bluuebunny/crossref_metadata_2025_split huggingface dataset:
Persistent Fatigue After Pregnancy: A Case Report
Authors: Naha Sowjanya , Parimi Joseph Theressa Nehu , Gundluru Rajani , Liu John Chen , Syed Hasan , Gusov Timur 
Published: May 2021

Abstract
Background: Pregnancy is characterized by physiologic immunosuppression and the postpartum period is often associated with rebound autoimmunity leading to unmasking of latent autoimmune disorders. Clinical Case: A thirty-one-year-old Caucasian female presented with generalized fatigue, myalgias and arthralgias that started three months after the birth of her first child. She was seen at a local hospital on multiple occasions and was treated symptomatically. She was noted to have orthostatic hypotension during these visits and was initiated on midodrine and fludrocortisone for presumed postural orthostatic tachycardia syndrome. When her symptoms did not abate, she was referred to our center for further care. At the time that we saw her, she reported nausea and vomiting in addition to the aforementioned symptoms. On careful questioning she also admitted to salt craving and unintentional weight loss of about 20 lbs over the past three months. She did not have a past history of autoimmune or endocrine disorders, but family history was positive for Grave’s disease and celiac disease in her aunt and mother respectively. Physical examination revealed hyperpigmentation of the face, knuckles, toes and abdominal scars. Random serum cortisol level was low (1.06 mcg/dL) with no perceptible response to ACTH stimulation (1.10 mcg/dL and 1.04 mcg/dL at 30 and 60 mins respectively). Serum aldosterone was undetectable (&lt;4 ng/dL) and dehydroepiandrosterone sulfate level was low (19 mcg/dL, n: 45–295 mcg/dL). The patient was immediately initiated on corticosteroid replacement therapy. Her symptoms rapidly resolved and she was discharged on maintenance dosing of hydrocortisone and fludrocortisone. ACTH was grossly elevated (577 pg/mL) and 21-Hydroxylase antibodies were positive, confirming a diagnosis of autoimmune adrenalitis. Conclusion: Symptoms of adrenal insufficiency are often non-specific and can overlap with physiological symptoms of pregnancy. Persistence of these symptoms after delivery should raise concerns for autoimmune adrenalitis precipitated by immune reconstitution in the postpartum period.
Pheochromocytoma as the Etiology of Cushing Syndrome Through Paracrine ACTH Signaling
Authors: Jaju Amruta , Williams Vanessa , Ali Mariam Murtaza , Rehman Anis , Imtiaz Sonaina , Jakoby Michael G 
Published: May 2021

Abstract
Introduction: Pheochromocytomas are rare catecholamine-secreting tumors of the adrenal medulla that may also secrete ACTH. There are approximately 100 cases of ACTH-producing pheochromocytomas reported in the peer reviewed literature, and they typically cause Cushing syndrome by significantly raising circulating ACTH levels. We report a pheochromocytoma causing apparent ACTH-independent Cushing syndrome by paracrine action of locally produced ACTH on ipsilateral adrenal cortex. Case: A 64-year-old female was referred for an incidentally discovered left adrenal mass. The mass was 4 cm and 37 Hounsfield units on non-contrast computed tomography, and the right adrenal gland was unremarkable. The patient’s history was notable for three years of resistant hypertension, and examination revealed stigmata of Cushing syndrome including moon facies, scattered bruises, and wide, pink striae. Three measurements of plasma metanephrines ranged from 3- to 4.5-fold elevated, and 24 h urine metanephrines were 5.2-fold elevated. Urine 24 h epinephrine was 2.7-fold elevated. Three 8 AM cortisol measurements on overnight dexamethasone suppression tests were 16.3–17.4 mcg/dL (&lt; 1.8), and 8 AM dexamethasone on one test was 494 ng/dL (140–295). Two midnight salivary cortisol measurements were 0.348 and 0.416 mcg/dL (&lt; 0.112), and 8 AM ACTH levels on two occasions were 6.8 and 7.9 pg/mL (7.2–63.3). After adrenergic blockade, the patient underwent left adrenalectomy. Her tumor stained for synaptophysin and chromogranin consistent with pheochromocytoma, and focal staining for ACTH was also observed. Hyperplasia of the adjacent adrenal cortex was present. Hypertension resolved after adrenalectomy, and the patient developed secondary adrenal insufficiency (8 AM cortisol and ACTH 1.0 mcg/dL [&gt; 15] and 2.9 pg/mL, respectively). Discussion: There are five published reports of pheochromocytoma and subclinical hypercortisolemia due to paracrine ACTH or IL-6 activity on ipsilateral adrenal cortex, but this case is distinguished by the occurrence of overt Cushing syndrome. Our patient had ACTH &lt; 10 pg/mL on two measurements, her pheochromocytoma showed focal staining for ACTH, and hyperplasia of adjacent adrenal cortex was observed. In contrast, median ACTH level was 5-6x above the upper limit of normal in a recent review of 95 cases of pheochromocytomas with Cushing syndrome due to ectopic ACTH secretion. If Cushing syndrome was due to bilateral adrenal hyperplasia independent of the patient’s pheochromocytoma, cortisol excess would not have resolved after unilateral adrenalectomy. Communication between cortical and medullary circulations through venous radicles provides a mechanism for ACTH produced by the patient’s pheochromocytoma to affect the function of adjacent cortex. This case demonstrates a novel mechanism by which ACTH from a pheochromocytoma can cause Cushing syndrome.
The Case of a Glucocorticoid-Induced Myopathy & Myasthenia Gravis Combination: Is There a Border?
Authors: Dzherieva Irina , Brovkina Snezhana , Volkova Natalia , Davidenko Ilia , Reshetnikov Igor , Yudin Maxim , Plyashkevich Maria , Merenkova Maria 
Published: May 2021

Abstract
Introduction: Glucocorticoid-induced myopathy is the sign of Cushing’s syndrome in 83%, but can also be consequence of exogenous administration of glucocorticoids. The patients with the compromised neuromuscular system (for example, because of myasthenia gravis) have a higher risk of this complication. Differential diagnosis of glucocorticoid-induced myopathy is challenging. Clinical case. A 77-year woman complained of difficulty in the act of breathing, swallowing, weakness in the limbs, inability to self-service, ptosis. Due to the growing complaints the patient was hospitalized to ICU. From anamnesis: She was diagnosed with myasthenia gravis 2 months ago. The presence of autoantibodies to the nicotine acetylcholine receptor was confirmed. Pyridostigmine bromide 60 mg/day, Methylprednisolone 20 mg/day were prescribed for 5 days. The patient noted some improvement. After the next neurologist’s examination the dose of Methylprednisolone was doubled. (It is not known for certain whether the doctor wanted to reduce the dose and the patient misunderstood.) She noted some worsening: weakness and speech difficulties increased. She returned to the previous dose after 3 days, but there was no improvement. Objectively: hypersthenic body type, BMI 39 kg/m2, predominant deposition of adipose tissue in the abdomen and face. Breathing without a ventilator. BP 250/100 mm Hg, heart rate 87 BPM. Laboratory tests revealed hyperkalemia of 8.76 mmol/l (3.5–5), creatinine of 481 mmol/l (44–124), hyperglycemia of 16 mmol/l. Glucocorticoid-induced myopathy was suspected, the administration of methylprednisolone was cancelled. The improvement of the condition was noted in 3 days. Blood pressure, glycaemia, levels of potassium and creatinine returned to normal. A biopsy of muscle revealed: atrophy of type I and II muscle fibers. There were no signs of necrosis, regeneration or inflammation. Thereby the diagnosis of glucocorticoid-induced myopathy was confirmed. Conclusion. Glucocorticoid-induced myopathy may look like a decompensation of neuromuscular disease. Since there are no accurate diagnostic tests nowadays the main argument of diagnosis is the paradoxical reaction after increasing the dose of glucocorticoids as well in this case. Even a short period of use of these drugs can lead to the development of side effects. It is necessary to regularly monitor the dynamics of the condition of such patients.
Type 4 Renal Tubular Acidosis (RTA) Induced by Spironolactone Use in Secondary Adrenal Insufficiency
Authors: Santos Claudia Villatoro , De Rose Lisa , Proudan Nikoletta 
Published: May 2021

Abstract
Type 4 RTA is caused by either decreased aldosterone production or resistance. Primary adrenal insufficiency results in decreased aldosterone whereas spironolactone can cause aldosterone resistance1. We present a case of spironolactone-induced type 4 RTA in a patient with suspected primary adrenal insufficiency.
A 70-year-old female with liver cirrhosis on spironolactone and chronic bronchitis on inhaled steroids (ICS) presented for altered mental status. Laboratories showed hyponatremia 131 mmol/L (135–145 mmol/L) and hyperammonemia 113 µmol/L (11–51 µmol/L). She was successfully treated with oral lactulose for hepatic encephalopathy. However, on day 3, she developed worsening hyponatremia (126 mmol/L) and hyperkalemia 5.8 mmol/L (3.5–5.4 mmol/L). Spironolactone was discontinued, and hyperkalemia improved after medical treatment. Nonetheless, hyperkalemia recurred with worsening hyponatremia (125 mmol/L), hypoglycemia (57 mg/dL), and mild non-anion gap metabolic acidosis without other signs or symptoms of adrenal insufficiency. On day 5, her morning cortisol was 1.5 µg/dL (5–20 µg/dL), with ACTH 11 pg/mL (6–70 pg/mL). Her hyperkalemia persisted (6.3–6.8 mmol/L), and she was started on oral patiromer. Due to suspected adrenal insufficiency, she received dexamethasone 10 mg daily, and endocrinology was consulted. On day 7, an ACTH stimulation test (250 µg IV) showed a baseline ACTH &lt;3 pg/mL, baseline cortisol 0.7 µg/dL (3–15 µg/dL), cortisol 30 minutes 9.9 µg/dL, and 60 minutes 12.2 µg/dL, consistent with incomplete response attributed to the supraphysiologic dexamethasone versus chronic ICS. On day 8, endocrinology discontinued dexamethasone and enoxaparin, and started hydrocortisone 10 mg orally in AM and 5 mg in PM. Aldosterone (measured at day 6) was 7.2 ng/dL (&lt;= 31.0 ng/dL), renin activity 3.1 ng/mL/hr (0.5–4.0 ng/mL/hr), and aldosterone/renin ratio 2.3 (&lt;= 25) consistent with hyporeninemic hypoaldosteronism since aldosterone and renin were inappropriately normal for the hyperkalemia. Repeat cosyntropin test on day 11 showed low ACTH (3 pg/mL), low baseline cortisol 1.1 µg/dL, cortisol 30 minutes 7.9 µg/dL, and 60 minutes 11.2 µg/dL, consistent with secondary adrenal insufficiency, ascribed to chronic ICS. Potassium level normalized seven days after spironolactone discontinuation, related to its approximate duration of action1. The patient was discharged with hydrocortisone 10 mg daily, and spironolactone was permanently discontinued.
Spironolactone use can result in type 4 RTA due to aldosterone resistance and mimic mineralocorticoid deficits characteristic of primary adrenal insufficiency.
1. O’Connell JE, Colledge NR. Type IV renal tubular acidosis and spironolactone therapy in the elderly. Postgrad Med J. 1993;69(817):887–889.
Variations in the Initial Presentation of a Rare Congenital Adrenal Hyperplasia: Steroidogenic Acute Regulatory Deficiency
Authors: Saha Priyanka , Hodax Juanita , DiVall Sara A , Kim Grace , Huang Alyssa 
Published: May 2021

Abstract
Background: Steroidogenic Acute Regulatory (StAR) deficiency is a rare form of congenital adrenal hyperplasia characterized by dysregulated cholesterol transport mediated by StAR enzyme across mitochondrial membranes. Adrenal dysfunction is due to the two-hit hypothesis: 1) defective StAR protein and 2) cholesterol accumulation in the adrenals and gonads. With variable cellular damage, adrenal crisis can occur early or late. Clinical cases: We present two cases of StAR deficiency with contrasting presentations. Case 1: A 9-day old ex full term female from a nonconsanguineous union presented to a rural hospital with hypothermia, lethargy, and poor feeding. She had hypoglycemia 41 mg/dL (60–105), hyponatremia 120 mEq/L (135–145), hyperkalemia 7.7 mEq/L (3.5–5.5) and cortisol &lt; 0.4 ug/dL (4.5–23). Baby was started on hydrocortisone (HCT) 100 mg/m2 and one-time fludrocortisone (FCT). She decompensated requiring chest compressions, intubation and pressors. She was transferred to our institution. Newborn screen was normal; she had typical female external genitalia. US demonstrated a uterus; ovaries and adrenals were not identified. Upon extubation and clinical improvement, her HCT was weaned to physiologic doses. She became hyponatremic requiring FCT and salt supplements. Post-HCT wean, ACTH level was 304 pg/mL (7–63) with aldosterone &lt; 4.0 ng/dL (6.5–86). Karyotype was 46,XX. Genetic analysis revealed a novel heterozygous likely pathogenic variant in the STAR gene, (STAR c.65-12_68del variant) without defect in the other STAR gene. Case 2: A 9-month-old ex full-term female of Iraqi descent from a nonconsanguineous union presented with fatigue, poor oral intake and weight loss from 50%-ile to 3%-ile. She had hyponatremia 122 mEq/L, hyperkalemia 8.0 mEq/L, but was normoglycemic. She was normotensive; EKG was normal. Parents noted progressive hyperpigmentation including her gums, palmar and plantar creases. She had typical external female genitalia with a hypoplastic clitoris (2 mm x 2 mm). ACTH stimulation test showed low cortisol (0.5 ug/dL) at 60 minutes. She was treated with HCT 100 mg/m2 for 5 days, then tapered to maintenance dosing, with FCT and salt supplements. Her ACTH level returned &gt; 5000 pg/ml. Aldosterone, 17-OH-Progesterone, 17-OH-Pregnenolone, 11-Deoxycortisol and androstenedione were undetectable. Pelvic US did not identify uterus or ovaries. Pelvic MRI identified bilateral inguinal testes with enlarged adrenal glands. Karyotype was 46, XY. We suspected StAR deficiency with sex-reversal. Genetic analysis revealed a known homozygous mutation in STAR (c.545G&gt;A). Conclusion: StAR deficiency is clinically indistinguishable from P450scc deficiency and genetic testing is needed. Both entities can present with early or delayed adrenal crisis. While classic for StAR deficiency, adrenal enlargement is inconsistent. Karyotype is vital to identify sex reversal.
Biochemical Tumor Marker Status and Its Role in Treatment Response in Patients Who Received High-Specific-Activity I-131 MIBG in Advanced Pheochromocytoma and Paraganglioma (PPGL): Results From a Pivotal Phase 2 Clinical Trial
Authors: Jimenez Camilo , Chin Bennett B , Noto Richard A , Noto Richard B , Dillon Joseph S , Solnes Lilja , DiPippo Vincent A , Stambler Nancy , Pryma Daniel A 
Published: May 2021

Abstract
Background: High-specific-activity iodine-131 meta-iodobenzylguanidine (HSA I-131 MIBG; AZEDRA®) has been approved for the treatment of adult and pediatric patients (pts) 12 years and older with iobenguane scan positive, unresectable, locally advanced or metastatic PPGL who require systemic anticancer therapy. We have previously presented data showing improved biomarker responses in pts treated with HSA I-131 MIBG. Here we report the impact of biomarker status on the study primary endpoint and objective tumor response. Methods: Pts with iobenguane-avid PPGL who were ineligible for surgery, failed prior therapy or not candidates for chemotherapy, and on a stable antihypertensive medication regimen were treated. Pts received up to two therapeutic doses, each at ~18.5 GBq (or 296 MBq/kg for pts ≤62.5 kg), administered ~90 days apart. Biomarkers were analyzed at baseline and over a 12-month efficacy period. Confirmed biochemical responses (at least ≥ 50% decrease in abnormal tumor marker value for all hypersecreted biomarkers) required subsequent responses to be identical to or better compared with the previous assessment. The primary endpoint was clinical benefit, defined as the proportion of pts with at least 50% reduction of all antihypertensive medication(s) for ≥6 months beginning during the efficacy period. The secondary endpoint, confirmed objective tumor response by RECIST, was also evaluated. Results: 68 pts received at least one therapeutic dose of HSA I-131 MIBG. For all pts with hypersecretory tumors (with a baseline biochemical marker level of ≥1.5× ULN) (n=60), a comparison of biomarker response with antihypertensive therapy yielded a correlation coefficient of 0.35 (P = 0.006; Fisher exact P = 0.012). For pts with norepinephrine only-hypersecreting tumors (n=31), a correlation coefficient of 0.47 (P = 0.008; Fisher exact P = 0.015) was observed. The overall biomarker response also correlated with objective tumor response (n=55) yielding a correlation coefficient of 0.36 (P = 0.007; Fisher exact P = 0.012) for all pts with hypersecreted biomarkers. Pts who were not biochemical hypersecretors for any biomarker (n=6) had only one responder for the primary endpoint and no objective tumor responses. Conclusions: The biomarker data from this study establish a moderate but statistically significant correlation between biomarker response following treatment with HSA I-131 MIBG and objective tumor response and durable reduction of antihypertensive therapy. This correlation was improved with norepinephrine only-hypersecreting tumors in pts with unresectable, locally advanced or metastatic PPGL.
A Case of Hypocalcemia Secondary to Infection With SARS-CoV-2 Virus
Authors: Khan Abdul Mannan , Lightell James , Majors Corey 
Published: May 2021

Abstract
Background: A Case of Hypocalcemia Secondary to Infection with SARS-CoV-2 Virus.
Clinical Case: A 40 year-old obese male presented to the emergency department with a five day history of nausea, vomiting, shortness of breath, and nonproductive cough. Symptoms progressed culminating in a single episode of pre-syncope leading to his seeking medical care. Positive testing for the presence of SARS-CoV-2 as well as findings from computed tomography of the patient’s chest led to a diagnosis of COVID-19 and the patient’s admission to a COVID-19 ward, where treatment with dexamethasone, doxycycline, and 2 L oxygen via nasal cannula began. Blood testing on admission revealed profound hypocalcemia (6.2 mg/dL total and 3.5 mg/dL ionized) as well as newly diagnosed diabetes mellitus type 2 (T2DM) (HbA1c 13.0% on admission). Further electrolyte disturbances noted were consistent with his history of vomiting and untreated T2DM. Thyroid stimulating hormone and thyroxine levels showed primary hypothyroidism, but the patient’s parathyroid hormone level (16.5 pg/mL) was inappropriately normal. No other causes for hypocalcemia were identified. The patient’s hypocalcemia was treated with intravenous calcium gluconate and rose consistently through day six of hospitalization. Calcium fell sharply between day six and seven (7.6 mg/dL to 7.3 mg/dL) coinciding with worsening respiratory symptoms and requiring a doubling of oxygen dose from 2 to 4 L with subsequent improvement in hypocalcemia once underlying pulmonary function improved. Discussion: SARS-CoV-2 infection presenting with hypocalcemia has been well documented without definitive explanation [1]. Further, while the precise mechanism of SARS-CoV-2 virion export is unclear, the patient’s worsening hypocalcemia, respiratory symptoms, and concurrent presumable increased viral load suggests this is caused by a calcium-dependent exocytotic process [2]. 1: Marazuela, M., Giustina, A. & Puig-Domingo, M. Endocrine and metabolic aspects of the COVID-19 pandemic. Rev Endocr Metab Disord 21, 495–507 (2020). https://link.springer.com/article/10.1007/s11154-020-09569-22: Fehr A.R., Perlman S. (2015) Coronaviruses: An Overview of Their Replication and Pathogenesis. In: Maier H., Bickerton E., Britton P. (eds) Coronaviruses. Methods in Molecular Biology, vol 1282. Humana Press, New York, NY. https://link.springer.com/protocol/10.1007%2F978-1-4939-2438-7_1.
A Case of Teriparatide Use in Nonunion Atypical Ulnar Fracture
Authors: Tun Yin Nwe , Russell Yan , Guber Helena Abby 
Published: May 2021

Abstract
Background: Atypical upper limb fracture is a rare complication of bisphosphonate use. The management of nonunion fractures is challenging, especially in patients who are not surgical candidates. Teriparatide, a novel anabolic drug for osteoporosis has been increasingly used off-label for treatment of nonunion fractures and bisphosphonate related atypical fractures of the lower extremity. The proposed mechanism of healing is by enhancement of callus formation and mechanical strength. Clinical Case: A 72 year-old woman with a history of bilateral lower extremity paralysis and bilateral upper extremity paresis, who mobilized short distances with Canadian crutches, had been treated for 15 years with alendronate, for osteopenia associated with multiple risk factors for osteoporosis. 11 months before referral, and a month after alendronate was discontinued, she sustained a muscle-spasm induced fracture of the mid-shaft of the right ulna. She was treated nonoperatively due to chronic osteomyelitis with recurrent bacteremia from a prior non-healing left ulnar fracture (with internal fixation). Bone density of the right forearm had been normal. Since the right ulna break was transverse with minimal comminution, located in the diaphysis, occurred after trivial force and exhibited delayed healing, it was thought to be an atypical fracture secondary to bisphosphonates. She was initiated on cyclical teriparatide injection 20 mcg subcutaneously daily, with 2 months on and 2 weeks off. In one year, patient responded with dramatic radiographic improvement by forming a large callus with almost complete healing of the fracture. Conclusion: Mid-forearm atypical fracture from long-term bisphosphonate use is rare and is at risk for nonunion. The management of atypical upper limb nonunion fracture in nonoperative patients is not well established. Case reports exist of patients with atypical upper limb fracture who are either treated conservatively, or surgically with fixation/bone grafting +/- teriparatide. Our case showed that teriparatide, when used cyclically, exerted positive osteogenic effect and improved healing of the nonunion of an atypical fracture of forearm in a patient who continued weight bearing activity on her only functional limb.