Megesterol acetate as an overlooked cause of hyperglycemia in end-stage renal disease: A case of polypharmacy.

OBJECTIVES: This case report highlights an overlooked cause of hyperglycemia and risk of polypharmacy in a patient with end-stage renal disease (ESRD). CASE SUMMARY: A 75-year-old non-English speaking male with T2DM, hypertension, coronary artery disease status post percutaneous coronary intervention, and ESRD secondary to IgG Kappa nephropathy on nightly peritoneal dialysis reported a loss of appetite, decrease in weight, and an increase in symptoms of depression. As a result of these symptoms, his nephrologist initiated megestrol acetate (MA), an agent commonly used in ESRD to help stimulate appetite and improve weight. After starting MA, his blood glucose (BG) significantly worsened, due to its glucocorticoid properties. Basal insulin was started to manage his hyperglycemia, but there was minimal improvement in BG. As the patient was referred to the endocrinology clinical pharmacist for diabetes management, it was identified that his weight loss began after starting dulaglutide, which led to a weight loss of 11 kg (12.9%). The Naranjo algorithm was used, and he had a score of 6, which is a probable reaction. The patient's endocrinology and nephrology teams agreed to discontinue MA and dulaglutide as they resulted in opposing effects on appetite and BG, as well as insulin glargine. The patient's BG was tightly controlled off MA and his appetite, weight, and mood improved off dulaglutide. PRACTICE IMPLICATIONS: This case report reflects the potential effects of polypharmacy in ESRD, resulting in poor patient outcomes and drug interactions. It is imperative that a comprehensive medication reconciliation is completed on all patients, especially for patients on dialysis. It is also important for healthcare professionals to be cognizant of medications that may exhibit glucocorticoid properties, which can cause hyperglycemia. Including a clinical pharmacist in the care team can assist with medication reconciliation, screening for drug interactions and polypharmacy, and optimizing chronic disease management.

Determinants of glucose metabolism and the role of NPY in the progression of insulin resistance in chronic migraine.

Background Chronic migraine has a well-documented association with increased insulin resistance and metabolic syndrome. The hypothalamus may play a role in the progression of insulin resistance in chronic migraine through the regulation of orexigenic peptides such as neuropeptide Y. Insulin resistance may lead to increased risk of future type 2 diabetes mellitus in patients with chronic migraine, which is more likely to occur if other pathogenetic defects of type 2 diabetes mellitus, such as impaired pancreatic ß-cell functions and defects in intestinal glucagon-like peptide-1 secretion after meals. We studied the relationship of fasting neuropeptide Y with insulin resistance, ß-cell function, and glucagon-like peptide-1 secretion in non-obese female chronic migraine patients. We also aimed to investigate glucose-stimulated insulin and glucagon-like peptide-1 secretions as early pathogenetic mechanisms responsible for the development of carbohydrate intolerance. Methods In this cross-sectional controlled study, 83 non-obese female migraine patients of reproductive age categorized as having episodic migraine or chronic migraine were included. The control group consisted of 36 healthy females. We studied glucose-stimulated insulin and glucagon-like peptide-1 secretion during a 75 g oral glucose tolerance test. We investigated the relationship of neuropeptide Y levels with insulin resistance and ß-cell insulin secretion functions. Results Fasting glucose levels were significantly higher in migraine patients. Plasma glucose and insulin levels during the oral glucose tolerance test were otherwise similar in chronic migraine, episodic migraine and controls. Patients with chronic migraine were more insulin resistant than episodic migraine or controls ( p = 0.048). Glucagon-like peptide-1 levels both at fasting and two hours after glucose intake were similar in chronic migraine, episodic migraine, and controls. Neuropeptide Y levels were higher in migraineurs. In chronic migraine, neuropeptide Y was positively correlated with fasting glucagon-like peptide-1 levels (r = 0.57, p = 0.04), but there was no correlation with insulin resistance (r = 0.49, p = 0.09) or ß-cell function (r = 0.50, p = 0.07). Discussion Non-obese premenopausal female patients with chronic migraine have higher insulin resistance, but normal ß-cell function is to compensate for the increased insulin demand during fasting and after glucose intake. Increased fasting neuropeptide Y levels in migraine may be a factor leading to increased insulin resistance by specific alterations in energy intake and activation of the sympathoadrenal system.

The impact of depression and ghrelin on body weight in migraineurs.

BACKGROUND: Comorbidity of migraine with anxiety and depression may play a role in the link between migraine and obesity. We examined the moderating and mediating roles of ghrelin in the relationship between depression (and anxiety) and body weight in newly diagnosed migraineurs. METHODS: Participants were 63 newly diagnosed migraine patients (using the ICHD-II criteria) and 42 healthy volunteers. Body mass index (BMI) was calculated by measuring height and weight. Ghrelin was assessed at fasting. Depression was assessed with the Hamilton Depression scale, and anxiety with the Hamilton Anxiety scale. RESULTS: The data did not support the mediating role of ghrelin in the relationship between depression (or anxiety) and BMI for either the migraine or the control group. The interaction between ghrelin and depression as well as anxiety was significant for the migraine group, but not for the control group. Depressed (or anxious) migraineurs had a positive association between ghrelin and BMI, whereas for the non-depressed (or non-anxious) migraineurs this association was negative. CONCLUSIONS: Depression and anxiety moderated the effect of ghrelin on BMI for migraineurs. Management of anxiety and depression might be regarded as part of migraine treatment.

Type 2 Diabetes Polygenic Score Predicts the Risk of Glucocorticoid-Induced Hyperglycemia in Patients Without Diabetes.

OBJECTIVE: To assess whether increased genetic risk of type 2 diabetes (T2D) is associated with the development of hyperglycemia after glucocorticoid treatment. RESEARCH DESIGN AND METHODS: We performed a retrospective analysis of individuals with no diagnosis of diabetes who received a glucocorticoid dose of ≥10 mg prednisone. We analyzed the association between hyperglycemia and a T2D global extended polygenic score, which was constructed through a meta-analysis of two published genome-wide association studies. RESULTS: Of 546 individuals who received glucocorticoids, 210 developed hyperglycemia and 336 did not. T2D polygenic score was significantly associated with glucocorticoid-induced hyperglycemia (odds ratio 1.4 per SD of polygenic score; P = 0.038). CONCLUSIONS: Individuals with increased genetic risk of T2D have a higher risk of glucocorticoid-induced hyperglycemia. This finding offers a mechanism for risk stratification as part of a precision approach to medical treatment.

Comparison of Pheochromocytoma-Specific Morbidity and Mortality Among Adults With Bilateral Pheochromocytomas Undergoing Total Adrenalectomy vs Cortical-Sparing Adrenalectomy.

Importance: Large studies investigating long-term outcomes of patients with bilateral pheochromocytomas treated with either total or cortical-sparing adrenalectomies are needed to inform clinical management. Objective: To determine the association of total vs cortical-sparing adrenalectomy with pheochromocytoma-specific mortality, the burden of primary adrenal insufficiency after bilateral adrenalectomy, and the risk of pheochromocytoma recurrence. Design, Setting, and Participants: This cohort study used data from a multicenter consortium-based registry for 625 patients treated for bilateral pheochromocytomas between 1950 and 2018. Data were analyzed from September 1, 2018, to June 1, 2019. Exposures: Total or cortical-sparing adrenalectomy. Main Outcomes and Measures: Primary adrenal insufficiency, recurrent pheochromocytoma, and mortality. Results: Of 625 patients (300 [48%] female) with a median (interquartile range [IQR]) age of 30 (22-40) years at diagnosis, 401 (64%) were diagnosed with synchronous bilateral pheochromocytomas and 224 (36%) were diagnosed with metachronous pheochromocytomas (median [IQR] interval to second adrenalectomy, 6 [1-13] years). In 505 of 526 tested patients (96%), germline mutations were detected in the genes RET (282 patients [54%]), VHL (184 patients [35%]), and other genes (39 patients [7%]). Of 849 adrenalectomies performed in 625 patients, 324 (52%) were planned as cortical sparing and were successful in 248 of 324 patients (76.5%). Primary adrenal insufficiency occurred in all patients treated with total adrenalectomy but only in 23.5% of patients treated with attempted cortical-sparing adrenalectomy. A third of patients with adrenal insufficiency developed complications, such as adrenal crisis or iatrogenic Cushing syndrome. Of 377 patients who became steroid dependent, 67 (18%) developed at least 1 adrenal crisis and 50 (13%) developed iatrogenic Cushing syndrome during median (IQR) follow-up of 8 (3-25) years. Two patients developed recurrent pheochromocytoma in the adrenal bed despite total adrenalectomy. In contrast, 33 patients (13%) treated with successful cortical-sparing adrenalectomy developed another pheochromocytoma within the remnant adrenal after a median (IQR) of 8 (4-13) years, all of which were successfully treated with another surgery. Cortical-sparing surgery was not associated with survival. Overall survival was associated with comorbidities unrelated to pheochromocytoma: of 63 patients who died, only 3 (5%) died of metastatic pheochromocytoma. Conclusions and Relevance: Patients undergoing cortical-sparing adrenalectomy did not demonstrate decreased survival, despite development of recurrent pheochromocytoma in 13%. Cortical-sparing adrenalectomy should be considered in all patients with hereditary pheochromocytoma.

LATE-ONSET CHOROIDAL METASTASIS FROM BREAST CANCER.

PURPOSE: Report occurrence of late-onset choroidal metastasis from breast cancer. METHODS: Retrospective chart review. RESULTS: The authors report 3 patients with choroidal metastasis from breast cancer that presented more than 20 years after diagnosis of the primary tumor. The choroidal metastases were the presenting feature of metastatic disease in all three patients, but after imaging, all patients had metastasis elsewhere as well. Two of the patients' tumors were known, ER+, and the hormone receptor status of the third patient was unknown. All three patients were treated with aromatase inhibitors with good response. CONCLUSION: Late onset of metastatic disease, an excellent response to hormonal therapy, and a prolonged survival despite presence of systemic disease suggests a milder variant within the broad category of breast cancer patients with uveal metastases. Awareness of this entity can minimize the risk of misdiagnosis and avoid potentially toxic local therapy.

Anterior Segment Optical Coherence Tomography of the Horizontal and Vertical Extraocular Muscles With Measurement of the Insertion to Limbus Distance.

PURPOSE: To assess the possibility of determining the insertion distance from the limbus of horizontal and vertical extraocular rectus muscles with anterior segment optical coherence tomography (AS-OCT). METHODS: The right eyes of 46 patients underwent AS-OCT. The horizontal and vertical extraocular rectus muscle insertion distances from the limbus were measured in a masked fashion by two pediatric ophthalmologists. RESULTS: Forty-two lateral rectus, 43 medial rectus, 35 inferior rectus, and 40 superior rectus muscles of the right eyes of 46 patients were included. Insertion to limbus measurements (mean ± SD) were as follows: lateral rectus = mean 6.8 ± 0.7 mm, range = 4.8 to 8.4 mm; medial rectus = mean 5.7 ± 0.8 mm, range = 4.3 to 7.8 mm; inferior rectus = mean 6.0 ± 0.6 mm, range = 4.8 to 7.0 mm; superior rectus = mean 6.8 ± 0.6 mm, range = 5.5 to 8.1 mm. The intraobserver and interobserver correlation coefficients for the insertion to limbus measurements of all four rectus muscles exceeded 0.75 (excellent correlation). CONCLUSIONS: The study showed that AS-OCT is capable of imaging all four of the rectus muscle insertions and measuring the insertion to limbus distance, and is the second AS-OCT study to image the superior and inferior rectus muscle insertions. The insertion to limbus measurements between examiners and on repeat measurements were consistent and reproducible. The ability to accurately image extraocular rectus muscle insertions may have future implications for the preoperative procedure planning in patients who have had previous surgery. [J Pediatr Ophthalmol Strabismus. 2016;53(3):141-145.].

The effect of multiple injections of ranibizumab on retinal nerve fiber layer thickness in patients with age-related macular degeneration.

PURPOSE: To evaluate the effects of multiple intravitreal injections of ranibizumab on retinal nerve fiber layer (RNFL) thickness in patients with wet age-related macular degeneration (AMD). METHODS: This observational, comparative study included patients with 10 or more total ranibizumab injections and involved the measurement of RNFL thickness at baseline. Twenty-nine eyes of 29 consecutive patients were evaluated via intraocular pressure (IOP) and measurements of the total and nasal RNFL thicknesses at the initial and final follow-up by using optical coherence tomography. The RNFL thickness values of the fellow eyes and 27 healthy eyes were used as the control group. The mean total and nasal RNFL thicknesses of the injection group were compared with those of the other two groups. At each visit, at every three injections, the IOP values of the study group were recorded and compared. The relationship between the number of injections and the mean RNFL thickness was assessed. RESULTS: The mean number of injections was 13.88 ± 3.81 (10-24). The mean RNFL thickness of the injection group was 92.3 ± 7.7 µm at baseline and 92.46 ± 8.1 µm at the last follow-up (p = 0.7). There were no statistically significant differences between the mean total and nasal RNFL thicknesses of the eyes with injections and the fellow eyes with no injections (p = 0.379, p = 0.897, respectively) or between those with injections and the healthy control group (p = 0.159, p = 0.273, respectively). There were no correlations between the number of injections and the mean total and nasal RNFL thicknesses (p = 0.854, p = 0.25, respectively). There was no statistical difference between the initial and final IOPs (p = 0.760). CONCLUSION: Long-term treatment with anti-vascular endothelial growth factor (VEGF) agents did not lead to significant changes in RNFL thickness in a patient population with wet AMD. Chronic therapy with intravitreal anti-VEGF agents does not appear to adversely affect RNFL thickness.