bluuebunny/crossref_metadata_2025 huggingface dataset:
A Unique Case of Corticomedullary Mixed Tumor Composed of Both Adrenal Cortical Cells and Pheochromocytes
Authors: Panja Srinivas R , Ali Safrin
Published: May 2021

Introduction or Background: Corticomedullary mixed tumors of the adrenal gland was first described in 1969 by Mathison and Waterhouse. It is defined as a single tumor mass of the adrenal gland that histopathologically has presence of adrenal cortical and medullary cells. Such mixed tumors involving the cortical and medullary components of the adrenal glands are very rare. Clinical Case (including diagnostic evaluation, treatment, and follow-up):A 67 year old woman with a history of hypertension and osteoporosis presents for incidental adrenal adenoma. Hypertension was controlled well with olmesartan 40mg, hctz 25mg, and amlodipine 2.5mg. Abdominal CT scan showed a 2.6 cm enhancing left adrenal nodule with delayed wash- out phase. Biochemical testing showed elevated plasma free metanephrine (132pq/ml, n < or = 57pq/ml) and abnormal 1mg dexamethasone suppression test (10.4mcg/dL, n <2mcg/dL). ACTH was suppressed. Patient underwent left adrenalectomy, after pretreatment with doxazosin. Surgical pathology report showed an unusual neoplasm consisting of a single nodule composed of intermixed aggregates of cortical cells and pheochromocytes displaying morphologic features of adrenal adenoma and pheochromocytoma. Also intermixed with the adenoma was a 3mm myelolipoma. Post surgery, the patient was treated with hydrocortisone for symptoms of adrenal insufficiency. Post surgery, she was able to stop amlodipine and hctz and is on 10 mg olmesartan on alternate days.. She remains on a weaning dose of hydrocortisone at the time of abstract submission. Clinical Lesson(s) or Conclusion(s) (emphasizing the learning point[s] and implications for clinical practice)This unique case report highlights the importance of appropriate workup for incidental adrenal adenoma and keeping in mind the rare possibility of mixed endocrine tumours. A single mixed tumor of the adrenal gland is rare but exhibits distinct morphologic features of both a cortisol producing tumor along with a pheochromocytoma. Furthermore, a concurrent intermixing of a myelolipoma within an adrenal corticomedullary mixed tumor is rarely reported.
Acute Kidney Injury in a Previously Healthy 15-Year-Old Patient: A Subtle Presentation of Addison’s Disease
Authors: Nguyen Minh , George Nicholas , Fakhoury Joseph , Ergun-Longmire Berrin
Published: May 2021

Introduction: Primary adrenal insufficiency (PAI), also known as Addison’s disease, is a disorder of the adrenal glands characterized by decreased levels of glucocorticoids and mineralocorticoids. It is a rare condition with a prevalence of 120 cases per million and is less frequently seen in the pediatric population. Here, we report a previously healthy 15-year-old patient with acute kidney injury (AKI) and PAI.

Case Presentation: The patient was admitted to the hospital after findings of abnormal laboratory studies, which included an elevated BUN (53 mg/dL), creatinine (1.39 mg/dL), calcium (11.3 mg/dL), potassium (5.6 mmol/L), and hyponatremia (126 mmol/L). These were performed at an outpatient visit due to three-week history of back pain, fatigue and emesis. On admission, he had stable vital signs. Physical examination revealed generalized darkening of skin, more noticeable on the knuckles and palmar creases, with hyperpigmented patches in oral mucosa and both upper extremities. Although his renal function, serum potassium and calcium levels normalized after intravenous hydration with normal saline, hyponatremia (128 mmol/L) continued. His urine analysis and renal ultrasound were normal. Due to his hyperpigmentation and persistent hyponatremia, PAI was suspected. An ACTH stimulation test revealed that basal and stimulated serum cortisol levels were low, 2.6 mcg/dL and 2.9 mcg/dL, respectively. His plasma ACTH level was elevated at 1,625 pg/mL and serum aldosterone level was low at <4.0 ng/dL. These results were consistent with PAI. The patient’s hyponatremia resolved after receiving stress dose hydrocortisone. He was discharged home on hydrocortisone and fludrocortisone with endocrinology follow up.

Discussion: PAI is well described in the literature, though reports in pediatrics vary. Patients may present with nonspecific symptoms such as unexplained weight loss, fatigue, diffuse abdominal pain, nausea, vomiting and muscular weakness. These symptoms may be of insidious onset, which often leads to delayed diagnosis. Physical signs include hypotension and hyperpigmentation. Characteristic biochemical findings are hyponatremia, hyperkalemia and hypoglycemia. Despite the electrolyte derangements, AKI is not a common presentation of PAI. There are only a few case reports associating these two diseases. In this case, his symptoms and abnormal electrolytes were initially considered to be the result of AKI of unknown origin. PAI only became a suspicion after a careful physical exam and persistent hyponatremia despite improvement of his AKI with fluid resuscitation. His low serum cortisol and aldosterone levels with elevated plasma ACTH confirmed the diagnosis of PAI.

Conclusion: This case highlights a unique presentation of PAI in an adolescent. A timely diagnosis reduces the risk of unwanted and potentially life-threatening complications such as an Addisonian crisis.
Adrenal Infarct as a Presenting Finding in Polycythemia Vera (PV)
Authors: Guruli Marie , Kantorovich Vitaly
Published: May 2021

Adrenal infarct as a presenting finding in Polycythemia Vera (PV)

Marie Guruli, Vitaly Kantorovich

Background: While hemorrhagic adrenal infarcts, usually bilateral, have been described in hematologic malignancies, usually PV, no hemorrhagic variant are exceedingly rare. Here we describe a single case of unilateral nonhemorrhagic adrenal infarct.

Case Presentation: 30-year- old male with past medical history of type 1 diabetes on insulin, presented with one day history of right upper quadrant (RUQ) abdominal pain. Initially pain was mild but slowly progressed to 10/10 intensity within the next several hours, felt like a sharp and stabbing pain with radiation up to the chest. Patient also reported to have difficulty breathing due to pain, along with nausea and vomiting. Laboratory results showed leukocytosis 11.2, H&H of 19.1/56.8, platelet count of 637, glucose of 283, alkaline phosphatase of 147. Abdominal ultrasonography reported nonspecific mild hepatomegaly and strongly suspected small thrombus within the IVC. Further work up included CTA study was negative for PE (pulmonary embolus), but MRI showed a filling defect in the suprarenal IVC along with right adrenal infarction. Patient was thermodynamically stable. Fortunately, cortisol was 21.3 and DHEA levels were 419, indicating no apparent effect on adrenal function. Patient underwent a bone marrow biopsy and was eventually diagnosed with PV. He was discharged in the stable condition with a close follow up with his endocrinologist for monitoring and repeat MRI for right adrenal infarct within the next few months.

Conclusion: This case illustrates the importance to screen patients with PV who presented with similar clinical presentation for possible adrenal insufficiency. It also highlights the importance of undertaking imaging for careful consideration, close follow up to prevent life threatening complications and even death.
Adrenal Insufficiency: Hidden Mimicker With Other Autoimmune Disease Potentials
Authors: Banjade Rabin , Upadhyay Binayak , Kharel Bidhisa
Published: May 2021

Background: Adrenal insufficiency has various nonspecific symptoms, which are often overlooked until the patient presents with a life-threatening adrenal crisis. Our patient presented during the COVID19 pandemic, which further blurred our diagnostic sense.

Clinical Case: A 26-year-old female presented with sudden intractable non-bloody non-bilious vomiting occurring every 30 minutes along with sharp epigastric pain radiating to her back, dizziness, and extreme fatigue for the last 2 days. She had similar but milder episodes in the past 2–3 years as well and endorsed unintentional weight loss for the same duration. She had been extensively investigated previously but was misdiagnosed as gastroparesis or anxiety and was prescribed medications for the same (pantoprazole, sucralfate, and Lexapro).

On presentation this time, she was hypotensive and tachycardic but partially responsive to IV fluids. Her BMI was 15.31 and the abdominal exam was benign. Her basic labs showed Na 125, K 4.9, Calcium 10.5, Cr 1, WBCs 9K, lipase 8, normal LFTs, TSH 6.96, Free T4 1.18. Infectious workup was done and the patient was started on empirical antibiotics. Negative infectious workup, hypotension partially responsive to IV fluid, along with hyponatremia and borderline high potassium level prompted us to check Cortisol. We found Cortisol of 1.3(very low for the degree of her illness). ACTH stimulation test with 250mcg IV cosyntropin showed cortisol of 1.3 at 30 minutes and 1.1 at 60 minutes confirming the diagnosis of adrenal insufficiency. Further workup revealed a positive 21 hydroxylase antibody and ACTH level of 322 (high due to lack of negative feedback to the pituitary). She was comprehensively tested for other autoimmune diseases which showed positive Endomysial IgA and Tissue Transglutaminase antibodies indicating asymptomatic celiac disease. She improved drastically after starting hydrocortisone. TSH was repeated in 3 months which was normal.

Conclusion: The onset of chronic adrenal insufficiency is very gradual with vague presentation and it may go undetected unless illness or other stress precipitates acute crisis as in our patient. Since autoimmune adrenalitis is the most common cause of primary adrenal insufficiency (Addison’s disease), patients with a confirmed diagnosis should also undergo workup for other autoimmune diseases.
Adrenoleukodystrophy as a Cause of Spastic Paraparesis and Hyperpigmentation
Authors: Chary Priyanka Kesavan , Rehman Aziz Ur , Bright Tamis Marie
Published: May 2021

Background: X-linked Adrenoleukodystrophy (X-ALD) is caused by an abnormal gene mutation on the X chromosome which codes for an abnormal ABC transporter, preventing transport of very long chain fatty acids (VLCFAs) into peroxisomes for beta oxidation. These VLCFAs, unable to be broken down, thus accumulate in the CNS, adrenal cortex, and Leydig cells of the testes. The clinical presentation depends upon the anatomical involvement, which most often includes the CNS and adrenal glands, and can be a cause of adrenomyeloneuropathy (AMN) or adrenal insufficiency.

Case Report: We report a 44 year old male who presented with 9 years of progressive spastic paraparesis. Physical exam was significant for lower extremity spasticity, 3/5 bilateral lower extremity weakness, and hyperpigmentation. His initial work-up for autoimmune disease, MRI brain, and lumbar puncture were unremarkable, and genetic testing for Hereditary Spastic Paraparesis was negative. However, due to advancing symptoms over the years with progression of spasticity, polyneuropathy, development of erectile dysfunction and significant hyperpigmentation, re-evaluation with MRI brain and EMG revealed diffuse symmetrical cerebral and cerebellar volume loss and axonal motor peripheral neuropathy, respectively. Due to hyperpigmentation, further work-up for VLCFAs was positive and presence of the ABCD1 mutation confirmed the diagnosis of X-ALD. Evaluation of adrenal glands yielded high ACTH of >2000 pg/mL (normal: 7.2–63.3) and low AM cortisol of 2.5 ug/dL (normal: 6.2–19.4). Insignificant increase of cortisol from 2.5 ug/dL to 2.7 ug/dL with cosyntropin confirmed primary adrenal insufficiency as the cause of hyperpigmentation with elevated ACTH. Surprisingly, his testosterone level was normal at 542 (normal: 250–1100 ng/dL) and suggestive of Leydig cell-sparing and neuropathy-induced erectile dysfunction. The patient was started on hydrocortisone for adrenal insufficiency with improvement in his fatigue and feelings of well-being. He received physical therapy and is being monitored closely for progression of AMN by Neurology.

Conclusion: Our case suggests that ALD should be considered in the differential diagnosis of unexplained paraparesis with associated hyperpigmentation in males. Moreover, timely diagnosis and medical intervention can prevent life-threatening adrenal crisis in such patients.
An Adult With Hair Loss! a Rare Case of Non-Classical 3β Hydroxysteroid Dehydrogenase (3β HSD) Deficiency
Authors: Patel Sabah , Agarwal Shubham , Butler Paula
Published: May 2021

Introduction: Congenital adrenal hyperplasia (CAH) is the most frequent cause of adrenal insufficiency and ambiguous genitalia in newborn. Unlike 21-hydroxylase and 11β- hydroxylase deficiencies, classical 3β hydroxysteroid dehydrogenase (3β HSD) deficiency affects steroid biosynthesis in both the adrenals and the gonads. We present a rare case of suspected 3β HSD in an adult with hair loss. Case: 33 years old with female with no PMH/prior pregnancies was referred to endocrinology for low testosterone, male pattern hair loss and decreased libido for 2 years. At onset of symptoms, she was following an intensive exercise regimen for weight loss and was using Oxandrolone for 2 months to promote muscle mass. She now reports increased axillary and pubic hair growth but loss of scalp hair as well as fatigue. Menarche was at 14 years. Menstrual cycles are regular but with hypomenorrhea. Physical examination showed normal BP, signs of male pattern hair loss on scalp. light terminal hair growth over abdomen, middle thighs and around areola but without galactorrhea. Labs remarkable for normal sodium and potassium, A1c 5.2%, ACTH of 7.2, Cortisol of 8.2 (5–25 µg/dl), TSH of 1.43 (0.5–5.0 mIU/L), Free T4 of 1.28 (0.8–1.8 ng/dl), Estrone 102 (17–200 pg/ml), Normal DHEA 133, Total testosterone <3 (8–60 ng/dl), Free testosterone 0.4 (0.3–1.9 ng/dL), LH 7 (1.0–18.0 mIU/mL), FSH 9.6 (2.0–12.0 mIU/mL), Estradiol 45.9 (15–350 pg/mL),low 17-hydroxyprogesterone of 11 (<80 ng/dL), DHEA-S of 88 (31–228 µg/dL), low Androstenedione of 28 (80–240 ng/dL) and Dihydrotestosterone 6.3 (normal). MRI brain revealed a normal pituitary gland, slightly enlarged for age. Co-syntropin stimulation test has been delayed due to the pandemic. Discussion: 3β HSD converts delta-5 steroids (pregnenolone, 17-hydroxypregnenolone, DHEA, androstenediol) to delta-4 steroids (progesterone, 17-hydroxyprogesterone, androstenedione, testosterone) respectively. Delta-4 steroids were low in our patient. Increased ratio of delta 5 steroids: delta 4 is characteristic of 3β HSD. Most cases of 3β HSD deficiency present as neonates with hyponatremia, hyperkalemia, and ambiguous genitalia but a non-salt wasting form has occasionally been described in older patients. The non-classical form often manifests as menstrual irregularities and hirsutism along with possible male pattern hair loss of varying degrees in women. The normal levels of estradiol and estrone are likely due to peripheral conversion of androstenedione by aromatase. 3β HSD deficiency is usually treated with steroids which helps resolve most symptoms. References: Simard J, Rheaume E, Mebarki F, Sanchez R, New MI, Morel Y, Labrie F. Molecular basis of human 3 beta-hydroxysteroid dehydrogenase deficiency. J Steroid Biochem Mol Biol. 1995 Jun;53(1–6):127–38.
An Opportunity Missed: Managing an Aggressive Adrenal Cortical Carcinoma
Authors: Jouneghani Nasrin Saleh , Al-Ramo Kathreen , White Wendy
Published: May 2021

Introduction: Adrenal cortical carcinoma (ACC) is a rare endocrine tumor with an incidence of up to 2 persons per million population. Complete surgical resection is the first-line therapy for localized tumors, while debulking surgery, radiation therapy, and/or chemotherapy may also be options for palliation in advanced ACC. Biochemical and radiographic evaluation of a newly discovered adrenal mass maximizes the opportunity for the patient to undergo a complete, margin-negative resection of the primary tumor, which is the most powerful determinate of long-term survival. Here we present the case of an extremely aggressive high grade adrenal cortical carcinoma that increased from 4 cm to 17 cm within 4 months, metastasizing to the lung, liver and left kidney prior to resection. Case summary: A 42-year-old woman presented to the Emergency Department (ED) with abdominal pain and was found to have hypokalemia and an incidental left adrenal mass measuring 4.9 x 4.6 cm. She was discharged home with instructions to follow up with her primary care physician for further workup. Unfortunately, she was lost to follow-up for 3 months. Her initial biochemical evaluation at follow-up did not show evidence of adrenal insufficiency or elevated metanephrines. A repeat outpatient CT chest abdomen pelvis revealed increased tumor size to 12.3 x 10.8 x 12.5 cm, with unclear renal vs adrenal origin, and multiple liver and lung metastases. She subsequently underwent left radical nephrectomy, adrenalectomy, splenectomy as well as a partial diaphragmatic resection 4 months after her initial ED presentation. The surgical specimen measured 17 x 11.5 x 8 cm. Endocrinology was consulted post-operatively to evaluate for relative adrenal insufficiency given hypotension & altered mental status. Further evaluation revealed new-onset hirsutism, male-pattern hair loss, proximal muscle weakness, and significant weight loss over the prior 3 months. Post-operative laboratory evaluation was significant for sustained hypokalemia of 2.4 mmol/L, 24 hour urine cortisol of 1326 mcg/24 hr (normal 3.5–45), as well as elevated DHEA-S of 994 mcg/dL (normal 27–240), and testosterone of 294 ng/dL (normal 10–75). Surgical pathology demonstrated a high-grade adrenal cortical carcinoma. Oncology was consulted and the patient was started on spironolactone for the hypokalemia, but declined any further therapy for her ACC and subsequently died 2 weeks later. Conclusion: This case illustrates how ACC can behave aggressively and further emphasizes the need for timely and complete biochemical evaluation of adrenal incidentalomas. This is particularly true with the presence of suspicious radiologic features such as size more than 4 cm and heterogeneous appearance. All patients with an adrenal incidentaloma should undergo biochemical and imaging evaluation, guided by thorough history-taking and physical exam, to ensure optimal outcomes.
An Overlooked Sequela of Long-Term Opioid Analgesic Use: A Case Report on Central Adrenal Insufficiency
Authors: Zhao Wei , Mohamed Issa , Humphries Derrek , Bankstahl Elizabeth
Published: May 2021

Background: Opioid use began to surge since late 1990s and has evolved into a full-fledge opioid epidemic. 2 million Americans aged 12 or older are estimated to have opioid use disorder. We hereby present a case of opioid-induced adrenal insufficiency (OIAI), an overlooked endocrinopathy in which chronic opioid use suppresses the hypothalamic-pituitary-adrenal axis.

Clinical Case: A 53-year-old African American female with past medical history of chronic pain syndrome presented with worsening fatigue and generalized weakness for a week, to the extent that she required full assistance to ambulate at home. Upon further inquiry, she also suffered from postprandial eipgastric pain and non-bloody diarrhea for several months. She has a 2-year use of Norco 10 mg/325 mg three times daily to manage her chronic pain. Her blood pressure was running low at 85/57 mmHg with no other abnormal vitals. Our first visual impression of her was a debilitated lady with low voice and slow body movements. Adrenal insufficiency was suspected and subsequently confirmed with low morning cortisol level (1.1 mcg/dL), low DHEAS level (25.3 mcg/dL) and subnormal response of cortisol (16.8 mcg/dL) to the cosyntropin stimulation test. Her ACTH level was less than 3 pg/mL. These laboratory findings were consistent with central adrenal insufficiency. Chronic steroid use, the most common culprit for adrenal insufficiency, was not found in her home medication list or prescription records. To further evaluate the underlying etiologies, we checked the pituitary hormones and found normal levels of LH, FSH, TSH, prolactin and IGF-1. Head CT 2 years prior was negative for any discernible mass. The suspicion for pituitary mass that markedly suppresses ACTH secretion only was reasonably low. The diagnosis of OIAI was made by excluding other causes. Endocrinology was consulted for the dosing of hydrocortisone. She improved physically after receiving hydrocortisone replacement therapy. Collaborative efforts were made to cut down her opioid dose.

Conclusions: OIAI is a longstanding overlooked condition in chronic opioid users of which clinicians should raise their awareness. The estimated prevalence of OIAI ranges from 9% to 29% depending on the daily dosage and total duration of opioid use. The case reports of OIAI, however, are only a few. Patients with OIAI could present with fatigue, weight loss, gastrointestinal symptoms, headache or muscular aches. Not only does OIAI impair patients’ quality of life and potentially escalate their opioid dosage by inexperienced prescribers, it also leads to catastrophic adrenal crisis following acute insults. The challenge clinicians face is to uncover the clinical clues suggesting OIAI, which are often hidden in a myriad of symptoms caused by chronic pain and other co-morbidities. Timely diagnosing OIAI is thus never more important in the midst of the unprecedented opioid epidemic.
An Unusual Case of Bilateral Adrenal Hyperplasia
Authors: De Castro Alicia , Comi Richard J , Crawford Andrew Robert , Radovanovic Natasa , Ammana Hima , Kwak Leigh
Published: May 2021

Background: Thrombocytopenia, anasarca, fever, reticulin fibrosis/renal failure, and organomegaly (TAFRO) syndrome is a variant of Castleman Disease, which is a rare lymphoproliferative disease that can be life threatening. Diagnosis is often delayed because of its nonspecific presentation. Bilateral adrenal hyperplasia has been a reported complication, however the majority of cases reported have been in Asian patients. Prior accounts of elevated ACTH in TAFRO have been in the context of adrenal insufficiency.

Clinical Case: A 28-year-old Caucasian male with a history of multiple sclerosis was seen in the ED with abdominal pain. On presentation, he was afebrile and normotensive. Physical exam was notable for cervical lymphadenopathy and abdominal tenderness. There was no facial rounding/plethora, bruising, abnormal striae, or proximal muscle weakness. He had normal blood counts, serum chemistry and liver function. An abdominal CT scan showed marked bilateral adrenal hyperplasia with pre-aortic, peri-aortic and retroperitoneal lymphadenopathy. An 8AM serum cortisol was 14.1 mcg/dl (4.8–19.6 mcg/dl) and adrenocorticotrophic hormone (ACTH) was elevated at 152 pg/ml (7.2–63 pg/ml). A repeat serum 8AM cortisol following low dose dexamethasone suppression test (LDDST) was 14.7 mcg/dl, however at that point the patient had developed new fevers and thrombocytopenia. Blood pressure, blood glucose and potassium remained normal. An MRI of the brain showed a normal appearing pituitary gland. An extensive infectious and rheumatologic evaluation was negative, and he underwent an inguinal lymph node biopsy which showed nodal expansion with histiocytes, consistent with TAFRO. High dose methylprednisolone and Siltuximab (an IL-6 inhibitor) were started, and his fever and abdominal pain resolved. He was discharged home on oral prednisone.

Conclusion: We describe a case of bilateral adrenal hyperplasia with elevated ACTH and non-suppressed cortisol on LDDST suggestive of ACTH-driven cortisol excess. However, interpretation of his LDDST is made difficult in the context of persistent fevers. Although we cannot definitively exclude pathologic hypercortisolism at this time, given his lack of suggestive features such as proximal muscle weakness, abnormal striae or hypokalemic alkalosis, his over-all presentation was more consistent with hyperplasia secondary to TAFRO rather than an underlying pathologic hypercortisolism. Adrenal hyperplasia has been noted in TAFRO, however its pathogenesis remains poorly understood. TAFRO should be added among the differentials for bilateral adrenal hyperplasia to facilitate early diagnosis and treatment.

References: Ducoux G, et al. Thrombocytopenia, Anasarca, Fever, Reticulin Fibrosis/Renal Failure, and Organomegaly (TAFRO) Syndrome with Bilateral Adrenal Hemorrhage in Two Caucasian Patients. Am J Case Rep. 2020;21:e919536.
Asymptomatic Pheochromocytoma With Delayed Resection Due to Covid-19 and Persistent Postoperative Hypertension
Authors: Menon Trisha , Sinha Avani G
Published: May 2021

Background: Pheochromocytoma is promptly treated by surgical removal and usually results in resolution of hypertension. This case discusses an asymptomatic patient with two new malignancies-breast cancer and pheochromocytoma- who had positive outcomes despite delayed resection of pheochromocytoma due to COVID-19, but with a persistence of postoperative hypertension.

Clinical Case: A 60 year old woman with newly diagnosed breast cancer presented for workup of an adrenal mass found on PET scan. An abdominal contrast CT-scan demonstrated a left 3.2 cm indeterminant adrenal mass. Initial laboratory testing demonstrated positive 24 hour urine metanephrines (metanephrine 951 mcg/24hr, n < 400 mcg/24hr for HTN and normetanephrine 1302 mcg/24hr, n < 900 mcg/24h for HTN) and plasma metanephrines (normetanephrine 826 pg/mL, n < 145 pg/mL and metanephrine 391 pg/mL, n < 62 pgmL), suggestive of pheochromocytoma. An MIBG scintigraphy showed tracer uptake in the left adrenal gland, suspicious for pheochromocytoma. The patient was started on alpha then beta blockade with plan for removal, but due to the COVID-19 pandemic, surgery was delayed. In the interim, breast cancer therapy was adjusted to avoid complications or symptoms from the possible pheochromocytoma. The patient had always been asymptomatic, even during the physical and emotional stress of cancer and chemotherapy. She only had a diagnosis of uncontrolled hypertension for four years prior to presentation, treated with Valsartan-Hydrochlorothiazide, with average systolic BP of 140–180, and diastolic BP of 80–100. With the addition of Doxazosin and Metoprolol, the patient’s BP improved, with all readings < 120/90. A left adrenalectomy was performed nearly six months after initial presentation, with final pathology report demonstrating moderately differentiated pheochromocytoma, with clean surgical margins. The patient remained hypertensive for months after the procedure, with initial systolic (SBP) readings of 150–160, and diastolic (DBP) readings of 90–100. However, follow up plasma metanephrine levels were normal (normetanephrine 165 pg/mL n < 191.8 pg/mL and metanephrine 22.1 pg/mL n < 88 pg/mL). The patient was then started on Amlodipine and Valsartan, with most recent SBP readings in the 130s.

Conclusion: This case demonstrated a clinically asymptomatic patient with persistent postoperative hypertension and normal plasma metanephrines, which has been demonstrated only in a minority of patients. Additionally, pheochromocytoma needs to be promptly removed if possible; this case demonstrated successful resection and clinical course despite the delay for this urgent surgery due to COVID-19.
Bilateral Familial Pheochromocytoma: Difficulty of Diagnosis and Management
Authors: Doghri Sohaib Khamal , Echchad Lamya , Azriouil Manal , Rifai Kaoutar , Iraqi Hind , Gharbi Mohamed Hassan El
Published: May 2021

Introduction: Bilateral pheochromocytoma is a rare tumor, often seen in the context of a family illness. The majority of pheochromocytomas are sporadic, but they can also occur within the framework of genetic diseases (10%): MEN2, VPL, NF1, familial paraganglioma (mutation of SDHB)⋯ In the context of a familial genetic disease, the pheochromocytoma can be either unilateral or bilateral, benign in 95% of cases and malignant in 5%. It still poses several problems related to its diagnosis, genetic aspects, especially in the absence of a family history. And the criteria of malignancy, given the non-existence to date of a certain & universal criterion that judges the malignancy of the tumor. We present through this article the exceptional case of “bilateral familial pheochromocytomas with strong suspicion of malignancy”.

Clinical Case: A 29-year-old lady, hypertensive since 4 years, admitted for exploration of severe secondary hypertension. She reports a triad of menard and severe lumbar pain, the somatic examination shows hypersensitivity of the flanks, a BP of 240/120 mmhg. the abdominal CT scan confirmed by an MRI show a right adrenal mass of 5 cm & another left of 1 cm, of suspicious appearance (irregular contours, areas of necrosis, heterogeneity, spontaneous density at 35 HU, a wash out at 33% with presence of L4 spinal angioma and peri-aortic lymph nodes. urinary methoxylated derivatives (UMD) returned high. The genetic study was positive VPL (on various radiological tests, there was just a spinal angioma) We retained the diagnosis of familal bilateral pheochromocytoma. In front of the clinical & radiological signs of malignancy, we decided to do: a right total adrenalectomy & a left partial adrenalectomy. Unfortunately, the blood pressure didn’t drop, and UMD were still positive; the anatomopathological study shows a pheochromocytoma with a PASS score estimated at 3 (benign!) Faced with conflicting clinical-radiological and histological data, we decided to total adrenalectomy without lymph node dissection and to closely monitor the progress. the post Op blood pressure was normalized and the UMD returned negative.

Conclusion: Malignant familial bilateral pheochromocytoma is a very rare & very difficult entity to diagnose, manage & monitor. A good management requires serious collaboration between: endocrinologist, radiologist, urologist, pathologist
Careful Evaluation of Cosyntropin Dose in the Diagnosis of Adrenal Insufficiency
Authors: Musurakis Clio , Chitrakar Solab , Sharag Randa Eldin , Shrestha Ekta , Pethe Gauri , Qureshi Faisal
Published: May 2021

Introduction: The use of the 250μg cosyntropin dose or otherwise called high-dose ACTH test is the gold standard test for diagnosis of primary adrenal insufficiency. The 1μg dose test or the low-dose test is mostly reserved for diagnosis of secondary adrenal insufficiency. Careful consideration of the results produced during the diagnostic process is imperative to avoid mislabeling of patients with a disease that requires lifelong treatment.

Case Report: This is the case of a 45-year-old female with a history of asthma and psoriasis who presented with emesis. Home medications included monthly TNF-alpha inhibitor injections for psoriasis, triamcinolone acetonide topical spray and budesonide-formoterol inhaler. On admission, she also had nausea, chills and diaphoresis, as well as palpitations, lightheadedness, and shortness of breath. When she arrived at the ER, vitals were remarkable for low blood pressure. Labs were unremarkable except for CMP concerning for anion gap metabolic acidosis, hyponatremia, and hypokalemia. A random serum cortisol was 6.4 mcg/dL, which was relatively low. ACTH was within normal range. Due to concern for adrenal insufficiency, a 1μg cosyntropin test was performed which showed a peak cortisol concentration of less than 18 mcg/dL. As the response was assessed as suboptimal, endocrinology was consulted to offer a treatment plan for steroids. However, the test was repeated using the gold standard 250μg cosyntropin dose and the patient then showed an adequate response and she was not started on steroids.

Conclusions: This is a case that demonstrates how the 250 μg ACTH or high-dose stimulation test should be used for diagnosis of primary adrenal insufficiency (AI), as it is the gold standard. The 1 μg ACTH or low-dose stimulation test can be used for diagnosis of primary AI but only when the high dose test is not available. On the other hand, the 1 μg ACTH stimulation test has been shown to be more sensitive than the 250 μg test in diagnosing secondary adrenal insufficiency. When using the most appropriate test correctly, the clinician can only then offer the patient the best treatment strategies. Our patient did not require chronic replacement therapy. The steroids in this case could have harmed the patient as chronic administration could cause adrenal gland suppression.
Catecholamine-Producing Adrenal Schwannoma: A Rare Pheochromocytoma Imposter
Authors: Chiu Christine E , Angell Trevor E
Published: May 2021

Background:Adrenal schwannoma is a tumor of the adrenal medulla that poses a pre-operative diagnostic challenge due to its non-specific imaging findings and rarity. Even more uncommon are functional catecholamine-producing adrenal schwannomas (CPAS) that can lead to the clinical presentation of catecholamine excess. Here, we present a case of biochemically and histopathologically confirmed CPAS and provide a review of the existing cases in the literature.

Clinical Case: A 43-year old woman with a history of hypertension was incidentally found to have a 4 cm left adrenal lesion. Computed tomography of the mass demonstrated indeterminate enhancement and washout characteristics. Upon evaluation, she had episodes of palpitations and fatigue without headache or flushing. Her medications were notable for metoprolol, vortioxetine, and lisdexamfetamine. Laboratory results were notable for elevated 24-hour urine metanephrine and normetanephrine of 551 mcg/24hr (normal: 58–203 mcg/24hr) and 927 mcg/24hr (normal: 88–649 mcg/24hr) respectively. Due to the possibility of pheochromocytoma, the patient elected for surgery and underwent laparoscopic left adrenalectomy after pre-treatment with an alpha-1-antagonist. Pathology demonstrated a 4.8 cm well-circumscribed tumor arising from the adrenal medulla that showed mostly hypercellular areas of spindled cells with wavy nuclei and focal nuclear palisading along with hypocellular areas with loose edematous stroma with focal areas of calcification and microcyst formation. IHC of the tumor cells was diffusely positive for S-100 and SOX-10, consistent with adrenal schwannoma. Laboratory results approximately 2 months post-operative on the same medications demonstrated normalization of 24-hour urine metanephrine and normetanephrine, confirming CPAS. A search of PubMed was performed using the search terms “adrenal schwannoma,” which returned 41 reports, of which 2 confirmed CPAS. Of the 3 cases, including ours, patients had a mean age of 44 years old and M:F ratio of 1:2. Each of the 3 tumors were left-sided with sizes ranging from 4.8 cm to 7.7 cm, which were all surgically removed. In the two previously published reports, the reported pre-operative laboratory markers were serum catecholamines and urine catecholamines, respectively, but neither compared levels to a reference range. In all cases, catecholamine levels normalized following surgical removal.

Conclusion: Adrenal schwannoma is a rare entity in the differential diagnosis of non-functioning adrenal incidentaloma, but it should be considered for catecholamine-producing adrenal tumors as well. A summary of published cases suggests that these are typically large tumors with possible female predominance. This case is the first to document levels of catecholamine metabolite concentrations in CPAS.
Cushing’s Syndrome Associated With an Adrenal Cavernous Hemangioma
Authors: Khan Rind Jubran Afzal , Saeed Zeb Ijaz
Published: May 2021

Introduction: Adrenal cavernous hemangiomas are rare benign tumors that arise from vascular endothelium and are often discovered incidentally on abdominal imaging. The majority are nonfunctioning; however, we present a case of adrenal Cushing’s syndrome in a patient with a cavernous adrenal hemangioma.

Case: A 72-year-old woman was referred for an incidental right adrenal mass. On questioning, she endorsed abdominal pain, sixty-pound unintentional weight gain over five years, truncal obesity, and easy bruising. Past medical history was relevant for hypertension. Her surgical history was extremely complicated, having had a perforated peptic ulcer, open cholecystectomy complicated by injury to the right ureter, incisional hernia repair, appendectomy, and hysterectomy with bilateral salpingo-oophorectomy.

She was first noted to have a right adrenal mass on a CT done eight years ago, measuring 3.8 x 3.2 cm. A repeat CT abdomen and pelvis now showed this mass to be 6.5 x 6.3 x 8.1 cm with unenhanced Hounsfield units of 29.6. Radiographically, this was a heterogeneous, solid, and cystic appearing mass with peripheral brisk arterial enhancement areas, which appeared to fill in on delayed imaging. The enhancement pattern of the lesion was consistent with an adrenal cavernous hemangioma. An MRI of the abdomen also demonstrated similar peripheral nodular enhancement favoring an adrenal cavernous hemangioma.

Functional testing for the adrenal mass was undertaken. Morning cortisol was 23.4 mcg/dl with ACTH low at 5.3 pg/ml, and DHEA-S 3 mcg/dl. She failed to suppress with overnight 1 mg dexamethasone with AM cortisol of 3.6 mcg/dl. Midnight salivary cortisol levels were high at 0.237 mcg/dl and 0.419 mcg/dl while a 24-hour urine free cortisol was normal at 15.2 mcg/d. She tested negative for pheochromocytoma and primary aldosteronism.

The patient was deemed a poor surgical candidate due to her history of multiple prior abdominal surgeries and a BMI of 46. Therefore, she underwent an IR angioembolization of the right adrenal mass instead. On follow-up CT, there was no significant change in the size of the lesion; however the degree of rim enhancement was slightly decreased. Post procedurally, her a.m. cortisol remained high-normal at 18.3 mcg/dL.. She is currently enrolled in a study for medical treatment of Cushing’s syndrome.

Discussion: Adrenal cavernous hemangiomas usually present incidentally in the 6th-7th decade of life with a female predominance. These lesions are often asymptomatic; however, abdominal pain is the most common presenting symptom. The majority of adrenal cavernous hemangiomas are hormonally quiescent and mineralocorticoid excess and/or subclinical Cushing’s syndrome is exceedingly rare. Our patient is unique in her presentation of adrenal Cushing’s with this lesion and the novel use of angioembolization to decrease the size of this vascular tumor.
Detection of Sex Steroid Expressions in Benign Versus Malignant Adrenal Tumor Tissue Homogenates With Western Blot Analysis
Authors: Oguz Seda Hanife , Gunaydin Gurcan , Emre Gedik , Sokmensuer Cenk , Dagdelen Selcuk
Published: May 2021

Background: Adrenocortical cancer (ACC) is a rare tumor with poor prognosis. The prognostic value of sex steroid expressions in ACC, was firstly shown by our group with immunohistochemistry staining in paraffin embedded blocks (1). Aim: To detect the presence of sex steroid expressions in different types of adrenal fresh tissue samples by Western Blot method. Method: Adrenal fresh tissue samples were isolated from benign (patient 1: adrenal hemangioma, n: 1 intratumoral + 1 extratumoral tissue samples) and malignant tumors (patient 2: ACC, n: 4 intratumoral tissue samples). Expressions of estrogen receptor alpha (Erα), progesterone receptor A (PR), androgen receptor (AR) and aromatase proteins were investigated using Western Blot method in the tissue lysates obtained. Monoclonal antibodies that recognize a single determinant of the obtained denatured proteins with high affinity and specificity were used. GAPDH was used as control protein. After the primary antibody incubation, the incubation phase was started with the secondary antibody produced against the organism in which HRP (Horseradish Peroxidase) conjugated primary antibody was produced in order to visualize the primary antibody. ECL (Enhanced chemiluminescence) solution containing luminol, which is the substrate of the peroxidase enzyme contained in HRP conjugated to the secondary antibody, was used to enable the proteins to which the secondary antibody was bound to emit chemoluminescence. Finally, the densitometric densities of the bands obtained by chemiluminescence imaging were determined. Results: Expression of ER, AR, PR and aromatase was demonstrated in fresh tissue samples obtained from ACC, adrenal hemangioma and normal adrenal cortex. PR expression was higher in ACC lysates. ER and AR expressions were higher in hemangioma and normal adrenal cortex, respectively. Aromatase expression was also higher in adrenal hemangioma while similar in cancerous and normal adrenal tissue samples. Conclusions: We have demonstrated the dissimilarities between the expressions of sex steroid receptors and aromatase by using Western Blot method in fresh tissue samples obtained from different types of adrenal masses, including ACC. It would be possible to develop an in vitro experimental ACC model that can test the effect of sex steroid receptor ligands on tumor growth in order to clarify their role in adrenal tumorigenesis. Reference:1. Oguz SH, Sokmensuer C, Bayraktar M, Dagdelen S. Estrogen, progesterone, and androgen receptor expressions predict the prognosis for adrenocortical carcinoma. Endocrine Society’s Annual Meeting, 23–26 March 2019, New Orleans - USA. Journal of the Endocrine Society, Volume 3, Issue Supplement_1, April-May 2019, SUN-352.
Ectopic Adrenal Tumor in a Patient With Untreated Congenital Adrenal Hyperplasia Due to 21-Hydroxylase Deficiency
Authors: Alba Eva L , Patel Kruti K , Levine Alice C
Published: May 2021

Case Presentation: A 43 year-old female was diagnosed at birth with non-salt wasting congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency and underwent clitoral reduction surgery. She was treated with hydrocortisone and had menarche at age 7 with irregular and heavy menses. At age 15 she had a D&C with removal of “something in her ovaries.” She stopped hydrocortisone at age 30 except for stress doses during illness. At age 35 she stopped oral contraceptives and thereafter has been amenorrheic. She presented with abdominal distention and constipation. On exam she had short stature, marked frontal and temporal balding, hirsutism, increased musculature and a large distended abdomen. Labs showed AM cortisol 3.1 mcg/dL (nl 10–20), ACTH 440 pg/ml (nl <46), 17-OH Progesterone 11000 ng/dL (nl <206), DHEAS 362 mcg/dl (nl <430), FSH 0.2 mIU/ml, LH 2.7 mIU/ml, testosterone 618 ng/dl (nl 10–75), and estradiol 162 pg/ml (nl post menopause <41). MRI showed a massive fibroid (30 cm), bilateral adrenal hyperplasia and a left paraaortic, retroperitoneal mass (5.9 cm). She underwent hysterectomy with removal of a 9.5 kg uterus containing degenerated fibroids, left adrenalectomy and removal of the left paraaortic mass that was initially read as oncocytic adrenal cortical neoplasm, metastatic. A similar oncocytic neoplasm was noted in the left adrenal gland and on further review with pathology the revised report read paraaortic mass, probable adrenal rest tumor.

Discussion: Excess androgens and chronically elevated ACTH levels in untreated CAH can lead to adverse effects beyond adrenal insufficiency and virilization. We present a woman with untreated classic CAH who developed a large fibroid and paraaortic adrenal cortical tumor. Fibroids have been described in CAH patients, a potential consequence of elevated androgens that are converted by aromatase in the endometrium to estrogens driving growth of fibroid tumors. Chronic ACTH can further act as a growth factor, leading to adrenal hyperplasia, adrenal tumors and ectopic adrenal rest tissue. Intra-adrenal tumors in untreated CAH are generally benign with rare cases of adrenal cortical carcinoma reported.

Ectopic adrenal rest tissue in untreated CAH is most commonly reported in testes. There have been rare case reports of ectopic adrenal rest tumors in the adnexa, broad ligament, and perirenal area. Our patient presents as an unusual case of ectopic adrenal rest tumor in the paraaortic region. Based on the atypical location and incomplete history available to the pathologist, it was initially read as metastatic adrenocortical carcinoma. Upon further review given the clinical information, the diagnosis was revised to indicate a pararenal adrenal rest tumor. This case highlights the importance of glucocorticoid compliance in CAH and the necessity to provide a clinical context for the pathologist in cases of extra-adrenal tumors in untreated CAH.
Excellent Maternal and Fetal Outcomes Associated With Early Detection and Treatment of Cushing’s Syndrome During Pregnancy
Authors: Wang Ally W , Xie Yan Yan Sally , Cheesman Khadeen C
Published: May 2021

Background: Despite its relative high prevalence in women of reproductive age, pregnancy is uncommon in Cushing’s syndrome (CS) as hypercortisolism typically results in anovulation and infertility. Early diagnosis and treatment are essential to reduce maternal and fetal complications.

Clinical Case: A 31-year-old woman with Type 2 diabetes mellitus and hypertension was referred for significantly elevated midnight salivary and urine cortisol levels consistent with CS. Six months after initial laboratory findings, she presented to our endocrinology clinic eight weeks pregnant with di/di twins. She reported worsening blood pressure and glucose control, mood fluctuations, and easy bruising for the past several months. Menses were regular prior to conception. Physical exam was notable for round facies, mild dorsal hump, and supraclavicular fullness. Lab tests at eight and thirteen weeks gestation respectively showed: elevated 24-hr urine free cortisol 368.5 and 597.5 ug/24hr (< 45); elevated midnight salivary cortisol 0.88 mcg/dL (<0.09) at eight weeks; ACTH <1.1 and 8.1 pg/mL (7.2 - 63.3); and elevated morning cortisol 34.2 and 36 ug/dL (6.2 - 19.4). Her hemoglobin A1C was 8.1% on metformin and Levemir. Pituitary MRI was normal. MRI of the abdomen without contrast demonstrated a 2.5 x 3.5 cm solid homogeneous mass in the right adrenal gland. The patient underwent successful right adrenalectomy at seventeen weeks gestation and was discharged on glucocorticoid replacement. Glucose control was labile due to non-compliance but otherwise the remainder of her pregnancy was uncomplicated. The patient delivered healthy twins at thirty-five weeks. At six months postpartum she is doing well on low dose hydrocortisone replacement. Most recent hemoglobin A1C was 5.7% without diabetes medication.

Conclusion: There is no consensus on the management of CS during pregnancy due to the rarity of this condition. CS in pregnancy is associated with high maternal and fetal morbidity and mortality, thus early diagnosis and prompt treatment is essential. Our case demonstrates the importance of discussing contraception with Cushing’s patients of reproductive age. It also adds to prior studies and showed that when treated early in pregnancy, either surgically or medically, maternal and fetal risks such as uncontrolled diabetes and fetal loss are significantly reduced. The ideal management of these patients is an area of ongoing investigation.