bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cushing Syndrome in the Setting of Chronic Dilated Cardiomyopathy: Can Treatment Improve Chronic Dilated Cardiomyopathy?
Authors: Pathak Leilani , Singh Shikha , Soni Lina , Zhou Ying Yin , Skwiersky Samara 
Published: May 2021

Abstract
Background: Cushing syndrome (CS) is well known to be associated with metabolic syndrome, venous thromboembolism, hypertension, left ventricular hypertrophy, and rarely dilated cardiomyopathy. The pathophysiological effects of hypercortisolism on the myocardium results in cardiomyocyte hypertrophy, myofibrillolysis, myocardial fibrosis, global longitudinal and circumferential strain. Our patient presents an example of CS in the setting of chronic heart failure with reduced ejection fraction, multiple thromboembolic events, and diabetes mellitus in a young adult.
Clinical Case: A 34-year male with a past medical history of dilated cardiomyopathy with biventricular failure and left ventricle ejection fraction of 10%, pulmonary embolism, diabetes mellitus, and gout presented with shortness of breath. On physical exam he presented with symptoms of CS: moon facies, supraclavicular fat pads, dorsal fat pads, purple striae of abdominal skin, truncal obesity, ecchymosis, and skin atrophy. Labs showed elevated morning cortisol after overnight 1 mg dexamethasone suppression test (cortisol 8.6 mcg/dl, n&lt; 5 mcg/dl), repeat morning cortisol after overnight 1 mg dexamethasone suppression test (cortisol 5.7 mcg/dl, n&lt; 5 mcg/dl), and ACTH-concentrations &lt;5 pg/ml. CT-scan was insignificant for adrenal hyperplasia. He was admitted and treated for acute congestive heart failure exacerbation with plans for definitive treatment of CS outpatient with further imaging studies.
Conclusion: The occurrence of CS induced heart failure results in increased mortality. There have been numerous accounts of resolution of cardiomyopathy after surgical treatment for CS secondary to adrenal adenoma. Our patient had a 10-year history of chronic dilated cardiomyopathy prior to cushingoid symptoms and confirmatory endocrinological data. The definitive treatment for CS syndrome in our patient would eventually be surgery targeting the source of hypercortisolism, however his cardiovascular risk factors would make him a poor surgical candidate. Severely reduced ejection fraction is a contraindication for generalized anesthesia needed for surgery. When surgery is contraindicated in CS medical management is recommended according to guidelines that target pituitary-directed medical treatments for Cushing’s disease and targeted therapies to treat ectopic ACTH syndrome. To our knowledge there have been few studies that demonstrate the effects of CS treatment on chronic conditions such as dilated cardiomyopathy. Studies have shown that surgical treatment for CS have reversed cardiomyopathy caused by CS but it still remains to be answered whether this same effect is achieved to some degree in chronic dilated cardiomyopathy.
Double Trouble: Co-Occurrence of Aromatase Deficiency and Non-Classic CAH in Three Siblings
Authors: Marinkovic Maja , Trujillo Marcela Vargas 
Published: May 2021

Abstract
Introduction: Aromatase deficiency (AD), an exceedingly rare autosomal recessive condition, causes virilization in females and tall stature with metabolic derangements in males. Clinical manifestations result from decreased estrogen production and androgen excess, but presentation varies based on residual aromatase activity. Non-classic CAH (NCCAH) is a relatively common disorder. Males are often asymptomatic or present with premature adrenarche (PA). Females are typically diagnosed during childhood/adolescence with PA, acne, hirsutism, or menstrual irregularities. We present three siblings with both conditions and describe their long-term follow-up. Cases: Identical twin sisters presented at birth with virilized genitalia. Evaluation revealed 46XX karyotype, transiently elevated testosterone (unchanged with hCG stimulation), normal 17OHP and normal ovarian tissue on gonadal biopsy. Due to sporadic follow-up, their diagnosis and care were delayed until age 15y when AD was confirmed with genetic testing (compound heterozygous: whole gene deletion on one allele and c.242A&gt;G (p.tyr81cys) mutation on the other). Both girls had acne, hirsutism and clitoromegaly, but reached spontaneous menarche at 11y and height within mid-parental height (MPH). Given the genetic nature of AD, younger brother was assessed and diagnosed with AD with the same mutation in CYP19A1. He had normal height-corrected BMD, lipids and glucose. His testosterone level was high-normal with undetectable estradiol. He had height below MPH with slow growth velocity, low IGF-1 and bone age (BA) within 2SD for age (BA 14y at CA 15y). GH stimulation test with estrogen priming revealed GH peak of 4.1 ng/ml, consistent with GH deficiency. All three siblings had high baseline and stimulated 17OHP which prompted genetic testing for CAH and confirmed NCCAH due to homozygous pVal282Leu substitution in CYP21A2. Treatment for both AD and NCCAH in females is combined estrogen+progesterone (usually given as an oral contraceptive pill), to replace estrogen and suppress androgen overproduction. The twin sisters elected clitoral reduction at age 19y with a satisfactory outcome. Their brother is not on any treatment at this time. At age 18y, his BA is still 14y-14.5y, as expected in AD, but atypical for NCCAH. Conclusion: Virilized genitalia in the newborn period prompted extensive evaluation of twin sisters that led to diagnosis of AD but also prompted assessment and diagnosis of their asymptomatic brother. Elevation of 17OHP, previously not described in AD patients, prompted testing for CAH and confirmed the unique finding of both AD and NCCAH in these three siblings. We postulate that the combined AD/NCCAH caused exacerbation of androgen excess in all three siblings. The short stature in our male patient is presumably due to GH deficiency.
Dual Adenomas: Detection of Cushing’s Syndrome of Adrenal Origin During Evaluation of Pituitary Macroadenoma
Authors: Fasen Madeline , Wehmeier Kent R , Kapadia Poonam Kalidas 
Published: May 2021

Abstract
Cushing’s syndrome is a rare and often severe disease associated with increased mortality and major metabolic complications with cardiovascular disease as the main cause of death. Adrenal masses are most often found by radiographic studies or autopsy as incidentalomas. The prognosis of Cushing’s syndrome is mainly affected by the difficulties in timely diagnosis and treatment of the disease, which remain a challenge due to its nonspecific presentation and multitude of etiologies. Herein, we present an atypical case of adrenal Cushing’s syndrome unveiled by the workup of a nonfunctioning pituitary macroadenoma. A 62 year-old woman presented with new intermittent headaches and worsening vision changes for the past year. She was found to have a large sellar mass measuring 2.7 x 2.4 x 3.0 cm invading the right cavernous sinus with displacement of the optic chiasm on brain magnetic resonance imaging (MRI). In the interim to neurosurgical evaluation, lab work performed to assess pituitary function showed an elevated late night salivary cortisol at 0.200 UG/DL (0.010–0.090 UG/DL range). Low early morning ACTH and elevated late night salivary cortisol, dexamethasone suppression test and 24 hour urine cortisol were observed and confirmed with repeat studies. These findings warranted a computed tomography (CT) adrenal mass protocol which revealed a left adrenal lesion consistent with a lipid rich adenoma measuring 4.9 x 3.5 x 4.1 cm in size. Subsequent urine catecholamines and metanephrines were within normal limits. The patient was admitted for transphenoidal pituitary resection with perioperative stress dose corticosteroids, but was only able to achieve partial resection due to large tumor size. Post-operatively the patient did well on a quick corticosteroid taper down to hydrocortisone 15 mg in AM and 5 in afternoon with hope to wean in the near future. Post-operative workup showed ACTH 4.6 pg/mL (7.2 – 63.3 pg/mL) and 8 am cortisol 24.7 MCG/DL (6.2–19.4 MCG/DL) which suggests autonomous adrenal secretion of cortisol. Once the patient has recovered from her partial pituitary resection she will be referred to general surgery for adrenalectomy. This case provided a review of a classic pituitary macroadenoma workup with an interesting twist to Cushing’s etiology as the cause was not from the pituitary as originally thought.
Ectopic Cushing’s Syndrome and Severe Hypocalcemia Due to Medullary Thyroid Cancer Responsive to Selpercatinib
Authors: Turin Christie Gloria , Brose Marcia S , White Caitlin A 
Published: May 2021

Abstract
Introduction: Cushing’s syndrome (CS) due to ectopic ACTH production from medullary thyroid carcinoma (MTC) is characterized by rapid progression of disease, leading to hyperglycemia and hypokalemia. However, hypercortisolemia leading to hypocalcemia is rarely seen. Initiation of selpercatinib greatly improved hypocalcemia and ectopic CS in this case. Clinical Case: A 41-year-old man with a history of MTC (variant RET p.M918T) post thyroidectomy in 2018 developed progressive weight gain, lower extremity edema, weakness, new onset diabetes, severe refractory hypocalcemia and hypokalemia requiring multiple hospitalizations. On initial presentation to our institution, he was lethargic, had multiple ecchymoses, peripheral edema and proximal myopathy. Laboratory evaluation revealed Ca 5.4 mg/dL (NR 8.9 - 10.3), albumin 3 g/dL (NR 3.5 - 5.1), iPTH 1.4 pmol/L (NR 1.6 - 6.9), 25-OH vitamin D 23 pg/mL (NR 25–80) while taking elemental calcium 1500 mg every 6h, calcitriol 0.25 mcg/d and vitamin D3 1000 IU/d. Serum cortisol measured at 9:30 pm was 136 ug/dL (NR 2.5–11.9), ACTH 1,145 pg/mL (NR 7.2–63.3) and 24-h UFC 27,629 ug/d consistent with CS due to ectopic ACTH production. Calcitonin and CEA were 18,687 pg/mL (NR 0–7.5) and 3,766 ng/mL (NR 0–4.7). CT abdomen revealed numerous bilateral liver lesions and bilateral adrenal hyperplasia. In addition to high doses of oral calcium and calcitriol, he required calcium drip up to 1.5mg/kg/hr for about 1 week. He simultaneously began cabozantinib, ketoconazole and metyrapone. Hospital course was complicated by infections and recurrent scrotal bleeding, so he was switched to selpercatinib. Two days after starting selpercatinib, ketoconazole was discontinued, and metyrapone has been gradually reduced. Most recent calcitonin was 149 pg/mL, CEA 97.8 ng/mL and 24-h UFC 10 ug/d on metyrapone 250 mg twice daily. Similarly, refractory hypocalcemia greatly improved, last serum Ca was 8.3 mg/dL on elemental calcium 480 mg/d. He has made significant clinical gains and has returned home from rehab. Clinical Lesson: Hypocalcemia is rarely described as a complication in patients with CS. Our patient had underlying hypoparathyroidism and vitamin D deficiency; however, hypocalcemia was initially refractory to high doses of calcium and calcitriol and only improved with treatment of CS. We suspect hypercortisolemia impaired 25 to 1,25 D activation, thereby reducing calcium absorption, and likely inducing hypercalciuria. These deleterious effects of severe hypercortisolemia combined with underlying hypoparathyroidism led to severe and refractory hypocalcemia requiring repeated admissions, and only improved once his ectopic CS due to MTC was recognized and controlled. The RET kinase inhibitor, selpercatinib, induced a rapid decline in calcitonin, CEA and ACTH levels, and with metyrapone, enabled control of hypercortisolemia and its complications.
Glucocorticoids and Pheochromocytoma- a Recipe for Disaster?
Authors: Chandrashekar Nikhitha , Asp Arnold Allan 
Published: May 2021

Abstract
Background: Pheochromocytomas are catecholamine-secreting tumors that arise from the chromaffin cells of the adrenal medulla. The catecholamine release manifests as episodic headaches, diaphoresis, and palpitations which can lead to hypertensive emergency known as a pheochromocytoma crisis(PC). This crisis can be precipitated by commonly used medications including corticosteroids, metoclopramide, and anesthetic agents like ketamine and halothane. Case report: We present a 60 year old Caucasian male with a past medical history significant for SVT on metoprolol and diltiazem and long-standing hypertension. He was admitted directly from the clinic to the ED after complaining of severe abdominal pain, multiple episodes of vomiting, and diaphoresis following prednisone intake for a presumed gout flare. He had a blood pressure of 180/100 and tachycardic to 120s on arrival. He was also found to be hypoxemic with a chest x-ray concerning for pulmonary edema along with evidence of a demand related type II NSTEMI. He underwent a CT abdomen pelvis with contrast which showed evidence of high grade distal ileum obstruction with no obstructing mass or inflammatory process. There was also 5-cm solid right adrenal mass which was initially thought to be an incidentaloma. Following stabilization, he underwent an exploratory laparotomy which did not show an obvious mechanical etiology of bowel obstruction. This raised concerns for a pheochromocytoma. Oral verapamil with doxazosin was started to provide appropriate alpha blockade. Subsequently, metoprolol was reintroduced for beta blockade. He was officially diagnosed with glucocorticoid-induced pheochromocytoma after his labs returned with elevated levels of serum metanephrines 43.7(0.00 - 0.49 nmol/L), serum normetanephrine 22.2 (0.00 - 0.89 nmol/L),), 24-hr urine epinephrine 1021 ug/g (0 - 20 ug/g), and 24-hr urine norepinephrine 838 ug/g (normal: 0 - 45 ug/g). Ultimately 3 weeks later he underwent successful R sided adrenalectomy and is doing well. Conclusion: This case demonstrates a rare but life-threatening adverse reaction associated with commonly used glucocorticoids in a patient with an undiagnosed pheochromocytoma. Pheochromocytomas are exceedingly rare and can go undiagnosed in up to 50 percent of patients (1). Failure or delays in diagnosis of PC can lead to increased morbidity and mortality. When managing a pheochromocytoma crisis, it is imperative to avoid selective beta-blockers, as it can worsen hypertension due to unopposed alpha agonism by the secreted catecholamines. This also demonstrates the importance of keeping a broad differential in order to avoid anchoring bias, particularly when there is conflicting clinical information. References: 1. Sutton MG, Sheps SG, Lie JT. Prevalence of clinically unsuspected pheochromocytoma. Review of a 50-year autopsy series. Mayo Clin Proc. 1981 Jun;56(6):354–60. PMID: 6453259.
Looking Beyond Diabetes: A Case of Worsening Hyperglycemia as a Manifestation of Ectopic Cushing’s Syndrome Secondary to an Adrenocorticotropic Hormone-Producing Pheochromocytoma
Authors: Anwar Kanwal , Alpertugna Ipek , Detelich Danielle , Balonov Konstantin , Tarnoff Michael , Vercollone Jeffrey , Siegel Richard D , Tischler Arthur S , Lechan Ronald M 
Published: May 2021

Abstract
A 76-year-old woman presented with worsening fasting hyperglycemia on routine blood sugar measurement, previously well-controlled on Metformin, requiring initiation of insulin. Her medical history included type 2 diabetes mellitus, hypertension, and aortic stenosis. Over the next few weeks, she developed bilateral upper and lower extremity proximal muscle weakness, episodes of confusion, rapid weight loss and increasing lower extremity edema. She did not have typical Cushingoid features of moon facies, easy bruising, centripetal obesity, abdominal striae, dorsocervical fat padding, or hyperpigmentation. Laboratory data revealed severe hypokalemia, elevated cortisol of 138 (3.7–19.4 ug/dL) and ACTH of 368 (6–50 pg/mL) consistent with ACTH-dependent Cushing’s syndrome. She was hospitalized for emergent therapy with etomidate infusion, potassium supplementation, and started on spironolactone. 24-hour urinary analysis demonstrated elevated catecholamines and metanephrines: epinephrine 552 (2–16 mcg/g cr), norepinephrine 1881 (7-5 mcg/g cr), metanephrine 4095 (21–153 mcg/g cr), normetanephrine 3920 (108–524 mcg/g cr).
CT abdomen showed 3.8 cm mass in the left adrenal gland with enhancing walls and central hypoattenuation and a normal contralateral adrenal gland. MR brain showed a partial empty sella without any mass. 123I-metaiodobenzylguanidine scintigraphy showed uptake in the left adrenal mass. Once cortisol was reduced to &lt;25 ug/dL, she was transitioned from etomidate to metyrapone; alpha-methyltyrosine and prazosin was also begun. Following left laparoscopic adrenalectomy, ACTH decreased to &lt;5 pg/mL confirming that the pheochromocytoma was the source of ectopic Cushing’s. Gross examination of the mass was notable for a spongy, tan, roughly spherical medullary neoplasm (3 cm in diameter) with a rim of brown and focally yellow adrenal cortex up to 4 mm thick. Marked diffuse adrenal cortical hyperplasia was noted. The tumor showed varied growth patterns, including solid areas and spongy, angioma-like areas with prominent small blood vessels. Immunohistochemical staining was positive for somatostatin receptor 2A, tyrosine hydroxylase and ACTH in tumor cells and negative for T-PIT. She was discharged on replacement hydrocortisone therapy, minimal insulin for diabetes and has shown substantial clinical improvement.
Cushing’s syndrome due to ectopic ACTH-producing pheochromocytoma is rare. Worsening hyperglycemia in the presence of hypertension, even without typical clinical findings of Cushing’s, should prompt further hormonal work up. The absence of the transcription factor TPIT, which is a lineage determinant for pituitary corticotrophs, suggests that novel pathways are involved in differentiation of cells that produce ectopic ACTH.
Malignant Testicular Paraganglioma: The Importance of Adequate Clinical Follow-Up
Authors: Alves Pantaleão Priscilla Maris Pereira , Leal Angela Cristina Cristina 
Published: May 2021

Abstract
Background: Paragangliomas (PGL) are rare neuroendocrine tumors derived from neural crest cells. The presence of metastases is the only absolute criterion of malignancy. Clinical Case: A 59 y.o. male patient reports the appearance of a tumor in the right inguinal region operated in 2014 with tumor removal and right orchiectomy, with anatomopathological (AP) outcome spermatic cord adenomathoid tumor and immunohistochemistry (IHC) compatible with PGL: Ki-67 1% (S 100 diffusely positive protein), diffusely positive chromogranin A, weak positive CD99. However, no new tests were performed in the follow-up. After 5 years, the patient started to present sporadic episodes of sweating, palpitations and increased tension levels after doxazosin suspension. Investigation for reoccurrence with Urinary Catecholamines: Noradrenaline (VR&lt; 97 mcg/24h) 112/179, Adrenaline (VR&lt; 27 mcg/24h) 4/4, Dopamine (&lt; 500 mcg/24h) 184/ 342, Plasma Metanephrines: Normetanephrines (VR&lt; 196 pg/ml) 880.7/ 2402 Metanephrines (VR&lt; 65 pg/ml) 44.6/ 53.1. Tests was performed: chest CT Multiple bilateral non-calcified pulmonary nodules with contrast enhancement, measuring 1.2 cm. Abdominal CT: Two retroperitoneal solid lesions located anteriorly to the inferior vena cava and aorta, in a discretely paramedian position on the right, intense arterial enhancement, with a hypoattenuating center. The largest lesion is located just below the emergence of the renal arteries and after the head of the pancreas and third portion of the duodenal. It measures 4.4 x 3.2 x 4.4 cm (LL x AP x CC). The smallest lesion is immediately inferior to the largest and measures 3.1 x 2.6 x 3.6 cm (LL x AP x CC). The lesions have contact with retroperitoneal vascular structures, notably with the inferior vena cava and with the vascular pedicle of the right kidney. Scintigraphy with MIBG: Radiopharmaceutical hyperconcentration in focal areas in the projections of lung fields, in greater number on the left, with intensity of uptake varying from mild to moderate; two contiguous focal areas in the median projection of mesogastrics, in moderate/acentuated degree. Patient was reoperated and removed abdominal lesions with new conclusive AP for PGL whit PASS 3, currently performing therapeutic MIBG for thoracic injury control. Clinical Lesson: Patients with lesions suggestive of PGL but without confirmatory AP should request IHC and clinical follow-up will be according to the findings in it.
Nephrotic Syndrome Following Resection of an Adrenal Incidentaloma:A Case Report
Authors: Batool Maria , Leen Eamon , Glavey Siobhan , Sreenan Seamus K , McDermott John 
Published: May 2021

Abstract
A 69 year old man had a 5 cm right adrenal lesion discovered incidentally while being investigated for a deterioration in previously well-controlled hypertension. Routine investigations including serum albumin were normal. Further investigation confirmed a non-functioning adrenal lesion. MRI revealed a ‘non-fat-containing T1 hyperintense indeterminate adrenal lesion with speckling of T2 hyperintensity, not typical for adenoma, hyperplasia, myelolipoma, haemangioma or pheochromocytoma’. An uncomplicated laparoscopic adrenalectomy was performed. Histology revealed a 118 g adrenal neoplasm, modified Weiss score 0, with abundant hyaline deposits.3 months later the patient complained of peripheral oedema. Investigations revealed a serum albumin of 24 g/L and 14 g of proteinuria in 24 hours. Serum protein electrophoresis revealed a monoclonal IgA type lambda band. Renal biopsy revealed amorphous material displaying apple green birefringence on staining with Congo Red, which stained with antibodies to lambda light chains, confirming AL amyloid. Therefore the patient’s resected adrenal specimen was retrieved and stained with Congo Red, revealing apple green birefringence in the walls of the blood vessels, confirming the presence of amyloidosis. Although adrenal gland involvement in secondary amyloidosis is common, adrenal involvement in primary amyloidosis is less well described. This case illustrates the indolent nature of primary amyloidosis, prior to the development of often catastrophic symptoms. Consideration should be given to Congo Red staining of resected pathologic specimens containing hyaline deposition, to potentially allow for earlier recognition of this devastating disease. A pathophysiologic link between the patient’s incidentaloma, adrenalectomy, and onset of nephrotic syndrome remains a matter for conjecture.