Hasil untuk "Diseases of the endocrine glands. Clinical endocrinology"

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Phoebe Wamalwa, Prisca Amolo

Hypothyroidism, affecting approximately 5% of the population, often remains undiagnosed, more so in developing countries. We report a 12-year-old girl with longstanding, untreated hypothyroidism who initially presented with proteinuria. History revealed recurrent vomiting, poor appetite, lethargy, and neurodevelopmental delays. Examination showed short stature, ptosis, outer eyebrow hair loss, myxedematous facies, dry skin, and hypertrophied calves. Investigations confirmed severe primary hypothyroidism, Hashimoto’s thyroiditis, which most commonly presents between the ages of 45 and 55 years, with elevated thyroid autoantibodies and an atrophic thyroid gland. Additional findings were dyslipidemia and moderate proteinuria, both of which resolved with levothyroxine, which also improved growth. However, weight fluctuations persisted due to treatment non-adherence from financial challenges. This case illustrates a broad and atypical spectrum of complications arising from longstanding, untreated primary hypothyroidism. Awareness of such varied clinical manifestations is essential for timely diagnosis and appropriate management.

Ruchi Desai, Fnu Sidra, S. Mirfakhraee et al.

Abstract Disclosure: R. Desai: None. F. Sidra: None. S. Mirfakhraee: None. J. Liwei: None. P. Polanco: None. S. Al Mutar: None. O. Hamidi: None. Background: Cyclic Cushing syndrome (CS) secondary to ectopic adrenocorticotrophic hormone (ACTH) from an appendiceal carcinoid is extremely rare with only a few published cases thus far. This is the first reported case of a patient with extensive metastatic disease on initial presentation. Clinical Case: A 24-year-old woman with no past medical history was referred to endocrinology after developing 60lb weight gain, acne, fatigue, heat intolerance, lower extremity swelling, palpitations, and anxiety over a 3-month period with secondary amenorrhea 6 months prior to presentation. Family history was significant for bronchial carcinoid in her mother. Physical exam was notable for moon facies, wide purple striae on abdomen, hirsutism, dorsocervical and supraclavicular fat pads. Laboratory workup showed hypokalemia (3.2 mmol/L, n = 3.5-5.3), elevated urine free cortisol (UFC) (473 mcg/24hours, n<50), normal ACTH (16 pg/mL, n = 6-50), normal AM Cortisol level (15.3 mcg/dL, n=5-22) and abnormal 1-mg dexamethasone suppression with cortisol 8.8 mcg/dL (n≤1.8). Repeat UFC two weeks later was still elevated (539 mcg/24 hours). Evaluation with CT abdomen and pelvis revealed a 3 cm enhancing appendiceal mass, enlarged periappendiceal mesenteric lymph nodes, and a 4 cm enhancing right hepatic lobe lesion. Further imaging with Ga-68 Dotatate PET/CT confirmed increased radiotracer uptake in the appendiceal mass, lymph nodes, hepatic mass, and right breast. The patient underwent liver biopsy and pathology showed well different neuroendocrine tumor (NET) grade 1 and positive ACTH stain. Genetic testing was negative. She was unable to tolerate ketoconazole and was initially treated with lanreotide 120mg every 4 weeks. Repeat biochemical testing one month after initiation of lanreotide showed elevated UFC (65mcg/24hrs), elevated ACTH (52 pg/mL) and elevated serum cortisol (36.2mcg/dL). Two weeks later ACTH decreased to 14 pg/mL and serum cortisol was <1 mcg/dL which was concerning for severe cyclic ectopic CS secondary to metastatic NET. She was managed with early bilateral adrenalectomy given severe cyclic CS with extensive tumor burden in a young female hoping to preserve fertility. The pathology of her right adrenal gland was notable for metastatic well differentiated neuroendocrine carcinoma. She was subsequently started on physiologic steroids and underwent extensive debulking surgery. 1.5 years later she had progression of disease requiring initiation of peptide receptor radionuclide therapy (PRRT) but has since been in remission. Conclusion: This case demonstrates the importance of individualized medical management of patients with ectopic ACTH syndrome and highlights the need for consideration of early bilateral adrenalectomy for patients with severe CS and metastatic disease. Presentation: Monday, July 14, 2025

Ji-Yeon Park, Joonyub Lee, Yoon-Hee Choi et al.

Background Guidelines for switching to triple combination therapy directly after monotherapy failure are limited. This study investigated the efficacy, long-term sustainability, and safety of either mono or dual add-on therapy using alogliptin and pioglitazone for patients with type 2 diabetes mellitus (T2DM) who did not achieve their target glycemic range with metformin monotherapy. Methods The Practical Evidence of Antidiabetic Combination Therapy in Korea (PEAK) was a multicenter, placebo-controlled, double-blind, randomized trial. A total of 214 participants were randomized to receive alogliptin+pioglitazone (Alo+Pio group, n=70), alogliptin (Alo group, n=75), or pioglitazone (Pio group, n=69). The primary outcome was the difference in glycosylated hemoglobin (HbA1c) levels between the three groups at baseline to 24 weeks. For durability, the achievement of HbA1c levels <7% and <6.5% was compared in each group. The number of adverse events was investigated for safety. Results After 24 weeks of treatment, the change of HbA1c in the Alo+Pio, Alo, and Pio groups were –1.38%±0.08%, –1.03%±0.08%, and –0.84%±0.08%, respectively. The Alo+Pio group had significantly lower HbA1c levels than the other groups (P=0.0063, P<0.0001) and had a higher proportion of patients with target HbA1c achievement. In addition, insulin sensitivity and β-cell function, lipid profiles, and other metabolic indicators were also improved. There were no significant safety issues in patients treated with triple combination therapy. Conclusion Early combination triple therapy showed better efficacy and durability than the single add-on (dual) therapy. Therefore, combination therapy with metformin, alogliptin, and pioglitazone is a valuable early treatment option for T2DM poorly controlled with metformin monotherapy.

Ivo Carrasco-Wong, Javiera M. Sanchez, Jaime A. Gutierrez et al.

Preeclampsia (PE) is a complex pregnancy syndrome characterized by hypertension with or without proteinuria, affecting 2–6% of pregnancies globally. PE is characterized by excessive release of damage-associated molecular patterns (DAMPs) into the maternal circulation. This DAMP-rich milieu acts on innate immune cells, inducing a proinflammatory state characterized by elevated cytokines such as IL-1β and IL-18. This proinflammatory state in the mother and placenta results in the endothelial dysfunction strongly associated with cardiovascular disorders. While the immediate maternal and fetal risks of PE are well-documented, accumulating evidence indicates that PE also confers long-term cardiovascular risks to the mother, including hypertension, coronary heart disease, stroke, and heart failure. The underlying mechanisms connecting PE to these chronic cardiovascular conditions remain unclear. This article explores the potential role of trained innate immunity (TRIM) as a mechanistic link between PE and increased long-term cardiovascular risk. We propose that the persistent exposure to DAMPs during PE may epigenetically reprogram maternal innate immune cells and their progenitors, leading to TRIM. This reprogramming enhances the inflammatory response to subsequent stimuli, potentially contributing to endothelial dysfunction and chronic inflammation that predispose women to cardiovascular diseases later in life. Understanding the role of TRIM in PE could provide novel insights into the pathophysiology of PE-related cardiovascular complications and identify potential targets for therapeutic intervention. Further research is warranted to investigate the epigenetic and metabolic alterations in innate immune cells induced by PE and to determine how these changes may influence long-term maternal cardiovascular health.

Sriram Gubbi, Rachel Wurth, Fady Hannah-Shmouni et al.

Melpomeni Peppa, Ioanna Mavroeidi

Juan R. Ulloque-Badaracco, Enrique A. Hernandez-Bustamante, Enrique A. Hernandez-Bustamante et al.

Background &amp; aimsMetabolic syndrome (MetS) is associated with life-threatening conditions. Several studies have reported an association of vitamin B12, folic acid, or homocysteine (Hcy) levels with MetS. This systematic review and meta-analysis assessed the association of vitamin B12, folic acid, and Hcy levels with MetS.MethodsPubMed, Scopus, Embase, Ovid/Medline, and Web of Science were searched up to February 13, 2023. Cross-sectional, case-control, or cohort studies were included. A random-effects model was performed using the DerSimonian and Laird method to estimate the between-study variance. Effect measures were expressed as odds ratios (OR) with their corresponding 95% confidence intervals (95% CI). Between-study heterogeneity was evaluated using Cochran’s Q test and the I2 statistic.ResultsSixty-six articles (n = 87,988 patients) were included. Higher vitamin B12 levels were inversely associated with MetS (OR = 0.87; 95% CI: 0.81–0.93; p &lt; 0.01; I2 = 90%). Higher Hcy levels were associated with MetS (OR = 1.19; 95% CI: 1.14–1.24; p &lt; 0.01; I2 = 90%). Folate levels were not associated with MetS (OR = 0.83; 95% CI: 0.66–1.03; p = 0.09; I2 = 90%).ConclusionHigher vitamin B12 levels were inversely associated with MetS, whereas higher Hcy levels were associated with MetS. Studies assessing the pathways underlying this association are required.

Takafumi Osaka, Masahide Hamaguchi, Michiaki Fukui

Background And Aims: Maintaining appendicular skeletal muscle mass is important for maintaining the quality of life of elderly patients with type 2 diabetes. The possibility of GLP-1 receptor agonists for maintaining appendicular skeletal muscle mass has previously been reported. We investigated changes in appendicular skeletal muscle mass, measured by body impedance analysis, in elderly patients who were hospitalized for diabetes self-management education. Methods: The study design was a retrospective longitudinal analysis of the changes in appendicular skeletal muscle mass in hospitalized patients over the age of 70 years. The study subjects consisted of consequential patients who received GLP-1 receptor agonist and basal insulin co-therapy or received basal insulin therapy. Body impedance analysis was performed on the day after admission and on the ninth day of admission. All patients received standard diet therapy and standard group exercise therapy 3 times per week. Results: The study subjects consisted of 10 patients who received GLP-1 receptor agonist and basal insulin co-therapy (co-therapy group) and 10 patients who received basal insulin (insulin group). The mean change in appendicular skeletal muscle mass was 0.78 ± 0.7 kg in co-therapy group and −0.09 ± 0.8 kg in the insulin group. Conclusions: This retrospective observational study suggests the possibility of favorable effects of GLP-1 receptor agonist and basal insulin co-therapy for maintaining appendicular skeletal muscle mass during hospitalization for diabetes self-management education.

Jinming Yao, Junyu Zhao, Junyu Zhao et al.

ObjectiveTo explore the relationship between short-term rapid hypothyroidism and blood lipid levels in patients with differentiated thyroid cancer (DTC).MethodsSeventy-five DTC patients scheduled to receive radioactive iodine ablation were enrolled. Levels of thyroid hormone and serum lipids were tested at two time points: the euthyroid before thyroidectomy, and the hypothyroid (off thyroxine). Then the collected data were analyzed.ResultsTotally 75 DTC patients enrolled, among them, 5o were female (66.67%) and 25 were male (33. 33%), with an average age of 52.24 ± 1.24 years old. The short-term rapid severe hypothyroidism induced by thyroid hormone withdrawal significantly aggravated dyslipidemia, particularly in patients with dyslipidemia before thyroidectomy (All P &lt; 0.01). However, there was no significant differences between blood lipid levels with different thyroid stimulating hormone (TSH) levels. And our study showed significant negative correlations between free triiodothyronine levels and the changes from euthyjroidism to hypothyroidism in total cholesterol (r=-0.31, P=0.03), triglycerides (r=-0.39, P=0.006), high density lipoprotein-cholesterol (HDL-C) (r=-0.29, P=0.042), and significant positive correlations between free thyroxine and the changes of HDL-C (r=-0.32, P=0.027) were identified in females, however, which were not observed in males.ConclusionShort-term rapids severe hypothyroidism caused by thyroid hormone withdrawal can lead to rapid significant changes in blood lipid levels. It is necessary to pay attention to dyslipidemia and its long-term effects after thyroid hormone withdrawal, especially in patients with dyslipidemia before thyroidectomy. Clinical trial registrationhttps://clinicaltrials.gov/ct2/show/NCT03006289?term=NCT03006289&amp;draw=2&amp;rank=1, identifier NCT03006289.

Claire Higham, Bo Abrahamsen

Sriram Gubbi, Rachel Wurth, Fady Hannah-Shmouni et al.

Melpomeni Peppa, Ioanna Mavroeidi

Peter Wolf, Alexandre Dormoy, Luigi Maione et al.

Objective: Pasireotide is a second-generation somatostatin receptor ligand (SRL) used for treating acromegaly. Its clinical use is limited by adverse effe cts on glucose homeostasis. The aim of this study was to evaluate longitudinal changes in beta-cell function and insulin sensitivity associated with pasireotide in patients not controlled by first-generation SRLs. Design: We performed a retrospective study. Methods: The efficacy (growth hormone (GH)/insulin-like growth factor (IG F-1) concentrations; tumor size) and effect on glucose homeostasis we re analyzed in 33 patients. Longitudinal data on oral glucose tolerance tests were available before, shortly (mean ± s.d., 6.1 ± 3.8 months) and long term (24.4 ± 11.1 months) after initiation of pasireotide in 14 patients. Insulin secretion (insulinogenic index; disposition index) and insulin sensitivity were calculated by validated indices. Results: Pasireotide-induced diabetes occurred in 12 patients (36%). It was mediated by impaired insulin secretion, which occurred shortly after initiation of treatment and then remained stable on long term (insulinogenic index, median (min; max), 80 (12; 542) vs 16 (6.4; 101) vs 25 (3.7; 396) pmol/mmol, respectively; P = 0.028; disposition index, 1.45 (0.42; 4.88) vs 0.53 (0.17; 2.63) vs 0.60 (0.22; 1.71), respectively; P = 0.024). No significant changes in insulin sensitivity were observed, despite a marked reduction of GH/IGF-1 concentrations. Older age and a worse glycemic control at baseline were the strongest predictors for hyperglycemia and the need for antidiabetic treatment. Conclusion: Worsening of glycemic control during pasireotide therapy is caused by an impaired insulin secretion, whereas insulin sensitivity is not affected. These findings might be important for the choice of antidiabetic treatment for pasireotide-induced hyperglycemia. Significance statement: Pasireotide, a second-generation SRL used for treating acromegaly, may be associated with glucose metabolism impairment. In a retrospective study of 33 patients, we observed that treatment with pasireotide was associated with normalization of serum IGF-1 in almost 60% of patients, but one -third of patients developed diabetes. In the patients who stopped pasireotide because of hyperglycemia, HbA1c promptly decreased. Longitudinal data in 14 patients show that diabetes is mediated by impaired insulin secretion, which occurred shortly and then remained stable on long term, while no significant changes in insulin sensitivit y were observed, despite a marked reduction of GH/IGF-1 concentrations. Older age and a wo rse glycemic control at baseline were the strongest predictors for hyperglycemia.

Inês Henriques Vieira, Dírcea Rodrigues, Isabel Paiva

The thyroid-stimulating hormone receptor (TSH-R) is predominantly expressed in the basolateral membrane of thyrocytes, where it stimulates almost every aspect of their metabolism. Several extrathyroidal locations of the receptor have been found including: the pituitary, the hypothalamus, and other areas of the central nervous system; the periorbital tissue; the skin; the kidney; the adrenal; the liver; the immune system cells; blood cells and vascular tissues; the adipose tissue; the cardiac and skeletal muscles, and the bone. Although the functionality of the receptor has been demonstrated in most of these tissues, its physiological importance is still a matter of debate. A contribution to several pathological processes is evident in some cases, as is the case of Grave’s disease in its multiple presentations. Conversely, in the context of other thyroid abnormalities, the contribution of the TSH-R and its ligand is still a matter of debate. This article reviews the several different sites of expression of the TSH-R and its potential role in both physiological and pathological processes.

Rong-Rong Zhu, Xu-Ping Gao, Xu-Ping Gao et al.

ObjectivesNon-alcoholic fatty liver disease (NAFLD) greatly affects cardiovascular disease, but evidence on the associations between NAFLD and markers of aortic calcification is limited. We aim to evaluate the association between NAFLD and aortic calcification in a cohort of Chinese adults using propensity score-matching (PSM) analysis.MethodsThis prospective cohort study involved adults who underwent health-screening examinations from 2009 to 2016. NAFLD was diagnosed by abdominal ultrasonography at baseline, and aortic calcification was identified using a VCT LightSpeed 64 scanner. Analyses included Cox proportional-hazards regression analysis and PSM with predefined covariates (age, gender, marital and smoking status, and use of lipid-lowering drugs) to achieve a 1:1 balanced cohort.ResultsOf the 6,047 eligible participants, 2,729 (45.13%) were diagnosed with NAFLD at baseline, with a median age of 49.0 years [interquartile range, 44.0–55.0]. We selected 2,339 pairs of participants with and without NAFLD at baseline for the PSM subpopulation. Compared with those without NAFLD, patients with NAFLD were at a higher risk of developing aortic calcification during follow-up; significant results were observed before and after matching, with the full-adjusted hazard ratios and corresponding 95% confidence intervals being 1.19 (1.02–1.38) and 1.18 (1.01–1.38), respectively (both p &lt; 0.05). In subgroup analyses, no interaction was detected according to age, gender, smoking status, body mass index, total cholesterol, low-density lipoprotein cholesterol, use of lipid-lowering drugs, hypertension, or type 2 diabetes.ConclusionsNAFLD may be independently associated with aortic calcification. Further studies are warranted to elucidate the possible underlying mechanisms.

Xinxin Zhang, Jinfeng Xiao, Xin Li et al.

BackgroundThe associations of dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS) with diabetic kidney disease (DKD) remained unclear. Thus, this cross-sectional study aimed to explore the associations of DHEA and DHEAS with the risk of DKD in patients with T2DM.MethodsThe information of 1251 patients with T2DM were included in this study. Serum DHEA and DHEAS were quantified using liquid chromatography-tandem mass spectrometry assays. Multivariate logistic regression analyses were used to assess the associations of DHEA and DHEAS with DKD as well as high urine albumin to creatinine ratio (ACR).ResultsIn men with T2DM, the risk of DKD decreased with an increasing DHEA concentration after adjustment for traditional risk factors; the fully adjusted OR (95% CI) for tertile3 vs tertile1 was 0.37 (0.19-0.70; P = 0.010 for trend). Similarly, when taking high ACR as the outcome, low DHEA levels were still significantly associated with increased odds of high ACR (OR, 0.37; 95% CI, 0.19–0.72 for tertile3 vs tertile1; P = 0.012 for trend). The restricted cubic spline showed that the risk of DKD gradually decreased with the increment of serum DHEA levels (P-overall = 0.007; P-nonlinear = 0.161). DHEAS was not independently associated with the risk of DKD in men. In contrast, no significant relationships were found between DHEA and DHEAS and the risk of DKD in women (all P &gt; 0.05).ConclusionsIn men with T2DM, low serum DHEA levels were independently related to the risk of DKD after adjustment for traditional risk factors. Our finding highlights the potential role of DHEA in the development of DKD in men with T2DM.

Claudia Pivonello, Roberta Patalano, Roberta Patalano et al.

Pituitary neuroendocrine tumors (PitNET) are commonly benign tumors accounting for 10-25% of intracranial tumors. Prolactin-secreting adenomas represent the most predominant type of all PitNET and for this subtype of tumors, the medical therapy relies on the use of dopamine agonists (DAs). DAs yield an excellent therapeutic response in reducing tumor size and hormonal secretion targeting the dopamine receptor type 2 (D2DR) whose higher expression in prolactin-secreting adenomas compared to other PitNET is now well established. Moreover, although DAs therapy does not represent the first-line therapy for other PitNET, off-label use of DAs is considered in PitNET expressing D2DR. Nevertheless, DAs primary or secondary resistance, occurring in a subset of patients, may involve several molecular mechanisms, presently not fully elucidated. Dopamine receptors (DRs) expression is a prerequisite for a proper DA function in PitNET and several molecular events may negatively modify DR membrane expression, through the DRs down-regulation and intracellular trafficking, and DR signal transduction pathway. The current mini-review will summarise the presently known molecular events that underpin the unsuccessful therapy with DAs.

D. Gardner, D. Shoback