Patient Characteristics, Disease Burden, Treatment Patterns and Outcomes in Patients with Acromegaly: Real-World Evidence from the Malaysian Acromegaly Registry.

Objective: This study aims to report the demographic features of patients with acromegaly, the disease burden, and the corresponding treatment patterns and outcomes in Malaysia. Methodology: This is a retrospective study that included patients from the Malaysian Acromegaly registry who were diagnosed with acromegaly from 1970 onwards. Data collected included patient demographics, clinical manifestations of acromegaly, biochemical results and imaging findings. Information regarding treatment modalities and their outcomes was also obtained. Results: Registry data was collected from 2013 to 2016 and included 140 patients with acromegaly from 12 participating hospitals. Median disease duration was 5.5 years (range 1.0 - 41.0 years). Most patients had macroadenoma (67%), while 15% were diagnosed with microadenoma. Hypertension (49.3%), diabetes (37.1%) and hypopituitarism (27.9%) were the most common co-morbidities for patients with acromegaly. Majority of patients had surgical intervention as primary treatment (65.9%) while 20.7% were treated medically, mainly with dopamine agonists (18.5%). Most patients had inadequate disease control after first-line treatment regardless of treatment modality (79.4%). Conclusion: This registry study provides epidemiological data on patients with acromegaly in Malaysia and serves as an initial step for further population-based studies.

Aggressive giant prolactinoma: a case report.

BACKGROUND: Managing treatment-resistant aggressive giant prolactinoma can be challenging, as the diagnosis is often complex, and treatment beyond dopamine agonists, surgery, and radiotherapy is limited. CASE PRESENTATION: A 21-year-old Malay woman first presented to our hospital at the age of 16 years with 1-year history of reduced vision and 2 years of amenorrhea. Her baseline prolactin level was 255,894 µIU/mL with secondary hypogonadism, and pituitary magnetic resonance imaging revealed a giant prolactinoma (2.8 × 3.2 × 4.2 cm3) with suprasellar extension and optic chiasmal compression. She was initially treated with cabergoline, and reductions in the prolactin level and tumor mass were achieved, leading to vision improvement and resumption of normal menstruation. However, she developed recurrent tumor growth and hyperprolactinemia, causing relapse of symptoms, and she needed surgery. Eventually, despite three tumor debulking surgeries and escalation of cabergoline doses up to 1 mg/day, her tumor progressed with aggressive characteristics. Following a multidisciplinary meeting, the patient is initiated on temozolomide therapy after considering the long-term side effects of radiotherapy in her case. CONCLUSION: This case highlights the importance of early identification of treatment-resistant prolactinoma and the need for a multidisciplinary approach in managing aggressive prolactinoma in young patients, particularly regarding timely implementation of temozolomide therapy.

Collision of Two Tumors: A Case Report of a Lung Adenocarcinoma With Metastasis to a Pituitary Adenoma.

A collision tumor involving metastasis to a pituitary adenoma is rare. We describe a case of a 68-year-old Bidayuh woman with underlying treatment-responsive lung adenocarcinoma, who presented with mass effect, panhypopituitarism and polyuria. Her initial imaging study reported pituitary macroadenoma, and she was treated with hormone replacement therapy. She then underwent transsphenoidal tumor debulking surgery with subsequent histopathological findings of a collision tumor of an adenocarcinoma with metastasis to a non-functioning pituitary adenoma.

The Effect of DPP4 Inhibitor on Glycemic Variability in Patients with Type 2 Diabetes treated with twice-daily Premixed Human Insulin.

OBJECTIVE: To evaluate the effect of adding DPP4 inhibitor (DPP4-i) on glycemic variability (GV) in patients with type 2 diabetes mellitus (T2DM) treated with premixed human insulin (MHI). METHODOLOGY: We conducted a prospective study in patients with T2DM on twice-daily MHI with or without metformin therapy. Blinded continuous glucose monitoring was performed at baseline and following 6 weeks of Vildagliptin therapy. RESULTS: Twelve patients with mean (SD) age of 55.8 (13.1) years and duration of disease of 14.0 (6.6) years were recruited. The addition of Vildagliptin significantly reduced GV indices (mmol/L): SD from 2.73 (IQR 2.12-3.66) to 2.11 (1.76-2.55), p=0.015; mean amplitude of glycemic excursions (MAGE) 6.94(2.61) to 5.72 (1.87), p=0.018 and CV 34.05 (8.76) to 28.19 (5.36), p=0.010. In addition, % time in range (3.9-10 mmol/l) improved from 61.17 (20.50) to 79.67 (15.33)%, p=0.001; % time above range reduced from 32.92 (23.99) to 18.50 (15.62)%, p=0.016; with reduction in AUC for hyperglycemia from 1.24 (1.31) to 0.47 (0.71) mmol/day, p=0.015. Hypoglycemic events were infrequent and the reduction in time below range and AUC for hypoglycemia did not reach statistical significance. CONCLUSION: The addition of DPP4-I to commonly prescribed twice-daily MHI in patients with T2DM improves GV and warrants further exploration.

Renin dependent hypertension caused by accessory renal arteries.

BACKGROUND: Hypokalemia in the presence of hypertension is often attributed to primary hyperaldosteronism as a cause of secondary hypertension, however secondary hyperaldosteronism may present similarly. Accessory renal arteries are variants in the vascular anatomy which are often thought to be innocuous but in some circumstances can cause renovascular hypertension leading to secondary hyperaldosteronism. CASE PRESENTATION: We report 2 cases of hypertension with secondary hyperaldosteronism associated with accessory renal arteries. Both patients presented with hypokalemia and further investigations revealed hyperaldosteronism with unsuppressed renin levels. Imaging studies showed the presence of accessory renal artery. CONCLUSION: Accessory renal arteries are a potential cause renovascular hypertension which can be detected via CT angiography or magnetic resonance angiography. Hormonal evaluation should be undertaken to determine whether its presence contributes to hypertension in the patient as targeted treatment such as aldosterone antagonist can be initiated. Surgical intervention or renal denervation may be considered in resistant cases.

Preserved glucagon-like peptide-1 responses to oral glucose, but reduced incretin effect, insulin secretion and sensitivity in young Asians with type 2 diabetes mellitus.

OBJECTIVE: Youth onset type 2 diabetes mellitus (YT2DM) is a globally rising phenomenon with substantial Asians representation. The understanding of its pathophysiology is derived largely from studies in the obese African-American and Caucasian populations, while studies on incretin effect are scarce. We examined the insulin resistance, ß-cell function (BC), glucagon-like peptide (GLP)-1 hormone and incretin effect in Asian YT2DM. RESEARCH DESIGN AND METHODS: This case-control study recruited 25 Asian YT2DM and 15 healthy controls, matched for gender, ethnicity and body mass index. Serum glucose, insulin, C peptide and GLP-1 were sampled during 2-hour oral glucose tolerance tests (OGTTs) and 1-hour intravenous glucose tolerance tests (IVGTTs). Insulin sensitivity was derived from the Quantitative Insulin Sensitivity Check Index (QUICKI), Oral Glucose Insulin Sensitivity Index (OGIS) in OGTT and surrogate index of SI from the minimal model (calculated SI, CSI). Acute insulin response (AIR) was obtained from IVGTT. Total BC was computed as incremental area under the curve of insulin/incremental area under the curve of glucose, during OGTT (BCOG) and IVGTT (BCIV), respectively. Disposition index (DI) was calculated using the product of insulin sensitivity and insulin secretion. GLP-1 response to oral glucose was calculated as incremental area under the curve of GLP-1 (ΔAUCGLP-1). Per cent incretin effect was estimated as 100×(BCOG-BCIV)/BCOG). RESULTS: The YT2DM had marked impairment in BC (>80% reduction in AIR and BCOG, p<0.001) and lower QUICKI (p<0.001), OGIS (p<0.001) and CSI (p=0.015) compared with controls. There was no difference in GLP-1 at all time points and ΔAUCGLP-1 but the per cent incretin effect was reduced in the YT2DM compared with controls (12.1±8.93 vs 70.0±4.03, p<0.001). CONCLUSIONS: Asian YT2DM showed similar GLP-1 response to oral glucose as controls but reduced incretin effect, BC and insulin sensitivity. The lack of compensatory mechanisms, as shown by the DI may be partly ascribed to the impaired incretin effect, similar to that of adult T2DM. TRIAL REGISTRATION NUMBER: NMRR-12-1042-13254.