bluuebunny/crossref_metadata_2025_split huggingface dataset:
Late Onset of Abiraterone Severe Hypokalemia Due to Unsuspected ACTH-Secreting NEC
Authors: Toral Fernando Pazos , Duran Ignacio , Schettini Isabel Alvarez 
Published: May 2021

Abstract
Clinical Case: 68-year-old male, Active smoker (30-40 packs/year), and moderate alcohol drinker. An increase in urinary frequency, nocturia, and a PSA of 116 µg/L led to the diagnosis of disseminated castration-sensitive prostate cancer (CSPC), advanced Gleason score (3 + 4 pT2), with bone and retroperitoneal metastases (CT). By 02/2018, he started androgen deprivation therapy (ADT) with Abiraterone (AB) 1000 mg, prednisone, and LHRH agonist. 15 months later, PSA levels decreased to 0.75 ng/ml without side effects and normal K+(3.7 mEq/L), when a CT scan revealed both liver and bone metastasis. During the progression study, two months later, the patient was admitted to the hospital for severe hypoK+ (1.7 mEq / L), normal renal function and metabolic alkalosis. Although abiraterone was discontinued, up to 460 mEq iv per day of K+ and spironolactone were required to maintain serum K+ above 2.5. 3 days later, the hormonal study revealed TSH 1.13 mU /L, ACTH 162 pmol/L, cortisol 258 nmol/L, aldosterone 105 pmol/L, renin (protein) 0.7 µU/mL and deoxycorticosterone 507 pmol/L. 11 days later, plasma cortisol was 967 nmol/L, ACTH 132pmol/L, and cortisoluria 1456 nmol/d. The suppression test with 1 mg of DXM for cortisol was 1162,5 nmol/L. DHEAS was &lt; 407 nmol/L. Liver biopsy showed a small cell neuroendocrine carcinoma (NEC), chromogranin (+), synaptophysin (+), CD56 (+), TTF-1 (+), PSA (-), Ki-67 90% and the granular cytoplasmic ACTH (+). The octreotide scan (+) revealed pathological uptake in L4, multiple uptakes in the liver, and in the axial skeleton. Treatment with Carboplatin plus Paclitaxel for NEC was started, completing 3 weekly doses with good tolerance and clinical benefit, but with the persistence of severe hypoK+ (2.5 mEq/L). Treatment with lanreotide 120 mg every 4 weeks was added, following a feeling of clinical improvement, the disappearance of edema, asthenia, and normalization of plasma K+ (3,4mEq/L). The patient died two months later from respiratory sepsis. Discussion: Several clinical trials have demonstrated that the combination of AB plus ADT prolongs overall survival in DCSPC. The CYP17 inhibition by AB increases ACTH leading to early secondary mineralocorticoid excess with hypokalemia and hypertension while the cortisol levels remain normal or low. Cortisol serum levels increased after AB was discontinued, whereas aldosterone serum levels remained low due to K+ regulatory feedback. The hormonal profile and the pathological and radiological studies revealed an ACTH-producing small cell NEC. In this patient, the previous treatment with BA has masked the clinical and hormonal profile of an ectopic Cushing syndrome. Therefore, Cyp17 inhibitors can mask adrenal or extra-adrenal processes characterized by alterations in steroid metabolism. This case has suggested a more thorough assessment of the adrenal hormonal profile including ACTH during BA treatment.
Salivary Estrogens Androgens and Aromatase Inhibitors by LC-MS/MS in Breast Cancer Patients Treated With Testosterone Pellets Combined With Aromatase Inhibitors
Authors: Zava David T , Kimball David W , Glaser Rebecca L 
Published: May 2021

Abstract
Introduction: High dose testosterone (T) has been used for treating hormone-sensitive breast cancers for many years. However, a drawback to T therapy is its propensity to convert to estradiol (E2) via aromatase, which can override the growth inhibitory effects of T and stimulate estrogen sensitive tumors. Aromatase is higher in some women than others, particularly those with active tumors, truncal obesity, and inflammatory conditions contributing to and caused by cancer. Oral aromatase inhibitors (AI) have been used to prevent conversion of T to E2. While this effectively reduces E2 burden, systemic oral AI require higher dosing, which often leads to severe side effects. As an alternative to oral AI therapy, researchers have found that T combined with a much lower dose of AI in a solitary pellet implant placed in the subcutaneous (SC) tissue, or alternatively, into the breast adjacent to a primary tumor, is effective in reducing tumor burden and maintaining a low systemic level of E2, while reducing the adverse side effects of very low E2. Study Design: In this case study we report on the use of an LC-MS/MS method to monitor salivary levels of E2, Estrone (E1), T, and the AIs Letrozole (LET) and Anastrozole (ANZ) following T + AI therapy in a breast cancer patient (intolerant of oral LET) with active (measurable) tumor in the breast and metastatic disease. Steroids and AIs were measured in saliva at baseline, 1 week, and 4 weeks after insertion of subcutaneous pellets containing ‘60 mg T + 4 mg ANZ’ and ‘60 mg T + 6 mg LET’. Results: LC-MS/MS (range values-pg/ml) for postmenopausal women, and baseline, week 1 and week 4 post treatment values for each steroid and AI were: E2: (range 0.3-0.9), 0.4, &lt; 0.3, &lt; 0.3; E1: (range 0.9-3.1), 1.0, &lt;0.4, &lt;0.4; T: (range 7-22), 6, 96, 48; ANZ: (range &lt;4), &lt; 4, 2063, 24; LET: (range &lt;4), &lt; 4, 744, 175. Self-reported (Pre/Post Therapy) estrogen deficiency symptoms such as hot flashes, night sweats, vaginal dryness, joint pain, and sleep disturbances were significantly improved post T+AI therapy. In addition, the intramammary tumor decreased in size &gt; 95% by month 5. Summary: These results show that low-dose SC AI therapy (4-6 mg/2-3 months = 0.1 mg/day) with T (120 mg/2-3 months = 1-2 mg/day) increases T to supra-physiological levels, prevents T metabolism to estrogens E2 and E1, reduces estrogen deficiency symptoms, and has beneficial effects on tumor growth inhibition. Simultaneous testing of sex-steroids E2, E1, T, and aromatase inhibitors LET and ANZ by LC-MS/MS provides a convenient means to monitor the bioavailable levels of these analytes and adjust them as necessary to optimize therapeutic efficacy and reduce adverse side effects.
Think Outside the Thorax: Doege-Potter Syndrome Presenting as a Retroperitoneal Mass
Authors: Gray Cater Taylor Lauren , Symczyk Oksana , Haider Adnan 
Published: May 2021

Abstract
Introduction: Non-islet cell tumor hypoglycemia (NICTH) is a rare paraneoplastic syndrome, occurring less commonly than insulinoma. These tumors produce high molecular weight insulin-like growth factor-2 or “big IGF-2”, resulting in hypoglycemia: big IGF-2 decreases glycogenolysis, gluconeogenesis, and glucagon release as well as increases glucose uptake by adipocytes and skeletal muscle. NICTH specifically associated with a solitary fibrous tumor (SFT) is known as Doege-Potter syndrome. Doege-Potter syndrome is seen most with thoracic SFT’s. This case study details the diagnosis and management of Doege-Potter syndrome due to retroperitoneal SFT.
Case Description: Our patient is a 68-year-old, white female who initially presented to an outside facility with a 3-week history of episodic neuroglycopenic symptoms temporarily relieved with eating. She reported night sweats but no weight change or fever. Medical history was notable only for hypertension and GERD. She had no personal or family history of diabetes. She was transferred to our facility for further evaluation of an 18.6 cm multilobular mass seen just inferior to the liver on abdominal CT. Whipple’s triad was confirmed with venous glucose sampling while inpatient. C-peptide, free/total insulin, and pro-insulin were collected during permissive hypoglycemia and were low. Morning cortisol and TSH were unremarkable. Additionally, sulfonylurea screen and insulin antibodies were negative. Ultrasound-guided biopsy of the lesion was positive for CD34 and STAT6, consistent with SFT. Refractory hypoglycemia was treated with D5W infusion until surgical resection of the retroperitoneal mass, after which, she had complete resolution of her hypoglycemia.
Discussion: This patient’s serum IGF-2 was within normal limits, consistent with reports of feedback inhibition exerted by increased levels of big-IGF-2. Therefore, the IGF-2:IGF-1 ratio is used to determine increased serum levels of big IGF-2, but this test is not widely available. SFT’s can recur within months to years of resection, necessitating surveillance. Recurrence is also more common with extrathoracic tumors. Surgical pathology noted tumor dimensions of 22 cm and 2270 g; mitotic rate was 1 per 10 hpf. Features typical of malignancy include large size (&gt;15 cm) and mitotic rate &gt;4 mitoses per hpf. This patient’s follow-up CT abdomen at 6 weeks did not show any findings to suggest recurrent or metastatic disease.
A Unique Case of Corticomedullary Mixed Tumor Composed of Both Adrenal Cortical Cells and Pheochromocytes
Authors: Panja Srinivas R , Ali Safrin 
Published: May 2021

Abstract
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 &lt; or = 57pq/ml) and abnormal 1mg dexamethasone suppression test (10.4mcg/dL, n &lt;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

Abstract
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 &lt;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

Abstract
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

Abstract
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

Abstract
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 &gt;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

Abstract
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 &lt;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 (&lt;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.