Random Cortisol Research Articles

Polyuria in a Patient With a Pituitary Mass

Background: Hypocortisolism can develop in patients with a pituitary mass because of hypopituitarism and is appropriately managed with steroid replacement. However, these patients often have co-existing endocrine derangements that can become clinically evident after administration of steroids. Clinical Case: A sixty-year-old Caucasian female with known non-small cell lung cancer on chemoimmunotherapy was admitted for management of an enlarging suprasellar mass. Her symptoms included nausea, vomiting and multiple syncopal episodes over the preceding three weeks. At the time of admission, physical examination was unremarkable. She was noted to be hypotensive with systolic blood pressure in the high 70s and was treated with intravenous fluids. Laboratory evaluation showed low random cortisol (0.99 ug/dL, n: 0.4-22.6 ug/dL), undetectable ACTH (<5 pg/mL, n: 7.2-63 pg/mL), low free thyroxine (1.01 ug/dL, n: 0.93-1.7 ug/dL), low free T3 (1.6 pg/mL, n: 2-4.4 pg/mL) and low TSH (0.023 ug/dL, n: 0.27-4.2 ug/dL), consistent with central hypothyroidism and secondary adrenal insufficiency. Importantly, she was normonatremic and normokalemic at admission. She was started on stress dose hydrocortisone (100 mg IV q8h) for presumed adrenal crisis. Following institution of steroid replacement therapy, the patient rapidly became polyuric while simultaneously developing hypernatremia. Her daily urine output peaked at 4400 mL corresponding temporally to a maximum serum sodium of 160 mmol/L. A single dose of 0.5 mg of desmopressin resulted in immediate lowering of daily urine output to 750 mL and appropriate improvement in urine osmolality from 147 mOsm/kg to 565 mOsm/kg, confirming a diagnosis of central diabetes insipidus (cDI). Conclusion: Hypocortisolism is known to impair free water excretion by stimulating arginine vasopressin (AVP) secretion through renal sodium loss and consequent volume depletion as well as direct feedback stimulation of corticotrophin releasing hormone (CRH) and AVP within the hypothalamus. Conversely steroid replacement leads to loss of feedback stimulation, unmasking cDI. This unique convergence of cDI with hypocortisolism is most often encountered in patients with hypopituitarism. Hence patients with secondary adrenal insufficiency should be carefully monitored for cDI after initiation of steroid replacement therapy.

Laparoscopic Bilateral Adrenalectomy Should Be an Early Consideration in Ectopic Adrenocorticopic Hormone Secretion

Introduction: Ectopic ACTH secretion (EAS) causes myriad metabolic derangements which may be effectively managed with laparoscopic bilateral adrenalectomy (LBA) in fit-for-surgery candidates. Clinical Case: A 67-year old woman with a remote 12-pack year smoking history presented with unintentional weight loss, cough, fever and chest pain. Imaging revealed a right-sided lung mass with liver lesions. Liver biopsy confirmed a well-differentiated neuroendocrine tumour (NET). Attempt at palliative lung resection was aborted due to disease extent. She was treated with multiple courses of chemotherapy but her disease progressed. Two years later, she presented with hypokalemia of 2.8 mmol/L (3.5 - 5.0 mmol/L) and uncontrolled hypertension. She was treated with spironolactone and oral potassium. She was notably hyperglycaemic with clinical features of cortisol excess. A random cortisol of 2742 nmol/L (<500 nmol/L), corresponding ACTH of 201 ng/L (5 - 50 ng/L) and lack of diurnal variation in cortisol day curve were in keeping with EAS. Metyrapone and spironolactone normalised blood pressure and biochemical derangement. With her initially high cortisol levels and its associated immunocompromised state, she developed pneumocystis jirovecii pneumonia (PCP), and was briefly admitted to the intensive care unit. In hospital, monitoring her response to EAS management necessitated multiple blood investigations, which proved burdensome for the patient. To effect definitive management of EAS and reduce invasive monitoring, she wished to have LBA and underwent an uneventful procedure. She was discharged on fludrocortisone and hydrocortisone along with lanreotide for primary disease management. Metyrapone and spironolactone were stopped. At initial outpatient follow up, she had normal blood pressure and electrolytes. By her report, her quality of life had improved tremendously, given the reduced need for multiple clinic visits and blood investigations. Unfortunately, her primary disease progressed with gradual deterioration of physical function. She died six months after LBA but, as per her desire, spent her final months with loved ones. Clinical Lesson: In patients with EAS who have unresectable primary disease but otherwise good performance status, LBA is a viable alternative to medical management and should be discussed with patients early after diagnosis.

Deep Venous Thrombosis in a Patient With Cushing’s Syndrome

Abstract Introduction: Cushing’s syndrome (CS) is associated with a prothrombotic state due to increased activation of several clotting factors. As such, patients are more susceptible to development of post-operative venous thrombosis. We present the case of a patient who underwent pituitary surgery for CS and subsequently developed acute lower extremity deep venous thrombosis (DVT) after stopping anticoagulation upon discharge. Case Report: A 57-year-old female presented with abdominal pain 1 month after gastric bypass surgery. She was found to have intra-abdominal abscesses and started on IV antibiotics. Upon further questioning, she endorsed 2-week history of coarse hair over chin, difficulty climbing stairs, and easy bruising. She had type 2 diabetes and hypertension, both diagnosed 2 years prior. Blood pressure was 169/88 on admission. On exam she had coarse hair on chin, central obesity, scattered ecchymoses, proximal muscle weakness, and no abdominal striae. Labs revealed potassium level of 1.9 mmol/L despite supplementation with 60 meq/day of potassium chloride. Workup showed random cortisol 45 mcg/dl, ACTH 114 pg/ml, elevated urinary free cortisol to 898.6 ug/24 hours, unsuppressed cortisol to 30.6 mcg/dL with low-dose dexamethasone and partial cortisol suppression to 11 mcg/dl with high-dose dexamethasone. MRI brain showed pituitary adenoma measuring 6 x 9 x 2 mm. CRH stimulation test showed rise of ACTH to 302 pg/ml and cortisol to 81.5 mcg/dl consistent with ACTH-dependent hypercortisolism from pituitary tumor. While hospitalized, the patient received thromboprophylaxis with SQ enoxaparin 40 mg daily. Patient was started on ketoconazole and subsequently underwent transsphenoidal resection to remove the pituitary tumor, which effectively reduced her serum cortisol levels. She was started on hydrocortisone replacement. She was discharged to a skilled nursing facility 2 weeks later. However, she did not receive thromboprophylaxis at the facility and was diagnosed with acute lower extremity DVT soon after hospital discharge. Discussion: CS is associated with increased risk of thromboembolic events. Although our patient received DVT prophylaxis in the hospital until discharge 2 weeks after surgery, she developed DVT soon after discharge. This emphasizes the increased susceptibility to development of venous thrombosis even after normalization of cortisol levels following pituitary surgery. A recent retrospective study showed that patients with CS are at higher risk of thromboembolism for approximately 30 to 60 days during the postoperative period. This case highlights that the clotting risk remains elevated in patients with CS for an extended period after successful surgery. In conclusion, patients with CS are at high risk of thromboembolism even after surgery and extended thromboprophylaxis should be considered.

Immune Checkpoint Inhibitor-Induced Hypophysitis in Renal Cell Carcinoma: Two Contrasting Case Presentations

Background: Increasing use of immune checkpoint inhibitor (ICI) therapy for malignancy has led to rising incidence of ICI-mediated endocrinopathies. We describe two varying cases of patients with renal cell carcinoma (RCC) who presented with ICI-mediated hypophysitis. Cases: Patient A: A 72 year old female with RCC (T1bN0M0) diagnosed after an incidental renal mass was found on CT scan following a motor vehicle accident. After nephrectomy, she received 5 cycles of nivolumab (6/2019 to 10/2019). One month later, she presented in severe DKA and was diagnosed with ICI-mediated diabetes (low c-peptide, negative autoantibodies). ICI therapy was stopped. In 4/2020, she experienced a drastic reduction in her insulin requirement (~30 units/day of basal/bolus insulin to ~6 units/day of basal insulin only). She had a primary care visit for fatigue, nausea, and anorexia. Biochemical evaluation showed hyponatremia, normokalemia, normoglycemia, and no acid-base disorder. One week later, she presented to the emergency department (ED) with worsening symptoms. She was hypotensive (94/56 mmHg), hyponatremic (129 mmol/L), normokalemic, and azotemic. Cosyntropin stimulation test (CST) showed an inappropriate response [ACTH <5 pg/ml; cortisol response of 0.4 to 8.1 µg/dl]. Brain MRI showed a partially empty sella. She was diagnosed with secondary adrenal insufficiency (AI) due to hypophysitis and started on steroid replacement. A repeat CST after 3 months did not show HPA axis recovery. Her presentation is unique because she developed secondary AI six months after nivolumab therapy. Patient B: A 43 year old female with RCC (T4N1M1) who received 4-cycles of ipilimumab and nivolumab (11/2019 to 1/2020). One month later, she presented to the ED with hypotension, anorexia, and fatigue. Biochemical evaluation showed severe DKA. She was diagnosed with ICI-mediated diabetes (low c-peptide, negative autoantibodies) and started on basal/bolus insulin. Her ICI-therapy was stopped. One month later, she was readmitted for hypotension and severe headaches and found to have hyponatremia (131 mmol/L), normokalemia, hyperprolactinemia (29 ng/ml), cortisol 4.5 µg/dl (previous random cortisol a month earlier was 33 µg/dl). Pituitary gland was normal on MRI. She was presumed to have secondary AI due to hypophysitis and started on steroid replacement. A CST performed after 3 months showed ACTH <5 pg/ml and cortisol response of 3.5 to 4.5 µg/dl. Her case was a usual presentation of ICI-mediated secondary AI as it occurred within 1-2 months of stopping ICI therapy. Conclusion: As we continue to learn about ICI-mediated endocrinopathies, it is imperative to document the variation in timing of presentation. ICI-mediated hypophysitis can present at any time after the initiation of therapy. Given this variation, there is need for routine screening and early treatment of hypophysitis to reduce ED visits and readmission rates.

Recalibration of thinking about adrenocortical function assessment: how the 'random' cortisol relates to the short synacthen test results.

BackgroundThe short synacthen test (SST) is the most commonly performed investigation to assess adrenal function. Appropriate criteria for when an SST is performed are subject to debate. We investigated how random serum cortisol levels relate to SST response.MethodsWe examined random cortisol measurements taken between 04.40–23.55 p.m. results of SST baseline and 30-/60-min cortisol performed over 12 months (225 SSTs) at Salford Royal Hospital. Serum cortisol was measured on the Siemens Centaur Analyser.A 30–60-min cortisol concentration of ≥450 nmol/L defined a pass; 350–449 nmol/L defined borderline.ResultsPatients only proceeded to SST if random cortisol was <400 nmol/L. For those not on corticosteroids for at least 2 weeks, 42/43 (97.7%) cases with random cortisol concentration of ≥200 nmol/L had an SST ‘pass’. The relation was less clear with corticosteroid treatment (19/35 cases; 54%).For those not taking glucocorticoid treatment (including inhaled/topical corticosteroids) in the previous 2 weeks, 91.8% of SSTs were pass/2.7% borderline/5.5% fail. For those on steroids, 51.9% of SSTs were a pass/11.4% were borderline.In relation to the postsynacthen cortisol pass cut-off of ≥450 nmol/L, in 15/207 (7.2%) of cases, the 60-min cortisol was ≥450 nmol/L (adequate adrenocortical function), but 30-min cortisol was below this. In all cases where the 30-min cortisol did indicate a pass (i.e. was ≥450 nmol/L) the 60-min cortisol was also ≥450 nmol/L.ConclusionOur findings suggest that if the random cortisol level is ≥200 nmol/L, regardless of the time of day and the person was not taking corticosteroid treatment in the previous 2 weeks, SST may not be needed. Our data also suggests that 60-min cortisol retains utility.

Plasma cortisol level and its relation to in-hospital mortality in acute kidney injury patients

Background Critically ill patients are at risk of developing critical illness-related corticosteroid insufficiency (CIRCI). This may present as hypotension, unresponsiveness to catecholamine infusions, and/or ventilator dependence. Acute kidney injury (AKI) usually complicates critically ill patients and is associated with hemodynamic instability. There is usually failure to predict the severity and to assess the response to therapy in AKI. The aim of this study was to assess the plasma cortisol level and its relation to hospital mortality in AKI patients. Patients and methods This is a prospective, observational study that included 66 patients with AKI admitted to the Dialysis and Nephrology Unit, Mansoura University Hospital, who were assessed clinically, followed by cortisol level assay done at the day of admission. Patients were followed clinically and biochemically till discharge. Patients were classified according to random plasma cortisol level into two groups: group 1 included 14 patients with random plasma cortisol of less than 10 μg/dl (CIRCI group) and group 2 included 52 patients with random plasma cortisol of greater than or equal to 10 μg/dl. Results There was a significant increase in platelet count in group 1 compared with group 2, while there was a significant decrease in serum potassium level in group 1 compared with group 2. Moreover, there was a significant decrease in urine output volume in group 1 compared with group 2 (P=0.03). Finally the hospital mortality rate was significantly higher in group 1 (CIRCI group) compared with group 2 (P=0.004). Conclusion AKI patients with low cortisol level at admission have higher mortality rate during the hospitalization period.

Outcomes of pituitary apoplexy: a comparison of microadenomas and macroadenomas

We aimed to assess clinical characteristics of apoplexy of pituitary microadenomas compared to macroadenomas. We retrieved clinical records of patients > 18years old, hospitalized in Rambam hospital between January 2001 and October 2017, with pituitary apoplexy and follow-up of at least one year. We compared clinical course and outcomes of apoplexy between patients with microadenomas and macroadenomas, and between patients who received conservative or surgical treatment. Statistical analysis was done using Fisher's exact and Mann-Whitney tests. Twenty-seven patients with pituitary apoplexy were included in the final analysis: mean age was 40.7 ± 12.5 years, 13(48%) were female, 7(26%) had microadenomas, and 21(78%) harbored clinically nonfunctioning pituitary adenomas. Upon admission, hyponatremia, random cortisol level of < 200nmol/L, and secondary hypothyroidism, were evident in 6/20, 8/18, and 4/18 patients with macroadenoma and 1/5, 2/5, and 1/6 patients with microadenoma, respectively (P = 1.0). Hypogonadotropic hypogonadism was evident in 9/12 men with macroadenoma. In 12 macroadenoma patients, the tumor abutted the optic chiasm, of whom eight had visual field defects. Fifteen patients with macroadenoma and two with microadenoma underwent transsphenoidal surgery. Median follow-up was 3years. At last follow-up visit, patients with microadenoma had lower rates of corticotropic deficiency or secondary hypothyroidism compared to macroadenoma patients (1/7 vs. 13/20 respectively, p = 0.033). Only two patients with macroadenomas had persistent visual field defects. Outcomes were comparable between conservative and surgical treatment groups. Long term pituitary hormone deficiencies are more common in pituitary apoplexy patients with macroadenomas. Apoplexy of pituitary microadenoma carries a more favorable prognosis.

The Adrenal Cortex, an Underestimated Site of SARS-CoV-2 Infection.

BackgroundThe majority of the critically ill patients may have critical illness-related corticosteroid insufficiency (CIRCI). The therapeutic effect of dexamethasone may be related to its ability to improve cortical function. Recent study showed that dexamethasone can reduce COVID-19 deaths by up to one third in critically ill patients. The aim of this article is to investigate whether SARS-CoV-2 can attack the adrenal cortex to aggravate the relative adrenal insufficiency.MethodsWe summarized the clinical features of COVID-19 reported in currently available observational studies. ACE2 and TMPRSS2 expression was examined in human adrenal glands by immunohistochemical staining. We retrospectively analyzed serum cortisol levels in critically ill patients with or without COVID-19.ResultsHigh percentage of critically ill patients with SARS-COV-2 infection in the study were treated with vasopressors. ACE2 receptor and TMPRSS2 serine protease were colocalized in adrenocortical cells in zona fasciculata and zona reticularis. We collected plasma cortisol concentrations in nine critically ill patients with COVID-19. The cortisol levels of critically ill patients with COVID-19 were lower than those in non-COVID-19 critically ill group. Six of the nine COVID-19 critically ill patients had random plasma cortisol concentrations below 10 µg/dl, which met the criteria for the diagnosis of CIRCI.ConclusionWe demonstrate that ACE2 and TMPRSS2 are colocalized in adrenocortical cells, and that the cortisol levels are lower in critically ill patients with COVID-19 as compared to those of non-COVID-19 critically ill patients. Based on our findings, we recommend measuring plasma cortisol level to guide hormonal therapy.

Prevalence of Adrenal Insufficiency and Glucocorticoid Use in Pediatric Pseudotumor Cerebri Syndrome.

The pathophysiology underlying pseudotumor cerebri syndrome (PTCS) is complex and not well understood. There are clear differences between PTCS in adults and pediatrics. Few and isolated case reports have suggested that adrenal function may be involved, yet no large cohort study has examined this relationship. We conducted a retrospective single-center study of children who presented with a diagnosis of PTCS and had cortisol testing measured between January 2010 and September 2019. We included all subjects meeting the revised PTCS diagnostic criteria after the chart review. Based on morning, random or 1-μg cosyntropin stimulated cortisol levels, adrenal functioning was classified as: (1) insufficient (peak cortisol <16 μg/dL and AM cortisol <5 μg/dL), (2) at risk (peak cortisol 16-20 μg/dL, AM cortisol 5-13 μg/dL, or random <13 μg/dL), or (3) sufficient (peak cortisol >20 μg/dL and AM or random cortisol >13 μg/dL). A total of 398 individuals were reviewed, and 64 were included for analysis. Of these, 40.6% were men, of mixed race and ethnicity with a mean age of 10.5 (SD 4.7) years. Of these, 23% and 52% had insufficient or at-risk cortisol levels. The majority of those in the insufficient (70%) or at-risk (80%) groups were exposed to topical, nasal, or inhaled glucocorticoids but not systemic. Only 60% and 12% of those with PTCS with insufficient or at-risk cortisol testing, respectively, underwent definitive testing with a stimulation test. Glucocorticoid use and hypocortisolism are prevalent in PTCS and need consideration as a potential underlying cause. Most children had insufficient or at-risk cortisol levels, and many did not undergo further testing/workup. Children who present with PTCS, particularly young, males should be evaluated for adrenal insufficiency and its risk factors, including nonsystemic steroids. Prospective studies are necessary to further evaluate the effect of cortisol in relation to pediatric PTCS.

ACUTE GENERALIZED EXENTHEMATOUS PUSTULOSIS MIMICKING SEPTIC SHOCK: UNUSUAL PRESENTATION OF AN UNUSUAL DISEASE

SESSION TITLE: Medical Student/Resident Critical Care Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Acute generalized exanthematous pustulosis (AGEP) is a rare disorder, characterized by the development of acute sterile pustules. It is mostly caused by drugs, with antibiotics being the most likely culprits. AGEP is a self-limiting disease with favorable prognosis in the vast majority of patients. We present a case of a woman, admitted to the intensive care unit (ICU) with an unusually severe form of AGEP mimicking septic shock. CASE PRESENTATION: A 45-year-old female with systemic lupus erythematosus (SLE), underwent left hip replacement due to avascular necrosis. She received prophylactic cephazolin and discharged two days after surgery with an uncomplicated post-operative course. Two days later, she was admitted to the ICU with fever (103.6 F), tachycardia, and hypotension (54/36 mmHg). On physical exam, she had diffuse small pustules on an erythematous base (Fig 1). The incision site showed no signs of infection (Fig. 2). Labs were significant for leukocytosis (WBC 22,000), neutrophilia (18,500), left shift (Bands 13.9), eosinophilia (160), acute kidney injury (Cr 5.3, baseline 0.8), increased inflammatory markers (ESR 19, CRP 32.7), procalcitonin (2.49) and lactic acidosis. Random cortisol was normal and urine analysis was clear. Chest X-Ray showed no infiltrates and left hip CT scan showed no hematoma or abscess. She was initially managed as septic shock, started on broad spectrum antibiotics and required 2 vasopressors. Her hemodynamic status dramatically improved by the second day. Given her typical eruption and no source of infection identified, she was diagnosed with AGEP and antibiotics were discontinued on day 2. Patient continued to improve; vasopressors were weaned off by the third day. Cultures showed no growth. Kidney function and lactate levels normalized by the fifth day and she was discharged from the hospital on day 11. The skin pustules gradually coalesced into plaques (Fig. 3, 4) with subsequent sloughing. DISCUSSION: AGEP is a rare acute cutaneous reaction, with characteristic numerous, pinhead-sized pustules on an edematous erythematous background. It commonly presents with fever, neutrophilia, and skin eruption. Thus, often misinterpreted as an acute infectious process. AGEP is self-limiting, tends to resolve spontaneously with cessation of the offending agent, and no further measures are usually required. Multi-organ involvement is rare and highly atypical of AGEP. In contrast to most reported cases of AGEP, our case demonstrated an atypical presentation with severe systemic involvement and multi-organ failure mimicking septic shock. The patient had SLE and was on chronic corticosteroid treatment, which might explain her unusual life-threatening course. CONCLUSIONS: Prompt diagnosis of AGEP is crucial as the mainstay of treatment is the withdrawal of the offending drug. Every effort should be made to distinguish it from other causes of shock, mainly infection. Reference #1: idoroff A, Halevy S, Bavinck JN, Vaillant L, Roujeau JC. Acute generalized exanthematous pustulosis (AGEP)--a clinical reaction pattern. J Cutan Pathol. 2001;28(3):113-9 Reference #2: Roujeau JC, Bioulac-Sage P, Bourseau C, Guillaume JC, Bernard P, Lok C, et al. Acute generalized exanthematous pustulosis. Analysis of 63 cases. Arch Dermatol. 1991;127(9):1333-8 Reference #3: Krishna S, Ortega-Loayza A, Malakouti N, Brinster N. A rapidly progressive and fatal case of atypical acute generalized exanthematous pustulosis. J Am Acad Dermatol. 2014;71(3):e89-90 DISCLOSURES: No relevant relationships by Mohamed Elmassry, source=Web Response No relevant relationships by Amr Ismail, source=Web Response No relevant relationships by Haneen Mallah, source=Web Response No relevant relationships by Barbara Mantilla, source=Web Response No relevant relationships by Jasmine Sekhon, source=Web Response No relevant relationships by Victor Test, source=Web Response No relevant relationships by Myrian Vinan Vega, source=Web Response

Adrenal Function and Vasoactive-Inotrope Score (VIS) in Children after Cardiac Surgery

Purpose: To determine if a difference exists in vasoactive-inotrope score (VIS) between children with adrenal insufficiency (AI) and those without AI undergoing cardiopulmonary bypass (CPB) at the Children’s Hospital of Georgia at Augusta University Health. Methods: This is a single center retrospective and prospective observational study of consecutive pediatric cardiothoracic surgery patients (January 2018 – September 2018). Children 18 years of age or younger undergoing cardiothoracic surgery and CPB with a random post-operative cortisol level were included in the study. Data collected included demographic data as well as pre-, intra-, …

Adrenal function following ACTH therapy for infantile spasms: A retrospective study

ObjectiveTo determine if treatment with ACTH for infantile spasms (IS) is associated with secondary adrenal insufficiency. Patients and methodsThis is a retrospective study of patients diagnosed with infantile spasms and treated with ACTH between 2007 and 2018 at Soroka University Medical Center (SUMC). We reviewed the records of patients who had a post-hormonal laboratory assessment of their adrenal function; either a low dose ACTH test or a random morning cortisol level and looked for laboratory or clinical signs of adrenal insufficiency. ResultsBetween the years 2007 and 2018, 45 children were diagnosed with IS at our Pediatric Neurology Unit, 20 patients were treated with ACTH, of them 14 children met the inclusion criteria and had a post-treatment laboratory assessment of adrenal function by low dose ACTH test or morning cortisol level. Five children had a normal low dose ACTH test, two had normal morning cortisol level, five were not conclusive, and two had subnormal levels of cortisol. None of the children showed clinical signs of adrenal insufficiency. ConclusionOur study adds to the limited literature on this topic and in contrast to previous publications suggests that adrenal suppression should not occur after ACTH treatment.

SAT-LB52 A Case of Cushing’s Syndrome in a Patient With Addison’s Disease

This is a case of a 56-year-old female with history of Addison’s disease, T1DM, hypothyroidism and Asthma. She was diagnosed with Addison’s disease after multiple hospital visits consistent with adrenal crises (Fatigue, weakness, salt craving, abdominal pain, hypotension, hyperpigmentation and hyponatremia). Multiple abdominal images including CT abdomen did not reveal any pathology. A random cortisol and ACTH were found to be abnormal at 0.5 and 3362, respectively. She was started on Hydrocortisone 10mg in the morning and 5mg in the evening. Her physical exam revealed diffuse hyperpigmentation including palmar creases and oral mucosa. There was no facial plethora or striae. She had no history of proximal myopathy, easy bruising, hypertension or osteoporosis. Upon follow up, exam revealed progressive worsening of her diffuse hyperpigmentation. A random cortisol and ACTH, without holding her Hydrocortisone, revealed 64.3 and >2000, respectively. Concern arose for the possibility for a pituitary corticotrophin adenoma or ectopic secretion of ACTH driving her hyperpigmentation. MRI showed the pituitary gland had normal appearances. As there is a positive correlation between basal plasma ACTH values and the size of the pituitary adenoma in patients with Cushing’s disease the differential of a pituitary corticotrophin adenoma was originally thought to be dropped lower on the list of differentials. Further workup was pursued with an 8mg Dexamethasone suppression test to take advantage of the fact that ACTH secretion by the pituitary adenomas in Cushing’s disease are only relatively resistant to negative feedback regulation by glucocorticoids while most ectopic ACTH production from non-pituitary tumors are completely resistant to feedback inhibition. ACTH levels went from >2000 down to 29 post 8mg Dexamethasone, which led to decreasing suspicion of an ectopic source of ACTH and further concern for a pituitary corticotrophin adenoma in addition to Addison’s disease. ACTH measurements are not widely used in documenting the adequacy of treatment of primary adrenocortical disease. The hormone is released in pulses, particularly in the early hours of the morning, and measurement of isolated samples is of limited value. Inappropriately normal to slightly elevated ACTH levels despite adequate glucocorticoid replacement in patient with adrenal insufficiency could be related to an altered pituitary sensitivity to cortisol suppression. Extremely elevated ACTH levels despite supra-physiological glucocorticoid replacement in a patient with Addison’s raises the question as to what is the source of ACTH?

SAT-236 Unusual Presentation of a Stable Pituitary Macroadenoma with Pituitary Apoplexy Causing SIADH and Pan-hypopituitarism

We are reporting a case of SIADH hyponatremia and pan-hypopituitarism in an otherwise stable appearing non-functional pituitary macroadenoma on MRI that suddenly developed apoplexy.Patient is a 52-year-old hispanic male with a history of a pituitary adenoma diagnosed initially on 06/2017 during MRI head for chronic headaches. MRI Pituitary on 07/2018 showed “well-circumscribed lesion” measuring approximately 12.7 x 14.8 x 13.4 mm in AP. Hormonal work up was normal in 06/2017, 01/2018, and 07/2018. In 07/2018 labs showed: IGF-1 247 ng/mL (65–222), ACTH 28 pg/mL (7–69), random cortisol 8.58 microg/dL (3.09–22.4), TSH 2.3 mIU/mL (0.4–5.5), fT4 1.06 ng/dL (0.8–1.8), LH 4.6 mIU/mL (0.98–79.7), FSH 6.2 MIU/mL (1–18), prolactin 2.92 ng/mL (2.1–24), and testosterone 310 ng/dL (87–814). Oral glucose tolerance test was done and showed: GH was 0.34 ng/mL at baseline and 1.01 ng/mL after 75 g oral glucose (equivocal result). Repeat IgF1 was normal after that.Subsequently, patient was admitted on 09/24/2018 with severe headaches, nausea, vomiting, polyuria, and polydipsia. He was hypotensive and tachycardic and was found to be hyponatremic with a Na of 124, lowest at 119 where hypertonic saline was given at that point. Urine output was 1.5 L in 24 hours while he was on an 0.8 L fluid restriction, and then 6 L the following day while he was on 1.5 L fluid restriction, serum osmolality was 251, urine osmolality was 1003, urine specific gravity was >1.030. Nephrology agreed to the diagnosis of SIADH.Blood work on 09/24 showed: random cortisol 0.67 microg/dL, TSH 0.19 mIU/mL, free T4: 0.63 ng/dL, ACTH 11 pg/mL, LH 2.4 mIU/mL, FSH 4.7 MIU/mL, testosterone 13 ng/dl. Patient was started on Levothyroxine 125 mcg and hydrocortisone stress dose. MRI brain was done and showed a pituitary macro-adenoma, measuring approximately 14 x 11 x 11 mm with no significant change in size since 6/30/2017, without optic nerve compression, no hemorrhage was mentioned. Work up for other causes of panhypopituitarism, i.e. hemochromatosis was done and was negative: Ferritin: 258 ng/mL (22–322). CT abdomen and pelvis was also done and showed normal adrenal glands. We thought about granulomatous infiltrative diseases like sarcoidosis since 1–25 (OH) vitamin D was high at 120 pg/mL (19.9–79.3). CT neck and chest was done but was negative for sarcoidosis or lymphadenopathy. Patient was seen outpatient by neurosurgery in 1/2019 and a repeat MRI was done which reported resolution of cystic and blood material from a pituitary adenoma, and per neurosurgery there is resolution of a pituitary cystic adenoma with apoplexy that now looks like a partial empty sella. Patient currently continues to be pan-hypopituitary requiring hydrocortisone, levothyroxine and testosterone replacement. SIADH has resolved.An otherwise non-functioning stable pituitary macroadenoma on MRI, can suddenly present as symptomatic apoplexy with SIADH and pan-hypopituitarism.

SAT-148 Ectopic ACTH Secretion Has Varied Presentation and Requires Individualized Treatment - One Size Does Not Fit All

Ectopic ACTH secretion (EAS) presents in myriad ways. We present five cases of EAS to highlight similarities and differences in presentation and treatment. The first woman with known metastatic lung neuroendocrine tumour (NET) for two years presented with facial fullness, proximal weakness, worsening hypertension and hypokalaemia. Random cortisol of 2742nmol/L (99.39mcg/dL), with adrenocorticotrophic hormone (ACTH) of 201ng/L (5-50), was in keeping with EAS. She received medical treatment followed by bilateral adrenalectomy with EAS resolution and development of adrenal insufficiency. She is doing well. The second woman with proximal weakness was evaluated by neurologists. All neurological tests were normal but facial fullness and easy bruising was noted. Random cortisol was 875nmol/L (31.71mcg/dL) and ACTH was 90 ng/L. Imaging revealed metastatic liver disease with unknown primary and biopsy confirmed NET. Cortisol rose despite medical treatment and she died within fifteen months. The third woman with significant smoking history presented with haemoptysis and breathlessness. A right lung mass was suspected on chest X-ray and confirmed with CT. Endobronchial ultrasound-guided biopsy revealed small cell lung cancer (SCLC). She developed generalised weakness and severe hypokalaemia. Random cortisol of 1645nmol/L (59.63mcg/dL) with ACTH of 282ng/L suggested EAS. Despite medical treatment, she died within two weeks. The fourth woman presented with confusion, hypertension and severe hypokalaemia. Morning cortisol of 8557nmol/L (310.19mcg/dL) and random ACTH of 73ng/L were suggestive of EAS. CT demonstrated left lung mass with widespread metastases. She deteriorated and died within 2 weeks. Our only man had incidentally discovered metastatic liver lesions on ultrasound. Further imaging revealed prostatic mass and biopsy showed small cell neuroendocrine cancer. He presented with severe hypokalaemia. Random cortisol was 1065nmol/L (38.61mcg/dL) and ACTH was 188ng/L. He was commenced on medical treatment but declined rapidly and died.All our patients had profound hypokalaemia and metastatic disease at presentation. Many patients do not exhibit classical cushingoid features as EAS tends to develop acutely and underlying malignancy drives weight loss. A high index of suspicion is required to make a diagnosis. EAS should be considered in patients with proximal myopathy, pigmentation, resistant or severe hypokalaemia or hypertension and known or suspected malignancy. Early and quick control of cortisol excess is essential to minimise cardiometabolic abnormalities, severe infections and thromboembolic complications. Prognosis depends upon age, frailty, comorbidity, nature of neoplasm and extent of hypercortisolaemia. Adrenolytics with or without bilateral adrenalectomy, reduction in tumour burden and management of complications are the mainstay of treatment.

SUN-LB12 Prenatal Trenbolone Exposure and External Genital Malformation: A Case Report

Background Trenbolone is a synthetic anabolic steroid used for muscle growth in livestock. Human use is not FDA approved. The active metabolite, 17β trenbolone is 3 times more potent an androgen than testosterone propionate. Prenatal trenbolone exposure in rats results in female offspring with external genital malformations including an increased anogenital distance (AGD). We now report a case of prenatal trenbolone exposure in humans. Clinical Case A 10 hour old baby delivered vaginally at 37 6/7 weeks of gestation with a birth weight of 3615 grams was admitted to the NICU for concern of ambiguous genitalia. Baby was born to 30 year old G6P3 mother who was HIV positive and adequately treated with Triumeq. She had irregular cycles prior to conception and pregnancy recognized at 14 weeks. Unlike her previous pregnancies, during this pregnancy she had acne and mildly increased facial hair. Prenatal cell-free DNA screening was 46XX and ultrasound showed female genitalia. The 9 year old half-sister and 5 year old brother are healthy. No family history of early neonatal deaths. On arrival blood glucose was 55 mg/dL (45-90). On exam baby had no obvious facial dysmorphic features or midline defects. Hand creases were normal and no extremity edema was noted. Genitalia appeared symmetrical and, showed prominent soft tissue of clitoris without corpus enlargement. No gonads were palpable in the groin or labioscrotal folds. Significant posterior labioscrotal fusion was noted. Anogenital ratio was 0.8 (normal <0.5). A single orifice at the base of the clitoral hood was noted, consistent with likely urogenital sinus. Additional history provided by mother included her disclosure of use of 200 mg of IM trenbolone weekly for 5 weeks, for muscle building, prior to her knowledge of being pregnant. Multidisciplinary care included pediatric endocrinology, genetics, pediatric urology, and pediatric infectious disease. Labs at 24 hours of life: Sodium - 139 mmol/L (131-144), Potassium - 5.3 mmol/L (3.2-5.7), Serum glucose - 75 mg/dL (45-90), Random cortisol - 34.1 mcg/dL (1.0-10.0), 17 hydroxyprogesterone - 124 ng/dL (<460), CAH diagnostic panel - normal with exception of elevation in Progesterone - 3400 ng/dL (5-53), Newborn screening - normal, Chromosomal analysis - 46,XX and absent SRY, Ultrasound pelvis - normal Müllerian structures and bilateral intra-abdominal gonads present. Baby was hemodynamically stable, voided well, gained weight by discharge on DOL 4. Baby was stable on follow-up in endocrinology clinic on DOL 10. Surgical repair of anatomic malformation to be performed at 6 months of age by urology team. Conclusion To our knowledge, this is the first report of virilization of female offspring following human prenatal exposure to trenbolone. Women must be cautioned that trenbolone poses risks of external genital malformation to the developing fetus.

SAT-104 Unraveling the Connection Between Cortisol and Pediatric Idiopathic Intracranial Hypertension

Background: Idiopathic intracranial hypertension (IIH) is a condition of elevated intracranial pressure without identifiable secondary causes. The childhood incidence is 0.7 per 100,000 and increases with age, obesity, and female gender. Few case reports in the literature, and our own experience, suggest there may be an association between IIH and adrenal insufficiency (AI) but the real extent is unknown. Aim: To describe the prevalence of AI in children presenting with IIH to a large pediatric referral center. Methods: Retrospective chart review identified all children who presented with IHH and had cortisol measured between January 2010 and September 2019. Based on morning, random or 1 mcg ACTH stimulated cortisol levels, adrenal functioning was classified as: (1) deficient (peak cortisol <16 μg/dl, AM cortisol <5 μg/dl), (2) at risk (peak cortisol 16 - 20 μg/dl, AM cortisol 5 - 13 μg/dl or random < 13 μg/dl), or (3) sufficient (peak cortisol >20 μg/dl, AM or random cortisol >13 μg/dl). Descriptive data present mean (+/- standard deviation), and chi-squared (χ 2) tests of differences are used to examine differences between the adrenal functioning groups. Results: Participants (N=64) were 40.6% male, of mixed ancestry (61% non-Hispanic white; 19% African-American, 16% Hispanic White and 5% Asian), with a mean age of 10.8 (4.8) years. Cortisol levels were obtained at an average of 0.6 (1.9) years after diagnosis of IIH; 23% and 52% of patients had insufficient or at risk cortisol levels. The majority of those in the insufficient (70%) or at risk (80%) groups were exposed to topical, nasal or inhaled corticosteroids, but not systemic. Only 60% and 12 % of those with IIH and insufficient or at risk cortisol testing, respectively, underwent definitive testing with a stimulation test. Adrenal function did not differ by age, race/ethnicity, zBMI, nor prolong exposure to steroids (> 2 weeks), time between IIH diagnosis and cortisol testing (all P>.05). Those in the deficient group were less likely to be female (33%) than those in the at risk (61%; χ 2=3.07, df=1, P=.001) or sufficient (81%; χ 2=7.30, df=1, P<.001) groups. Those with AI were more likely to have history of asthma (53%; vs: 18% at risk and 12% normal; both P>.05) Conclusions: Steroid use and AI are common in IIH and need consideration as a cause of IIH development. Appropriate diagnosis and treatment of AI in children who present with IIH may lead to its resolution, significantly impacting clinical outcomes of these children. In our cohort, the majority had AI or at risk cortisol levels, and many did not undergo further testing. All young children who present with IIH should be evaluated for steroid exposure, including non-systemic steroids, and undergo evaluation for AI. Caution should be utilized in pediatric providers prescribing these medications. More prospective studies are required to evaluate the effects of steroid use in relation to IIH development.

MON-263 Renal Cell Cancer Metastasis to the Pituitary Masquerading as a Non-Functioning Adenoma

A 47 yr. old male with history of RCC and hypertension was seen in pituitary clinic for management of a pituitary mass. He initially presented to an outside hospital with persistent headaches, unintentional weight loss, severe fatigue, dizziness, cold intolerance, low libido and difficulty with erections. CT head showed a pituitary mass. Lab work revealed pan-hypopituitarism with adrenal insufficiency [random cortisol 0.7 ug/dL (4- 19 ug/dL); ACTH 13 pg/mL (7-63 pg/mL)], hypothyroidism [T4 0.52 ng/dL (0.7-1.5 ng/dL); TSH 0.1 mIU/L (0.45-4.5 mIU/L)] and hypogonadism [total testosterone 15 ng/dL (200-1000 ng/dL); LH of 0.6 mIU/mL (1.5-9.3 mIU/mL); FSH of 3.5 mIU/mL (1.6- 8.0 mIU/mL)]. Prolactin was slightly elevated at 34 ng/mL (2- 18 ng/mL) from stalk compression. IGF-1 was 78 ng/mL (Z score -1.2).When we saw him, he was already on hormone replacement with significant improvement in symptoms. He had no visual field defects or symptoms of diabetes insipidus (DI). As for his history of RCC, he underwent a partial left nephrectomy in 2015, followed by a completion nephrectomy shortly after. Pathology was consistent with clear cell RCC. He did not receive any adjuvant therapy; Follow up imaging studies were reportedly negative for recurrence. Pituitary MRI showed a 1.6 X 1.4 X 1.5 cm enhancing sellar and suprasellar mass without compression of optic chiasm. He was thought to have a presumed non-functioning adenoma, and chose to proceed with trans-spenoidal surgery (TSS). Intra operatively, a very vascular tumor was encountered, which could only be debulked safely. Pathology was consistent with metastatic clear cell RCC. A follow up CT showed innumerable lung nodules and a 3.2 cm right adrenal nodule consistent with metastases. He completed stereotactic radiation to the sella and is currently on Ipilimumab and Nivolumab for immunotherapy.MP is uncommon, and seen in 1-4% of patients with cancer in autopsy studies. Breast (40%) and Lung cancer (25%) are the most common tumors causing MP in women and men respectively, with very few case reports of RCC MP (2.6%). DI is the most common symptom of MP, which is thought to be due to direct vascular supply from hypophyseal arteries to the posterior pituitary. Interestingly in RCC MP, anterior pituitary dysfunction is more prevalent (90%) compared to DI (24%). There is also a tendency for suprasellar extension, causing vision loss. Radiologic features that could help distinguish MP from an adenoma include a rapidly enhancing sellar mass, erosion of sellar floor or posterior clinoid process, infundibular thickening, and the presence of intra-tumoral vascular flow voids. There reportedly is no benefit to using FDG- PET to diagnose MP from RCC. There are no standardized treatment guidelines and the choice of treatment is also influenced by the extent of systemic disease.

SAT-339 Calcium Level in a Patient with Rhabdomyolysis. A Tale of Two Phases

Background: Calcium kinetics can be challenging during the different phases of rhabdomyolysis1. We herein report a case of sever hypercalcemia refractory to hemodialysis following a period of hypocalcaemia that developed in a patient with rhabdomyolysis. Case: A 27-year-old male patient was diagnosed with meningoencephalitis complicated with septic shock, continuous seizures, rhabdomyolysis, acute kidney injury and oliguria. His creatinine was 219 μmol/L (53–115), urea was 8 mmol/L (2.5–6.4). Creatine kinase (CK) was significantly high above assay range. Corrected serum calcium was 1.82 mmol/L (2.12- 2.52), phosphate was 0.48 mmol/L (0.81–1.58). He required intermittent sessions of hemodialysis and antibiotics therapy which both have been initiated since the first day of admission. Initially he had hypocalcaemia but as rhabdomyolysis improved, his calcium levels started to rise to reach normal levels by day 13 post admission. By day 16, he started to gradually develop hypercalcemia. Initially, it was 2.73 mmol/L and in another 10 days it was 3.39 mmol/L and reached maximum of 3.90 mmo/L despite the intermittent dialysis sessions. PTH was supressed at 0.62 Pmol/L. Over that time, his renal functions and urine output were gradually improving.The clinical impression was PTH independent hypercalcemia and the work up for that was initiated. CT chest, abdomen and pelvis did not reveal any suspicious masses, lytic bone lesions, or lymphadenopathies. His acid fast bacilli stain and culture were both negative. His chest imaging did not show any findings to suggest sarcoidosis. TSH was normal and random cortisol was 339.2 nmol/l with albumin 20g/L. HIV serology came back negative.He received Calcitonin 500 IU BID for three days and Denosumab 120 mg SC in order to control the hypercalcemia along with, cautious intravenous hydration. Within one week after Denosumab therapy, serum corrected calcium decreased to 3.07 mmol/L. After another week, corrected calcium reached 2.53 mmol/L. When his urine output improved further and his calcium levels dropped, hemodialysis was discontinued. His calcium level later normalised to 2.49 mmol/L.After ruling out the common differential of PTH independent hypercalcemia, and from the diuretic phase the patient went through with concomitant hypercalcemia following hypocalcaemia, it was concluded that the cause of hypercalcemia was rebound hypercalcemia following rhabdomyolysis recovery. Conclusion: hypercalcemia can complicate the recovery phase of rhabdomyolysis. Careful monitoring of calcium levels and management are warranted.

SUN-293 Acute and Long Term Evaluation of Pituitary Functions in Patients with Advanced Heart Block Requiring Pacemaker Implantation: A Pilot Study

Background: Neuronal hypoxia and neuro-inflammation accompanying conditions like traumatic brain injury, stroke, cerebrovascular accidents and sub-arachnoid haemorrhage has been associated with hypopituitarism. Neuronal insults of similar magnitude and hypopituitarism [Growth Hormone (GH), gonadotropin and TSH deficiency in 27.2%, 9.0% and 2.2% patients respectively] has also been noted in a single study till date conducted in patients of ventricular arrhythmias requiring cardio-pulmonary resuscitation1. Patients with heart block, a more frequent form of cardiac arrhythmia usually presents with haemodynamic compromise and may be predisposed for developing either acute or delayed hypopituitarism which has never been studied before. Aims and objective: Our study was aimed at exploring whether pituitary dysfunction occurs in patients presenting with heart block and requiring pacemaker implantation. We analysed anterior pituitary functions in these cohort of patients during acute hospitalization and later during follow. Study design: Cross sectional prospective study Materials and Methods: Fifty-one patients were included in the study (mean age-65.98±10.9years; 34 men & 17 women). Pituitary hormonal profile was done within 48 hours of presentation and after a mean follow up of 12.52 ± 2.2 months. Total T3, total T4, free T4, TSH, FSH, LH, Testosterone (in men), Estradiol (in women), Prolactin, and random Cortisol were measured in all participants at baseline and in follow-up. Fixed dose Glucagon (weight<90kg-1mg; ≥90kg-1.5mg) stimulation test was done in follow-up to assess GH and cortisol axes. Results: Among 30 (out of 50) patients who turned up for follow-up, GH, cortisol and TSH deficiency was noted in 50% (n-15), 13.3% (n-4) and 3.2% (n-1) of subjects, respectively. Pan-hypopituitarism characterised by deficiency of at least two hormonal axes was seen in 16.7% (n-5) patients. Conclusion: Significant delayed hypopituitarism especially GH deficiency was seen among patients of heart block. Implications: This novel finding if reproduced in subsequent studies will result in unearthing of a significant etiology of hypopituitarism which could potentially become the most common cause of acquired adult onset hypopituitarism considering the huge burden of patients with heart block. Heightened cardiovascular risk due to hypopituitarism in these patients may be reversed by active screening and replacement of deficient hormones.