On Primary Adrenal Insufficiency with Normal Concentrations of Cortisol - Early Manifestation of Addison's Disease.

Primary adrenal insufficiency (AI) is an endocrine disorder in which hormones of the adrenal cortex are produced to an insufficient extent. Since receptors for adrenal steroids have a wide distribution, initial symptoms may be nonspecific. In particular, the lack of glucocorticoids can quickly lead to a life-threatening adrenal crisis. Therefore, current guidelines suggest applying a low threshold for testing and to rule out AI not before serum cortisol concentrations are higher than 500 nmol/l (18 µg/dl). To ease the diagnostic, determination of morning cortisol concentrations is increasingly used for making a diagnosis whereby values of>350 nmol/l are considered to safely rule out Addison's disease. Also, elevated corticotropin concentrations (>300 pg/ml) are indicative of primary AI when cortisol levels are below 140 nmol/l (5 µg/dl). However, approximately 10 percent of our patients with the final diagnosis of primary adrenal insufficiency would clearly have been missed for they presented with normal cortisol concentrations. Here, we present five such cases to support the view that normal to high basal concentrations of cortisol in the presence of clearly elevated corticotropin are indicative of primary adrenal insufficiency when the case history is suggestive of Addison's disease. In all cases, treatment with hydrocortisone had been started, after which the symptoms improved. Moreover, autoantibodies to the adrenal cortex had been present and all patients underwent a structured national education program to ensure that self-monitored dose adjustments could be made as needed.

DHEAS and Differential Blood Counts as Indirect Signs of Glucocorticoid Excess in Adrenal Non-Producing Adenomas.

The majority of incidentally discovered adrenal tumors are later characterized as non-producing adrenocortical adenomas (NPA). We asked whether laboratory abnormalities in parameters that reflect glucocorticoid action can be found in patients with NPA despite their nature of being clinically unapparent. Since glucocorticoids are potent immunosuppressants we studied blood counts and differential blood counts along with corticotropin and dehydroepiandrostenedione sulfate (DHEAS) blood concentrations, as well as cortisol values before and after an overnight 1 mg dexamethasone suppression test. We compared the results of normal individuals, of patients with adrenal adenomas and normal hormone profiles and with subclinical autonomous glucocorticoid hypersecretion, as well as overt cortisol excess. We found that almost all indices of the blood counts were significantly different between the patients groups. In particular, patients with adrenal non-producing adenomas already showed signs of glucocorticoid excess, including relative lymphocytopenia, lowered DHEAS, and ACTH concentrations than control individuals. We also found that the extent of lymphocytopenia correlated with the concentrations of DHEAS and ACTH, and DHEAS correlated well with ACTH. We conclude that the basal ACTH and DHEAS values along with the differential blood counts give good information on the extent of glucocorticoid excess and that silent adrenal adenomas seem to oversecrete glucocorticoids at concentrations that already alter these parameters.

Biomechanics of the osteoporotic spine, pain, and principles of training.

INTRODUCTION: A fracture is a clinical manifestation of osteoporosis and is one of the main causes of functional limitations and chronic pain in patients with osteoporosis. Muscle and coordination training are recommended to the patients as general measures. We inquired whether sling training is better than traditional physiotherapy in relieving pain and improving abilities of daily living. METHODS: Fifty patients with osteoporosis were divided into two groups. Group A performed conventional physiotherapy, while Group B performed sling training exercises. Data were collected before and after the intervention and after 3 months. The registered parameters were stamina, posture, and pain. Posture, torques, and the associated strength of spinal muscles were studied in a biomechanical model in order to estimate the forces acting on the spine. Furthermore, the factors that exerted a positive impact on the success of therapy were registered. RESULTS: Forty-four patients (88%) completed the study. Positive effects of the training were noted in both groups, but significantly better effects were observed in the group that performed sling training. A reduction of pain independent of the number of fractures, significantly reduced torques, and reduced muscle strength were registered. CONCLUSIONS: Specific training programs helped to increase muscle strength and straightening the back thereby reducing the force needed on a permanent basis and decreasing torque in the spine. Sling training was more effective in that than traditional physiotherapy.

Trend of antihyperglycaemic therapy and glycaemic control in 184,864 adults with type 1 or 2 diabetes between 2002 and 2014: Analysis of real-life data from the DPV registry from Germany and Austria.

AIMS: To analyse time trends of antihyperglycaemic therapy and glycaemic control in adult subjects with type 1, or type 2 diabetes between 2002 and 2014 in Germany/Austria. METHODS: 184,864 adults with diabetes (35,144 type 1 diabetes (T1D), 149,720 type 2 diabetes (T2D)) from the DPV-database documented between 2002 and 2014 were included. Regression models were applied for antihyperglycaemic therapy in T2D (non-pharmacological, OADs only, insulin±OADs), insulin therapy in T1D (CT, ICT, CSII) and T2D (BOT, SIT, CT, ICT, CSII), for the use of insulin analogues, and for glycaemic control (HbA1C, severe hypoglycaemia), adjusting for confounders sex, age, and diabetes duration. RESULTS: In T1D, CT (2002:19.7%; 2014:16.0%) and ICT (2002:66.8%; 2014:52.4%) decreased, while CSII increased from 13.5% to 31.5%. In T2D, non-pharmacological treatment became less frequent (2002:36.0%, 2014:21.8%), the use of OADs (2002:19.3%, 2014:28.9%) and insulin±OADs (2002:44.6%, 2014:49.4%) increased. BOT increased from 7.9% to 18.9%, SIT decreased from 12.0% to 8.3%. ICT slightly increased (2002:44.0%, 2014:45.3%), CT decreased (2002:35.8%, 2014:27.2%). Insulin analogues were used more frequently in T1D (rapid-acting:2002:46.8%, 2014:84.8%; long-acting:2002:26.0%, 2014:54.8%) and in T2D (rapid-acting:2002:26.0%, 2014:43.5%; long-acting:2002:13.7%, 2014:53.6%). Until 2011, HbA1C increased in T1D and T2D, but then decreased again. High variability in the rate of hypoglycaemia was observed. CONCLUSIONS: This observational study indicates an increased use of insulin pumps in T1D. In T2D, non-pharmacological therapy decreased, and insulin therapy, particular as BOT, rose. An increase in the use of rapid- and long-acting insulin analogues was present in both patient-groups. Time trend was less clear in glycaemic control.

Altered bone metabolism and bone density in patients with chronic pancreatitis and pancreatic exocrine insufficiency.

CONTEXT: Due to maldigestion, pancreatic exocrine insufficiency (PEI) in chronic pancreatitis may lead to deficiencies in fat-soluble vitamins, including vitamin D. This may, in turn, can cause disturbances in bone metabolism and reduce bone mineral density. OBJECTIVE: To conduct a prospective study of maldigestion, bone metabolism, and bone mineral density in a group of patients with chronic pancreatitis. METHODS: A total of 50 male patients with proven chronic pancreatitis (36/50 alcohol; 42/50 smokers) were studied. Pancreatic exocrine function was assessed using the fecal elastase-1 test. Blood and urine samples were analyzed for parameters related to pancreatitis, nutrition, endocrine status, and bone metabolism. Bone mineral density was measured with dual-energy X-ray absorption (DXA) and conventional vertebral X-rays. A standardized questionnaire for osteoporosis was given. RESULTS: Twenty-eight of the patients had PEI (fecal elastase-1 <200 µg/g), 25 had bone pain, and 21 had a history of bone fractures. Serum 25-OH-cholecalciferol and urine calcium were decreased and deoxypyridinoline concentrations were increased in urine. Serum calcium, bone-specific alkaline phosphatase, and parathyroid hormone were within normal limits. There was no statistical correlation between three classes of fecal elastase-1 (<100 µg/g; 100-200 µg/g; >200 µg/g) and calcium, 25-OH-cholecalciferol, or deoxypyridinoline. Of the 15 patients who underwent DXA, 5 had normal bone mineral density (T score >-1), 9 had osteopenia (T score from -1 to - 2.5), and 1 had osteoporosis (T score <-2.5). There was a trend toward a correlation between low fecal elastase-1 and low T scores (P=0.065). Low fecal elastase-1 correlated with low bone mineral density in conventional X-rays (P<0.05). Patients receiving pancreatic enzyme replacement therapy (PERT) had significantly higher DXA values (P<0.05). CONCLUSIONS: Patients with chronic pancreatitis have osteoporosis, along with abnormal bone metabolism and reduced bone mineral density as measured by DXA and X-ray. PERT is associated with less osteopathy.

Effects of physical therapy on quality of life in osteoporosis patients - a randomized clinical trial.

SUMMARY: The aim of this prospective randomized single-center study was to investigate whether sling exercise therapy is superior to conventional exercises in osteoporosis patients. BACKGROUND: Patients with osteoporosis frequently experience fractures of the vertebral body, which may cause chronic back pain and other symptoms. These, in turn, may lead to immobilization, muscular atrophy, and restrictions in activities of daily living. The situation can be improved with specific medication and physiotherapy. We explored the effects of a variety of physical treatments on activities of daily living in patients with osteoporosis. METHOD: Fifty patients were randomly allocated to two treatment groups. Group A received traditional physiotherapy (PT) while group B underwent sling exercise therapy (ST). Both treatments were given twice a week for three months. The results of the treatment were registered on the quality of life questionnaire (Qualeffo-41) devised by the International Osteoporosis Foundation. After a further three months with no specific exercise treatment, we again tested all patients in order to draw conclusions about the long-term effects of both types of exercise. RESULTS: Forty-four patients (88%) completed the study. Patients were assigned to small groups (a maximum of 5 patients in each group) and thus received individual attention and motivation. Quality of life was improved in both groups; a significantly greater improvement was registered in patients who performed sling exercises (Global score Qualeffo: p = 0.002). CONCLUSION: The test results confirm the known positive effects of physical therapy on the quality of life of osteoporosis patients, as well as the fact that sling exercises are a sound alternative treatment for this condition.