Biochemical Abnormalities Research Articles

Impact of the COVID-19 pandemic on dispensing medicines in the community pharmacy.

The world has faced an unprecedented challenge since COVID-19 emerged as a pandemic, which has led to quarantine and disruptions in drug services. During the pandemic, drug use habits and availability changed, causing a shift in behaviors and, in turn, medicine misuse. In Iraq, this is a major problem because many medicines can be easily obtained. The study aims to describe the pattern of dispensing medications during the pandemic and to evaluate the biochemical and pathological consequences. The analytical, observational, cross-sectional study was performed via a compiled questionnaire for 400 random pharmacists, and the analysis and interpretation of the biochemical and medical reports. Results revealed that dispensing of medications since the COVID-19 outbreak has increased by 74%, and the demand for medicines seems higher than required in comparison to the periods before the pandemic, while 60% of the dispensed medicines were taken just in case needed. In addition, the availability of medicines decreased by 61%, and the dispensing of common medicines increased due to the belief in their prophylactic action. Several biochemical abnormalities and pathological consequences were recorded due to the irrational use of medicines, and the highest percentage (12%) was seen in hepatic and liver enzymatic dysfunction and 8% for the endocrine and hormonal abnormalities. It can be concluded that most of the dispensed medicines were not used on a therapeutic or scientific basis during the pandemic.

Impact of COVID lockdown: Increased prevalence of symptomatic Vitamin D deficiency in adolescents

BackgroundDuring the COVID lockdown in India, which lasted for more than a year, all schools were closed and children were homebound. When the lockdown was lifted, we observed an increased prevalence of Vitamin D deficiency(VDD) in adolescents. We want to highlight the effect of home lockdown on adolescents, which can predispose such children to VDD. AimTo document the increased prevalence of symptomatic VDD in adolescents after COVID lockdown and to study the symptoms, biochemical abnormalities, and response to therapy in this subset. MethodsThis prospective observational study was done from November 2021 to May 2022 with a minimum follow-up of six months. InclusionsConsecutive children presenting with gait abnormalities, proximal myopathy, and pains, with documented VDD. Exclusion: Genetic, neuromuscular disorders, juvenile rheumatoid arthritis, chronic renal failure, thyroid disorders and those on anti-epileptic medications and vitamin D supplementation in the past 6 months were excluded from the study. We recorded the symptomatology, biochemical abnormalities, and muscle weakness and followed their improvement after Vitamin D and Calcium supplementation. ResultsA statistically significant increase in symptomatic VDD in adolescents, in six months post-lockdown was noted. Thirty-one adolescents between 9 to 14 years were studied. All cases were relieved of pain and muscle power normalized in 12 weeks. ConclusionProlonged house arrest may cause VDD in adolescents. Physicians should consider VDD in adolescents with myopathy and pain after pandemic lockdowns. Supplementation of Vitamin D and calcium resolves most symptoms except deformities. Follow-up is needed until growth spurt completion for recurrence of symptoms.

Neuroprotective Potential of Silymarin against Rotenone induced motor deficits in Wistar Rats

AbstractBackgroundParkinson’s disease is a hypokinetic disorder characterized by selective loss of dopaminergic in substantia nigra pars compacta (SNPc) region of mid‐brain. Dopaminergic degeneration of neurons is considered to be due to oxidative stress, neuroinflammation, neurons mitochondrial dysfunction and glutamate excitotoxicity etc. Silymarin was selected as an investigational drug, due to its numerous activities in current research, it possesses substantial antioxidant and neuroprotective functionalities and it has been reported to produce anti‐oxidant, anti‐inflammatory and neuromodulatory actions in previous studies.MethodIn the current study we have investigated the role of Silymarin against rotenone induced motor deficit and biochemical abnormalities in Wistar rats. Rats were treated with 1.5mg/kg rotenone subcutaneously for 35 days. Silymarin (50,100 and 200 mg/kg i.p.) was administered after 30 minutes of rotenone administration from day 7th to 35th day. Rotenone caused significant reduction in motor functions and body weight and produced elevation in striatal oxidative burden.ResultThe biochemical analysis revealed that there is reduction in the level of anti‐oxidants (GSH, Catalase, and SOD) in the animals following rotenone administration. Whereas Silymarin treated rats were stable and regained their body weight. In addition Silymarin significantly attenuated rotenone induced motor deficit and striatal oxidative stressConclusionOutcomes of the current study suggest neuroprotective potential of Silymarin and its ability to correct movement disability and thus could prove to be useful candidate molecule in the management of motor disorders.

NEUROPROTECTIVE EFFECT OF PALIPERIDONE IN LPS INDUCED ANIMAL MODEL OF AD

AbstractBackgroundAlzheimer’s disease is a progressive neurological condition, that impairs cognition and memory. Extracellular beta‐amyloid plaques and intracellular neurofibrillary tangle formation are the two hallmarks while cognitive decline, neurotransmitter deficit, neuroinflammation, mitochondrial dysfunction, decreased cerebral glucose uptake, and oxidative stress has been known to contribute to the pathogenesis of AD. The present study was designed to investigate the neuroprotective potential of Paliperidone on intracerebroventricular (i.c.v.) Lipopolysaccharide‐induced experimental dementia of Alzheimer’s type.MethodLPS was administered by the i.c.v route on 1st day of the study in rats. Paliperidone was administered (1mg/Kg and 2mg/kg/day i.p) from the 1st to 21st day in LPS‐infused rats. Morris water maze, open‐field test, and object recognition parameters were used to assess learning, memory, behavioral changes and locomotor activity in rats. LPS infusion rapidly causes neuroinflammation and oxidative‐nitrosative stress.ResultThese markers were determined in the cortical and hippocampal brain regions of rats. While paliperidone treatment attenuates the LPS‐induced behavioral and biochemical abnormalities in rats by reducing levels of Malondialdehyde (MDA), reduced glutathione (GSH), and increasing levels of catalase. The neurodegeneration in Hippocampus and cortex regions was observed through histopathological examination. The observed cognitive improvement following paliperidone in LPStreated rats may be due to its antioxidant and anti‐inflammatory activity and restoration of cholinergic functions.ConclusionOur results suggest the therapeutic potential of paliperidone in cognitive disorders such as AD. However, more investigations are required to evaluate the potential of paliperidone in boosting memory and cognition and preventing neuronal damage.

NEUROPROTECTIVE EFFECT OF PERILLYL ALCOHOL IN EXPERIMENTAL SPORADIC AD

AbstractBackgroundAlzheimer’s is most common neurodegenerative disorder characterized by memory loss due to accumulation of amyloid‐ β fibrils. There are different pathologies that count for AD like neuro inflammation. This study highlights the role of oxidative stress and inflammation in progression of AD where as Perillyl alcohol (POH) shows antioxidative & anti‐inflammatory properties.MethodSprague Dawley ICV‐STZ (3mg/kg) rats (250‐300g, 7‐8 weeks) were treated with Perillyl alcohol treated with three different doses of (25, 50 and 100mg/kg p.o.) for 13 days from 15th to 27th day. Weight measured on 1st and 28th day. Behavioral analysis done using Open Field Test and Morris Water Maze.ResultPerillyl alcohol treatment significantly attenuates declined body weight in ICV‐STZ induced dementia in rats, showed significant increase in crossing number, and active time. Dementia induced rats were unable to discriminate familiar and novel objects, which is improved by POH. POH attenuates STZ induced acquisition deficits and retention time, increased MDA and nitrite levels. POH attenuated depleted levels of GSH, Catalase, SOD comparable to standard drug donepezil, POH decreased AChE levels in cortex and hippocampus.ConclusionStudy outcomes demonstrate neuroprotective potential of Perillyl alcohol against ICV‐STZ administration of streptozotocin induced behavioural and biochemical abnormalities. Biventricular STZ infusion produced significant impairment in learning, memory, cholinergic hypofunction and elevation in hippocampal oxidative stress in rats. Rats showed poor learning, memory and unable to discriminate between familiar & novel objects in MWM and ORT. POH administration significantly attenuated STZ induced biochemical consequences. Observed beneficial effects of POH include restored cholinergic functions and antioxidant mechanism

Tryptophan Prevents the Development of Non-Alcoholic Fatty Liver Disease.

The main aim of this research is to study the protective effects of tryptophan on the histomorphological and biochemical abnormalities in the liver caused by a high-calorie diet (HCD), as well as its ability to normalize mitochondrial functions in order to prevent the development of non-alcoholic fatty liver disease (NAFLD). The study was conducted in male Wistar rats aged 3 months at the start of the experiment. Control animals (group I) were fed a standard diet. Group II experimental animals were fed a diet with an excess of fat (45%) and carbohydrates (31%) for 12 weeks. Group III experimental animals also received L-tryptophan at a dose of 80 mg/kg body weight in addition to the HCD. The presence of NAFLD, functional activity, physiological regeneration, and the state of the liver parenchyma and connective tissue were assessed using physiological, morphological, histo-morphometric, biochemical, and biophysical research methods. HCD induced the development of NAFLD, which is characterized by an increase in liver weight, hypertrophy of hepatocytes and an increase in the concentration of lipids, cholesterol and triglycerides in liver tissue. Increased alanine aminotransferase activity in the liver of obese rats also confirm hepatocytes damage. Tryptophan added to the diet lowered the severity of NAFLD by reducing fat accumulation and violations of bioelectric properties, and prevented a decrease in mitochondrial ATP synthesis. The addition of tryptophan can have a potential positive effect on the liver, reducing the severity of structural, biochemical, mitochondrial and bioelectric damage caused by HCD.

STUDY OF PREVALENCE AND RISK FACTORS OF POLYCYSTIC OVARIAN SYNDROME AMONG ADOLESCENT AND YOUNG ADULTS OF RAMA UNIVERSITY

Background: There is little epidemiological data from India on the prevalence and risk factors associated with polycystic ovarian syndrome (PCOS). The objectives of the present study were to estimate the prevalence of PCOS using different criteria among adolescents and young women and to evaluate risk factors associated with PCOS. Materials and Methods: A total of 200 participants, adolescents (12-17 years, n = 100) and young women (18-30 years, n =100), were recruited. Participants who were overweight and having menstrual disorders or biochemical abnormalities were invited for ultrasonographic examination. A standardized questionnaire assessed the regularity of menstrual cycles, body hair growth, skin, body weight, sleep, and androgen excess. The ovarian volume and follicular size were assessed transabdominally. Prevalence of PCOS was assessed by the Rotterdam, AE-PCOS, and NIH criteria.Study period - 1st January 23 - 31st August 23 Results: The mean age of participants with PCOS was 21 ± 6.069 years and those without PCOS was 19.62±5.583 years. Mean body weight, body mass index, fasting insulin, systolic and diastolic blood pressures were significantly higher in the PCOS group. Prevalence of polycystic ovaries on ultrasonography was observed in 78.6% of the women with PCOS as against 5% in women without PCOS. Obesity (OR: 7.34, 95% CI: 1.95- 27.27), insulin resistance (OR:5.62, 95% CI :0.461 - 0.982) and hypertension (OR: 10.76, 95% CI: 0.916 - 0.998) were significantly associated with PCOS . Overall, the Prevalence of pcos was highest among female AGE GROUP 17-30YRS . Conclusion: There is a high prevalence of PCOS in today society, which emphasizes the need for urgent preventive and control measures. Early diagnosis and assessment of risk factor is therefore crucial in incorporating lifestyle and dietary modifications for weight reduction and better control of blood pressure at a younger age to further prevent long-term reproductive and metabolic disorders.

Clinical Risk Factors Associated with Poor Outcomes in Snake Envenoming: A Narrative Review.

Snakebite-related fatalities disproportionately affect populations in impoverished socio-economic regions, marked by limited access to adequate healthcare and constrained antivenom availability. Early medical intervention is pivotal in mitigating mortality and morbidity associated with snakebite envenoming (SBE). While clinical assessment remains fundamental in treating SBE, this review aims to spotlight objective parameters that could also affect outcomes. Selected studies that identify factors associated with poor outcomes are predominantly region-specific, single-site, and observational, yet collectively reveal similar findings. They consistently report factors such as treatment delays, susceptibility in vulnerable groups such as children and pregnant women, as well as various biochemical and haematological abnormalities. Acute kidney injury (AKI), low platelets, leucocytosis, abnormal coagulation, and elevated creatine kinase (CK) all show an association with poor outcomes. Furthermore, recognising rare and unusual SBE presentations such as adrenal insufficiency, severe hypertension, intracranial haemorrhage, acute angle closure glaucoma, and bowel ischaemia also has a bearing on outcomes. Despite the integration of these parameters into clinical decision tools and guidelines, the validation of this evidence is limited. This review underscores the imperative for high-quality, multi-centre studies aligned with consensus-driven Core Outcome Sets (COS) and Patient-Reported Outcome Measures (PROMS) to validate and strengthen the current evidence.

A Study on Acute & Chronic Hepatobiliary Manifestations of Sickle Cell Syndromes - Clinical, Biochemical, and Ultrasonographic Abnormalities

A Study on Acute & Chronic Hepatobiliary Manifestations of Sickle Cell Syndromes - Clinical, Biochemical, and Ultrasonographic Abnormalities

Effect of hydroalcoholic extract of Trigonella foenum-graecum leaves on wound healing in type 1 diabetic rats.

Diabetes describes a group of metabolic disorders characterised by increased blood glucose concentration. People living with diabetes have a higher risk of morbidity and mortality than the general population. In 2015 it was estimated that there were 415 million (uncertainty interval: 340-536 million) people with diabetes aged 20-79 years, and 5.0 million deaths attributable to diabetes. When diabetic patients develop an ulcer, they become at high risk for major complications, including infection and amputation. The pathophysiologic relationship between diabetes and impaired healing is complex. Vascular, neuropathic, immune function, and biochemical abnormalities each contribute to the altered tissue repair. The use of herbal medicine has increased and attracted the attention of many researchers all over the world. In this study, we have evaluated the effect of 500mg/kg hydroalcoholic extract of Trigonella foenum-graecum leaves (TFG-E) on wound healing in diabetic rats using a full-thickness cutaneous incisional wound model. Wounds of treated animals showed better tensiometric indices, accelerated wound contraction, faster re-epithelialisation, improved neovascularisation, better modulation of fibroblasts and macrophage presence in the wound bed and moderate collagen formation.

A Conceptual Study of Vrikka and Vrikkaroga w.s.r. Chronic Kidney Disease: A Review

Abstract: The primary goal of Ayurveda is illness elimination and the preservation of healthy persons' health. Mutravaha sroto vikaras are described in Ayurvedic literature. Acharya Vagbhata explains Mutravaha sroto vikara has been classified as Mutra Atipravritti and Mutra Apravritti, which is a unique contribution. Mutra Atipravritti vikara, such as Prameha, and Mutra Apravrittija vikara, such as Asmari, Mutrakricchra, and others Mutraghata.Because the symptoms of Mutrakricchra and Mutraghata appear to be overlapping, Acharya Dalhana, Chakrapani, and Vijayarakshita have distinguished both entities. This distinction is due to the greater severity of "Vibhanda" or "Avarodha" (obstruction) in Mutraghata. Here Chronic Kidney Disease (CKD) encompasses a spectrum of different pathophysiologic process associated with abnormal kidney function. Manifested initially as a biochemical abnormality eventually the excretory, metabolic and endocrine dysfunctions of the kidney leads to the development of clinical symptoms and signs of renal failure, which are referred to as uremia. The disease, which begins in the kidney, spreads to all of the body's systems and tissues, eventually killing the patient. Chronic Kidney Disease is a global danger to health in general, and particularly to poor nations, because treatment is costly and must be sustained indefinitely.

LCZ696 attenuates sepsis-induced liver dysfunction in rats; the role of oxidative stress, apoptosis, and JNK1/2-P38 signaling pathways

AimSepsis is a serious inflammatory response to infection with an annual incidence rate of >48 million cases and 11 million fatalities worldwide. Furthermore, sepsis remains the world's fifth-greatest cause of death. For the first time, the current study aims to evaluate the possible hepatoprotective benefits of LCZ696, a combination of an angiotensin receptor blocker (valsartan) and a neprilysin inhibitor prodrug (sacubitril), on cecal ligation and puncture (CLP)-induced sepsis in rats. Main methodsCLP was employed to induce sepsis. Hepatic malondialdehyde (MDA), reduced glutathione (GSH), superoxide dismutase (SOD), interleukin-6 (IL-6), IL-1β, tumor necrosis factor-alpha (TNF-α), and caspase 3 were assessed using ELISA. Serum alanine transaminase (ALT) and aspartate transaminase (AST) were also measured. Western blot assay was used to determine the expression of JNK1/2 and P38 proteins. The histology of liver tissues was also examined. Key findingsCLP resulted in significant elevation of AST, ALT, MDA, IL-6, IL-1β, TNF-α, and caspase 3 levels, and up-regulation of p/t JNK1/2, and p/t P38 proteins, as compared to the sham group. However, level of GSH, and SOD activity were reduced in CLP group. LCZ696 significantly improved all the previously mentioned biochemical and histological abnormalities better than using valsartan alone. SignificanceLCZ696 substantially ameliorated CLP-induced liver damage, compared to valsartan, by reducing proinflammatory mediators, inhibiting the JNK1/2 and P38 signaling pathway, and attenuating apoptosis.

Estimation of serum levels of Parathyroid hormone, Vitamin D, Calcium and Phosphorus to study their association with age, gender, disease duration, and severity of chronic plaque psoriasis: Results of a case control study

: Psoriasis is a chronic inflammatory disease characterized by rapid turnover of epidermal keratinocytes; presenting clinically as erythema, induration, and scaling Parathyroid hormone (PTH) is secreted by parathyroid glands and its elevated levels may be seen in psoriasis and several other disorders of keratinization. PTH/PTH-related peptide receptors are present in dermal fibroblasts & regulate proliferation and maturation of fibroblasts and keratinocytes. Release of PTH is under the feedback regulation of serum Ca2+, Vit.D and PO: To assess the Parathyroid hormone levels in patients of Psoriasis along with Vitamin D, Serum Calcium and Serum Phosphorus levels.: Out of the 50 cases aged between 18 and 91 years majority of patients i.e 22 (44%) were in the age group of 18-40 years followed by 20 (40%) patients in 41-60 years age group. Eight (16%) patients were above >60 years. 32 (64%) patients who had psoriasis for less than ≤60 months while 18 (36%) patients had psoriasis for more than >60 months Serum PTH (normal 10–65pg/ml), Vitamin D(normal 20-50(ng/ml), calcium (normal 9-11mg/dl and phosphorus (normal 2.5-4.5mg/dl) levels were measured after overnight fasting. : A total of 50 psoriasis patients along with 50 non-psoriatic age and sex matched controls were recruited for the study. There were 28 males and 22 females in the patient group aged between 18 and 91 years (mean±SD 43.52±16.23 years). The mean age of controls was 47.12±16.29 years with 19(38%) subjects in 18-40 years age group and 21(42%) in 41-60 years age group. Amongst the cases, there were 10(20%) patients who had abnormal PTH levels (six had elevated levels of PTH and four patients with low PTH levels) while 40(80%) had normal levels (mean±SD 47.97±25.46 pg/ml). : The interpretation of our observation remains complex and any conclusion for the significance of these biochemical abnormalities remain conjectural. Moreover, association of psoriasis with abnormal biochemical parameters remains debatable in view of limited number of studies whether abnormal biochemical parameters can serve as markers of severity and their correction can lead to improvement in the disease needs confirmation with more well designed experimental and prospective clinical studies.

Establishment of age- and -gender specific reference intervals for amino acids and acylcarnitines by tandem mass spectrometry in Turkish paediatric population.

We determined age- and gender-specific reference intervals (RIs) for acylcarnitines and amino acids by tandem mass spectrometry (MS/MS) in the Turkish paediatric population by using laboratory information system (LIS) data. A total of 9156 MS/MS results of children between 0-18 years of age, were downloaded from the LIS. Premature infants and newborns followed in the intensive care unit were excluded and only the first result of each patient attending outpatient clinics was included. Children with a known or suspected diagnosis of metabolic disease, malignancy, epilepsy, mental retardation, or genetic disorder were excluded. Laboratory results were evaluated and children with any pathological laboratory finding were excluded, resulting in a final sample size of 3357 (2029 boys and 1328 girls). Blood was collected by capillary puncture and spotted on Whatman 903 filter paper cards and analysed by MS/MS (Shimadzu LCMS-8050, Shimadzu Corporation, Kyoto, Japan). Data were evaluated for age and gender differences and age partitioning was performed according to the literature and visual evaluation of the data. Age subgroups were: ≤ 1 month, 2 months-1 year, 2-5 years, 6-10 years, and 11-18 years. There were significant age-related differences for the majority of amino acids and acylcarnitines thus age dependent RIs were established. Gender-specific RIs were established for tyrosine, leucine-isoleucine, isovalerylcarnitine (C5) and hexadecanoylcarnitine (C16). Establishing age-related RIs can enhance the quality of medical care by facilitating early diagnosis and therapy, especially in certain metabolic disorders presenting with mild biochemical abnormalities and subtle clinical manifestations.

Hypocalcemia in combination with hyperphosphatemia impairs muscle cell differentiation in vitro

PurposeHypoparathyroidism is a rare endocrine disorder characterized by low or absent secretion of parathyroid hormone (PTH), which leads to decreased calcium and increased phosphorus levels in the serum. The diagnosis of hypoparathyroidism is based on the identification of the aforementioned biochemical abnormalities, which may be accompanied by clinical manifestations. Symptoms of hypoparathyroidism, primarily attributed to hypocalcemia, include muscle cramps or spasms, facial, leg, and foot pain, seizures, and tingling in the lips or fingers. The treatment of hypoparathyroidism depends on the severity of symptoms and the underlying pathology. Over the long term, calcium supplements, active vitamin D analogs, and thiazide diuretics may be needed. In fact, in patient cohorts in which optimal disease control still remains elusive, replacement therapy with recombinant parathyroid hormone analogs may be contemplated. Despite the predominantly neuromuscular symptoms of hypoparathyroidism, further effects of parathyroid hormone deficiency at the muscle cell level remain poorly understood. Thus, the aim of our study was to evaluate the effects of hypocalcemia in combination with hyperphosphatemia on muscle cells differentiation in vitro.MethodsC2C12 cells, an in vitro model of muscle cells, were differentiated for 2 or 6 days in the presence of hypocalcemia (CaCl2 0.9 mmol/l) and moderate (PO4 1.4 mmol/l) or severe (PO4 2.9 mmol/l) hyperphosphatemia, or combinations of both conditions. Cell differentiation and expression of genes linked to muscle differentiation were evaluated.ResultsThe combination of hypocalcemia with hyperphosphatemia induced a significant reduction (50%) in differentiation marker levels, such as MyoD (protein 1 for myoblast determination) and myogenin on the 1st day of differentiation, and MHC (myosin heavy chains) after 6 days of differentiation compared to control. Furthermore, this condition induced a statistically significant reduction of insulin-like growth factor-1 (IGF-1) mRNA expression and inhibition of IGF signaling and decrease in ERK phosphorylation compared to control cells.ConclusionsOur results showed that a condition of hypocalcemia with hyperphosphatemia induced an alteration of muscle cell differentiation in vitro. In particular, we observed the reduction of myogenic differentiation markers, IGF-1 signaling pathway, and ERK phosphorylation in differentiated skeletal myoblasts. These data suggest that this altered extracellular condition might contribute to the mechanisms causing persistence of symptoms in patients affected by hypoparathyroidism.

FRI230 Cystic Pheochromocytoma

Abstract Disclosure: S. Saberi: None. A 67-year-old woman presented with right abdominal tenderness, abdominal distention, gas and belching. Her blood pressure was 134/70, pulse 84 with no palpable abdominal mass. Her medical history includes depression and anxiety which developed 17 years prior and later resolved. She was diagnosed with hypertension approximately 20 years earlier initially well-controlled with candesartan-hydrochlorothiazide 16-12.5 mg daily and metoprolol succinate ER 50 mg daily. Two years prior to presentation her blood pressure rose to the 180s/90s requiring doubling of her candesartan-hydrocholorothiazide. An abdominal ultrasound was obtained which showed an abdominal mass. Subsequently, a CT of the abdomen and MRI of the abdomen with and without contrast were obtained revealing a 10 cm predominantly cystic adrenal mass with partial irregular wall thickening and nodularity causing mass effect on the inferior vena cava, liver and right kidney. Results of lab testing revealed an elevated plasma free metanephrines 1187 pg/ml (normal < 57 pg/ml), plasma free normetanephrines 1911 pg/ml (normal < 148 pg/ml), total free metanephrines and normetanephrines 3098 pg/ml (normal < 205 pg/ml). Her other adrenal biochemical evaluation was normal. She underwent open right adrenalectomy after adequate pre-operative blockade. Post-operatively her plasma free normetanephrines decreased to 0.47 nmol/L (normal < 0.90 nmol/L) and plasma free metanephrines were less than 0.20 nmol/L (normal < 0.50 nmol/L). Cystic Pheochromoctyoma: Spontaneous rupture of cystic pheochromocytoma can cause an adrenergic crisis. Cystic pheochromocytoma may develop due to hemorrhage within the lesion, necrosis and subsequent cyst formation (1). Patients may present with abdominal pain, GI symptoms or palpable masses rather than classic symptoms of pheochromocytoma (2).The differential diagnosis of cystic adrenal lesions includes lymphangiomas, pseudocysts of other surrounding structures (such as liver, pancreas, kidney, spleen, retroperitoneal and urachal and mesenteric cysts), dermoids, adrenal carcinoma, hydatid cysts of the adrenal glands (3).Small case series report the incidence of adrenal cysts in adrenal disease as 5.1% (4). A female predominance has been reported in prior studies (4). More commonly cystic adrenal lesions are unilateral and present in persons aged 30s-50s (2). Adrenal cysts are classified based on their origin as endothelial cysts derived from malformation of the lymphatic or arteriovenous systems, pseudocysts derived from prior hemorrhage, epithelial cysts with thin wall and serous fluid, or parasitic cysts. Necrosis and liquefaction in the adrenal lesion may lead to fluid accumulation and a cystic appearance. Large cysts are at risk for hemorrhage and rupture. All adrenal cysts require biochemical evaluation. Particular attention should be paid to predominantly cystic masses with any solid component as up to 7% of these may be malignant (5). Uniform guidelines for surgical management of these lesions have not been well established. Patients with symptoms such as abdominal pain, biochemical abnormalities, complications such as pressure on adjacent organs or rupture with cyst content leakage, suspicion of malignancy, cysts larger than 5 cm or increasing size of the cyst should be considered for surgical intervention (5, 6). In patients presenting with abdominal pain and hypertension who are found to have a cystic adrenal lesion pheochromocytoma should be considered. Presentation: Friday, June 16, 2023

THU440 A Case Of Osteomalacia In A Young Adult Female With Premature Ovarian Insufficiency

Abstract Disclosure: I.H. Kasimoglu: None. T. Vu: None. J.Q. Dai-Ju: None. Background: Osteomalacia is a condition due to inadequate mineralization during the bone-remodeling process. Common causes of bone demineralization include Vitamin D deficiency and low calcium intake. Consequently, the treatment often involves both Vitamin D and calcium supplementation, corresponding dietary modifications, and adequate exposure to sunlight. Clinical Case: 34-year-old female with past medical history of sickle cell disease s/p allogenic bone marrow transplant in 11/2020, brain toxoplasmosis infection 3/2021, secondary amenorrhea due to premature ovarian insufficiency diagnosed in 12/2021, was referred to endocrinology for management of osteomalacia. Dexa Scan from 11/2021 reported lower bone density than expected compared with the same age/gender group (Z-Scores: Left Hip – 0.3, Neck –1.4, and L1-L4 –3.6). Vitamin D 25-OH level was 8.3 (n>30) ng/mL and serum calcium level as low as 5.8 (n8.6-10.3) mg/dL in 3/2021, PTH-I elevated to 459 (n10-68) pg/mL, alkaline phosphatase elevated to 166 (n34-104) U/L. The patient was encouraged to increase Vitamin D3 to 4000 iu daily and calcium intake to 1200 mg daily. After discussion with patient of benefits and risks of hormone replacement, patient was started on very low dose of estradiol patch (0.025mg/day) for concern of prior history of pulmonary embolism, and progesterone 100 mg oral daily 3/2022. Vitamin D 25-OH, PTH, serum and 24 hr urine calcium have been within normal range since 9/2022. Dexa Scan from 11/2022 showed significant improvement of bone density (32.0% increase of lumbar spine, 11.2% increase of left hip). This case of osteomalacia resulting from Vitamin D deficiency and subsequent secondary hyperparathyroidism demonstrates that it is imperative to recognize and treat Vitamin D deficiency because it restores bone strength and prevents fractures while simultaneously correcting biochemical abnormalities (1). This case is also interesting as the patient still carries an increased risk of bone density loss complicated by underlying premature ovarian insufficiency and hypoestrogenic state. Thus, by providing patients with the appropriate Vitamin D and calcium supplementation recommendations along with hormone replacement therapy in young adults, it is possible to rehabilitate their overall bone health as well as reduce future risks of fractures. Conclusion: Adequate Vitamin D and calcium supplementation is important for the management of osteomalacia. In patients with premature ovarian insufficiency, it is even more imperative to promote supplementations, dietary modifications, and sunlight exposure in conjunction with traditional agents of hormonal therapy to promote overall bone health. Reference: 1) Bhan A., et al. Osteomalacia as a result of vitamin D deficiency. Endocrinol Metab Clin North Am. 2010;39(2):321–331. 10.1016/j.ecl.2010.02.001 Presentation: Thursday, June 15, 2023

SAT440 DRESS/DHIS-associated Thyroiditis And Hypophysitis

Abstract Disclosure: I.R. Ranasinghe: None. M.S. Elston: None. V. Boyle: None. Introduction: Drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms (DRESS/DIHS) is a severe life-threatening adverse reaction to specific drugs, including cephalosporin antibiotics (1). It is characterised by rash, fever, eosinophilia, lymphadenopathy, and inflammation of internal organs. Endocrine complications in the form of thyroid disease and Type 1 Diabetes have been reported following DRESS/DIHS (2). We report a case of thyroiditis and hypophysitis following cephalosporin-associated DRESS/DIHS. Case: A 21-year-old male farmer suffered a tractor crash accident resulting in hospitalization for bilateral compound distal femur fractures. He had no past medical history of note. One month later, he developed a maculopapular rash involving his limbs, mouth ulcers, fever, liver function derangement and eosinophilia. Punch biopsy was consistent with DRESS/DHIS. A 2- week tapering course of prednisone was initiated at 40mg daily in conjunction with a topical corticosteroid for 9 days with resolution of rash. Review of medication charts identified the most likely causative agent as cefazolin. An Endocrine consult was requested a month later due to new hypercalcemia. Investigations revealed new onset thyrotoxicosis and a decreasing morning cortisol over the following week despite having stopped all steroids one month earlier, normal ACTH, mildly elevated prolactin and secondary hypogonadism. Short Synacthen test showed suboptimal response. TRAb were negative and technetium thyroid scanning demonstrated a thyroiditis. MRI pituitary was unremarkable. He was commenced on hydrocortisone replacement for symptomatic cortisol deficiency. Biochemical abnormalities gradually normalized and his hydrocortisone ceased with symptomatic resolution. Endocrine involvement, particularly pancreas and thyroid has previously been reported in cases of DHIS/DRESS (3) (4). In this case, DHIS/DRESS-associated hypophysitis with thyroiditis may explain the clinical findings of pituitary dysfunction affecting multiple pituitary axes and the gradual recovery to normal pituitary function.

THU465 Significant Improvement In Bone Mineral Density Following Treatment For Tumor Induced Osteomalacia

Abstract Disclosure: L.C. McHan: None. M. Augustine: None. Background: Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome characterized by renal phosphate wasting and impaired activation of vitamin D due to excess secretion of FGF23, often from phosphaturic mesenchymal tumors (PMTs). TIO typically presents with months to years of bone pain, muscle weakness, and fractures often leading to functional decline. Given these nonspecific symptoms, diagnosis of TIO can be delayed for years. Removal of the tumor is curative, though it can sometimes be a challenge to localize. For those whose tumors are unable to be localized or removed, medical management with phosphorus and vitamin D is recommended. Patients with TIO have low bone mineral density (BMD) at time of diagnosis. Case Reports: We are presenting two cases of TIO, one managed surgically and one managed medically. Patient 1 is a 45-year-old man with Fabry disease who presented with years of progressive pain, difficulty ambulating, and multiple fractures. Lab workup revealed low serum phosphorus, elevated urinary phosphorus, elevated FGF23, and negative genetic testing for heritable causes of hypophosphatemic osteomalacia. DOTATATE imaging identified a subcutaneous left flank mass, which was excised resulting in improvement in symptoms and resolution of biochemical abnormalities. Additionally, lumbar spine (LS) bone mineral density (BMD) nearly doubled; prior to diagnosis of TIO, LS BMD was 0.601 g/cm2 and 8 months after surgical excision of the tumor, LS BMD was 1.178 g/cm2. Patient 2 is a 55-year-old nonverbal man with autism and intellectual disability who presented with months of progressive difficulty ambulating, presumed pain, functional decline, and multiple fractures. Workup revealed low serum phosphorus, elevated urinary phosphorus, and elevated FGF23 concerning for TIO. He was initiated on phosphorus and vitamin D supplementation, but no culprit tumor has been identified despite multiple scans over the course of years. However, the patient has had a significant improvement in functioning with medical management in addition to a remarkable 48% improvement in LS BMD, from 0.855 g/cm2 prior to diagnosis of TIO and 1.264 g/cm2 following 3 years of medical management. Clinical Lessons: In our review of the literature, there are few case reports and case series documenting the significant improvements in BMD with treatment of TIO. In our experience, two patients who had months to years of debilitating symptoms exhibited remarkable improvements in symptoms and marked improvement in LS BMD following treatment. This emphasizes the importance of recognizing the diagnosis of TIO, as even when the causative tumor is not identified, treatment typically has a significant impact on patient functioning and quality of life. Presentation: Thursday, June 15, 2023

OR23-03 Sustained Normalization Of Mineral Homeostasis In Autosomal Dominant Hypocalcemia Type 1: Results From A Phase 2 Study Over 18 Months Of Encaleret (CLTX-305) Treatment (NCT04581629)

Abstract Disclosure: R.I. Gafni: Advisory Board Member; Self; Ascendis Pharma, Hypoparathyroidism Association. Grant Recipient; Self; Calcilytix Therapeutics. I.R. Hartley: Grant Recipient; Self; Calcilytix Therapeutics. K.L. Roszko: Grant Recipient; Self; Calcilytix Therapeutics. E.F. Nemeth: Consulting Fee; Self; Calcilytix Therapeutics. K.A. Pozo: Grant Recipient; Self; Calcilytix Therapeutics. A. Mathew: Employee; Self; Calcilytix Therapeutics. M. Roberts: Employee; Self; Calcilytix Therapeutics. S.H. Adler: Employee; Self; Calcilytix Therapeutics. M.T. Collins: Grant Recipient; Self; Calcilytix Therapeutics. Autosomal dominant hypocalcemia type 1 (ADH1), caused by gain-of-function calcium-sensing receptor gene (CASR) variants, is characterized by low parathyroid hormone (PTH) levels, hypocalcemia, hypercalciuria, hyperphosphatemia and hypomagnesemia. Conventional therapy (calcium and active vitamin D) worsens hypercalciuria, which may result in renal complications. Calcilytics that act as negative allosteric modulators of the calcium-sensing receptor (CaSR), like encaleret, decrease the sensitivity of hyperactive receptors to extracellular calcium and normalize biochemical abnormalities in ADH1 rodent models. This Phase 2b open-label study of the oral investigational calcilytic encaleret was comprised of 3 periods followed by a long-term extension (LTE). Conventional therapy was discontinued prior to encaleret initiation. Periods 1&2 included dose-finding and safety/tolerability evaluation. Period 3 (P3) optimized dosing and assessed safety and efficacy over 24 outpatient weeks; participants were then allowed to continue in the LTE. Thirteen adults with ADH1 were enrolled and encaleret was individually titrated to normalize albumin-corrected calcium (cCa) and minimize hypercalciuria. Encaleret was well-tolerated with no serious adverse events reported. There were no treatment discontinuations or withdrawals prior to the LTE; one participant withdrew during the LTE for family planning. The mean±SD encaleret sulfate dose at the end of P3, Week 24 (P3W24) was 86±70mg BID, remaining stable at LTE Month 12 (LTEM12) (n=11) (71±62mg BID). Mean±SD values taken 4-hours post-dose for P3W24 and LTEM12 compared to baseline (BL) are presented. PTH levels were low at BL (6.3±7.8 pg/mL [nl 10-65]), normal at P3W24 (35.3±10.2), and remained consistent through LTEM12 (36.9±15.2 [p<0.01]). Similarly, hypocalcemia at BL (cCa=7.1±0.4 mg/dL [nl 8.4-10.2]) was normal at P3W24 (9.2±0.5); eucalcemia was maintained through LTEM12 (9.2±0.4 [p<0.01]). BL hypercalciuria (395±216 mg/d [nl <250-300]) decreased to 202±83 at P3W24 and normalization was sustained through LTEM12 (177±94 [p<0.05]). BL blood phosphate (4.5±1.1 mg/dL [nl 2.3-4.7]) decreased by P3W24 (3.4±0.4) and was maintained at LTEM12 (3.4±0.5 [p<0.01]). Blood magnesium increased (BL 1.7±0.2 mg/dL [nl 1.6-2.6]); P3W24 2.0±0.2; LTEM12 2.1±0.2 [p<0.01]). Bone turnover markers increased from BL (n=7) (CTX=253±111 pg/mL; P1NP=34±10 mcg/L) by P3W24 (n=13) (CTX=744±565; P1NP=104±87) and remained elevated at LTEM12 (CTX=988±652; P1NP=83±49 [p<0.01]. This study represents a molecularly targeted, precision medicine approach to the treatment of ADH1. The consistent and sustained results from over 18 months of outpatient encaleret treatment are clinically meaningful and support Phase 3 evaluation of the efficacy and safety of encaleret as the first potential treatment indicated for ADH1. Presentation: Saturday, June 17, 2023