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Summary Background COVID-19 can lead to multiorgan failure. Dapagliflozin, a SGLT2 inhibitor, has significant protective benefits for the heart and kidney. We aimed to see whether this agent might provide organ protection in patients with COVID-19 by affecting processes dysregulated during acute illness. Methods DARE-19 was a randomised, double-blind, placebo-controlled trial of patients hospitalised with COVID-19 and with at least one cardiometabolic risk factor (ie, hypertension, type 2 diabetes, atherosclerotic cardiovascular disease, heart failure, and chronic kidney disease). Patients critically ill at screening were excluded. Patients were randomly assigned 1:1 to dapagliflozin (10 mg daily orally) or matched placebo for 30 days. Dual primary outcomes were assessed in the intention-to-treat population: the outcome of prevention (time to new or worsened organ dysfunction or death), and the hierarchial composite outcome of recovery (change in clinical status by day 30). Safety outcomes, in patients who received at least one study medication dose, included serious adverse events, adverse events leading to discontinuation, and adverse events of interest. This study is registered with ClinicalTrials.gov , NCT04350593 . Findings Between April 22, 2020 and Jan 1, 2021, 1250 patients were randomly assigned with 625 in each group. The primary composite outcome of prevention showed organ dysfunction or death occurred in 70 patients (11·2%) in the dapagliflozin group, and 86 (13·8%) in the placebo group (hazard ratio [HR] 0·80, 95% CI 0·58–1·10; p=0·17). For the primary outcome of recovery, 547 patients (87·5%) in the dapagliflozin group and 532 (85·1%) in the placebo group showed clinical status improvement, although this was not statistically significant (win ratio 1·09, 95% CI 0·97–1·22; p=0·14). There were 41 deaths (6·6%) in the dapagliflozin group, and 54 (8·6%) in the placebo group (HR 0·77, 95% CI 0·52–1·16). Serious adverse events were reported in 65 (10·6%) of 613 patients treated with dapagliflozin and in 82 (13·3%) of 616 patients given the placebo. Interpretation In patients with cardiometabolic risk factors who were hospitalised with COVID-19, treatment with dapagliflozin did not result in a statistically significant risk reduction in organ dysfunction or death, or improvement in clinical recovery, but was well tolerated. Funding AstraZeneca.

Contains fulltext : 245825.pdf (Publisher’s version ) (Closed access) BACKGROUND: Phaeochromocytoma or paraganglioma (collectively known as PPGL) in pregnant women can lead to severe complications and death due to associated catecholamine excess. We aimed to identify factors associated with maternal and fetal outcomes in women with PPGL during pregnancy. METHODS: We did a multicentre, retrospective study of patients with PPGL and pregnancy between Jan 1, 1980, and Dec 31, 2019, in the International Pheochromocytoma and Pregnancy Registry and a systematic review of studies published between Jan 1, 2005, and Dec 27, 2019 reporting on at least five cases. The inclusion criteria were pregnancy after 1980 and PPGL before or during pregnancy or within 12 months post partum. Eligible patients from the retrospective study and systematic review were included in the analysis. Outcomes of interest were maternal or fetal death and maternal severe cardiovascular complications of catecholamine excess. Potential variables associated with these outcomes were evaluated by logistic regression. FINDINGS: The systematic review identified seven studies (reporting on 63 pregnancies in 55 patients) that met the eligibility criteria and were of adequate quality. A further 197 pregnancies in 186 patients were identified in the International Pheochromocytoma and Pregnancy Registry. After excluding 11 pregnancies due to potential overlap, the final cohort included 249 pregnancies in 232 patients with PPGL. The diagnosis of PPGL was made before pregnancy in 37 (15%) pregnancies, during pregnancy in 134 (54%), and after delivery in 78 (31%). Of 144 patients evaluated for genetic predisposition for phaeochromocytoma, 95 (66%) were positive. Unrecognised PPGL during pregnancy (odds ratio 27·0; 95% CI 3·5-3473·1), abdominal or pelvic tumour location (11·3; 1·5-1440·5), and catecholamine excess at least ten-times the upper limit of the normal range (4·7; 1·8-13·8) were associated with adverse outcomes. For patients diagnosed during pregnancy, α-adrenergic blockade therapy was associated with fewer adverse outcomes (3·6; 1·1-13·2 for no α-adrenergic blockade vs α-adrenergic blockade), whereas surgery during pregnancy was not associated with better outcomes (0·9; 0·3-3·9 for no surgery vs surgery). INTERPRETATION: Unrecognised and untreated PPGL was associated with a substantially higher risk of either maternal or fetal complications. Appropriate case detection and counselling for premenopausal women at risk for PPGL could prevent adverse pregnancy-related outcomes. FUNDING: US National Institutes of Health.

Varicella-zoster virus (VZV) has been known to cause various eye disorders in both immunocompetent and immunocompromised patients. We present a case of a forty-nine-year-old female patient with acquired immunodeficiency syndrome (AIDS) who presented with headache, fever, and blurred vision. Cerebrospinal fluid (CSF) analysis was consistent with VZV meningitis. Magnetic resonance imaging (MRI) of the brain showed enhancement of the right optic nerve indicative of optic neuritis. She responded well to acyclovir and steroids and discharged on the same. Four weeks after discharge, she presented with sudden onset blindness in the left eye. A cerebral angiogram revealed left retinal artery occlusion and was treated with tissue plasminogen activator (tPA). Funduscopic examination showed patchy areas of necrosis in the periphery which were rapidly progressive, diagnostic of posterior outer retinal necrosis (PORN). She was started on ganciclovir and cidofovir and experienced significant improvement in her visual acuity.

Heart failure is responsible for a significant part of diabetes-associated cardiovascular mortality and morbidity. Sodium-glucose cotransporter-2 (SGLT-2) inhibitors are novel agents approved for the treatment of diabetes mellitus; in recent clinical trials, these agents have shown a significant reduction in cardiovascular death and hospitalization secondary to heart failure. Clinical trials with specific heart failure outcomes have shown the benefit of SGLT-2 inhibitors in reducing the mortality and morbidity associated with heart failure. The guidelines for the management of diabetes mellitus recommend the preferential use of SGLT-2 inhibitors in patients with a history of cardiovascular disease. SGLT-2 inhibitors are potential game changers in the treatment of heart failure. Guidelines for prescription of these agents help assess risk-benefit analysis and personalize treatment for maximal benefit.

Patients with the recovery of kidney function after an episode of acute kidney injury (AKI) have better outcomes compared to those without recovery. The current systematic review is conducted to assess the rates of kidney function recovery among patients with AKI or severe AKI requiring kidney replacement therapy (KRT) within 100 days after hematopoietic stem cell transplant (HSCT). Methods The Ovid MEDLINE, EMBASE, and Cochrane databases were systemically searched from database inceptions through August 2019 to identify studies reporting the rates of recovery from AKI after HSCT. The random-effects and generic inverse variance methods of DerSimonian-Laird were used to combine the effect estimates obtained from individual studies. Results A total of 458 patients from eight cohort studies with AKI after HSCT were identified. Overall, the pooled estimated rates of AKI recovery among patients with AKI and severe AKI requiring KRT within 100 days were 58% (95%CI: 37%-78%) and 10% (95%CI: 2%-4%), respectively. Among patients with AKI recovery, the pooled estimated rates of complete and partial AKI recovery were 60% (95%CI: 39%-78%) and 29% (95%CI: 10%-61%), respectively. There was no clear correlation between study year and the rate of AKI recovery (p=0.26). Conclusion The rate of recovery from AKI after HSCT depends on the severity of AKI. While recovery is common, complete recovery is reported in about two-thirds of all AKI patients. The rate of recovery among those with AKI requiring renal replacement therapy (RRT) is substantially lower.

Catheter-related bloodstream infection (CRBSI) with hemodialysis catheters are associated with increased mortality, morbidity and pose significant financial burden on healthcare. Antibiotic and antimicrobial locking solutions are effective in reducing risk of CRBSI. From inception to April 2020, we looked for relevant clinical controlled trials throughout the following databases: EBSCO, PubMed, Cochrane CENTRAL, MEDLINE, EMBASE, clinicaltrial.gov, and Google Scholar performing a metanalysis comparing antibiotic and antimicrobial lock solutions to heparin. Twenty-six studies with 4,967 patients reported the incidence of catheter-related bacteremia (CRB). The overall pooled risk ratio (RR) showed that the intervention group was associated with a significantly lower incidence of CRB by 30% compared with heparin (RR = 0.30, 95% confidence interval [CI] [0.25, 0.36], p < 0.001). Subgroup analysis showed that administration of antibiotic regimens led to a decreased risk of CRB episodes by 28% compared with the heparin group (RR = 0.28, 95% CI [0.21, 0.37], p < 0.0001). Antimicrobial solutions was associated with reduced risk of CRB by 32% compared with patients of the control group (RR = 0.32, 95% CI [0.25, 0.41], p < 0.0001). A test of subgroup differences was revealed no significant favoring of any of the two interventions. Both antibiotic and antimicrobial solutions are effective in reducing CRBSI.

Numerous epidemiological studies have shown explicit sex and gender differences in the respiratory system under both physiological and pathological conditions. Here, we review the impact of sex steroids, with emphasis on androgens, upon the respiratory system in two endocrine hyperandrogenemic clinical scenarios: polycystic ovary syndrome and postmenopausal women. The primary sex hormones are testosterone in men and estrogens in women. Interestingly, in women, the plasma concentration of testosterone is much higher than estradiol; however, whether and how the excess of androgens may affect the respiratory system in women remain unclear. Hence, here we review some of the evidence that highlights the crucial role of androgens modulating respiratory physiology in these hyperandrogenemic endocrine conditions.

• The skeletal system can be divided into two compartments: the appendicular skeleton predominantly made of cortical bone and the axial skeleton predominantly made of trabecular bone. • Osteoporosis is a disorder of compromised bone strength with an increased propensity for fracture. Postmenopausal osteoporosis is due to estrogen deficiency while senile osteoporosis is due to aging. • Decreased osteoblastic activity, increased production of reactive oxygen species, imbalance of adipogenesis and osteoblastogenesis, impaired DNA repair, and vitamin D deficiency all play roles in the pathogenesis of senile osteoporosis. • The prevalence of osteoporosis increases with age, with two-thirds of women over 90 years affected. Hip and vertebral fractures are a cause of significant mortality, morbidity, and economic burden. Risk factors for osteoporosis and osteoporosis associated with glucocorticoid treatment, obesity, diabetes mellitus, and sarcopenia are particularized. • Osteoporosis is diagnosed if there is a history of fragility or fracture or a T-score of • Treatment in older patients with osteoporosis is detailed. Exercise, fall prevention, calcium, and vitamin D supplementation as well as most antiosteoporotic agents are described.

Hypothalamic diseases cause secretory dysfunction of its releasing hormones subsequently resulting in hypopituitarism. Knowledge of the hypothalamic nuclei, fibers, connections, and their specific functions guide the clinician on potential consequences with hypothalamic disorders. Etiologies for hypothalamic conditions range from malignancy, autoimmune conditions, infection, trauma, functional, vascular insufficiency, and iatrogenic, among others. Iatrogenic hypothalamic disorders can be classified according to the general treatment and/or diagnostic modality the patient was exposed to resulting in hypothalamic disorder. Knowledge of these specific modalities can potentially guide planning for diagnostics and treatment approaches involving the hypothalamus. This chapter focuses on iatrogenic hypothalamic disorders due to medical or non-surgical and surgical testing, pharmaceuticals, or procedures and will provide insight on how to potentially prevent or avoid these iatrogenic effects.

A 45-year-old man was referred to endocrine for the evaluation of hypercalcaemia. The calcium was elevated, vitamin D was low with a normal parathyroid hormone. Dual-energy X-ray absorptiometry scan revealed osteoporosis at the lumbar spine and femoral neck. A 24-hour urine collection revealed low urinary calcium, which was believed to be secondary to vitamin D deficiency. A diagnosis of primary hyperparathyroidism was made. The patient underwent a four-gland parathyroid exploration surgery in which three of his parathyroid glands were removed. The pathology was consistent with benign parathyroid tissue. Post surgery, the patient had persistently elevated calcium levels. He was then started on bisphosphonate and cinacalcet for osteoporosis and hypercalcaemia, respectively. Genetic analysis of familial hypocalciuric hypercalcaemia (FHH) showed a p.arg15cys mutation in the AP2S1 gene, confirming the diagnosis of FHH type 3.

Globally, diabetes mellitus is a leading cause of kidney disease, with a critical percent of patients approaching end-stage kidney disease. In the current era, sodium-glucose co-transporter 2 inhibitors (SGLT2i) have emerged as phenomenal agents in halting the progression of kidney disease. Positive effects of SGLT2i are centered on multiple mechanisms, including glycosuric effects, tubule—glomerular feedback, antioxidant, anti-fibrotic, natriuretic, and reduction in cortical hypoxia, alteration in energy metabolism. Concurrently, multiple kidney and cardiovascular outcome studies have reported remarkable advantages of SGLT2i including mortality benefits. Additionally, the superiority of combination therapies (SGLT2I along with metformin/DDP-4 Inhibitors) in treatment-naïve diabetic patients is further looked into with potential signal towards glycemic and blood pressure control. Reported promising results initiate a gateway for future research targeting kidney outcomes with combination therapies as an initial approach. In the current paper, we summarize leading cardiovascular and kidney outcome trials in patients with type 2 diabetes, the role of SGLT2i in non-diabetic proteinuric kidney disease, and the potential mechanisms of action of SGLT2i with special focus on combination therapy as an initial therapeutic approach in treatment-naïve diabetic patients.

Bone and mineral disorders are common after organ transplantation. Osteoporosis post transplantation is associated with increased morbidity and mortality. Pathogenesis of bone disorders in this particular sub set of the population is complicated by multiple co-existing factors like preexisting bone disease, Vitamin D deficiency and parathyroid dysfunction. Risk factors include post-transplant immobilization, steroid usage, diabetes mellitus, low body mass index, older age, female sex, smoking, alcohol consumption and a sedentary lifestyle. Immunosuppressive medications post-transplant have a negative impact on outcomes, and further aggravate osteoporotic risk. Management is complex and challenging due to the sub-optimal sensitivity and specificity of non-invasive diagnostic tests, and the underutilization of bone biopsy. In this review, we summarize the prevalence, pathophysiology, diagnostic tests and management of osteoporosis in solid organ and hematopoietic stem cell transplant recipients.

Introduction: Thyrotoxic periodic paralysis (TPP) is a rare and potentially lethal complication of hyperthyroidism. It is characterized by sudden onset paralysis associated with hypokalemia. Management includes prompt normalization of potassium, which results in resolution of the paralysis. Definitive treatment of hyperthyroidism resolves TPP completely. Case presentation: A 23-year-old African American male patient presented to the emergency room at the University of Mississippi Medical Center, USA in November 2016 with sudden onset quadriplegia. He also endorsed a history of weight loss, palpitations, heat intolerance and tremors. The patient reported similar episodes of quadriplegia in the past, which were associated with hypokalemia and resolved with normalization of potassium levels. Physical examination was significant for exophthalmos, smooth goiter with bruit consistent with the diagnosis of Graves’ disease. Laboratory assessment showed severe hypokalemia, hypomagnesemia, suppressed thyroid stimulating hormone (TSH) and high free thyroxine (T4). Urine potassium creatinine ratio was less than one, indicating transcellular shift as the cause of hypokalemia. After normalization of potassium and magnesium, the paralysis resolved in 12 hours. He was started on methimazole. On follow up, the patient was clinically and biochemically euthyroid with no further episodes of paralysis. Take-away lesson: TPP is a rare and reversible cause of paralysis. Physicians need to be aware of the diagnostic and treatment modalities as delayed recognition in treatment could result in potential harm or unnecessary interventions.

In-111 pentetreotide (Octreoscan) is a radiolabeled somatostatin analog with high binding affinity to somatostatin receptors (SSTR) used in somatostatin receptor scintigraphy (SRS). Pentetreotide labelled with In-111 is widely used due to its high affinity to SSTR 2 and 5. SSTR are expressed on neuroendocrine cells as well as several non-neural and non-endocrine cells with varying levels of density. We retrospectively reviewed articles and publications related to octreoscan accumulation in sites that classically do not have high concentrations of SSTR as well as in organs and tissues from diseases which are not usually diagnosed by octreoscan. The significance of a positive uptake as assessed by octreoscan in non-somatostatin receptor related diseases is not fully understood yet. Localization of octreotide in non-oncological disease states such as inflammation is due to presence of SSTR in activated immunological cells, over-expression by activated cells in the respective tissue and SSTR expression by blood vessels. In granulomatous diseases, over-expression of SSTR2 preferential binding sites were detected in epitheloid and giant cells. The purpose of the current study is to identify octreoscan localization in non-somatostatin receptor related disease sites to better understand the mechanism of this nonspecific accumulation which may help expand the clinical utilization of functional imaging utilizing somatostatin receptor scintigraphy in diagnosis and perhaps therapy.

Patient: Male, 42 Final Diagnosis: Bullosis diabeticorum Symptoms: Skin rash Medication: — Clinical Procedure: Debridement Specialty: Metabolic Disorders and Diabetics Objective: Rare co-existance of disease or pathology Background: Bullosis diabeticorum (BD) is a condition characterized by recurrent, spontaneous, and non-inflammatory blistering in patients with poorly controlled diabetes mellitus. While etiopathogenesis remains unclear, roles of neuropathy, vasculopathy and UV light are hypothesized. Most literature reports negative direct and indirect immunofluorescence findings in diabetics with bullous eruptions. Porphyria cutanea tarda, bullous pemphigoid, epidermolysis bullosa, and pseudoporphyria are other differential diagnoses of bullous lesions, and they must be excluded. Case Report: We present a 42-year-old African American male with long standing poorly controlled insulin dependent diabetes mellitus with blisters on his left hand and feet. The blisters were noticed three weeks prior to presentation and, thereafter, rapidly increased in size and spontaneously ruptured. Physical examination revealed a multitude of both roofed and unroofed bullous painless skin lesions. Hematoxylin and eosin (H&E) staining dramatized the dermal-epidermal blistering and re-epithelization process. Direct Immunofluorescence (DIF) was positive for 2 + IgG deposition in the already thickened basement membrane of the capillaries of the superficial vascular plexus. After debridement, his wounds greatly improved with over three months of aggressive wound care. Conclusions: Primary immunologic abnormality likely plays no role in the onset of BD. To date, only one article has reported nonspecific capillary-associated immunoglobulin M and C3. This is the first case of BD with IgG deposition in the superficial capillary basement membrane. Positive findings on DIF suggest vasculopathy. Dermal microangiopathy, secondary to immunologic abnormality, is a possible underlying pathogenesis to bullae formation. Punch biopsy with DIF can be an additional diagnostic modality in the management of such cases.

BackgroundWhile acute kidney injury (AKI) is commonly reported following hematopoietic stem cell transplant (HCT), the incidence and impact of AKI on mortality among patients undergoing HCT are not well described. We conducted this systematic review to assess the incidence and impact of AKI on mortality risk among patients undergoing HCT.MethodsOvid MEDLINE, EMBASE and the Cochrane Databases were searched from database inceptions through August 2019 to identify studies assessing the incidence of AKI and mortality risk among adult patients who developed AKI following HCT. Random-effects and generic inverse variance method of DerSimonian–Laird were used to combine the effect estimates obtained from individual studies.ResultsWe included 36 cohort studies with a total of 5144 patients undergoing HCT. Overall, the pooled estimated incidence of AKI and severe AKI (AKI Stage III) were 55.1% (95% confidence interval (CI) 46.6–63.3%) and 8.3% (95% CI 6.0–11.4%), respectively. The pooled estimated incidence of AKI using contemporary AKI definitions (RIFLE, AKIN and KDIGO criteria) was 49.8% (95% CI 41.6–58.1%). There was no significant correlation between study year and the incidence of AKI (P = 0.12) or severe AKI (P = 0.97). The pooled odds ratios of 3-month mortality and 3-year mortality among patients undergoing HCT with AKI were 3.05 (95% CI 2.07–4.49) and 2.23 (95% CI 1.06–4.73), respectively.ConclusionThe incidence of AKI among patients who undergo HCT remains high, and it has not changed over the years despite advances in medicine. AKI after HCT is associated with increased short- and long-term mortality.

A 55-year-old female patient was presented with severe dyspnea due to sudden onset of heart failure (ejection fraction (EF)

Diabetes mellitus (DM) and chronic kidney disease (CKD) are two chronic diseases whose prevalence and coprevalence are on the rise. CKD is also the most debilitating and expensive complication of DM while management of DM in CKD is most challenging. CKD is developing in much younger patients with DM, and its presentation is also changing. Various methods of glycemic assessment are affected by CKD and dosage of DM medications needs to be adjusted according to the kidney function. One of the significant barriers to glycemic control in DM patients with CKD is hypoglycemia; close monitoring of glucose levels is essential. Dialysis affects the glucose homeostasis and insulin pharmacokinetics; therefore diabetic medication regimen needs to be adjusted accordingly. Kidney transplants are being increasingly performed as an alternative to dialysis. With the increased survival of transplants secondary to improved immunosuppressive regimen, the prevalence of post-transplant diabetes mellitus is on the increase. Good glycemic control is necessary for the survival of the transplant.

Non-islet cell hypoglycemia (NICH) is hypoglycemia due to the overproduction of insulin-like growth factor-2 (IGF-2) and its precursors which can activate the insulin receptor. Typically, large mesenchymal and epithelial tumors can cause NICH. Diagnosis is confirmed by finding an elevated IGF-2/IGF-1 ratio. The mainstay of treatment is surgical excision. Glucocorticoids may be used in cases where surgery is not possible. We present two cases of NICH with different outcomes. A 33-year-old male patient admitted with altered mental. He was found walking naked outside his house. Laboratory assessment revealed severe hypoglycemia. Further evaluation showed low levels of insulin, C-peptide, and beta-hydroxybutyrate along with an elevated IGF-2/IGF-1 ratio confirming the diagnosis of NICH. Computed tomography (CT) of the abdomen showed a massive tumor of the liver consistent with hepatocellular carcinoma. Since the patient refused surgery, he was started on prednisone however the hypoglycemia persisted. A 54-year-old female patient with a history of type 2 diabetes mellitus (DM) admitted with recent onset hypoglycemia. Despite stopping her insulin, she continued to have hypoglycemia necessitating the administration of high concentrations of intravenous dextrose. Further evaluation showed low levels of insulin, C-peptide, and beta-hydroxybutyrate along with an elevated IGF-2/IGF-1 ratio consistent with the diagnosis of NICH. CT abdomen showed a 24 cm tumor near the uterus. The pathology was consistent with a gastrointestinal stromal tumor (GIST). After surgical excision of the tumor, the hypoglycemia resolved.

Introduction: Secondary osteoporosis is due to an identifiable cause of osteoporosis. Hypophosphatasia is a rare cause of secondary osteoporosis and needs to be considered when evaluating osteoporosis in young people. We present a case of secondary osteoporosis initially thought to be a result of malabsorptive disorder and chronic steroid use, with eventual diagnosis of autosomal dominant hypophosphatasia as the primary underlying cause. Clinical Case: A 24 year old male who was seen for evaluation of osteoporosis. He reported an extensive history of fractures about 26 in total, including wrist, shoulders, nose, and metatarsals. Past history was also significant for bowed legs at birth requiring osteotomies and spontaneous loss of several teeth with root intact, requiring extractions. He was also diagnosed with Crohn’s disease at 17 years old and history of steroid use, however was not on steroids at time of initial evaluation. He was diagnosed with bilateral avascular necrosis at age 18 years and needed bilateral hip replacement at age 20 years. There was no family history of skeletal disorders. DEXA scan obtained for the assessment of bone density revealed a Z score of -2.6 in the lumbar spine and -2.1 in the distal forearm. Further evaluation for secondary causes of osteoporosis revealed a normal TSH, PTH, tryptase, vitamin D and testosterone levels. Bone turnover markers were normal except for a low alkaline phosphatase. It was noted that the patient had a persistently low alkaline phosphatase for the last 6 years despite his frequent fractures. Hypophosphatasia was suspected given the history and the low alkaline phosphatase levels. Pyridoxal 5-phosphate was elevated at 77mcg/L (normal 5-50mcg/L). Genetics evaluation revealed a heterozygous, missense mutation in ALPL gene, confirming diagnosis of autosomal dominant hypophosphatasia. He was started on enzyme replacement therapy with asfotase alpha. Conclusion: Hypophosphatasia is a rare metabolic bone disease due to a deficiency of alkaline phosphatase which may present from infancy to adulthood. Diagnosis is made by finding a low alkaline phosphatase level and elevated 5 pyridoxal phosphate. Enzyme replacement therapy with asfotase alpha is the mainstay of treatment. It is probably underdiagnosed secondary to its rarity and therefore must be considered in any young patient who presents with osteoporosis. References: Mornet, E. and Nunes. M.E. Hypophosphatasia. 2007 Nov 20. In: Adam, M.P., Ardinger, H.H., Pagon, R.A., et al., editors. Gene Reviews [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2018. Demay, M.B. and Krane, S.M. 2016. Disorders of Mineralization. In Jameson, J.L., DeGroot, L.J., et al., editors. Endocrinology: Adult and Pediatric. 7th Edition. Philadelphia (PA): Saunders. p 1241.

Autoimmune polyglandular Syndrome Type 1 (APS-1) is an autoimmune disease due to defects in the AIRE gene. It is characterized by a triad of hypoparathyroidism, mucocutaneous candidiasis, and Addison’s disease. We present a case of pigmented paravenous retinochoroidal atrophy associated with APS-1. Case description: A 14 year old female who was admitted for cramps in her hands secondary to hypocalcemia. Past medical history is significant for recurrent vaginal candidiasis and panic attacks. Laboratory assessment revealed low parathyroid hormone and hypocalcemia confirming the diagnosis of hypoparathyroidism. After 4 months she presented with vomiting, and dizziness. Serum cortisol levels were low consistent with the diagnosis of adrenal insufficiency. Further evaluation revealed a mutation in the APS-1 gene. At 28 years she presented with complaints of blurred vision and blind spots for a year. Initial ophthalmologic evaluation revealed a visual acuity of 20/60 in the right eye and 20/50 in the left eye. Anterior segment assessment was normal. Fundoscopy revealed presence of speculated pigment and atrophy of the macula long with attenuated retinal vessels. Optical coherence tomography did not show any macular edema. Visual field assessment was normal. She was diagnosed with pigmented paravenous chorioretinal atrophy. Anti-retinal antibodies were positive for 30-kDa, 36-kDa, 40-kDa, and 46-kDa confirming the autoimmune etiology of the disorder. Over the next 2 years, her visual acuity decreased to 20/400 in the right eye and 20/80 in the left eye. Conclusion: APS-1 is a rare disease associated with numerous autoimmune disorders, beyond the classic clinical triad. Pigmented paravenous chorioretinal atrophy is a previously unreported manifestation of APS-1. Unfortunately no definitive treatment exists for retinal degeneration.

A 61-year old female patient who was referred to the endocrine clinic for evaluation of an elevated alkaline phosphatase. She was originally referred to gastroenterology (GI), however no GI causes of elevated alkaline phosphatase was found. Upon fractionation, it was noted that she had elevation in bone specific alkaline phosphatase. Past history was significant for hypertension, atrial fibrillation and menopause 6 years ago. She was also noted to have multiple drug allergies manifesting as urticaria and flushing. Review of the past records revealed a persistently elevated alkaline phosphatase over the last two years. She had no history of falls or fractures. Computed tomography (CT) abdomen done to rule out biliary pathology, revealed osteosclerotic and osteolytic lesion in the pelvis concerning neoplastic disease. Bone marrow biopsy however, was negative for cancer but consistent with systemic mastocytosis (SM). Dual Energy X-ray absorbimetery (DEXA) scan revealed osteoporosis Serum tryptase levels were elevated; further genetic analysis showed a positive CKIT D816 mutation. She was started on bisphosphonates (initially alendronate and then ibandronate). Upon follow up at two years she had not experienced any fractures and her bone mineral density also had improved significantly.

The worldwide prevalences of diabetes mellitus (DM) and of heart failure (HF) have collectively been on the rise. HF accounts for a large portion of the cardiovascular mortality and morbidity associated with DM. DM increases the risk of developing heart failure by promoting atherosclerosis and exerting direct deleterious effects on the myocardium. Sodium-glucose co-transporter-2 (SGLT-2) inhibitors are agents approved for the treatment of DM; they exert their anti-hyperglycemic effects by blocking renal reabsorption of glucose and inducing glycosuria. SGLT-2 inhibitors have consistently decreased the hospitalization rate of HF and cardiovascular mortality in several clinical trials. SGLT-2 inhibitors also possess anti-inflammatory, anti-fibrotic, and antihypertensive in addition to beneficial effects on the myocardial metabolism, which may account for their heart failure benefits. However, further research still needs to be done to evaluate the use of SGLT-2 inhibitors in non-diabetic patients and their efficacy in preventing or treating different heart failure phenotypes.

Hospitalists and primary care physicians encounter renal disease daily. Although most cases of acute kidney injury (AKI) are secondary to dehydration and resolve by giving fluids, many cases of AKI are due to not uncommon but unfamiliar causes needing nephrology evaluation. Common indications to consult a nephrologist on an emergency basis include hyperkalemia or volume overload in end stage renal disease patients (ESRD). Other causes of immediate consultation are cresenteric glomerulonephritis / rapidly progressive glomerulonephritis in which renal prognosis of the patient depends on timely intervention. The following evidence-based key information could improve patient care and outcomes. Abbreviations: AKI: Acute kidney injury ESRD: End stage renal disease patients

A 50-year-old man with a history of prostate cancer with extensive bone metastasis and hypocalcaemia presented with muscle aches and cramps. Physical exam was significant for Chvostek’s and Trousseau’s sign. Laboratory assessment was consistent with profound hypocalcaemia. This was believed to be due to hungry bone syndrome secondary to advanced prostate cancer. He was treated with intravenous calcium, vitamin D and calcitriol. He also received three doses of radium(223) therapy. After therapy, hypocalcaemic episodes resolved. Follow-up after 2.5 years showed continued resolution of hypocalcaemia.

Aim. To present a case of Graves’ disease complicated by methimazole induced agranulocytosis treated with therapeutic plasma exchange (TPE) and review of the literature. Case Presentation. A 21-year-old patient with a history of Graves’ disease presented to the endocrine clinic. His history was significant for heat intolerance, weight loss, and tremors. Upon examination he had tachycardia, smooth goiter, thyroid bruit, and hyperactive reflexes. He was started on methimazole and metoprolol and thyroidectomy was to be done once his thyroid function tests normalized. On follow-up, the patient symptoms persisted. Complete blood count done showed a white blood cell count of 2100 (4000–11,000 cells/cu mm) with a neutrophil count of 400 cells/cu mm, consistent with neutropenia. He was admitted to the hospital and underwent 3 cycles of TPE and was also given filgrastim. He improved clinically and his thyroxine (T4) levels also came down. Thyroidectomy was done. He was discharged on levothyroxine for postsurgical hypothyroidism. Conclusion. Plasmapheresis may be useful in the treatment of hyperthyroidism. It works by removing protein bound hormones and also possibly inflammatory cytokines. Further studies are needed to clarify the role of various modalities of TPE in the treatment of hyperthyroidism.

Cushing syndrome secondary to ectopic Adrenocorticotrophic (ACTH) hormone secretion is an uncommon entity mostly caused by small cell lung cancer or bronchial carcinoids. It can be characterised by absence of classical cushingoid features. Ectopic ACTH syndrome is characterised by severe and progressive hypercortisolemia. Thus, prompt identification and treatment can significantly decrease morbidity in affected patients. A 57-year-old male patient with a history of Stage 4 squamous cell cancer of the lung presented with worsening hyperglycemia and hypokalemia. Physical exam was notable for facial plethora and hypertension. Hormonal testing showed a very high serum cortisol, ACTH and 24 hours urinary free cortisol levels. MRI of the brain was normal. A diagnosis of ectopic ACTH syndrome was confirmed. The patient was started on Ketoconazole and his cortisol levels improved. The patient was discharged and eventually was lost to follow up.

Wernicke’s encephalopathy is a neurological disorder secondary to the deficiency of vitamin B1 (thiamine). The classic symptoms consist of nystagmus, ophthalmoplegia, ataxia and mental status changes.1 Initially, this was described by Carl Wernicke in 1881 as acute haemorrhagic polioencephalitis.2 Wernicke’s encephalopathy is mostly described in association with malnutrition and alcoholism.1 However, it has been increasingly being noted in various other settings. There is also evidence that this may be an underdiagnosed condition as several cases may not manifest the classical triad of symptoms. Prompt diagnosis and treatment are essential as any delay or undertreatment can result in irreversible complications. We report a case of gestational hyperthyroidism causing Wernicke’s encephalopathy. To our knowledge, there have been only four previous cases of gestational hyperthyroidism causing Wernicke’s encephalopathy in the literature.3–7 A 34-year-old G3P2 11-week 6-day-old pregnant female patient presented to the emergency department with a history of confusion, nausea and vomiting. Prior to this, she was admitted a month ago for hyperemesis. At that point, thyroid function tests showed a suppressed thyroid-stimulating hormone (TSH) of 0.01 (0.27–4.2 ng/dL) and high free thyroxine (FT4) of 3.88 (0.9–1.7 ng/dL). Thyroid-stimulating immunoglobulin and thyroid receptor antibody were negative ruling out Graves’ disease. She was diagnosed as having gestational hyperthyroidism and treated with hydration and antiemetics, no thionamides were given; her FT4 trended downwards and she was discharged. Since discharge, she continued to have vomiting, and also developed worsening of her mental status. Although she was prescribed prenatal vitamins, she was unable to take them secondary to persistent vomiting. She had a 30 lb weight loss in the last 1 month. Vitals on admission showed tachycardia of 134 beats/min and a temperature of 98.1. On examination, she was cachectic and had difficulty answering questions. No exophthalmos or thyromegaly was noted. Heart and lung examination was normal except …

Denosumab is a monoclonal antibody directed against the receptor activator of nuclear factor kappa B ligand (RANKL). Denosumab has been shown to reduce the risk of skeletal-related events, including spinal cord compression, pathologic fracture and hypercalcemia of malignancy in patients with bone metastases. Hypocalcemia is a known side effect of denosumab, occurring in an estimated 8-14% of the patients. Here, we present an asymptomatic patient with stage-5 chronic kidney disease and severe hypocalcemia who had received denosumab 1 month earlier.

Diabetes mellitus (DM) and chronic kidney disease (CKD) are intricately intertwined. DM is the most common cause of CKD. Adequate control of DM is necessary for prevention of progression of CKD, while careful management of the metabolic abnormalities in CKD will assist in achieving better control of DM. Two of the key organs involved in glucose production are the kidney and the liver. Furthermore, the kidney also plays a role in glucose filtration and reabsorption. In CKD, monitoring of glycemic control using traditional methods such as Hemoglobin A1c (Hba1c) must be done with caution secondary to associated hematological abnormalities in CKD. With regard to medication management in the care of patients with DM, CKD has significant effects. For example, the dosages of oral and non-insulin anti-hyperglycemic agents often need to be modified according to renal function. Insulin metabolism is altered in CKD, and a reduction in insulin dose is almost always needed. Dialysis also affects various aspects of glucose homeostasis, necessitating appropriate changes in therapy. Due to the aforementioned factors glycemic management in patients with DM and CKD can be quiet challenging.

A 21-year-old male patient presented to the endocrine clinic with a history of congenital hypopituitarism. He had adrenal insufficiency, hypothyroidism and hypogonadism, which were being adequately replaced. At age 4, he was brought to the clinic with failure to thrive and small stature. He had

A 50-year-old female patient with no significant medical history presented with left knee pain. Radiographs of the knee showed a circumferential swelling of the distal femur suggestive of neoplasia. Further evaluation revealed multiple lesions in the left iliac bone and proximal femur. Biopsy was suggestive of a reparative granuloma or an aneurysmal bone cyst. Laboratory assessment showed hypercalcaemia and elevated parathyroid hormone consistent with severe primary hyperparathyroidism. Osseous survey was significant for salt and pepper appearance of the skull. Ultrasound of the neck and (99m)Tc-sestamibi parathyroid scintigraphy localised a left parathyroid adenoma/carcinoma. Parathyroidectomy was successful, and a large parathyroid adenoma was excised. Six months later, the patient was doing fine with her gait returning to normal. On follow-up 2 years later, she had no recurrence of the lesions.

A 27-year-old male patient who presented to the emergency room with complaints of sweating, palpitations, heat intolerance, insomnia and weight loss for the last 3 months. His medical history was significant for hypertension. On examination, he was tachycardic, hypertensive, had tremors of the upper extremities and a smooth goitre with a thyroid bruit. Laboratory assessment revealed a suppressed thyroid-stimulating hormone, high free thyroxine and positive thyroid receptor antibodies. Complete blood count showed pancytopenia. As part of the work-up for pancytopenia, haptoglobin, ferritin, Coombs test, reticulocyte count hepatitis B and C antibodies were done, all of which were normal. Patient was started on methimazole, propranolol and hydrocortisone. His symptoms improved through the hospital course and he was subsequently discharged. Thyroidectomy was done once the patient’s hyperthyroidism was controlled. Levothyroxine was started for the control of postsurgical hypothyroidism. Six months after thyroidectomy, the patient was euthyroid and the pancytopenia resolved.

To the Editor: Magnetic resonance imaging (MRI) is the preferred imaging modality to evaluate pituitary tumors; however a normal MRI scan has to be interpreted with caution. We present a case of pituitary germinoma with a normal MRI at presentation. A 15-y-old boy was evaluated for short stature, polyuria and polydipsia in our clinic. Family history was unremarkable. Patient’s height at 6 y was 105.6 cm (5th percentile), at 13 y 128.75 cm (3rd percentile) and, at 15 y was 133.1 cm (

Background Congenital unilateral absence of the vas deferens occurs in 0.5%–1.0% of males. It has been associated with various genitourinary abnormalities, including renal agenesis. We report a case of congenital unilateral absence of the vas deferens found incidentally during vasectomy in a patient with known unilateral renal agenesis. Case presentation A 24-year-old male presented to our urology clinic requesting vasectomy. His past history was significant for left renal agenesis. Following successful right vasectomy, several attempts to locate the left vas deferens were unsuccessful. We diagnosed congenital unilateral absence of the vas deferens. Follow-up semen analysis showed azoospermia. Conclusion As vasectomies are increasingly performed in outpatient settings, it is imperative that physicians be aware of this condition, which can be recognized by a simple physical exam. Recognition could prevent unnecessary surgery and prompt providers to investigate for associated abnormalities.