose in the Diagnosis of Adrenal Insufficiency

Introduction: The use of the 250μg cosyntropin dose or otherwise called high-dose ACTH test is the gold standard test for diagnosis of primary adrenal insufficiency. The 1μg dose test or the low-dose test is mostly reserved for diagnosis of secondary adrenal insufficiency. Careful consideration of the results produced during the diagnostic process is imperative to avoid mislabeling of patients with a disease that requires lifelong treatment. Case Report: This is the case of a 45-year-old female with a history of asthma and psoriasis who presented with emesis. Home medications included monthly TNF-alpha inhibitor injections for psoriasis, triamcinolone acetonide topical spray and budesonide-formoterol inhaler. On admission, she also had nausea, chills and diaphoresis, as well as palpitations, lightheadedness, and shortness of breath. When she arrived at the ER, vitals were remarkable for low blood pressure. Labs were unremarkable except for CMP concerning for anion gap metabolic acidosis, hyponatremia, and hypokalemia. A random serum cortisol was 6.4 mcg/dL, which was relatively low. ACTH was within normal range. Due to concern for adrenal insufficiency, a 1μg cosyntropin test was performed which showed a peak cortisol concentration of less than 18 mcg/dL. As the response was assessed as suboptimal, endocrinology was consulted to offer a treatment plan for steroids. However, the test was repeated using the gold standard 250μg cosyntropin dose and the patient then showed an adequate response and she was not started on steroids. Conclusions: This is a case that demonstrates how the 250 μg ACTH or high-dose stimulation test should be used for diagnosis of primary adrenal insufficiency (AI), as it is the gold standard. The 1 μg ACTH or low-dose stimulation test can be used for diagnosis of primary AI but only when the high dose test is not available. On the other hand, the 1 μg ACTH stimulation test has been shown to be more sensitive than the 250 μg test in diagnosing secondary adrenal insufficiency. When using the most appropriate test correctly, the clinician can only then offer the patient the best treatment strategies. Our patient did not require chronic replacement therapy. The steroids in this case could have harmed the patient as chronic administration could cause adrenal gland suppression.

Immune Check Point Inhibitors Triggering Non Autoimmune Polyendocrinopathy

The superlative therapeutic response of cancer immunotherapy is activation of the immune system against cancer cells. Currently, one of the most considered immune system enhancer are the immunomodulatory antibodies well known as checkpoint inhibitor therapy. Among this type of treatment, programed cell death-1 receptor blocker, is one of the most sought-after therapies on demand now a day. Notwithstanding the important clinical benefits of this therapeutic modality, serial autoimmune adverse effects and variety of atypical presentations of life-threatening endocrinopathies are expected to occur.We present a case of a 78-year-old man with dyslipidemia and lung CA who was referred to our clinic after developing electrolyte disturbances with associated dizziness and fatigue one month after Pembrolizumab therapy initiation. Physical exam was unremarkable. Laboratory data was consistent with mild hyponatremia, hyperkalemia and adequate fasting blood sugar levels. Aldosterone levels were extremely low, ACTH levels were extremely high with inappropriate low total cortisol response and negative 21-Hydroxylase antibodies. Diagnosis of primary adrenal insufficiency was established and Fludrocortisone 0.05 mg PO daily therapy was started with further resolution of hyponatremia and initial symptoms. In addition, concurrent primary hyperthyroidism along with thyroid RAIU-Scan results were consistent with thyroiditis, but TSI and TPO’s antibody levels were unexpectedly negative. Eventually, a suspicious thyroid nodule was identified requiring biopsy. Initial FNA results showed a follicular lesion of undetermined significance followed by a benign finding when repeated after six months. During follow up, patient’s primary hyperthyroidism converted to severe primary hypothyroidism without any intervention for her prior hyperthyroidism. Patient’s TPO’s levels remain undetectable and his current status is post-thyroiditis with residual primary hypothyroidism. Primary adrenal insufficiency also persist and its antibodies have not yet been identified either.It is known that autoimmunity can predispose to the development of primary adrenal and thyroid disorders in patients undergoing PD-1 receptor blockers therapy against cancer. Both disorders are increasingly recognized and reported as one of the most common adverse effects presenting in patients treated with these agents. However, to our knowledge, cases of non-immune related adverse effects are barely documented. This case of uncommon endocrine manifestations related to checkpoint inhibitors therapy is meritorious of being reported since it should raise awareness in the medical community for prompt identification of signs and symptoms, as well as to offer adequate management, accurate treatment and provide a better standard of care.

PTH-Independent Hypercalcemia in Undiagnosed Adrenal Insufficiency

In contrast to PTH-dependent hypercalcemia, the differential diagnosis of PTH-independent hypercalcemia is extensive. Thorough history and physical examination can help direct the clinician in the right direction and avoid extensive and unnecessary work up.A 27-year-old-female with a medical history significant only for untreated subclinical hypothyroidism was admitted to the hospital for hypercalcemia and acute kidney injury after presenting with dizziness, nausea, vomiting, dyspnea, and multiple syncopal episodes prior to admission. Serum calcium on presentation was elevated to 15.9 (8.5–10.2 mg/dL) with an intact parathyroid hormone level of 3.6 (8.5–75 pg/mL). On initial presentation, she was hypotensive, tachycardic, and was noted to be underweight with a body mass index of 17 kg/m2. The patient’s skin was diffusely hyperpigmented, with increased pigmentation in the creases of her hands and on the sides of her fingers. Further lab evaluation was remarkable for hyponatremia and hyperkalemia as well as an undetectable 8 AM cortisol of <1.0 (7–25 µg/dL), adrenocorticotropic hormone (ACTH) level significantly elevated to >1,250 (6–58 pg/mL), aldosterone <4 (<21 ng/dL), and plasma renin activity elevated to 18 (<0.6–3 ng/mL/h). Antibodies to 21-alpha hydroxylase were positive, confirming a diagnosis of Addison’s disease. Prior to the workup confirming an elevated ACTH and low cortisol levels, the patient was treated with aggressive intravenous fluid repletion and calcitonin with overnight improvement in calcium to 11.4 mg/dL. After the diagnosis of primary adrenal insufficiency was confirmed, she was treated with stress doses of intravenous hydrocortisone then gradually tapered to physiologic doses of oral hydrocortisone and fludrocortisone with resolution of her hypercalcemia by the fourth day of hospitalization.Adrenal insufficiency is a known but uncommon cause of PTH-independent hypercalcemia, but the exact mechanism is unknown. Hypercalcemia is thought to result from a combination of a hypovolemic state seen in adrenal insufficiency which leads to decreased urinary calcium excretion as well as increased bone resorption, which may result from increased serum sclerostin concentrations.Adrenal insufficiency should be considered in the differential of PTH-independent hypercalcemia. This case highlights the improvement in hypercalcemia that is seen with correction of glucocorticoid deficiency, and supports delaying additional work up for other PTH-independent causes until appropriate treatment has been given.

PD-1 Inhibitors Induced Primary Hypoadrenalism

Abstract Background: Primary adrenal insufficiency is known to be induced by certain medications, including anesthetics, antimycotic and antiparasitic medications. However, it is rarely being reported that caused by antitumor immune checkpoint inhibitors PD-1. Clinical Case: A 82-year-old female with a significant history of lung adenocarcinoma status post of recent Pembrolizumab therapy. She presented with multiple complaints, including increasing confusion, mainly memory loss, generalized aches, and pains who was found to have recurrent hyponatremia with a sodium level of 122, treated with water restriction and sodium tablets. Initial screening labs were suggestive of adrenal insufficiency: level of ACTH was within the normal range (11 pg/dL, normal range 7.2–63 pg/dL), level of cortisol was low (1.6 ng/dL, normal range 3–23 pg/dL). MRI brain without contrast ruled out metastatic disease. An ACTH-stimulating test was performed, with the results revealing an inadequate cortisol response at 0, 30, and 60 minutes(1.4 ug/gl, 8.5 ug/dl, 11.9 ug/dl, normal range 18–20 ug/gl). Therefore, a diagnosis of primary adrenal insufficiency was made. The patient was prescribed a daily oral dose of 5 mg of hydrocortisone. Her symptoms improved after a few days, and her hydrocortisone gradually increased to 15 mg daily, and her energy and memory were back to baseline after six months. Conclusion: This is a rare case of primary adrenal insufficiency caused by Pembrolizumab using for non-small lung cancer treatment. With the growing use of Pembrolizumab, it is necessary to be aware of possible adrenal insufficiency that could be associated with receiving pembrolizumab therapy amid any clinical suspicion. Reference: Chang, L.S., et al., Endocrine Toxicity of Cancer Immunotherapy Targeting Immune Checkpoints. Endocr, Rev, 2019. 40(1): p. 17–65

Differential diagnosis of primary adrenal insufficiency in a young male with mental retardation and axonal sensorimotor polyneuropathy

Differential diagnosis of primary adrenal insufficiency in a young male with mental retardation and axonal sensorimotor polyneuropathy

Hyperkalemia in a patient with myasthenia gravis: case presentation

BackgroundMyasthenia gravis (MG) is the most common disorder of neuromuscular transmission, and it is typified by fluctuating degrees and variable combinations of weakness in the ocular, bulbar, limb, and respiratory muscles. Under rare circumstances, MG can be accompanied by Addison’s disease.Case presentationHere, we reported the case of a 57-year-old Chinese woman with MG. She experienced progressive muscle weakness for 1 week. MG with acute exacerbation was initially suspected. However, further biochemistry tests found mild hyperkalemia (5.6 mEq/L) and a lower renal potassium excretion rate. Consequently, low aldosterone action was highly suspected. Further findings included a suppressed cortisol level, a higher adrenocorticotropic hormone concentration, and 21-hydroxylase antibody positivity, supporting a diagnosis of primary adrenal insufficiency due to autoimmune adrenalitis.ConclusionWe successfully demonstrated that adrenal insufficiency could be diagnosed, due to the presence of hyperkalemia. This case suggested a need for clinicians to consider the possible coincidence of adrenal insufficiency in a patient with MG and hyperkalemia. Early hormone supplementation should be begun.