Endocrine and Metabolic Science最新文献

Introduction

Hypothyroidism is a very common endocrine disorder routinely treated with levothyroxine replacement therapy. Despite treatment to biochemical euthyroidism, some individuals continue to have hypothyroidism-related symptoms. Many individuals with hypothyroidism also have low levels of calcitonin. Our aim was to evaluate the effects of calcitonin treatment on quality of life in hypothyroid individuals treated with levothyroxine.

Methods

Adult, hypothyroid individuals were treated with nasal calcitonin spray, 200 international units daily for 6 weeks. Participants completed a modified City of Hope Quality of Life questionnaire prior to initiating calcitonin and after completing 6 weeks of therapy. Perception of quality-of-life benefit with calcitonin was also assessed.

Results

Improvements in quality-of-life scores with calcitonin treatment from 184.77 to 148.44 (p = 0.342) were not statistically significant. Also, only one individual perceived any benefit with calcitonin therapy.

Conclusion

Treatment with nasal calcitonin spray in individuals with hypothyroidism on levothyroxine replacement therapy did not result in quality-of-life benefit.

Clinical experience shows that older people with hyperthyroidism display fewer signs or symptoms compared to younger people with hyperthyroidism. Moreover, older people with normal thyroid function tests display several clinical features of hypothyroidism. These observations suggest that there may be an age-related resistance to the actions of thyroid hormones (TH). Indeed, laboratory experiments have consistently documented an age –related blunting of response to exogenously administered TH. This resistance to TH action has been attributed to reduced cellular transport of TH, possibly reduced nuclear receptors of TH and reduced cytosolic deiodinase activity. In light of these observations, along with epidemiologic studies, the diagnosis and treatment of thyroid disease in older people differ from the current treatment guidelines of younger people with thyroid disease. It is noteworthy that the age-related resistance to TH is distinct from the congenital TH resistance syndromes where plasma TH levels are increased. This distinction is explained by the age-related changes in pituitary responsiveness to the feedback inhibition by TH and reduced thyroid gland response to thyrotropin. The current evidence suggests that the age-related resistance to TH is an adaptive process to prolong life span. At the present time, it is not known if younger people can also experience premature resistance to TH and may have symptoms of hypothyroidism in the face of normal plasma TH concentrations.

Background

Adrenocortical carcinoma (ACC) is a rare malignancy with a reported incidence of 0.5–2 cases per million population per year. Literature is scarce on this malignancy with poor prognosis and limited treatment options. The objective of this report was to report a single-center experience of this rare malignancy.

Methods

A retrospective chart review (1997–2019) was performed on patients diagnosed with ACC via surgical pathology. Data were subsequently split into two time periods defined by the date of initial presentation: 1996–2007 and 2008–2019.

Results

52 patients were identified, 55.8 % were female, and the mean age at the time of surgery was 53 years. Most common presentations (25 % each) were: incidentalomas, abdominal pain, or hormonal hypersecretion. Laboratory evidence of hormonal hypersecretion was identified in 40.4 %. Among those patients, elevated 24-hour urinary free cortisol was the most common finding in both time periods.

The overall 5-year survival rate was 53.1 % and showed significant improvement in recent years when compared between the two time periods, 85.7 % vs 40.0 %. P = 0.004.

Conclusion

Overall, the most common presentation of ACC was found to be equally distributed among incidentaloma, hormonal hypersecretion, and abdominal pain. Hypercortisolism, a recognized poor prognosticator, was the most frequent form of hormonal hypersecretion. The 5-year survival rate for ACC was noted to be poor in general; however, it was observed to be substantially higher in more recent years. More research is necessary to further understand this malignancy in order to optimize management and improve outcomes.

Clinical relevance

This report provides a valuable contribution and expands the knowledge base for this important yet rare malignancy. The objective of this study was to report a single-center experience of ACC by characterizing patients diagnosed with this rare disease and managed at our institution and assessing their outcomes.

Diabetic retinopathy (DR) is the most common ophthalmological complication of diabetes mellitus (DM) and a leading cause of preventable visual impairment. In DM, retinal neurodegenerative changes precede microvascular changes which can be assessed by electrophysiological and advanced imaging techniques. Studies measuring retinal neurodegenerative changes in DM were systematically evaluated in this review. Included studies have assessed retinal neurodegeneration in diabetic rodents by combining clinically used diagnostic techniques and molecular assays. Significant impairment was noticed in electrophysiology data in the diabetic retina as compared to the non-diabetic retina. Also, a significant reduction in synaptic protein levels was noticed in the diabetic retina compared to the non-diabetic retina. Even though retinal neurodegeneration was noticed, no vascular abnormalities were seen in the diabetic retina. However, little is known about molecular mechanisms behind diabetic retinal neurodegeneration (DRN), which explains the need for further investigation to detect DR in the early stages of diabetes.

Objective

While the field of pediatric endocrinology, and the American Board of Pediatrics, continues expanding training to include gender-affirming care, many pediatric endocrinology fellowship programs do not have formal curriculum for this patient population. Members of the Pediatric Endocrine Society (PES) that have a special interest in transgender health designed a curriculum based on Endocrine Society practice guidelines to expand the knowledge of gender affirming care for medical trainees' and faculty.

Methods

PES members designed a 5-part self-guided educational module series with embedded knowledge questions. Uniquely, medical ethical reflections were included within each module. Participants completed baseline demographic and baseline and follow-up knowledge surveys.

Results

Most participants were pediatric endocrinology fellows and 44 % percent (n = 21) completed all study components, including the follow up knowledge survey. Knowledge question data analysis demonstrated knowledge gained in medical management of pubertal youth and surgical interventions.

Conclusion

This is the first medical education curriculum in gender-affirming care created by pediatric endocrinologists grounded in the Endocrine Society practice guidelines. This study demonstrates medical knowledge gained in caring for gender diverse youth and is the first to incorporate ethical considerations for this patient population. While initially designed for pediatric endocrinology trainees and faculty, this curriculum may be of great utility for any provider interested in caring for gender diverse youth.

Objective

To analyze associations between adiposity and the renin-angiotensin-aldosterone system (RAAS) in a large African American (AA) cohort.

Methods

Cross-sectional associations of adiposity (body mass index [BMI], waist circumference [WC], waist:height ratio, waist:hip ratio, leptin, adiponectin, leptin:adiponectin ratio [LAR], subcutaneous [SAT] and visceral adipose tissue [VAT], and liver attenuation [LA]) with aldosterone, plasma renin activity (renin), and aldosterone:renin ratio (ARR) were assessed in the Jackson Heart Study using adjusted linear regression models.

Results

A 1-SD higher BMI was associated with a 4.8 % higher aldosterone, 9.4 % higher renin, and 5.0 % lower ARR (all p < 0.05). Log-leptin had the largest magnitude of association with renin (30.2 % higher) and ARR (9.6 % lower), while the strongest association of aldosterone existed for log-LAR (15.3 % higher) (all 1-SD, p < 0.05). SAT was only associated with renin. VAT was associated with higher aldosterone, renin, and ARR. Liver fat was associated with aldosterone and renin, but not ARR. Associations of WC, BMI, and SAT with aldosterone were greater in men while the association with VAT was greater in women (p-interactions < 0.05).

Conclusion

Multiple measures of adiposity are associated with the RAAS in AAs. Further studies should examine the role of RAAS in obesity-driven cardiometabolic diseases.

Background of study

Studies have shown that women with polycystic ovarian syndrome (PCOS) undergo perturbations of the hypothalamic-pituitary ovarian axis, and frequently suffer from menstrual dysfunction leading to anovulation and infertility. Involvement of mineralocorticoid receptor (MR) activation has been implicated in metabolic/endocrine disorders. Therefore, we hypothesize that mineralocorticoid receptor blocker, spironolactone (SPL) would attenuate hypothalamic-ovarian dysfunction associated with PCOS in rat model.

Materials and methods

Female Wistar rats that were eight-week-old were allotted into groups. The control group received vehicle (distilled water; p.o.), letrozole (LET)-treated group received LET (1 mg/kg; p.o.), LET+SPL-treated group received letrozole plus SPL (0.25 mg/kg, p.o.). The treatment was done once daily for 21 days uninterruptedly.

Results

The LET-induced PCOS animals showed increase in testosterone and LH/FSH ratio and hypothalamic and ovarian lipid profile, lipid peroxidation and inflammatory biomarkers (NF-κB and TNF-α) with a significant decrease in hypothalamic/ovarian glutathione and hypothalamic kisspeptin. However, these alterations were improved following administration of SPL.

Conclusion

The present study therefore demonstrates that MR blockade by low-dose spironolactone alleviates hypothalamic-ovarian dysfunction associated with PCOS by improving hypothalamic kisspeptin level.

Background

Obesity, type 2 diabetes, and major depression are common comorbidities in aging populations. Metformin (MF) mimics effects of caloric restriction (CR) which increases health and life spans. CR suppresses central TRH activity resulting in bradycardia and suppression of energy expenditure. TRH and TRH-like peptides with sequence pGlu-X-Pro-NH₂, (X-TRH) where ‘X’ can be any amino acid residue, have anorectic, antidepressant, anxiolytic, analeptic, anti-epileptic, neuroprotective and anti-aging effects. The present studies compare the effects of CR and oral MF on expression of TRH and TRH-like peptides. CR experiment: Sixteen male Sprague-Dawley rats divided into 4 groups: ad libitum fed (CR-CON), 24 h fasted (CR-AC), fed (ADF1) or fasted (ADF2) 24 h after 10 days of alternate day fasting. MF experiment: Sixteen rats divided into 4 groups: water (MF-CON), 6 mg MF/ml water 24 h (MF-AC), 10 days MF (CHR) or 8 days MF then 48 h water (WD).

Results

Comparison of chronic MF and ADF2 treatment effects on TRH and TRH-like peptide levels in testis revealed a consistent pattern for peptide responses observed in the two experiments with Glu-TRH > Val-TRH > TRH > Peak 2 > Trp-TRH > Phe-TRH > Tyr-TRH. TRH levels increased in heart during CR and MF treatment consistent with cardiac responses to congestive heart failure and infarction.

Conclusions

Because TRH reverses aging-induced testicular degeneration and mediates the pathophysiology of congestive heart failure these tripeptides may participate in the therapeutic effects of MF in ameliorating the cardiometabolic risk factors and fertility impairments associated with type 2 diabetes.

Context

COVID-19 is a new viral infection affecting mainly the respiratory system with involvement of many other organs. Thyroid dysfunction has been described in COVID-19 but data are still unclear and conflicting on its frequency, severity and relationship with the outcome.

Patients and methods

We assessed thyroid function tests (TFT) in 50 patients admitted to our institution with confirmed COVID-19 infection. We excluded patients known to have thyroid diseases or taking drugs that may affect thyroid function. Serum free thyroxine (FT4), thyrotropin (TSH) and triiodothyronine (T3) were measured once or more during the first 10 days after admission. In about 50 % of the cases, a follow up TFT was obtained during the first year after discharge (at a median follow up of 6 months).

Results

We included 50 patients, 29 males (58 %) and 21 females (42 %). The median age was 47 years (range 25–89). Overall, TFTs were completely normal in all patients except for minor transient abnormalities in 5 patients (10 %) as follows: three patients had a mild transient elevated TSH, one had a mild transient suppressed TSH and one patient had a mildly low FT4 with normal TSH. There were no differences between the follow up TFTs obtained after discharge and TFTs obtained during admission in the acute phase.

Conclusion

In this study, thyroid dysfunction during acute COVID-19 infection was rare, mild and transient. However, the study might not be powered enough to detect an association between thyroid dysfunction and the severity of illness and further studies are needed to assess this issue. Late-onset thyroid dysfunction does not seem to occur in COVID-19 infection during the next year after discharge.

Obesity among aging women is associated with increased risk for metabolic and cardiovascular diseases. Weight-loss has been shown to reduce disease risk; however, it remains unclear how changes in adipokines following weight-loss are associated with markers of metabolic and cardiovascular health in women. The aim of this study was to determine the effects of a 3-month intensive lifestyle management-focused weight-loss program on the interactions between adipokines, total and regional body composition, and biomarkers of cardiovascular and metabolic health. Women who were overweight or obese (n = 43, age = 49.2 ± 1.5 years, body mass index (BMI) = 34.5 ± 0.9 kg/m²; waist circumference (WC) = 99.8 ± 2.2 cm) completed a 3-month weight-loss program consisting of a reduced energy intake to 1200–1500 kcals/day combined with a progressive walking program targeting 300 min/wk. At 3-months, average body mass was reduced 8.3 % (ΔBMI −8.0 %; ΔWC −6.6 %). Weight-loss lowered fasting glucose (−12.1 %), insulin (−23.2 %), total cholesterol (−11.0 %), and LDL-C (−12.2 %) concentrations, and HOMA-IR (−32.4 %). Leptin was decreased 32.6 %, high molecular weight (HMW) adiponectin increased 25.0 %, and adiponectin:leptin ratio increased 1.27-fold. The change in fat mass was positively correlated with Δleptin (r = 0.527) and inversely correlated with Δadiponectin:leptin ratio (r = −0.547). The ΔHMW adiponectin inversely correlated with Δinsulin (r = −0.360) and ΔHOMA-IR (r = −0.304), and ΔLDL-C (r = −0.305), whereas Δleptin correlated with Δtriglyceride (r = 0.366) and Δtotal cholesterol (r = 0.402). Weight-loss in women who were overweight and obese was associated with a reduction in leptin and increase in HMW adiponectin and adiponectin:leptin ratio. Correlations revealed that changes in these adipokines were uniquely associated with improvements in select markers of metabolic and cardiovascular disease risk.