bluuebunny/crossref_metadata_2025_split huggingface dataset:
MON-343 The Mystery of Recurrent PTH-Independent Hypercalcemia with Severe Hypophosphatemia
Authors: Shaikh Bilal , Pulipati Vishnu Priya , Meier Garnet 
Published: May 2020

Abstract
Background
The differential diagnoses for PTH independent hypercalcemia with hypophosphatemia are broad. Careful history with systematic evaluation for possible etiologies is necessary for accurate diagnosis and timely therapeutic intervention.
Clinical Case
A 72-year old female was referred to our clinic for evaluation of hypercalcemia with low iPTH level. Review of lab workup over the past two years showed frequent occurrences of mild hypercalcemia, low iPTH and moderate to severe hypophosphatemia. She denied use of calcium, vitamin D, Vitamin A or herbal supplements and over the counter (OTC) medications. Age-appropriate cancer screening was up to date. She had no clinical evidence of granulomatous diseases or malabsorption syndrome. Labs revealed corrected calcium (cCa) 9.9 (8.5-10.5 mg/dL), iPTH 6.36 (12-88 pg/mL), phosphate 1.5 (2.5-4.5 mg/dl), magnesium 1.6 (1.8-2.7 mg/dl), 25-OH Vit D 30 (30-100 ng/mL), PTHrP 12 (14-27 pg/mL), 1,25 OH Vit D 32 (18-72 pg/ml), TSH 1.8 (03-5.6 uIU/mL), GFR 49 (&gt;90 mL/min/1.73 m2) and bicarbonate 30 (23-31 mEq/L). FGF23, 1-mg ODST and SPEP were normal. 24-hour urine phosphate was 3 mg/24h, ruling out renal phosphate wasting.
Two months later, she developed myalgia and generalized weakness. Labs showed cCa 11.3mg/dl, iPTH 3.79 pg/ml, phosphate &lt;1 mg/dl, magnesium 1.2 mg/dl, bicarbonate 33 mEq/L. She was hospitalized for severe hypophosphatemia. Here, she revealed she was intermittently taking a “milky” antacid obtained from Mexico, for her GERD. She required IV phosphate and magnesium replacement and her mineral abnormalities normalized within 24 hours. She was advised to stop use of OTC antacids and provided daily phosphate and magnesium supplementation. 4 weeks later, she developed recurrent hypercalcemia 10.4 mg/dl, hypophosphatemia 1.1 mg/dl and alkalosis with bicarbonate 35 mEq/L, which corrected with supervised phosphate and magnesium supplementation and restricted access to home OTC medications.
Discussion
Milk-alkali syndrome, characterized by the triad of hypercalcemia, metabolic alkalosis and renal failure, has been classically associated with ingestion of large amounts of milk and absorbable alkali. Once a common cause of hypercalcemia, its incidence declined rapidly with advent of new therapies for PUD. Recently, this syndrome, now described as calcium-alkali syndrome (CAS) has re-emerged due to use of high dose calcium carbonate supplements and OTC antacids, with a prevalence of 9-12% among hospitalized patients with hypercalcemia.
We hypothesize our patient’s mineral abnormalities are explained by CAS. High doses of calcium from antacids can bind phosphate in the gut, leading to poor phosphate absorption and hypophosphatemia.
Conclusion
CAS is emerging as a frequent cause of hospital admissions for hypercalcemia. Severe hypophosphatemia can be a rare manifestation. Primary therapy is withdrawal of offending agent.
MON-357 Craniofacial Deformities with Hypercalcemia: A Rare Case of Co-Existing Primary Hyperparathyroidism and Paget’s Disease of the Bone Since Young Adulthood
Authors: Nagaratnam Shamharini , Mustafa Norlaila , Karupiah Malathi 
Published: May 2020

Abstract
Background:
Primary Hyperparathyroidism (PHPT) and Paget’s Disease of the Bone (PDB) are two distinct bone mineral disorders which rarely co-exist. It has been very scarcely reported in the elderly but almost unheard of in young adults.
Clinical case
A middle-aged Indian lady presents with multiple and recurrent facial and jaw bony swellings, since the age of 12. She had normal developmental as a child, without visual, auditory deficits or limb deformities. No family history of hypercalcemia or endocrine disorders was elicited. At initial diagnosis, biochemical parameters were consistent with PHPT, with mild to moderate hypercalcemia (2.6-3.0 mmol) and concomitant hypophosphatemia (0.6-0.8 mmol/L), elevated intact PTH 10.6pmol/L and ALP persistently more than 350 U/L. She had undergone multiple surgeries to remove the bony swellings, presumed to be brown tumours. She developed medullary nephrocalcinosis approximately 30 years after onset of illness. Over a span of three decades, numerous modalities were employed in attempt to localise the parathyroid lesion, including imaging (ultrasonography, sestamibi with SPECT CT, FDG PET),angiography, venous sampling and exploratory neck surgeries which were unsuccessful. Due to failure in localising the offending parathyroid lesion, it was conceded to maintain her on medical therapy.She was initially started on oral phosphate therapy, intranasal calcitonin and subsequently calcimimetics. Aside from rising ALP levels, her other biochemical parameters remained static. Her diagnosis was re-evaluated when she presented with osteomyelitis of the right mandible requiring surgery. Pre -operative CT imaging showed mixed lytic and sclerotic lesions at the mandible, maxilla, facial bones and skull. It also revealed diffuse thickening of the calvarium with narrowing of the posterior fossa resulting in hydrocephalus, requiring a ventriculoperitoneal shunt insertion. Histopathological examination of the mandible showed a background of osteosclerosis. These findings were inconsistent with PHPT and was most often described in PDB. On the other hand, a repeated skeletal survey showed generalised osteopenia in the small bones of the hand with subperiosteal and terminal phalanges reabsorption which was in keeping with PHPT. Her pelvis, spine and long bones remained normal and bone densitometry was preserved. It was concluded that this patient was suffering from dual pathology, PHPT and PDB and was commenced on bisphosphonates.
Conclusion:
This lady presented with two diseases which simulate each other despite not being etiologically linked. The aberrancy in the age of onset and the overlapping clinical features of the dual pathology imposed a significant challenge in making the correct diagnosis. Retrospectively, histopathological examination of the bone at an earlier stage of disease may have been the key to solving this perplexing case.
SUN-662 Praliciguat, a Clinical-Stage Soluble Guanylate Cyclase Stimulator, Improves Lipid Handling and Insulin Sensitivity in Diet-Induced Obese Mice
Authors: Schwartzkopf Chad D , Liu Guang , Hadcock John R , Currie Mark G , Masferrer Jamie L , Jones Juli E 
Published: May 2020

Abstract
Praliciguat (PRL) is a soluble guanylate cyclase (sGC) stimulator which in animal models distributes broadly to tissues and elicits hemodynamic, anti-inflammatory, anti-fibrotic, and metabolic effects. Here, we assessed metabolic effects of PRL in a mouse diet-induced obesity model.
Six-week-old male C57BL/6N mice were maintained on a low-fat diet (LFD, lean mice) or placed on a 60% high-fat diet (HFD, obese mice). At age 14 weeks, one group of obese mice was maintained on HFD (obese controls) and one group of obese mice was switched to HFD formulated with PRL to achieve a Cmax similar to a 6-mg/kg oral dose (PRL-treated mice). After 38 days of treatment, an oral lipid tolerance test (LTT) was conducted. In a 2nd study under the same dosing paradigm, overnight fasted blood and organs were collected on day 28.
As reported previously (1), compared to obese controls, PRL-treated mice had lower fasting insulin (-28%), HOMA-IR (-26%) and triglycerides (-16%) as well as lower plasma triglycerides AUC after LTT (-34%). Gene expression and phosphorylated proteins associated with insulin pathways were measured in liver, skeletal muscle and white adipose tissue. PRL treatment normalized expression of genes involved in lipid handling (liver Pnpla3, Slc27a1, Lpl; muscle Lipe; white adipose tissue Fdft1, Ppara). Expression of proinflammatory genes (liver Tnf; muscle Ccl2; white adipose tissue Akt1, Icam1) was lower in PRL-treated mice than in obese controls. Liver insulin signaling was assessed by determining pAKT (T308) and pAKT (S473), markers of PI3K pathway activity and pERK, a marker of MAPK pathway activity. Compared to lean mice, pAKT (T308) and pERK were lower in obese controls, whereas pAKT (S473) was similar; PRL-treated mice had higher pAKT (T308) and pAKT (S473) compared to obese controls while pERK was unchanged. In skeletal muscle and white adipose tissue, levels of pVASP, a key mediator of the sGC pathway, were higher in PRL-treated mice than in obese controls.
In summary, PRL improved insulin sensitivity and lipids in diet-induced obese mice by affecting mechanisms of lipid handling, inflammation, and insulin signaling in key tissues associated with metabolism.
1. Author information excluded, 1924-P: Praliciguat, a Clinical-Stage sGC Stimulator, Improves Insulin Sensitivity, Lipid Tolerance, and Energy Utilization in a Mouse Diet-Induced Obesity Model Housed at Thermoneutrality. Diabetes, 2019. 68(Supplement 1): p. 1924-P.
MON-184 Disrupted ACTH-Cortisol Temporal Coupling in Healthy Men After an Overnight Fast, and the Modulatory Role of Orally Ingested Macronutrients
Authors: Iranmanesh Ali , Veldhuis Johannes D 
Published: May 2020

Abstract
While long term fasting is reported to augment the corticotropic function, effect of short term (overnight) fasting on ACTH-cortisol coordinated release pattern and potential effect(s) of nutrient intake is not fully defined. Eleven healthy men (age: 33-70 yrs, BMI 20.4-31.5 kg-m2) were studied after overnight fast on 4 separate days, involving oral ingestion of 300 ml of either water, dextrose, protein, or lipid solutions. Test meals were isocaloric (400 kcal). Sessions were 6.5 h long, starting at 0800-0900 hrs. Blood was collected at 10-min intervals for ACTH (pg per mL), and cortisol (µg per dL) measurements. Linear regression, cross-correlation, deconvolution, and ApEn were used for data analyses. ACTH and cortisol concentration time series during short-term fast (water day) were found not to be chronologically coupled per linear regression (r2= 0.0014, P=0.82), and cross-correlation (r= - 0.156, lag=150 min) statistics. Oral intake of the 3 macronutrients improved the temporal relationship between ACTH and cortisol concentrations, verified by linear regression (r2:P- dextrose 0.54:0.0001, protein 0.65: 0.0001, lipid 0.42:0.0001), and cross-correlation (r:lag in min- dextrose 0.8:10, protein 0.77:10, lipid 0.78:20). Oral ingestion of either macronutrient did not significantly alter mean ACTH and cortisol concentrations and their respective secretion pattern (total, pulsatile, basal) over the period of 6.5 hr. However compared to the control (water) session, dextrose ingestion evoked less frequent and larger ACTH secretory bursts, and more regular ACTH and cortisol secretory patterns. In this study, we have observed lack of concordance between ACTH and cortisol after overnight fasting, which is restored with oral intake of macronutrients. This effect appears to be uniform among the 3 macronutrients, except for less frequent and lager ACTH bursts and more regular ACTH and cortisol release events after dextrose intake. These findings and the specific role of nutrients being direct or via physiologic nutrient-induced hormonal adaptation warrants future investigation.
MON-462 Rebel Nodule or Reluctant Gland? the Challenge Presented by Heterophile Antibodies
Authors: Sharma Pranjali , Ding Linda , McGarvey Megan Elizabeth 
Published: May 2020

Abstract
Introduction:
Interpretation of thyroid function tests (TFTs) in background of non-specific symptoms concerning for hypothyroidism, has become challenging with assay interference. Heterophile antibody interferences are both test and laboratory platform dependent. We present a case of a toxic nodule erroneously diagnosed as isolated central hypothyroidism due to heterophile antibody interference.
Case:
A 38 year old lady was referred to Endocrinology for possible central hypothyroidism with symptoms of progressive fatigue, 40lb unintentional weight loss, poor appetite, nausea, intermittent diarrhea/constipation, occasional cold intolerance and intermittent lightheadedness. TFTs suggested low TSH 0.175 mcIU/ml (N 0.35-3.8 mcIU/ml) and low FT4 0.74 ng/dl (N 0.8-1.8 ng/dl). Pituitary hormone evaluation revealed normal ACTH, AM cortisol, IGF-1, prolactin and FSH. A pituitary MRI was normal.
Two months later, she had worsening fatigue, anxiety with palpitations and tremors, and 14lb weight gain. TFTs again confirmed low TSH (0.575 mcIU/ml) and lower FT4 (0.70 ng/dl). Empirical weight-based levothyroxine (LT4) supplementation was initiated for central hypothyroidism. Six weeks later, TFTs showed hyperthyroidism (TSH &lt;0.005 mcIU/ml, FT4 1.57 ng/dl). The patient endorsed worsening lightheadedness and palpitations on LT4, which resolved on LT4 discontinuation. One month later, TFTs were abnormal again (TSH 0.047 mcIU/ml, FT4 0.74 ng/dl).
Due to persistent discordance in symptoms and biochemical tests, TFTs were evaluated for heterophile antibody interference. While HAMA-treated TSH remained low (0.04 mIU/l), FT4 by equilibrium dialysis (FT4 ED) was normal (1.1 ng/dl, regular assay 0.74 ng/dl), suggesting subclinical hyperthyroidism. A thyroid uptake scan confirmed an autonomous toxic right thyroid nodule with suppressed remaining gland. Patient ultimately underwent 15 mCi RAI ablation of the nodule. TFTs done 1 month post-RAI suggested normal TSH (1.2 mcIU/ml) and normal FT4 ED (1 ng/dl). Previous symptoms have since resolved.
Conclusion:
Current methods of TFTs are generally reliable in diagnosing and monitoring thyroid disease. Rarely, medications, supplements, and endogenous antibodies can bind to TSH, T4 or lab reagent, resulting in inaccurate values. This has become increasingly common with use of high dose biotin. TSH with HAMA/heterophile antibodies and FT4 ED are more accurate forms of diagnostic testing.
When approaching patients with symptoms not consistent with typical hypo- or hyperthyroidism and are not responding as expected to therapy, it is important to consider more accurate testing to rule out assay errors.
References:
1. Soh SB, Aw TC. Laboratory Testing in Thyroid Conditions - Pitfalls and Clinical Utility. Ann Lab Med. 2019;39(1):3-14. doi:10.3343/alm.2019.39.1.3
2. Spencer C., PhD. Assay of Thyroid Hormones and Related Substances
SUN-086 Pilot Study Using Aromatase Inhibitor in Puberty of Boys With Partial Androgen Insensitivity: Report of Three Cases
Authors: Maciel-Guerra Andrea Trevas , de Andrade Juliana Gabriel Ribeiro , de Souza Arina Tavares , Campos Mariana Baldini , Marques-Junior Hercules Oliveira , Guaragna Mara Sanches , Fabbri-Scallet Helena , de Mello Maricilda Palandi , Guerra-Junior Gil 
Published: May 2020

Abstract
Background: Partial Androgen Insensitivity Syndrome (PAIS) (OMIM # 312300) is one of the causes of Disorders/Differences of Sex Development with 46,XY karyotype and normal or increased testosterone secretion that results in atypical genitalia. In general, it is caused by inactivating mutations on AR gene (Xq12 - OMIM * 313700), therefore it presents an X-linked recessive inheritance. Individuals raised as males have incomplete puberty with micropenis, sparse hairs, gynecomastia and increased LH, testosterone and estradiol serum levels. Therefore, the use of aromatase inhibitor in these cases becomes a logical indication aiming to increase testosterone levels in the tentative of supplanting its peripheral resistance and decreasing estrogen levels. Objective: To present clinical and laboratory data during the first year of use of aromatase inhibitor in puberty of three boys with confirmed molecular diagnosis of PAIS. Results: All subjects used letrozole (2.5 mg daily during 12 months). None reported significant side effects. Cases 1 and 2 are brothers (p.Ala596Tre). Case 1: Onset of treatment at age 12; height changed from 158 cm (z = +1.15) to 166 cm (z = +1.21), Tanner from G2P2T2 to G3P3T1, penis from 4.0 to 6.5 cm, LH from 7.5 to 18.3 IU/L (NR: 1.5 to 9.3 IU/L), testosterone from 361 to 1,347 ng/dL (NR: 165 to 763 ng/dL), estradiol from 35 to &lt;5.0 pg/mL (NR: &lt; 40 pg/mL) and bone age remained at 13 years. Case 2: Onset of treatment at age 11; height changed from 156 cm (z = +1.71) to 163 cm (z = +1.80), Tanner from G2P2T2 to G3P3T1, penis from 3.5 to 5.5 cm, LH from 4.8 to 12.4 IU/L (NR: 1.5 to 9.3 IU/L), testosterone from 259 to 1,069 ng/dL (NR: 165 to 763 ng/dL), estradiol from 28 to &lt;5.0 pg/mL (NR: &lt; 40 pg/mL) and bone age remained at 12.5 years. Case 3 (p.Ser597Arg): Onset of treatment at age 12; height changed from 153 cm (z = +0.49) to 161 cm (z = +0.55), Tanner from G2P2T1 to G3P3T1, penis from 4.0 to 7.0 cm, LH from 8.5 to 17.2 IU/L (NR: 1.5 to 9.3 IU/L), testosterone from 280 to 889 ng/dL (NR: 165 to 763 ng/dL), estradiol from 32 to &lt;5.0 pg/mL (NR: &lt; 40 pg/mL) and bone age remained at 13.5 years. Discussion: There are no reports in the literature of the use of aromatase inhibitor in PAIS. The results of this pilot study (gynecomastia regression, significant testosterone level increases with decrease in estradiol levels, increment in height without bone age advancing, progression of puberty and penile growth) are sustaining for the indication of this treatment in boys with PAIS during puberty.
SAT-220 A Misdiagnosis Causing a Feared Complication
Authors: Mroueh Gabriela , Burks James K 
Published: May 2020

Abstract
Adrenal incidentalomas are being increasingly found with the widespread use of thoracic and abdominal imaging. Clinicians must determine the nature of the mass to decide what treatment, if any, is needed. All patients should undergo biochemical testing to rule out hypercortisolism, pheochromocytoma and if hypertension is present, primary hyperaldosteronism. These patients should ideally be evaluated by endocrinologists as misdiagnosis can lead to complications.
A 60-year-old African American female with a history of hypertension and type 2 diabetes, was admitted to the internal medicine ward with intractable vomiting, abdominal pain and hypotension. Two weeks prior to admission, she had undergone a left sided adrenalectomy for a diagnosis of primary hyperaldosteronism. An adrenal adenoma was incidentally found 1 year before surgery during abdominal imaging done for diverticulitis. She was immediately referred to a surgeon for further work up and evaluation. The work up done for the adrenal incidentaloma included renin, aldosterone and plasma fractionated metanephrines. Plasma renin was low (0.2 ng/mL/hr, n: 0.5-4.0 ng/mL/hr), and Aldosterone was normal (8.1 ng/dL, n&lt;16 ng/dL) and the Aldosterone/ Renin ratio was elevated. No confirmatory test was done and no evaluation for hypercortisolism was done either. Plasma fractionated metanephrines were normal.
During current hospitalization, an AM cortisol was 1.5 mcg/dL (n: 6-28 mcg/dL). An ACTH stimulation test was done which showed an inadequate response. She was subsequently started on stress dose steroids with rapid improvement in her symptoms. She was discharged with hydrocortisone and has been followed in our endocrinology clinic. She has yet to fully recover HPA axis but is currently on low dose Hydrocortisone and doing well.
This patient was misdiagnosed with primary hyperaldosterenism when she most likely had subclinical hypercortisolism. Patients with primary hyperaldosteronism typically have plasma aldosterone &gt; 15 ng/dL and low levels of plasma renin, with a ratio of plasma aldosterone to plasma renin activity &gt; 20. Low levels of both plasma renin activity and aldosterone suggest nonaldosterone mineralocorticoid excess. Cushing syndrome can cause similar findings. Confirmatory tests should be done, and most patients require bilateral catheterization of the adrenal veins to measure cortisol and aldosterone levels to confirm whether the aldosterone excess is unilateral or bilateral. A 1 mg overnight dexamethasone suppression test is recommended for all adrenal incidentaloma patients to exclude asymptomatic hypercortisolism.
OR19-01 IHC-Guided Capture of Adrenocortical Zones from Archival Formalin-Fixed, Paraffin-Embedded Adrenal Tissue Allows the Study Of RNA Expression Profiles
Authors: Plaska Samuel , Baker Jessica , Blinder Amy , Lim Jung Soo , Rainey William E 
Published: May 2020

Abstract
Introduction: Characterization of human adrenal RNA has relied on fresh tissue, or laser capture from OCT-embedded frozen tissue. These approaches have allowed identification of differences between zones of the adrenal cortex, but the need for fresh or frozen material has limited access for most researchers and has limited the number of samples that can be studied. In order to expand tissue availability and researcher access, we examined the use of archival formalin-fixed, paraffin-embedded (FFPE) adrenals for the capture and analysis of RNA from each adrenal zone.
Methods: 13 normal adrenals were obtained from deceased renal donors. Following FFPE, tissue serial sections were examined for zonal histology. Immunohistochemistry (IHC) was used to guide the capture of specific adrenal zones from FFPE tissue. CYP11B2, CYP17A1, and CYB5A IHC was used to visualize the zona glomerulosa (ZG), zona fasciculata (ZF), and zona reticularis (ZR) respectively. Serial unstained sections were then dissected under a dissection microscope based on IHC-guided visualization of the ZG, ZF, and ZR. Following capture of zones and isolation of RNA, quantitative PCR (qPCR) was used to examine zonal expression of transcripts for the IHC markers. Using housekeeping genes for normalization, specific zonal markers identified successfully isolated zones.
Results: Adrenals with clear zonal expression of CYP11B2 (ZG), HSD3B2 (ZG/ZF), and CYB5A (ZR) were included for study. Based on marker inclusion criteria, 3 ZG, 3 ZF, 3 ZR, and 3 medulla samples were studied. Using these samples, confirmatory markers of ZG (VSNL1), ZF (CYP17A1), ZR (SLC27A2), and medulla (TH) were analyzed by qPCR. Levels of these transcripts segregated as expected in the adrenal zones.
Discussion: The use of archival normal and pathologic adrenal tissue for RNA analysis would increase the number of samples available to many research groups. Our data demonstrates the ability to capture and use FFPE tissue for the capture and analysis of RNA. Future comparison of normal adrenal zones to adrenal tumor phenotypes will improve our understanding of tumor biology and provide potential genetic markers for targeted therapeutics.