All Articles

Adekunle Olowu

Consultant Family Physician, Primary Health Care Corporation, Doha, Qatar

Assistant Professor, Weill Cornell Medicine, Doha, Qatar

Clinical Assistant Professor, Qatar University College of Medicine, Doha, Qatar

COVID-19 affected routine healthcare significantly and impaired the capability of healthcare organizations to deliver quality healthcare to achieve expected patient outcomes, including the care of patients with rare diseases. The rationale for this review is to highlight the important contribution of telemedicine technology to improving care quality of patients with rare diseases in a pandemic era.

Aims and Objective: To explore the role and impact of telemedicine digital technology usage and user satisfaction in patients with rare diseases in the last two years since the COVID-19 pandemic.

Methodology: An electronic database search was conducted using the PRISMA guide with search terms ‘telemedicine’ and ‘rare diseases’ in the last 2 years since the COVID-19 pandemic. The final search identified about 10 papers after screening, applying the exclusion criteria and sorting for eligibility and relevance.

Results: Of the 10 papers reviewed, 6 were research articles while 4 were review articles. For the research papers there were 5239 participants or responders in total, with 1476 (28.2%) patients, 50 (0.01%) carers and 3713 (70.9%) clinicians and workers. The average age recorded by 4 of the research papers was 43.4 years while one paper particularly emphasized that telemedicine digital technology was used preferably by clinicians below 50 years of age. 52.5% of Clinician and Worker participants in 2 Studies were Male while 47.5% were Female, while only 22% of patient participants were Male, with 78% being Female. One paper recorded the proportion of patients who used telemedicine as 22.8 %, a second recorded the highest proportion of clinicians’ telemedicine usage as 59.8%, a third paper concluded the highest number of carers who were satisfied with telemedicine usage was 90%, with 58% also supporting its usage and a fourth recorded that 86% of patients were satisfied with its usage. However, another paper recorded that 26% of clinicians (psychiatrists) were not keen to use telemedicine.

Conclusion: This review concludes that there is some evidence that telemedicine digital technology is a viable option and can be a long-term solution to primary care patients’ access to quality care in the post-pandemic era, including patients with rare diseases. International collaboration of clinicians via electronic or digital platforms will enhance quality of care, especially targeted to younger male physicians below the age of 50. Guidelines and protocol for its use within governmental laws and legal boundaries need to be strictly followed to ensure patient safety, reduce waiting times and achieve positive patient outcomes.

Joslyn Cabral¹, Martha Camacho Rodriguez¹, Gareb Feumba Othniel¹, Jessica Gordon¹, Stephanie Sanchez¹, Shervin Assari^1,2*

¹Department of Urban Public Health, Charles R. Drew University School of Medicine and Science, Los Angeles, California, USA

²Department of Family Medicine, Charles R. Drew University School of Medicine and Science, Los Angeles, California, USA

Background: One of the best recognized health effects of high educational attainment is lower body mass index (BMI), however recent research suggests that this association might be racialized and differ for Black and White individuals.

Aims: To investigate whether race moderates the inverse association between educational attainment and BMI as adults.

Methods: This study was a cross-sectional analysis of Midlife in the United States (MIDUS) Refresher with a total sample size of 1972 adults, 128 of whom are Black and 1842 of whom are White, above the age of 24 in the United States. The sample was randomly selected. Educational attainment and income were independent variables. BMI was the outcome. Linear regression was used for multivariable analysis. SPSS was used for data analysis.

Results: Income was inversely associated with BMI. There was a statistical interaction between race and educational attainment suggesting a weaker inverse association between education and BMI for Black than White adults.

Conclusion: Opposite to the pattern for Whites, being a highly educated individual in the US does not lend protection against high BMI for Black people. This finding may reflect racism, social stratification, and marginalization of Black Americans in the US, regardless of their education. High BMI of highly educated Black Americans may be due to poor nutrition, low physical activity, and/or low walkability of neighborhood; however, such conclusions require additional research.

Viktor I. Goudochnikov

Biochemistry, Member of ISOAD, Santa Maria – RS, Brazil

The review is presented about contribution of glucocorticoids and stress to programming / imprinting phenomena. After their definition, possible mechanisms of such phenomena are described, including the role of glucocorticoids in ontopathogenic model, as well as the ways of diminishing adverse effects of these hormones. It is outlined that health professionals should participate in educational campaigns for decreasing adverse actions of stress and glucocorticoids, especially in perinatal period. Moreover, DOHaD concept should be introduced to the contents of university courses in biomedical sciences.

Guangzhe Zheng^1,4#, Shihao Bi^2#, Jiayu Ren¹, Sijin Liu^1,3, Bin Shi^2*

¹Medical Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, China

²Neck-Shoulder and Lumbocrural Pain Hospital of Shandong First Medical University, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, China

³State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, China

⁴Department of Urology, Tianjin Institute of Urology, The Second Hospital of Tianjin Medical University, Tianjin, China

^#These authors contributed equally.

Occupational exposure to particulate matter (PM) induced pulmonary fibrosis has aroused broad public concern. Pulmonary interstitial fibrosis is a central pathologic process of pneumoconiosis. Meanwhile, ferroptosis is a newly defined iron-dependent programmed cell death (PCD) that features increased intracellular labile iron and lethal accumulation of lipid peroxidation. Ferroptosis has been found to involve particulate-induced cytotoxicity. Recent studies have suggested that ferroptosis is closely associated with the occurrence and progression of pulmonary fibrosis. Here, we present a mini review to summarize the main mechanisms responsible for PM-induced pulmonary fibrosis via inducing macrophage ferroptosis to provide new insights into basic and clinical research of pulmonary fibrosis.

Anthony C. Hackney^1,2*, Gabriel H. Zieff¹, Amy R. Lane¹, Johna K. Register-Mihalik¹

¹Department of Exercise & Sport Science, University of North Carolina, Chapel Hill, NC, USA

²Department of Nutrition, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, USA

We examined whether endurance training for a standard marathon (42.2 km) had a greater influence on male libido than more generalized endurance exercise training. We surveyed adult men (>1000) who regularly engaged in endurance running to evaluate exercise training histories-patterns and libido characteristics. Our participants were primarily recruited from North America and Europe. Results indicate men conducting marathon training had lower libido scores (p<0.05; ~20%, d=0.44) than those not doing such specific training. Factors most related to libido were: 1) the number of years of training, and 2) the proportion of high-intensity effort conducted in training (inverse relationships); regardless of whether marathon training was performed or not. Our survey approach did not allow us to determine the cause of the reduced libido, but we speculate it could relate to: 1) chronic physical fatigue from high volumes of exercise training, 2) behavioral accommodations in energy expenditure, or else ‘Relative Energy Deficiency in Sport’ (RED-S) syndrome, and/ or 3) endocrinological adaptations as a result of the exercise training (i.e., low testosterone). From a practical perspective, we recommend couples attempting conception should inform their healthcare providers of the male partner’s exercise habits concerning endurance running as this may be a factor relative to potential infertility.

Sigridur Fjalldal¹, Lars Stenberg², Sanaz Gabery³, Sven Karlsson⁴, Eva Marie Erfurth^4*

¹Department of Internal Medicine, Helsingborg Hospital, Sweden

²Department of Diagnostic Radiology, Skåne University Hospital, Lund, Sweden

³Translational Neuroendocrine Research Unit, Department of Experimental Medical Science, Lund University, Lund, Sweden

⁴Department of Endocrinology, Skåne University Hospital, Lund, Sweden

Context: Autoimmune hypothalamitis (AHT) is extremely rare and appears on the Magnetic resonance Imaging (MRI) as a predominant suprasellar mass. There are only a few case reports of AHT in the literature and none was presented together with hypothalamic obesity (HO). Methods of prediction of hypothalamus (HT) damage are included as the pathogenesis of HO.

Case description: A 19-year-old female was operated with a transcranial operation due to a large suprasellar mass with symptoms of visual deficiencies and headache. The diagnosis of AHT was confirmed in specimen of lymphocyte-dominated infiltration with plasma cells, neutrophils and fibrocytes. The operation reduced the AHT mass and a further reduction was accomplished by long-term oral Prednisone. Directly after operation she suffered from hypothalamic obesity which worsened after the introduction of Prednisone treatment. During Prednisone treatment a reduction in the inflammation mass and improvement of vision was recorded. She was treated with glucagon-like peptide 1 receptor agonist and Metformin as treatment for her diabetes mellitus type II and with supplementations of her pituitary insufficiencies. The patient exhibits dramatic weight reduction while on a strict caloric diet at two follow-up occasions. However, this effect was reversed once the patient had stopped the calorie restricted diet.

Conclusion: The coexistence of AHT and HO is extremely difficult to treat as the former involves Prednisone treatment. Pharmacological intervention of HO has had limited effect on weight, but extreme diet was successful, however with short endurance.

Qilu Yu^1,3, Maurice C. Johnson, Jr.¹, Howard A. Fishbein^1*, Rebecca J. Birch¹, Xiaoshu Zhu¹, Russ Mardon¹, Wilson Pace², Sunitha M. Mathew¹, Holly L. Sawyer¹, Lori S. Merrill¹, Keith D. Umbel¹, Sophia Jang¹

¹Westat, Rockville, MD, USA

²DARTNet, Aurora, CO, USA

³National Center for Complementary and Integrative Health (NCCIH), National Institutes of Health (NIH), Bethesda, MD, USA

We identified trajectories of diabetes risk factors in the Longitudinal Epidemiologic Assessment of Diabetes Risk (LEADR) cohort analyzing 8 years of electronic health records on 1.4 million patients, and investigated associations between trajectories and progression to new onset Type 2 diabetes.

Design and Methods: Analyzing LEADR data (2010-2016), we applied Latent Class Trajectory Analysis (LCTA) to classify patterns of risk factor change. There were 824,043 patients with BMIs; 955,128 patients with systolic blood pressures; 957,491 patients with diastolic blood pressures; 300,137 patients with HDLs; 267,553 patients with non-HDL cholesterols; and 297,026 patients with triglycerides. Patients had to have data for all risk factors being assessed. Association between trajectories and incidence of type 2 diabetes for 94,551 patients was assessed using negative binomial regression analysis.

Results: Compared to a static BMI trajectory, those with a sustained weight increase (25%+ from starting BMI) were at higher risk of type 2 diabetes over 4.8 years of follow-up (range 2.0 to 8.0 years) (adjusted rate ratios ranged 1.53-1.62, p-value<0.05). Patients with a BMI decrease trajectory (of ~10%), were at reduced risk of diabetes (adjusted rate ratios ranged 0.54-0.74, p-value<.05). BP and lipid trajectories had significant associations with diabetes onset.

Conclusions: Regardless of the starting BMI, those who increased their BMI by 25% within two years and maintained the higher weight were significantly at increased risk of type 2 diabetes. Monitoring BMI change and other known risk factor trajectories, BP and lipids, are additional tools for identifying patients at risk for type 2 diabetes.

Adekunle Olowu^1*, Adel Abbas Alzehairy²

¹Consultant Family Medicine, Al Thumama Health Centre, Primary Health Care Corporation, Doha, Qatar

²Formerly Specialist Family Medicine, Al Thumama Health Centre, Primary Health Care Corporation, Doha, Qatar

Adrenal cysts are rare lesions that could be epithelial, endothelial, parasitic or haemorrhagic¹, as well as pseudocysts. Haemorrhagic adrenal cysts are extremely rare and are often asymptomatic, so diagnosis can be really challenging. This can prove really difficult for primary care physicians who are often the frontline clinicians these patients tend to present to. They are usually benign lesions and do not often cause mortality if detected early and prompt surgery is done, as was the case with the patient in our case report⁴. When they do become symptomatic, they can present with different systemic symptoms as documented in literature, including in our case report^2,4. Diagnosis is usually through Ultrasound and CT Scan and management is largely laparoscopic or open excision depending on the size of the lesion, surgical expertise and local protocol. Most patients make full recovery and mortality is extremely low³. The aim of this review is to provide a broader overview of the subject, highlight salient points in several studies relating to haemorrhagic cysts, provide an up to date follow up information on the index patient in our case report and to explore possible areas for future study^4,6. This review also includes a suggested management algorithm and intends to emphasize the fact that patients who present in primary, urgent or emergency care settings with persistent non-specific symptoms should be investigated for rare diseases.

Maurice C. Johnson, Jr.¹, Howard A. Fishbein¹*, Rebecca Jeffries Birch¹, Qilu Yu², Russ Mardon¹, Wilson Pace³, Natalie Ritchie⁴, Jennifer K. Carroll⁵, Daniella Meeker⁶

¹Westat, Rockville, MD, USA

²National Center for Complementary and Integrative Health (NCCIH), National Institutes of Health (NIH), Bethesda, MD, USA

³DARTNet, Aurora, CO, USA

⁴University of Colorado/Denver Health and Hospitals Authority, USA

⁵University of Colorado, USA

⁶University of Southern California, USA 

Objective: This study examined the influential role of making a prediabetes diagnosis resulting in the subsequent delay in onset of type 2 diabetes.

Research Design and Methods: Using electronic medical records, a multivariable logistic regression model examined demographic and clinical risk factors associated with a prediabetes diagnosis among patients with HbA1c evidence of prediabetes. A multivariable non-proportional Cox regression examined development to type 2 diabetes (maximum 7 year follow-up).

Results: Analysis includes 40,970 patients with incident prediabetes (76.8% undiagnosed). Logistic regression showed higher baseline HbA1c levels significantly influenced assigning a prediabetes diagnosis: compared to patients with HbA1c level 5.7-5.9% (low), OR 1.66 (99% CI 1.54-1.78) for HbA1c level 6.0-6.2% (medium) and OR 1.62 (CI 1.43-1.83) for HbA1c level 6.3-6.4% (high). Cox model results, which included an interaction between HbA1c and prediabetes diagnosis, found HbA1c the most significant predictor. Patients with diagnosed prediabetes progressed to type 2 diabetes slower than those undiagnosed. Comparing diagnosed patients to undiagnosed within the same HbA1c level, HRs ranged from 0.47 (CI 0.37-0.61) in the high HbA1c level to 0.83 (CI 0.67-1.02) in the low HbA1c level.

Conclusions: From the LEADR cohort (1) HbA1c levels were the principle factor associated with risk for prediabetes diagnosis. Modeling development to diabetes, baseline HbA1c was the significant predictor of risk. Findings suggest assignment of a prediabetes diagnosis is associated with slower development of diabetes and this protective benefit of being diagnosed increases with a higher baseline HbA1c. Prediabetes diagnosis is useful for delaying onset of type 2 diabetes.

Nitchakarn Laichuthai¹, Ralph A. DeFronzo²*

¹Hormonal and Metabolic Disorders Research Unit and Excellence Center in Diabetes, Hormone, and Metabolism, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, and Division of Endocrinology and Metabolism, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand

²Diabetes Division, UT Health San Antonio and Texas Diabetes Institute, San Antonio, Texas, USA

Newly discovered abnormal glucose tolerance is common in patients who present with acute myocardial infarction (MI). These individuals are at very high risk for recurrent major adverse cardiovascular events (MACE), cardiovascular (CV) mortality, and all-cause mortality compared to normal-glucose-tolerant individuals who present with acute MI. Early and aggressive intervention with lifestyle and pharmacologic treatment are essential for the prevention of prediabetes progression to diabetes and recurrent cardiovascular events in this high risk population. Management, both with regard to prevention of recurrent cardiovascular events and development of diabetes, has been poorly addressed in current cardiology and diabetes guidelines. In this article, we review current evidence regarding the use of glucagon-like peptide 1 receptor agonists (GLP-1 RAs), sodium glucose cotransporter 2 inhibitors (SGLT2i), and pioglitazone to prevent recurrent cardiovascular events and propose areas of research to be explored in the future.

Salma Ahi

Research Center for Noncommunicable Diseases, Jahrom University of Medical Sciences, Jahrom, Iran

Sunil J. Wimalawansa

Professor of Medicine, Endocrinology & Nutrition, Cardiometabolic and Endocrine Institute, NJ, USA

In addition to being involved in the regulation of calcium and phosphate metabolism and the musculoskeletal functions, vitamin D has immune modulatory effects through several independent pathways. Its active hormone, calcitriol [1,25(OH)2D] effect both innate and adaptive immune systems essential for optimal immune functions. Vitamin D deficiency exacerbates immune-related disorders, including type 1 diabetes, multiple sclerosis, rheumatoid arthritis, psoriasis, respiratory infections, including COVID-19. In those with COVID-19, complications and the number of deaths is higher in those who are older than 70 years, persons with a darker skin colour and/or ethnic minorities living in colder climatic regions, institutionalized persons, and with pre-existing chronic diseases. These groups of people have exceedingly high prevalence of severe vitamin D deficiency and thereof weaker immune systems. Collectively, these increases the vulnerability to microbial infections, particularly respiratory viruses, and for developing severe complications and deaths. Vitamin D related immune protective effects includes, the generation of anti-microbial peptides cathelicidin and defensins and antibodies against invading pathogens; the initiation of immune defences via natural killer cells, macrophages, and epithelial cells; the enhanced expression of angiotensin-converting enzyme 2 (ACE-2) and diminish expression of inflammatory cytokines; and reduce replication and enhance elimination of viruses from the body. The severity of complications and deaths associated with COVID-19 markedly increases in the presence of severe hypovitaminosis D: serum 25(OH)D concentration of less than 10 ng/mL. Excess complications and deaths from COVID-19 can be cost-effectively prevented with rapidly boosting the immunity using upfront loading, high doses of vitamin D; this will create an equivalent of internal “body armour”-defence system, that protects against COVID-19.

Lorena V. Rincones Rojas, Amenaida C. Ferrer Marcano, Juan S. Mojica Muñoz, Angelica M. García, Luis G. Celis*

Faculty of Medicine – Universidad de la Sabana, Bogotá, Colombia

Overweight and obesity are considered a global epidemic in the twenty first century, it is a multifactorial disease due, in part, to a genetic component. The most common genetic alteration is one that affects the neuroregulatory pathway of Leptin, a fundamental hormone for appetite regulation. Mutations that affect the LEP gene are present in the different exons of this gene and have been described for many years. Although obesity due to a genetic mutation is not the most common cause, its diagnosis is of paramount importance since it can affect the quality of life and life expectancy of the patients suffering from this condition.

The purpose of this mini review is to present up-to-date evidence regarding Leptin gene mutations, possible treatment strategies such as Leptin Replacement Therapy (LRT), leptin sensitizers and anti-inflammatory drugs, and discuss the importance of stablishing health policies worldwide to achieve a timely and successful approach to this disease.

Dawood Khan, R Charlotte Moffett*

SAAD Centre for Pharmacy and Diabetes, Ulster University, Coleraine, Northern Ireland, UK

Polycystic ovary syndrome (PCOS) is a common endocrine disorder associated with infertility which affects one in ten women in the United Kingdom. Women with PCOS are typified by insulin resistance, gestational diabetes and obesity. Therefore, a close association between reproductive function and nutrition is postulated. However, regulatory pathways common to energy and reproductive function have received little attention. Recent research shows rapid amelioration of infertility, PCOS and type 2 diabetes following Roux-en-Y bariatric surgery (RYGB). This occurs prior to weight loss suggesting involvement of gut derived factors. Therefore, gut hormones emerge as key players in the regulation of both energy homeostasis and possibly reproductive function. Alteration of gut peptide levels including GLP-1, GIP, PYY, ghrelin, NPY and neurotensin post-bariatric surgery suggest a plausible mechanism behind beneficial effects of RYGB. Furthermore, expression of gut peptide receptors within the reproductive axis strengthen the idea of involvement of these hormones in the remission of fertility post-surgery. The present commentary discusses the role of these important gut peptides and their receptors in the regulation of female reproductive system in the light of a recent article published by our laboratory. Understanding the functional relationship between the gut and reproductive axis will help us to identify novel and less invasive alternatives to bariatric surgeries for reproductive and related metabolic disorders.

Aurelio Lo Buglio, Francesco Bellanti, Gianluigi Vendemiale*

Centre for Aging Research - Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy

Malnutrition is associated to poor clinical outcomes, especially in hospitalized patients. High prevalence of low-grade chronic inflammation, low skeletal muscle mass, and insulin resistance are often found in malnourished patients. Increasing evidence shows how these effects can be partially reverted through an adequate intake of food or using specific dietary supplementation. In this scenario, Mediterranean Diet (MD) demonstrated positive effects on the nutritional status, with important clinical finding in hospitalized patients such as low rate of length of stay and in-hospital mortality.

The aim of this review is the summary of the main evidence about the role of Mediterranean diet on health and clinical outcomes in hospitalized elderly patients.

Santosh Ramakrishnan¹*, Mohammed Yousuf Khan¹, Anantharaman Ramakrishnan², Shanmugasundar Gopal³, Rohit Warrier⁴

¹Consultant Endocrinologist & Diabetologist, Magna centres for Obesity, Diabetes & Endocrinology, Hyderabad, India

²Consultant Endocrinologist & Diabetologist, Magna centres for Obesity, Diabetes & Endocrinology, Bangalore, India

³Consultant Endocrinologist & Diabetologist, Magna centres for Obesity, Diabetes & Endocrinology, Chennai, India

⁴Consultant Diabetologist, Magna centres for Obesity, Diabetes & Endocrinology, Bangalore, India

Psoriasis is an immune mediated chronic skin disease associated with components of metabolic syndrome like obesity and type-2 diabetes. Previously, anti-diabetic drugs especially insulin sensitizers (metformin and pioglitazone) have shown positive outcomes in subjects with psoriasis¹. Recently, many case series and longitudinal observational studies previously have demonstrated improvement in psoriasis with GLP1 agonist therapy when followed up for 8-12 weeks^2,3. We report a patient with psoriasis and Type2 DM in whom a marked improvement in psoriasis was seen with liraglutide therapy, even with a short course of therapy for 4 weeks, which has not been previously recorded, to the best of our knowledge. This could be due to our subject possibly being a better GLP-1 responder based on baseline characteristics of relatively higher BMI and HbA1c⁴.

Catherine E. Kerr¹*, Sarah D. Hackman², Gary L. Francis¹

¹Department of Pediatrics1, Endocrinology and Diabetes, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA

²Department of Pathology and Laboratory Medicine2, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA

Santosh Ramakrishnan¹*, Anantharaman Ramakrishnan², Rohit Warrier³, Shanmugasundar Gopal⁴

¹Consultant Endocrinologist & Diabetologist, Magna centres Clinics for Obesity, Diabetes & Endocrinology, Hyderabad, India

²Consultant Endocrinologist & Diabetologist, Magna centres Clinics for Obesity, Diabetes & Endocrinology, Bangalore, India

³Consultant Diabetologist, Magna centres Clinics for Obesity, Diabetes & Endocrinology, Bangalore, India

⁴Consultant Endocrinologist & Diabetologist, Magna centres Clinics for Obesity, Diabetes & Endocrinology, Chennai, India

We describe a case where we effectively managed chronic, uncontrolled type 2 diabetes with hydroxychloroquine (HCQS) as an add on therapy, wherein the patient was on multiple oral hypoglycemic agents along with a combination of injectable incretin/insulin therapy prior to HCQS initiation. Six months into combination therapy with HCQS, the target HbA1c was achieved for the first time in the patient’s recent history at a much lower daily insulin dose (56% requirement drop), which has never been documented before. This combination also resulted in significant weight loss. We make a case for advocating the use of HCQS to the available routine diabetes therapeutic agents, especially if the blood sugars fail to achieve target levels in spite of being on intensive management with insulin and for the obese phenotype.

Paolo Lissoni¹*, Antonio Bastone¹, Arianna Lissoni¹, Franco Rovelli¹, Giuseppe Di Fede¹

¹Institute of Biological Medicine, Milan, Italy

Several clinical studies have shown that blood pressure (BP) declines during the night in the healthy subjects, and that BP circadian rhythm tends to disappear with age. The mechanisms responsible for BP circadian rhythm and its aging-dependent loss need to be further understood. At present, it is already known that the two main hormones provided by hypotensive activity, consisting of the cardiac hormone atrial natriuretic peptide (ANP) and the pineal indole hormone melatonin (MLT), are mainly produced during the night, whereas hypertensive hormones, such as cortisol, are mainly produced during the early period of light phase. Then, the circadian variations of BP would be the consequence of changes in the neuroendocrine system. On this basis, a preliminary study was performed to establish which relation may exist among BP, ANP and MLT rhythms in the healthy subjects. The study included 20 65-year younger, and 20 65-year older healthy subjects. In 65-year younger subjects, both systolic and diastolic BP mean values significantly decreased during the night, whereas no significant difference occurred in the 65-older ones, because of BP values decreased in the night only in 13/20 (65) subjects. In addition, within the 65-year older group, both ANP and MLT night mean values were significantly higher in subjects with BP rhythm than in those, who had no BP daily variations. These preliminary results would suggest that age-dependent loss in the circadian rhythm of BP may be caused by the concomitant loss in the circadian secretion of at least two major hypotensive hormones, such as ANP and MLT.