SERUM MORNING CORTISOL AS A SCREENING TEST FOR ADRENAL INSUFFICIENCY.

Objective: To evaluate the performance of morning serum cortisol (MSC) compared to a 10 mg adrenocortico-tropic hormone (ACTH) stimulation test in the diagnosis of adrenal insufficiency (AI). Methods: A retrospective, cross-sectional analysis of ACTH stimulation tests were conducted. From a total of 312 potentially eligible ACTH stimulation tests, 306 met the inclusion criteria. The population was randomized into 2 groups: test (n = 159) and validation (n = 147). In the test group, the receiver operating characteristics curve test evaluated the diagnostic performance of MSC. Results: A subnormal cortisol response to ACTH was found in 25.8% of the test group. The area under the curve values of MSC to predict AI at +30 minutes, +60 minutes, or at maximal cortisol response were 0.874, 0.897, and 0.925 (95% confidence interval [CI] 0.81 to 0.92, 0.83 to 0.93, and 0.87 to 0.96). The Youden index was 234.2 mmol/L with a sensitivity of 83.3% (95% CI 65.2 to 94.3%), and a specificity of 89.1% (95% CI 82.4 to 93.9%). Positive and negative predictive values were 64.1% (95% CI 47.1 to 78.8%) and 95.8% (95% CI 90.5 to 98.6%). There was no difference in age, gender, AI prevalence, or mean serum cortisol at +30 or +60 minutes in the validation group; however, a lower mean MSC value was found. Lower sensitivity and specificity values (88.3% and 60%, respectively) were found for the 234.2 mmol/L cutoff value. Conclusion: This study supports the role of MSC as a first-step diagnostic test in patients with clinically suspected AI. The short stimulation test could be omitted in almost half of the cases. Prospective and longitudinal studies to reproduce and confirm the cutoff values proposed are warranted. Abbreviations: ACTH = adrenocorticotropic hormone; AI = adrenal insufficiency; AUC = area under the curve; CI = confidence interval; HPA = hypothalamic pituitary adrenal; ITT = insulin tolerance test; MSC = morning serum cortisol.

Acanthosis nigricans in the knuckles: An early, accessible, straightforward, and sensitive clinical tool to predict insulin resistance.

Any clinical/biochemical marker revealing obesity or diabetes before their appearance is valuable. Insulin resistance (IR) is present in both disorders many years before occurrence. Accordingly, we determined whether acanthosis nigricans (AN) in the knuckles is associated to higher insulin and homeostasis model assessment for estimated insulin resistance (HOMA-IR) index values, and assessed the influence of body-mass index (BMI) and the diagnostic performance of AN in the knuckles to detect IR. In this cross-sectional controlled study, we included men or women, 18 to 23 years old, with or without AN in the knuckles. In 149 cases with AN in the knuckles and 145 controls, fasting insulin was higher in cases (13.45 µU/mL ± 7.8 vs. 8.59 µU/mL ± 3.63, P < .001, respectively). Mean HOMA-IR index was also higher (2.86 ± 1.68 vs. 1.78 ± 0.77, P < .001). A significant increase in fasting insulin and HOMA-IR values between and within BMI groups from normal through obese category was identified in controls and cases. By multivariate regression analysis, cases with normal BMI were significantly associated to a HOMA-IR ≥2.5 (OR = 3.09, CI95% = 1.75-5.48, P = .001). A model of AN in the knuckles, normal BMI, and increased waist circumference allowed identifying 2 out of 3 cases with HOMA-IR index ≥2.5. AN in the knuckles could be addressed with two aims: as an easy, accessible, and costless diagnostic tool suggesting hyperinsulinemia secondary to IR, and, an early marker of IR even in the absence of overweight or obesity.

Metformin Use and Vitamin B12 Deficiency: Untangling the Association.

BACKGROUND: Current evidence linking vitamin B12 deficiency with metformin use is inconsistent. Hence, there is uncertainty regarding the diagnostic approach in this scenario. Furthermore, this possible association has not been studied in the complete spectrum of patients with diabetes. MATERIALS AND METHODS: We conducted a cross-sectional, controlled study with the objective of assessing differences in serum vitamin B12 levels among patients with and without diabetes with different metformin-treatment regimens. A total of 150 participants were recruited: patients with diabetes (group 1: metformin alone ≥850mg/day, group 2: patients with type 2 diabetes naive to treatment and group 3: metformin ≥850mg/day, in addition to any other oral glucose lowering agent or insulin, or both) and without diabetes (group 4: polycystic ovary syndrome or group 5: healthy individuals). Serum vitamin B12, folate levels and complete blood counts were obtained for the entire population. Methylmalonic acid and homocysteine were obtained for patients when vitamin B12 levels were found to be borderline or low. RESULTS: When patients with or without diabetes were compared, no significant difference was found in relation to their vitamin B12 levels (517.62 versus 433.83; P = 0.072). No difference in vitamin B12 levels was found among participants with metformin use and metformin naive participants (503.4 versus 462.3; P = 0.380). CONCLUSIONS: Irrespective of metformin use, no significant difference in the serum levels of vitamin B12 was observed, both in patients with and without diabetes. In the light of the body of evidence and the results of this study, a universal recommendation for vitamin B12 deficiency screening cannot be made.

Tumour-induced Osteomalacia Secondary to a Sarcoma.

Tumour-induced osteomalacia (TIO), is a rare paraneoplasatic syndrome found in >95% of benign tumours that secrete fibroblast growth factor 23 - a phosphaturic circulating hormone. A rare case of a TIO secondary to a sarcoma, in a 21-year old man with history of bone fractures and distinctive physical and biochemical characteristics is presented and discussed.

Osmotic demyelination syndrome as the initial manifestation of a hyperosmolar hyperglycemic state.

Osmotic demyelination syndrome (ODS) is a life-threatening demyelinating syndrome. The association of ODS with hyperosmolar hyperglycemic state (HHS) has been seldom reported. The aim of this study was to present and discuss previous cases and the pathophysiological mechanisms involved in ODS secondary to HHS. A 47-year-old man arrived to the emergency room due to generalized tonic-clonic seizures and altered mental status. The patient was lethargic and had a Glasgow coma scale of 11/15, muscle strength was 4/5 in both lower extremities, and deep tendon reflexes were diminished. Glucose was 838 mg/dL; serum sodium and venous blood gas analyses were normal. Urinary and plasma ketones were negative. Brain magnetic resonance revealed increased signal intensity on T2-weighted FLAIR images with restricted diffusion on the medulla and central pons. Supportive therapy was started and during the next 3 weeks the patient progressively regained consciousness and muscle strength and was able to feed himself. At 6-month follow-up, the patient was asymptomatic and MRI showed no residual damage. In conclusion, the association of ODS with HHS is extremely rare. The exact mechanism by which HHS produces ODS still needs to be elucidated, but we favor a rapid hypertonic insult as the most plausible mechanism.

Pure androgen-secreting adrenal adenoma associated with resistant hypertension.

Pure androgen-secreting adrenal adenoma is very rare, and its diagnosis remains a clinical challenge. Its association with resistant hypertension is uncommon and not well understood. We present an 18-year-old female with a 10-year history of hirsutism that was accidentally diagnosed with an adrenal mass during the evaluation of a hypertensive crisis. She had a long-standing history of hirsutism, clitorimegaly, deepening of the voice, and primary amenorrhea. She was phenotypically and socially a male. FSH, LH, prolactin, estradiol, 17-hydroxyprogesterone, and progesterone were normal. Total testosterone and DHEA-S were elevated. Cushing syndrome, primary aldosteronism, pheochromocytoma, and nonclassic congenital adrenal hyperplasia were ruled out. She underwent adrenalectomy and pathology reported an adenoma. At 2-month followup, hirsutism and virilizing symptoms clearly improved and blood pressure normalized without antihypertensive medications, current literature of this unusual illness and it association with hypertension is presented and discussed.

Efficacy and safety of rosiglitazone plus metformin in Mexicans with type 2 diabetes.

BACKGROUND: Type 2 diabetes is a growing problem in Mexico. The present study was undertaken to evaluate the efficacy and safety of rosiglitazone 2 mg or 4 mg twice daily (bd) in combination with metformin 2.5 g/day in Mexican patients whose type 2 diabetes was inadequately controlled with metformin alone. METHODS: This randomized, double-blind, placebo-controlled study was conducted at four centers in Mexico. A total of 116 patients were randomized to metformin 2.5 g/day plus placebo (n=39), metformin 2.5 g/day plus rosiglitazone 2 mg bd (n=37), or metformin 2.5 g/day plus rosiglitazone 4 mg bd (n=40) for 26 weeks. RESULTS: Mean hemoglobin A(1c) (HbA(1c)) levels decreased significantly from baseline to Week 26 in the rosiglitazone 2 mg bd (-0.7%; p=0.0052) and 4 mg bd (-1.2%; p=0.0008) groups, but increased in the placebo group (+0.3%; p=0.2651). Mean fasting plasma glucose and fructosamine levels also improved significantly with metformin plus rosiglitazone therapy in a dose-ordered manner compared with placebo (p