bluuebunny/crossref_metadata_2025_split huggingface dataset:
Epinephrine to the Rescue: Identifying the Offending Side in Bilateral (B/L) Macronodular Adrenal Hyperplasia (BMAH) With Cushing Syndrome (CS) and Hyperaldosteronism
Authors: Vedere Tarunya , Madhavan Parvathy , Malchoff Carl D 
Published: May 2021

Abstract
Management of ACTH-independent CS in the setting of B/L adrenal masses can be challenging. We present a patient with concomitant cortisol and aldosterone hypersecretion and B/L adrenal masses who was treated with unilateral adrenalectomy (UA) based on simultaneous B/L adrenal vein sampling (AVS) results normalized to plasma epinephrine levels, to correct for flow and dilution. A 60-year-old lady presented for evaluation of incidentally discovered B/L adrenal masses. CT abdomen with contrast revealed B/L lobulated adrenal glands measuring 3.4 x 5.5 x 4.1 cm on the right and 3.8 x 4.2 x 2 cm on the left (pre contrast density of 37 and 44 Hounsfield Units respectively). She had a recent diagnosis of HTN and prediabetes. She reported fatigue, easy bruising, and muscle weakness. Family history was notable for a sister with CS and B/L adrenal masses who was successfully treated with UA. On physical examination her BP was 160/94 mm Hg and she did not have an obvious cushingoid appearance. Laboratory testing included an elevated AM serum cortisol level of 16.6 mcg/dL following 1 mg of dexamethasone given at 11 pm the previous night. ACTH was &lt;1.0 pg/mL consistent with ACTH-independent CS. She had a serum aldosterone level of 26.6 ng/dL(4.0 - 31.0 ng/dL),simultaneous plasma renin activity of 0.5 ng/ml/hr (0.5–4 ng/ml/hr) and serum potassium level of 4.4 mmol/l. She underwent B/L simultaneous AVS. Given concomitant hyperaldosteronism, plasma epinephrine levels were measured to determine successful catheter placement and to correct for flow and dilution between the adrenal veins. Right adrenal vein to peripheral vein cortisol ratio was 9.27 (&gt; 6.5) consistent with cortisol hypersecretion. The right to left cortisol ratio was 2.3 (&gt;/= 2.3), consistent with right sided predominance. Right to left ratio of the epinephrine corrected cortisol level was 2.7. She underwent right adrenalectomy, and pathology showed macronodular adrenal hyperplasia. Postoperatively, she had resolution of HTN and normalization of 24 hour urine free cortisol. UA is increasingly becoming recognized as a successful treatment for BMAH due to lower risk of adrenal crisis when compared to B/L adrenalectomy. In a recent publication, remission from CS was seen in 94.4 % of patients with BMAH following UA, with recurrence in 19% of patients. The mean time to recurrence was 5 years. We utilized cutoff values that were previously reported for cortisol lateralization in interpreting AVS. Our patient attained remission of CS 9 months post UA. Epinephrine levels were not significantly different between the adrenal veins, possibly due to simultaneous AVS, so we were also able to calculate epinephrine corrected cortisol ratios. Simultaneous B/L AVS with epinephrine to localize autonomous hypercortisolism in the setting of concomitant hyperaldosteronism can be beneficial in guiding surgical management of patients.
Levetiracetam Treatment Causing False Negative Screening Test in a Woman With Aldosterone Producing Adenoma
Authors: Sawah Ahmed , Mallisho Abdullah , Abd Ulmalik Alshareef Muneera , Alzahrani Amirah Husseian 
Published: May 2021

Abstract
Background: Endocrine hypertension accounts for 5–10% of hypertensive population, with primary hyperaldosteronism being the most frequently encountered diagnosis. Biochemical tests are subject to interference with many drugs that may lead to false positive or negative results.
We present a case of aldosterone producing adenoma associated with false negative screening test due to Levetiracetam use.
Clinical Case: A 30 year-old Middle Eastern woman was referred to endocrinology clinic for evaluation of secondary hypertension and persistent hypokalemia. Six years ago, she presented to emergency room during the 3rd trimester of her second pregnancy with severe preeclampsia and seizure. Postpartum, she was discharged on Levetiracetam (Keppra) 500 mg orally BID. Upon follow up visits, she continued to have persistent elevation of blood pressure readings with spontaneous hypokalemia ranging 2.5–3.2 mEq/L. She was started on Perindopril 10 mg daily and potassium supplement. Amlodipine 5 mg daily was added shortly later on. Clinically, she had regular menstrual cycle. She did not have plethora, central obesity, easy bruising, or proximal muscle weakness. Her review of systems including thyroid-related symptoms were normal. There was no family history of hypertension or adrenal tumors. On examination, BP 180/110, pulse rate 78, weight 58 kg and BMI 25. Her physical examination was otherwise unremarkable. After holding Perindopril for 4 weeks, biochemical tests showed creatinine 0.52 mg/dL (0.49–1.1), urea 16.8 mg/dL, potassium 2.9 mEq/L (3.5–5.2), direct renin concentration (DRC) 100.6 pg/mL, aldosterone 54.25 ng/dL. Plasma fractionated metanephrines were normal and morning cortisol level after 1 mg overnight dexamethasone suppression test was 0.72 mcg/dL. Renal arterial doppler showed normal renal blood flow without any significant stenosis. Despite increasing potassium supplement she continued to have hypokalemia. As levetiracetam was reported by literature review to cause severe hypokalemia, it was stopped after discussion with neurology. Four weeks later, repeated DRC was suppressed 4.0 pg/mL with elevated aldosterone 62.73 ng/dL. Furthermore, primary hyperaldosternism was confirmed after normal saline suppression test revealed unsuppressed aldosterone 15 ng/dL. An Adrenal CT scan showed a small hypodense right adrenal lesion measuring 11x9 mm with a pre-contrast density of 7 HU and post contrast absolute washout more than 60%. Patient elected to undergo right adrenalectomy. 24 hours post surgery, aldosterone level dropped to 4.0 ng/dL and potassium increased to 5 mEq/L. Fortunately, hypertension and hypokalemia have both resolved after surgery. Conclusion: We are first to report that Levetiracetam can cause unsuppressed direct plasma rennin concentration (DRC) and potentially could result in a false negative screening test for primary hyperaldosteronism.
Presentation of ACTH Independent Cushing’s as Severe Insulin Resistance During Pregnancy
Authors: Faisal Sobia , Kaur Manmeet , Samat Ashish 
Published: May 2021

Abstract
Introduction: Cushing’s syndrome is very rare in pregnancy with around 200 cases reported in literature. It remains a diagnostic dilemma as pregnancy itself is a hypercortisolemic state. Several clinical characteristics of Cushing’s syndrome such as insulin resistance and hirsutism may overlap with normal variants of pregnancy and therefore leading to a missed diagnosis. We hereby present a case of a young pregnant woman with severe insulin resistance, with workup consistent with Cushing’s syndrome.
Clinical Case: This was a 27-year-old pregnant woman with DM type 2 diagnosed about 7 years ago. During her pregnancy she was started on insulin and was later admitted to the hospital at 32 weeks for inpatient management of pre-eclampsia and uncontrolled hyperglycemia. Endocrine was consulted for severe insulin resistance and persistent hyperglycemia. On exam patient was noted to be obese with facial plethora, frontal balding and significant facial hirsutism. During the pregnancy she had noted significant weight gain with substantial worsening of frontal balding and hirsutism. Her current pregnancy was spontaneous but was after many years of trying to conceive. Prior pregnancy 8 years ago was uncomplicated with no history for GDM at that time. Review of recent pre-pregnancy imaging revealed left adrenal mass measuring 3.5 cm with 40 HU which measured around 2 cm 8 years ago. Biochemical work up revealed elevated 8 am cortisol at 35.4 ug/dL (ref range 6.2 - 19.4) with suppressed ACTH &lt;5 pg/mL (6 – 50). Testosterone was high at 299 ng/dL (8 – 48) and DHEAS was low normal at 37 mcg/dL (18 – 391). Plasma and 24 hour urine metanephrine collection results were normal. 24-hour urine free cortisol was measured and was elevated at 628.5 mcg/24(4.0–50.0). Midnight salivary cortisol was 0.87 mcg/dL (&lt;OR=0.09). Patient was managed conservatively with plan for surgical intervention post-delivery. Pregnancy was complicated by PPROM at 35 weeks with subsequent cesarean section. Baby was of average weight but developed mild hyperbilirubinemia which required short NICU stay. On reevaluation at 4-week postpartum period, repeat biochemical workup revealed elevated cortisol of 22.5 mcg/dL, ACTH &lt;5 pg/ml, elevated 24-hour urine cortisol 163.9 mcg/24h with appropriate urinary creatinine. Testosterone level was improved postpartum to 9 ng/dL. DHEAS was 39 mcg/dL. Repeat imaging with CT with adrenal protocol revealed left adrenal mass measuring 2.3 cm with 20 HU with absolute washout of 79%. She was started on ketoconazole is now awaiting surgical intervention.
Conclusion: We suspect that this patient may have had pregestational subclinical Cushing’s syndrome which eventually progressed to Cushing’s syndrome during pregnancy. Although this is a rare finding during pregnancy, workup for Cushing’s should be considered in pregnant women with severe insulin resistance, hirsutism, hypertension and pre-eclampsia.
Primary Aldosteronism as the Initial Presentation of Adrenocortical Multiple Hormone Producing Tumor
Authors: Uehara Erika , Nagata Tomohiro , Ota Tomoko , Ogawa Tomoe , Minegishi Rieko , Yoshii Keisuke , Naiki Yasuhiro , Horikawa Reiko 
Published: May 2021

Abstract
Introduction: Primary aldosteronism (PA) accounts for ∼10% of cases of hypertension in adults, however it’s a rare disease in children. We present a rare pediatric case with PA as the initial presentation of adrenocortical multiple hormone producing tumor. Case: A 7-year-old Japanese girl, who had right-sided hypoplastic leg and foot syndactyly, presented to our hospital due to abnormal ECG of ST depression at V6 on school health check-up. She showed normal growth, no signs of virilization nor Cushingoid appearance. She had elevated blood pressure (164/98 mmHg), low potassium (2.6–3.0 mEq/L) and low cardiac ejection fraction (30–40%). Her plasma aldosterone concentration (PAC) was 441 pg/mL and aldosterone/renin ratio (ARR) was 1470. Contrast-enhanced CT and MRI showed a right adrenal mass (34×22×30 mm) with high lipid content, which led to the diagnosis of primary aldosteronism by the right adrenal adenoma. Adrenal venous sampling failed to identify localization of aldosterone production. Since the possibility of bilateral production of aldosterone remained, the girl was treated with multiple anti-hypertensive medicine including spironolactone and potassium supplementation. Although the serum potassium levels were maintained within normal range, exercise-induced PVCs occurred 6 months after first visit. Abdominal US showed no changes in size of the tumor. Ten months later, she showed gradual weight gain without growth deceleration. Twelve months later, abdominal US revealed apparent enlargement of the right adrenal mass, and MRI scan showed a 156% increase in size of the right adrenal mass (32×50×53 mm). She showed further weight gain with moon face, hirsutism and acne. Hormonal analysis revealed elevated serum and urine cortisol levels (30–40μg/dL and 269–337 μg/m2/day, respectively), and suppressed ACTH levels with no diurnal variation. Serum testosterone levels elevated to 1.00 ng/mL and serum DHEA-S to 273 μg/dL. Retrospective analysis of serum testosterone at the first visit was already mildly elevated to 0.47 ng/mL. Although no distant metastases were detected before surgery, direct liver invasion was found at right adrenal tumor rejection. Clinical Lessons: Primary aldosterone producing adenoma is extremely rare in childhood. In our case, initially the adrenal tumor produced aldosterone predominantly, and it revealed to produce glucocorticoid and androgen later on. Androgen producing adrenal tumor in children tends to have malignant nature. Although initial presentation was compatible with the primary aldosteronism, intense follow-up with detailed monitoring of various hormone levels and images, and early surgical intervention should be considered.
Resistant Hypertension Due to Familial Hyperaldosteronism Type III: First Report From Indian Sub-Continent
Authors: Alam Sarah , Goyal Alpesh , Kandasamy Devasenathipathy , Bansal Virinder Kumar , Asuri Krishna , Agarwal Shipra , Khadgawat Rajesh 
Published: May 2021

Abstract
Background: Familial hyperaldosteronism type III (FH-III) is caused by germline mutations in KCNJ5 gene. FH-III presents with phenotypic variability from spironolactone-responsive hypertension to massive adrenal hyperplasia requiring bilateral adrenalectomy. Till date, seven different pathogenic mutations in KCNJ5 gene have been identified. Here we describe a sporadic FH-III case, due to a Gly151Arg mutation, first from Indian subcontinent, presenting with extremely high plasma aldosterone concentration (PAC) values, further expanding our knowledge of this rare condition. Clinical Case: A 24-year-old female, symptomatic since age of 5 years with periodic limb weakness and gradual increase in frequency of episodes over the years. Her blood pressure (BP) was recorded for first time at 9 years of age, and it was 170/110 mm Hg. On evaluation at this time, PAC was highly elevated at 1007 ng/dL and plasma renin activity (PRA) was suppressed at 0.04 ng/ml/h with aldosterone renin ratio (ARR) of 25,175 ng/dL per ng/mL/h (&gt;20 suggestive of primary aldosteronism). CT scan demonstrated mild enlargement of bilateral adrenal glands. A presumptive diagnosis of Glucocorticoid-remediable aldosteronism was made. She was started on dexamethasone, spironolactone and nifedipine but was not improved. Dexamethasone was stopped after 1 year of initiation. Before presenting to our referral center in 2018, she was having uncontrolled hypertension with recurrent episodes of hypokalemic paralysis. She was on maximal doses on four antihypertensive agents, further increased to six agents (including spironolactone 100 mg BD), and potassium chloride supplementation (120 mEq/day). Despite this, she had a serum potassium of 2.6 mEq/L. Her biochemical investigations demonstrated that PAC was 2070 ng/dL, direct renin concentration (DRC) was 2.35 µIU/mL (PRA 0.2 ng/ml/h) and ARR was 880.9 ng/dL per µIU/mL. CT scan revealed massive bilateral adrenal hyperplasia. Genetic analysis by whole exome sequencing detected KCNJ5 (p.Gly151Arg) mutation, confirming the diagnosis of FH-III. She was subjected to bilateral adrenalectomy and she became normokalemic. Dramatic reduction in antihypertensives with BP control achieved only on amlodipine post-operatively. Genetic testing of family members was not done but they were normotensive and normokalemic. Histopathological examination revealed bilateral adrenal hyperplasia. PAC levels up to 297 ng/dL have been described previously in FH-III but our patient had exceedingly high-level of 2070 ng/dL. Conclusion: This case demonstrates florid clinical and biochemical manifestations of FH-III and gradual worsening of symptoms, consistent with progression of disease with age. It illustrates that proper investigations and treatment can lead to remission of symptoms. Further studies are warranted to elucidate the full clinical and biochemical spectrum of FH-III.
Transaminitis Evaluation Leads to the Incidental Diagnosis of Familial Paraganglioma Due to SDHB Mutation
Authors: Okafor Anderson , Yelangi Anitha , Samantray Julie 
Published: May 2021

Abstract
Background: Paragangliomas are rare neuroendocrine tumors. Patients with succinate dehydrogenase subunit B (SDHB) gene mutations are predisposed to developing paraganglioma/pheochromocytoma. We are presenting the case of an incidental finding of a paraganglioma during an evaluation for transaminitis.
Clinical Case: A 23-year-old male with a medical history of right hydrocele repair as a teenager was evaluated with an ultrasound of the abdomen for elevated liver enzymes and right upper quadrant discomfort. The ultrasound revealed a large lobular solid vascular 13.8 x 8.1 x 11.3 cm mass in the mid abdomen. He underwent a CT of the chest, abdomen and pelvis which demonstrated a large retroperitoneal mass measuring 16 x 10 x 13.7 cm within the right mid abdomen. The mass was described as a large centrally necrotic peripherally enhancing right retroperitoneal mass displacing the IVC anteriorly. The patient subsequently underwent an image-guided biopsy of the mass and the pathology revealed it was a paraganglioma. The patient denied any history of hypertension, orthostasis, headaches or palpitations. Biochemical workup for plasma catecholamines, plasma metanephrines, 24-hour urine catecholamines and metanephrines and cortisol were unremarkable. His transaminitis also resolved. He underwent a retroperitoneal paraganglioma excision and the final pathology was consistent with paraganglioma and negative for capsular invasion. He was referred to a genetic counsellor for testing since paragangliomas can be inherited. He also mentioned a family history of breast cancer in his mother and HTN and prostate cancer in his father. His test revealed that he had a c.289A&gt;T mutation in his SDHB gene. He was encouraged to share the information with his family to help them understand the implications of his genetic test result. He underwent a surveillance PET scan which showed multiple osseous lesions in his temporal calvarium, sphenoid, spine and sacrum suggestive of metastasis. Repeat imaging with a DOTATATE PET scan showed stable disease. His transaminitis was transient, and we did not find a correlation to his paraganglioma. His imaging tests showed no liver metastasis. A CT of the head showed no evidence of intracranial metastasis. The current plan is to continue surveillance. His older brother underwent a genetic testing. He tested positive for the same SDHB mutation and underwent biochemical and imaging tests which were unremarkable. He too will continue surveillance.
Conclusions: Patients with a succinate dehydrogenase subunit B (SDHB) gene mutations are predisposed to developing paraganglioma/pheochromocytoma. The tumors produce catecholamines, but can be biochemically silent as in our patient. They are inherited in an autosomal dominant manner. Our case highlights the importance for genetic counseling which increases the chances of early screening and surveillance in affected family members for optimal multidisciplinary management of patients.
A Case of Psychosis Due to Acute Hypocalcemia From Hypoparathyroidism
Authors: Nehu Parimi Joseph Theressa , Liu John Chen , Gundluru Rajani , Naha Sowjanya , Gusov Timur , Syed Hasan , Gardner Michael J 
Published: May 2021

Abstract
A 61-year-old female with past medical history of depression, hypoparathyroidism (hypoPtH), and hypothyroidism had disappeared from her home and was found wandering a few hours away with persecutory delusions, visual and auditory hallucinations. Serum calcium (Ca) was 6.3 mg/dL (range 8.6–10.2), albumin 3.7 g/dL (range 3.5–5.2) and ionized Ca 0.89 mmol/L (range 1.12–1.30). She was admitted and treated with Ca and calcitriol. Work-up for altered mental status was negative except for hypocalcemia (hypoCa) and scattered bilateral basal ganglia calcifications (BGC) with cortical and subcortical frontal lobe calcifications on CT. Psychiatry diagnosed delirium due to hypoCa. Acute psychosis resolved once Ca levels improved. Diagnosis of idiopathic hypoPtH was in 1997. Her regimen included Ca citrate 1500mg daily and 10 mcg of Forteo twice daily. She had skipped her medications for at least 2 days prior to presentation.
Her medical records revealed that she was seen for severe depression, progressive gait abnormalities, slowed movements, and imbalance, in 2015. CT scan and MRI brain showed BGC. Her son gave a history of multiple admissions for psychosis, violence, delusions with agitation, and wandering at times when the patient was hypoCa, which was diagnosed as schizophrenia. Neuropsychiatric disturbances are commonly associated with hypercalcemia. Review of literature found a few case reports of psychosis and hypoPtH 1,2 BGC is common in hypoPtH. Psychotic symptoms due to BGC include auditory hallucinations, delusions of influence, paranoid states, and complex perceptual distortions.3,5 HypoCa is associated with cognitive impairment. Neurological manifestations tend to improve with Ca correction, but psychiatric symptoms do not improve substantially.4,5 Further studies are needed in hypoPtH with BGC to appropriately diagnose organic psychosis. This is important in management of the vicious cycle of psychiatric illness leading to noncompliance resulting in psychosis. Prevention of BGC will play a key role. References: 1. Finan M, Axelband J. This is your brain on calcium: psychosis as the presentation of isolated hypoparathyroidism. Am J Emerg Med. 2014;32:945.e1-4. 2. Ang AW, Ko SM, Tan CH. Calcium, magnesium, and psychotic symptoms in a girl with idiopathic hypoparathyroidism. Psychosom Med. 1995;57:299–302. 3. Burns K, Brodaty H. Fahr’s disease and psychosis. In: Sachdev PS, Keshavan MS, editors. Secondary schizophrenia. Cambridge: Cambridge University; 2010. p. 358–66. 4. Maiti A, Chatterjee S. Neuropsychiatric manifestations and their outcomes in chronic hypocalcaemia. J Indian Med Assoc. 2013;111:174–7.
5. Amara A, Novais C, Coelho M, Silva A, Curral R, Brandao I, Torres A. Organic psychosis due to hypoparathyroidism in an older adult: a case report. Braz. J. Psychiatry; 2016; 38(4)