A Challenging Case of Diabetes in a Patient With XXYY Syndrome.

48 XXYY syndrome is a rare polyploidy often compared with Klinefelter syndrome because of shared features such as tall stature, neurocognitive diseases, hypogonadism, and cardiac malformations. This population is believed to be predisposed to type 2 diabetes because of the presence of hypogonadism and central adiposity. We present a patient with XXYY syndrome who had an atypical and difficult-to-manage diabetes presentation. The patient was nonadherent to medication regimen with poorly controlled diabetes and hemoglobin A1c ranging from 12% to 14% (16.5-19.6 mmol/L). He lacked history of diabetes ketoacidosis, raising the question of maturity-onset diabetes of the young. Workup was negative for glutamic acid decarboxylase-65 and pancreatic islet cell antibody testing. Genetic testing for 5-gene panel for maturity-onset diabetes of the young was also negative. Distinct parts of his presentation make an accurate diabetes diagnosis very challenging. Clinicians should be aware of diabetes associations in patients with XXYY syndrome for optimization of care.

A Sweet Paradox: Severe Insulin Resistance and Hyperglycemia in Asymptomatic COVID-19 Infection.

There is a well-established association between hyperglycemia and severe coronavirus disease 2019 (COVID-19) infection, regardless of the diagnosis of diabetes prior to the infection. However, it is unusual for patients with a mild infection to present with severe hyperglycemia and insulin resistance requiring intravenous insulin therapy. Uncontrolled hyperglycemia is associated with worse outcomes in COVID-19, making it crucial to achieve optimal glycemic control, which occasionally requires IV insulin therapy. We report a patient with type 1 diabetes mellitus (T1DM), on hemodialysis, who presented with diabetic ketoacidosis (DKA) due to non-adherence to insulin. He was found to be incidentally positive for COVID-19 on admission. Although he was asymptomatic and did not require steroids for the treatment of COVID-19, he was noted to have persistent severe hyperglycemia requiring unusually high levels of intravenous insulin. This proposes that even a mild infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can trigger a systemic response that can lead to downstream manifestations including insulin resistance and severe hyperglycemia. Interestingly, our patient had three admissions within the past six months as well as another admission two weeks after the current presentation with DKA secondary to insulin non-compliance, all of which required IV insulin for <24 hours following which he was transitioned to a basal-bolus insulin regimen with well-controlled glucose levels.

Giant Prolactinoma Presenting With Facial Nerve Palsy and Hemiparesis.

BACKGROUND: Giant prolactinomas are an exceedingly uncommon type of pituitary adenomas that usually occur in men, and cause extremely high prolactin levels and mass-related symptoms. Rarely, patients may experience neurological deficits resembling ischemic events. METHODS: We describe an unusual case of a young man who presented with stroke-like symptoms and was found to have a giant prolactinoma. CLINICAL CASE: A 25-year-old man presented with left facial droop and gradually progressing upper and lower extremity weakness for evaluation of stroke. He reported recent weight gain and erectile dysfunction. Physical examination revealed left homonymous hemianopsia, left VII nerve palsy, and left hemiparesis. Magnetic resonance imaging of the brain showed an enormous mass in the sella turcica, which invaded the sphenoid sinus and right side of the skull base. Prolactin level was elevated at 13 580 ng/mL, and the testosterone level was low. The patient was started on cabergoline and had marked improvement in his symptoms in a few months. Fifteen months after starting treatment, he has had more than 90% reduction in tumor volume and a 93% reduction in prolactin level. CONCLUSION: Giant prolactinomas are uncommon and present with compressive symptoms that can be mistaken for a stroke. Our case is a unique report of a facial nerve palsy and hemiparesis secondary to giant prolactinoma in the absence of stroke or pituitary apoplexy.

PROINSULIN-PREDOMINANT PANCREATIC NEUROENDOCRINE TUMOR-INDUCED HYPOGLYCEMIA AFTER ROUX-EN-Y GASTRIC BYPASS SURGERY.

OBJECTIVE: To present a case of recurrent hypoglycemia following Roux-en-Y gastric bypass (RYGB) surgery whose etiology was determined to be a proinsulin-predominant pancreatic neuroendocrine tumor (a proinsulinoma). METHODS: A case report along with a brief discussion and review of the pertinent literature is presented. RESULTS: The patient is a 62-year-old female who presented with symptomatic hypoglycemia 11 years after RYGB surgery. Initial workup revealed low insulin levels with elevated proinsulin levels. A 72-hour fast confirmed the presence of proinsulin-induced hypoglycemia secondary to a pancreatic neuroendocrine tumor (PNET). She underwent distal pancreatectomy with splenectomy and a PNET tumor was successfully removed with resolution of her symptoms. CONCLUSION: Hypoglycemia after RYGB surgery is a well-established syndrome. While there are several etiologies for this, PNETs (including proinsulinomas) should be considered in the differential diagnosis in this population. Proinsulinomas are an increasingly recognized cause of hypoglycemia. Proinsulin levels must always be included as part of the workup of hypoglycemia in an adult.

Serum sclerostin levels negatively correlate with parathyroid hormone levels and free estrogen index in postmenopausal women.

CONTEXT: Sclerostin is a negative regulator of bone formation. OBJECTIVE: The aim of the study was to compare serum sclerostin levels in premenopausal and postmenopausal women and evaluate its relationship to estrogen, TH, bone turnover, and bone mass. DESIGN, SETTING, AND PARTICIPANTS: We conducted a cross-sectional observational study of healthy community-dwelling pre- and postmenopausal women. INTERVENTION(S): There were no interventions. MAIN OUTCOME MEASURE(S): We compared serum sclerostin levels in pre- and postmenopausal women and correlated sclerostin levels with female sex hormones, calciotropic hormones, bone turnover markers, and bone mineral density. RESULTS: Premenopausal women were 26.8 yr old, and postmenopausal women were 56.8 yr old. Postmenopausal women had lower values for estradiol (30 +/- 23 vs. 10 +/- 4 pg/ml; P < 0.001), estrone (61 +/- 24 vs. 29 +/- 10 pg/ml; P <0.001), and free estrogen index (FEI) (6 +/- 4 vs. 3 +/- 2 pmol/nmol; P = 0.008) and significantly lower bone mineral density at all sites compared to premenopausal women, with no significant differences in levels of PTH, 25-hydroxy or 1,25-dihydroxy vitamin D levels. Postmenopausal women had significantly higher serum sclerostin levels (1.16 +/- 0.38 ng/ml vs. 0.48 +/- 0.15 ng/ml; P < 0.001). Because most of the premenopausal women were on oral contraceptives, subsequent analyses were limited to postmenopausal women. There were significant negative correlations between sclerostin and FEI and sclerostin and PTH in this group. Using multiple regression analysis, both FEI (beta = -0.629; P = 0.002) and PTH (beta = -0.554; P = 0.004) were found to be independent predictors of sclerostin levels in postmenopausal women. CONCLUSIONS: Our findings suggest that serum sclerostin levels are regulated by both estrogens and PTH in postmenopausal women. These findings need to be explored further in larger prospective studies.

Effects of estradiol and the angiotensin II receptor blocker irbesartan on vascular function in postmenopausal women.

OBJECTIVE: Estradiol and angiotensin receptor blockers have prominent effects on the renin-angiotensin-aldosterone system. The purpose of this study was to determine whether irbesartan, an angiotensin receptor blocker, has a greater effect on vascular function when combined with estradiol, compared with irbesartan alone, in hypertensive postmenopausal women. DESIGN: Fifty-one women were studied while off any antihypertensive medications or hormone therapy at baseline and after randomization to one of four treatment arms for 12 weeks: (1) irbesartan and estradiol, (2) irbesartan and placebo, (3) estradiol and placebo, and (4) placebo/placebo. Estradiol and placebo arms served as control groups. Blood pressure, brachial reactivity, aldosterone, insulin, glucose, 24-hour urinary catecholamines, urinary sodium, and creatinine were measured. Fisher's exact test was used for comparison of differences in blood pressure in the treatment arms. Paired t test and analysis of variance were also performed for within- and between-group analysis. RESULTS: A significantly larger number of women in the irbesartan and estradiol group had a decrease of 5 mm Hg or more in both systolic and diastolic blood pressures (P < 0.05) compared with irbesartan alone group. Forearm vascular reactivity was increased significantly compared with baseline (P < 0.05), and there was a significant decrease in the serum aldosterone level after treatment compared with baseline (P < 0.05) in the irbesartan and estradiol combination group. Fasting glucose and insulin, urinary sodium/creatinine ratio, and catecholamines were similar at each time point. CONCLUSIONS: The results suggest that irbesartan and estradiol, when used in combination, may cause a greater lowering of blood pressure in postmenopausal hypertensive women. This effect may be mediated via increased vasodilation and lower aldosterone levels. These results warrant further testing in larger clinical trials.

Bone health and aging: implications for menopause.

Osteoporosis is one major health condition that contributes to excess morbidity and mortality in women after menopause. In the past, hormone therapy (HT) was prescribed commonly for symptoms of menopause, and there was also evidence that HT protected against osteoporosis. Recently, however, the overall health risks have been reported to exceed benefits, with the beneficial effects seen only in the decreased incidence of hip fractures and colon cancer. The role of HT in menopausal women is unclear at this time, although many women may require it to reduce menopausal symptoms. Osteoporosis may be an area where the benefit of using HT may outweigh the risks in a select group of women. Further, because lower than usual doses of estrogen have been shown to reduce menopausal symptoms and to protect bone, additional research will likely expand physicians' current knowledge of the use of HT in menopausal women. This article reviews the use of low-dose estrogen to promote bone health in postmenopausal women.