Assessment of Serum Electrolytes and Glycated Hemoglobin Level in Non-diabetic Iron-Deficient Anaemic Patients.

INTRODUCTION: The WHO has recognised iron deficiency anaemia (IDA) as the most common nutritional deficiency in the world, with 30% of the population being affected by this condition. The patient's glycemic status during the past three months is shown by the glycated haemoglobin A1C (HbA1c) test. According to several studies, iron deficiency can increase HbA1C levels without affecting blood sugar levels. HbA1C levels of ≥ 6.5% have been approved by the American Diabetes Association (ADA) as a diagnostic indicator for diabetes mellitus (DM). An imbalance in serum electrolyte levels and anaemia have been linked by several studies.  Aim: To analyze the effect of iron deficiency anaemia on HbA1c levels and serum electrolytes in an adult non-diabetic population. METHODS: This was a descriptive cross-sectional study conducted in Shri BM Patil Medical College, Hospital and Research Centre, Vijayapura, Karnataka, India from January 2021 to June 2022. A total of 65 moderate to severe normoglycemic iron deficiency anemia patients between 18 to 75 years were enrolled in the study after fulfilling inclusion and exclusion criteria. A detailed history, clinical and biochemical examination was performed including HbA1c levels. The results were pooled and statistical analyses were performed using Statistical Package for Social Sciences (SPSS) version 20 (IBM Corp., Armonk, NY, USA). RESULTS: We found elevated HbA1c levels (5.67±1.1%) in non-diabetic iron-deficient anaemia individuals, and elevation was more in women of reproductive age group (30.8%). There was a statistically significant Spearman negative correlation between hemoglobin and HbA1C levels. Also, 16 patients had hyponatremia with a mean haemoglobin (Hb) of 4.8 g/dL and one patient had hyperkalemia with a mean Hb of 3.2 g/dL which was statistically non-significant. CONCLUSION: In this study haemoglobin and HbA1c had a statistically significant positive correlation with serum sodium and a negative correlation with serum potassium in moderate to severely iron-deficient anaemic patients, especially females of the reproductive age group.

The Relationship Between Adverse Childhood Experiences and Diabetes in Central Michigan Adults.

OBJECTIVE: Adverse childhood experiences (ACEs) predispose individuals to poor health outcomes as adults. Although a dose-response relationship between the number of ACEs and certain chronic illnesses has been shown, the impact of ACEs on diabetes is not thoroughly understood. We investigated the prevalence of ACEs in patients with diabetes and the potential relationship to the severity of diabetes. METHODS: Patients with diabetes (both type 1 and type 2) or obesity were surveyed from the Endocrinology & Diabetes Center at McLaren Central Michigan in Mount Pleasant, Michigan. A validated, standard ACE questionnaire was administered to quantify the number of adverse childhood events that patients have experienced. A retrospective chart analysis was then conducted, addressing the relationship of ACEs with the severity of disease in the diabetes group and the obesity group. The number of ACEs was correlated with disease comorbidities, complications, and measurable quantities, such as body mass index (BMI) and hemoglobin A1c (HbA1c). RESULTS: ACE scores in both diabetes and obesity groups were shown to have a greater prevalence compared to the general ACE average in Michigan. ACE scores also positively correlated to BMI and HbA1c in the diabetes group. Those with higher ACE scores in the diabetes group were also more likely to have depression and anxiety. CONCLUSION: ACE screening may lead to a greater understanding of the severity of and progression of diabetes. Ultimately, these results could provide support to potential interventional studies leading to the altered management of diabetes in patients with ACEs, or preventative intervention to children with ACEs. ABBREVIATIONS: ACE = adverse childhood experiences; BMI = body mass index; HbA1c = hemoglobin A1c; T1DM = type 1 diabetes mellitus; T2DM = type 2 diabetes mellitus.

AGING, DIABETES, AND FALLS.

KEY POINTS Falls are a major health issue for older adults, leading to adverse events and even death. Older persons with type 2 diabetes are at increased risk of falling compared to healthy adults of a similar age. Over 400 factors are associated with falls risk, making identification and targeting of key factors to prevent falls problematic. However, the major risk factors include hypertension, diabetes, pain, and polypharmacy. In addition to age and polypharmacy, diabetes-related loss of strength, sensory perception, and balance secondary to peripheral neuropathy along with decline in cognitive function lead to increased risk of falling. Designing specific interventions to target strength and balance training, reducing polypharmacy to improve cognitive function, relaxation of diabetes management to avoid hypoglycemia and hypotension, and relief of pain will produce the greatest benefit for reducing falls in older persons with diabetes. Abbreviation: DPN = diabetic polyneuropathy.

AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS AND AMERICAN COLLEGE OF ENDOCRINOLOGY POSITION STATEMENT ON TESTING FOR AUTONOMIC AND SOMATIC NERVE DYSFUNCTION.

This document represents the official position of the American Association of Clinical Endocrinologists and the American College of Endocrinology. Where there were no randomized controlled trials or specific U.S. FDA labeling for issues in clinical practice, the participating clinical experts utilized their judgment and experience. Every effort was made to achieve consensus among the committee members. Position statements are meant to provide guidance, but they are not to be considered prescriptive for any individual patient and cannot replace the judgment of a clinician.

mHealth Intervention to Improve Diabetes Risk Behaviors in India: A Prospective, Parallel Group Cohort Study.

BACKGROUND: In low/middle income countries like India, diabetes is prevalent and health care access limited. Most adults have a mobile phone, creating potential for mHealth interventions to improve public health. To examine the feasibility and initial evidence of effectiveness of mDiabetes, a text messaging program to improve diabetes risk behaviors, a global nonprofit organization (Arogya World) implemented mDiabetes among one million Indian adults. OBJECTIVE: A prospective, parallel cohort design was applied to examine whether mDiabetes improved fruit, vegetable, and fat intakes and exercise. METHODS: Intervention participants were randomly selected from the one million Nokia subscribers who elected to opt in to mDiabetes. Control group participants were randomly selected from non-Nokia mobile phone subscribers. mDiabetes participants received 56 text messages in their choice of 12 languages over 6 months; control participants received no contact. Messages were designed to motivate improvement in diabetes risk behaviors and increase awareness about the causes and complications of diabetes. Participant health behaviors (exercise and fruit, vegetable, and fat intake) were assessed between 2012 and 2013 via telephone surveys by blinded assessors at baseline and 6 months later. Data were cleaned and analyzed in 2014 and 2015. RESULTS: 982 participants in the intervention group and 943 in the control group consented to take the phone survey at baselne. At the end of the 6-month period, 611 (62.22%) in the intervention and 632 (67.02%) in the control group completed the follow-up telephone survey. Participants receiving texts demonstrated greater improvement in a health behavior composite score over 6 months, compared with those who received no messages F(1, 1238) = 30.181, P<.001, 95% CI, 0.251-0.531. Fewer intervention participants demonstrated health behavior decline compared with controls. Improved fruit, vegetable, and fat consumption (P<.01) but not exercise were observed in those receiving messages, as compared with controls. CONCLUSIONS: A text messaging intervention was feasible and showed initial evidence of effectiveness in improving diabetes-related health behaviors, demonstrating the potential to facilitate population-level behavior change in a low/middle income country. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ACTRN): 12615000423516; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=367946&isReview=true (Archived by WebCite at http://www.webcitation.org/6j5ptaJgF).

Poor correlation of serum alpha-subunit concentration and magnetic resonance imaging following pituitary surgery in patients with nonfunctional pituitary macroadenomas.

OBJECTIVE: To review the clinical utility of measuring serum alpha-subunit as a marker for residual tumor in a group of patients with surgically resected nonfunctional pituitary adenomas. METHODS: In this retrospective cross-sectional chart review using the pituitary database at the Cleveland Clinic, we identified patients with nonfunctional pituitary macroadenomas over a 4-year period (2000-2004) and selected those patients who had an elevated alpha-subunit concentration measured before pituitary surgery. Presurgery and post-surgery measurements of alpha-subunit, luteinizing hormone, follicle-stimulating hormone, and thyroid-stimulating hormone were documented. Findings from preoperative and postoperative pituitary magnetic resonance imaging (MRI) were reviewed. RESULTS: We identified 54 patients who were evaluated for nonfunctional pituitary macroadenomas during the study period. Of the 39 who underwent pituitary surgery, 34 had a serum alpha-subunit concentration measured before surgery. Eight of 34 patients had elevated preoperative alpha-subunit levels with a median value of 1.8 ng/mL (range, 1.0-3.4 ng/mL). Of the 8 patients, 7 had follow-up MRI a median of 12 months (range, 6-52 months) after surgery. One patient was lost to follow-up. Three of 7 patients had persistently elevated alpha-subunit levels postoperatively; in 2 of these 3, MRI did not identify residual tumor. Among the 4 patients with postoperative normalization of alpha-subunit, 2 patients had residual tumor on MRI. CONCLUSION: The discrepancy between alpha-subunit levels and postoperative MRI calls into question the value of routine alpha-subunit measurement as a tumor marker in patients with nonfunctional pituitary macroadenomas.

The utility of peripheral thyrotropin mRNA in the diagnosis of follicular neoplasms and surveillance of thyroid cancers.

BACKGROUND: Thyroid cells in peripheral circulation express uniquely thyrotropin receptor (TSHR) mRNA, and their detection may aid thyroid cancer management. METHODS: Since 2002, 258 patients had prospective TSHR mRNA measurement by quantitative RT-PCR from peripheral blood before and/or after thyroidectomy. Thyroid cancer detection was assessed from known clinical diagnostic criteria and mRNA for patients with follicular neoplasms (n = 64) and long-term cancer follow-up (n = 13). RESULTS: Adding TSHR mRNA to fine-needle aspiration biopsy (FNAB) maintained high sensitivity (90%) but improved specificity (73%) for thyroid cancer diagnosis. When FNAB specimens indicated follicular neoplasm, a decision algorithm combining TSHR mRNA and abnormal thyroid ultrasound features correctly diagnosed all cancer patients (100% sensitivity) and would have spared operation for benign disease in 38%. Elevated TSHR mRNA on postoperative day 1 predicted persistent/recurrent cancer. During long-term thyroid cancer surveillance, TSHR mRNA had a 91% concordance with radioactive iodine whole body scan (WBS)-detectable disease, agreed with thyroglobulin (Tg) levels in 64% of patents, missed disease in 5%, but was more sensitive to detecting disease than Tg levels in 31% of patients, including all patients with Tg antibodies. CONCLUSIONS: Detecting circulating thyroid cancer cells is useful for initial thyroid cancer diagnosis and postoperatively predicts recurrent cancer. This novel test promises to enhance thyroid cancer patient care by management algorithms that combine histologic, genomic, and clinical criteria.

Hypothyroidism in patients with metastatic renal cell carcinoma treated with sunitinib.

Sunitinib is an inhibitor of the vascular endothelial growth factor and platelet-derived growth factor receptors, and it has antitumor activity in metastatic renal cell carcinoma and gastrointestinal stromal tumors. To further investigate the fatigue associated with sunitinib therapy, thyroid function tests were performed on patients with metastatic renal cell carcinoma who were receiving sunitinib. Seventy-three patients with metastatic renal cell carcinoma were treated with sunitinib at the Cleveland Clinic Taussig Cancer Center, and 66 of them had thyroid function test results available. Fifty-six (85%) of the 66 patients had one or more abnormality in their thyroid function test results, consistent with hypothyroidism, and 47 (84%) of the 56 patients with abnormal thyroid function tests had signs and/or symptoms possibly related to hypothyroidism. Thyroid hormone replacement was undertaken in 17 patients, and symptoms improved in nine of them. Thyroid function test abnormalities appear to be common in patients with metastatic renal cell carcinoma treated with sunitinib, and routine monitoring is warranted.

Thyroid-stimulating hormone receptor messenger ribonucleic acid measurement in blood as a marker for circulating thyroid cancer cells and its role in the preoperative diagnosis of thyroid cancer.

CONTEXT: Thyroid cancer cells express TSH receptor (TSHR) mRNA, and its measurement in the circulation may be useful in the diagnosis/management of differentiated thyroid cancer (DTC). OBJECTIVE: Our objective was to assess the diagnostic value of circulating TSHR mRNA for preoperative detection of DTC in patients with thyroid nodules. PATIENTS: We measured TSHR mRNA levels by RT-PCR in 258 subjects: 51 healthy subjects and 207 patients (thyroid nodules, n = 180; recurrent thyroid cancer, n = 27) with fine-needle aspirations (FNA) and/or thyroid/neck surgery. Eighty-nine patients also had d-1 postoperative levels assessed. OUTCOME MEASURES: TSHR mRNA levels were compared with FNA cytology for cancer detection preoperatively and serum thyroglobulin and/or whole-body 131I scans postoperatively. RESULTS: Based on cytology/pathology, 88 patients had DTC and 119 had benign thyroid disease. The TSHR mRNA levels in cancer patients were significantly higher than in benign disease (P < 0.0001). At a cutoff value of 1.02 ng/microg total RNA, the TSHR mRNA correctly classified 78.7% of patients preoperatively (sensitivity = 72.0%; specificity = 82.5%). Of 131 patients with FNA and surgery, 51 were FNA positive (all cancer), 17 were FNA negative (15 benign, two cancer), and 63 were indeterminate. TSHR mRNA correctly diagnosed DTC in 16 of 24 (67%) and benign disease in 29 of 39 (74%) patients with indeterminate FNA (combined sensitivity = 90%; specificity = 80%). Combining TSHR mRNA and ultrasound features for follicular lesions correctly classified all follicular cancers and could have spared surgery in 31% of these patients with benign disease. TSHR mRNA has a short life in circulation, and normalized levels on postoperative d 1 correlated with disease-free status, whereas elevated levels predicted residual/metastatic disease. CONCLUSIONS: TSHR mRNA measured with FNA enhances the preoperative detection of cancer in patients with thyroid nodules, reducing unnecessary surgeries, and immediate postoperative levels can predict residual/metastatic disease.

Role of metabolically active hormones in the insulin resistance associated with short-term glucocorticoid treatment.

BACKGROUND: The mechanisms by which glucocorticoid therapy promotes obesity and insulin resistance are incompletely characterized. Modulations of the metabolically active hormones, tumour necrosis factor alpha (TNF alpha), ghrelin, leptin and adiponectin are all implicated in the development of these cardiovascular risk factors. Little is known about the effects of short-term glucocorticoid treatment on levels of these hormones. RESEARCH METHODS AND PROCEDURES: Using a blinded, placebo-controlled approach, we randomised 25 healthy men (mean (SD) age: 24.2 (5.4) years) to 5 days of treatment with either placebo or oral dexamethasone 3 mg twice daily. Fasting plasma TNFalpha, ghrelin, leptin and adiponectin were measured before and after treatment. RESULTS: Mean changes in all hormones were no different between treatment arms, despite dexamethasone-related increases in body weight, blood pressure, HDL cholesterol and insulin. Changes in calculated indices of insulin sensitivity (HOMA-S, insulin sensitivity index) were strongly related to dexamethasone treatment (p < 0.001). DISCUSSION: Our data do not support a role for TNF alpha, ghrelin, leptin or adiponectin in the insulin resistance associated with short-term glucocorticoid treatment.

Giant invasive pituitary prolactinoma with falsely low serum prolactin: the significance of 'hook effect'.

The authors report a case of a patient with giant, invasive skull base tumor extending to the parasellar area discovered incidentally during the work-up for decreased memory. The patient's neurological exam was otherwise unremarkable. Endocrine evaluation performed at a local hospital showed a moderate hyperprolactinemia 103 ng/ml (normal up to 20 ng/ml). Given the large size of the tumor, the elevated prolactin (PRL) was interpreted to be secondary to stalk effect and patient underwent debulking surgery through a transcranial approach. Immunostaining of the excised tumor tissue was strongly positive for prolactin. His prolactin was found to be 13,144 ng/ml in our lab after surgery confirming the diagnosis of invasive giant prolactinoma. The patient developed a complete right third, fourth and sixth nerve palsy postoperatively. He was started on Cabergoline with normalization of his prolactin level and more than 50% decrease in residual tumor size over 9 months periods. There has been no clinically significant improvement in his right eye ophthalmoplegia since surgery. This case highlights the importance of 'Hook Effect' resulting in falsely low prolactin level, which may have significant therapeutic implication.

Effects of short-term glucocorticoids on hemostatic factors in healthy volunteers.

OBJECTIVE: Increased circulating levels of hemostatic factors have been associated with arterial and venous thrombosis. Although in vitro evidence suggests that glucocorticoids may activate hemostasis and inhibit thrombolysis, no controlled in vivo studies have examined the effects of glucocorticoids on hemostatic factors. We hypothesized that a 5-day treatment course of dexamethasone would increase circulating levels of hemostatic and anti-fibrinolytic factors. METHODS: We randomized 24 healthy men ages 19-39 to receive either dexamethasone 3 mg twice daily versus placebo for 5 days. Parameters examined before and after the intervention included: clotting factors VII, VIII, and XI, von Willebrand factor (vWF), D-dimer, PAI-1, soluble CD40-ligand (sCD40-ligand), and fibrinogen. RESULTS: Dexamethasone tended to modestly increase clotting factors levels and fibrinogen without significantly affecting PAI-1, D-dimer or sCD40-ligand. Factor VII increased by a mean of 13% (p = 0.04 versus placebo), factor VIII by 27% (p = 0.0008), factor XI by 6% (p = 0.01), and fibrinogen by 13% (p = 0.05). CONCLUSIONS: Glucocorticoids may increase the activity of clotting factors in vivo. This may contribute to the reported increased risk of thrombosis in patients with sustained exposure to glucocorticoids.

Effects of short-term glucocorticoids on cardiovascular biomarkers.

CONTEXT: Glucocorticoids are known to acutely increase blood pressure, suppress inflammation, and precipitate insulin resistance. However, the short-term effects of glucocorticoids on other cardiovascular risk factors remain incompletely characterized. OBJECTIVE: Our objective was to determine the effects of a short course of dexamethasone on multiple cardiovascular biomarkers and to determine whether suppression of morning cortisol in response to low-dose dexamethasone is correlated with cardiovascular risk markers in healthy volunteers. DESIGN: We conducted a randomized, double-blind, placebo-controlled study. SETTING: The study took place in a tertiary care hospital. STUDY SUBJECTS: Twenty-five healthy male volunteers, ages 19-39 yr, participated in the study. INTERVENTION: Subjects received either 3 mg dexamethasone twice daily or placebo for 5 d. Subjects also underwent a low-dose (0.5 mg) overnight dexamethasone suppression test. MEASURES: Parameters examined before and after the 5-d intervention included heart rate, blood pressure, weight, fasting lipid variables, homocysteine, renin, aldosterone, insulin resistance (homeostasis model assessment), high-sensitivity C-reactive protein, B-type natriuretic peptide, flow-mediated and nitroglycerin-mediated brachial artery dilatation, and heart rate recovery after exercise. All measurements were done in the morning hours in the fasting state. RESULTS: Dexamethasone increased systolic blood pressure, weight, B-type natriuretic peptide, and high-density-lipoprotein-cholesterol. Dexamethasone decreased resting heart rate, high-sensitivity C-reactive protein, and aldosterone and tended to attenuate nitroglycerin-mediated vasodilatation. There was no effect on flow-mediated vasodilatation, diastolic blood pressure, triglycerides, low-density-lipoprotein-cholesterol, nonesterified fatty acids, homocysteine, or heart rate recovery. The response of circulating cortisol to low-dose dexamethasone had no significant correlation with any of the cardiovascular risk markers. CONCLUSIONS: Short-term glucocorticoids elicits both favorable and unfavorable effects on different cardiovascular risk factors. Manipulation of specific glucocorticoid-responsive physiological pathways deserves further study.

Clinical utility of noncontrast computed tomography attenuation value (hounsfield units) to differentiate adrenal adenomas/hyperplasias from nonadenomas: Cleveland Clinic experience.

Radiological characterization of an adrenal tumor as adenoma may decrease the need for follow-up imaging studies, biopsies, and unnecessary adrenalectomies. We retrospectively reviewed 299 adrenalectomies in 290 patients at Cleveland Clinic Foundation over a recent 5-yr period to assess the value of noncontrast Hounsfield units (HU) in characterizing whether an adrenal mass is adenoma or nonadenoma. The mean (+/- SD) HU value for the adrenocortical adenoma/hyperplasia group was 16.2 +/- 13.6 and significantly lower (P < 0.0001) than primary adrenocortical cancers (36.9 +/- 4.1), metastases (39.2 +/- 15.2), and pheochromocytomas (38.6 +/- 8.2). The sensitivity and specificity for 10- and 20-HU cutoff values to differentiate adenomas/hyperplasias from nonadenomas were 40.5 and 100% and 58.2 and 96.9%, respectively. The size of the adrenal tumor had less value with only 40.7 and 81.3% sensitivity and 94.7 and 61.4% specificity for 2- and 4-cm cutoff values. A combination of less than or equal to 4-cm adrenal mass size and noncontrast computed tomography HU less than or equal to 20 had 42.1% sensitivity and 100% specificity. Our study, the largest with surgical histopathology as the gold standard for diagnosis, supports a noncontrast computed tomography attenuation value of 10 HU as a safe cutoff value to differentiate adrenal adenomas/hyperplasias from nonadenomas.

Detection of thyrotropin-receptor messenger ribonucleic acid (mRNA) and thyroglobulin mRNA transcripts in peripheral blood of patients with thyroid disease: sensitive and specific markers for thyroid cancer.

Because thyroid cancer cells express functional TSH receptors (TSHR), TSHR-mRNA in peripheral blood might serve as a tissue-/cancer-specific marker. We measured circulating TSHR-mRNA by RT-PCR in 51 normal controls, 27 patients with benign thyroid disease, 67 patients with treated differentiated thyroid cancer (DTC), and eight patients with newly diagnosed DTC, preoperatively. Results were compared with thyroglobulin (Tg) mRNA and serum Tg levels. TSHR-mRNA signals were not detected in normal controls and in 24 of 27 (89%) patients with benign thyroid disease. All 19 patients with treated DTC with evidence of distant or local disease tested positive for TSHR-mRNA (sensitivity 100%). Among patients with no evidence of disease, TSHR-mRNA was detected in 1 in 48 (specificity 98%). Six of the eight newly diagnosed DTC patients tested preoperatively were positive for TSHR-mRNA. The concordance between TSHR-mRNA and Tg-mRNA and between TSHR-mRNA and serum Tg was 95%. Fourteen patients with DTC (21%) had Tg antibodies, three with local disease (all positive for TSHR-mRNA), and 11 with no evidence of disease (all negative for TSHR-mRNA). Our results indicate that TSHR-mRNA and/or Tg-mRNA in peripheral blood are both equally sensitive and specific markers for monitoring thyroid cancer patients. Their principal value resides in the Tg antibody-positive patients in whom a positive or a negative mRNA value might have indicated or obviated the need for a whole-body scan. Furthermore, the high specificity combined with their ability to predict thyroid cancer preoperatively suggests a potential role in detecting thyroid cancer in patients with thyroid nodules.

Propylthiouracil-induced chemical hypothyroidism with high-dose tamoxifen prolongs survival in recurrent high grade glioma: a phase I/II study.

BACKGROUND: High-dose tamoxifen has had disappointing results as a palliative therapy in recurrent glioma. Insulin-like growth factor 1 (IGF-1) is a thyroid hormone modulated naturally occurring antagonist of tamoxifen-induced cytotoxicity. Thyroid function was suppressed to reduce IGF-1 levels in glioma patients and high-dose tamoxifen administered. MATERIALS AND METHODS: Propylthiouracil was used to induce chemical hypothyroidism in 22 patients with recurrent glioma. Tamoxifen was started within one month and given in escalating doses from 40 mg twice a day up to 80 mg 3 times a day. No significant toxicity developed. RESULTS: Eleven out of 22 patients became hypothyroid. No patients experienced symptoms of clinical hypothyroidism. Median survival was significantly longer in the hypothyroid group (10.1 months versus 3.1 months); p = 0.03. There was a significant decrease in blood levels of IGF-1 (p = 0.02). in hypothyroid patients. CONCLUSION: Patients treated for recurrent high-grade gliomas with high-dose tamoxifen had significantly longer survival when chemical hypothyroidism was induced with propylthiouracil.