Etiology-, Sex-, and Tumor Size-Based Differences in Adrenocorticotropin-Dependent Cushing Syndrome.

OBJECTIVE: To examine demographic, clinical, and biochemical differences in patients with adrenocorticotropin (ACTH)-dependent Cushing syndrome (CS) based on etiology, sex, and tumor size. METHODS: This was a single-center study of 211 patients with ACTH-dependent CS followed for 35 years. Patients were stratified into 3 groups based on etiology: Cushing disease (CD)/transsphenoidal surgery, Cushing disease/total bilateral adrenalectomy (CD/TBA), and ectopic ACTH secretion (EAS). Patients were also stratified based on sex and tumor size (nonvisualized, microadenoma, and macroadenoma). RESULTS: CD was the commonest cause of ACTH-dependent CS (190; 90%). Most patients presented in the third decade (median age, 29 years). Clinical features, cortisol, and ACTH were significantly greater in the EAS group. The CD/TBA group had more nonvisualized tumors (22% vs 8%; P = .000) and smaller tumor size (4 vs 6 mm; P = .001) compared with the CD/transsphenoidal surgery group. There was female predominance in CD (2.06:1) and male predominance in EAS (2:1). Men had shorter duration of symptoms (2 years; P = .014), were younger (23 years; P = .001), had lower body mass index (25.1 kg/m2; P = .000), and had more severe disease (low bone mineral density, hypokalemia). Macroadenomas were frequent (46; 24.2%), and ACTH correlated with tumor size in CD (r = 0.226; P = .005). CONCLUSION: Our cohort presented at an earlier age than the Western population with a distinct, but slightly lower, female predilection. Patients with CD undergoing TBA had frequent negative imaging. Men had a clinical profile suggesting aggressive disease. Microadenoma and macroadenoma were difficult to distinguish on a clinicobiochemical basis.

Clinical profile and outcome of patients with acromegaly according to the 2014 consensus guidelines: Impact of a multi-disciplinary team.

AIM: The diagnosis and treatment of acromegaly, a rare and possibly curable disease, has undergone a paradigm shift in the past few decades. Our aim was to study the changing trends in clinical presentation, management and outcome of the disease in the last fifteen years. METHODOLOGY: 271 consecutive patients with acromegaly treated at the Departments of Endocrinology and Neurosurgery, PGIMER, Chandigarh, between 2000 and 2014, were included in the study. Clinical and hormonal profiles, comorbidities, treatment modalities, outcome and mortality data were evaluated. The cure rate was assessed according to the present consensus criteria. RESULTS: The gender distribution was equal with the mean age (±SD) of 37.1 ± 12.3 years at diagnosis. The average lag period to diagnosis was 4.7 ± 4.2 years. The most common presenting manifestations were acral enlargement and headache followed by visual deficits. The overall mortality rate was 5%, with the perioperative mortality being 1.5%. The most prevalent comorbidities in our series were hypertension (17.7%), diabetes mellitus (16.2%), arthropathy (11.8%) and obstructive sleep apnea (10.3%). Overall, 2 patients in our series suffered from extra-pituitary neoplasms and 12 patients had apoplexy as the presenting manifestation. As per the present consensus criteria, cure rate in our series was 28.5%. The cure rate was only 7.9% when many surgeons were operating. It increased to 25.5% when surgeries were being performed by one surgeon exclusively; and, when a sub-specialty clinic exclusively for pituitary diseases was set up, the cure rates improved upto 56%. CONCLUSION: Acromegaly has wide-ranging manifestations from acral enlargement to altered sensorium; incidental diagnosis was not prevalent in our series. Majority of the cases were due to the presence of a pituitary macroadenoma. Better cure rate can be achieved only when a dedicated group of multi-disciplinary team is involved.

Teriparatide (recombinant human parathyroid hormone [1-34]) increases foot bone remodeling in diabetic chronic Charcot neuroarthropathy: a randomized double-blind placebo-controlled study.

BACKGROUND: Currently, there is no consensus regarding the medical treatment of chronic Charcot neuroarthropathy (CN) of foot, except for effective off-loading. Because tarsal bones are predominantly trabecular, teriparatide may improve the macroarchitecture of foot bones in chronic CN. METHODS: People with diabetes and chronic CN were randomized to receive either 20 µg teriparatide or placebo subcutaneous daily for 12 months. Thirty-eight patients were screened and data were analyzed for 20. The maximum standardized uptake (SUVmax ) value of 18 F-FDG PET/CT the region of interest, bone turnover markers and foot bone mineral density BMD were determined. The primary outcome measure was change in SUVmax g/ml. RESULTS: Mid-foot was the most common region involved. After 12 months, SUVmax increased from 30.6 ± 14.7 to 37.7 ± 18.0 (P = 0.044) in the teriparatide group, but decreased from 27.6 ± 12.2 to 22.9 ± 10.4 with placebo (P = 0.148). The estimated treatment difference (ETD) was 11.9 ± 4.3 (95% CI 2.9, 20.8; P = 0.012). Similarly, P1NP increased with teriparatide (19.8 ± 5.5; P = 0.006) but decreased with placebo (-5.1 ± 3.8 ng/mL; P = 0.219); ETD was 24.8 ± 6.6 (95% CI 10.8, 38.8; P < 0.001) and CTX increased in both the teriparatide and placebo groups. Foot BMD increased by 0.06 ± 0.04 g/cm2 (P = 0.192) with teriparatide, but decreased by -0.06 ± 0.08 g/cm2 with placebo (P = 0.488; intergroup comparison, P = 0.096). CONCLUSION: Teriparatide increases foot bone remodeling by an osteoanabolic action in people with CN.

The predictors of recovery from diabetes mellitus following neurosurgical treatment of acromegaly: A prospective study over a decade.

OBJECTIVE: The natural history of glucose intolerance (GI) in patients with acromegaly undergoing surgical treatment has not been fully understood. This study was aimed to unravel the prevalence and predictors of recovery from GI in these patients in a prospective multivariate model. MATERIALS AND METHODS: Patients with acromegaly treated between 2007 and 2016 were prospectively studied with respect to demographics, clinicoradiological features, comorbidities, and hormonal investigations before surgery and at regular follow-up. The independent predictors of recovery from diabetes were analyzed. RESULTS: There were a total of 151 patients with active acromegaly included in the study. The median baseline growth hormone (GH) and insulin-like growth factor (IGF)-1 levels were 25 and 811 ng/mL, respectively. Diabetes mellitus (DM) and pre-diabetes were noted in 93 (61.6%) and 20 (13.2%) patients, respectively. Following surgical treatment, the median HbA1c decreased significantly from 6.4% to 5.5% (P < 0.001), with 46.8% having complete recovery from DM or pre-diabetes. This glycemic recovery had significant association with both biochemical (P = 0.001) and radiological remission (P = 0.01). The recovery from DM had a greater association with post-operative IGF-1 than GH, especially among those with discordant GH and IGF-1 levels (60% in normal IGF-1 and high GH vs. 20% in high IGF-1 and normal GH). Post-operative IGF-1 had a significant impact on recovery from DM (P = 0.01) independent of age, body mass index, duration of DM, and pre-operative HbA1c. CONCLUSION: Nearly half of the patients with acromegaly with DM or pre-diabetes had glycemic recovery, influenced by biochemical and radiologic remission. Post-operative IGF-1 appears to be the strongest independent determinant of recovery from DM.

Impact of post-meal and one-time daily exercise in patient with type 2 diabetes mellitus: a randomized crossover study.

BACKGROUND: To evaluate the effectiveness of short-timed post-meal and one-time daily exercise on glycemic control in patients with T2DM. METHODS: Sixty-four T2DM patients were randomised into crossover design. Group A (n = 32) underwent post-meal exercise (moderate-intensity brisk walking covering 1500-1600 steps for 15 min, starting 15 min after each meal) from d1 to d60 followed by one-time daily exercise (45 min pre-breakfast brisk walking at stretch covering 4500-4800 steps) from d61 to d120, while it was vice versa for the group B (n = 32). The five-point blood glucose profile was performed on d1, d30, d60, d90 and d120, and HbA1c on d1, d60 and d120. Fitness wrist band was used for step-counting to ensure the intensity of exercise and compliance to exercise protocol. RESULTS: Group A patients showed a significant improvement in five point blood glucose profile and HbA1c after performing post-meal exercise (p < 0.001), which was mitigated after switchover to one-time daily exercise (p < 0.001). While, group B patients showed improvement in glucose profile and HbA1c (p < 0.001) after performing post-meal exercise, as compared to one-time daily exercise. Further, on pooled analysis (post-meal versus one-time daily exercise group) the beneficial effect of post-meal exercise on glucose profile and HbA1c was consistent as compared to one time daily exercise and the significance persisted on comparison between the two groups. No hypoglycemic events were noted between the groups during the study period. CONCLUSION: Post-meal exercise is more effective than routine one-time daily exercise for glycemic control in T2DM patients.

The microbiology of diabetic foot infections in patients recently treated with antibiotic therapy: A prospective study from India.

AIM: Clinicians often treat clinically infected diabetic foot ulcers without information from cultures of the wound. The results of wound cultures may also be affected by previous antibiotic therapy. Thus, we aimed to study the microbial isolates, and antimicrobial sensitivity of previously treated patients with a clinically infected DFU. RESEARCH DESIGN AND METHODS: 293 consecutive patients with clinically infected DFU on prior antimicrobial treatment within the immediate past few days for a duration greater than one week were evaluated for microbial etiology, antibiotic sensitivity and final outcomes. Appropriate tissue samples i.e. purulent drainage, soft-tissue and/ or bone were obtained for aerobic/anaerobic cultures and antimicrobial sensitivities. 71 patients with missing prior antibiotic data were excluded. RESULTS: 313 tissue samples obtained from 222 patients isolated 317 causative organisms. Most of the culture results from tissue specimens were mono-microbial (93.2%) compared to 37% in our previous cohort of 60 patients. Pseudomonas aeruginosa was the most common organism isolated on culture of bone (26.9%) or soft tissue (23.2%) specimen, respectively. Only 23% and 64% of P. aeruginosa isolates and 5.6% and 44% of Acinetobacter sp. were sensitive to quinolones and cephalosporins, respectively. CONCLUSIONS: Clinically infected DFU recently treated with antibiotics have predominant monomicrobial and multi drug-resistant infection. Quinolones as an empirical antibiotic choice may not be appropriate in this setting.