Trends of Diabetes-Related Hospital Admission in Emerging Adults in the State of California

Abstract Background: As adolescents with diabetes transition to adulthood, they may demonstrate poorer adherence to treatment regimens and may be vulnerable to complications such as diabetic ketoacidosis (DKA) or severe hypoglycemia. A number of important factors have been identified as risk factors for these poor outcomes, including loss of health insurance coverage, increased risk-taking behaviors, and difficulty coping with added responsibility. National data may inform efforts to improve health outcomes and prevent complications for vulnerable young adults during this challenging transition to independence. Objectives: To estimate the incidence of diabetes-related admissions and to describe the characteristics among youth and young adults with type 1 (T1D) and type 2 diabetes (T2D) in the state of California. Study design and method: This is a retrospective cohort study using the inpatient database from the Office of Statewide Health Planning and Development during the years 2014 to 2018. Individuals aged 13–24 years hospitalized with DKA, or hypoglycemia, were identified by ICD codes. Results: A total 28,754 admission encounters were recorded. Mean ages for T1D and T2D were 17.3±5.6 years and 17.9±4.6 years, respectively. Hospitalization rates increased with age with a significant rise during the transition to adulthood, from 70.3/100,000 population at age 17 to 132.2/100,000 population at age 19 in T1D. Among hospital admissions in T1D and T2D, 16.3% and 18.7% were Black young adults respectively (p <.001). More young adults were on public insurance when compared to youth (64.1% vs 45.1% in T1D; 68.4% vs 50.4% in T2D, p <.001), and approximately 48.8% and 41.6% were from the lowest income quartile in T1D and T2D respectively (p <.001). There was no difference in mean length of hospital stay, but hospital charges were higher among young adults with both types of diabetes when compared to youth ($41,370 vs$36,160 in T1D; $37,218 vs$30,991 in T2D, p <.001). More young adults were admitted for severe cases such as DKA or hypoglycemia with coma in T1D, with rates tripling from 0.3/100,000 population in youth to 1.0/100,000 population in young adults. Conclusion: We demonstrated a significant rise in admission rates during the transition to adulthood in individuals with T1D. Among admissions in both types of diabetes, there were significantly more Black young adults who were on public insurance with lower socioeconomic status. This population group had poorer health outcomes with higher incidence for moderate and severe complications, and they cost more hospital charges than the youth population with both types of diabetes. Our findings suggest that the US healthcare system fails many emerging adults with diabetes, particularly for people of color, and that improving the medical transition is crucial. More resources should be focused on this at-risk population from a healthcare system perspective

Aortic pulse wave velocity in children with Cushing syndrome: A window into a marker of early cardiovascular disease.

ObjectiveTo investigate early signs of cardiovascular arterial remodelling in paediatric patients with Cushing syndrome (CS) in comparison with normative values from healthy children.Study designThe metrics used to assess cardiac health were from thoracic aorta and carotid MRI. Scans were performed on 18 children with CS (mean: 12.5 ± 3.1 years, range: 6.0-16.8 years, 10 female). Pulse wave velocity (PWV), aortic distensibility (AD) and carotid intima-media thickness (cIMT), well-validated measurements of cardiac compromise, were measured from the images and compared to normative age-matched values where available.ResultsPatients with CS had significantly higher PWV compared to age-adjusted normal median control values (4.0 ± 0.7 m/s vs. 3.4 ± 0.2 m/s, respectively, P = 0.0115). PWV was positively correlated with midnight plasma cortisol (r = 0.56, P = 0.02). Internal and common cIMT were negatively correlated with ascending AD (r = -0.75, P = 0.0022, r = -0.69, P = 0.0068, respectively).ConclusionPulse wave velocity data indicate that paediatric patients with CS have early evidence of cardiovascular remodelling. The results suggest the opportunity for monitoring as these changes begin in childhood

MON-040 11-Oxygenated C19 Steroids in Polycystic Ovarian Syndrome

Abstract BACKGROUND: Polycystic ovarian syndrome (PCOS), an endocrine and reproductive disorder consisting of hyperandrogenism, menstrual dysfunction and ovarian changes, affects 6–20% of reproductive aged women worldwide. While hyperandrogenemia is traditionally determined by evidence of elevated testosterone (T), this hormone can be difficult to accurately measure in women with relatively lower circulating levels compared to men. Recent studies have suggested that four adrenal androgens known as 11-oxygenated C19 steroids (11OxyAs), specifically 11-ketotestosterone (11KT), may be good alternative markers for hyperandrogenism in PCOS. Using a multiethnic population seeking evaluation for PCOS symptomatology, we sought (1) to investigate the utility of 11OxyAs to differentiate women with and without NIH PCOS relative to classical androgens such as T, androstenedione (A4) and DHEAS levels, and (2) to evaluate the relationship of 11OxyAs to clinical findings of androgen excess. Methods: Using the University of California, San Francisco PCOS Tissue Bank, serum samples from 131 women seen for a PCOS evaluation were selected sequentially and identified as PCOS or non-PCOS (controls) based on meeting NIH criteria at the time of evaluation. In addition to obtaining gonadotropin and metabolic profiles, classical androgens and 11OxyAs were measured using mass spectrometry. The relationship of these androgens to modified Ferriman-Gallwey (mFG) scores and ovarian morphology were also assessed. Results: Out of 131 women selected, 83 met NIH PCOS criteria at the time of evaluation and 48 did not (controls). Age and BMI did not differ among the two groups. As expected, total T, A4 and LH were all significantly higher in NIH PCOS. A trend towards higher HOMA-IR levels was also seen in NIH PCOS, but this did not reach statistical significance (3±3.9 mg/dL vs. 1.9±1.7 mg/dL, p = 0.12). No difference was seen in all four 11OxyAs between NIH PCOS and controls. Unlike previous studies, we also did not find mean 11KT levels to exceed that of T in both controls (T 393±143 pg/mL vs. 11KT 389±206 pg/mL) and PCOS (T 530±245 pg/mL vs. 11KT 388±201 pg/mL). In addition, no relationship was seen between HOMA-IR and 11β-hydroxyandrostenedione (11OHA4) or 11-ketoandrostenedione (11KA4) levels. Within PCOS, DHEAS and A4 were noted to have a weak but inverse relationship to BMI (r2 0.05 p = 0.05; r2 0.08 p = 0.007), whereas no correlation was seen between any of the four 11OxyAs or T and BMI. Lastly, 11OxyAs, T, and A4 levels did not predict mFG scores or polycystic ovarian morphology. Conclusions: 11OxyAs levels were not statistically higher among women with NIH PCOS compared to at risk women who did not meet NIH criteria. There was no significant relationship between these androgens and mFG scores or ovarian morphology. Further studies are necessary to show the utility of 11OxyAs levels as a marker for hyperandrogenism or metabolic risk

Cushing disease in a patient with nonbullous congenital ichthyosiform erythroderma: lessons in avoiding glucocorticoids in ichthyosis.

Nonbullous congenital ichthyosis erythroderma (CIE) is an autosomal recessive disorder of ineffective keratinization. We present a unique case of a 16-year-old female with CIE who developed Cushing disease (CD) at age 13 with concomitant worsening of her skin disease. After transsphenoidal resection of her pituitary adenoma, she had both resolution of her Cushing symptoms and significantly milder skin manifestations of her CIE. To the best of our knowledge, this is the first reported case of a patient with both CD and CIE, one that is important in demonstrating the role of glucocorticoids in this disorder

Bone mineral density in patients with inherited bone marrow failure syndromes.

BackgroundPatients with inherited bone marrow failure syndromes (IBMFS) may have several risk factors for low bone mineral density (BMD). We aimed to evaluate the prevalence of low BMD in IBMFS and determine the associated risk factors.MethodsPatients with IBMFS with at least one dual-energy X-ray absorptiometry (DXA) scan were evaluated. Diagnosis of each IBMFS, Fanconi anemia (FA), dyskeratosis congenita, Diamond-Blackfan anemia, and Shwachman-Diamond syndrome was confirmed by syndrome-specific tests. Data were gathered on age, height, and clinical history. DXA scans were completed at the lumbar spine, femoral neck, and forearm. BMD was adjusted for height (HAZ) in children (age ≤20 years). Low BMD was defined as a BMD Z-score and HAZ ≤-2 in adults and children, respectively, in addition to patients currently on bisphosphonate therapy.ResultsNine of thirty-five adults (26%) and eleven of forty children (27%) had low BMD. Adults with FA had significantly lower BMD Z-scores than those with other diagnoses; however, HAZ did not vary significantly in children by diagnosis. Risk factors included hypogonadism, iron overload, and glucocorticoid use.ConclusionsAdults and children with IBMFS have high prevalence of low BMD. Prompt recognition of risk factors and management are essential to optimize bone health

ARMC 5 Variants and Risk of Hypertension in Blacks: MH- GRID Study.

Background We recently found that ARMC 5 variants may be associated with primary aldosteronism in blacks. We investigated a cohort from the MH - GRID (Minority Health Genomics and Translational Research Bio-Repository Database) and tested the association between ARMC 5 variants and blood pressure in black s. Methods and Results Whole exome sequencing data of 1377 black s were analyzed. Target single-variant and gene-based association analyses of hypertension were performed for ARMC 5, and replicated in a subset of 3015 individuals of African descent from the UK Biobank cohort. Sixteen rare variants were significantly associated with hypertension ( P=0.0402) in the gene-based (optimized sequenced kernel association test) analysis; the 16 and one other, rs116201073, together, showed a strong association ( P=0.0003) with blood pressure in this data set. The presence of the rs116201073 variant was associated with lower blood pressure. We then used human embryonic kidney 293 and adrenocortical H295R cells transfected with an ARMC 5 construct containing rs116201073 (c.*920T>C). The latter was common in both the discovery ( MH - GRID ) and replication ( UK Biobank) data and reached statistical significance ( P=0.044 [odds ratio, 0.7] and P=0.007 [odds ratio, 0.76], respectively). The allele carrying rs116201073 increased levels of ARMC5 mRNA , consistent with its protective effect in the epidemiological data. Conclusions ARMC 5 shows an association with hypertension in black s when rare variants within the gene are considered. We also identified a protective variant of the ARMC 5 gene with an effect on ARMC 5 expression confirmed in vitro. These results extend our previous report of ARMC 5's possible involvement in the determination of blood pressure in blacks

Pseudohypoaldosteronism type 1 due to novel variants of SCNN1B gene.

UnlabelledAutosomal recessive pseudohypoaldosteronism type 1 (PHA1) is a rare disorder characterized by sodium wasting, failure to thrive, hyperkalemia, hypovolemia and metabolic acidosis. It is due to mutations in the amiloride-sensitive epithelial sodium channel (ENaC) and is characterized by diminished response to aldosterone. Patients may present with life-threatening hyperkalemia, which must be recognized and appropriately treated. A 32-year-old female was referred to the National Institutes of Health (NIH) for evaluation of hyperkalemia and muscle pain. Her condition started in the second week of life, when she was brought to an outside hospital lethargic and unresponsive. At that time, she was hypovolemic, hyperkalemic and acidotic, and was eventually treated with sodium bicarbonate and potassium chelation. At the time of the presentation to the NIH, her laboratory evaluation revealed serum potassium 5.1 mmol/l (reference range: 3.4-5.1 mmol/l), aldosterone 2800 ng/dl (reference range: ≤21 ng/dl) and plasma renin activity 90 ng/ml/h (reference range: 0.6-4.3 ng/ml per h). Diagnosis of PHA1 was suspected. Sequencing of the SCNN1B gene, which codes for ENaC, revealed that the patient is a compound heterozygote for two novel variants (c.1288delC and c.1466+1 G>A), confirming the suspected diagnosis of PHA1. In conclusion, we report a patient with novel variants of the SCNN1B gene causing PHA1 with persistent, symptomatic hyperkalemia.Learning pointsPHA1 is a rare genetic condition, causing functional abnormalities of the amiloride-sensitive ENaC.PHA1 was caused by previously unreported SCNN1B gene mutations (c.1288delC and c.1466+1 G>A).Early recognition of this condition and adherence to symptomatic therapy is important, as the electrolyte abnormalities found may lead to severe dehydration, cardiac arrhythmias and even death.High doses of sodium polystyrene sulfonate, sodium chloride and sodium bicarbonate are required for symptomatic treatment

Bilateral Pheochromocytoma Due to Von Hippel Lindau With Adrenal-Sparing Adrenalectomy in a Child

Abstract Background: More than 40% of pediatric pheochromocytoma or paragangliomas have associated underlying genetic germline mutation. (1) Clinical Case: We present an 8-year-old male who arrived the emergency department with hypertension to 170/115. MRI of the abdomen revealed bilateral well demarcated adrenal masses with central necrosis. Urine metanephrines showed elevated normetanephrine of 15244 µg/24 hr (reference range, 58 - 670 µg/24 hr) and normal urine metanephrines. Urinary vanillylmandelic acid was mildly elevated 35 mg/gCr and homovanillic acid was normal. MIBG scan revealed increased radiotracer activity correlating to the bilateral adrenal masses without evidence of metastasis. Diagnosis of bilateral pheochromocytomas was made. Genetic testing revealed a novel, heterozygous, pathogenic variant of VHL tumor suppressor gene, consistent with Von Hippel-Lindau syndrome. Perioperative blockade was achieved with prazosin, amlodipine, and metoprolol. Due to low likelihood of metastasis in pheochromocytomas due to VHL, adrenal sparing bilateral adrenalectomy was attempted and resulted in 15% sparing of left adrenal gland vs radial bilateral adrenalectomy. (2) Clinical Lessons: 1. Endocrine etiologies of hypertension, although rare, are important causes of hypertension in the pediatric population. 2. Genetic testing prior to surgical intervention could determine surgical course and preservation of adrenals. 3. A multidisciplinary approach to care and referral to a center with experienced surgery, oncology, nephrology, endocrinology, anesthesiology, critical care and genetics is crucial to maximizing outcomes with pheochromocytoma. Reference: 1. NGS in PPGL (NGSnPPGL) Study Group, Toledo RA, Burnichon N, Cascon A, Benn DE, Bayley JP, Welander J, Tops CM, Firth H, Dwight T, Ercolino T, Mannelli M, Opocher G, Clifton-Bligh R, Gimm O, Maher ER, Robledo M, Gimenez-Roqueplo AP, Dahia PL. Consensus Statement on next-generation-sequencing-based diagnostic testing of hereditary phaeochromocytomas and paragangliomas. Nat Rev Endocrinol. 2017 Apr;13(4):233–247. 2. King KS, Prodanov T, Kantorovich V, Fojo T, Hewitt JK, Zacharin M, Wesley R, Lodish M, Raygada M, Gimenez-Roqueplo AP, McCormack S, Eisenhofer G, Milosevic D, Kebebew E, Stratakis CA, Pacak K. Metastatic pheochromocytoma/paraganglioma related to primary tumor development in childhood or adolescence: significant link to SDHB mutations. J Clin Oncol. 2011 Nov 1;29(31):4137–42

Postoperative Diabetes Insipidus and Hyponatremia in Children after Transsphenoidal Surgery for Adrenocorticotropin Hormone and Growth Hormone Secreting Adenomas.

OBJECTIVES: To define the incidence and risk factors of postoperative sodium alterations in pediatric patients undergoing transsphenoidal surgery (TSS) for adrenocorticotropic hormone and growth hormone secreting pituitary adenomas. STUDY DESIGN: We retrospectively reviewed 160 patients ≤18 years of age who had TSS for pituitary adenomas at our institution from 1999 to 2017. Variables included daily serum sodium through postoperative day 10, urine specific gravity, and medications administered. We examined associations between sex, repeat surgery, manipulation of the posterior pituitary (PP), tumor invasion into the PP, tumor type and size, cerebrospinal fluid (CSF) leak, lumbar drain insertion, body mass index, puberty, and development of diabetes insipidus (DI) or syndrome of inappropriate antidiuretic hormone secretion (SIADH). RESULTS: Mean age was 12.9 ± 3.4 years (female = 81). Patients had adrenocorticotropic hormone (150/160) and growth hormone (10/160) producing adenomas. Forty-two (26%) patients developed DI. Among the 37 of 160 who required desmopressin acutely, 13 of 37 required it long term. Risk of long-term need for desmopressin was significantly higher in patients who had CSF leak 9 of 48 (P = .003), lumbar drain 6 of 30 (P = .019), manipulation 11 of 50 (P < .001), or invasion 4 of 15 (P = .022) of the PP. Sixty patients developed hyponatremia, 19 because of SIADH, 39 to hypotonic fluids and 2 to cerebral salt wasting syndrome. Patients with SIADH were placed on fluid restriction; 1 received salt tablets. CONCLUSIONS: Among 160 children who underwent TSS for pituitary adenomas, the incidence of DI and SIADH after TSS was 26% and 14%, respectively. Combined risk factors for DI and/or SIADH include female sex, manipulation of and/or tumor invasion into the PP, and CSF leak or lumbar drain. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00001595 and NCT00060541