Doses Of Hydrocortisone Research Articles

Anastrozole improves height outcomes in growing children with congenital adrenal hyperplasia due to 21-OHD.

Hyperandrogenemia resulting in estrogen-mediated accelerated bone maturation and early growth plate fusion contributes to short stature in children with congenital adrenal hyperplasia (CAH) due to 21OHD. Aromatase inhibitors block androgen conversion to estrogen and have been used off-label in children with short stature to improve adult height. There are no adequately powered studies examining the use of aromatase inhibitors in children with CAH with advanced bone age and reduced predicted adult height. Records of CAH patients treated with anastrozole were reviewed. Z-scores of bone age, predicted adult height and height corrected for bone age were examined over an 8-year period. Outcome changes were analyzed using weighted mixed-effects models, adjusting for sex, diagnosis, age at diagnosis, and average hydrocortisone dose before and during treatment with anastrozole. In 60 patients (26 females, 52 classic, 8 non-classic) started on anastrozole therapy, the mean bone age Z-score decreased from 4.2 to 2.0 at 4 years and 1.3 at 6 years (both p <0.001); predicted adult height Z-score improved from -2.1 to -0.45 at 4 years and 0.18 at 6 years (both p <0.001); corrected height Z-scores improved from -1.7 to -0.33 at 4 years and 0.18 at 6 years (p <0.001). There was no significant difference in the average total daily hydrocortisone dose used before or during treatment. Anastrozole decreased the rate of bone maturation and led to improved height outcomes, indicating that anastrozole could have a role as an adjunct therapy in children with CAH and advanced bone age.

Circulatory collapse requiring mechanical circulatory support in a child with autoimmune adrenal insufficiency: a case report

BackgroundWe report a rare case of new onset autoimmune adrenal insufficiency in childhood, presenting with severe shock requiring mechanical circulatory support. In the current era of readily available imaging, laboratory and other diagnostic investigations, medical history and careful physical exam can often provide valuable diagnostic information for timely therapy.Case presentationA 7-year-old boy with a history of mild intermittent asthma, presented with severe cardiogenic shock requiring extracorporeal membrane oxygenation (ECMO). Bronzing of his entire body was noted on physical exam. Stress dose hydrocortisone was given for suspected adrenal insufficiency. After weaning from ECMO and extensive rehabilitation, the patient recovered and was discharged home.ConclusionPrimary adrenal insufficiency (PAI) should be considered in the context of physical exam and laboratory findings, even in the presence of circulatory shock.

7498 Pituitary Apoplexy Associated With COVID 19 Infection in a 55 Year Old Filipino Male: A Case Report

Abstract Disclosure: C.L. Macrohon: None. J.Y. Mercado: None. R.G. Gan: None. Introduction: Pituitary apoplexy is a rare fatal disorder resulting from acute ischemia or hemorrhage of the pituitary gland. Major predisposing factors include patients with anti-thrombotic drugs. However, there has been an increasing number of cases reported associating COVID- 19 and pituitary apoplexy. Case: This is a case of a 55-year-old Filipino male, who came in with right eye ptosis and blurring of vision associated with headache and dizziness. Significantly, 2 weeks prior the patient had developed cough and colds. On admission, he was noted to be febrile and presented with a visual acuity of light perception on the right eye and hand movements on the left. Plain MRI of the brain revealed a well-circumscribed hemorrhagic sellar-suprasellar mass with mass effect on adjacent structures worrisome for pituitary apoplexy. Incidentally, patient tested positive for COVID- 19. Hormonal work- up revealed hypopituitarism presenting with central hypothyroidism and hypogonadism. Patient was then started on Hydrocortisone 100mg intravenously as loading dose then 50mg intravenously every 6 hours to cover for adrenal insufficiency. At this point, thyroid hormone replacement was also started at 100mcg/day. Initially, patient was scheduled for endoscopic endonasal transsphenoidal surgery. However, due to euvolemic hyponatremia with a serum sodium of 119mmol/L secondary to SIADH, surgery was delayed and was performed on the fourth day of admission. Post- operatively, patient had improvement of vision and was eventually discharged stable without any complications. He was sent home on thyroid hormone replacement and steroids were discontinued since adrenal insufficiency was ruled out with a post operative serum Cortisol of 27.27ug/dL taken 24 hours after last dose of hydrocortisone. Discussion: COVID- 19 with associated hypophysitis or pituitary apoplexy has been reported in literature. The pituitary gland was proposed as possible targets of SAR- CoV-2 due to the presence of ACE- 2 receptors on the surface of their cells. Hazzi et al. discussed that infection by COVID-19 could play a role in the disruption of the equilibrium between the high energy demand and limited blood supply of underlying adenomas. They also discussed on possible routes of entry of COVID 19 particularly thru the nasopharyngeal epithelium via olfactory nerve or pass through blood brain barrier or thru the median eminence. Other possible contributing factors may be due to coagulopathy, endothelial dysfunction and hypercoagulative state seen in COVID- 19. Conclusion: With increasing reports of pituitary apoplexy in the setting of SARS-COV-2 infection there is a possibility that COVID 19 may be a risk factor for pituitary apoplexy. Hence, the prevalence of COVID- 19 may increase risk of patients with underlying pituitary tumors to develop pituitary apoplexy. Presentation: 6/2/2024

7761 Unmasking The Uncommon: A Case Of Primary Adrenal Insufficiency Presenting As Severe Hypercalcemia

Abstract Disclosure: A. Misbah: None. Z. Al-Hiti: None. A. Saleh: None. M. Joda: None. K. Rajamani: None. Adrenal insufficiency is a recognized but uncommon cause of hypercalcemia. The exact mechanism remains unknown; however, it is thought to be a combination of the hypovolemic state in adrenal insufficiency leading to decreased urinary clearance, as well as increased bone resorption. We present a case of primary adrenal insufficiency presenting with severe hypercalcemia. A 41 year old female with a past medical history of osteopenia, recently diagnosed postural orthostatic tachycardia syndrome (POTS), and hyponatremia attributed to SIADH presented with complaints of weakness and poor oral intake. She also reported a history of nausea, vomiting, weight loss, fatigue, and dizziness, for the last few months. She reported feeling well prior to a COVID-19 infection a few months back. At presentation, she was hypotensive with a blood pressure of 70/50 mmHg, while her other vital signs were stable. She appeared ill, and was noted to have dry oral mucous membranes. There was no increased pigmentation noted on exam. Initial laboratory evaluation revealed sodium of 130 (135-145 mmol/L), potassium of 5.3 (3.5-5.1 mmol/L), and creatinine of 1.7 (0.5-0.8 mg/dL). She had severe hypercalcemia with a calcium level of 15.5 (8.3-10.6 mg/dL) and had a blood glucose level of 53 (70-100 mg/dL). Venous blood gas indicated metabolic acidosis. Morning cortisol was low at 1 (3-23 ug/dL). Serum ACTH was elevated at 775 (0-46 pg/mL). Cosyntropin stimulation test confirmed primary adrenal insufficiency. She underwent work-up for hypercalcemia, which revealed a suppressed PTH, normal levels of PTHrP, vitamin D, and vitamin A. Serum and urine protein electrophoresis was normal. She was initially managed in the ICU and received aggressive fluid resuscitation. She was started on stress dose of hydrocortisone, which was then tapered to physiological doses of oral hydrocortisone and fludrocortisone. Subsequent improvements were observed in blood pressure, laboratory abnormalities, and normalized serum calcium levels. She was discharged home on hydrocortisone and fludrocortisone. On follow-up, she was doing well with the resolution of her symptoms. This case highlights the importance of recognizing adrenal insufficiency as one of the causes of hypercalcemia. Although hypercalcemia as a consequence of adrenal insufficiency is well-documented, the exact prevalence is not known but is estimated to be around 6%. After excluding more common diseases such as primary hyperparathyroidism and malignancy, the possibility of adrenal insufficiency should be considered as a cause of hypercalcemia. Treatment involves hormone replacement as well as hydration, bringing resolution to symptoms. Her presentation was unique, also due to the fact that her initial symptoms were diagnosed as POTS as well as SIADH. Given the onset of symptoms after a COVID-19 infection a few months ago, there could also be a potential link between the two. Presentation: 6/3/2024

8424 Complex Management Of Adrenal Insufficiency In Pregnancy: A Challenging Case

Abstract Disclosure: T. Avanessian: None. H. Alsamarraie: None. Background: Physiologic changes, including changes in the HPA axis and RAAS, during pregnancy pose challenges in the management of adrenal insufficiency in pregnant women. This case report discusses the management of adrenal insufficiency in a young primigravida female with Addison’s disease. Clinical Case: At 19.5 weeks of gestation, a 26-year-old primigravida, previously diagnosed with Addison’s disease 5 years ago, presented to an acute care center for syncopal episodes. The pregnancy had been complicated by persistent nausea and vomiting, labeled as hyperemesis gravidarum, and recurrent syncopal episodes, resulting in 6 ED visits and 3 hospitalizations, with symptoms improving each time after IV hydration and then returning within a few days. At presentation, the patient reported lightheadedness, sweating, palpitations, dyspnea, fatigue, nausea, vomiting, and a 10 lb weight loss since the beginning of pregnancy. The pre-pregnancy regimen was hydrocortisone 10 mg in the morning and 5 mg in the afternoon, with fludrocortisone 0.1mg daily. At 8 weeks of gestation, due to increased fatigue and hypotension, the hydrocortisone dose was doubled, while fludrocortisone was continued the same. During admission, blood pressure ranged from 67/37 to 90/56 mmHg, and heart rate ranged between 93-103 bpm. On labs, electrolytes were normal, and the serum renin level was elevated at 5.803 ng/ml/hr (0.167-5.380). Treatment included IV hydration and hydrocortisone 40 mg in the morning and 20 mg in the afternoon. Despite symptom improvement, blood pressure remained low. Thus, fludrocortisone was increased to 0.1 mg twice daily. Within 3 days, all symptoms improved, allowing for the down-titration of the hydrocortisone dose. The patient was discharged with hydrocortisone 30 mg at 8 AM, 10 mg at 3 PM, 5 mg at 7 PM, and fludrocortisone at 0.1 mg twice daily. Conclusion: Managing symptoms of adrenal insufficiency during pregnancy is challenging due to the overlap of symptoms and signs with physiologic manifestations of pregnancy. The use of biochemical testing is limited, given the physiological activation of RAAS and progressive increases in renin, CRH, ACTH (from both pituitary and placental sources), and cortisol during pregnancy. Monitoring mineralocorticoid requirements is further complicated by physiological changes in blood pressure and interstitial fluid status. While some literature suggests that adjusting fludrocortisone may not be necessary, as an increase in glucocorticoid dose can compensate, determining the correct dose of glucocorticoid and mineralocorticoid replacement should be tailored to each patient and their specific symptoms.

12516 Bilateral Adrenalectomy And Bariatric Surgery For Hormonal And Metabolic Control Of Classic Congenital Adrenal Hyperplasia

Abstract Disclosure: G. Palú: None. A.M. Rodrigues: None. Background: Hyperandrogenism is sometimes difficult to control in female patients with classic congenital adrenal hyperplasia (CAH), requiring supra-physiologic glucocorticoid dose with its metabolic consequences. Clinical Case: A 25-year woman with salt-losing CAH has been followed since she was born, requiring high glucocorticoid dose (hydrocortisone dose equivalent 50-75 mg), in addition to fludrocortisone (0.1-0.15 mg/day), without control of hyperandrogenism (testosterone and androstenedione levels more than 3 times ULN). She progressively gained weight, reaching 116 kg (256 pounds) and BMI of 46 kg/m2 when she was 17 years old. Bilateral adrenalectomy was performed in 2016 for disease control and to lower glucocorticoid dose. Androgen levels were supressed, glucocorticoid dose was reduced to 5mg prednisone (hydrocortisone dose equivalent 20mg) and she lost 10 kg of weight, but she remained in class III Obesity (BMI 42.5 kg/m2). Serious adrenal crises were not reported after bilateral adrenalectomy. Pharmacologic obesity treatment was done (sibutramine plus topiramate) and she lost 16 kg of weight, reaching 90 kg and a BMI of 36 from April 2017 to February 2020. She stopped treatment during the COVID- 19 pandemic and regained weight, reaching 106 kg again. She was lost to follow-up and returned in November 2023. In May 2022, she was submitted to a gastric bypass in a country town. She achieved 71 kg with a BMI of 28. She was feeling very well, taking post-bariatric vitamins and minerals, combined oral contraceptive, prednisone 5 mg/day (hydrocortisone dose equivalent 20 mg/day) and fludrocortisone 0.1 mg/day. Until now, she did not have any adrenal crises requiring parenteral glucocorticoid use. Conclusion: Even though treatment was aggressive with two surgeries that could lead to increased risk of adrenal crises, the patient had a benign course. New medicines that block CRH or ACTH action in CAH patients could prevent excessive glucocorticoid doses and weight gain and would be a better alternative to bilateral adrenalectomy in cases such as this one. 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

12530 Inferior Petrosal Sinus Sampling In Cushing’s Disease

Abstract Disclosure: A. Gondhi: None. S. Antharam: None. I. Moledina: None. Inferior Petrosal Sinus Sampling in Cushing’s Disease Introduction: Cushing's disease (CD) is the most common cause of endogenous Cushing syndrome( CS) caused by ACTH secreting pituitary tumor. MRI is typically used for imaging, but standard MRI may only detect 50% of microadenomas. In these cases, inferior petrosal sinus sampling (IPSS) is the gold standard in detecting pituitary source of ACTH. Case presentation:A 53-year-old man presented with signs and symptoms of CS: fatigue, weight gain, decreased libido, mood swings, new onset prediabetes. Physical examination revealed cushingoid appearance with facial flushing, easy bruising, abdominal purple striae. Initial work up revealed ACTH dependent CS: elevated late night Salivary cortisol 0.39 mcg/dL (&amp;lt;0.09 mcg/dL), 24hr urine free cortisol 192 mcg/24 hour (4 – 50 mcg/24 hour)Non suppressed cortisol 8.1 mcg/dL (&amp;lt;1.8 mcg/dL) after 1mg dexamethasone suppression test8 AM ACTH 56 pg/ml (7.2 – 63 pg/ml), DHEAS 491 mcg/dL (38-318 mcg/dL)Pituitary hormonal work up: normal Prolactin 7.8 ng/mL (2.6-13.1 ng/mL)Low TSH 0.29 ng/ml (0.45-5.3 ng/ml) with normal Free T4 0.76 ng/dl (0.58-1.6 ng/dl)Low Total Testosterone 150 ng/dl (175-781 ng/dl), Low FSH&amp;lt;0.7 mInt units/ml(1.27-19.26 mInt units/ml), Low LH 1 mInt units/ml (1.24- 8.62 mInt units/ml), Normal IGF 180 ng/mL (65-222 ng/mL), A1C 6% (Prediabetes – 5.7-6.4) MRI Brain showed normal pituitary gland. IPSS was performed with DDAVP: +2, +5, +10, +15: Right/ periphery ratio- 31.8, 10.75, 7.6, 5.3. left/periphery ratio- 26.6, 18.8, 8.3, 7.5. All the ratios &amp;gt;=3, which showed clear central to peripheral gradient. and no left or right difference consistent with Cushing's disease. Subsequently, a transsphenoidal pituitary gland resection was performed. Suspicious tissue was excised from both sides during the surgery, showing positive ACTH immunostaining, consistent with pituitary microadenoma. Post-operative labs showed significant improvement with normalization of Cortisol 3.2 mcg/dl, ACTH 45 pg/ml, TSH 3.14 ng/ml, FT4 0.61 ng/dl, FSH 1.7 mInt units/ml, LH 2.4 mInt units/ml, Prolactin 7.1 ng/ml, A1C 5.4 %He was discharged on physiological dose of Hydrocortisone and passed cortisol stimulation test (3.4 mcg/dl ---&amp;gt; 18.1 mcg/dl) Conclusion: Distinguishing between CD and ectopic ACTH secretion is crucial due to the differing treatment options. The most accurate method for differentiation is IPSS, which boasts high sensitivity and specificity compared to other analyses. Despite its invasiveness, IPSS is associated with rare adverse events, making it a valuable tool in clinical practice. Presentation: 6/3/2024

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 &amp;lt;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: &amp;gt;59), AST 435 IU/L (Ref: 5-34), ALT 269 IU/L (Ref: &amp;lt;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

6693 Hypopituitarism in Pregnancy

Abstract Disclosure: N.A. Mcheik: None. H. Howarth: None. Background: Hypopituitarism in pregnancy requires careful management to ensure both maternal and fetal well-being. Disruptions of the pituitary gland in pregnancy can be due to adenomas, pituitary infarction, autoimmune disease, trauma, etc. Complications of hypopituitarism in pregnancy stem from inadequate production of thyroid stimulating hormone, growth hormone, gonadotropins and cortisol. Hormone replacement therapy will be necessary in such cases. For instance, patients in late pregnancy may require an increased dose of hydrocortisone due to the rise of corticosteroid-binding globulin. Patients may need increased doses of glucocorticoid therapy during labor given the major surgical stress. Antenatal care should include close follow up with endocrinologists and obstetricians and regular assessment of maternal hormone levels and fetal growth. Case: We present a case of a 37-year-old female G3P0020 at 24 weeks who presented with complaint of constant headache for 6 days. Associated with photophobia, intermittent blurry vision, nausea, and vomiting. She was admitted and given 1 g Magnesium bolus as well as Robaxin and Tylenol for headache without relief. Given persistence of symptoms and non-focal neurologic exam, MRI brain was completed that showed an enlarged pituitary gland with blood products. MRI pituitary showed an approximately 1.3 x 1.2 x 1.8 cm hemorrhagic lesion on the right side of pituitary gland with fluid level, most in keeping with hemorrhagic pituitary apoplexy. Thyroid function studies were consistent with central hypothyroidism with a low TSH 0.05, low Ft4 0.5, and normal Ft3 2.4. Luteinizing hormone was 0.1 mIU/mL (&amp;lt;1.5 normal in pregnancy), follicle stimulating hormone was &amp;lt;0.5 mIU/mL (&amp;lt;0.1 normal in pregnancy), estradiol &amp;gt;5000 pg/mL (1278-7192 normal in pregnancy), and prolactin 254 ng/mL (80-400 normal in pregnancy). IGF-1 was normal at 148 ng/ml. Morning cortisol was low at 1.8 ug/dL and ACTH was 9 pg/mL (low normal). Cortrosyn stimulation test at 60 minutes was normal at 17.7 ug/dL, however, given clinical improvement on steroids, the clinical picture is consistent with central hypoadrenalism. For treatment, she was started on IV hydrocortisone 50 mg every 8 hours and oral levothyroxine 100 mcg daily. The patient was discharged home on oral hydrocortisone 20 mg daily in the morning and 10 mg daily in the afternoon with close follow up. Conclusion: Ultimately, the management of hypopituitarism in pregnancy requires a personalized approach to hormone replacement and obstetric care and this is done through multidisciplinary care involving endocrinologists and obstetricians to optimize outcomes for both the mother and the baby. Presentation: 6/1/2024

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 &amp;lt; 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 (&amp;lt; 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

12391 When Pressure Drops, Consequences Rise: A Case Of Pituitary Apoplexy And Watershed Infarcts

Abstract Disclosure: D. Moreno Watashi: None. H.R. Alkaissi: None. M.B. Sharma: None. Introduction: Pituitary apoplexy (PA) results from sudden hemorrhaging and infarction of the pituitary gland, typically within a pituitary adenoma. The primary symptom is a sudden, severe headache, often followed by acute endocrine dysfunction, ophthalmoplegia and visual or neurological disturbances. Case Description: A 68-year-old male with a past medical history of hypertension presented to the emergency department with acute chest and upper back pain, beginning one day prior. No history of smoking, alcohol intake or drug use. Blood pressure (BP) on arrival was 180/95 mmHg. Initial labs revealed mild electrolyte abnormalities. Troponins were normal, but ECG showed diffuse T wave inversion and ST depression. CT angiography revealed a type B aortic dissection. He was managed in the critical care unit with continuous esmolol intravenous (IV) infusion and planned for endovascular repair. During his stay, he became disoriented and hypotensive. MRI from the brain incidentally discovered a pituitary macroadenoma measuring 2.9x2.2x3cm and recent infarcts, with a distribution concerning for hypoperfusion. Fundoscopy concerning for optic chiasm compression. Labs indicated secondary hypothyroidism and hypogonadism (TSH 0.3 uUI/ml, free T4 0.88 ng/dL, total testosterone 56.3 ng/dL). Neurosurgical intervention was deferred until after aortic repair. Endovascular aortic repair was performed with episodes of hypotension. Post-procedure, the patient developed fever (39.5°C) and worsening mental status. Head CT revealed an increased suprasellar extension of the pituitary macroadenoma and vasogenic edema, consistent with hemorrhage of the lesion. He was started on stress doses of hydrocortisone, levothyroxine 125mcg and managed conservatively due to a high surgical risk. Discussion: PA's extrinsic risk factors include angiographic procedures, endocrinological dynamic tests, anticoagulation therapy, exogenous estrogen administration, orthopedic and cardiac surgeries (due to BP fluctuations). The intrinsic risk factors are non-functioning adenomas, macroadenomas and suprasellar extension. Treatment is focused on immediate correction of endocrine derangements and relieving local compression. Stress dosage of corticosteroids should be administered IV as soon as the diagnosis is confirmed to prevent life-threatening corticotropic deficiency. Neurosurgical decompression via a transsphenoidal approach is the definitive therapy to relieve local compression with severe visual loss, obtundation or rapidly progressive course. The potential outcomes are based on the extent of hemorrhage, necrosis, and edema. PA should be treated as a medical emergency in the setting of hemodynamic changes from acute corticotropic deficiency and irreversible neurological damage from acute intracranial compression. The risk factors for PA should be known to assist in early diagnosis. Presentation: 6/1/2024

8403 A Rare Presentation: Mucosal Melanoma with Pituitary Gland Involvement

Abstract Disclosure: L.R. Sepulveda-Garcia: None. L. El Musa Penna: None. W. Medina-Torres: None. J. Segarra-Villafane: None. Z. Maisonet-Feliciano: None. I. Arroyo-Gomez: None. L.A. Gonzalez-Rodriguez: None. M. Alvarado-Santiago: None. M. Ramirez-Vick: None. Introduction: Sinonasal mucosal melanoma (SNMM) is a rare form of aggressive melanoma with poor prognosis, compromising less than 1% of all melanoma. The most frequently reported symptoms include nasal obstruction and epistaxis, but the manifestation of symptoms may occur late and be nonspecific, causing delays in diagnosis and resulting in a less favorable prognosis. Here we report a rare case of mucosal melanoma with pituitary gland involvement initially thought to be a pituitary adenoma. Clinical Case Description: A 22-year-old male with no previous medical history was found with a biopsy proven pigmented epithelioid melanocytoma (PEM) in the palate. Three weeks after the biopsy, the patient presented with a severe headache, prompting the performance of a CT scan that revealed a pituitary macroadenoma. Several days later he developed acute right eye ptosis requiring emergency evaluation. The patient reported mild epistaxis, headaches, and nausea of 2 weeks duration associated with lack of erections and diminished libido. Physical exam was remarkable for sinus bradycardia, right eye ptosis, and a palate bluish pigmentation. Hormonal work up revealed a prolactin of 23 ng/mL (3.46-19.40), TSH of 2.22 uIU/mL (0.27-4.20), fT4 of 0.37 ng/dL (0.93-1.70), total testosterone &amp;lt;0.007 ng/mL (1.88-6.84), free testosterone of 0.001 ng/mL (0.032-0.168), FSH of 0.41 mIU/mL (2.6-11.0), and LH of 0.27 mIU/mL (0.4-7). Serum cortisol and ACTH levels were found to be low at &amp;lt;1.00 µg/dL (3.7-19.40) and 5.98 pg/mL (0.00-46.00), respectively, but these were taken while patient was given dexamethasone by neurosurgery for headaches. Brain MRI was remarkable for 3.4 cm x 3.3 cm x 3.5 cm sellar mass extending inferior into the sphenoid sinus, posteriorly into the right ethmoid air cells, superiorly into the suprasellar cistern with upward displacement of the optic chiasm, as well as bilateral cavernous sinus invasion. Case outcomes: A diagnosis of hypopituitarism was made. Physiologic doses of hydrocortisone were started after being found with central adrenal insufficiency. This replacement unmasked an arginine vasopressin deficiency also requiring desmopressin therapy. Central hypothyroidism was treated with levothyroxine and treatment for the hypogonadotropic hypogonadism was deferred in the meantime. Biopsy of right sphenoid sinus revealed a mucosal melanoma. Revised pathology slides led to the conclusion that palate PEM was an independent entity to the mucosal melanoma Case discussion: Prognosis is poor in patients with SNMM since this tumor is usually diagnosed at advanced stages. In this case, the sellar mass was initially thought to be a pituitary adenoma that later was found to be an extension of a mucosal melanoma. This case serves as a reminder of the critical role that differential diagnosis plays in evaluating sellar masses. Presentation: 6/1/2024

7277 Diabetic Ketoacidosis As The First Manifestation Of Ectopic Cushing’s Syndrome

Abstract Disclosure: R.S. Medeiros: None. Introduction: Ectopic Cushing’s Syndrome (ECS) represents 10-20% of all ACTH-dependent CS, and the majority of cases arise from lung carcinoids. These indolent lesions usually evolve clinically over 6-24 months, whereas carcinomas are associated with faster onset of ECS. Diabetic Ketoacidosis (DKA) as a presenting manifestation of Cushing’s Syndrome (CS) is very rare, with the few cases published to date related to Cushing’s disease. Clinical Case: A 42-year-old woman was admitted in the emergency room with DKA and COVID-19. During stabilization, florid CS was clinically suspected. She reported a 6-month history of secondary amenorrhea, lack of concentration and memory, easy bruising, proximal myopathy with frequent falls evolving to daily life dependency from relatives. She also reported a 2-month diagnosis of dyslipidemia, Diabetes and hypertension, and a diagnosis of atypical pneumonia 6 months ago. Physical exam showed typical cushingoid appearance, especially for marked limb sarcopenia and proximal myopathy. An overnight dexamethasone suppression test (morning cortisol: 25.7 ug/dL), 24h urinary free cortisol (UFC; 1072.5 ug/dL; reference: &amp;lt;176) and serum cortisol at 23h00 (25.5 ug/dL) confirmed CS. ACTH-dependent CS was diagnosed. She had non-suppressible serum cortisol in high dose dexamethasone suppression test, and CRH stimulation test was suggestive of Cushing’s disease only by a 20% rise of cortisol at 30 minutes. Pituitary MRI was normal. Inferior Petrosal Sinus sampling was postponed for several months due to healthcare strikes. The patient started 750 mg of metyrapone in three divided doses but rapidly decreased the dose and stopped it due to clinical resolution of CS, a dramatic improvement of all glucocorticoid-related comorbidities leading to discontinuation of statin, insulin, main oral anti-hyperglycemic and antihypertensive medications, and normal midnight salivary cortisol and 24h UFC. She remained in this eucortisolemic state for 12 months. Thoracic CT scan revealed thymic hyperplasia and a 25x15 mm well-defined nodule in the lingula. A 68Ga-DOTANOC PET/CT showed a single uptake in the same lung region. The patient underwent lingulectomy plus excisional biopsy of interlobar lymph nodes, and pathology revealed a low-grade neuroendocrine tumor (Ki67&amp;lt;2%, &amp;lt;2 mitosis) without involved lymph nodes. The patient is weaning off from physiologic doses of hydrocortisone. Conclusion: DKA can rarely be the presenting manifestation of severe CS, including ECS. Clinicians should suspect on this etiology of DKA based on clinical signs and cumulative morbidity not typical of a young patient. This hint would lead to the expedite implementation of targeted therapies for initial stabilization of the CS patient, and the timely institution of a proper diagnostic approach and definitive treatment of this challenging patients. Presentation: 6/2/2024

7658 A Case of Recurrent Cardiac Tamponade as Initial Presentation of Primary Adrenal Insufficiency

Abstract Disclosure: A. Farooq: None. A. Ghumatkar: None. J. Snitzer: None. Introduction:Cardiac tamponade, a life-threatening emergency, can be associated with primary adrenal insufficiency (Addison Disease), and accurate diagnosis requires a high degree of clinical suspicion in patients with uncertain etiology and nonspecific signs and symptoms. Case Presentation:A 58-year-old female with a history of Hashimoto thyroiditis was evaluated in the hospital for two episodes of cardiac tamponade requiring emergent pericardiocentesis within one month. The patient had been experiencing symptoms of fatigue, nausea, lightheadedness, dizziness, hiccups, and tanned skin for the past year. She also had a recent flu-like illness with nausea and vomiting four months before her current presentation. Her vitals were notable for hypotension during these episodes. Her lab work showed hyponatremia (128 mEq/L, reference range: 136-145 mEq/L) with normal potassium and glucose levels. Her thyroid function tests were within normal limits on her home levothyroxine dosage (TSH 4.588 IU/ml, reference range: 0.5-8.9 IU/ml). An ACTH stimulation test was performed based on the patient's clinical presentation, consistent with adrenal insufficiency. Her baseline cortisol level was 5.9 mcg/dL (reference range: 6.7-22 mcg/dL), a post-ACTH stimulation level of 6.7 mcg/dL after 30 minutes, and 6.0 mcg/dL after 60 minutes. Her 21 alpha-hydroxylase antibody titer was also positive for Addison Disease (231U/mL, reference range &amp;lt;1 IU/mL). A CT scan of the abdomen with intravenous contrast was done, which revealed no abnormality of the adrenal glands. She was treated with stress doses of hydrocortisone during hospitalization and discharged with maintenance dosage and follow-up with endocrinology. She had another episode of acute adrenal crisis about a month later but had no pericardial effusion this time and responded well to the treatment with stress doses of steroids. She has remained healthy at 14 years of follow-up. Conclusion: This case emphasizes the need to consider adrenal insufficiency in the evaluation of cardiac tamponade or pericardial effusions, especially in patients with existing autoimmune glandular disorders. This patient may have autoimmune polyglandular syndrome type 2 (APS-2), which is a cluster of two or more endocrine glandular disorders primarily diagnosed in adulthood and predominant in females. The risk of adrenal crisis is more than twofold in Addison disease due to APS-2. Lastly, this case highlights that hiccups can be related to adrenal insufficiency, with pathophysiology possibly involving diaphragmatic irritation due to adrenal inflammation that resolves with treatment. Presentation: 6/3/2024

6693 Hypopituitarism in Pregnancy

Abstract Disclosure: N.A. Mcheik: None. H. Howarth: None. Background: Hypopituitarism in pregnancy requires careful management to ensure both maternal and fetal well-being. Disruptions of the pituitary gland in pregnancy can be due to adenomas, pituitary infarction, autoimmune disease, trauma, etc. Complications of hypopituitarism in pregnancy stem from inadequate production of thyroid stimulating hormone, growth hormone, gonadotropins and cortisol. Hormone replacement therapy will be necessary in such cases. For instance, patients in late pregnancy may require an increased dose of hydrocortisone due to the rise of corticosteroid-binding globulin. Patients may need increased doses of glucocorticoid therapy during labor given the major surgical stress. Antenatal care should include close follow up with endocrinologists and obstetricians and regular assessment of maternal hormone levels and fetal growth. Case: We present a case of a 37-year-old female G3P0020 at 24 weeks who presented with complaint of constant headache for 6 days. Associated with photophobia, intermittent blurry vision, nausea, and vomiting. She was admitted and given 1 g Magnesium bolus as well as Robaxin and Tylenol for headache without relief. Given persistence of symptoms and non-focal neurologic exam, MRI brain was completed that showed an enlarged pituitary gland with blood products. MRI pituitary showed an approximately 1.3 x 1.2 x 1.8 cm hemorrhagic lesion on the right side of pituitary gland with fluid level, most in keeping with hemorrhagic pituitary apoplexy. Thyroid function studies were consistent with central hypothyroidism with a low TSH 0.05, low Ft4 0.5, and normal Ft3 2.4. Luteinizing hormone was 0.1 mIU/mL (&amp;lt;1.5 normal in pregnancy), follicle stimulating hormone was &amp;lt;0.5 mIU/mL (&amp;lt;0.1 normal in pregnancy), estradiol &amp;gt;5000 pg/mL (1278-7192 normal in pregnancy), and prolactin 254 ng/mL (80-400 normal in pregnancy). IGF-1 was normal at 148 ng/ml. Morning cortisol was low at 1.8 ug/dL and ACTH was 9 pg/mL (low normal). Cortrosyn stimulation test at 60 minutes was normal at 17.7 ug/dL, however, given clinical improvement on steroids, the clinical picture is consistent with central hypoadrenalism. For treatment, she was started on IV hydrocortisone 50 mg every 8 hours and oral levothyroxine 100 mcg daily. The patient was discharged home on oral hydrocortisone 20 mg daily in the morning and 10 mg daily in the afternoon with close follow up. Conclusion: Ultimately, the management of hypopituitarism in pregnancy requires a personalized approach to hormone replacement and obstetric care and this is done through multidisciplinary care involving endocrinologists and obstetricians to optimize outcomes for both the mother and the baby. Presentation: 6/1/2024

7839 Assess Management of Adrenal Insufficiency in Melanoma Patients Treated with Cancer Immunotherapy

Abstract Disclosure: W. Lin: None. L. Min: None. Despite high prevalent of adrenal insufficiency in melanoma patients treated with cancer immunotherapy, no study has examined the management of adrenal insufficiency in these patients. We performed this retrospective, longitudinal cohort study at Mass General Brigham, Boston, aims to characterize the management of adrenal insufficiency in melanoma patients. Patients were identified through our RPDR search tool, and medical record reviews were conducted. Three patient groups were analyzed: Melanoma with secondary adrenal insufficiency group (Mel_SAI, n=74), Melanoma matched control group (Mel_Con, n=69), and Pituitary macroadenoma-related adrenal insufficiency matched control group (Pit_Con, n=37). We compared self-perceived quality of life, glucocorticoid replacement dose, and clinic visit. Mel_SAI patients exhibited significantly higher incidences of anxiety (43.1%, 95%CI: 32.3-54.6), fatigue (73.6%, 95%CI: 62.4-82.4), pain (58.3%, 95%CI: 46.8-69.0), and insomnia (36.1%, 95%CI: 26.0-47.6), as compared to Pit_Con group (21.6%, 11.4-37.2; 24.3, 13.4-40.1; 29.7%, 17.5-45.8; 5.4%, 1.5-17.7, respectively). The initial hydrocortisone dose was higher for Mel_SAI (30mg qd, 95%CI: 20.5-25.1) compared to Pit_Con (15mg qd, 95%CI: 12.8-18.3). Additionally, the Mel_SAI group had fewer endocrinology clinic visits (3, 95%CI: 3.40-5.04) than the Pit_Con group (9, 95%CI: 7.35-10.9). Subgroup analysis indicated a higher mortality risk (HR 2.61, 95% CI 1.11-6.13) in Mel_SAI patients with fewer than three endocrinology visits over five years. Compared to the Mel_Con group, Mel_SAI patients also showed higher incidences of fatigue (71.6%, 95%CI: 60.5-80.6; Mel_Con: 55.1%, 95%CI: 43.4%-66.2%), but lower rates of depression (25.7%, 95%CI: 17.1-36.7; Mel_Con: 43.5%, 95%CI: 32.4-55.2) and appetite loss (24.3%, 95%CI: 16.0-35.2; Mel_Con: 47.8%, 95%CI: 36.4-59.4). No significant difference in other self-perspective symptoms. Furthermore, Mel-SAI patients had more oncological clinic visits (71, 95%CI: 74.0-109.2) than those in the Mel_Con group (41, 95%CI: 42.1-64.1). Our study suggests that most self-perceived quality of life in the Mel_SAI group is related to melanoma rather than adrenal insufficiency. Therefore, a higher initiating dose of hydrocortisone in melanoma patients with adrenal insufficiency may not be necessary. However, increasing endocrine clinic visits in cancer patients with cancer immunotherapy-related adrenal insufficiency may improve their survival outcomes. Presentation: 6/3/2024

8665 Female Fertility In Patients With Classic And Non-Classic Congenital Adrenal Hyperplasia Under Modified-Release Hydrocortisone (MR-HC)

Abstract Disclosure: L. Tschaidse: None. H.F. Nowotny: None. M. Auer: None. C. Lottspeich: None. M. Bidlingmaier: None. J. Hawley: None. B.G. Keevil: None. N. Reisch: None. Background: Female patients with classic and non-classic (NC) CAH struggle with fertility, due to androgen excess, elevated progesterone and 17-hydroxyprogesterone (17OHP) levels, causing anovulation, impairment of endometrial development and menstrual irregularities. The typical approach to treating infertility often includes an increase in glucocorticoid (GC) dose. However, this poses a potential risk of side effects. Limited observational data on modified-release hydrocortisone (MR-HC), which better mimics the physiological diurnal rhythm of cortisol secretion, indicates improved fertility in female and male patients with classic CAH. Therefore, the aim of this study was to investigate fertility in women with classic and non-classic CAH before and after switching to MR-HC. Methods: 21 adult female patients with CAH (14 classic; 5 NC) with a median (range) age of 33.0 (30.0) years, premenopausal and without hormonal contraception, were enrolled in this prospective, observational, single-centre study. The data collection took place before (conventional GC preparation) and after dose-equivalent switching the medication to MR-HC. In addition to clinical parameters such as menstrual cycle and desire to conceive, the collection of morning serum and daily saliva profiles was conducted, measuring progesterone, 17OHP, androstenedione (A4), testosterone, 11-ketotestosterone (11KT) as well as 11-hydroxyandrostenedione (11OHA4). Results: Before study inclusion, 4/21 patients had an irregular cycle, 5/21 were amenorrhoeic and 10/21 patients had a desire to have children. There was no difference in median (range) hydrocortisone dose equivalent before and after switching to MR-HC (25.0 (50.0) vs. 25.0 (30.0), p=.441). Median (range) morning serum concentrations between 8-10 am were not different before and after switch to MR-HC for progesterone (5.9 (55.5) vs. 5.0 (58.8), p=.823), 17OHP (5.9 (362.1) vs. 5.7 (73.7), p=.280), A4 (2.9 (25.6) vs. 2.5 (6.9), p=.106), testosterone (0.8 (3.5) vs. 0.7 (1.5), p=.063), 11KT (0.4 (7.4) vs. 0.2 (2.6), p=.242) and 11OHA4 (0.8 (12.9) vs. 0.9 (10.4), p=.231). Concerning saliva day profiles, we found a significantly lower median (range) 17OHP level in early morning saliva (43.0 (526.9) vs. 19.4 (264.3), p=.049). 5/9 patients with menstrual irregularities reported menstrual regularisation within and 5/10 patients with a desire to have children became pregnant after switching to MR-HC. Conclusion: Our preliminary data show clinical improvement in fecundity and fertility under MR-HC in both women with classic and NC CAH without a dose increase of glucocorticoids. Under MR-HC replacement lower 17OHP concentrations in early morning saliva reflect better hormonal control over night contributing to ovulatory cycle regulation and improved fertility. Presentation: 6/1/2024

8800 A Case of Hypopituitarism Due to Sheehan Syndrome

Abstract Disclosure: N. Akabogu: None. S. Dejhansathit: None. F. Marium: None. B. Stanley: None. E.M. Bazuaye: None. L.S. Krusniak: None. L.G. Kurukulasuriya: None. U.Z. Khan: None. Background: Sheehan syndrome, which is also known as postpartum pituitary infarction, refers to the necrosis of the anterior pituitary gland due to postpartum hypovolemia, hemorrhage, shock, resulting in various degrees of hypopituitarism. The pituitary gland enlarges during pregnancy due to estrogen stimulation and becomes hyper-vascular, making it prone to infarction with postpartum hemorrhage. The initial symptoms include hyponatremia, weakness, weight loss, but the most prominent specific symptoms are inability to nurse and postpartum amenorrhea. Depending on the severity of hypopituitarism, symptoms may develop within the first few days to weeks after delivery or may take months to years to develop. Case presentation: 35year-old Caucasian female with a medical history of gestational diabetes, hyperlipidemia, and hypertension, who presented to the hospital with flu-like symptoms, leg pain, abdominal pain, and proximal muscle weakness. The evaluating hospitalist observed that patient appeared sluggish and spoke with a deep coarse voice, which concerned him for hypothyroidism. Thyroid function test revealed undetectable free T4 with inappropriately normal TSH of 1.38 – consistent with secondary hypothyroidism. Additional history from patient uncovered 9 months history of constant fatigue, weight gain, dry skin, hair loss, cold intolerance, and intermittent ankle swelling. There is no history of brain irradiation or head trauma. She has 4 biological children, and her last childbirth 3years ago was complicated by severe bleeding from her incision site, requiring transfusion of 6 units of blood. She has been amenorrheic since and is neither on birth control nor had hysterectomy. Physical exam showed mildly enlarged tongue, diffuse pallor, dry scaly skin on upper arms, scanty eyebrows, and slowed speech. Further work-up for pituitary insufficiency showed secondary adrenal insufficiency, secondary hypogonadism, low prolactin, and growth hormone deficiency. There was no evidence of AVP deficiency. Other lab and clinical findings were hypoglycemia, hyperlipidemia, elevated CK, elevated Cr, pericardial effusion, and diastolic hypertension. Pituitary MRI showed markedly attenuated and flattened pituitary gland with no focal mass. Patient was given stress dose hydrocortisone and thyroid hormone replacement, initially IV then oral. Following hydrocortisone and thyroid hormone replacement, her diastolic BP, hypoglycemia, CK, and Cr improved. Further management plans include initiating estrogen (plus progesterone) for bone health. Conclusion: Although Sheehan syndrome is rare in developed countries, it does occur. This case emphasizes the importance of detailed history taking, to discover the root of patients’ presentation. Even though TSH is the screening test for thyroid disease, when pituitary etiology is suspected, it is important to also check a free T4. Presentation: 6/1/2024

6419 Cushing’s Syndrome due to Metastatic Pancreatic Neuroendocrine Neoplasm With Incidental Pituitary Microadenoma

Abstract Disclosure: A. Ibrahim: None. L. Esper: None. R. Jain: None. N. El Asmar: None. Introduction: Pancreatic neuroendocrine neoplasms (PNENs) are rare with a reported incidence of 1-2/100,000. While the majority are non-functional, insulinomas and gastrinomas are the most common functional PNENs. Our case of ACTH-producing PNENs is extremely rare. Case presentation: A previously healthy 47-year-old female was hospitalized for worsening dyspnea. Her symptoms included rapid weight gain, skin hyperpigmentation, and lower extremity edema. Her exam was notable for elevated blood pressure of 181/120 mmHg, moon facies, purple abdominal striae, and proximal myopathy. Her lab analysis showed a cortisol level of 42 mcg/dL (6.2-19.4), ACTH of 254 pg/ml (7.2-63), DHEA sulfate of 171 mcg/dl (41-243), HbA1C 7%, K of 3 mmol/l and 24H urine cortisol &amp;gt;2100 mcg/24hrs. A post low-dose DST cortisol level was 42.7 mcg/dl. CT chest demonstrated an ill-defined hypodense lesion in the region of the pancreatic head. MRI abdomen revealed a 3 x 2.3 x 2.3 cm mass in the pancreatic head and many small enhancing lesions within the right lobe of the liver. Adrenal glands appeared normal. Subsequent PET CT scan with GA 68 DOTOTATE showed increased uptake in the pancreatic head mass and in the right hepatic lobe. Her pituitary MRI revealed a right pituitary gland 6 mm hypointense lesion, possibly a microadenoma. A high dose DST resulted in a cortisol level of 80 mcg/dl mostly consistent with ectopic ACTH secretion. EUS-guided biopsy of the pancreatic mass showed a well-differentiated neuroendocrine tumor that stained positive for ACTH, chromogranin, synaptophysin, and CD56. Treatment with Ketoconazole 600mg q6h and Octreotide 50mg q6h was started 3 days before surgery to control acute hypercortisolism as she developed acute psychosis. The patient subsequently underwent a Whipple procedure with successful resection of the pancreatic mass. Post-op, her ACTH levels dropped to 19 pg/ml with a cortisol level of 6 mcg/dl. Final pathology showed a well-differentiated grade 3 neuroendocrine tumor with a KI-67 labeling index greater than 20%. After surgery, the patient received a short course of stress dose hydrocortisone which was tapered off over the following 2 months. The patient is being followed for planning further intervention given the aggressive grade of the tumor and hepatic metastases. Conclusion: Ectopic ACTH-producing PNENs are rare. An accurate and timely diagnosis, while challenging, is key. Patients usually present with rapidly progressing symptoms that could cause life-threatening complications such as thrombosis and sepsis. We demonstrated the importance of utilizing a multidisciplinary team approach and starting cortisol-lowering medications early given the complexity of the disease, requiring rapid intervention and lifelong follow-up. Presentation: 6/3/2024