bluuebunny/crossref_metadata_2025_split huggingface dataset:
Laparoscopic Bilateral Adrenalectomy Should Be an Early Consideration in Ectopic Adrenocorticopic Hormone Secretion
Authors: Francis-Emmanuel Patrice M , Siddique Rana M , Soong Elaine , Tauni Rahat A , Wijenaike Nishan A 
Published: May 2021

Abstract
Introduction: Ectopic ACTH secretion (EAS) causes myriad metabolic derangements which may be effectively managed with laparoscopic bilateral adrenalectomy (LBA) in fit-for-surgery candidates. Clinical Case: A 67-year old woman with a remote 12-pack year smoking history presented with unintentional weight loss, cough, fever and chest pain. Imaging revealed a right-sided lung mass with liver lesions. Liver biopsy confirmed a well-differentiated neuroendocrine tumour (NET). Attempt at palliative lung resection was aborted due to disease extent. She was treated with multiple courses of chemotherapy but her disease progressed. Two years later, she presented with hypokalemia of 2.8 mmol/L (3.5 - 5.0 mmol/L) and uncontrolled hypertension. She was treated with spironolactone and oral potassium. She was notably hyperglycaemic with clinical features of cortisol excess. A random cortisol of 2742 nmol/L (&lt;500 nmol/L), corresponding ACTH of 201 ng/L (5 - 50 ng/L) and lack of diurnal variation in cortisol day curve were in keeping with EAS. Metyrapone and spironolactone normalised blood pressure and biochemical derangement. With her initially high cortisol levels and its associated immunocompromised state, she developed pneumocystis jirovecii pneumonia (PCP), and was briefly admitted to the intensive care unit. In hospital, monitoring her response to EAS management necessitated multiple blood investigations, which proved burdensome for the patient. To effect definitive management of EAS and reduce invasive monitoring, she wished to have LBA and underwent an uneventful procedure. She was discharged on fludrocortisone and hydrocortisone along with lanreotide for primary disease management. Metyrapone and spironolactone were stopped. At initial outpatient follow up, she had normal blood pressure and electrolytes. By her report, her quality of life had improved tremendously, given the reduced need for multiple clinic visits and blood investigations. Unfortunately, her primary disease progressed with gradual deterioration of physical function. She died six months after LBA but, as per her desire, spent her final months with loved ones. Clinical Lesson: In patients with EAS who have unresectable primary disease but otherwise good performance status, LBA is a viable alternative to medical management and should be discussed with patients early after diagnosis. References1. Alberda et al., Endoscopic bilateral adrenalectomy in patients with ectopic Cushing’s syndrome. Surgical Endoscopy 2012; 26:1140-1145
2. Reincke et al., A critical reappraisal of bilateral adrenalectomy for ACTH-dependent Cushing’s syndrome. Eur Journal of Endocrinology 2015, 173M23-M32
The Story of a Radiologically Undetectable, Testosterone Producing Leydig Cell Tumor
Authors: Kappus Natalie , Karadsheh Oday , Jayathilaka Dhammi K K , Dandona Paresh 
Published: May 2021

Abstract
Introduction: Leydig stromal cell tumors are uncommon ovarian tumors that produce testosterone leading to hyperandrogenism. We present a case of a 63 year old lady with significantly elevated testosterone levels that did not have clear ovaries visualized on imaging, but was subsequently found to have a Leydig cell tumor on pathology after ovarian resection.
Clinical Case: A 63 year old female with a past medical history of COPD, hypothyroidism, hyperlipidemia, hypertension and uterine fibroids status post hysterectomy and left oophorectomy in 1995 was referred to endocrinology for hirsutism. The patient reported first noticing abnormal hair growth approximately one year prior to presentation having developed increasingly coarse and thick facial hair, abdominal wall hair, and chest hair. On physical examination, she was noted to have coarse hair across her upper lip and chin continuous along the jawline along with fine, dark hair diffusely across her anterior abdomen. Initial laboratory cell evaluation revealed total testosterone 378 ng/dL, free testosterone 53ng/dL, DHEAS 64 ug/dL. Repeat labs drawn three months later confirmed the markedly elevated total testosterone of 362 ng/dL and free testosterone 44.2 ng/dL, concentrations normally seen in males. A CT scan of the abdomen and pelvis was done and did not reveal any masses. In addition, no ovaries were appreciated on imaging. A transvaginal ultrasound also did not reveal any clear ovaries. The patient ended up undergoing a right oophorectomy. Histological examination was consistent with a Leydig cell tumor. Following oophorectomy, her testosterone concentrations normalized (5ng/dL) and hirsutism began to regress.
Clinical Lesson: Hyperandrogenism in women is typically classified into non-tumorous and tumorous. The differential for non-tumorous hyperandrogenism includes PCOS, congenital adrenal hyperplasia (CAH), and ovarian hyperthecosis. Tumorous causes include ovarian tumors such as Sertoli-Leydig cell tumors, hilus cell tumors, and theca cell tumors. Adrenal tumors secreting testosterone are extremely rare. Often with these tumors, there is significantly increased testosterone levels (&gt; 140ng/dL) and rapid progression of symptoms. Sex cord stromal tumors account for only 5-8% of all ovarian tumors with Leydig stromal tumors a rare group that accounts for less than 0.1% of all ovarian tumors. The tumors are functional producing testosterone leading to marked hyperandrogenism and virilization. They are also usually benign and unilateral. This patient had hyperandrogenism manifested by hirsutism with markedly elevated testosterone concentrations. In addition, this case is unique in that a CT scan and transvaginal ultrasound did not clearly demonstrate her right ovary. Despite having a normal appearing right ovary during surgery, patient was found to have Leydig cell tumor following histological examination.
Acute Adrenal Infarct in a Pregnant Female With Severe Abdominal Pain
Authors: Warda Firas , Gandhi Gunjan Yogendra 
Published: May 2021

Abstract
Background: The differential diagnosis for pregnant patient presenting with abdominal pain is broad. Adrenal infarction is a rare cause of such presentation. Clinical Case: A 24-year-old woman, 30 weeks pregnant, presented to the emergency room with severe, sharp, left upper quadrant abdominal pain that radiated to the back and was associated with nausea and vomiting. Abdominal exam showed tenderness to light palpation in the left upper area with voluntary guarding. Genitourinary exam revealed a closed cervical os. Abdominal MRI noted a T2 hypointense left adrenal gland with loss of normal diffusion restriction. Edematous changes were identified within the left perinephric and anterior pararenal spaces. Left adrenal gland non-hemorrhagic infarction with necrosis was diagnosed, and patient was started on enoxaparin. Patient was admitted for hydration and pain control. A morning serum cortisol was equivocal at 10.3 µg/dL with a mid-normal ACTH of 38.9 pg/mL. ACTH stimulation noted a suboptimal cortisol response with a serum cortisol at baseline of 9.1 µg/dL, at 30 minutes 10.7 µg/dL, and at 60 minutes 11.0 µg/dL. Patient was started on stress dose intravenous hydrocortisone. Evaluation for thrombophilia was undertaken and patient initiated on therapeutic weight-based enoxaparin. Investigations for etiology included normal factor V leiden, proteins C and S activity, antithrombin III antigen, antiphospholipid screening, C3 and C4 complement, anti-double stranded DNA antibody, anti-neutrophil cytoplasmic antibody, cryoglobulin, homocysteine, and factor II mutation. Factor VIII activity was increased &gt;200%, which is within expected range during pregnancy. Patient was heterozygous for MTHFR C677T and A1298C mutations. Hydrocortisone was tapered and patient discharged on a physiologic dose, in addition to enoxaparin. Conclusion: Unilateral adrenal infarction is an uncommon entity in general, and even more uncommon during pregnancy (1). Thrombophilia evaluation is warranted as antiphospholipid syndrome and MTHFR gene mutations have been associated with this condition. Given the rarity of this disease, it may not be included in the differential diagnosis of pregnant patients who present with acute abdominal pain. MRI is superior to other imaging modalities due to its sensitivity in detecting adrenal infarct and even hemorrhage, if present. Unfortunately, there are no guideline on managing such patients, but the focus is usually placed on anticoagulation to prevent the infarction of the contralateral adrenal gland, with cautious monitoring as hemorrhagic conversion is possible. Screening patient for adrenal insufficiency for prompt supplementation of corticosteroids if needed is necessary, while attempting to find the underlying cause. Reference: (1) Green P., et al. Unilateral adrenal infarction in pregnancy. BMJ Case reports. 2013; bcr2013009997
Bilateral Adrenal Adenomas Attributed to Extrapulmonary Mycobacterium Tuberculosis
Authors: Elmaaz Ahmed , Akel Alberto Antonio Franco , Belokovskaya Regina 
Published: May 2021

Abstract
Introduction: Adrenal infections are rare, with the Mycobacterium tuberculosis (MTB) being the most common causative agent in the developing world. MTB usually spreads to the adrenal glands hematogenously where it may be clinically manifested years after systemic infection. Here, we present a case of bilateral adrenal MTB infection associated with MTB peritonitis. Case Presentation: A 46-year-old male, from Ecuador, without significant medical history and no medical follow-up presented to the emergency room with a two-week history of abdominal pain, nausea, diarrhea, and significant weight loss. He denied fever, cough, or night sweats. No smoking, alcohol, or illicit drug use. He works as a construction worker without a history of sick contacts. Vital signs were stable, with abdominal distension and fluid shifting dullness on exam. Blood work revealed leucocyte count of 5.58K (4-11K), INR 1.2 (0.9–1.1), Sodium 132 mEq/L (136–145 mEq/L) with albumin 3.3 mg/dL (3.5–5.2 mg/dL), total bilirubin level, 1.3 mg/dL (0–1.2 mg/dL), and AST and alkaline phosphatase levels, 73 U/L (0–40 U/L) and 186 U/L (40–129 U/L) respectively. Computerized tomography (CT) of the abdomen showed large ascites, omental nodularity, calcified gall bladder, bilateral adrenal nodules, and multiple abdominal lymphadenopathies. Chest CT revealed right apical reticulonodular densities. A diagnostic paracentesis revealed an exudative effusion with serum ascites albumin gradient of 0.7, and negative acid fast bacilli (AFB) and adenosine deaminase enzyme. Ascitic cellular analysis was negative for malignant cells. AFB blood and sputum cultures were negative, though Quantiferon gold test was positive and a skin tuberculin test was 13x13mm. Tumor markers CA19-9, CEA, and alpha-fetoprotein came back negative. Additionally, serum aldosterone, plasma metanephrines, DHEA-S, AM Testosterone, ACTH, and morning cortisol levels were normal. The patient had a negative 1-mg dexamethasone suppression test. Positron emission tomography (PET) scan showed a hypermetabolic left adrenal mass (4.9x3.2 cm) and nodular peritoneum with no fluorodeoxyglucose (FDG) uptake in the enlarged abdominal lymph nodes. Peritoneal biopsy analysis revealed non-caseating granuloma positive for MTB. The adrenal biopsy was not performed given the extensive intra-abdominal disease. The patient was started on anti-MTB treatment (Isoniazid, rifampicin, pyrazinamide, and ethambutol) with significant clinical improvement and a slight decrease in the adrenal masses following abdominal imaging. Conclusion: Extrapulmonary MTB should be part of a differential diagnosis for bilateral adrenal masses. Adrenal glands could be infected by a variety of pathogenic microorganisms either by direct contact or hematogenous dissemination. A high index of suspicion is required for the diagnosis of MTB in patients with atypical presentation.
Bypassing the Adrenals: A Rare Case of Adrenal Insufficiency Following Bariatric Surgery
Authors: Raco Joseph , Shamloul Norhan , Jain Rohit 
Published: May 2021

Abstract
Background: Adrenal insufficiency (AI) is a life-threatening disorder that is generally caused by primary adrenal failure or by hypothalamic-pituitary impairment of the corticotropic axis. Patients often present with fatigue, hypotension, anorexia, and weight loss. There are few reported cases of AI following bariatric surgery; a type of procedure designed to cause weight loss and anorexia - two of the cardinal symptoms of AI. Establishing a diagnosis of AI in patients who have undergone bariatric surgery can be challenging due to symptom overlap, but it is of critical importance given that an acute stressor has the potential to precipitate adrenal crisis with risk of death. Clinical Case: A 42-year-old woman presented 15-months after sleeve gastrectomy with biliopancreatic diversion and duodenal switch with nausea, vomiting, decreased oral intake, weight loss, weakness and fatigue. Her symptoms were severe, requiring admission to the hospital and were initially thought to be a result of her bariatric surgery. Initial intake exam and labs were notable for mild hypotension, persistent hypoglycemia with hemoglobin A1c &lt;3.4%. Further evaluation revealed a low AM cortisol (5.5 μg/dL) and diagnosis of AI was confirmed by a failed cosyntropin stimulation test with cortisol levels of 7.0 μg/dL and 10.6 μg/dL 30- and 60-minutes after cosyntropin administration, respectively. Her diagnosis remained confounded by the presence of concomitant micronutrient deficiencies including copper, zinc, vitamin D and vitamin B6. Furthermore, she was found to have low insulin and c-peptide levels of 1 μU/mL and 0.4 ng/ml, respectively, despite persistent hypoglycemia. The patient was treated with enteral nutrition via nasojejunal feeds and glucocorticoid replacement therapy with daily oral hydrocortisone and fludrocortisone. Each of her symptoms improved after initiation of steroid replacement therapy and she was discharged home. Conclusion: Clinicians should keep a high degree of suspicion for adrenal insufficiency in patients who have undergone bariatric surgery due to the degree of symptom overlap in this population.
Cardiac Arrest in a Child with Non-classic Lipoid Congenital Adrenal Hyperplasia Associated with a New STAR Gene Mutation
Authors: Yan Yun , Thiffault Isabelle , Tsai Sarah , He Luke , De Luca Francesco 
Published: May 2021

Abstract
Introduction: Steroidogenic acute regulatory (STAR) protein regulates steroid hormone synthesis by transporting cholesterol into mitochondria. STAR gene mutations lead to lipoid congenital adrenal hyperplasia (LCAH), the rare but most severe form of congenital adrenal hyperplasia in children. We present an unusual case with an episode of cardiac arrest in a young girl during an acute febrile illness and later she was diagnosed with adrenal insufficiency secondary to a non-classic LCAH. Case: 2-year 11-month-old previously healthy white female was brought to an urgent care clinic due to severe lethargy and a seizure-like activity during a fever illness. She was found to have an undetectable blood glucose level and went into cardiac arrest shortly after arrival. CPR was performed for approximately 11 minutes. She then developed sever respiratory distress and was intubated. She was transferred to the PICU with IV sodium bicarbonate given en route. On admission, her body weight was 13.26 kg (36.80th percentile), height 90 cm (17.56th percentile), and BMI 16.17 (62.88th percentile). Her physical exam revealed normal external female genitalia and normal skin pigmentation. Lab evaluation revealed normal sodium and potassium but elevated anion gap, hyperuricemia, elevated creatinine kinase, abnormal liver function tests and abnormal coagulation profile. Brain MRI revealed findings consistent with hypoxic-ischemic encephalopathy. Renal function improved within 24 hours and hepatic function returned to normal after 20 days. Due to her severe hypoglycemic event, a high-dose ACTH stimulation test was performed. The results were consistent with adrenal insufficiency: baseline cortisol level, 7.3 μg/dL; 30 minutes cortisol, 7.8 μg/dL; 60 minutes cortisol, 9 μg/dL (normal response, ≥18 mcg/mL at 30 or 60 minutes). The baseline ACTH level was significantly elevated, 1688 pg/mL (0–46) as well as the renin activity, 24.3 ng/hour (1.7–11.2). Genetic testing revealed a 46 XX karyotype. STAR gene analysis identified compound heterozygosity; a novel deletion (c.811delC, p.Leu271Cysfs*50) and a previously reported missense mutation (c.661G&gt;A, p.Gly221Ser). The girl is now 11 years old and exhibits normal growth, normal cognitive development, and she has developed early signs of puberty (Tanner stage 2 for breast). She takes daily hydrocortisone, fludrocortisone and stress dose hydrocortisone as needed. Conclusion: In non-classic LACH, the onset is generally late or not acute. Initial clinical features are variable and nonspecific. For this reason, non-classic LCAH may be overlooked. Adrenal crisis is a life-threatening complication, and it is important that clinicians are aware of
the clinical features of non-classic LCAH and consider it in the differential diagnoses. Genetic testing for STAR should be considered in individuals with non-autoimmune primary adrenocortical insufficiency.
Concurrent Pseudohyperaldosteronism and Primary Glucocorticoid Deficiency From Posaconazole
Authors: Chang Julia J , Villar-Prados Alejandro , Stevens David A , Wang Xiao-Yan , Chen Julie 
Published: May 2021

Abstract
Background: Posaconazole can cause pseudohyperaldosteronism via inhibition of 11-beta hydroxylase and 11-beta-hydroxysteroid dehydrogenase type 2 (1). The accumulation of 11-deoxycorticosterone and increased cortisol-to-cortisone ratio in the kidney causes apparent mineralocorticoid excess. The effect of posaconazole on the glucocorticoid axis is less established.
Clinical Case: A 56-year-old Hispanic man with a history of chronic septic arthritis of the left ankle from Coccidioides presented with 3 months of malaise, nausea, weight loss of 30 pounds, and recurrent hypokalemia. He was recently switched from long-term fluconazole therapy to posaconazole around the time his symptoms began. His initial labs at our hospital were notable for low potassium (2.9 mmol/L, nl 3.5–5.5 mmol/L) and a random cortisol of 5.8 mcg/dL (nl ≥2.0 mcg/dL). A Cosyntropin stimulation test revealed elevated ACTH (168 pg/mL, nl 7.2–63.3 pg/mL) with minimal rise of cortisol from 4.6 to 7.2 mcg/dL at 1 hour after Cosyntropin administration (nl ≥18 mcg/dL at 1-hour post-Cosyntropin). His plasma renin activity was below detection (&lt;0.6 ng/ml/h, nl 0.6–3.0 ng/mL/h), consistent with renin suppression from apparent mineralocorticoid excess. Hydrocortisone for glucocorticoid deficiency was started. A posaconazole determination indicated elevation (5240 ng/mL, usual therapeutic range ≥1000 ng/mL). His posaconazole was stopped, and he was switched back to fluconazole. Three months later, his symptoms were improved with regain of lost weight. Repeat Cosyntropin stimulation test showed ongoing primary glucocorticoid deficiency (ACTH 123 pg/mL, cortisol 4.1 mcg/dL at 1-hour post-Cosyntropin) but normal levels of plasma renin activity (1.2 ng/mL/h), aldosterone (8.6 ng/dL, nl ≤21 ng/dL), and potassium. Quantiferon TB and 21-hydroxylase antibody tests were negative. Hydrocortisone has been continued with plans to repeat Cosyntropin testing in 3 months to reassess.
Conclusion: Pseudohyperaldosteronism with glucocorticoid deficiency requiring hydrocortisone treatment has thus far not been reported with posaconazole. Our case shows that posaconazole may lead to true primary glucocorticoid deficiency that can persist after discontinuation of posaconazole and reversal of pseudohyperaldosteronism.
Reference: (1) Sanchez-Niño MD, Ortiz A. Unravelling drug-induced hypertension: Molecular mechanisms of aldosterone-independent mineralocorticoid receptor activation by posaconazole. Clin Kidney J 2018;11(5):688–90.
Differentiating Between CAH and PCOS Using Hormone Levels and LC-MS/MS
Authors: Hauck Zane Z , Kimball David W , Zava David T 
Published: May 2021

Abstract
Introduction: PCOS is one of the most common endocrine issues affecting women today, with almost 10% of women suffering from this condition. CAH is a rarer disease that affects both men and women at a rate of around 1:1000 people. The problem with these two disorders arises in the fact that variants of these conditions may have very similar clinical presentations. This makes a proper diagnosis and treatment protocol difficult. Both PCOS and CAH present with high androgens but differ in that the former usually presents with high cortisol/insulin resistance, and the latter with low cortisol and aldosterone. Another difficulty in diagnosis is due to CAH presenting itself in 4 variants; 21-hydroxylase deficiency, the most common with over 95% prevalence, 11-hydroxylase deficiency, 3β-hydroxysteroid dehydrogenase type 2 deficiency, and 17α-hydroxylase deficiency. We have developed and validated an LC-MS/MS assay using a first morning saliva that measures a full panel of steroids necessary to clearly differentiate PCOS from all 4 variants of CAH. This full spectrum of steroids includes precursors of the active steroids (pregnenolone sulfate, DHEA, androstenedione) as well as parent steroids (progesterone, testosterone, estradiol, cortisol, aldosterone) and their precursors (17-OH progesterone) and downstream metabolites (11-hydroxycortisol, corticosterone) that differentiate PCOS from CAH and define the 4 variants of CAH. Clinical Case: We will present several example case reports showing that PCOS presents with high androgens and normal to high cortisol and aldosterone, and in sharp contrast, classic CAH presents with high androgens and 17-hydroxy progesterone, but very low steroids distal to 21-hydroxylase deficiency (i.e low 11-deoxycortisol, cortisol, cortisone, corticosterone, and aldosterone). In contrast the more rare variant of 11-hydroxylase deficiency shows a typical pattern of low cortisol and cortisone and elevated 11-deoxycortisol. 3β-hydroxysteroid dehydrogenase type 2 deficiency is extremely rare to see in an adult as most babies born with this condition do not survive. 17α-hydroxylase deficiency is also very rare but shows elevated progesterone, 11-deoxycorticosterone, corticosterone, and aldosterone. For all these cases aldosterone can be tricky to interpret as there are multiple mechanisms at which aldosterone is produced and thus should not be used as a definitive marker for CAH.