AM Cortisol Research Articles

7071 Cushing disease presenting with Dilated Cardiomyopathy

Abstract Disclosure: H. Majeed: None. C. Nguyen: None. R. Galagan: None. D. Lovre: None. Background: Hypercortisolism manifests with numerous ways due to the wide distribution of glucocorticoid receptors. Here we describe a case of Cushing’s disease presenting with reversible non-ischemic cardiomyopathy. Case Presentation: A 30-year-old male presented to ER with palpitations, dyspnea, and atypical chest pain. His exam was notable for a BMI of 30.26 kg/m2, HR 76 bpm and BP of 200/110 mm Hg. His EKG revealed Left ventricular hypertrophy. Echocardiogram (ECHO) showed an EF of 25-30% with diffuse hypokinesis. An angiogram demonstrated normal coronary anatomy. He was started on Lisinopril, Carvedilol, and Spironolactone for non-ischemic cardiomyopathy. He also complained of a 40 lb weight gain, loss of libido, hot flashes and breast tenderness. He was referred to endocrinology. Initial evaluation demonstrated total testosterone (TT) of 171 ng/dl (286-1511 ng/dl), FSH 3.8 IU/L (2-12 IU/L), LH 5.6 IU/L (2-9 IU/L) consistent with secondary hypogonadism. Further pituitary workup revealed AM cortisol level 31.22 mcg/dl (4.3-22.4mcg/dl), ACTH 79 pg/ml (7.2 - 63.3pg/ml), IGF-1 257 ng/mL (88-246 ng/mL), Prolactin 23.7 ng/dl (2.1- 17.7ng/dl), TSH 0.54 mIU/l (0.35-3.74mIU/l) and FT4 0.6 ng/dl (0.76-1.46 ng/dl). A 24hr urine cortisol was 167 ug(0-50ug/24h) and midnight salivary cortisol 0.160 ug/dl (<0.010-0.090 ug/dl). An overnight 1mg dexamethasone suppression test (DST) resulted in AM cortisol of 20.95 mcg/dl (<1.8mcg/dl) and 8mg DST cortisol fell from 34 mcg/dl to 4.16 mcg/dl. A pituitary MRI revealed a left 6 mm x 4 mm microadenoma. He was treated with levothyroxine pre-op for central hypothyroidism. He underwent transsphenoidal resection of the pituitary adenoma. Post-op AM cortisol was 1.1 mcg/dl. His steroid withdrawal syndrome was treated with a prolonged course of tapered hydrocortisone. Two months post-op ECHO showed EF of 55-60%. His BP normalized on carvedilol alone. Eighteen months post-op he no longer required any hormone replacement. Repeat ACTH 24.4 pg/ml, Total Testosterone 584ng/dl, TSH 0.57 mIU/l and FT4 0.93 and 24hr urine cortisol was 24ug/dl, MN salivary cortisol <0.10 ug/dl confirming remission of his cushing's disease and resolution of secondary hypogonadism and hypothyroidism. Conclusion: Prolonged hypercortisolism can cause abnormal cardiac remodeling resulting in cardiomyopathy. Surgical remission of Cushing’s disease reverses hypercortisolism which may restore normal cardiac function. Presentation: 6/2/2024

7392 Unilateral Adrenal Embolization In Cushing Disease-A Lifesaving Emergent Procedure

Abstract Disclosure: M. Sadiq: None. B. Irshad: None. A. Haider: None. Case presentation: A 59-year-old female was diagnosed with Cushing Disease (CD) thirteen years ago with symptomatic hypercortisolism. Hypokalemia and elevated 24-hour urine cortisol (392 ug/24 hr, n 0-50 ug/24 hr) were noted at the time of diagnosis. Following LDDST, morning cortisol was 30.5 ug/dl, and HDDST showed greater than 50% suppression. A pituitary macroadenoma with bilateral cavernous sinus extension was noted on MRI Sella. Due to cavernous sinus invasion, she was not considered a surgical candidate and underwent Gamma knife radiation. 24-hour urine cortisol decreased significantly (20 ug/24 hours). Two years follow-up MRI brain showed an empty Sella and AM cortisol was noted to be normal at 12.2 ug/ dl with no evidence of AI. She was lost to follow-up and reestablished almost ten years after her initial gamma knife and was symptomatic from hypercortisolism. 24-hour urine cortisol at 85.4 mcg/24 hr, abnormal salivary cortisol x 2 (0.24 and 0.20 mcg/dl n < 0.09 mcg/dl) confirming hypercortisolism. MRI of Sella showed recurrent adenoma with bilateral sellar masses. She was referred to Neurosurgery and was started on Ketoconazole and Paseriotide once-monthly injections. She developed new onset diastolic heart failure & upper GI bleeding, requiring hospitalization. High ACTH level of 668 pg/ml (n. 6.6- 65 pg/ ml). 8 am cortisol was 107.6 ug/dl which was suppressed to 16.1 after 8 mg overnight Decadron. Repeat Gamma knife was planned but due to her decline, it was decided to do unilateral adrenal artery embolization to reduce hypercortisolism. IR-guided adrenal artery embolization of the left middle & inferior adrenal arteries was performed. She required stress dosing of HC post-embolization which was tapered off while monitoring 8 am cortisol which started to rise & 24-hour cortisol levels were noted to be normal (51.2 mcg/24 H) on post-embolization day eight. Gamma knife radiation treatment was performed a month later after which she was noted to have GWS and required Hydrocortisone 15/10 mg twice daily, which she has been taking to date. 24-hour urine cortisol remains normal at 11.8 mcg/24 h. Discussion: Treatment for CD is primarily surgical. Radiotherapy is a second-line alternative in tumors that are non-amenable to surgery. Radiotherapy takes time to achieve its full effect. Cushing Disease patients with significant hypercortisolism and resultant complications require urgent treatment. Unilateral Adrenalectomy is described in literature to curb the cortisol burden . Similarly Unilateral Adrenal artery embolization offers less invasive approach to treat patients considered unfit for surgery. Conclusion: Unilateral adrenal artery embolization can be considered a bridging treatment in CD to reduce cortisol burden and improve the metabolic profile following which a more definitive treatment such as repeat surgery or radiotherapy can lead to long-term remission. Presentation: 6/1/2024

7667 Cushing’s Puzzle: Echinococcal Pituitary Cyst In A Rare Encounter

Abstract Disclosure: E. Sari: None. F. Erenler: None. Introduction: Echinococcus is a rare parasitic infection endemic in the Mediterranean, Middle East, South America and Africa, which can cause cystic disease in several organs. Central nervous system involvement is known to comprise 1-2% of all cystic echinococcal disease. Hereby, we report a case of an opportunistic pituitary echinococcus infection in a patient with hypercortisolism due to adrenocortical adenoma with initial misdiagnosis of Cushing’s disease. Clinical Case: A 40-year-old South American female with poorly controlled T2DM on oral agents and hypertension presented to the ER with abdominal pain and subsequent CT of the abdomen with contrast showed a right adrenal mass measuring up to 2.8 cm. A follow up CT with adrenal protocol confirmed 3.3 cm right adrenal mass, 46 HU in precontrast images with >50% washout. Review of records revealed that a recent MRI brain with contrast was performed for headache evaluation and showed an incidental 5x7x4 mm lesion in the pituitary gland. Endocrinology evaluation revealed 24-hour urine volume 1800 mL, elevated free cortisol levels 277.6 mcg/24hr (RR: 4.0-50.0 mcg/24hr), creatinine of 0.67g/24hr (RR: 0.50-2.15g/24hr). 1 mg dexamethasone suppression test showed AM cortisol of 28.7 mcg/dL. ACTH was elevated at 67 pg/mL (RR: 6-50 pg/mL). FSH, LH, and GH were normal. Presumed diagnosis of ACTH-dependent hypercortisolism was made and she underwent bilateral inferior petrosal sinus sampling with confirmed successful cannulation but this was inconclusive due to low ACTH levels. Follow-up MRI of the pituitary gland showed T1 bright, T2 isointense circumscribed lesion measuring 7x6x3 mm at anterior pituitary gland with a thin rim of peripheral enhancement consistent with cystic features. She underwent transsphenoidal resection of the pituitary lesion and the pathology specimen showed parasites consistent with echinococcosis. Infectious disease was consulted, and the patient started on albendazole. Post-operative laboratory evaluation was notable for persistently elevated AM cortisol, 24-hour urine free cortisol levels, and low ACTH levels, confirming ACTH independent hypercortisolism. She underwent right adrenal nodule resection and pathology was consistent with adrenocortical adenoma. Post-adrenalectomy AM cortisol levels were < 2 mcg/dL, indicating the resolution of hypercortisolism along with substantiating the diagnosis of primary adrenocortical hyperfunction. Conclusion: To the best of our knowledge, this is the first case report of an opportunistic echinococcus infection presenting as a pituitary lesion in the setting of Cushing Syndrome. We would like to highlight the importance of recognizing opportunistic infections, including Echinococcus as a potential etiology in the setting of hypercortisolism, especially for patients from endemic regions. Presentation: 6/2/2024

8479 A Challenging Case of Hypercortisolism in an Adult Patient With McCune Albright Syndrome

Abstract Disclosure: P. Kesavan Chary: None. S. Jasim: None. Background: McCune Albright Syndrome (MAS) is a rare genetic disorder that occurs due to a spontaneous post-zygotic missense mutation in the GNAS gene resulting in activating gain of function mutations in G-proteins. MAS classically presents as a triad of café-au-lait skin pigmentation, fibrous dysplasia of bone, and precocious puberty. However, continuous autonomous stimulation of endocrine glands can also result in various other endocrinopathies. We present a rare case of hypercortisolism due to bilateral multinodular adrenal hyperplasia (BMAH) in an adult patient with MAS. Case Report: A 38 year old female had MAS, clinically manifested by precocious puberty, renal phosphate wasting with rickets and osteomalacia, fibrous dysplasia of bone with history of multiple fractures, growth hormone excess, and multinodular thyroid status-post total thyroidectomy. A surveillance CT abdomen showed bilateral (right 3.8 x 1.3 cm and left 1.0 x 0.9 cm) adrenal adenomas with low intrinsic attenuation and washout. On diagnosis, the patient had an AM cortisol of 32.5 ug/dL (6.2-19.4 ug/dL) after a low-dose dexamethasone suppression test (DST), and an AM cortisol of 27.3 ug/dL after a high-dose DST. Late night salivary cortisol was 0.518 ug/dL (<0.010-0.090 ug/dL), 24-hour urine cortisol was 78 ug/24hrs (6-42 ug/24hrs), and ACTH was <1.5 pg/mL (7.2-63.3 pg/mL). The patient was initially asymptomatic and monitored for a few months, but subsequently developed easy bruising, recurrent skin infections, and irritability. The patient declined surgical intervention and was initiated on Osilodrostat. Shortly after medication initiation, she was hospitalized for perforated diverticulitis, hypokalemia, and hypomagnesemia. During hospitalization, AM Cortisol was 49 mcg/dL (4.8-19.5 mcg/dL) and 24-hour urine cortisol was 1023 mcg/24hrs (normal range 3.5-45 mcg/24hrs; the patient’s level prior to admission was 170-190 mcg/24hrs). Osilodrostat was held and the patient was initiated on Etomidate infusion. Once plasma cortisol levels normalized, she resumed Osilodrostat prior to discharge. The patient subsequently tried multiple medical therapy options before undergoing a bilateral adrenalectomy as a definitive treatment choice. Conclusion: The gain of function mutations in MAS result in autonomous endocrine gland function that can manifest clinically as various endocrinopathies. While the most common endocrinopathies in MAS are precocious puberty, hyperthyroidism, and pituitary dysfunction, active surveillance is critical to monitor for less common presentations such as hypercortisolism. This is the first report of adrenal Cushing’s in an adult patient with MAS. Presentation: 6/3/2024

7469 A Case of Severe Transient Hypercortisolism In a Patient With Bacterial Meningitis

Abstract Disclosure: R. Harxhi: None. D.V. Mihailescu: None. Background: Increased cortisol levels are known to occur in states of significant stress caused by acute illness. This may be attributed to stress leading to a rise in the corticotrophin releasing hormone thereby increasing adrenocorticotrophic hormone levels. This may consequently result in severe transient hypercortisolism and bilateral adrenal structural changes.Clinical case:A 55-year-old female with a past medical history of HTN and pre-diabetes presented to the hospital with a headache and altered mental status starting the day prior to admission. On arrival, she was found to be hypertensive, confused and was diagnosed with acute bacterial meningitis caused by streptococcus pneumoniae. Initial labs were notable for a potassium level of 2.5 mEq/L (normal 3.5-5 mEq/L). Work-up of persistent hypokalemia revealed a cortisol of 54.83 ug/dL (normal 6.7-22.6 ug/dL), ACTH 166 pg/mL (normal 9-50 pg/mL), aldosterone < 1 ng/dL (normal 3-16 ng/dL), and renin 0.57 (normal 0.25-5.82). CT of the abdomen showed bilateral periadrenal fat stranding, larger on the left with no adrenal nodules. On physical exam, patient did not exhibit any cushingoid features. Significantly elevated AM cortisol levels persisted despite treatment with high dose dexamethasone as part of the meningitis regimen (20 mg) resulting in unsuppressed AM cortisol of 9.22 ug/dL. An MRI of the brain showed a partially empty sella rendering a pituitary adenoma unlikely. Patient’s clinical status improved rapidly, and hypokalemia resolved. A low dose dexamethasone suppression test performed 9 days post admission produced an appropriately suppressed cortisol (1.0 ug/dL) and ACTH (14 pg/mL) levels, thus confirming a functional response to acute illness. Conclusion: This is a rare case of severe transient hypercortisolism with periadrenal congestion (“fat stranding”) resulting in hypokalemia (likely due inappropriate activation of mineralocorticoid receptors) in the setting of acute illness. There have been a very limited number of similar cases reported in literature, particularly with respect to CNS infections. It is important to recognize the response to acute stress could produce significant elevation of cortisol levels leading to the activation of mineralocorticoid receptors, therefore mimicking primary hyperaldosteronism. Presentation: 6/1/2024

5132 Unraveling the Enigma: A COVID-19 Triggered Revelation of Adult Idiopathic ACTH Deficiency

Abstract Disclosure: K.A. Arao: None. A.E. Gadbois: None. Introduction: Adult idiopathic ACTH deficiency (AIAD) is a rare and potentially life-threatening condition that is frequently misdiagnosed or even missed. We present a case of AIAD in a patient who exhibited altered mental status alongside a COVID-19 infection and was fortunately diagnosed after responding to empiric treatment with oral steroids for another condition. Case Presentation: A 76-year-old man was admitted to the hospital for bilateral leg weakness. His hospital stay was complicated by the development of febrile episodes and delirium. He tested positive for COVID-19, and the rest of infectious work-up yielded negative results. He then received a course of remdesivir. In the evaluation of his delirium, a CT scan of the brain, MRI of the brain, and lumbar puncture with CSF analysis were done, all of which were unremarkable. Initially, the delirium was attributed solely to COVID-19 infection. After consultation with neurology and rheumatology, the patient received empiric treatment with prednisone 5 mg twice daily for possible polymyalgia rheumatica as a cause of his bilateral leg weakness. His mental status significantly improved following steroid administration. With the improvement in symptoms, an AM cortisol test was added on his morning blood tests, revealing a cortisol level of 2.56 mcg/dL with an albumin level of 2.3 g/dL, raising concerns for adrenal insufficiency. An outpatient endocrinology evaluation recommended transitioning from prednisone to physiologic twice-daily dosing of hydrocortisone. An ACTH stimulation test was performed, which peaked at an AM cortisol of 6.1 mcg/dL, with a baseline ACTH level of 4.1 pg/mL. A review of the recent brain MRI showed no pituitary pathology. Other pituitary hormones were normal, and he was eventually diagnosed with AIAD. He was subsequently maintained on physiologic dosing of hydrocortisone, resulting in clinical stability. Discussion: AIAD is characterized by secondary adrenal insufficiency, normal production of other pituitary hormones, and the absence of structural pituitary pathology. The etiology of AIAD remains unknown, with most cases attributed to an autoimmune process. AIAD can have diverse clinical manifestations and may only become more apparent with triggers like infections or illnesses. As in our case, the COVID-19 infection likely unmasked the underlying AIAD, presenting with altered mental status. Identifying AIAD can be challenging, leading to high rates of misdiagnosis and clinical omission. Physicians should consider AIAD when dealing with unexplained altered mental status, as the administration of a simple treatment with steroids can be life-changing. Presentation: 6/3/2024

7741 Artri King As A Cause Of Adrenal Insufficiency

Abstract Disclosure: Q. Aziz: None. S. Fatima: None. A.L. Champion: None. K.E. Izuora: None. IntroductionDietary supplements are highly unregulated and may have substance that can be harmful. Due to its easy availability, more patients may have access to these supplements which can cause detrimental health outcomes, such as adrenal insufficiency. Clinical Case Patient is a 46 year old female with past medical history of hypertension and obesity presents to the hospital for worsening left hip pain, which started 2 weeks ago. She heard a crack in her left hip and denied any trauma or injury prior. She was found to have subtrochanteric fracture. Nine months ago, she had right hip pain and was unable to bear weight. Physical exam was notable for alopecia in frontal and temporal region, dorsocervical fat pad, multiple bruises, round facies, and multiple purple straie. She also reported a 50 pound weight gain in the last year. She stated that she took an over the counter “pain medication”, but denied any supplements. Due to the non-traumatic fracture and physical features, AM cortisol was ordered for suspicion of Cushing’s Syndrome by primary team and was low at 2.4. Endocrinology team was consulted. Cosyntropin stimulation test showed baseline AM cortisol level 1.4 and 1 hour after cosyntropin, cortisol was 8.3. ACTH 3.4, testosterone undetectable, androstendione undetectable, Aldosterone 42.2, DHEA undetectable. It was found later that patient was taking an over the counter supplement called Artri King, up to 4 tablets a day. Artri King has been advertised as a supplement for joint and muscle pain and contains unknown amount of dexamethasone and diclofenac. She was soon placed on hydrocortisone for adrenal insufficiency and was titrated down. The hypothalamic-pituitary-adrenal (HPA) axis can be suppressed with as low as 5 mg prednisone equivalent a day. This can lead to inadequate adrenal response to stress. If a patient has prolonged exposure to exogenous steroids, insufficient ACTH secretion can lead to atrophy of the zona fasciculata and reticularis, resulting in reduced ability to secrete cortisol. Therefore, it is important to help withdraw patient from glucocorticoids. When initiating glucocorticoid withdrawal, hydrocortisone may be helpful due to short half life, allowing HPA axis more opportunity to recover. Adrenal atrophy may be slowly reversible, but 4 years after diagnosis of glucocorticoid induced adrenal insufficiency, recovery of adrenal function is unlikely to occur. ConclusionsIt is important to obtain a thorough history, especially for supplements. Many supplements are not regulated and can pose harm to our patients. Adrenal insufficiency due to glucocorticoids may not only occur from steroid injections, long course of prescription glucocorticoids, but can include supplements if it is hidden from the ingredient list. Presentation: 6/3/2024

6400 An Unusual Presentation of Silent Corticotroph Pituitary Macroadenoma

Abstract Disclosure: N. Mon: None. V. Lohano: None. B. Williams: None. N. Lehman: None. R. Kulkarni: None. S.L. Mokshagundam: None. Silent Corticotroph Pituitary Adenomas (SCA) are a rare group of nonfunctioning pituitary adenomas (NFA) comprising 3-6% of all pituitary adenomas and up to 20% of corticotroph adenomas. SCA are biologically and clinically distinct from Cushing disease and NFA. SCA present with headache, visual field impairment, hypopituitarism, and pituitary apoplexy. We present a case of SCA with the initial presentation of syncope with undetectable ACTH and very low AM cortisol level.A 67 year-old-female was incidentally found to have a pituitary macroadenoma in MRI brain for syncope work up in 2017. MRI reported 1.4 x 1.2 x 1.3 cm sellar mass with suprasellar extension, minimal mass effect on the optic chiasm and no cavernous sinus invasion. Initial labs showed ACTH <5 (7.2-63.3 pg/mL), AM cortisol 0.8 (6-28ug/dl), Prolactin 101.1 (3.3-27 ng/mL), TSH 0.08 (0.34-5.60 uIU/mL), Free T4 0.6 (0.58-1.64 ng/dL), FSH 1.7 (2-5 mIU/mL), LH <0.2 (1-13 mIU/mL), IGF-1 33 ( 41-279 ng/mL). ACTH stimulation test: cortisol 0.5 ug/dl at baseline, 5.8 ug/dl at 60min. She was diagnosed with panhypopituitarism and hyperprolactinemia due to stalk effect. Hydrocortisone and Levothyroxine (LT4) were started. She underwent pituitary macroadenoma resection for optic chiasm decompression in 2017. Pathology reported pituitary neuroendocrine tumor (pitNET), but no immunostaining was done at that time. Follow up MRI in 2019 showed residual pituitary tumor. In 2023, she endorsed headaches, mood changes, fatigue and weight gain. Physical exam was unremarkable except BMI 34.75. Prolactin, Free T4, IGF-1 were normal. MRI in 2023 revealed recurrent and enlarging pituitary adenoma (1.9 x 1.4 x 1.6 cm) with suprasellar extension, abutting the optic chiasm, and left cavernous sinus invasion with internal carotid artery encasement. She underwent revision transsphenoidal resection of pituitary tumor to decompress the optic chiasm with plan for subsequent focused radiation to the cavernous sinus portion. Postoperative period was uneventful and hydrocortisone and LT4 were continued on discharge. Final pathology reported silent corticotroph lineage pitNET with low Ki67, immunostaining positive for TPIT, CAM5.2, and negative for ACTH. ACTH-negative SCA are a rare subtype and more likely to have lower ACTH levels, and multiple microcysts on MRI than ACTH-positive SCA. New WHO classification of pitNET highlights the histological typing and subtyping based on immunostaining of pituitary lineage transcription factors as the cornerstone for accurate classification. SCA are more biologically aggressive tumors with a high propensity of recurrence and resistance to conventional treatment. TPIT and ACTH immunostaining significantly improved the diagnosis of SCA and thereby close clinical follow up for early recognition and management of SCA recurrence. Absence of serum markers of recurrence makes this challenging. Presentation: 6/1/2024

7025 Acute Psychosis and the Diagnosis of Cushing’s Syndrome: Lessons Learned from a Patient with a Long History of Obesity

Abstract Disclosure: S. Modi: None. L. Belalcazar: None. Background: Although the association of hypercortisolism and psychosis is well established, acute psychosis remains a very rare manifestation of Cushing’s syndrome, especially in the absence of previous psychiatric history. We present lessons learned from a patient in whom the diagnosis of Cushing’s syndrome was missed until the onset of acute psychosis helped identify his underlying endocrine disorder. Clinical Case: A 31-year-old male presented to the Emergency Department after being found down on the street. The patient had superficial lacerations that were suspected to be self-inflicted due to a suicide attempt, but later found to be the result of auditory hallucinations. He had no previous psychiatric history and no history of suicidal ideation. His medical history was positive for obesity since adolescence and a recent diagnosis of hypertension. His family noted that for the past several months he had been experiencing headache, fatigue, muscle weakness and, more recently, insomnia, restlessness, and confusion. Weight gain was noted, but of unknown magnitude. On admission, he was agitated and hallucinating. He was initially sedated with dexmedetomidine and started on quetiapine. Physical examination revealed Cushingoid features with truncal obesity (body mass index of 35 kg/m2), facial plethora, and dorsocervical fat pad; no abdominal striae were present. Labs showed mild hypokalemia. His AM cortisol was markedly elevated at > 123 ug/dL (normal 4.5-23.0 ug/dL) with an ACTH level at 144 pg/mL (normal 7.2-63.3 pg/mL). MRI Brain showed a 1.9 cm pituitary macroadenoma with small suprasellar extension. With a diagnosis of Cushing’s disease, later confirmed by pathology, he underwent transsphenoidal resection. AM cortisol on post-operative day 3 was 3.2 ug/dL (normal 4.5-23.0 ug/dL). Maintenance-dose steroids were started due to evidence of post-surgical corticotroph suppression. Notably, there was marked improvement in his anxiety, paranoia, and confusion post-operatively. Quetiapine and blood pressure medications were discontinued after discharge. Conclusion: In this patient, the diagnosis of Cushing’s syndrome was missed when initially presenting with new onset hypertension in the setting of long-standing obesity. Despite months of symptoms compatible with the diagnosis, it was not until he developed acute psychosis and a careful history was obtained, that the diagnosis of Cushing’s syndrome was entertained. Psychosis is present in only 3-8% of reported cases of Cushing’s syndrome. This case illustrates the importance of including Cushing’s syndrome in the differential diagnosis of acute psychosis, especially in patients without previous psychiatric history. It also highlights the need of excluding secondary causes of hypertension in young adults, with particular attention to Cushing’s syndrome in those who present with obesity, even if long-standing. Presentation: 6/1/2024

6556 Does Autoimmune Hashimoto’s Hypothyroidism Mask the Diagnosis of Ehlers-Danlos-Syndrome?

Abstract Disclosure: S. Azmat: None. U. Rafat: None. J.L. Gilden: None. Does Autoimmune Hashimoto’s Hypothyroidism Mask the Diagnosis of Ehlers-Danlos Syndrome? Background: Hypothyroidism is well-known to be associated with muscle weakness and fatigue. There are other etiologies for decreased muscle tone such as Ehlers-Danlos syndrome (EDS) which is group of connective tissue disorders characterized by joint hypermobility, skin hyperextensibility and tissue fragility. Other rheumatological and cardiac conditions associated with this syndrome can pose diagnostic challenges. We present case of 32-year-old female presenting with facial muscle weakness and newly diagnosed Hashimoto’s hypothyroidism. We highlight importance of keeping EDS as another differential in patients with muscle weakness allowing for accurate, prompt diagnosis and treatment to be done in timely manner. Case Description: A 32-year-old female professional musician was referred to Endocrine for mouth muscles weakness and decreasing ability to play her French Horn wind instrument with vocal dystonia and the question of whether these were symptoms of hypothyroidism. She was noted to have mild thyroid enlargement and abnormal thyroid function tests with positive thyroid antibodies. Initial TSH was 7.506 uIU/mL(0.55-4.78), free T4 0.9 ng/dL (0.76-1.46), peroxidase antibody = 96,061U/mL (0-60) and thyroglobulin of 134.9 U/mL (0-60). She also reported low energy, intermittent difficulty swallowing and decreased muscle strength. There was no prior personal and family history of hypo/hyperthyroidism or any other disorders. VS were normal, physical exam showe d no thyromegaly, reflexes revealed objective decrease but normal muscle strength. The skin was noted to be hyperextensible with passive hyperextension of fifth metacarpophalangeal joint beyond 90 degrees, thumb to flexor aspect of forearm and elbows bilaterally with positive Beighton criteria for EDS. She later admitted to intermittent palpitations and easy bruising. Subsequent lab tests were negative ANA, anti-mitochondrial, PCEL and striated muscles antibodies. Additionally she had normal IGA, PTH, AM cortisol- ACTH, vitamin B12 levels with negative 21 hydroxylases antibodies and celiac titers. She was started on levothyroxine 25 mcg and recommended for Cardiology evaluation and genetic testing. Physiotherapy was started. Upon six months follow-up she clinically felt better with improved muscle strength, swallowing and energy level. Repeat lab testing showed improved TSH of 2.67 uIU/mL(0.55-4.78) with free T4 of 1.0 ng/dL (0.76-1.46). Conclusion: This case demonstrates that although muscle weakness can be symptom of hypothyroidism one must evaluate all patients for other possible causes. We highlight importance of keeping EDS as a differential especially in female patients with muscle weakness. Though history and physical exam is crucial allowing for prompt diagnosis and treatment for other conditions. Presentation: 6/1/2024

6853 A Curious Case of MACS

Abstract Disclosure: M. Dillon: None. A. Syeda: None. V. Kantorovich: None. Introduction: Mild autonomous cortisol secretion (MACS) is characterized by biochemical evidence of mild hypercortisolemia inducing metabolic comorbidities without any obvious phenotypic stigmata of Cushing’s syndrome (CS). This case highlights the challenges faced in the diagnosis and management of MACS. Case: A 76-year-old female with past medical history of class II obesity (BMI 31.83 kg/m2), type 2 diabetes mellitus, hypertension, hyperlipidemia, osteoporosis and chronic kidney disease stage IIIb was diagnosed with MACS after an overnight 1 mg dexamethasone suppression test (DST) showed unsuppressed 8 AM cortisol of 2.4 mcg/dL (<1.8 mcg/dL). Dexamethasone level was appropriate at 355 ng/dL (180-550 ng/dL), ACTH was <5 pg/mL (6-50 pg/mL) and DHEA-S was normal. Late night salivary cortisol (LNSC) levels were elevated to 0.12 mcg/dL (< 0.09 mcg/dL). The 24-hour urine cortisol level was normal. Baseline 8 AM cortisol level was 17 mcg/dL and ACTH was 19 pg/mL. Abdominal CT scan showed a 1 cm left adrenal nodule of 25 HU density and a normal right adrenal with no atrophy. Phaeochromocytoma and primary hyperaldosteronism work up was negative. She started on Mifepristone 300 mg daily and titrated up to 600 mg daily. She presented to our institution one month later with 1 week of nausea, vomiting and muscle weakness. Laboratory studies revealed acute kidney injury with creatinine of 6.69 mg/dL (baseline Cr 1.5 mg/dL) and rhabdomyolysis with creatinine kinase level of 12,819 U/L (24-173 U/L) and urine myoglobin level of 888 ng/mL (0-13 ng/mL). It was evident that her catastrophic presentation was from development of adrenal insufficiency in the setting of Mifepristone glucocorticoid receptor blockade. The drug was discontinued immediately. She was treated with intravenous hydration and intermittent diuretics. Over 10 days, her clinical status gradually improved and creatinine decreased to baseline levels. Discussion: MACS is a challenging diagnosis as cortisol levels are affected by several variables including obesity, drugs, and poorly controlled diabetes. Hence, a meticulous evaluation is mandated before confirming the diagnosis. Our patient’s baseline cortisol and ACTH levels were normal, and her DST and LNSC levels were mildly elevated. Unilateral cortisol producing adenoma causes contralateral gland atrophy due to suppressed ACTH. This was not evident in our patient, thus making the diagnosis questionable. Adrenalectomy is the treatment of choice in MACS with adrenal adenoma. Off label medical management with Mifepristone, a glucocorticoid receptor antagonist, is being pursued in select cases and was trialed due to our patient's age and surgical risk. Mifepristone is approved for the treatment of hyperglycemia due to CS. The data supporting its use in MACS is sparse. Therefore, it is important to be aware of associated risks of Mifepristone when advising patients. Presentation: 6/3/2024

8283 Diabetes Mellitus in Patients with Hemochromatosis- A Diagnostic and Therapeutic Challenge

Abstract Disclosure: U. Rafat: None. M. Siddiqui: None. J.L. Gilden: Other; Self; Novartis Pharmaceuticals. A. Moid: Other; Self; Novartis Pharmaceuticals. Background: Primary Hemochromatosis is a genetic condition most commonly due to two sets of mutations in the Human homeostatic iron regular Protein (HFE) gene. HFE modulates the expression of hepcidin, which regulates intestinal iron absorption, plasma iron concentration and distribution of iron in tissues. Hemochromatosis patients are at high risk for developing diabetes mellitus (DM) due to iron overload in the pancreas with damage to Beta cells and impaired insulin secretory capacity. Hemochromatosis is often called Bronze Diabetes due to brown discoloration of the skin from accumulation of iron, and is characterized by hepatic fibrosis, fatigue, arthralgias, cirrhosis, DM, arthropathy, pigmentation and cardiomyopathy. Case: We present a Caucasian male with homozygous hereditary hemochromatosis, diagnosed by liver biopsy at age 40 due to transaminitis and Ferritin level of 1500 ng/mL and Genetic testing- 2 copies of HFE gene pathogenic variant (C282Y). He was later diagnosed with DM age 51, started on Metformin and referred to Endocrine clinic with abdominal bloating, and polyarticular arthralgias. Physical exam=Vital Signs normal (WT. 231lbs, BMI 34), with splenomegaly, but normal musculoskeletal exam and skin without bronze discoloration. Both parents had T2DM. Lab- Hb a1c 8.7% (0.0-5.6), Iron saturation 71% (10-50), Ferritin 66.3 ng/mL (26-388), C-Peptide 3.30 ng/ml (0.81-3.85), with glucose level of 119 mg/dL, and negative IA-2 <5.4 U/mL, negative Islet cell antibody, GAD 65 <5 IU/mL (nl <5), Insulin Autoantibody <0.4 U/mL (nl <0.4), and Zinc Transporter 8 antibodies <10 U/mL (nl <15). Liver tests- AST 39 U/L(10-37), ALT 77 U/L (10-65), ALP 89 U/L (45-117), total bilirubin 1.1 mg/dL(0.2-1.2). Hormonal evaluation included TSH 1.2 uIU/mL (0.55-4.78), ACTH 19 pg/mL (0-47), AM Cortisol 16.28 ug/d (5.30-22.50) IGF1 158 ng/mL (50-317) FSH 9.6 mIU/mL(l.40-18.10), LH 5.09 mIU/mL (1.50-9.30), Prolactin 7.40 ng/mL(2.10-17.70), total testosterone 374 ng/dL(250-1100), free testosterone 66.2 pg/mL (35.0-155.0). Echocardiogram-left ventricular hypertrophy and thick right ventricular wall with concerns for iron overload. Hba1c improved to 6.6% on Metformin. Fructosamine 351umol/L (151-300). In the absence of advanced cardiac, hepatic and other organ involvement, and presence of elevated C-peptide and high BMI, this patient is being managed as T2DM, with low threshold to initiate insulin therapy considering possibility of concomitant Bronze DM. Conclusion: It is important to determine type of DM, so appropriate management options can be devised. While insulin is recommended for management in Bronze Diabetes, insulin sensitizers, such as metformin and/or GLP 1 agonists can be used in type 2 DM. One must also consider therapy based upon the risk of cancer and acute pancreatitis in the setting of pancreatic iron overload, when considering antihyperglycemic therapies. Presentation: 6/2/2024

8475 Automated Insulin Delivery System with Concentrated Regular U500 Insulin in Cushing Syndrome

Abstract Disclosure: F. Erenler: None. J. Aurora: None. Background: Concentrated regular U-500 (U-500R) insulin is commonly used in patients with T2DM, who are highly insulin-resistant, requiring more than 200 units of insulin per day. Utilizing U-500R reduces the number of daily injections, decreases injection volume, and improves cost effectiveness. There has been a case report with U-500R in an automated insulin delivery (AID) system with successful results (1). To our knowledge there is no data on AID system use in Cushing patients with T2DM using U-500R. We present a case of a patient with Cushing Syndrome (CS) with poor BG control using >250 units/day of SC U-500R with improved BG control after switching to Omnipod 5 AID system. Clinical Case: A 57 y.o. male initially presented with hypogonadotropic hypogonadism and subsequently diagnosed with ACTH-dependent CS, which is complicated by obesity, uncontrolled T2DM, lower extremity wounds, and DVTs. He was diagnosed with CS with multiple abnormal 1 mg dexamethasone suppression tests (DST) (max AM cortisol 5.9 mcg/dL; RR <1.8 mcg/dL, dexamethasone level 300), elevated urine free cortisol (UFC) (max UFC/Cr 77.6 mcg/mg/L; RR: 5-64 mcg/24-hr) and elevated salivary cortisol (max cortisol 0.2 mcg/dL; RR: <0.09 mcg/dL). He had suppressed cortisol with 8 mg DST. An MRI sella showed left-sided hypoechoic 0.9 cm mass. Desmopressin (DDAVP) stimulation test and Ga-68 DOTATATE-PET scan were negative. As a result of his abnormal MRI sella and elevated cortisol, he underwent transsphenoidal surgery of the left pituitary. Pathology was non-diagnostic for a pituitary adenoma. Post-op 24-hr UFC and 1 mg DST levels remained high. DDAVP stimulation test and Ga-68 DOTATATE-PET were repeated post-op and were negative. Due to complications of CS, he was initially treated with cabergoline, but switched to osilodrostat due to intolerances. He is currently on 2 mg BID dose and 24-hr UFC has been normal since then (UFC 20 mcg/L, Cr 0.67 mg, UFC/Cr 12 mcg/mg/L). He continued to have uncontrolled hyperglycemia despite normalization of UFC. On his CGM data, he was in target range (70-180 mg/dL) 5% of the time despite using U-500R 95 units SC TID. Given his severe hyperglycemia and insulin resistance, he was switched to an AID system with U-500R and his time in target range improved over 60% after a month of use and his total daily dose of insulin decreased to less than 200 units. Conclusion: U-500R proved to be safe and effective with Omnipod 5 AID. To our knowledge, this is the first reported patient with CS using U-500R with Omnipod 5 AID. In patients without CS, the AID algorithm continuously kept BG well below the set target, especially overnight. Notably, our patient did not have this overnight hypoglycemia trend, which should be expected with his disease. We are hoping to increase the awareness of U-500R with AID systems, especially for patients with incurable CS. Reference:1.Aurora J Jr, Saraswat A. J Endocr Soc. 2023;7(Suppl 1):bvad114.873. Presentation: 6/3/2024

12337 Nivolumab Induced Secondary Adrenal Insufficiency And Hypothyroidism In A Patient With Graves’ Disease: A Case Report

Abstract Disclosure: F. Sajid: None. J. Kaur: None. A. Zatsepina: None. M. Khan: None. C.A. Resta: None. Introduction: We present a case of a patient with Graves’ disease who developed concurrent secondary adrenal insufficiency (SAI) and primary hypothyroidism while undergoing treatment with nivolumab for non-small cell lung cancer (NSCLC). This case sheds light on the immune-related adverse events (irAEs) associated with immune checkpoint inhibitor (ICI) therapy. Case Presentation: A 63-year-old woman with a history of Graves’ disease and NSCLC undergoing neoadjuvant chemoimmunotherapy was admitted with hyponatremia. She was diagnosed with Graves’ disease a year before and was treated with methimazole (MMI). When she was diagnosed with Graves’ disease, her TSI was 1.64 IU/L (<0.55). Before starting nivolumab, TSH had normalized at 0.5 MCIU/mL on MMI therapy. She started nivolumab 3 months before admission. One month after starting nivolumab, her TSH was <0.01. By the time she was admitted, she had severe hypothyroidism and SAI with sodium 116 mmol/L (135-149), TSH 40.34 mIU/mL (0.39-4.08), free T4 <0.25 ng/dL (0.8-1.8), TSI 21.2 IU/L (0.00-0.55) Total Cortisol 0.4 ug/dL (6.7-27.6), AM Cortisol 0.6 ug/dL, ACTH <1.5 pg/mL (7.2-63.3), LH 75.5 IU/L (7.7-58.5), and FSH 179 IU/L (25.8-134.8). MMI was discontinued due to hypothyroidism. She was started on replacement therapy with levothyroxine and hydrocortisone. Subsequent sodium levels normalized. Discussion: Nivolumab has emerged as a promising immunotherapy for NSCLC. Our patient developed irAEs following nivolumab treatment. Notably, this case represents only the third documented case to our knowledge of both primary hypothyroidism and secondary adrenal insufficiency occurring post-nivolumab treatment. Workup for our patient revealed two irAE’s. She developed primary hypothyroidism and isolated ACTH deficiency with other pituitary function remaining normal. The pattern of thyroid profile over time was consistent with thyroiditis due to ICI therapy. TSI increased, ruling out remission from Graves’ disease. Even after discontinuing methimazole, she remained hypothyroid. Hence, in this case, ICI effectively acted as definitive therapy for her Graves’ disease. Conclusion: This case sheds light on the intricate interplay between nivolumab therapy, pre-existing autoimmune conditions such as Graves’ Disease, and the emergence of irAEs. This case underscores the importance of vigilant monitoring of serum sodium levels, and thyroid and pituitary function tests in patients undergoing immunotherapy. Presentation: 6/1/2024

7432 Secondary Adrenal Insufficiency Caused By Concurrent Treatment With Budesonide And Itraconazole

Abstract Disclosure: F. Anjum: None. M.G. Jakoby: None. Introduction: Inhaled corticosteroids (ICS) are unlikely to affect corticotroph axis function even at high doses due to low systemic absorption. However, co-treatment with drugs that reduce hepatic clearance of ICS may predispose patients to secondary adrenal insufficiency (AI). We report a case of secondary AI that occurred during concurrent treatment with budesonide and itraconazole. Case presentation: A 42-year-old female with longstanding asthma managed with inhaled budesonide (160 μg twice daily) was started on itraconazole (200 mg twice daily) for management of pulmonary histoplasmosis. Over the next three months, she experienced severe fatigue, and laboratory evaluation was notable for an undetectable (< 0.4 μg/dL) 8 AM cortisol level. Serum sodium (140 mM, 136-145) and potassium (4.6 mM, 3.5-5.1) were unremarkable, and a diagnosis of drug induced secondary AI was made. Treatment with hydrocortisone (15 mg in the morning, 5 mg in the evening) was started, and the patient’s infectious disease specialist stopped itraconazole, substituting posaconazole (300 mg daily) for an additional six months. Her pulmonologist substituted fluticasone (250 μg twice daily) for budesonide. After an approximate two-month hydrocortisone taper, 8 AM ACTH level was easily detectable (37.2 pg/mL, 7.2-63.3), though 30 min stimulated cortisol level was subnormal (11.1 μg/dL, expected > 18). Hydrocortisone was successfully tapered off over an additional two-months (30 min stimulated cortisol 23.4 μg/dL). Discussion: The literature on ICS induced secondary AI is generally case reports and series, and the incidence is very low (1.1/10,000 patient-years at risk). Limited oral bioavailability, high deposition in lungs, extensive protein binding, and robust hepatic clearance are factors that minimize the effects of ICS on corticotroph axis function. However, concurrent treatment with potent CYP3A4 inhibitors like itraconazole can significantly reduce hepatic clearance of ICS and predispose to systemic effects, including Cushing syndrome when high dose ICS are prescribed or secondary AI at lower doses. In a series of 25 cystic fibrosis patients co-treated with itraconazole and budesonide, 11/25 (44%) developed secondary AI. Our patient likely developed secondary AI but not Cushing syndrome due to treatment with low dose budesonide. This case illustrates the importance that endocrinologists recognize CY3A4 inhibiting drugs as a risk factor for secondary AI in patient treated with ICS. Presentation: 6/3/2024

8790 A Case Of Ectopic Cushing’s Syndrome Secondary To Diffuse Idiopathic Pulmonary Neuroendocrine Cell Hyperplasia (DIPNECH)

Abstract Disclosure: T. Goettemoeller: None. R. Lopez Fanas: None. K. Cedeno: None. A. Manavalan: None. Introduction: Ectopic Cushing’s syndrome is a rare disease accounting for <20% of cases of endogenous Cushing’s syndrome. DIPNECH is a poorly understood lung disease characterized by abnormal proliferation of neuroendocrine cells in the bronchial mucosa. It can be a precursor to pulmonary carcinoid tumors and has rarely been associated with ACTH production. Clinical Case: A 70-year-old female with intellectual disability and hypertension presented with diffuse edema and weakness. Examination was notable for hypertension, anasarca, and hirsutism. In addition to hypokalemia and metabolic alkalosis, hypercortisolism was observed: random serum cortisol - 50.1 ug/dL, late-night salivary cortisol - 1.72 mcg/dL (normal < 0.09 mcg/dL) and 24-hour urine free cortisol - 1,845.9 mcg (normal: 4.0 – 50.0 mcg/24h). Cortisol level remained > 25 ug/dL after high-dose dexamethasone suppression test. Ketoconazole was initiated and titrated to achieve normal 24-hour urine free cortisol levels and spironolactone was added to manage hypokalemia. An MRI of the sella and pituitary was unremarkable while an abdomen and chest CT identified a 2.5 cm well-circumscribed right middle lobe pulmonary nodule and mild thickening of the bilateral adrenal glands. A gallium-DOTATATE scan revealed a 2.1 cm right middle lobe pulmonary nodule with mildly increased uptake. A transbronchial biopsy of the right middle lobe nodule confirmed a carcinoid tumor. Immunohistochemistry (IHC) staining was positive for CHR, SYN, CD56, and AE1/3. Ki-67 stain showed a low proliferative index. A right middle lobectomy was performed with pathology revealing two typical carcinoid tumors measuring 2.8 and 0.7 cm each, with multiple carcinoid tumorlets and foci of neuroendocrine cell hyperplasia consistent with DIPNECH. IHC staining for ACTH was positive in the carcinoid tumors and tumorlets. Four days after surgery, AM cortisol was 8.1 ug/dL and potassium levels and blood pressure normalized off ketoconazole and spironolactone. The patient was discharged, but was readmitted a month later for anasarca, lethargy, hypokalemia, and metabolic alkalosis. A recurrence of Cushing’s syndrome was confirmed, and medical therapy was resumed. A chest CT revealed post-surgical changes. Her course was complicated by an aspiration event, septic shock, PEA arrest, resuscitation, and intubation. The patient’s care was ultimately transitioned to hospice. Conclusion: Florid Cushing’s syndrome due to ectopic ACTH production associated with DIPNECH is an exceedingly rare condition. Early recognition and treatment are crucial to prevent the numerous complications that may arise, and close follow-up after tumor removal is critical to ensure continued remission has been achieved. Presentation: 6/1/2024

6409 Successful Treatment Of Severe Ectopic ACTH-dependent Cushing’s Syndrome With Osilodrostat

Abstract Disclosure: K.A. Lee: None. C. Mendes Pessoa: None. W. Huang: Consulting Fee; Self; WH, Honoraria from Consulting and Speaking received from Recordati Rare Disease. Background: Cushing’s syndrome due to ectopic ACTH secretion is rare and may progress rapidly, making treatment very challenging. Previous case reports have described therapeutic options including adrenal steroidogenesis inhibitors, bilateral adrenalectomy (BAL), and adrenal embolization with success. Clinical Case: A 27-year-old woman with metastatic neuroendocrine tumor presented with sudden onset and rapidly progressing symptoms of fatigue, muscle weakness, acne and weight gain within two weeks. Laboratory findings confirmed severe Cushing’s syndrome due to ectopic ACTH secretion: AM cortisol 173.4 µg/dL (5-25), ACTH 1425 pg/mL (7.2-63.3), 24 hour urine cortisol 29,498 mcg/24hr (4-50), DHEA-Sulfate 1314 µg/dL (65 - 380), and testosterone 133 ng/dL (0-100). She was also found to have severe hypokalemia, hypocalcemia and hyperglycemia (despite an HbA1C of 6.2 at 2 weeks before presentation). CT- scan showed diffuse thickening of the bilateral adrenal glands. Due to widely metastatic disease in the peritoneum, BAL was considered non-feasible. The patient was admitted to hospital and initiated on osilodrostat at 20mg twice daily (after correction of hypokalemia) with close monitoring of her electrolytes, cortisol, EKG and steroid withdrawal symptoms. There was a rapid improvement of cortisol levels in response to osilodrostat. During treatment, she developed steroid withdrawal symptoms for which she was started on medium dose hydrocortisone. Bilateral adrenal arterial embolization was attempted but ultimately needed to be converted to right only adrenal gland embolization due to a hypertensive urgency and difficulty with catheterization. Her symptoms of Cushing’s syndrome significantly improved with the treatment. During her hospitalization, her hypokalemia was managed with spironolactone and potassium supplement, hypocalcemia with calcium supplement, and hyperglycemia with basal and bolus insulins. With significant improvement of cortisol levels, her hypocalcemia and hyperglycemia resolved and required no further treatment. Her potassium levels normalized and spironolactone was stopped. She remains on potassium supplement to keep K level at upper half of normal range to avoid long QTc. After discharge, her morning cortisol levels (before morning dose of hydrocortisone) continued to decrease and her osilodrostat dose was gradually tapered to 5mg once daily at night. Hydrocortisone was continued as part of the block-and-replace regimen. Conclusion: This case described a unique sudden onset and rapid progression of ectopic ACTH dependent Cushing’s syndrome and successful utilization of a block-and-replace approach by using the steroidogenesis inhibitor osilodrostat in prompt control of the hypercortisolism and related comorbidities. We also explored the feasibility of adrenal embolization for definitive management in the context of unfeasible BAL. Presentation: 6/2/2024

7668 Rhabdomyolysis Associated with Severe Hypothyroidism

Abstract Disclosure: H. Soe: None. P. Mikkilineni: None. Background: Over 70% of the patients with newly diagnosed hypothyroidism can present with muscle complaints such as weakness, fatigability, cramps, myalgia. However, rhabdomyolysis, which is the rapid breakdown of skeletal muscle cells, is the rare presentation. Clinical Case: A 70-year old male patient with history of rheumatoid arthritis, hyperlipidemia, prior CVA (left hemispheric subcortical stroke) 6 months ago without residual deficit presented to the hospital with poor oral intake and generalized muscle weakness for 3 weeks. He was unable to get out of bed without assistance and also needed adult diapers. Found to have new-onset severe hypothyroidism with TSH 228 uIU/ml (Ref: 0.350-4.940) and FT4 <0.40 ng/dL (Ref: 0.70-1.50), positive TPO antibody 197 IU/ml (Ref: 0-34). No prior thyroid labs were available and no known history of thyroid disorder was recorded. He has never been on Amiodarone or Lithium before. On physical exam, he was alert and oriented. There was no goiter or palpable thyroid nodule. There was no focal neurological deficit and no peripheral edema. There were no other signs and symptoms pertinent to hypothyroidism except mild bradycardia (HR 56-60) and borderline low blood pressure. AM cortisol was 10.1 ug/dL (Ref: 3.7-19.4). EKG showed low-voltage sinus bradycardia. Echocardiogram was normal. Urinalysis was positive for large blood but only 3 RBCs were present which raised the suspicion of rhabdomyolysis. Creatinine kinase (CK) was 15,584 IU/L (Ref: 30-200). Other laboratory studies were significant for acute renal failure with mild hyperkalemia and mild hypocalcemia, also transaminitis; BUN 130 mg/dl (Ref: 8-26), Creatinine 9.51 mg/dl (Ref: 0.72-1.25), eGFR 5 ml/min/1.73 m2 (Ref: >59), AST 435 IU/L (Ref: 5-34), ALT 269 IU/L (Ref: <55), ALP 171 IU/L (Ref: 40-150). On medication review, he was started on Atorvastatin 80 mg daily during prior admission for CVA 6 months ago. He received IV fluids, s/p 1 dose of Hydrocortisone 100 mg IV, Levothyroxine IV 200 mcg, followed by Levothyroxine IV 50 mcg daily x 3 days and switched to Levothyroxine PO 100 mcg daily (weight-based dose). Atorvastatin was on hold. He became anuric during the hospital course and received 2-3 sessions of hemodialysis. 3-4 days later, CK was trending down to 3000 IU/L, FT4 improved to 0.54 ng/dl and there was also significant improvement in kidney and liver functions. The patient was diagnosed with acute renal failure secondary to rhabdomyolysis associated with severe hypothyroidism caused by Hashimoto's thyroiditis, in the setting of high dose statin use. Conclusion: Clinicians should raise the suspicion of rhabdomyolysis in a patient with severe hypothyroidism, especially in patients with recent high dose statin use as rhabdomyolysis can be a rare and fatal complication of severe hypothyroidism, in the presence of precipitating factors. Presentation: 6/2/2024

6891 Exclusive Normetanephrine Secreting Pheochromocytoma In A Young Male

Abstract Disclosure: E. Askar: None. H. Moran: None. IntroductionPheochromocytomas and paragangliomas arise from chromaffin cells and produce excessive catecholamines. Hypertension is their primary clinical symptom. they differ in their catecholamine secretory phenotype; paragangliomas typically secrete norepinephrine, while pheochromocytomas typically secrete epinephrine. Here, we present a case 21-year-old male with pheochromocytoma with elevated norepinephrine but normal epinephrine levels.Case presentationA 21 -year-old male with no past medical history presented with episodes of palpitations, sweating, and elevated blood pressure. He also reported abdominal pain. On admission, his blood pressure was 143/92 mmHg, pulse was 71/min, respiration was 16/min, and oxygen saturation was 100% in room air. The rest of physical exam was not significant. His electrolyte panel was normal. Computed tomography (CT) abdomen and pelvis with contrast was performed and showed a right adrenal mass measuring 4.9 x 4.0 x 6.5 cm which is predominantly hypoattenuating (approximately 30 Hounsfield units) with thick nodular rim of enhancement. Hormonal workup showed normal serum testosterone, DHEA-S, AM cortisol, ACTH, aldosterone, plasma metanephrine, and urine metanephrine, but profoundly high plasma normetanephrine 3641.6 (0.0-210.1) pg/mL. His 24-hour urinary normetanephrine was elevated at 14874 (80-440) ug/24hr, confirming a pheochromocytoma. The high norepinephrine level in the setting of normal epinephrine raised suspicion for Von Hippel Lindau (VHL). He was started on alpha and beta blockage and had laparoscopic removal of the right adrenal gland. The pathology report confirmed the diagnosis of pheochromocytoma confined to right adrenal. The patient was then referred for genetic testing. Conclusion: Pheochromocytoma can be a part of familial disorders, although being sporadic in nature most of the time. As demonstrated in our case, the hallmark of pheochromocytoma associated with VHL is nearly exclusive normetanephrine secretion and a high ratio of normetanephrine to metanephrine. Confirmation and testing of genes aid in proper monitoring and follow-up. The preferred course of treatment is radical resection. Presentation: 6/2/2024

6937 A Rare Case of Pembrolizumab-induced Multiple Endocrinopathies Presenting with Acute Adrenal Crisis Secondary to Isolated ACTH Deficiency - A Case Report

Abstract Disclosure: R. Abdelmasih: None. W. Pan: None. Introduction: Pembrolizumab is an immune checkpoint inhibitor (ICI) that blocks programmed cell death receptor 1 (PD-1) which took a massive leap in the oncology world. However, we are still understanding more about its immune-related adverse events (irAEs). Here we report a case of adrenal crisis due to pembrolizumab-induced hypophysitis and adrenalitis. Case Description: A 74-year-old male with a history of left renal cell carcinoma post left nephrectomy 5 years ago, complicated with lung metastasis for which Pembrolizumab was started. 5 months after, patient developed hypothyroidism and was started on Levothyroxine. 3 months later, Patient presented with lethargy and hypotension. Physical exam revealed hypotension (MAP of 55), fever, and acute encephalopathy. AM cortisol 4.2 ug/dL, Patient was started on IV pressors and a stress dose of Hydrocortisone. Hemodynamics improved, and Hydrocortisone was tapered down. ACTH stimulation test revealed a subnormal response of cortisol 0.2, 1.7, and 2.7 ug/dL at 0, 30, and 60 minutes respectively in the setting of very low ACTH of < 1.5 pg/ml, other pituitary hormones were checked, revealing normal insulin-like growth factor was 116 ng/mL, LH 15.29 mIU/mL, and FSH 27.45 mIU/mL. TSH was high 15 mIU/mL and free T4 was 1.4 ng/dl, levothyroxine dose was increased, and hydrocortisone was maintained at 10 in am and 5 in pm with excellent response. Discussion:ICIs inhibit the immunological pathways that control T-cell activation, leading to multiple immune-related endocrinopathies. Thyroiditis is the most reported one (30%), though anti-PD1-induced hypophysitis is exceptionally rare (< 1%). To date, the pathophysiology of pembrolizumab-induced central AI is not clearly understood, it’s presumed that it causes lymphocytic hypophysitis often presenting with isolated ACTH deficiency. Also, Pembrolizumab-induced primary adrenal insufficiency has seldom been reported and not yet understood, interestingly, anti-steroidogenic enzyme antibodies were absent in those few most reported cases which suggests a different mechanism compared to traditional primary AI. We suggest that our patient had combined primary and secondary adrenal insufficiency based on ACTH stim test result with very low cortisol responses in the setting of very low ACTH, which we believe is what led to such severe presentation of adrenal crisis. Diagnosis of PD1-induced AI can be challenging due to the overlapping of advanced malignancy and AI presentation. A higher level of suspicion is prompted especially in patients who experienced other endocrine irAEs (as our patient who had PDL-1-induced hypothyroidism). We present this case to shed light on this rare yet potentially fatal endocrine adverse event that can be reversed by prompt diagnosis and timely management due to the increasing use of pembrolizumab. More cases are needed for a better understanding of such a rare adverse event. Presentation: 6/2/2024