Outcome of pituitary hormone deficits after surgical treatment of nonfunctioning pituitary macroadenomas.

OBJECTIVES: Nonfunctionning pituitary macroadenomas (NFPMA) are benign tumors that cause symptoms of mass effects including hypopituitarism. Their primary treatment is transsphenoidal surgery. We aimed to determine the outcome of pituitary hormone deficits after surgical treatment of NFPMA and to identify factors predicting hormonal recovery. DESIGN: We retrospectively included 246 patients with NFPMA diagnosed and operated in one of the two participating centers. All hormonal axes were evaluated except growth hormone (GH). Postoperative improvement of pituitary endocrine function was considered if at least one hormonal deficit had recovered and a lower total number of deficits was observed 1 year after surgery. RESULTS: 80% (n = 197) of patients had one or more pituitary deficits and 28% had complete anterior hypopituitarism. Besides GH, the gonadotropic and thyrotropic axes were the most commonly affected (68% and 62%, respectively). The number of hypopituitary patients dropped significantly to 61% at 1 year (p < 0.001) and a significant improvement was observed for all hormonal axes, except central diabetes insipidus. Among patients with preoperative hypopituitarism, 88/175 (50%) showed improved pituitary function at 1 year. Both hyperprolactinemia at diagnosis and a lower tumor diameter independently predicted favorable endocrine outcome. CONCLUSIONS: Hypopituitarism is present in 80% of patients with NFPMA and nearly half of them will benefit from sustained improvement after surgery. Hyperprolactinaemia at diagnosis and lower tumor dimensions are associated with favorable endocrine prognosis. This supports the option of early surgery in NFPMA patients with pituitary deficits independent of the presence of visual disturbances.

Short-term effects of perindopril-amlodipine vs perindopril-indapamide on blood pressure control in sub-Saharan type 2 diabetic individuals newly diagnosed for hypertension: A double-blinded randomized controlled trial.

Poor blood pressure (BP) control contributes to complications in sub-Saharan African (SSA) type 2 diabetic individuals. Experts have advocated the use of combination therapies for effective BP control in these patients. The suggested combinations should include a RAAS antagonist and either a CCB or a thiazide diuretic; however, their efficacy is yet to be established in SSA. We investigated the short-term effects of two combination therapies on BP control in SSA type 2 diabetic individuals. This was a double-blinded randomized controlled trial conducted at the Yaoundé Central Hospital (Cameroon) from October 2016 to May 2017. We included type 2 diabetic patients, newly diagnosed for hypertension. After baseline assessment and 24-hour ABPM, participants were allocated to receive either a fixed combination of perindopril + amlodipine or perindopril + indapamide for 42 days. Data analyses followed the intention-to-treat principle. We included fifteen participants (8 being females) in each group. Both combinations provided good circadian BP control after 6 weeks with similar efficacy. Twenty-four-hour SBP dropped from 144 to 145 mm Hg vs 128 to 126 mm Hg with perindopril-amlodipine and perindopril-indapamide, respectively (P = 0.003 for both groups). Twenty-four-hour DBP dropped from 85 to 78 mm Hg (P = 0.013) vs 89 to 79 mm Hg (P = 0.006) in the same respective groups. No significant adverse effect was reported. A fixed initial combination of perindopril-amlodipine or perindopril-indapamide achieved similar effective BP control after 6 weeks in SSA type 2 diabetic individuals with newly diagnosed hypertension. Therefore, these combinations can be used interchangeably in this indication.

Acute phase ketosis-prone atypical diabetes is associated with a pro-inflammatory profile: a case-control study in a sub-Saharan African population.

BACKGROUND: It is unknown whether inflammation plays a role in metabolic dysfunction on ketosis-prone diabetes (KPD). We aimed to assess the inflammatory profile in sub-Saharan African patients with KPD during the acute ketotic phase as well as during non-ketotic hyperglycemic crises. METHODS: We studied 72 patients with non-autoimmune diabetes: 23 with type 2 diabetes mellitus (T2D), and 49 with KPD, all admitted in hyperglycemic crisis (plasma glucose ≥250 mg/dl). The T2D and KPD groups were matched by sex, age, and Body Mass Index. KPD was sub-classified into new-onset ketotic phase (n = 34) or non-ketotic phase (n = 15). We measured TNF-α, MCP-1, MIP1-α, IL-8, MIP1-ß, and VEGF in the serum of all participants. RESULTS: TNF-α and IL-8 were higher in participants with KPD compared to those with T2D (p = 0.02 TNF-α; p = 0.03 IL-8). TNF-α and IL-8 were also higher in the ketotic phase KPD group compared to the T2D group (p = 0.03 TNF-α; p < 0.001 IL-8) while MIP1-α was lower in people with ketotic phase KPD compared to their T2D counterparts (p = 0.03). MIP1-α was lower in the ketotic phase KPD group compared to the non-ketotic phase KPD group (p = 0.04). MCP-1 was lower in non-ketotic phase KPD compared to T2D (p = 0.04), and IL-8 was higher in non-ketotic phase KPD compared to T2D (p = 0.02). CONCLUSIONS: Participants with KPD had elevated pro-inflammatory cytokines compared to their T2D counterparts. Ketotic phase KPD is associated with a different pro-inflammatory profile compared to non-ketotic phase KPD, and the inflammatory profile appears to be comparable between non-ketotic phase KPD and T2D patients.

Human herpesvirus 8 infection DNA positivity is associated with low insulin secretion: A case-control study in a sub-Saharan African population with diabetes.

BACKGROUND: Viruses have been considered potential triggers for the development of diabetes. This study assessed insulin secretion and insulin sensitivity in human herpesvirus 8 (HHV8)-infected and uninfected sub-Saharan African people with diabetes. METHODS: In all, 173 people with non-autoimmune diabetes were enrolled consecutively: 124 with type 2 diabetes mellitus (T2DM) and 49 with ketosis-prone diabetes (KPD) admitted in hyperglycemic crisis. Those with KPD were further subdivided into those with new-onset ketotic-phase KPD (n = 34) or non-ketotic phase KPD (n = 15). All participants were screened for HHV8-specific antibodies and genomic DNA. Blood samples were collected for analysis of fasting glucose, HbA1c, lipid profile, and C-peptide, with insulin resistance and secretion estimated by homeostasis model assessment. RESULTS: Among the 173 diabetic participants, 88 (50.9%) were positive for HHV8 antibodies (Ac-HHV8+), including 15 (8.7%) positive for HHV8 DNA (DNA-HHV8+). The seroprevalence of HHV8 was similar between T2DM (55.6%) and KPD (61.2%) subjects. Of those with and without ketotic-phase KPD, 35.3% and 46.7% were Ac-HHV8+, respectively. Body mass index was significantly in lower DNA-HHV8+ than DNA-HHV8- subjects. Low-density lipoprotein and total cholesterol were significantly higher, but C-peptide and homeostatic model assessment of ß-cell function (HOMA-ß) were significantly lower in DNA-HHV8+ than DNA-HHV8- participants. After excluding DNA-HHV8+ participants, triglyceride concentrations were significantly higher in Ac-HHV8+ (n = 73) than Ac-HHV8- (n = 85) subjects. In contrast, HOMA-ß was significantly higher among Ac-HHV8+ than Ac-HHV8- participants. CONCLUSIONS: In the present study, HHV8 DNA positivity was associated with low insulin secretion in this sub-Saharan African diabetes population.

Acute glycaemic effects of co-trimoxazole at prophylactic dose in healthy adults.

BACKGROUND: Cases of severe hypoglycaemia were reported in HIV/AIDS patients receiving high dose of the sulfonylurea co-trimoxazole for opportunistic infections. Whether co-trimoxazole at prophylactic dose would induce similar side effects is unknown. We aimed to investigate the acute effects of co-trimoxazole at prophylactic dose on glucose metabolism in healthy adults. METHODS: We enrolled 20 healthy volunteers (15 males and 5 females) aged 23.0 (SD 2.0) years, with mean BMI of 22.3 (SD 3.6) Kg/m2 with normal glucose tolerance, hepatic and renal function. We performed a 75-g oral glucose tolerance test (OGTT) with and without concomitant oral co-trimoxazole administered 60 min before the test. Blood glucose response was measured using a capillary test at baseline and at 30, 60, 90, 120 and 180 min following oral glucose load on the two occasions. C-peptide response was also measured. Absolute values of blood glucose and C-peptide with and without co-trimoxazole were compared using the Wilcoxon test. RESULTS: During the OGTT without co-trimoxazole (control) vs. the OGTT with co-trimoxazole (test), the glycaemia varied from 4.83 (SD 0.39) mmol/l vs. 4.72 (SD 0.28) mmol/l at T0 (P = 0.667), to 8.00 (SD 1.11) mmol/l vs. 7.44 (SD 0.78) mmol/l at T30 (P = 0.048), 8.00 (SD 1.17) mmol/l vs. 7.67 (SD 1.00) mmol/l at T60 (P = 0.121), 7.33 (SD 0.94) mmol/l vs. 7.11 (SD 0.83) mmol/l at T90 (P = 0.205), 6.78 (SD 1.00) mmol/l vs. 6.67 (SD 1.00) mmol/l at T120 (P = 0.351) and 4.72 (SD 1.39) mmol/l vs. 4.72 (SD 1.56) mmol/l at T180 (P = 0.747). The ratio of area under the glycaemia curve during the control and test investigation was 96.7 %, thus a 3.3 decreased glycaemic response (p = 0.062). A decrease of glycaemia by more than 10 % occurred in 6/20 participants at T30, 7/20 participants at T60 and 1/20 participant at T30 and T60. None of the volunteers experienced co-trimoxazole-induced hypoglycaemia. At the same time, the C-peptide response during the control vs. the test investigation varied from 278.1 (SD 57.5) pmol/l vs. 242.8 (SD 42.5) pmol/l at T0 (P = 0.138), to 1845.6 (SD 423.6) pmol/l vs. 2340.6 (SD 701.3) pmol/l at T60 (P = 0.345) and 1049.8 (SD 503.1) pmol/l vs. 1041.63 (SD 824.21) pmol/l at T180 (P = 0.893). CONCLUSION: Ninety minutes after its administration, co-trimoxazole induced a significant reduction of the early glycaemic response to oral glucose in parallel with a 27-% increase in insulin secretory response. Co-trimoxazole induced within 120 min a more than 10-% blood glucose reduction in 2/3 of participants. However none of the volunteers experienced hypoglycaemia.