Adrenal Enlargement Research Articles

Hypercorticosteronemia induces hyperphagia and obesity in human growth hormone transgenic rats

Hyperphagia and subsequent obesity are important public health issues due to the associated risks of developing serious diseases. Certain stressors play a major role in the development of hyperphagia. In previous studies, we established a line of human growth hormone transgenic (TG) rats that exhibit hyperphagia and obesity from a young age. We recently demonstrated that voluntary running on a running wheel alleviates hyperphagia in TG rats. Wheel running provides environmental enrichment for rodents and plays a role in relieving stress. These results suggested that stress is the major factor inducing hyperphagia in TG rats. Thus, in the present study, we evaluated activation of the hypothalamus–pituitary–adrenal axis. TG rats showed bilateral enlargement of adrenal glands and hypercorticosteronemia, although their hypothalamic CRH level was comparable to that of wild-type (WT) rats. The ACTH-immunoreactive area was larger and the serum ACTH level in the dark phase was higher in TG rats than in WT rats. Adrenalectomy reduced the food intake of TG rats to a level comparable to that in WT rats, and supplying glucocorticoids recurred hyperphagia in TG rats. These treatments did not affect the food intake of WT rats. Rearing TG rats under group housing prevented hyperphagia and hypercorticosteronemia. These results suggest that glucocorticoids are appetite stimulants, and that TG rats exhibit increased sensitivity to the appetite-stimulating effect of glucocorticoids.

7404 Evaluation Of Cortisol Reserve And Adrenal Imaging In Patients With Graves’ Disease Before And Six Months After Treatment

Abstract Disclosure: P. Sharma: None. S. Mir: None. S. Mohd Patto: None. A.H. Bhat: None. B. Dar: None. M. Bhat: None. Introduction: There is scarcity of data regarding the effect of thyrotoxicosis on cortisol metabolism and adrenal gland size. An increase in cortisol metabolism can deplete the functional reserve of adrenal cortex and lead to adrenocortical insufficiency even when there is no pre-existing Addison's disease. In developing countries patients with Graves’ disease present in advanced states of thyrotoxicosis. Besides they are also exposed to a variety of environmental stresses such as recurrent febrile illnesses, salt, and water loss due to manual labour in hot and humid climates etc., which can precipitate an adrenal crisis in the presence of compromised adrenal reserve. So present study was undertaken to assess cortisol reserve and adrenal gland size in patients with treatment naive Graves' disease. Objectives- The present study, was undertaken to assess cortisol reserve and adrenal imaging in patients with treatment naive Graves' disease. Specific information in this regard would help alert physicians dealing with clinical thyrotoxicosis in developing countries of tropics to the possibility of co-existing adrenal decompensation and adopt appropriate life saving measures promptly. Material & Methods: We examined 38 treatment-naive Graves' Disease patients at GMC, SSH, Srinagar, Kashmir, INDIA. Basal cortisol and cortisol response to ACTH were measured before and after six months of treatment, alongside adrenal CT imaging. Results: In hyperthyroid state, Graves' patients exhibited significantly lower basal cortisol compared to euthyroid and healthy controls (306 vs. 410 vs. 421 nmol/l, p < 0.05). 23.6% patients had subnormal cortisol response to ACTH(250ug). Those with T3 ≥ 400 ng/dl had lower cortisol response (560±133 nmol/l) and delta cortisol response than T3 < 400 ng/dl (724 ± 294 nmol/l, 213+/-73 vs. 428+/-265 nmol/l). After achieving euthyroid state, cortisol levels improved significantly (410±213 nmol/l vs. 306 ± 103 nmol/l, p < 0.05). Adrenal CT scans in 34 patients was done out of which 19 showed statistically significant increases in gland thickness, width, and AP diameter compared to controls (p < 0.01, p < 0.05. Repeat CT in 26 patients demonstrated resolution of hyperplasia (p < 0.05). Conclusion: Treatment-naive Graves' disease patients have compromised adrenocortical reserve and adrenal gland enlargement. Adrenal changes are reversible after achieving euthyroid state. These findings support steroid supplementation in impending thyrotoxic crisis and highlight a unique feature of reversible adrenal gland enlargement in this context. Keywords: Graves’ Disease, Adrenal hyperplasia, Cortisol reserve. Presentation: 6/3/2024

12572 Incidental Adrenal Enlargement On Ct Scan In South Brooklyn Health, How Often Is It Functional?

Abstract Disclosure: R. Ruggiero: None. N. Simon: None. Background: Incidental findings of adrenal hyperplasia are increased due to the widespread rise in cross sectional imaging, as well as improvement of imaging modalities. There is a lack of literature reporting on the prevalence of incidental adrenal hyperplasia. One study reported a prevalence of 11.3%. Adrenocortical hyperplasia can result from endocrine disorders such as ACTH dependent and independent Cushing syndrome, primary aldosteronism, Multiple Endocrine Neoplasia type 1, and congenital adrenal hyperplasia. Other reported causes are radiographic adrenal enlargement of unknown cause and without clinical or biochemical manifestations, inflammation, neoplasms, and depression. Most cases are a radiographic finding with no clinical significance. One study reported that 69.23% of cases were nonfunctional. There are currently no guidelines in place for biochemical evaluation of incidental adrenocortical hyperplasia. Patients are typically referred to endocrinology services. Objective: The purposes of this study was to: 1. Evaluate the number of patients referred to endocrinology clinic for incidental abnormal adrenal imaging. 2. Examine the percentage of abnormal adrenal imaging findings on CT scan, in particular adrenal hyperplasia, that are hormonally active. Methods: This was a retrospective study of patients who were referred to endocrinology clinic or electronic endocrine consult for incidental abnormal adrenal imaging, excluding those with clear diagnosis of masses, nodules, adenomas, or cysts. Data collected included demographics, type of study imaging and radiologist reader, hormonal studies, comorbid conditions such as diabetes mellitus, hypertension, obesity, osteoporosis, as well as visit type to endocrinology service (e-consult vs in person). Results: The total number of consults referred to endocrinology during this period was 138. Due to repeat referral or having an adrenal pathology other than hyperplasia, 83 patients were excluded from analysis. There were 55 patients with isolated adrenal hyperplasia, 86% of whom were Caucasian, 11% Hispanic, and 78% of patients were female. Median age 63 years old. Hypertension was noted in 69% of patients, 36% had diabetes mellitus or dysglycemia, 36% were obese, and 1.8% had osteoporosis. Imaging reading was performed by 3 radiologists, 75% of cases reported by one reader. Only 5% of referrals were answered as an e-consult. About 27% of patients did not show up to establish care. Hormonal workup was completed by 60% of the patients, with 16 % having abnormal findings. One patient required confirmatory workup. No patients required treatment. Conclusion: Adrenal Hyperplasia is often an incidental radiologic finding, that can be reader dependent. Most cases are nonfunctioning without abnormal findings on hormonal workup. E-Consultation can be an efficient tool to help PCP and reduce endocrine clinic visits. Presentation: 6/1/2024

8034 Putting the Pieces Together: Carney Complex, A Hyper-Rare Congenital Neoplastic Syndrome

Abstract Disclosure: G. Fontanazza: None. A.R. Conforti: None. K. Bird: None. M. Caplan: None. Intro: Carney complex (CNC) is an autosomal dominant disorder characterized by multisystem neoplasia that primarily affects the thyroid, pituitary, and adrenal glands. Its prevalence is not well established, as only 750 cases have been reported worldwide. This condition arises when an inactivating PRKAR1A gene mutation results in dysregulated cell proliferation and tumorigenesis. Complications include the potential for malignant transformation and systemic manifestations, necessitating comprehensive management and ongoing surveillance of disease progression. Case: The patient is a 58-year-old woman who initially presented as a teenager with complaints of hirsutism, truncal obesity, and violaceous abdominal striae. Initial workup revealed a low-dose dexamethasone suppression test that resulted in a non-suppressed cortisol levels. She also had undetectable adrenocorticotropic hormone (ACTH) levels. Imaging revealed no pituitary masses and demonstrated slight bilateral adrenal enlargement without adenomas. Despite these results, she was empirically treated for presumed pituitary-dependent Cushing's disease and received external beam radiation. Despite treatment, she continued to have episodes of hypercortisolism that were apparent clinically and biochemically. Over time, she developed a cardiac myxoma with six cerebrovascular accidents and multiple benign tumors. As an adult, she underwent extensive endocrine evaluation, which revealed urine cortisol excretion that paradoxically rose in response to dexamethasone. ACTH levels were always undetectable, even when she was significantly hypercortisolemic. Genetic testing revealed a homozygous mutation in the melanocortin-2 receptor (MC2R). Accordingly, she elected to have a bilateral adrenalectomy and was started on hydrocortisone and fludrocortisone. Discussion: The patient exhibited ACTH-independent micronodular adrenal hyperplasia and its most frequent variant, primary pigmented nodular adrenocortical disease. Bilateral pigmented nodular hyperplasia is a finding which can occur in association with CNC and cause episodic hypercortisolism. These patients have been shown to respond to dexamethasone with a paradoxical increase in glucocorticoid excretion. While management requires ongoing surveillance, this patient had not been diagnosed until later in life and did not have regular screening. When speculating on the late detection, her story reflects the parable of the blind men and the elephant: endocrinology managed Cushing's disease, cardiology managed atrial myxoma, and oncology managed osteochondromyxomas. Limited perspective with specialized management and an inability to see the whole picture led to prolonged diagnosis with unfortunate sequelae. This report encourages physicians to develop perspective awareness and to consider the entire picture when treating patients. Presentation: 6/2/2024

Alterations in the Hypothalamic-Pituitary-Adrenal Axis as a Response to Experimental Autoimmune Encephalomyelitis in Dark Agouti Rats of Both Sexes.

Multiple sclerosis (MS) is a chronic inflammatory disease that affects the central nervous system, usually diagnosed during the reproductive period. Both MS and its commonly used animal model, experimental autoimmune encephalomyelitis (EAE), exhibit sex-specific features regarding disease progression and disturbances in the neuroendocrine and endocrine systems. This study investigates the hypothalamic-pituitary-adrenal (HPA) axis response of male and female Dark Agouti rats during EAE. At the onset of EAE, Crh expression in the hypothalamus of both sexes is decreased, while males show reduced plasma adrenocorticotropic hormone levels. Adrenal gland activity is increased during EAE in both males and females, as evidenced by enlarged adrenal glands and increased StAR gene and protein expression. However, only male rats show increased serum and adrenal corticosterone levels, and an increased volume of the adrenal cortex. Adrenal 3β-HSD protein and progesterone levels are elevated in males only. Serum progesterone levels of male rats are also increased, although testicular progesterone levels are decreased during the disease, implying that the adrenal gland is the source of elevated serum progesterone levels in males. Our results demonstrate a sex difference in the response of the HPA axis at the adrenal level, with male rats showing a more pronounced induction during EAE.

Uncommon adrenal rest tumors and massive adrenal enlargement in adult with congenital adrenal hyperplasia mimicking metastasis from pleomorphic sarcoma

BackgroundCongenital adrenal hyperplasia (CAH) encompassed a bunch of autosomal recessive disorders characterized by impaired cortisol levels due to an enzymatic deficiency in steroid synthesis. In adult male patients with CAH, a frequent complication related to poor disease control is the development of ectopic adrenocortical tissue in the testes, named testicular adrenal rest tumors (TART). Conversely, ovarian adrenal rest tumors (OART) in females are extremely rare and adrenal rests in sites other than gonads are so uncommon to have been described only few times in literature.Case presentationWe report a case of a male patient with untreated CAH and oncologic history of pleomorphic sarcoma who presented with massive bilateral adrenal enlargement and adrenal rest tumors in peri-lumbar and peri-cecal sites, which mimicked metastasis from sarcoma.ConclusionsThe development of massive adrenal enlargement and ectopic adrenal rest tumors in sites other than gonads, even if very uncommon, should be suspected in patients with CAH and prolonged periods of undertreatment.

MRI-based adrenal gland volume is associated with cardiovascular alterations in individuals without prior cardiovascular disease

Aim of this study was to analyse the associations of cardiovascular health and adrenal gland volume as a rather new imaging biomarker of chronic hypothalamic–pituitary–adrenal (HPA) axis activation. The study population originates from the KORA population-based cross-sectional prospective cohort. 400 participants without known cardiovascular disease underwent a whole-body MRI. Manual segmentation of adrenal glands was performed on VIBE-Dixon gradient-echo sequence. MRI based evaluation of cardiac parameters was achieved semi-automatically. Cardiometabolic risk factors were obtained through standardized interviews and medical examination. Univariate and multivariate associations were derived. Bi-directional causal mediation analysis was performed. 351 participants were eligible for analysis (56 ± 9.1 years, male 58.7%). In multivariate analysis, significant associations were observed between adrenal gland volume and hypertension (outcome hypertension: Odds Ratio = 1.11, 95% CI [1.01, 1.21], p = 0.028), left ventricular remodelling index (LVRI) (outcome LVRI: β = 0.01, 95% CI [0.00, 0.02], p = 0.011), and left ventricular (LV) wall thickness (outcome LV wall thickness: β = 0.06, 95% CI [0.02, 0.09], p = 0.005). In bi-directional causal mediation analysis adrenal gland volume had a borderline significant mediating effect on the association between hypertension and LVRI (p = 0.052) as well as wall thickness (p = 0.054). MRI-based assessment of adrenal gland enlargement is associated with hypertension and LV remodelling. Adrenal gland volume may serve as an indirect cardiovascular imaging biomarker.

A case of enlarged adrenal glands in fetus as a prenatal marker of congenital adrenal hyperplasia (CAH)

A case of enlarged adrenal glands in fetus as a prenatal marker of congenital adrenal hyperplasia (CAH)

Adrenocortical hemorrhage following intravenous tetracosactide in a dog with hypercortisolism.

To summarize findings from a case of adrenocortical hemorrhage following tetracosactide injection during ACTH stimulation testing for monitoring of trilostane therapy in a dog. A 12-year old neutered male dog with adrenal-dependent hypercortisolism. 4 hours after ACTH stimulation testing, the patient developed vomiting, lethargy, and abdominal pain. Abdominal ultrasound was performed before and after an ACTH stimulation test. Following ACTH stimulation testing, there was progressive bilateral adrenal enlargement and free abdominal fluid had developed. This was considered to be caused by adrenocortical inflammation and hemorrhage secondary to the synthetic ACTH analog, tetracosactide, used during stimulation testing. A resting cortisol performed 5 hours after tetracosactide injection was not consistent with iatrogenic hypoadrenocorticism. The patient was managed with analgesia, IV fluids, and corticosteroids and made a full recovery. To the authors' knowledge, this was the first reported case of adrenocortical hemorrhage following administration of a synthetic ACTH analog in a dog. This should be considered as a rare potential complication of ACTH stimulation testing.

Bilateral adrenal histoplasmosis in a Malaysian tertiary hospital: Report of four cases

Rationale: Adrenal histoplasmosis can present as bilateral adrenal enlargement with constitutional symptoms and/or adrenal insufficiency. Often these patients are initially investigated as secondary adrenal metastases before eventually their diagnosis established by histopathological examination of the adrenal tissues. Patients concerns: We report 4 cases of patients aged 55-78 who presented with hypocortisolism and bilateral adrenal masses. Diagnoses: Bilateral adrenal histoplasmosis. Interventions: Three patients received antifungal treatment for at least one year while 1 patient passed away before the initiation of antifungal treatment. Outcomes: Two patients’ adrenal function recovered not requiring any steroid replacement, while 1 patient still requires long-term steroid replacement. Lessons: Adrenal histoplasmosis should be excluded in patients from endemic areas presenting with bilateral adrenal masses and adrenal insufficiency. Usually patients have an exposure to bird droppings, bat guano or soil contaminated with histoplasmosis fungi. Histopathological examination of biopsied adrenal tissues is still the gold standard investigation as serology and molecular diagnostic methods are still not widely available in most centers in Malaysia.

Beyond the three P's: adrenal involvement in MEN1.

Adrenal lesions (ALs) are often detected in patients with multiple endocrine neoplasia type 1 (MEN1). However, they are not well described in MEN1, making their clinical management unclear. This study examined the prevalence and outcomes of ALs found in MEN1. We performed a retrospective chart review of patients diagnosed with MEN1 from 1990 to 2021. ALs were diagnosed using abdominal or thoracic imaging and classified as being unilateral or bilateral, having single or multiple nodules, and as having diffuse enlargement or not. Measurable nodular lesions were analyzed for their size and growth over time. Patients' clinical and radiographic characteristics were collected. We identified 382 patients with MEN1, 89 (23.3%) of whom had ALs. The mean age at detection was 47 ± 11.9 years. We documented 101 measurable nodular lesions (mean size, 17.5 mm; range, 3-123 mm). Twenty-seven nodules (26.7%) were smaller than 1 cm. Watchful waiting was indicated in 79 (78.2%) patients, of whom 28 (35.4%) had growing lesions. Functional lesions were diagnosed in 6 (15.8%) of 38 that had functional work-up (diagnoses: pheochromocytoma (n = 2), adrenocorticotropic hormone-dependent hypercortisolism (n = 2), hyperandrogenism (n = 1), hyperaldosteronism (n = 1)); surgery was indicated for 5 (83.3%; n = 12 nodules), 2 of whom had bilateral, diffuse adrenal enlargement. Two patients were diagnosed with adrenocortical carcinoma and two with neoplasms of uncertain malignant potential. Radiographic or clinical progression of ALs is uncommon. Malignancy should be suspected on the basis of a lesion's growth rate and size. A baseline hormonal work-up is recommended, and no further biochemical work-up is suggested when the initial assessment shows nonfunctioning lesions.

Histoplasmosis: A Mimicker of Granulomatosis with Polyangitis

A 31-year-old male from the southern part of India with no known comorbidities presented with painful oral erosions over his palate following a dental procedure. Over 2 months, it progressed to the desquamation of blackish necrotic skin, gingival hypertrophy associated with intermittent fever and odynophagia. He had elevated acute-phase reactants. Biopsy of the gingiva showed necrotising vasculitis. ANCA was weakly positive for the cytoplasmic pattern by immunofluorescence. The HRCT chest showed a single cavitating nodule in the right upper lobe and a non-cavitary nodule in the left upper lobe with right maxillary sinus thickening. With the above clinical and biopsy findings, granulomatosis with polyangiitis was the first consideration. He was referred to our centre since the oral lesions did not improve and nodular swellings developed on the palate. The examination showed cervical lymphadenopathy, which was subjected to an excision biopsy. It showed extensive areas of necrosis with karyorrhectic debris and numerous intracellular and extracellular round-to-ovoid spore-like structures. Special stains were positive for histoplasmosis. Abdomen imaging showed adrenal enlargement. Cultures were negative, which could be due to the fact that he was on multiple medications. He was treated with amphotericin and itraconazole. His symptoms improved. But later, he had worsening clinical parameters suggestive of a progressive disseminated form of histoplasmosis. In spite of aggressive efforts, he couldn’t be resuscitated owing to the dissemination of the organism. Even though considered to be more common in immunosuppressed individuals in nonendemic areas, it is reported in immunocompetent individuals as well and should be strongly suspected if the clinical picture fits so for early diagnosis and aggressive management to prevent fatal complications. There have been only fewer case reports of histoplasmosis from the southern part of India. ANCA is only rarely reported false positively in histoplasmosis.

FRI212 Adrenalitis Caused By Proteus Mirabilis In An Immunocompetent Patient

Abstract Disclosure: J.O. Abdelkarim: None. U. Tarabichi: None. M. Jakoby: None. Infectious adrenalitis with Mycobacterium tuberculosis remains the leading cause of primary adrenal insufficiency in developing countries, but the incidence of adrenalitis from infection with other bacterial species is quite low. We present a patient with radiographic evidence of adrenalitis during an infection with Proteus mirabilis that resolved after antimicrobial treatment.An 86-year-old male with an indwelling Foley catheter presented to the hospital for evaluation of abdominal pain and distension. The patient was afebrile and normotensive. Examination was notable for a distended bladder and obstructed urinary catheter. Computed tomography (CT) revealed a dense right lower lobe infiltrate and bilaterally enlarged, hypointense adrenal glands with irregular margins. Radiographic findings were new compared to a CT scan obtained approximately 10 weeks before admission to hospital. Turbid and malodorous urine was drained after replacement of the patient’s urinary catheter, and urine culture grew > 105 CFU/mL Proteus mirabilis. Antibiotics were dosed before blood cultures were drawn, and no organisms were grown from blood cultures. Since there was no clinical or biochemical evidence (e.g. hyponatremia or hyperkalemia) of primary adrenal insufficiency, an ACTH stimulation test was deferred. The patient responded well to replacement of his urinary catheter and antibiotics and was discharged to his extended care facility three days later. A CT scan obtained 10 days after treatment showed resolution of the changes to the patient’s adrenal glands observed on admission imaging.The radiographic changes are most plausibly due to P. mirabilis bacteremia and adrenalitis. The patient had urine culture confirmed infection with P. mirabilis and radiographic evidence of disseminated infection in the right lung and adrenal glands. Adrenal enlargement is well described in cases of acute M. tuberculosis adrenalitis, and radiographic changes of adrenalitis resolved after successful treatment of the patient’s infection. P. mirabilis has been documented as an etiology of Waterhouse-Friderichsen syndrome and cultured from an adrenal abscess. Blood cultures in this case were almost certainly negative due to timing relative to initial antibiotic doses. Injury to the adrenals in bacterial adrenalitis is thought to occur due to multiple mechanisms including direct infection of the glands, endotoxemia, vasculitis, and disseminated intravascular coagulation (DIC). Hemorrhage appears to occur in about 60% of cases. Elevated ACTH level is postulated as a factor predisposing to adrenal hemorrhage, and this prompted deferral of stimulation testing to evaluate adrenal function since there was no clinical evidence of primary adrenal insufficiency. Early management of the patient’s infection likely prevented the occurrence of adrenal insufficiency and deterioration of his clinical status. Presentation: Friday, June 16, 2023

FRI229 Bilateral Adrenal Hemorrhage Following Deep Tissue Body Massage

Abstract Disclosure: M. Antony: None. S. Gundlapally: None. P. Russell: None. S. Storm: None. S. Patel: None. V. Verma: None. R. Kant: None. Introduction: Adrenal hemorrhages have been reported in patients undergoing ACTH stimulation test using bovine- source ACTH. It can also be seen in severe stressful situations such as septicemia and extensive thermal burns due to sudden and profound adrenocortical stimulation by endogenous ACTH. Idiopathic spontaneous adrenal hemorrhage and motor vehicle accident induced adrenal hemorrhage have also been rarely reported. Coagulopathy, thromboembolic disease, and postoperative state are 3 major risk factors associated with bilateral adrenal hemorrhage. We present a unique case of a patient who presented with bilateral adrenal hemorrhage following deep tissue body massage. Clinical Case: A 44-year-old male with a past medical history of recurrent pulmonary embolism (PE) and deep venous thrombosis (DVT) due to lupus anticoagulant disorder status-post inferior vena cava (IVC) filter and recent change from Coumadin to Xarelto presented to the ED with a chief complaint of right upper quadrant (RUQ) pain extending to the right flank. Patient experienced unrelenting pain after a deep-tissue massage one week prior to presentation. Patient was seen two days prior to admission for similar complaints, but was discharged after reassuring CT abdomen/pelvis, ultrasound, and labs. He returned after pain worsened, and a repeat CT showed right adrenal hemorrhage and enlargement. Patient denied all other symptoms except pain. Vitals included BP of 144/84 mmhg, RR 20/min, HR 89/min, temp of 98.1°F, and SpO2 of 99%. Physical exam was notable only for RUQ pain and right CVA tenderness. Initial labs showed normal CBC including HGB 13.6g/dL (13-17 g/dL), HCT 37.5% (38.5-52%), and PLT 181K/microL (150-450 K/microL). Glucose 120mg/dL (70-99mg/dL), Na 129mmol/L (135-146 mmol/L), K 3.3mmol/L (3.5-5.2 mmol/L), Cl 87mmol/L (98-107 mmol/L), anion gap 17mmol/L (4-15mmol/L). LFT, serum lipase and CPK were non-contributory. PT was elevated at 24.7s (10-13s) and INR was 2.1 (0.9-1.2). Anticoagulation was stopped for three to four weeks, and nonsurgical management was recommended. Potassium supplementation was given, and the patient was continued on his hypertension medications. On further investigation, origin of the hemorrhage was determined to be traumatic secondary to the massage during which the masseuse walked on the patient. The patient was discharged after three days but was readmitted after continued abdominal pain and hyponatremia. He was diagnosed with a left-sided adrenal hemorrhage on repeat CT scan twelve days after identification of the first. Medical management was successful. Conclusion: Adrenal hemorrhage is a potentially life-threatening condition often caused by trauma, severe burns, or septicemia. Anticoagulant therapy and thromboembolic disease, as seen in our patient, are also risk factors. The atypical trauma induced by the patient's massage likely initiated the hemorrhagic event. Presentation: Friday, June 16, 2023

SAT326 Massive Adrenomyelolipomas Due To Longstanding CAH

Abstract Disclosure: Q. Aziz: None. A. Champion: None. Introduction: Congenital Adrenal Hyperplasia (CAH) is an autosomal recessive disorder caused by deficiency in adrenal corticosteroid biosynthesis. 21 Hydroxylase Deficiency is common in 90-95% of CAH cases and have a defect in converting 17 OH Progesterone to 11 deoxycortisol. Therefore, they have an increase in ACTH secretion due to the decrease negative feedback drive along with excess adrenal androgens. Adrenal myelolipoma are common in patients with CAH and the tumors are benign and lipomatous. Clinical Case: Patient is a 47 year old female with past medical history of CAH presents to the clinic for evaluation of generalized fatigue and abdominal pain. She was diagnosed with CAH- 21 hydroxylase deficiency at birth and required vaginal reconstruction surgery. She was on hydrocortisone and fludrocortisone until age 18, but thereafter stopped taking medications or seeing physicians for nearly 30 years. CT abdomen/pelvis showed large bilateral adrenal myelolipomas, right adrenal gland measuring 23.2 cm and left adrenal gland measuring 20 cm. MRI confirmed enlarged adrenal glands. Initial labs included ACTH 299, 17-OH Progesterone >2000, 11 deoxycorticosterone 23.6, total testosterone 160, free testosterone 30.3, DHEA-S 192, Cortisol 2.8. She was started on fludrocortisone 50 mcg and Hydrocortisone 10 mg in the morning and 5 mg in the evening and was referred to an endocrine surgeon out of state, but surgery was not offered due to concerns of medication nonadherence. She returned to clinic 6 months after presentation, she admitted to missing multiple doses of her hydrocortisone. Repeat CT Abdomen and Pelvis showed severe compression of the IVC and right lobe of the liver along with mild compression of the kidneys and pancreas. To improve adherence, she was switched to prednisone, and eventually dexamethasone 0.75mg and fludrocortisone 100mcg. She complains of fatigue but improved abdominal pain. After a period of good adherence with medication administration, she was referred to a local surgical oncologist who agreed to do bilateral adrenalectomy due to mass effect. Conclusion: CAH is a challenging chronic disease with variable penetrance in phenotype, ranging from mild hirsutism to frank adrenal insufficiency. Massive adrenomyelolipomas are thought to be ACTH driven, especially seen in undertreated and longstanding CAH. Without the 21 hydroxylase enzyme to convert 17 OH Progesterone to 11 deoxycortisol, levels of ACTH rise. While these myelolipomas are benign and can generally be monitored, surgery should be considered if the size impairs function of surrounding organs. Bilateral adrenalectomy can also be considered in patients with CAH for refractory hypertension, hyperandrogenism and virilization, Cushing syndrome, infertility, or mass effect. Presentation: Saturday, June 17, 2023

FRI226 Ectopic Cushing’s Syndrome Of Unknown Primary Origin With Etomidate Use

Abstract Disclosure: C. Ohammah: None. J. Lloyd: None. T. Abdulwahid: None. R. Tangri: None. C. Musgrove: None. K. Selk: None. Background: Ectopic Cushing's syndrome (ECS) is rare and requires adrenolytic agents to control hypercortisolism until a definitive plan can be made to treat the underlying cause. We present a case of ECS of unknown primary origin causing immunosuppression due to the hypercortisolism that responded with etomidate infusion. Case: A 61-year-old male who presented to the hospital after a few weeks of increasing weakness, dyspnea, and hemoptysis. In the months prior to his admission, he was found to have persistent hypokalemia, COVID pneumonia, and new onset diabetes mellitus. On admission, his examination was remarkable for proximal hip flexor weakness. Labs were significant for metabolic alkalosis, hyperglycemia (A1c 7.7%) and persistent hypokalemia requiring about 300 mEq of potassium daily. CT chest, abdomen and pelvis was remarkable for aspiration pneumonia, vertebral compression fracture, and bilateral adrenal enlargement. Blood cultures grew Staphylococcus Aureus (MSSA) (suspected lung source) and Candida albicans. Treatment with vancomycin and caspofungin was initiated and narrowed to cefazolin after speciation. His MSSA cleared rapidly however, fungemia was persistent after 1.5 weeks of treatment. MRI brain was unremarkable for causative lesion. Further testing revealed elevated morning cortisol (136.2ug/dL) confirmed on repeated testing and elevated ACTH (653pg/mL). Serum metanephrines were normal. A high-dose dexamethasone suppression was unremarkable. In the following days, he developed respiratory failure secondary to a spontaneous hemothorax requiring intubation and ICU admission. He was started on an etomidate infusion given abnormal liver enzymes and unavailability of metyrapone. The infusion was titrated every 6 hours based on cortisol levels. His liver enzymes improved and ketoconazole was added but later discontinued due to development of thrombocytopenia. His cortisol level decreased (21.5ug/dL) and fungemia cleared. Arrangement for bilateral adrenalectomy was made but the patient decompensated and developed shock requiring pressors. After a goals of care discussion, he was transitioned to comfort measures and eventually passed. Conclusion: ECS is rare, and the diagnosis is challenging and often delayed. Ectopic ACTH can result from various malignancies. Medical management with adrenolytic agents should be considered early in the management of ECS until a definitive plan is made. Etomidate, ketoconazole, metyrapone, and mitotane can be used to treat hypercortisolism to achieve medical adrenalectomy. Bilateral adrenalectomy should be considered in patients without adequate response to adrenolytic agents. This case describes the severity of hypercortisolism from an ectopic ACTH production causing refractory hypokalemia and immunosuppression resulting in fatal infections. We highlight the use of etomidate to control hypercortisolism. Presentation: Friday, June 16, 2023

THU518 Ectopic Cushing Syndrome In A Case Of Ewing Sarcoma

Abstract Disclosure: M. Fasen: None. S.E. Mayson: None. Background: Ewing sarcoma (ES) is a rare and aggressive neoplasm occurring in bone and soft tissue in children to young adults. It is part of a spectrum of neoplastic diseases known as the ES family of tumors that display varying degrees of neuroendocrine features. Ectopic Cushing’s syndrome (ECS) is also a rare but severe condition associated with unregulated ACTH or CRH secretion by neuroendocrine tumors (NETs) that can cause severe hypercortisolism. The most common tumors associated with ECS include small cell lung carcinoma, bronchial carcinoid and medullary carcinoma of the thyroid gland. Sarcomas causing ECS are extremely rare with only a handful of cases reported in the literature, mostly in children. Herein we detail what we believe to be the first reported case of ECS occurring in an adult male patient with ES. Clinical Case: A 23-year-old man with ES metastatic to pancreas, liver and bone was admitted to the hospital with acute on chronic back pain and lower extremity weakness, and subsequently diagnosed with cord compression and neutropenia from chemotherapy. New onset hypertension and refractory hypokalemia were observed prompting endocrinology consultation. Physical examination revealed facial fullness, central obesity and wide violaceous striae on his abdomen and axillae. Biochemical evaluation demonstrated blood glucose consistently over 300 mg/dL, serum potassium 2.5 mmol/L, renin 0.9 ng/ml/hr (0.2-1.6 ng/ml/hr), aldosterone renin ratio < 3.3, morning cortisol 73 ug/dL (4-22 ug/dL), and ACTH 1020 pg/mL (72-63 pg/mL). A 1 mg overnight dexamethasone suppression test yielded a serum cortisol of 90 ug/dL and 24-hour urine free cortisol was 6388 ug/d (<60 ug/d). MRI brain demonstrated a normal pituitary gland, and FDG PET-CT showed new areas of uptake in bone concerning for metastatic progression and new bilateral adrenal enlargement without nodularity. High dose dexamethasone suppression testing was deferred in the context of rapid neuropsychiatric deterioration characterized by somnolence and psychosis. The decision was made to treat immediately with spironolactone and ketoconazole, as well as insulin for hyperglycemia management. His mental status, blood pressure, serum potassium, glucose and cortisol improved following the initiation and titration of medical therapy. He was discharged home with addition of metyrapone and hospice support. Two months later the patient succumbed to his illness. Conclusion: The severity of hypercortisolism is a negative predictor of survival and prompt control should be the main therapeutic goal along with prevention of cortisol-induced complications in patients with ECS. ACTH and CRH immunostaining of the patient’s ES histopathology slides is pending. Presentation: Thursday, June 15, 2023

FRI220 Primary Bilateral Macronodular Adrenal Hyperplasia: A Rare Cause Of Cushing Syndrome

Abstract Disclosure: Y. Ortiz: None. A.M. Aviles Melendez: None. M.M. Mangual Garcia: None. J.M. Garcia-Mateo: None. Primary bilateral macronodular adrenal hyperplasia (PBMAH) is a highly heterogenous entity whose pathophysiology remains largely unclear, representing less than 2% of Cushing syndrome (CS) cases, which leads to a challenging diagnosis. Many patients have a mild clinical picture and remain undiagnosed until abdominal imaging for unrelated reasons reveals bilateral adrenal enlargement. Hereby, we describe the case of a patient presented with abdominal pain and clinical hypercortisolism due to PBMAH. Case of a 42-year-old female with past medical history of arterial hypertension, referred for evaluation due to bilateral adrenal masses found on abdominal CT scan performed after patient presented with abdominal discomfort. On initial evaluation, patient refers a 50 pounds weight gain, increase in abdominal circumference, muscle weakness and sudden onset of facial and abdominal hair growth. Physical examination reveals dorsocervical fat pad, proximal muscle weakness, moon facies, facial and abdominal hirsutism. Abdominal CT scan with adrenal protocol showed bilateral adrenal lesions, with largest measuring 2.8 and 3.9 cm on the left side, with attenuation of 16 and 7.4 Hounsfield units. The absolute and relative washouts for the first were 76.6% and 61.6%, and for the second 73.5% and 67.1%, both consistent with adenomas. Laboratory results showed late night salivary cortisol levels of 4.60 ug/dl and 4.80 ug/dl, values which may be high or even normal due to ineffective steroidogenesis on PBMAH. Other labs consisted of low dose 1 mg dexamethasone suppression test: 4.80 ug/dl, and ACTH level: 9.60 pg/ml, which confirms clinical hypercortisolism, indeterminate for ACTH-independent cause. Desmopressin test was not performed, since levels may not be fully suppressed in PBMAH due to ectopic production by adrenal glands, leading to an erroneous diagnosis of ACTH-dependent CS. DHEA level of 618 ug/dl can also be increased, which could lead to a diagnosis of adrenocortical carcinoma. Considering risk of recurrence, risk for adrenal insufficiency, and lower documented complications, unilateral left-sided adrenalectomy was chosen as the best surgical treatment, despite bilateral adrenalectomy being the gold standard for diagnosis. Surgical pathology report showed Adrenocortical adenoma with associated myelolipomatous foci of 7.5 cm in greatest dimension. Despite limited data regarding unilateral adrenalectomy, it appears to convey clinical and biochemical benefits in most cases. Initial remission reported reaches more than 90% with low risk of recurrence between 10-15%. Adrenal insufficiency, despite the presence of residual hyperplastic adrenal tissue, occurs in about one-third of patients and is usually transient. Our case is a great example of the importance of individualization of management options based on therapy benefits, and decreased risks of future complications. Presentation: Friday, June 16, 2023

Complete recovery after glucocorticoid replacement therapy in a case of primary adrenal insufficiency caused by adrenal tuberculosis infection.

Symptoms of primary adrenal insufficiency (PAI) are commonly nonspecific, causing the disease to be misdiagnosed or often delayed, and patients may present to the hospital with a life-threatening crisis. Previous case reports have documented that patients in this condition often require lifelong glucocorticoid replacement therapy. This study aimed to present a noteworthy outcome of PAI caused by adrenal tuberculosis infection, demonstrating complete recovery after six months of glucocorticoid replacement therapy. A 38-year-old Indonesian man presented to the endocrinology clinic in a tertiary hospital with a chief complaint of epigastric pain. The patient experienced nausea, vomiting, loss of consciousness, weight loss, excessive sweat, decreased appetite, weakness, and dizziness in the past 2 weeks. Laboratory examinations revealed hyponatremia, elevated adrenocorticotropic hormone, and suppressed morning plasma cortisol level. A non-contrast-enhanced abdominal MRI showed unilateral right-side adrenal enlargement and calcification. The patient's Mantoux test was positive. Corticosteroids and anti-tuberculosis therapy were administered. After 6 months, hydrocortisone was discontinued due to the patient's good clinical condition and normal morning plasma cortisol levels. After a 1-year follow-up, the patient remained asymptomatic with normal cortisol levels. We hypothesized several reasons for this unique outcome: (i) the patient was relatively young compared to previous cases, suggesting an adequate immune system may play a role; (ii) despite a 1-month delay in diagnosis and treatment, the absence of skin hyperpigmentation suggested an acute presentation, potentially contributing to the favorable outcome; and (iii) the absence of comorbidities potentially positively impacted the patient's outcome. Symptoms of adrenal insufficiency are often nonspecific and may only become apparent once significant damage has occurred to the adrenal gland. Clinical adjustments and a comprehensive understanding of epidemiological knowledge are necessary for diagnosing patients with endocrine diseases in limited-resource settings. Complete recovery in primary adrenal insufficiency caused by tuberculosis infection might be due to younger age, acute presentation, and absence of comorbidities.

Ultrasonographic Measurement of Fetal Adrenal Gland Size for the Prediction of Success of Induction of Labor Among Primigravida Beyond 40Weeks Gestation.

As the pregnancy advances beyond term, the risk of perinatal morbidity and mortality increases. Hence to prevent these complications associated with postterm pregnancy, induction of labor is done, as per our institution protocol between 40 and 41weeks of gestation. Induction has its own drawback, so it is essential to identify the women with high chances of failure of induction of labor, to prevent the morbidities associated with induction failure. To study the role of ultrasonographic fetal adrenal gland enlargement for the prediction of success of labor induction among primigravida beyond 40weeks gestation. Low-risk primigravidas beyond 40weeks gestation, scheduled for induction of labor, were enrolled for the study. Fetal adrenal gland dimensions were measured by using abdominal probe Philips HD 7XE and general electronics logiq P6 pro or any ultrasound machine equipped with 7.5-10MHz linear array probe and 3.5-5MHz curved array probe. The fetal adrenal gland length, width and ratio were statistically significant between the successful versus failed induction groups. The cutoff fetal zone ratio > 0.36 for the prediction of successful induction of labor had 90% sensitivity, 89% specificity, 93% PPV and 75% NPV. Fetal zone enlargement (fetal zone ratio > 0.36) is a strong predictor of successful induction of labor as compared to TVL and Bishop's score. It can be used for screening the women, who are destined for induction failure, so that adverse effects of induction of labor can be avoided.