AM Cortisol Research Articles

SAT-189 Pheochromocytoma as a Rare Cause of Elevated Blood Pressure During Pregnancy

Endocrine causes of elevated blood pressure during pregnancy are considered a rare, mainly when compared to the more frequent pregnancy-related hypertensive disorders. Thus, the diagnosis of endocrine-related secondary hypertension cases and the outcome of pregnancy will largely depend upon a high clinical suspicion.A 28 year-old female, presented in pregnancy with elevated, difficult to control blood pressure, leading to induced delivery of a preterm 32 week baby. The baby was admitted to the NICU, where she stayed for 3 weeks.After delivery, Patient was evaluated in the Endocrine Clinic. She reported episodes of pulsatile headaches, palpitations and excessive sweating for the past 1 year. Each episode would last around 10 minutes and resolved spontaneously. Systolic blood pressure during these episodes was in the 200s and would return back to normal afterwards.Past medical, surgical and social history was unremarkable. She reported that her mother died suddenly in her 30s from an unknown cause. Physical exam, including blood pressure, was unremarkable in the clinic.The patient underwent a work up for secondary causes of hypertension after delivery. Tests included plasma metanephrines: 327pg/ml (<57pg/ml), plasma normetanephrines: 7,135pg/ml (<148pg/ml), Chromogranin A 768 ng/ml (<93ng/ml) and a 24 Hour fractionated total metanephrines: 10,170 mcg/24hrs (40-412mcg/24h). She had normal TSH, aldosterone, renin and AM cortisol level.CT scan of chest, abdomen and pelvis showed a large right retroperitoneal, heterogeneously enhancing mass, measuring 5.8 x 3.7 x 8.3 cm, which encircles the aorta approximately 180 degrees, without evidence of vascular invasion.Diltiazem three times a day was initiated for preoperative blood pressure control. After 2 weeks, she underwent laparoscopic resection. Pathology showed lesional cells that are positive for synaptophysin and chromogranin while negative for AE1/3 and sustentacular cells that are highlighted by S100, thus supporting a diagnosis of paragangliomas.Postoperatively, the patient was weaned off all blood pressure medications. Repeat testing showed plasma metanephrines: 26 pg/ml and plasma normetanephrines: 164 pg/ml. The patient is scheduled to establish care with Endocrine Genetics Clinic.A timely diagnosis of pheochromocytoma during pregnancy can dramatically affect maternal and fetal mortality rates (1). This case illustrates the importance of a high clinical suspicion for pheochromocytoma as a cause of elevated blood pressure during pregnancy, particularly in patients who lack other characteristics typical of pregnancy related hypertension disorders (proteinuria, edema, etc.) or present with an elevated blood pressure early in pregnancy.

MON-462 Rebel Nodule or Reluctant Gland? the Challenge Presented by Heterophile Antibodies

Introduction:Interpretation of thyroid function tests (TFTs) in background of non-specific symptoms concerning for hypothyroidism, has become challenging with assay interference. Heterophile antibody interferences are both test and laboratory platform dependent. We present a case of a toxic nodule erroneously diagnosed as isolated central hypothyroidism due to heterophile antibody interference.Case:A 38 year old lady was referred to Endocrinology for possible central hypothyroidism with symptoms of progressive fatigue, 40lb unintentional weight loss, poor appetite, nausea, intermittent diarrhea/constipation, occasional cold intolerance and intermittent lightheadedness. TFTs suggested low TSH 0.175 mcIU/ml (N 0.35-3.8 mcIU/ml) and low FT4 0.74 ng/dl (N 0.8-1.8 ng/dl). Pituitary hormone evaluation revealed normal ACTH, AM cortisol, IGF-1, prolactin and FSH. A pituitary MRI was normal.Two months later, she had worsening fatigue, anxiety with palpitations and tremors, and 14lb weight gain. TFTs again confirmed low TSH (0.575 mcIU/ml) and lower FT4 (0.70 ng/dl). Empirical weight-based levothyroxine (LT4) supplementation was initiated for central hypothyroidism. Six weeks later, TFTs showed hyperthyroidism (TSH <0.005 mcIU/ml, FT4 1.57 ng/dl). The patient endorsed worsening lightheadedness and palpitations on LT4, which resolved on LT4 discontinuation. One month later, TFTs were abnormal again (TSH 0.047 mcIU/ml, FT4 0.74 ng/dl).Due to persistent discordance in symptoms and biochemical tests, TFTs were evaluated for heterophile antibody interference. While HAMA-treated TSH remained low (0.04 mIU/l), FT4 by equilibrium dialysis (FT4 ED) was normal (1.1 ng/dl, regular assay 0.74 ng/dl), suggesting subclinical hyperthyroidism. A thyroid uptake scan confirmed an autonomous toxic right thyroid nodule with suppressed remaining gland. Patient ultimately underwent 15 mCi RAI ablation of the nodule. TFTs done 1 month post-RAI suggested normal TSH (1.2 mcIU/ml) and normal FT4 ED (1 ng/dl). Previous symptoms have since resolved.Conclusion:Current methods of TFTs are generally reliable in diagnosing and monitoring thyroid disease. Rarely, medications, supplements, and endogenous antibodies can bind to TSH, T4 or lab reagent, resulting in inaccurate values. This has become increasingly common with use of high dose biotin. TSH with HAMA/heterophile antibodies and FT4 ED are more accurate forms of diagnostic testing.When approaching patients with symptoms not consistent with typical hypo- or hyperthyroidism and are not responding as expected to therapy, it is important to consider more accurate testing to rule out assay errors.

SUN-160 Development of Adrenocortical Carcinoma in an Adrenal Nodule After Nine Years of Size Stability on Imaging: A Case for Critical Review of Efficacy of Radiographic Size Criteria

BACKGROUND: Current consensus guidelines for adrenal incidentalomas smaller than 4 cm recommend re-evaluation up to 2 years. Although there is no consensus for imaging surveillance beyond 2 years, in general, stability in size over time is considered a sign of benign nature. Clinical Case: A 50-year-old African-American woman presented to Endocrinology for resistant hypertension since age 30 and an enlarging right adrenal nodule. She was obese, weighing 138.8 kg with a BMI of 55.97 kg/m2, without clinical Cushingoid features. At her first visit she was taking the following antihypertensives: amlodipine, losartan, hydrochlorothiazide, and clonidine patch. She took no other prescription medications. Her baseline metabolic blood profile was normal. Further testing revealed a profile consistent with possible primary hyperaldosteronism and subclinical Cushing’s syndrome: plasma aldosterone 17 ng/dl, plasma renin activity 0.232 ng/ml/hour, ACTH 10 pg/ml, AM cortisol 8.3 mcg/dl, DHEAS 30 mcg/dl, and 1mg dexamethasone suppression test resulted in cortisol of 7.6 mcg/dl (normal < 1.8 mcg /dl) with a simultaneous dexamethasone level of 357 ng/dl (140 – 295 ng/dl). However, 24-hour urinary free cortisol and urinary metanephrines were within reference ranges. Further confirmatory tests were not performed due to her imaging findings, as described below.The earliest abdominal imaging was a CT abdomen with contrast in 2005 which measured a 2.1 cm right adrenal mass. For various reasons she had repeat CT contrast imaging in 2006, 2007, 2012, and 2014 demonstrating no changes in the dimensions of her adrenal nodule, noting all the studies were performed with contrast only and without Hounsfield unit (HU) measurements. In 2017, a CT abdomen with adrenal protocol demonstrated a right adrenal mass measuring 4 cm x 3.5 cm (increased from 2.1 X 1.2 cm in 2014), characterized by 43 HU pre-contrast, 71 HU post-contrast, and an absolute washout of 29%. Due to high suspicion for malignancy, a PET-CT was performed with FDG, which revealed high uptake in the right adrenal mass.She was referred for a right adrenalectomy and pathology showed adrenocortical carcinoma with some infiltration into adipose tissue. There was a high mitotic index (42 per 50 high powered fields) and Ki67 of 35%, classified as Stage III pT3NxM0. She was referred to oncology and treated with external radiation to the adrenal bed along with initiation of mitotane. Conclusion: This case infers that long-term size stability of an adrenal nodule does not confer full confidence of a benign process. Compared with previous reports in the literature describing long latencies for ACC, this is one of the longest records of size stability over 9 years followed by a size increase 3 years later.

SAT-449 Factors Associated with Reduced Thyroid Hormones in Cushing Syndrome Patients Before and After Surgical Cure

Background: Hypercortisolemia adversely affects thyroid hormone secretion. We previously described the temporal pattern of thyroid function recovery in 23 patients (1). However, the factors leading to suppression and recovery of the hypothalamic-pituitary-thyroid (HPT) axis in Cushing’s syndrome (CS) are not fully understood. We performed two separate studies to investigate these factors. Methods: In study 1, we examined patients (pts, n=62) with CS who underwent curative surgery and recorded their serum morning and evening cortisol, ACTH, tumor volume and duration of symptoms and 24-hour urine free cortisol (UFC) at baseline and the morning serum free T4, TSH and T3 at six-month intervals after cure. Data were log-transformed and Pearson correlations were performed. Linear mixed models were used to study factors that predict recovery of thyroid function. In study 2, we examined the diurnal variation of TSH by performing hourly TSH measurement between 3—7 PM and 12—4 AM on a cohort of pts (n=45) before surgery. Wilcoxon Signed-Rank method was used for comparisons of mean TSH across time and Pearson correlations were performed on log-transformed data. P values <.05 were considered significant. Results: Study 1: In this larger cohort, we confirmed previous findings of suppressed or low normal fT4 and TSH values with active hypercortisolism, with normalization after cure that reflected changes in the T3:TSH, fT4:TSH and T3:fT4 ratios. There were inverse linear correlations between log10 UFC, serum AM and PM cortisol; and log10 TT3, fT4 and TSH before surgery. Independent negative prognosticators of circulating fT4 recovery included UFC greater than 1000mcg/day (nl: 3.5—45mcg/day), duration of symptoms of less than one year, and ACTH levels greater than 60pg/mL(nl: 5—45pg/mL) Study 2: The nocturnal (12 - 4AM) TSH surge was reduced, so that the difference in day and night TSH values was not statistically significant; this contrasts with the 30—50% nocturnal TSH increase above daytime values seen in healthy subjects. There was an inverse relationship between UFC and nocturnal TSH, daytime TSH and TBG values, but there was no direct relationship between UFC and percent changes in nocturnal TSH values. Conclusions: Our findings suggest that a deficit in TSH stimulation of the thyroid gland may explain the reduction in T3 and T4 levels. There is a dose-response relationship between various measures of hypercortisolemia and both thyroid hormones and the pattern of TSH secretion. Finally, the severity of hypercortisolism correlates with a longer time to recovery of the HPT axis in pts with CS after curative surgery. 1. Shekhar S et al. HPG and HPT Axes in Cushing Syndrome. J Endocr Soc, 3 S1, April May 2019

Evidence of Systemic Absorption of Enteral Budesonide in Patients with Fontan-Associated Protein-Losing Enteropathy.

To evaluate for evidence of systemic glucocorticoid absorption in cases of Fontan-associated protein-losing enteropathy (PLE) treated with enteral budesonide, we reviewed the charts of 27 patients with Fontan-associated PLE followed at Children's Hospital Colorado from 2005 to 2018. Cases were excluded for lack of budesonide thserapy or a treatment duration of less than 6months. Charts were examined by two endocrinologists for review of prior biochemical endocrine evaluations, alterations in linear growth, and physical exam findings consistent with steroid excess. Twelve patients met inclusion criteria. Eight had prior documented cortisol screening. Three patients were tested while on treatment with a median fasting AM cortisol of 0.9 mcg/dL; two of these had a concomitantly measured ACTH, both below the detectable limit. Five patients were tested while weaning or having discontinued budesonide, with a median fasting AM cortisol of 9.1 mcg/dL. Eleven patients had decreases in height velocity associated with starting budesonide. Six patients had documentation of cushingoid features by an endocrinologist. In this cohort of children treated with budesonide for PLE following Fontan, clinical signs of systemic glucocorticoid absorption were frequent. Cortisol secretion was suppressed while on therapy, with adrenal recovery noted once budesonide was discontinued. Growth failure and cushingoid features were common findings. While these findings should be confirmed in larger cohorts, we recommend that the evaluation for systemic absorption of exogenous steroids be considered in patients treated with long-term enteral budesonide given the potential risk for adrenal crisis in times of physiologic stressors.

Symptomatic Pituitary Metastases: Two Case Reports with Contrasting Clinical Presentations

To report 2 interesting cases of pituitary metastasis (PM) with differing presentations, and briefly review the literature regarding the incidence, presentation, and natural history of PMs. Case report and literature review. Patient 1 had known widely metastatic papillary thyroid cancer and presented with signs and symptoms of anterior pituitary dysfunction. He was found to have an undetectable AM cortisol. Further lab evaluation showed complete anterior panhypopituitarism. Pituitary magnetic resonance imaging (MRI) revealed an infiltrative pituitary lesion, which was presumed to be a meta-static lesion from his thyroid cancer. Patient 2 presented with an acute increase in urinary frequency and polydipsia. Water deprivation testing confirmed central diabetes insipidus (DI). Brain MRI showed an infiltrative pituitary lesion, which was the first sign of recurrent metastatic colon cancer. Subsequently, he developed the rapid onset of complete anterior panhypopituitarism. Review of the literature shows that when PMs produce symptoms, the most common presentation has traditionally been central DI. However, this is shifting as the incidence of anterior dysfunction and cranial nerve abnormalities is rising in more recent reviews. Central DI has traditionally been the most common presenting symptom of PM, however symptoms reflective of anterior pituitary dysfunction and cranial nerve abnormalities are being reported with increasing frequency. PM should remain in the differential in any form of pituitary dysfunction.

Neurobiology of Female Homicide Perpetrators.

Neurobiology of female homicide perpetrators is not well understood. Data from private interviews and examinations of females were re-analyzed comparing those who committed homicide (n = 9); other violent crimes, no known homicide (n = 51); nonviolent crimes, no known violent convictions (n = 49); and noncriminals (n = 12). Homicide perpetrators suffered the most childhood sexual abuse (CSA); most recent abuse; had the most neurological histories, mainly traumatic brain injuries (TBIs); most health care access for abuse-related injuries; lowest AM and PM salivary cortisol; and greatest proportion who committed crime under the influence of alcohol. Only CSA, years since last abuse, TBI, neurological histories, and health care access for abuse-related injuries were significant. Those who committed homicide under the influence of alcohol suffered the most recent abuse and had the lowest AM cortisol and flattest diurnal cortisol slope (DCS) compared with others; though the n precludes determining significance. Amount of time since last abuse, AM cortisol and DCS progressively decreased as crime severity increased; other variables progressively increased as crime severity increased. These preliminary findings suggest that low AM cortisol, flat DCS, greater CSA frequency and severity, recent abuse, TBIs, and health care access for abuse-related injuries could be risk factors for females committing homicide. Further study is needed due to the small n of homicide perpetrators. Abuse victims may be at greater risk for alcohol use and cortisol dysregulation associated with perpetrating violence, especially homicide. Frontal lobe damage from TBIs may decrease ability to control behaviors associated with emotions from the limbic system. Health care providers released these women when their abuse-related injuries were not life-threatening; yet, they were life-threatening for victims of their subsequent homicides. Females accessing health care for abuse-related injuries present a critical opportunity for violent crime prevention interventions.

Visual Vignette

Case Presentation: A 25-year-old woman presented with galactorrhea to the endocrinology clinic. She had regular menstrual cycles until she began depot medroxyprogesterone a few years prior. She denied headaches or visual changes. She had no significant past medical or surgical history. On exam, she had a normal visual field on confrontation test. She did not have appreciably delayed reflexes or dry skin. Lab evaluations revealed a prolactin of 69 ng/mL (normal, 3.0 to 30.0 ng/mL). Prolactin dilution ruled out a hook effect. Other hormones levels were: TSH >150 mIU/L (normal, 0.40 to 4.50 mIU/L), free T4 0.4 ng/dL (normal, 0.8 to 1.8 ng/dL), and AM cortisol 13.4 mcg/dL (normal, 4.0 to 22 mcg/dL). Thyroid peroxidase antibody was 394 IU/mL (normal, <9 IU/mL) and thyroglobulin antibody was 2 IU/mL (normal, ≤1 IU/mL). LH was <0.2 mIU/mL (normal in midfolicular phase, 2.12 to 10.89 mIU/mL) and FSH was 4.6 mIU/mL (normal in midfollicular phase, 3.85 to 8.78 mIU/mL). Visual field testing revealed mild field cut bilaterally. Magnetic resonance imaging (MRI) of the brain revealed a 2 × 1.5 × 1 cm pituitary mass impinging on the optic chiasm (Fig. 1). The patient was initiated on levothyroxine which resulted in resolution of galactorrhea and hyperprolactinemia. It also led to a significant reduction of the size of the pituitary mass (Fig. 2) and resolution of the visual field defect within one year. What is the diagnosis? Fig. 2 View Large Image Figure Viewer

SUN-396 Subclinical Cushing's Syndrome: Should We Treat?

Background: Subclinical (mild) Cushing’s syndrome (SCS) is a common finding in incidental adrenal masses. Recent studies have shown there is increased morbidity and mortality with SCS. We present two cases that illustrate the importance of aggressive treatment of SCS. Clinical Case: A 66-yr-old female with multiple sclerosis and HTN presented to the ER with a 3-week history of hypertensive paroxysms >200/110. HTN previously has been well controlled with metoprolol and olmesartan. Evaluation for pheochromocytoma was negative. ACTH was <5 pg/mL, AM cortisol 14.6 mcg/dL, 24-hr-urine cortisol 108.4 mcg/d (RR <50), and 1 mg dexamethasone suppression test showed plasma cortisol 1.9 mcg/dL (RR <1.8). Patient was maintained on Toprol XL, amlodipine, amiloride, clonidine patch, and clonidine tablets. She continued to experience hypertensive paroxysms in addition to fatigue, hypersomnolence, proximal muscle weakness and developed pre-diabetes (HbA1c 6.1%). CT abdomen showed left adrenal thickening; 8 AM cortisol 23.4 mcg/dL (RR 6-18.4) and 11 pm salivary cortisol 0.145 mcg/d (RR <0.112). Mifepristone 300 mg QD and spironolactone 50 mg QD were initiated. Within 2 months, patient had resolution of hypertensive swings, was off clonidine, had a 25-50% improvement in muscle strength, and HbA1c 5.9%. Clinical Case: A 67-yr-old male with coronary disease and HTN presented with a BP of 240/130. Work up revealed left adrenal mass of 1.5 x 2.9 x 1.4cm. Endocrine work up was negative except for 24-hr-urine cortisol 100 mcg/day (RR <50). Patient maintained on 4 antihypertensive medications. He continued to have borderline HTN, weight gain, and developed pre-diabetes (FBG 116). CT scan at 6 months showed decreased L adrenal adenoma of 1.7 cm. Two years after initial presentation, 1 mg dexamethasone test showed AM cortisol 1.9 mcg/dL (RR <1.8), 11 pm salivary cortisol x2 negative, and repeat 24-hour urine cortisol 58 mcg/d (RR <50). Physical exam was negative for Cushingoid features. Patient was pretreated with mifepristone and underwent L adrenalectomy. Pathology was consistent with nodular adrenal hyperplasia with positive ACTH staining. Six months following surgery, improved blood pressure and glycemic control were noted allowing medication dose reduction. Discussion: It is important to recognize that patients with adrenal SCS are at increased risk for metabolic disease, cardiovascular incidents, and mortality. Patients should be monitored closely, and treatment can result in improved metabolic parameters and quality of life. Reference: Di Dalmazi, G., et al. (2014). Cardiovascular events and mortality in patients with adrenal incidentalomas that are either non-secreting or associated with intermediate phenotype or subclinical Cusing’s syndrome: 15-year retrospective study. The Lancet Diabetes & Endocrinology, Vol 2, Issue 5, 396-405.

SUN-395 Intermittent Hypogonadotropic Hypogonadism Associated with Cyclic Cushing’s Disease

Introduction: Cyclic Cushing’s syndrome is defined as cortisol excess which fluctuates with periods of normal cortisol secretion, usually associated with Cushing’s disease (CD). Majority of cyclic CD patients exhibit clinical features of hypercortisolism which vary with the “cycle” of disease. We present a case of a patient without overt signs or symptoms of CD and biochemical evidence of intermittent hypogonadism which was associated with the cyclic nature of CD. Case: A 67 year old male with history of mild diabetes mellitus type 2 and hypertension was referred to endocrinology for evaluation of hypercortisolism after a routine screening CT chest revealed a 1.1 cm mass in the right adrenal gland. He had no typical manifestations of hypercortisolism other than mild fullness of bilateral supraclavicular fossae. His screening labs showed 24 hour urine free cortisol level of 243.3 ug (ref. range 4-50) with aldosterone-renin ratio, plasma renin activity and metanephrines within normal limits. After 1 mg dexamethasone suppression, AM serum cortisol was 24 mcg/dL (7-23) with ACTH 42 pg/mL (7-69). AM cortisol remained unsuppressed after 8 mg of dexamethasone as well. MRI brain showed no evidence of pituitary adenoma. Inferior petrosal sinus sampling (IPSS) revealed significantly increased central-peripheral ACTH ratio of 57 at 2 minutes post IV Acthrel 100 ug. Surprisingly, another AM Cortisol was found to be 8 mcg/dL with ACTH of 43 pg/mL. This prompted further 24h-urine cortisol tests with at least 3 elevated and 2 normal results (ranging from 9.1-203 mcg) meeting the consensus-based diagnostic criteria of cyclic Cushing’s disease. He also had intermittent hypogonadotropic hypogonadism with testosterone levels associated with rise and fall of cortisol levels. His free testosterone was 24 and 53 pg/mL (47-244) measured a few months apart which correlated with PM cortisol of 25 ug/dL (3-12) and AM cortisol of 11 ug/mL, respectively. He was also diagnosed with primary hyperparathyroidism. Genetic testing did not detect MEN1 gene mutation. He underwent partial transsphenoidal hypophysectomy and parathyroidectomy, following which he was treated with daily prednisone being gradually tapered off. Up till date he has had clinical improvement in his physical exam and diabetes, along with free testosterone level of 62 pg/mL and normal serum calcium levels. Conclusion: Clinicians should have a high index of suspicion for cyclic CD in patients being screened for hypercortisolism particularly those with mild or no clinical manifestations. Paradoxical responses to dynamic testing are often noted and thus IPSS results may be confounded if not in the active Cushing phase. It is important to remember while interpreting lab results that comorbid disorders like hypogonadism may also show cyclic nature dependent on the cycle of CD the patient may be in.

SUN-380 A Case of Cushing Syndrome

Introduction: Cushing's syndrome is characterized by over-secretion of cortisol. Etiologies of Cushing’s syndrome can be ACTH dependent or independent. This highlights a case of ACTH independent Cushing’s secondary to an adrenal lesion. Clinical case: A 28 year old lady presents to Endocrine clinic for evaluation of secondary amenorrhea for 2 years. She was previously evaluated by a gynecologist who performed a progesterone challenge test with no response. The patient reports mild acne during adolescence but denies excess hair growth, or voice deepening. She notes weight gain primarily distributed in her abdomen and face. She reports fatigue, anxiety, easy bruising, intermittent headaches as well as some polydipsia and polyuria. She is not experiencing peripheral muscle weaknessm galactorrhea, or problems with peripheral vision. Her medications are fish oil, multivitamin, and probiotic. Physical exam is notable for BMI of 21.7 kg/m2, round face with increased facial plethora, and an increased posterior fat pad. Significant labs include DHEA sulfate 15mcg/dL (18-391mcg/dL), FSH 6.3mlU/mL, estradiol <15pg/mL for a non-premenopausal woman (19-357pg/mL), total testosterone 3ng/dL (2-45ng/dL), prolactin 25.9 ng/dL (3.0-30 ng/dL). Her ACTH is <5pg/mL (6-50pg/mL) and AM cortisol followed by 1 mg dexamethasone of 22.9mcg/dL (<2.0mcg/dL). Repeat low dose dexamethasone suppression test is significant for AM cortisol 20.7 mcg/dL (4-22mcg/dL) and dexamethasone 258ng/dL. CT Abdomen is performed revealing a left sided adrenal mass. The patient undergoes unilateral adrenalectomy with pathology demonstrating an adrenal cortical adenoma. Her post-operative midnight salivary cortisol levels are appropriately low. Given some symptoms of adrenal insufficiency of dizziness and weakness she undergoes a slow hydrocortisone taper. Her menstrual cycles gradually return, facial plethora and sites of abnormal fat deposition resolve. She reports a significant improvement in her psychological wellbeing with decreased anxiety and increased functionality. Conclusion: The signs and symptoms of Cushing’s syndrome are attributable to the presence of hypercortisolism. While there are signs highly suggestive of Cushing’s syndrome including central obesity with wasting of the extremities, increased dorsocervical fat pad, easy bruising and wide purple striae, symptoms can be subtle, leading to a delay in diagnosis. Our patient presented with a complaint of amenorrhea. Menstrual irregularities are very common in women with Cushing’s syndrome. These symptoms are due to suppression of gonadotropin-releasing hormone secretion secondary to hypercortisolemia, with resultant decrease in levels of FSH and LH. A high level of suspicion is important in order to diagnose Cushing’s syndrome as curative treatment leads to a significant improvement in morbidity and the patient’s quality of life.

SUN-432 A Case of Sellar Plasmacytoma Masquerading as Pituitary Carcinoma with Hypopituitarism

Background: Sellar plasmacytomas are rare tumors arising from clonal plasma cells localized to the sellar/parasellar region. They may mimic other pituitary pathology such as pituitary adenomas, chordomas, meningiomas or metastatic carcinomas in both clinical manifestations and radiographic evidence. Certain features such as predominance of cranial nerve palsies and absence of hypopituitarism appear to be more common with sellar plasmacytomas. We present an interesting case of a sellar plasmacytoma, initially mistaken for pituitary carcinoma, with rapid development of hypopituitarism and systemic multiple myeloma. Case: A 75 year old healthy male presented with sudden onset left eye diplopia and retro-orbital pain. Left eye ptosis and diplopia with left lateral and upward gaze were noted on exam. Initial MRI brain revealed a 17mm soft tissue mass involving pituitary and clivus, extending into the left superior orbital fissure, concerning for pituitary carcinoma. With the exception of low LH (1.2) and testosterone (25), baseline pituitary hormone labs, complete blood count and metabolic panel were within normal limits. Within 1 month, he acutely presented with fever, confusion, weakness, and bony pains. Repeat pituitary labs showed low ACTH < 5, AM cortisol 4.3, TSH 0.07, FT4 0.5. New findings of acute renal injury, hypercalcemia, anemia with elevated Mspike, Kappa light chain 39.7 (0.3-2.0mg/dl), kappa/lamda ratio 66.2 (0.3-1.6) and beta2microglobulin 4484 were found. Repeat MRI brain noted multifocal osseous metastatic disease with left sellar and cavernous sinus lesion contiguous with clival osseous lesion displacing pituitary gland, concerning for plasmacytoma. PET/CT showed focal lytic lesions in clivus and posterior left iliac bone. Bone marrow biopsy confirmed 70% myeloma involvement with kappa monotypic plasma cell population. He was started on hydrocortisone, levothyroxine, chemotherapy and XRT. Conclusion: The rarity of plasmacytomas, combined with their clinical presentation and imaging characteristics similar to other sellar tumors, can often result in misdiagnosis. Accuracy of diagnosis is critical, as sellar plasmacytomas and underlying multiple myeloma (present in 50% of cases) require XRT and systemic chemotherapy respectively rather than surgery. Although pituitary function is usually preserved in plasmacytomas, our case shows that acute anterior pituitary dysfunction can be an early presenting sign.

SUN-436 Severe Hyponatremia as the Presenting Feature of Partially Empty Sella

Introduction: We report a case of severe acute on chronic hyponatremia meeting the laboratory diagnostic criteria of SIADH. Subsequent evaluation showed secondary adrenal insufficiency due to partially empty sella. Hyponatremia completely resolved following hydrocortisone treatment. Clinical Case: A 76-year-old man with history of hypothyroidism and SIADH was admitted with weakness, fatigue, and leg cramps for the past 3 months. He was staying in a cabin with a broken air conditioner during the summer when his symptoms started. Physical exam revealed mild dry mucus membranes, normal skin turgor, capillary refill less than 2 sec., bradycardia, and no skin hyperpigmentation. He was found to have acute-on-chronic hyponatremia with a serum sodium of 115 mEq/L (baseline 124 mEq/L-130 mEq/L), which worsened with initial volume resuscitation. Lasix and salt tablets were not effective treatment. Other labs showed a low serum osmolality (241 mOsm/kg), high urine osmolality (598 mOsm/kg), high urine sodium (121 mmol/L), low serum uric acid (2.7 mg/dL, n 3.3-8.5 mg/dL), normal TSH, and a low normal AM cortisol (5.7 ug/dL, n 4.0-17.0 ug/dL). A subsequent cosyntropin stimulation test confirmed adrenal insufficiency with a 60 min cortisol of 10.3 ug/dL. ACTH was inappropriately normal (23 pg/mL, n 7-69 pg/mL) indicating a central etiology. In addition, he had a mildly elevated prolactin (23 ng/mL, n 4-15 ng/mL), inappropriately normal TSH (2.83 uIU/mL, n 0.30-4.50 uIU/mL), low normal total T4 (5 ug/dL, n 4.9-11.7 ug/dL), and a mildly low total T3 (52.3 ng/dL, n 58.0-159.0 ng/dL) suggesting a possible secondary hypothyroidism. A pituitary MRI revealed partially empty sella without evidence of pituitary adenoma. The patient was started on stress-dose hydrocortisone with subsequent increased urine output (4 L within 8 h of initial treatment) and increased serum sodium as well. To prevent rapid sodium correction, one dose of desmopressin was given with a low rate hypertonic saline to equilibrate the desmopressin effect. Hydrocortisone was tapered to maintenance dose, and the fluid restriction was discontinued to prevent dehydration. His home Levothyroxine dose was increased, and he was discharged with a serum sodium of 133 mEq/L. As an outpatient, his sodium has normalized with continued treatment. Discussion: Secondary adrenal insufficiency is characterized by euvolemic hyponatremia with biochemical features of SIADH without hyperkalemia. ADH increases due to the lack of cortisol negative feedback loop and the reduction in systemic blood pressure and cardiac output from cortisol deficiency. Hyponatremia corrects rapidly with steroid treatment, which turns off ADH and causes free water excretion. Desmopressin and hypertonic saline can be effectively used to prevent or stop rapid sodium correction. An interesting feature about this case is that partially empty sella is the cause for hypopituitarism.

SAT-316 MAX-Related Bilateral Pheochromocytoma Associated with Subclinical Adrenal Insufficiency: A Case Report

INTRODUCTION: Loss-of-function mutation in the MYC-associated factor X (MAX) gene causes hereditary pheochromocytoma (PCC) that are frequently bilateral or multifocal1. Adrenal insufficiency (AI) associated with unresected bilateral PCC has not been previously described. We hereby present a case of subclinical AI in a patient with bilateral PCC. CLINICAL CASE: An otherwise healthy 30-year-old woman was found to have a pathogenic MAX gene mutation (c.228delG) after undergoing genetic testing for a significant family history of PCC in 3 relatives. She participated in high-intensity interval training 5 times per week and denied episodes of palpitations, flushing, diaphoresis, or dizziness, but endorsed frequent pulsatile tinnitus and morning headaches. She had a history of hypertension in late pregnancy which had been presumed gestational. Exam was notable only for manual BP 152/110 mmHg, HR 110 bpm, and a faint resting tremor. Lab work was consistent with PCC: plasma norepinephrine 12417 pg/mL (ref <874) and normetanephrine 26 nmol/L (ref <0.9); urine norepinephrine 3378 mcg/24h (ref <135) and normetanephrine 16620 mcg/24h (ref <500). AM cortisol was 10.9 mcg/dL (ref 5-20) with a high normal ACTH of 46 pg/mL (ref 0-46) and low DHEA-S of 23 mcg/dL (ref 75-530). She had no prior history of glucocorticoid exposure, and thyroid studies were normal. CT imaging revealed bilateral contrast-enhancing heterogeneous adrenal masses (R: 3.5 x 2.2 cm; L: 4.6 x 4.5 cm). She was treated with alpha- then beta-adrenergic blockade and subsequently underwent surgical removal of both adrenal tumors with sparing of the superior adrenal cortices bilaterally. Plasma and urine catecholamines and metanephrines normalized a week post-operatively, and she began to report fatigue and dizziness. Two weeks post-operatively, midday plasma levels of cortisol, DHEA-S, and ACTH were 6.3 mcg/dL, <15 mcg/dL, and 118 pg/mL, respectively. Standard-dose 250mcg ACTH stimulation test confirmed AI with peak cortisol of 15.1 mcg/dL. Replacement hydrocortisone was initiated with prompt resolution of symptoms. CONCLUSIONS: Individuals with a pathogenic MAX mutation require prompt screening for PCC as symptoms may be subtle despite significant biochemical abnormalities. Large PCCs may also impact hormone synthesis by the adjacent adrenal cortex. Even prior to surgery, this patient had subclinical AI as evidenced by a high-normal plasma ACTH and clearly low DHEA-S. The latter is the earliest adrenal steroid to decline in patients with primary or central AI2. It is unclear whether her worsening adrenal function after surgery was a surgical complication or due to dramatic decline in circulating catecholamines. Regardless, loss of adrenal androgen production warrants close follow-up for development of AI. REFERENCES: (1) Burnichon N et al. Clin Cancer Res 2012;18:2828 (2) Sayyed Kassem L et al. JCEM 2012;97:3655

MON-332 Metastatic Pancreatic Neuroendocrine Tumor: A Very Rare Cause of Ectopic ACTH Production (ACTHoma)

Introduction Ectopic ACTH syndrome (EAS)is responsible for 10% of Cushing’s syndrome. Multiple tumors, most commonly small cell carcinoma of lung are associated with EAS. Pancreatic neuroendocrine tumors (pNETs) are usually associated with secretion of pancreatic polypeptide, gastrinomas, insulinomas, glucagonomas and vasoactive intestinal peptide (VIPomas). EAS or “ACTHomas” are rarely associated with pNETs. Case 76y/o man with ah/o hairy cell leukemia, bladder cancer (both in remission), and stage M1 unresectable pNET tumor with liver metastases presented with generalized weakness. Discovery of his pNET was incidentally noted during routine surveillance with CT monitoring following successful bladder cancer treatment six years ago. Treatment of his pNET initially began with Everolimus and then switched to Lanreotide injections. No evidence of Cushing’s Syndrome at the time of diagnosis. The lesions remained stable in size and patient was doing well. Physical exam was notable for lethargy, frailty, and absence of Cushingoid features. Labs showed serum glucose 231mg/dl, sodium 141mEq/L, potassium 2.4mEq/L, AM cortisol 116 ug/dL (range 6.7-22.6ug/dl) and ACTH was 209.6pg/mL (range 7.2-63.3pg/mL). Renin-aldosterone levels were normal. Cortisol level did not suppress with low dose or high dose dexamethasone. His hospital course was significant for persistent hypokalemia despite aggressive supplementation, difficult to control blood glucose, and worsening kidney function. EAS with pNET is very refractory to management and may be rapidly progressive. They occasionally demonstrate classic manifestations of Cushingoid features. However, they often lack the traditional phenotypic features of Cushing syndrome. Treatment options for EAS in the setting of an unresectable tumor include medical management versus bilateral adrenalectomy. Metyrapone, a cortisol synthesis inhibitor, can be an effective therapy. Ketoconazole, an antifungal that inhibits cortisol production can be an alternative, but may need weeks to achieve control. Etomodate can rapidly reduce cortisol levels, but requires intensive care monitoring. Somatostatin analogs may be effective by reducing ectopic ACTH production and stabilize tumor growth. Medical versus surgical management of Cushing’s syndrome was discussed with the patient and family, but they opted for hospice care. Conclusion We present a case of pNET associated with late onset EAS without obvious signs of Cushing’s syndrome. To our knowledge this late presentation of ACTH secretion in the setting of a stable pNET has not been previously reported in the literature. EAS due to pNET is rare and metabolic abnormalities can occur rapidly without other Cushingoid manifestations which can pose significant management challenges. High index of suspicion is required for early diagnosis. Due to the aggressive nature, the 5 years survival rate is 16%.

SUN-182 When Insulin Is Not Enough...

Introduction: Multiple factors contribute to hyperglycemia in hospitalized patients, such as underlying medical conditions, pathophysiological stress, and medications. The development of transient insulin resistance is a known cause of hyperglycemia in both diabetic and non-diabetic patients. Rarely, patients can develop extreme insulin resistance, defined as having an insulin requirement of more than 3 units/kg/day. We report a case of extreme insulin resistance in a patient admitted with diabetic ketoacidosis (DKA) mediated by anti-insulin receptor antibodies. Case: 91 y/o F with history of CLL and IDDM (diagnosed three months prior, Last Hemoglobin A1C 14.2%) that was brought to the ED by EMS after being found covered in urine, lethargic and confused. On admission, she was found to be tachycardic, afebrile, normotensive, BMI 28.71. On physical exam she was diaphoretic and altered, but moving all extremities. She showed no findings consistent with acromegaly, hirsutism, red striae, moon-like facies, buffalo hump, or acanthosis nigricans. Initial labs included pronounced leukocytosis of 29.24, potassium of 5.9, glucose of 655, Anion Gap 25, HCO3 4, Beta Hydroxybutyrate 91.55, Lactic Acid 4.1, BUN 33, and a serum Cr of 1.49. UA showed: +30 protein, +80 ketones, Glucose >500, (-) nitrite and leukocyte esterase, & 2+ WBCs. The urine was positive for Bence Jones Protein Lambda Type. Her Kappa/Lambda Ratio was WNLs at 1.42 mg/L. UCx & BCx were negative. Patient was admitted to the ICU with an insulin drip following our hospital’s DKA protocol. After admission, she became hypotensive with increase work of breathing, for which she was intubated and started on vasopressin. On the second day of admission, Endocrinology was consulted due to inability to control blood glucose levels despite maximizing the rate of IV insulin infusion and persistent acidosis. Additional labs revealed a normal TSH, FT4, AM cortisol, IGF-1 27 ng/mL, AM Glucagon, Troponin, CEA and CA-125. Hemoglobin A1C was 8.9%. On the third day of admission, patient’s blood glucose levels persisted in the 400s-500s despite increasing her insulin infusion to 21 units/h and adding 15 units of HumuLIN R/per hour plus Insulin Glargine 40 units twice daily. She received over 900,000 U of insulin in the first 72 hours of hospitalization. In the setting of critical condition without a clear path to recovery, the family decided to pursue palliative care with comfort measures. Patient expired two hours after palliative extubation. Four days after patient expired, the blood work for the antibodies was received. The results were consistent with Negative Islet Cell Antibody, Negative GAD-65 Ab, & Positive Insulin Autoantibody (more than 50 U/ML). Conclusion: This case highlights the importance of considering immune-mediated IR along with other more common causes of IR in hospitalized patients with marked insulin demands.

MON-342 Calcitriol-Mediated Hypercalcemia in Adrenal Diffuse Large B-Cell Lymphoma

Background: Hypercalcemia of malignancy can present with a suppressed intact PTH level in response to various etiologies including elevated PTH-rP, increased calcitriol production via activation of the enzyme 1-alpha hydroxylase, or osteolytic bone lesions. PTH-independent hypercalcemia with elevated 1,25-dihydroxyvitamin D (calcitriol) levels should prompt evaluation for granulomatous disorders including sarcoidosis, tuberculosis, and lymphoma. Here we present a case of calcitriol-mediated hypercalcemia secondary to a rare, adrenal diffuse large B-cell lymphoma. Clinical Case: A 61-year-old female presented with fatigue, myalgias, and generalized weakness. On admission, calcium was 14.1 mg/dL (8.9-10.3), phosphorus 2.4 mg/dL (2.3-4) and iPTH was suppressed to 3.6 pg/mL (8.5-75). CT scan revealed a 30-35 Houndsfield unit, 14 x 9 x 13 cm left adrenal mass. Workup included PTH-rP 0.3 pmol/L (<2.0) and calcitriol 109 pg/mL (18-78). Serum and urine electrophoresis were negative for monoclonal protein spikes. Further hormonal evaluation revealed normal serum and urine metanephrines, 24-hour urine cortisol 64 mcg/24h (3.5-45), 8 AM cortisol 1.9 ug/dL following 1 mg dexamethasone suppression (<1.8), midnight salivary cortisol 87 ng/dL (<100), DHEA-S 16.2 mcg/dL (<15-157), and 11-deoxycortisol 24 ng/dL (10-79). Angiotensin-converting enzyme level was normal at 10 U/L (8-53). Her hypercalcemia improved with intravenous fluids and calcitonin. She was not a surgical candidate as PET/CT revealed multiple para-aortic and mesenteric hypermetabolic lymphadenopathy, left breast soft tissue density, and a lesion in the right posterior pelvis likely indicative of metastatic disease. Nuclear bone scan ruled out bone metastases. Para-aortic biopsy was considered technically difficult in this patient so she underwent CT-guided core needle biopsy of the adrenal mass which confirmed high-grade CD5-positive diffuse large B-cell lymphoma. Immunohistochemical staining was positive for CD20, BCL2, BCL6, MUM-1, and Ki-67 90%. She completed 6 cycles of chemotherapy with rituximab, cyclophosphamide, vincristine, doxorubicin, and prednisone (R-CHOP). Repeat PET/CT following completion of chemotherapy showed no residual disease however one month later, she presented with acute encephalopathy with MRI brain showing a large frontal lobe tumor concerning for relapse. She received 1 cycle of intrathecal methotrexate and cytarabine however these were discontinued due to severe deconditioning. She now remains on oral ibrutinib. Conclusions: Primary adrenal lymphomas are a rare cause of non-Hodgkin lymphomas with less than 150 cases noted in the literature. Lymphoma should be included in the differential of patients presenting with PTH-independent hypercalcemia given the aggressive nature of the disease and associated high mortality.

MON-LB071 Panhypopituitarism Causing a Life Threatening Prolonged QT Interval Which Can Be Reversible with Treatment of Underlying Endocrine Disorders

Introduction: Panhypopituitarism can lead to major metabolic consequences as a result of multiple hormonal deficiencies. However, its association with life-threatening arrhythmias is not well known. Only a few cases have been reported in the literature. Case Report: A 38 year old woman with no past medical history presented with amenorrhea. She was found to have a high prolactin level and subsequent MRI showed a 2.7 cm pituitary adenoma. She underwent transsphenoidal resection and developed panhypopituitarism after surgery. She was placed on hydrocortisone, levothyroxine and desmopressin but was not been compliant with the medications. A few months later, she had a sudden onset syncopal episode without any prodromal symptom. On presentation, she had a heart rate of 43 bpm and prolonged QT/QTc of 668/564ms. Laboratory tests were significant for a troponin of 0.8ng/ml, n <0.03ng/ml, severe hypothyroidism (FT4 0.1ng/dl, n 0.8-2.2ng/dl; FT3 1.03pg/ml, n 2.77-5.27pg/ml) and adrenal insufficiency (AM cortisol <0.2mcg/dL, n 4.5-22.7mcg/dL). There were no other clinical findings to explain this. Her syncopal episode strongly suggested a VT/VF arrest. Echocardiogram showed no structural heart disease. She was treated appropriately for her hypothyroidism and adrenal insufficiency; and she wore a wearable defibrillator while the endocrine disorders were corrected. After treatment, her bradycardia resolved and her QT interval normalized. Genetic screening for underlying Long QT Syndromes was negative. Clinical Lesson: Panhypopituitarism, including hypothyroidism and adrenal insufficiency, can cause life threatening arrhythmias such as ventricular tachycardia and fibrillation. This can lead to extensive noninvasive and invasive cardiac testing and intervention. It is critical that clinicians be aware that these arrhythmias can be reversed by correcting the underlying endocrine disorders. Unless otherwise noted, all abstracts presented at ENDO are embargoed until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. s presented at a news conference are embargoed until the date and time of the news conference. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.

SUN-379 Transformation of Adrenal Adenoma into Adrenocortical Carcinoma in a Cushing Syndrome Patient after Surgery

Background: Adrenocortical carcinoma (ACC) is a rare and aggressive malignancy with annual incidence of 0.5-2.0 cases/million. More unusual is transformation of benign adrenal adenoma to ACC after complete resection. Clinical case: A 72 year old woman with prior history of presumed nonfunctional left (L) adrenal adenoma presented with Cushing’s Syndrome (CS) in 2016. Imaging showed increase in size of her L adrenal adenoma from 1.5 cm in 2007 to 3.7 cm in 2016. On CT, it had a 1.6 X1.3 cm internal hypodense component, -15 Hounsfield units (HU), and surrounding solid component 78 HU on portal venous phase with 42% relative washout. Biochemical testing suggested ACTH-independent CS: elevated cortisol 33.79 ug/dL (4.30-22.40ug/dL), abnormal 1 mg dexamethasone suppression test (DST) cortisol 33.59 ug/dL (4.30-22.40ug/dL), ACTH undetectable <5 pg/mL (7.2-63 pg/mL), low-dose 48hr DST cortisol 37.21 ug/dL (4.30-22.40 ug/dL), normal metanephrine < 0.20 nmol/L (<0.50 nmol/L), normal normetanephrine 0.41 nmol/L (<0.90 nmol/L), aldosterone < 4.0 ng/dL (n < 21 ng/dL). She underwent uncomplicated robotic resection of the adenoma. Surgical pathology was consistent with benign adenoma, Weiss Score = 2 - mitotic rate 12/50 HPF; more than 33% diffuse architecture. She recovered well and weaned off hydrocortisone. In February 2018 she developed recurrent symptoms of CS. Repeat tests showed midnight salivary cortisol 1250 ng/dL (n <100 ng/dL), AM cortisol 39.7 ug/dL (4.30-22.40ug/dL), DHEA-S 205 (<15 - 157 mcg/dL), ACTH <5 pg/mL (7.2-63 pg/mL). Repeat MRI showed large lobulated heterogeneous L adrenal mass increased in size compared to prior despite interval resection- overall size 6.8 x 4.1 x 5.9 cm, with new scattered enhancing nodules superior & posterior to L kidney. She was again referred for surgical resection with high suspicion of conversion to ACC. She had repeat robotic resection with conversion to open L adrenalectomy and L nephrectomy, splenectomy, partial pancreatectomy, and resection of a small piece of the diaphragm. Repeat surgical pathology showed metastatic ACC with metastases to the diaphragm, omentum, perinephric and perisplenic adipose tissue, and positive margins. Post-operatively she has been treated with mitotane, cisplatin, etoposide, and doxorubicin. She is currently on mitotane therapy alone due to cardiotoxicity from her chemotherapy. Conclusion: This is an uncommon case of transformation of benign adrenal adenoma to metastatic ACC. This highlights the uncertainties regarding postoperative follow-up of adrenal adenomas and the potential need for continued surveillance post-resection. Reference: Fareau GG, et al. Diagnostic challenges in adrenocortical carcinoma: recommendations for surveillance after surgical resection of selected adrenal nodules. Endocr Pract. 2007, Oct; 13(6):636-41

SUN-291 17 Year Old Male with Galactorrhea and Elevations in Prolactin and ACTH in the Setting of a Pituitary Microadenoma

Pituitary adenomas are uncommon in children with an incidence of 0.1 per million. Prolactinomas are the most frequent, followed by ACTH-secreting adenomas, whereas TSH-, GH- and non-functioning adenomas are less frequently encountered. Plurihormonal pituitary adenomas, though extremely rare have also been reported, with ACTH/Prolactin and ACTH/GH being the most common. (Lubov B. Mitrofanova, 2017) A 17 year old male presented with bilateral ‘milky’ areolar discharge for the past 2 weeks. He also had a history of chronic headaches and decreased energy for the past 6 months. Initial evaluation at his PCP’s office showed an elevated prolactin of 90.2 ng/mL (4.0-15.2) and normal TSH and free T4. At presentation to endocrinology, physical exam showed weight of 106.8 kg >99%ile, height of 182.8 cm, 85%ile, BMI of 32, 98%ile, and blood pressures 117/50 mmHg, 50th/10th%ile respectively. He was also noted to have circumferential acanthosis nigricans of the neck, gynecomastia, Tanner V pubic hair, and 20 mL testes bilaterally; no striae, nuchal adiposity or areolar discharge was noted. Subsequent biochemical testing at 0900 showed prolactin, 100.7 ng/mL (4.0-15.2), ACTH, 177 pg/mL (<47), cortisol, 21.6 ug/dL (5.3-22.5), FSH 0.8 mU/mL (1.5-12.4), LH 1.5 mU/mL (1.8-10.8), with T4, TSH and IGF-1 within normal limits. An MRI of the brain showed a 3 mm microadenoma in the adenohypophysis. Given elevated prolactin, ACTH and high normal morning cortisol, there were concerns for Cushing’s disease, and midnight salivary cortisols were obtained, which were normal: 0.033, 0.036 and 0.040 ug/dL (<0.259). He was then started on cabergoline, titrated up to 0.5 mg twice a week. After 3 months, he had resolution of the areolar discharge and a decrease in headache frequency as well as improved energy. His repeat labs showed prolactin, 8.4 ng/mL, AM cortisol 17.4 ng/mL, though ACTH was quantity not sufficient. Hyperprolactinemia is most commonly caused by a pituitary adenoma, and symptoms in men include gynecomastia, areolar discharge, fatigue and decreased libido. Plurihormonal adenomas, though a rarity, must be considered when an adenoma is confirmed by imaging, and should trigger screening for other pituitary hormonal abnormalities. Treatment with D2-receptor agonists has been shown to be an effective treatment for some plurihormonal adenomas, likely dependent on D2 receptor expression of the particular adenoma in question (Shalini Kunasegaran, 2017). Lubov B. Mitrofanova, P. V. (2017). Plurihormonal cells of normal anterior pituitary: Facts and conclusions. Oncotarget, 8(17): 29282-29299. Shalini Kunasegaran, M. S. (2017). An unusual case of Cushing's syndrome due to bihormonal ACTH-prolactin secreting pituitary macroadenoma with rapid response to cabergoline. BMJ Case Reports, 10.1136/bcr-2017-219921 .