Are serum thyroid hormone, parathormone, calcium, and vitamin D levels associated with lumbar spine degeneration? A cross-sectional observational clinical study.

PURPOSE: Low back pain (LBP) impairs the quality of life and rises healthcare costs. The association of spine degeneration and LBP with metabolic disorders have been reported, previously. However, metabolic processes related with spine degeneration remained unclear. We aimed to analyze whether serum thyroid hormones, parathormone, calcium, and vitamin D levels were associated with lumbar intervertebral disc degeneration (IVDD), Modic changes, and fatty infiltration in the paraspinal muscles. METHODS: We cross-sectionally analyzed a retrospective database. Patients who visited internal medicine outpatient clinics with suspect of endocrine disorders and chronic LBP were searched. Patients with biochemistry results within 1 week before lumbar spine magnetic resonance imaging (MRI) were included. Age- and gender-matched cohorts were made-up and analyzed. RESULTS: Patients with higher serum free thyroxine levels were more likely to have severe IVDD. They were also more likely to have fattier multifidus and erector spinae at upper lumbar levels, less fatty psoas and less Modic changes at lower lumbar levels. Higher PTH levels were observed in patients with severe IVDD at L4-L5 level. Patients with lower serum vitamin D and calcium levels had more Modic changes and fattier paraspinal muscles at upper lumbar levels. CONCLUSION: Serum hormone, vitamin D, and calcium levels were associated with not only IVDD and Modic changes but also with fatty infiltration in the paraspinal muscles, mainly at upper lumbar levels in patients with symptomatic backache presenting to a tertiary care center. Complex inflammatory, metabolic, and mechanical factors present in the backstage of spine degeneration.

Lumbar intervertebral disc degeneration, end-plates and paraspinal muscle changes in children and adolescents with low-back pain.

The prevalence of low-back pain (LBP) in adolescents ranges from 7 to 72%. We aimed to define the radiologic characteristics of the lumbar spine in children and adolescents with LBP with/without leg pain. Two hundred and fourteen children and adolescents, who were born between 2001 and 2009 and had lumbar spine MRI for LBP with/without leg pain, were evaluated in terms of intervertebral disc degeneration (IVDD), end-plates and paraspinal muscle changes on lumbar spine MRIs. Severe IVDD was detected at all lumbar levels except for L2-L3. Modic changes were present in 4.2% of the patients. Modic changes were more common in patients with severe IVDD than in those with mild-to-moderate IVDD. Severe IVDD was significantly associated with Modic changes at the corresponding L1-L2 and L3-L4 disc levels. Girls had significantly more fatty infiltration in the paraspinal muscles when compared to boys. The risk of having severe IVDD concomitant with Modic changes was high [odds ratio (OR), 8.6]. The OR was 20.7 for predicting the presence of severe IVDD at any level if Modic changes presented particularly at the L3-L4 level. The ORs of Modic changes presented at any lumbar level at the background of fat-infiltrated multifidus at L3-L4 and L4-L5 levels were 8.3 and 9.1, respectively. Fatty infiltration in the paraspinal muscles and IVDD were closely associated with Modic changes in children and adolescents with LBP. Lumbar IVDD in children and adolescents could be the result of a mechanical pathology.

A new radiological index for the assessment of higher body fat status and lumbar spine degeneration.

OBJECTIVE: Obesity has been proposed as a risk factor for low back pain (LBP) and intervertebral disc degeneration (IVDD). Even though body mass index (BMI) is used as a parameter for obesity, it could not represent percentage and distribution of the body fat. Subcutaneous fat tissue thickness (SFTT) was proposed as one of the magnetic resonance imaging (MRI) parameters to evaluate the percentage of the body fat. In this study, we aimed to find out whether SFTT at lower back correlated with LBP and spine degeneration. MATERIALS AND METHODS: We retrospectively reviewed a database of the patients with LBP. Concomitantly, asymptomatic control subjects were retrieved. Patients and control subjects were evaluated in terms of IVDD and Modic changes at all lumbar levels on MRI. SFTT was measured both on MRI and computed tomography (CT) scans, where applicable. RESULTS: SFTT at the lumbar spine had moderate-to-strong correlations with BMI. SFTT at L1-L2 level was significantly associated with severe IVDD at L5-S1 level, and Modic changes at L4-L5 and L5-S1 levels. BMI had no significant association with severe IVDD and Modic changes at lumbar spine. BMI and mean SFTT of all lumbar levels had ORs of 0.735 (95% CI: 0.631-0.857, p < 0.001) and 1.389 (95% CI: 1.266-1.524, p < 0.001) in predicting symptomatic subjects with LBP. CONCLUSION: SFTT at upper lumbar levels could predict severe IVDD and Modic changes better than BMI, specifically in men. SFTT was better than BMI in predicting a symptomatic patient with LBP.

Hormonal and radiologic outcomes after gamma knife radiosurgery for nonfunctioning pituitary adenomas.

BACKGROUND: Gamma knife radiosurgery (GKRS) is an established treatment option for residual and recurrent nonfunctioning pituitary adenoma (NFPA). This investigation assessed hormonal and radiologic outcomes after adjuvant and primary GKRS for NFPAs. METHODS: This retrospective study included 252 patients with NFPA who underwent GKRS at a single center between 2005 and 2016. GKRS was performed as adjuvant procedure in 216 (85.8%) patients and as primary procedure in 36 (14.2%) patients. Characteristics of these two groups were compared. RESULTS: Mean age was comparable between adjuvant and primary GKRS groups (48.3 ± 12.6 vs. 52.2 ± 13.2 years, respectively, p > 0.05). Adjuvant GKRS and primary GKRS groups were similar in terms of the mean prescribed radiation dose and tumor volume (15.1 ± 2.7 vs. 15.3 ± 1.9 Gy and 4.2 ± 3.6 vs. 3.1 ± 2.5 cm3, respectively, p > 0.05 for both). The rate of endocrine deficiency during 5-year follow-up showed similar trend in adjuvant and primary GKRS groups (3.7%, 8.7%, and 14.8% vs. 5.6%, 13.9%, and 27.8% at first, third, and fifth year time points, respectively). Tumor control rates were also similar (98.6%, 96.3%, and 93% vs. 100%, 97.3%, and 94.5% at first, third, and fifth year time points, respectively). In both groups, tumor volume >5 cm3 was associated with higher rate of hypopituitarism and tumor progression. CONCLUSIONS: GKRS was effective both as adjuvant and primary procedure in patients with NFPA. Radiation dose of ≤13.5 Gy was associated with lower tumor control rate and tumor volume >5 cm3 was associated with higher rates of hypopituitarism and tumor progression.

Gamma knife radiosurgery for high-risk lactotroph adenomas: Long-term results.

Gamma Knife radiosurgery (GKRS) for lactotroph adenomas (LAs) or prolactinomas is limited due to the effectiveness of medical treatments and surgery. Cases who are refractory to medical treatment and/or surgery may be managed with GKRS. We aimed to describe the effectiveness of GKRS for high-risk lactotroph adenomas (HRLAs) and LAs that were medically and surgically refractory. We analyzed our series of patients with HRLAs and LAs who were managed with GKRS following failed medical treatment and surgery and who had at least three years of follow-up. A total of 52 patients (22 HRLAs and 30 LAs) were included in the analysis of radiological, endocrine, and clinical outcomes. Radiological control was achieved in 68.2% of subjects in the HRLA group and 96.7% of subjects in the LA group. Hormonal control was achieved in 68.2% of patients in the HRLA group and 80% of patients in the LA group. On univariate analysis, hormonal control was significantly associated with pre-treatment volume (p = 0.007), higher margin dose (p = 0.002) and Ki-67 proliferative index (p = 0.007). Complications involved new pituitary hormone deficiencies in 19.2% of patients and asymptomatic peripheral visual field defect in 1.9% of patients. To the best of our knowledge, this is the first study to examine the effectiveness of GKRS in LAs and HRLAs, with the highest median follow-up in the literature. High hormonal control rate, even in HRLAs, and lower complication rates suggest that GKRS should be part of the techniques for managing treatment refractory LAs.

Gamma knife radiosurgery in patients with Cushing's disease: Comparison of aggressive pituitary corticotroph tumor versus corticotroph adenoma.

Aggressive pituitary corticotroph tumors causing Cushing's disease are rare, and there is limited data about their clinical management. Here, we aimed to report our long-term experience with gamma knife radiosurgery (GKRS) as adjuvant treatment in patients with residual or recurrent pituitary corticotroph tumors. This retrospective study included 45 adult patients (M/F, 7/38; mean age, 40.2 ±â€¯13.1 years) with residual tumor or recurrence after initially successful surgical resection. Single-session GKRS was performed in all patients. Tumors with a Ki-67 value higher than 3 % and radiologic invasion to surrounding tissues were classified as aggressive tumor group. Clinical, hormonal and radiological findings were compared between the aggressive (n = 10) and non-aggressive adenoma (n = 35) groups. Following GKRS, tumor volumes were significantly reduced in both groups. The mean time to hormonal remission in the non-aggressive group was significantly shorter than in the aggressive group (23.5 ±â€¯6.3 vs 33.0 ±â€¯5.0 month, respectively, p < 0.05). New-onset hypopituitarism was identified in only seven patients (15 %) after GKRS in the whole cohort. The present study introduces several essential findings about aggressive corticotroph tumors. First, aggressive behavior tends to occur more frequently in male subjects. Second, time to GKRS was significantly shorter in the aggressive group. Moreover, a tumor volume ≥2 cm3 may be associated with clinical aggressiveness in corticotroph tumors. In conclusion, we suggest that early adjuvant GKRS is an effective treatment option in aggressive pituitary corticotroph tumors.

Frequency and Role of CDKN2A Deletion in High-Risk Pituitary Neuroendocrine Tumors.

The underlying mechanisms of aggressive pituitary neuroendocrine tumors (pitNETs) are still unclear. The p16 protein, encoded by the CDKN2A tumor suppressor gene on chromosome 9p21, is commonly reported to be lost in numerous types of cancer. For this reason, this study examined to examine the status of homozygous deletion of CDKN2A in high-risk pitNETs. Thirty-eight high-risk pitNETs (30 male, 8 female) were analyzed for CDKN2A deletion by fluorescent in situ hybridization (FISH). Demographic characteristics such as sex, patient age at operation, and sellar magnetic resonance imaging findings including tumor size and invasion status were recorded. The frequency of CDKN2A homozygous deletion by FISH was 3/38 (7.89%) in the high-risk pitNET group. All of these three cases with CDKN2A homozygous deletion were invasive densely granulated lactotroph tumors (p = 0.000). CDKN2A deletion was not correlated with patient age, sex, cavernous sinus invasion (CSI), and tumor size (p > 0.05). The Ki-67 proliferation index was significantly correlated with CDKN2A homozygous deletion (p = 0.003). The mean Ki-67 proliferation index was 10.7% in pitNETs with CDKN2A homozygous deletion and the Ki-67 proliferation index in the whole study group was 4.1%. CSI was significantly correlated with the morphofunctional tumor types including lactotroph tumor, invasive null cell tumor, and invasive gonadotroph tumor (p = 0.021). These findings suggest a close correlation between inactivation of p16 gene and invasive lactotroph tumors. Further investigations are needed to expand on the mechanism of p16 (CDKN2A) gene deletion in high-risk pitNETs.

Is diabetes mellitus a risk factor for modic changes?: A novel model to understand the association between intervertebral disc degeneration and end-plate changes.

OBJECTIVE: Mechanical failure and inflammatory response are two mechanisms proposed for the development of Modic changes, even though they have not been clearly demonstrated, yet. Diabetes mellitus (DM) harbors micro- and macroangiopathy due to the irreversible glycation of proteins, increased oxidative stress, and inflammation. In this study, we aimed to identify whether DM was associated with Modic changes in terms of inflammatory process. METHODS: We conducted a cross-sectional study using our prospectively collected retrospective database of patients with DM who had visited the outpatient clinics at a university hospital. In 3999 patients with DM, 266 had spinal MRI due to cervical, thoracic or low back pain. We included patients, who had lumbar spine MRIs due to low back and/or leg pain and blood draw for HbA1c simultaneously. We analyzed 48 symptomatic patients with DM. We had also symptomatic patients without DM as control group. RESULTS: Severe intervertebral disc degeneration was significantly associated with Modic changes. Severe intervertebral disc degeneration had no significant association with serum HbA1c percentage and DM duration. Patients with Modic changes at any lumbar level had significantly higher HbA1c percentages, and longer duration of DM than those without Modic changes. Symptomatic patients with DM had higher rates of Modic changes compared to symptomatic ones without DM. CONCLUSIONS: Severity and duration of DM were both closely associated with Modic changes, whereas the association of severity and duration of DM with severe intervertebral disc degeneration remained unclear.

The effect of two different high-flux dialysis membranes on insulin resistance in non-diabetic end-stage renal disease patients.

OBJECTIVE: The aim of this study was to investigate the effect of two different types of high-flux dialysis membranes on insulin resistance among patients who are receiving hemodialysis (HD) due to end-stage renal failure (ESRF). MATERIALS AND METHODS: Forty-six (21 female, 25 male) patients were included in the study, who were on HD treatment due to stage-5 chronic renal failure. Prior to the study, fasting insulin resistance via Homeostasis Model Assessment-Insulin Resistance (HOMA-IR) and fractioned urea clearance (Kt/V) values were calculated using the urokinetic model. The polysulfone (PS) dialysis membrane of all patients included in the study was replaced with "polyarylethersulfone, polyvinylpyrrolidone, polyamide (PPP)" high-flux membrane that has the same surface area over 12 weeks. At the end of the 12-week period, HOMA and Kt/V values were recalculated. RESULTS: At the end of the 12-week period, Kt/V values rose statistically significant from 1.575 to 1.752 (p = 0.002). HOMA-IR values declined, though not statistically significant, from 3.268 to 2.926 (p = 0.085). PPP high-flux membrane increased the Kt/V values significantly compared to the PS membrane, while it decreased the insulin resistance and increased insulin sensitivity. CONCLUSION: The two different types of high-flux dialysis membranes used for HD have different effects on insulin sensitivity. Compared to the PS membrane, PPP high-flux membrane decreased insulin resistance by increasing insulin sensitivity among non-diabetic ESRF patients.

Severe hypokalemia probably associated with sertraline use.

OBJECTIVE: To report a case of ventricular fibrillation caused by severe hypokalemia probably associated with sertraline use. CASE SUMMARY: A 48-year-old male patient experienced ventricular fibrillation and cardiac arrest 2 hours after an uneventful coronary angiography procedure, which revealed normal, unobstructed coronary arteries. Blood chemistry was immediately obtained, revealing a very low potassium (K+) level of 2.44 mEq/L. Other blood electrolytes, including magnesium, ECG, and corrected QT intervals, were all within normal limits. A thorough search for an etiology of hypokalemia, including adrenal gland causes, herbal product consumption, and toxic exposure, did not reveal any identifiable cause. This led us to consider the only drug he was on--sertraline 50 mg per day--as the possible culprit. DISCUSSION: There has been no clear identification of severe hypokalemia associated with sertraline use in the literature. However, there have been a considerable number of self-reported cases of hypokalemia in patients on sertraline therapy. Scoring according to the Naranjo adverse drug reaction scale revealed a probable relationship between severe hypokalemia and sertraline use in our patient. No clear pathogenic mechanism for the effect of sertraline on serum K equilibrium is known. However, considering the number of self-reported incidences and this case report, the effect of sertraline on serum K levels warrants consideration. CONCLUSIONS: This is the first documented case report of severe hypokalemia probably associated with sertraline use.

Silent myocardial ischemia in middle-aged asymptomatic patients with type 2 diabetes in Turkish population.

The authors investigated silent myocardial ischemia in unselected consecutive middle-aged asymptomatic patients with type 2 diabetes without any evidence of coronary heart disease documented by treadmill exercise test. Ninety asymptomatic patients with type 2 diabetes (48 men; mean age: 49 +/-6 years) were included in the study. Mean duration of diabetes in the study group was 4 +/-4.2 years (range 1 to 21 years); 38% of the study population, diabetes duration was only 1 year). All patients were subjected to treadmill exercise test with Bruce protocol. A positive test was noted in 4 of 90 (4%) study patients. Two male patients (4%) and 2 (4%) women patients developed exercise-induced ST-segment depression, but none had concomitant chest pain. Diabetics with silent myocardial ischemia were older (55 +/-3 years vs 49 +/-6 years, p = 0.04) than those without silent myocardial ischemia. Also, diabetics with silent myocardial ischemia had higher fibrinogen level (372 +/-51 vs 307 +/-71 mg/dL, p = 0.04) than diabetics without silent myocardial ischemia. In treadmill exercise test, diabetics with silent myocardial ischemia had lower total exercise time and peak workload (375 +/-30 vs 474 +/-115 seconds, p = 0.04; 7.3 +/-0.5 vs 8.9 +/-1.9, p = 0.04, respectively) than without silent myocardial ischemia. Insulin resistance is associated with a variety of atherosclerosis risk factors. Exercise test findings show increased cardiac sympathetic activity and parasympathetic withdrawal in increased insulin resistance.

The effects of rosiglitazone treatment on the fibrinolytic system in patients with type 2 diabetes mellitus.

Patients with type 2 diabetes mellitus (DM) are at risk for the development of cardiovascular diseases, which can in part be explained by disturbances in the hemostatic and fibrinolytic systems. The effects of rosiglitazone treatment on the fibrinolytic system and insulin sensitivity in patients with type 2 DM were assessed. Twenty-four patients with type 2 DM and 28 healthy subjects were enrolled in the study. Plasma global fibrinolytic capacity (GFC), tissue plasminogen activator (t-PA), and plasminogen activator inhibitor-1 (PAI-1) levels were measured. Insulin resistance was calculated by hoemostasis model assessment. Patients with type 2 DM then were placed on rosiglitazone (4 mg/day, for 12 weeks) in addition coexistent medication, and baseline tests were repeated. There was no difference between mean t-PA levels of the two groups. PAI-1 levels were higher in diabetic patients than control subjects (p < 0.01). Diabetic patients had lower GFC and t-PA/PAI-1 levels than control subjects (p < 0.05, p < 0.05). PAI-1 levels were positively correlated with waist circumference in diabetic group (r = 0.4, p < 0.05). After rosiglitazone treatment, there was no difference in mean plasma levels of GFC, t-PA, PAI-1 and t-PA/PAI-1 in diabetics. Insulin sensitivity significantly improved after the addition of rosiglitazone treatment in diabetic patients (p < 0.01). The short-term and low-dose treatment with rosiglitazone in type 2 diabetic patients has no effects on the fibrinolytic system, although it improves insulin sensitivity.

Global fibrinolytic capacity in patients with subclinical hypothyroidism.

Subclinical hypothyroidism (SH) represents the earliest stages of hypothyroidism but the benefits of detecting and treating SH are not well known. The aim of this study was to evaluate the alterations in global fibrinolytic capacity (GFC), which indicates the overall fibrinolytic activity, in patients with SH. The study group comprised of 15 patients with SH and 15 healthy controls. The GFC was significantly lower in patients with SH than in control group (p<0.002). This result suggests a relative hypercoagulable state in SH.