24-hour Urinary Free Cortisol Research Articles

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

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

8014 Cushing’s Syndrome: Two Sides of The Spectrum

Abstract Disclosure: M. Aguilera: None. A. Vu: None. J. Shakil: None. R. Al-Ward: None. Introduction: Cushing’s syndrome (CS) is a rare condition with an annual incidence of 2-8 per million. Endogenous CS is mainly due to corticotroph adenoma of the pituitary followed by excessive glucocorticoid production from adrenal and ectopic sources. CS has significant morbidity and mortality hence the need for timely diagnosis. The varied presentations often pose great challenges in identifying the source of hypercortisolism. We present two unusual cases of CS with distinct clinical presentations and atypical laboratory profiles. Case 1: 25-year-old male with no medical history presented with 9 months of facial puffiness, weight gain, fluid retention, hypertension and blurred vision. Physical examination revealed round facies, bilateral supraclavicular fat pads and wide abdominal striae. Laboratory workup showed markedly elevated ACTH 537 pg/mL [7.2-63 pg/mL], serum cortisol 8.5 ug/dL [6.2-19.4 ug/dl], 24-hour urine free cortisol (UFC) 30 [5-62 ug/24H] and normal late-night salivary cortisol (LNSC). Repeat workup a month later showed serum cortisol of 56ug/dL, ACTH 874 pg/dL, 24-hour UFC of 11880ug/24H and elevated LNSC. Pituitary MRI showed a large heterogenous 3.1 cm partially cystic sellar mass with suprasellar extension. Due to significantly elevated ACTH and short duration of symptoms, we suspected an ectopic source. Due to initial negative testing, except for high ACTH level, a silent corticotroph adenoma was also considered. The patient underwent transsphenoidal resection resulting in significant decrease of cortisol and ACTH postoperatively. Pathology showed a corticotroph adenoma with Ki-67 index of <1%. Case 2: 47-year-old woman with medical history of obesity, polycystic ovary syndrome and a stable 1 cm lung nodule since 2020, presented with fluid retention, worsening acne and resistant hypertension over a 1-year period. She required hospitalization for hypertensive emergency and hypokalemia. Laboratory data showed morning serum cortisol 28 ug/dL, ACTH of 90.1 pg/mL, 24-hour UFC 346 ug/24H, elevated LNSC on two occasions and cortisol 24.3 ug/dl after a 1mg dexamethasone suppression. MRI did not show a pituitary mass. PET dotatate scan revealed a tracer avid 1 cm right upper lobe pulmonary nodule. She underwent a right upper lobe lobectomy, resulting in a significant decrease in cortisol and ACTH levels on postoperative day 1. Pathology confirmed a typical carcinoid tumor. Discussion: High ACTH levels and a short symptom duration often point to ectopic production, paraneoplastic syndromes or corticotroph carcinomas. Cushing's disease typically exhibits mildly elevated ACTH levels, but our cases deviate from this norm, complicating source identification. This atypical presentation highlights the complexity of Cushing's syndrome, challenging conventional diagnostic paradigms. Presentation: 6/1/2024

8036 A Rare Case of Cushing’s Syndrome Caused by a Pulmonary Carcinoid Tumor

Abstract Disclosure: A.C. Tep: None. F.M. Wolf: None. Introduction: The most common causes of ectopic ACTH (adrenocorticotropic hormone) syndrome include bronchial carcinoid tumors and other neuroendocrine tumors. Ectopic ACTH syndrome (EAS) can be difficult to diagnose. Differentiating Cushing’s disease and EAS is difficult, as ACTH-secreting tumors are often small and easily missed on imaging. Case Presentation: A 32-year-old male with a history of hypothyroidism presented with a 6-month history of facial rounding. He also noticed a dorsocervical fat pad, muscle weakness in the extremities, easy bruising, and elevated blood pressure progressing over the same period. A 24-hour urine free cortisol was elevated to 1797 mcg. Two salivary cortisol tests performed 1 hour after the patient’s usual bedtime had values of 4.4 ug/dl and > 1.000 ug/dl. Both the urine and salivary cortisol results were exceedingly high. ACTH was elevated (150 pg/ml). An MRI of the pituitary gland was normal without evidence of an adenoma. Frequently, ACTH-secreting pituitary adenomas are small enough that they are missed on MRI; however, given our patient’s rapid clinical presentation, additional imaging was performed to identify an ectopic source. A CT Chest/Abdomen/Pelvis showed a 1.2 cm nodule in the right middle lobe of the lung. The right middle lobe was resected, and pathology revealed a carcinoid tumor. His cortisol levels slowly decreased postoperatively and eventually normalized. At his one-month post-operative visit, his symptoms were all improving but not yet resolved. Discussion: This patient was found to have Cushing's syndrome due to ectopic ACTH production from a pulmonary carcinoid tumor. The patient demonstrated clinical improvement after resection of the tumor. Pulmonary carcinoid tumors are rare neuroendocrine epithelial tumors that account for 2-5% of all lung tumors. The annual incidence of these tumors is 2.3-2.8 cases per million people. Endogenous Cushing's syndrome is either ACTH-dependent or ACTH-independent. In ACTH-dependent Cushing's syndrome, the ACTH can either be from the pituitary or an ectopic source. Once ACTH-dependent disease is confirmed, a pituitary MRI is performed to evaluate for an ACTH-secreting pituitary adenoma; this is called Cushing’s disease. Some patients undergo inferior petrosal sinus sampling to confirm the source is central and to determine laterality before transsphenoidal resection of the adenoma. If the source of ACTH is not from the pituitary, obtaining a CT or MRI of the chest and abdomen locates tumors in most patients. At times a functional study, such as an octreotide or PET-DOTATE scan, is done to confirm the diagnosis before proceeding with surgical resection to avoid unnecessary removal of an incidental tumor. Ectopic ACTH production often causes a more rapid progression of Cushingoid features, which can be a clue to the diagnosis of this condition. Presentation: 6/1/2024

5074 Licorice Root Supplement As A Cause Of Hypokalemic Hypertension

Abstract Disclosure: G. Gill: None. S.M. Harman: None. L.A. Robles: None. A 67-year-old female Veteran presented to an emergency room with a one-day history of high blood pressure, chest tightness, and exertional dyspnea. Her blood pressure was 162/90 mm Hg, pulse regular at 71 BPM, and pain level 5/10. She had a history of hypertension, stable on hydrochlorothiazide alone, hyperlipidemia, anxiety, and depression. Physical exam was benign. EKG revealed normal sinus rhythm at 60 BPM, normal axis, a prolonged QT interval of 510 ms, and no ST changes. Lab evaluation showed a low potassium of 2.4 mEq/L, sodium 145 mEq/L. Other lab measurements (CBC, liver function tests and cardiac enzymes) were within laboratory reference ranges. Medications included topiramate for migraine and over-the-counter supplements for constipation, “thyroid health,” and a topical “testosterone booster” prescribed by a non-allopathic practitioner. Her hypokalemia was attributed to hydrochlorothiazide and topiramate and both were discontinued. She was started on nifedipine for blood pressure control and 40 mEq/day of potassium for hypokalemia. Within 2 weeks of discharge, she presented again with elevated blood pressure and a plasma potassium of 4.0 mMol/L. Further history revealed that her constipation supplement consisted of licorice root (glycyrrhiza glabra) extract 900 mg per capsule, of which she took 3 to 4 capsules daily. The patient was advised to discontinue all supplements. Thyroid function tests were within normal limits. Due to a suspicion of hyperaldosteronism, the ED physician requested an abdominal CT scan which showed a 1 cm, -17.5 Hounsfield unit, right adrenal nodule. Also consistent with hyperaldosteronism, plasma renin activity (PRA) was suppressed at 0.07 ng/mL/hr. However, a serum aldosterone level was less than 1 ng/dL. Her 24-hour urinary metanephrines were normal and a 24-hour urine free cortisol was 31.6 mcg/dL. Morning plasma cortisol was 5.1 mcg/dL. A tentative diagnosis of licorice-induced hyperaldosteronism was made and the patient was treated with a taper of spironolactone. After discontinuing spironolactone, blood pressure was 116/70mmHg and serum potassium was 4.5 mMol/L with a PRA of 0.66 ng/mL/hr and serum aldosterone of <5.0 ng/dL. The syndrome of factitious hyperaldosteronism due to licorice consumption has been well described. The mechanism, inhibition of renal (type 2) 11-beta-hydroxysteroid dehydrogenase by glycyrrhizic acid, allowing cortisol to exercise its considerable mineralocorticoid action, is well understood. Most prior reports have been in patients habitually consuming licorice candy, usually imported, since conventional licorice sold in the U.S. is artificially flavored. Our report illustrates the importance of obtaining a history of use of over-the-counter supplements and assessing their ingredients and the fact that presence of an adrenal nodule and a low PRA does not always indicate endogenous hyperaldosteronism. Presentation: 6/2/2024

7183 Histoplasmosis Of Adrenal In An Immunocompetent Patient From Arizona: A Surprising Biopsy

Abstract Disclosure: R. Habibi: None. S. Penquite: None. N. Ebrahimi: None. R. Cardenas Lara: None. Introduction: Histoplasmosis of adrenal gland in the context of disseminated infection is a rare entity in a non-endemic area. Early diagnosis and treatment can save one’s life. Here we present a case of a patient from Arizona who was referred to us with a large adrenal mass initially resembling malignancy. Presentation: A 58-year-old male with no significant medical history from Bisbee Arizona presented to our clinic with significant weight loss of 120 pounds in 8months, jaundice, fatigue, nausea and vague abdominal pain. He had an abdominal CT scan in a rural area hospital which showed a left adrenal 4.2 x 4.3 x 3.7 cm mass with average HU=40, with interval development from a CT scan 6months prior to that which showed left adrenal 1.5 x 1.3 x 1.3 cm mass. He had the initial CT scan after a mechanical fall. He was experiencing sweating, dizziness and low blood pressure of 90/60 mmhg, but used to have hypertension. Physical examination revealed diffuse jaundice in an ill appearing cachectic individual. Laboratory data were significant for total bilirubin of 4.9, direct bilirubin 0.7. Plasma metanephrines and normetanephrines, 24-hour urine free cortisol, morning cortisol levels and DHEA sulfate were normal. Other findings on the CT scans of head, chest and abdomen were soft tissue thickening between the right posterior 10th and 11th ribs along with hepatosplenomegaly, nodular lung lesions with calcified granuloma, sub centimeter brain lesions within the left putamen/external capsule junction with corresponding mild edema. During the following month after initial visit he developed bilateral tongue masses with dysphagia along with enlarging bilateral adrenal lesions, measuring up to 4.4 cm on the right and 5.2 cm on the left. The patient was admitted to hospital for further extensive work up. He underwent biopsies of left adrenal mass and tongue lesions which demonstrated necrotizing granulomatous inflammation with fungal elements compatible with histoplasmosis. Liposomal amphotericin B was started, which was quickly switched to itraconazole 200mg twice a day once lumbar puncture result was normal. His transient low blood pressures resolved. He was seen in clinic after few weeks with overall improving symptoms. Follow up with imaging of adrenal in few months is planned. He is currently in his third month of treatment for histoplasmosis with itraconazole. Discussion: The presentation of disseminated histoplasmosis can resemble malignancy as illustrated in this case. Southwest of the United States is an unusual geographical area for such infection. Initial unilateral involvement of adrenal as a mass in an immunocompetent individual is also uncommon. Considering dramatic response to antifungal treatment, a clinician should suspect such rare infections when seeing a nonfunctional adrenal mass with rapidly progressive constitutional symptoms. Presentation: 6/3/2024

6426 Pregnancy-induced ACTH-independent Cushing Syndrome: A Rare Phenomenon Secondary To Aberrant Receptors On Adrenal Glands

Abstract Disclosure: K. Manglani: None. S.T. Sharma: None. Pregnancy-induced hypercortisolism is a rare phenomenon with very few cases reported in the literature. The pathogenesis is thought to be secondary to the expression of aberrant LH/hCG receptors on the adrenal gland that stimulate cortisol production in pregnancy. We present a case of a 31-year-old female with no past comorbidities until her first pregnancy in 2017 when she gained around 50lbs, developed violaceous striae, acne, hirsutism, depression with suicidal ideation for which she was hospitalized twice, and underwent emergent C-section at 34 weeks’ gestation due to pre-eclampsia. She was referred to the Endocrinology clinic post-delivery, and screening for Cushing syndrome was negative at that time: 24-hour urinary free cortisol (UFC), late-night salivary cortisol (LNSC) and 1-mg dexamethasone (dex) suppression test (DST) were normal. She presented again in 2020 during her second pregnancy at 14 weeks gestation, with 20lb weight gain in the first trimester, acne, hirsutism, and easy bruising. Labs showed cortisol of 22.4 mcg/dL (6.2-19.4), ACTH <1.5 pg/mL, total testosterone 168 ng/dL (8-48), androstenedione 751 ng/dL (41-262), DHEAS 91.2 mcg/dL (84.8-378), 24-hour UFC 277 mcg/day (6-42), LNSC 0.671 mcg/dL, 1mg DST with post-dex cortisol 24 mcg/dL (dex level 58 ng/dL), and 8-mg DST with post-dex cortisol level of 28.2 mcg/dL (dex level 457 ng/dL). Testing was consistent with ACTH-independent Cushing syndrome. Ultrasound and MRI of the abdomen/pelvis showed normal adrenal glands with no hyperplasia or mass. Given worsening hypercortisolism and her course during a prior pregnancy, medical treatment with metyrapone was initiated. We started at a dose of 500 mg daily and gradually increased to 1500 mg with close monitoring of her blood pressure and cortisol levels. She underwent vaginal delivery at 38 weeks’ gestation, and the baby required a brief stay in the NICU for respiratory distress but was otherwise doing well. The patient developed secondary adrenal insufficiency post-delivery requiring hydrocortisone, with recovery of her HPA axis in around 10 weeks. Since then, she has been off hydrocortisone with normal UFC, ACTH, and cortisol levels. This case enables discussion regarding the underlying etiology, diagnostic difficulties, and management of this rare condition. Although the exact etiology is unknown, the postulated mechanism is aberrant LH/hCG receptor expression given the patient’s presentation during each pregnancy, normal cortisol levels between both pregnancies, and a brief period of adrenal insufficiency post-delivery. Management of hypercortisolism during pregnancy remains challenging. Metyrapone, a steroidogenesis inhibitor, can be considered for control of hypercortisolemia during pregnancy (off-label) in select cases to prevent maternal and fetal complications. Presentation: 6/1/2024

6640 Utility of bilateral inferior petrosal sinus sampling for diagnosis and management of Cushing's disease in children ; a case report

Abstract Disclosure: V. leal: None. L. Socha: None. S.S. Awadalla: None. The causes of adrenocorticotropic hormone (ACTH)-dependent Cushing's syndrome (CS) are Cushing's disease (CD) and ectopic ACTH syndrome (EAS). The differential diagnosis of CS and the localization of lesions in CD and EAS are often challenging. The utility of bilateral inferior petrosal sinus sampling (BIPSS), an important test in adults, is less defined in children.A 16-year-old girl was referred for evaluation and treatment of Cushing syndrome she experienced weight gain, secondary amenorrhea, and back pain. 24-hour urinary free cortisol and low-dose dexamethasone suppression tests suggested Cushing syndrome. Adrenocorticotropic hormone (ACTH) level and high-dose dexamethasone suppression test confirmed Cushing disease. Pituitary magnetic resonance reported a microadenoma. To rule ectopic ACTH syndrome, and localize the pituitary tumor, bilateral inferior petrosal sinus sampling (BIPSS) was performed with desmopressin to stimulate ACTH. Finally, the patient was diagnosed with Cushing disease due to right ACTH-secreting pituitary microadenoma and underwent endoscopic endo-nasal transsphenoidal surgery.In conclusion , BIPSS can be a valuable tool not only for discriminating between pituitary origin and ectopic ACTH-secreting Cushing syndrome, but also for providing precise localization of pituitary adenomas, thereby facilitating appropriate treatment. Presentation: 6/1/2024

7302 Efficacy And Hepatotoxicity Of Ketoconazole In Cushing’s Syndrome

Abstract Disclosure: H. Elenius: None. R. McGlotten: None. S.T. Sharma: None. L.K. Nieman: None. Medical therapy (Rx) of Cushing’s Syndrome (CS) is complicated by variable efficacy, delays to treatment goal and adverse reactions. Ketoconazole (KTZ) use is limited by hepatotoxicity. We retrospectively reviewed records of 65 inpatients receiving KTZ for CS between 2004-2023 to assess efficacy and hepatotoxicity. 24-hour urinary free cortisol (UFC), AM serum cortisol (F), liver function tests (LFTs: alanine transaminase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP)) and daily doses of KTZ were noted. Patients were excluded if they received other medical Rx for CS or strong CYP3A4 inducers/inhibitors; baseline (base) or endpoint F/LFTs were unavailable; or if they received KTZ within 4 days prior to base labs. 35 patients (pts) were evaluated for efficacy. Treatment success was defined as F ≤12 mcg/dL. 17 pts (49%) achieved goal F at a median of 3 days (1-11, IQR 2.5-5.5). Compared to uncontrolled pts, there was no difference in Rx duration, base UFC or F, or initial or final KTZ doses, including when adjusted for base UFC, F, weight or body surface area. The absolute and percent dose increases and the F level prompting an increase did not differ between groups. Pts who reached goal had fewer days (d) between dose increases than uncontrolled pts (median 2 vs 4 d, p=0.025). Of 19 pts on a stable KTZ dose for ≥3 d after an increase, mean F decreased from d 0 to d +1 (-19%, p=0.01), +3 (-38%, p=0.0001) and +4 (-25%, p=0.04). D +3 F decreased from d +1 (-14%, p=0.03) and +2 (-13%, p=0.03). After d+3 no further reduction was seen (but likely biased by subsequent dose changes or discharge after d +3). 37 pts were evaluated for toxicity during KTZ Rx. Of 3 pts with a base LFT ≥3 times upper limit of normal (3ULN), LFTs rose ≥30% in 1, improved to <3ULN in 1 and did not change in the last pt. Of 34 pts with base LFTs <3ULN, a ≥30% rise of ≥1 LFT was seen in 27. Of these, 10/27 had ≥1 LFT rise to ≥3ULN after a minimum cumulative dose of 3400 mg and at least 4 days of Rx. Compared to the other 24, these 10 pts had higher means of base AST (75 vs 54% of ULN, p=0.046), cumulative KTZ doses (10080 vs 4071 mg, p=0.0015), and daily KTZ doses (927 vs 650 mg, p=0.004). AST and ALT increased by ≥30% before ALP (AST vs ALP: 4 vs 6 d, p=0.08). After KTZ was stopped or reduced, LFTs reached <3ULN at a median of 3 days (1-10, IQR 1.5-8.5) in 9 pts; pt 10 improved by discharge. 15/27 with an LFT rise ≥30% continued the same KTZ dose; LFTs stayed ≤ULN in 8, rose to >ULN in 5 and improved from base >ULN to ≤ULN in 2. By the end of inpt KTZ Rx (median 6 d, range 1-27, IQR 4-9), 13 pts (35%) had ≥1 LFT rise from ≤ULN to >ULN, 4 (11%) had ≥1 LFT improve from >ULN to ≤ULN. 12 stayed >ULN (32%); 8 (22%) stayed ≤ULN. Our data supports raising KTZ doses every 72 hours for rapid control. Base AST correlates with liver toxicity risk and tends to rise before ALP. An LFT rise ≥30% is seen in most pts and should not prompt Rx cessation if <3ULN. KTZ improves LFTs in a minority of pts, likely from cortisol reduction. Presentation: 6/3/2024

8319 Pituitary Apoplexy Leads to the Spontaneous Resolution of Hypercortisolism Secondary to Cushing Disease: A Clinical Case

Abstract Disclosure: N. Sweis: None. J. Sanchez Perez: None. M. Fariduddin: None. R.M. Sargis: None. D.J. Toft: None. S. Reutrakul: None. Background: Pituitary apoplexy is a potentially fatal condition involving the infarction or hemorrhage of the pituitary gland. Rarely, it can occur in the setting of an ACTH-secreting pituitary adenoma. Clinical Case: A 27-year-old female with a past medical history of obesity, spontaneous miscarriages, and amenorrhea presented to the ER with an acute onset frontal headache of throbbing quality, associated with nausea and vomiting. The headache began two days prior, rapidly intensified, and did not improve with oral acetaminophen. CT of the head revealed an enlarged pituitary gland, while neurovascular imaging showed no abnormalities. Her neurologic examination was normal. She denied visual changes, photophobia, neck rigidity, fevers, chills, or recent infections. Furthermore, she endorsed a weight gain of about 40 pounds over the past year despite no change in dietary habits. This was accompanied by amenorrhea, hair thinning, itchy comedonal acne, hirsutism, and a loss of libido. Her physical examination was remarkable for the presence of cushingoid features including violaceous abdominal striae, facial acne, moon facies, a dorsal fat pad, and acanthosis nigricans around the neck and axillae. Pituitary MRI with and without contrast showed an enlarged sellar and suprasellar macroadenoma measuring approximately 2.1x1.4x1.2 cm abutting the optic chiasm. The visualized lesion contained hemorrhagic products, suggesting pituitary apoplexy. Biochemical testing on admission included a low morning plasma cortisol of 6.5 ug/dL (ref. range: 6.7-22.6 ug/dL), a 24-hour urine free cortisol of 12.0 (<=45.0 ug/24 hour), and an elevated ACTH of 145.0 pg/mL (7.2 - 63.3 pg/mL). A1c was 5.8% (<5.7%). Serum levels of prolactin, IGF1, GH, LH, FSH, TSH, Free T4, estradiol, total and bioavailable testosterone were within normal limits. She was evaluated with an ACTH stimulation test, which showed a morning cortisol level of 1.2 ug/dL at baseline, lower from prior. Cortisol levels were adequately increased at 19.6 ug/dL and 22.6 ug/dL, 30 and 60 minutes after the administration of Cosyntropin 250 mcg, respectively (>=18 ug/dL after 30-60 mins). The level of ACTH at the time was also decreased to 76.6 pg/mL. The patient was therefore started on steroid replacement therapy with hydrocortisone and later underwent transsphenoidal resection of the pituitary mass without complications. Histopathological examination of the resected mass showed pituitary adenoma cells with diffuse weak to moderate ACTH staining, most consistent with a sparsely granulated corticotroph pituitary adenoma. Conclusion: We report an interesting case of Cushing disease that spontaneously resolved after pituitary apoplexy. Our case underlines the importance of close monitoring of such patients who may rapidly undergo a period of adrenal insufficiency after hypercortisolism. Presentation: 6/3/2024

8604 Ectopic Cushing’s Syndrome Associated with a Metastatic Pancreatic Mixed Neuroendocrine Non-neuroendocrine Neoplasm (MiNEN) with Amphicrine Features

Abstract Disclosure: A. DeMarsilis: None. C. Jiang: None. O. Lavrynenko: None. D. Motavalli: None. C. Musurakis: None. Z.H. Taxin: None. E.D. Rosen: Advisory Board Member; Self; Source Bio, Inc.. Consulting Fee; Self; Novartis Pharmaceuticals, Gensaic. M.S. Irwig: None. Background: Ectopic Cushing’s Syndrome (CS) makes up 9-18% of ACTH-dependent CS cases, of which fewer than 15% are attributed to pancreatic neuroendocrine tumors (1). Mixed neuroendocrine non-neuroendocrine neoplasms (MiNENs) are rare, aggressive carcinomas, often driven by high-grade neuroendocrine components, with a poor prognosis (2). Amphicrine neoplasms contain neuroendocrine and exocrine components in the same cell. Clinical Case: A 34 year-old woman with asthma, hypertension, and depression presented with new onset lower extremity edema, facial hirsutism, mood changes, polyuria and polydipsia. She had an elevated morning serum cortisol of 52 ug/dL (normal < 20) with plasma ACTH 42 pg/mL (normal < 50), 24-hour urine free cortisol of 1003 mcg (normal < 50), K+ of 2.6 mEq/L, and fasting glucose 164 mg/dL. CT showed multiple hepatic lesions, pulmonary nodules, a pancreatic tail lesion, and lymphadenopathy concerning for metastatic disease. Her adrenal glands were thickened bilaterally without nodules. A pituitary MRI was normal. These findings were concerning for ectopic CS. She was admitted due to rapidly developing symptoms. Potassium, insulin, sitagliptin, and prophylactic anticoagulation were started. Spironolactone and ketoconazole were initiated while awaiting biopsy results of liver and pancreas lesions. Osilodrostat was not available and a trial of metyrapone was poorly tolerated. The liver and pancreatic tail lesion biopsy revealed metastatic MiNEN with amphicrine features, of pancreatic origin, with Ki67 proliferation index of 70%. Section staining of pancreas and liver biopsies were negative for ACTH. A Ga-68 Dotatate scan showed minimal uptake, so octreotide was not prescribed. Palliative chemotherapy was planned. Although ketoconazole was titrated to 1600 mg/day, urine free cortisol levels and serum free cortisol levels did not reach target. Cushing disease was considered but not suspected, as ACTH levels remained modest despite a relative decrease in cortisol level. Given significant morbidity from uncontrolled hypercortisolism, and plans for urgent initiation of systemic chemotherapy, after multidisciplinary discussion the patient was treated with a surgical bilateral adrenalectomy. Post-operative morning serum cortisol measured 8.3 ug/dL. After one week, palliative chemotherapy with FOLFIRINOX (oxaliplatin, leucovorin, fluorouracil, and irinotecan) was initiated. She was discharged home on stress dose steroids with plan for taper. Conclusion: Ectopic ACTH secretion is a rare phenomenon, particularly when presenting with a rare case of metastatic pancreatic MiNEN with amphicrine features, associated with significant morbidity. To improve tolerance and survival of further treatment, early surgical bilateral adrenalectomy should be considered.

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

8673 Exploring A Case Study On Navigating Complexities In Endocrine Health And Reproductive Challenges

Abstract Disclosure: S.Y. Rizvi: None. E. Villanueva: None. Introduction: Polycystic ovary syndrome (PCOS) is a common endocrine disorder affecting many reproductive-age women, characterized by irregular menstrual cycles, hirsutism, and challenges with fertility. In this case study, we delve into the medical history of a 24-year-old female presenting with PCOS-related symptoms, hirsutism, and infertility, unraveling the multifaceted aspects of her healthcare journey. Case Description: This patient's diagnostic path began when she received an initial diagnosis of PCOS in her home country due to irregular menstrual periods and clinical signs of hirsutism. Her treatment included metformin, but it was interrupted when she relocated to the United States. Upon her arrival in the U.S., her medical course took an unexpected turn as further evaluations revealed elevated salivary cortisol (++), and a 24-hour urine free cortisol recorded 94.2 mcg (normal 4-50 mcg), indicating hypercortisolism. DHEAS: 730 mcg/dl (normal 18-390 mcg/dl), 17-hydroxyprogesterone: 508 (pre-midluteal: 431), free testosterone: 13 pg/ml (normal 0.1-6.4 pg/ml), with normal CBC, TSH, prolactin, and TPO. CT scan showed large 4.8 cm left adrenal mass. These findings indicated adrenal Cushing's syndrome, leading to referral to a tertiary care hospital's endocrine surgeon. Two months post-adrenalectomy, successful removal of the adrenal mass left the patient with relative adrenal insufficiency. Hydrocortisone replacement therapy was initiated, addressing Cushing's syndrome and revealing a potential factor contributing to infertility. Postoperatively, the patient entered the first trimester unexpectedly, complicating her case. Ensuring proper hydrocortisone levels became crucial for her well-being and the fetus, prompting a collaborative approach with obstetricians and maternal-fetal medicine specialists for optimal pregnancy care. Despite ongoing PCOS effects, including hirsutism, treatment options were limited by pregnancy constraints, deferring Aldactone due to its contraindication during pregnancy. Continuous monitoring included hormonal assessments, metabolic panels, and thyroid tests, aiming to balance adrenal insufficiency, PCOS symptoms, and a healthy pregnancy. Conclusion: This case emphasizes challenges in differentiating PCOS from adrenal Cushing's due to overlapping symptoms. Despite classic symptoms, the initial PCOS misdiagnosis highlights the need for vigilance and comprehensive diagnostics. Complex cases underscore the importance of individualized management and interdisciplinary collaboration. Positive outcomes in complex endocrine disorders and pregnancy are attainable through accurate diagnoses and tailored treatments. The case underscores the critical importance of meticulous evaluation for successful outcomes in challenging medical scenarios. Presentation: 6/3/2024

8233 Cushing Disease Presenting As Severe Persistent Hypokalemia

Abstract Disclosure: G. Palaguachi: None. A. Randhawa: None. M. Sattar: None. G. Mahajan: None. J. Karam: None. Introduction: The clinical presentation of Cushing Disease represents a wide spectrum of clinical and laboratory findings, including electrolyte derangements such as hypokalemia. In this case report, we describe a patient in whom the admission for severe persistent hypokalemia prompted the diagnosis of Cushing Disease. Clinical Case: A 35-year-old woman with history of type 2 diabetes, hypertension, and hyperlipidemia, presented to the Emergency Department with worsening bilateral lower extremities swelling, impairing her ability to walk, found to have severe hypokalemia with K level of 2.8 (3.4-4.8 mmol/L), in additional to right pubic rami fracture, left breast abscess, oral thrush, and severe hyperglycemia with HbA1C of 15.4%. Additional history was relevant for hirsutism, scalp hair thinning, weight gain, and amenorrhea of few months duration. Physical examination was significant for round face, thin scalp hair, oral thrush, facial hirsutism, central obesity, wide abdominal striae, onychomycosis, thin skin with multiple ecchymoses, bilateral lower extremity edema, and thin extremities. Her hypokalemia was resistant to therapy and K level remained in 3.2-3.5 mmol/L range on the third week of admission despite oral and intravenous potassium replacements and spironolactone high dose therapy at 100mg twice a day. Additional laboratory testing showed Cortisol 25.0 (6.70 - 27.60 ug/dL) and normal Aldosterone and renin levels. Given absence of otherwise clear etiology of hypokalemia, and presence of multiple features of Cushing’s syndrome, further inpatient evaluation included 24-hour Urine Free Cortisol level that came back at 2754 (3.5 - 45.0 mcg/24hour), 1 mg Dexamethasone Suppression Test Cortisol of 24.9 (6.70 - 27.60 ug/dL), ACTH of 151.0 (7.2 - 63.3 pg/mL), and 8 mg Dexamethasone Suppression Test Cortisol of 14.2 (6.70 - 27.60 ug/dL). MRI Pituitary showed a pituitary adenoma (0.7 x 0.3 cm) with cavernous sinus involvement. A diagnosis of Cushing disease was made and the patient underwent transsphenoidal surgery on the fourth week of hospital stay with diffuse ACTH staining of the tumor. Postoperatively, cortisol levels were not suppressed suggesting persistent disease, but hypokalemia resolved while on Spironolactone. Conclusion: This patient had several classical features of hypercortisolemia with associated hyperglycemia, recurrent infections, and bone fractures, however the finding that connected the dots and prompted establishing her diagnosis was her severe refractory hypokalemia. Although not a defining feature of Cushing Disease, and usually more pronounced with ectopic ACTH secretion, severe and/or persistent hypokalemia can be part of the presenting symptoms. This case demonstrates the importance of including Cushing Disease as part of the differential diagnosis of persistent hypokalemia in correlation with other clinical signs and diagnostics. Presentation: 6/2/2024

8411 Ectopic ACTH-dependent Cyclical Cushing’s Syndrome- the Art of Hide-and-seek

Abstract Disclosure: H. Mon: None. A. Kapoor: None. S. Qureshi: None. M. Martineau: None. K. Meeran: None. Case report: A 72-years-old lady was admitted with hypokalaemia, hyperglycaemia with metabolic alkalosis with background hypertension, type2 diabetes, osteoporosis and right-sided breast cancer treated with chemotherapy and radiotherapy 3years ago. She was previously seen in Endocrinology Clinic for similar episode and deemed not having Cushing’s or Conn’s syndrome on workup. During this admission, although there was no obvious Cushingoid appearance, there was refractory hypokalaemia. On further exploration, there were previous admissions with similar episodes in UK and in her home country, within the same year, a few months apart. Therefore, endocrinology workup was conducted for suspected cyclical Cushing’s syndrome. It demonstrated raised 24-hour urinary free cortisol of 5643 nmol/24hour (reference range 0-164 nmol/24hours), unsuppressed low dose dexamethasone suppression test with cortisol level of 800 nmol/L and increased ACTH level of 429 ng/L. MRI (pituitary) showed no pituitary lesion with probable empty sella and CSF filled. However, CT (thorax) showed enlarging lesion (previously from 1cm to 1.6cm) in the left lower lobe, concerning lung metastasis or primary lung malignancy. PET scan showed left lower lobe nodule having low-grade activity with likelihood of indolent malignancy and appearances of physiologic adrenal hyperplasia. Management: Given persistently high cortisol levels during admission with ongoing hyperglycaemia and refractory hypokalaemia, metyrapone was started and titrated accordingly. Her clinical condition including potassium and cortisol levels effectively responded to metyrapone. Gallium scan was booked for detail localization with ongoing lung MDT (multidisciplinary team meeting) and neuroendocrine tumour MDT.However, after starting metyrapone, she had type 1 respiratory failure, not responding to initial antibiotics. After excluding other possible respiratory aetiologies, empirical treatment for Pneumocystosis pneumonia (PCP) was initiated, after which blood test for Beta-D-glucan was found out to be significantly raised, supporting the presumptive diagnosis. Conclusion: Our case highlighted the following interesting points 1. diagnostic challenges, due to the fluctuating nature of cyclical Cushing’s syndrome, presenting with recurrent hypokalaemia. 2. the interesting nature of likely ACTH-dependent cyclical Cushing’s syndrome, progressing into florid Cushing’s syndrome, with efficacy to metyrapone 3. rare and compelling combination of 3 conditions of Cyclical Cushing’s syndrome, being ectopic ACTH-dependent and complicated by Pneumocystosis pneumonia (PCP). Presentation: 6/1/2024

8169 Bilateral Inferior Petrosal Sinus Sampling Using Metyrapone as a Reliable Alternative to Differentiate Between Cushing Disease and Ectopic ACTH Syndrome- A Single Center Experience

Abstract Disclosure: M. Azmath: None. S. Faisal: None. C. Caetano: None. T. Vedere: None. H. Aftab: None. B. Tendler: None. C. Malchoff: None. Introduction: Bilateral IPSS is a crucial test in accurately diagnosing Cushing disease (CD) and differentiating it from ectopic ACTH syndrome (EAS). [1] CRH stimulated IPSS is the gold standard technique but cannot be performed due to current shortage of CRH. Metyrapone is a safe and reliable alternative to CRH that can stimulate corticotrophs to secrete ACTH and hence used for IPSS. [2] We would like to share a single center experience using a novel low dose metyrapone protocol for IPSS that successfully helped differentiate CD and EAS. Methods: This was a retrospective analysis of patients presenting with Cushing syndrome. Initial diagnosis was confirmed based on standard testing including 24-hour urinary free cortisol (UFC), late night saliva concentrations (LNSC) and MRI. Metyrapone 500 mg every 4 hours for 3 doses was administered orally starting midnight prior to IPSS performed in the morning. ACTH levels drawn during initial evaluation for Cushing syndrome was compared to ACTH values post metyrapone from the peripheral vein sample to calculate a gradient. Ultimately, pituitary CD or EAS was confirmed based on cure following surgery and /or positive ACTH of tumor staining on pathology and/or concordant results with CRH stimulated IPSS. Results: There were 9 patients, out of which 5 had pituitary CD, and 4 had EAS. Pre ACTH levels for patients ranged between 14.5 and1164 pg/ml (normal reference range 6-50). Following metyrapone, ACTH level rose to 40-4705 pg/ml (normal reference range 6-50). The increase in ACTH levels ranged from 81-547% pre and post metyrapone. An average of 5-6 ACTH samples were drawn during IPSS. Catheterization was successful in all patients and was confirmed by IR. The mean central to peripheral (C/P) ACTH ratio for patients with confirmed CD was 20.53 in comparison with a ratio of 1.34 in patients with EAS. IPSS was confirmed to be diagnostic for pituitary CD if the peak ratio after metyrapone administration was more than 3. No adverse effects were observed during or after the procedure and no hospitalization was required pre-procedure. Discussion: We present single center experience with a novel low dose metyrapone protocol for IPSS. Our protocol was successful in increasing ACTH/cortisol secretion by tumorous cells as evidenced by increase in ACTH levels post metyrapone. It is an easy oral protocol which proved to be safe without the risk for adrenal insufficiency that can occur with higher doses. It also mitigates the small thromboembolic risk that can occur with DDAVP administration. A clear distinction in C/P ACTH ratios was observed in patients with CD versus EAS as early as the 3rd sample. In conclusion, our low dose metyrapone protocol was safe and reliable in accurately differentiating between CD and EAS in small sample of patients at our institution. Presentation: 6/1/2024

12215 A Rare Cause Of Cushing's Syndrome: Acth-producing Pheochromocytoma

Abstract Disclosure: S. Jimenez Salazar: None. C. Aguilar Londoño: None. N. Aristizabal Henao: None. N. Buitrago Gómez: None. S. Saldarriaga Betancur: None. D.L. Beltran: None. J.L. Torres: None. Background: Cushing's syndrome is a severe endocrine disorder caused by chronic, autonomous, and excessive cortisol secretion. Among all causes, ectopic ACTH production continues to be one of the most challenging diagnoses. Rarely, pheochromocytomas secrete hormones other than catecholamines, including ACTH and CRH. The secretion of these hormones can alter the clinical presentation and make the diagnosis more difficult. Clinical Case: A previously 60-year-old woman with hypertension and no other relevant medical history presented with unintentional weight loss of 16 kg and constipation. Physical examination revealed a moon face, supra-labial and chin facial hair. Laboratory studies demonstrated hypokalemia (potassium 3.02 mEq/L, n: 3.5-5 mEq/L) and newly diagnosed diabetes (HbA1c 8.69%, n <5.7% and fasting glucose 282 mg/dL, n: 70-100 mg/dL), both difficult to control. Considering the clinical and biochemical findings, hypercortisolism was evaluated by measuring 24-hour urinary free cortisol (1853 mcg/24h, n: 4-176 mcg/24h), nocturnal serum cortisol (40.9 mcg/h, n:<7.5 mcg/h), and 1 mg dexamethasone suppression test (43.1 mcg/h, n:<1.8 mcg/h), confirming cortisol excess. ACTH was measured (95 pmol/mL, n: 4.7-48.5 pg/mL) suggesting ACTH-dependent cause, leading to a dynamic test with high doses of dexamethasone (8mg) with suppression greater than 50% and normal pituitary MRI, both compatible with an extrahypophyseal cause. Peripheral imaging evaluation was conducted with cervical-thoracic CT scan and abdominal MRI confirming the presence of a complex adrenal mass. Among adrenal hyperfunction studies, primary hyperaldosteronism was ruled out (Aldosterone 9.8 ng/dL, n: 1-32 ng/dL and Plasma Renin Concentration 1.1 ng/dL, n: 0.16-2.3 ng/dL), and pheochromocytoma was confirmed (Normetanephrines 2725.4 mcg/24h, n: 0-600 mcg/24h and Metanephrines 1550 mcg/24h, n: 0-350 mcg/24h). Considering the described adrenal lesion with biochemical behavior, the possibility of ectopic ACTH production from pheochromocytoma was studied. Therefore, ketoconazole 200mg every 8 hours was initiated for hypercortisolism control and adrenergic blockade protocol as pre-surgical preparation for adrenalectomy. Potassium levels (4.48 mEq/L, n: 3.5-5 mEq/L) and glucose levels (93 mg/dL, n: 70-100 mg/dL) normalized after the procedure. Pathology and immunohistochemistry confirmed the diagnosis of an ACTH-producing pheochromocytoma. Conclusion: Pheochromocytoma is a rare cause of ectopic ACTH secretion where pre-surgical management of catecholamine excess and hypercortisolism is crucial, and adrenalectomy is often curative. Reference: (1) Elliott PF, Berhane T, Ragnarsson O, Falhammar H. Ectopic ACTH- and/or CRH-Producing Pheochromocytomas. J Clin Endocrinol Metab 2021;106:598-608. Presentation: 6/1/2024

5165 Cushing’s Disease And Primary Aldosteronism Confounded By A Non-functioning Solitary Adrenal Incidentaloma

Abstract Disclosure: J.G. Friedman: None. W. Huang: None. Background: Adrenal incidentalomas are common, affecting ∼2% of the general population. The presence of adrenal incidentaloma necessitates biochemical testing for hypersecretion, however hypercortisolism and/or hyperaldosteronism may not necessarily originate from the nodule that prompted the initial workup. Clinical Case: A 53-year-old man with a history of obesity and hypertension was referred for workup of a 2.4 x 1.4 cm R adrenal nodule that was incidentally discovered on an abdominal CT to rule out pancreatitis. He was noted on examination to have some Cushingoid features. He was on three antihypertensives (amlodipine 10 mg, carvedilol 50 mg, and spironolactone 50 mg) with adequate blood pressure control and no hypokalemia. He denied spells nor exogenous steroid exposure. Initial testing for hypersecretion showed an elevated cortisol 8.7 ug/dL (<1.8) after 1 mg dexamethasone with adequate dexamethasone level, aldosterone concentration (PAC) 9 ng/dL (3-16), plasma renin activity (PRA) 0.7 ng/mL/h (0.25-5.82), potassium of 3.8 mmol/L (3.5-5.1), and normal plasma metanephrines. Further testing revealed elevated 24-hour urinary free cortisol 81.3 mcg/24h (4-50) and elevated late night salivary cortisol 0.10 and 0.13 mg/dL (<0.09). Baseline 8 AM ACTH was not suppressed 16.3 pg/mL (7.2-63.6). DDAVP stimulation resulted in an increase in cortisol and ACTH suggestive of Cushing’s disease, which was confirmed by inferior petrosal sinus sampling (IPSS). Pituitary MRI showed a 3.6 mm L-sided microadenoma. He underwent transsphenoidal resection with pathology consistent with an ACTH-staining pituitary adenoma. Immediate post-op cortisol nadir was 4.9 ug/dL. A few weeks after surgery, he underwent retesting for primary aldosteronism notable for PAC 14 ng/dL, PRA 0.58 ng/mL/h, and K 4.0 mmol/L. After oral salt loading, 24-hour urine aldosterone was 14.4 mcg/24h (<12) with urine sodium 247 mmol/L/24h (>200). He completed AVS which lateralized to the L adrenal gland despite a R adrenal nodule. He underwent L adrenalectomy with significant improvement in blood pressure which is now well-controlled on carvedilol monotherapy with normalization of PRA to 1.94 ng/ml/h. The R adrenal nodule remains stable in size and appearance on follow up imaging. Conclusion: The presence of an adrenal adenoma with concomitant biochemical evidence of hormonal excess cannot inherently be attributed to nodular autonomous function without further workup. Other hormonal assessment including ACTH level and localization studies are necessary prior to any surgical procedure to avoid missed diagnoses of Cushing’s disease and contralateral primary aldosteronism in the presence of a non-functioning adrenal nodule. Presentation: 6/1/2024

7385 Prevalence of Central Hypothyroidism in Cushing Syndrome and Thyroid Function Tests After Cushing Treatment

Abstract Disclosure: T. Kunavisarut: None. A. Sriwijitkamol: None. Cushing syndrome can be associated with thyroid dysfunction. We investigated the association between Cushing syndrome and thyroid dysfunction. We conducted a retrospective study at Siriraj Hospital in Thailand and analyzed thyroid function tests in 80 Cushing's patients. The inclusion criteria were patients diagnosed with Cushing syndrome with thyroid function tests recorded at diagnosis of Cushing syndrome. Patients who had an abnormal thyroid function test at diagnosis of Cushing syndrome must have a thyroid function test after treatment of Cushing syndrome. Of the 80 patients, sixty-five patients (81.2%) had normal thyroid function at diagnosis, 12 patients (15%) had central hypothyroidism and three patients (3.8%) had subclinical hyperthyroidism.Interestingly, among 12 patients who had central hypothyroidism, eight patients (66.7%) were diagnosed with Cushing disease. Three patients (25%) were diagnosed with adrenal Cushing syndrome and one patient (8.3%) was diagnosed with ectopic Cushing syndrome. This finding suggested that central hypothyroidism may not be exclusively due to the mass effect of the pituitary tumor on the normal pituitary because adrenal Cushing syndrome and ectopic Cushing syndrome can also cause central hypothyroidism. Among 12 patients with central hypothyroidism at diagnosis of Cushing syndrome, nine patients (75%) normalized their thyroid function after remission of Cushing syndrome without Levothyroxine replacement. Moreover, patients with central hypothyroidism had significantly higher median 24-hour urine-free cortisol levels than euthyroid patients (1030.5 ug/day vs. 404.5 ug/day, p=0.017), indicating a potential correlation between cortisol excess and low FT4 levels. These findings suggest that hypercortisolism in Cushing syndrome can suppress the hypothalamic-pituitary-thyroid axis, but this suppression is often reversible with successful Cushing's treatment. This study highlights the importance of central hypothyroidism, which can occur in all types of Cushing syndrome. If the patients did not have hypothyroid symptoms, Levothyroxine replacement may not be necessary. For patients who already received Levothyroxine and had normal thyroid function tests, Levothyroxine can be carefully tapered and potentially discontinued because successful Cushing syndrome treatment can ultimately normalize thyroid function tests. Presentation: 6/1/2024

6568 A Novel Case of Liddle Syndrome in Siblings: Insights into a Rare Genetic Mutation

Abstract Disclosure: A.B. Humrickhouse: None. M. Peltsverger: None. Introduction: Liddle syndrome (LS) is an inherited form of hypertension caused by a mutation in the epithelialsodium channel (ENaC). This condition is characterized by hypertension (HTN), hypokalemia,hyporeninemia, and metabolic alkalosis, although clinical presentation can vary. Asymptomaticearly-onset HTN is common, and if left undiagnosed, it can lead to advanced renal disease,cardiovascular complications, stroke, and even sudden death. Treatment typically involves theadministration of ENaC blockers such as amiloride and triamterene. We present a novel case ofLS in two siblings resulting from a missense mutation in the SCNN1B gene. Case Presentation: The patient is a 24-year-old Hispanic female who presented for evaluation of poorly controlledHTN and severe hypokalemia of 2.9 mmol/L during the first trimester of pregnancy. She wasdiagnosed with HTN at age eighteen. The family history was notable for resistant HTN in herfather and younger brother. Biochemical evaluation revealed normal plasma-free metanephrinesand 24-hour urine-free cortisol. Low plasma renin activity (0.530 ng/mL/hr) and aldosterone(<1.0 ng/dL) were detected on multiple tests. The urine-free cortisol-to-cortisone ratio was <0.5,excluding the diagnosis of apparent mineralocorticoid excess syndrome. The diagnosis of LS wasconfirmed by genetic analysis, which identified a novel heterozygous mutation, c.1859 A>G(Tyr620Cys), in the SCNN1B gene, which had not been reported in the literature to date. Thesame mutation was identified in her brother. The patient was treated with a high dose ofamiloride (15 mg daily), which controlled her HTN and hypokalemia throughout her pregnancy. Discussion: LS is an autosomal dominant disorder with genetic heterogeneity. It is characterized by HTN,low plasma aldosterone and renin activity, and increased potassium excretion. This leads tohypokalemia and metabolic alkalosis. LS is caused by germline mutations found in theSCNN1A, SCNN1B, and SCNN1G genes, which encode the alpha, beta, and gamma subunits ofthe ENaC channel. These mutations lead to enhanced sodium reabsorption in the kidneys,independent of aldosterone. Our patient was diagnosed with hypertension at the age of 18.However, the diagnosis of LS was not made until six years later when she presented during herfirst trimester of pregnancy. Treatment with amiloride effectively controlled her hypertension andhypokalemia, which allowed her to deliver a healthy child. Amiloride was also prescribed for thepatient's brother. A combination of biochemical analysis and genetic testing enables a betterunderstanding of the various clinical presentations, ensuring appropriate treatment andprevention of end-organ damage. Genetic counseling is essential for families affected by LS. Presentation: 6/1/2024