Andromachi Vryonidou

Bilateral adrenal incidentalomas differ from unilateral adrenal incidentalomas in subclinical cortisol hypersecretion but not in potential clinical implications

OBJECTIVE To investigate the possibility of a different prevalence of subclinical Cushings syndrome (SCS) and potentially related morbidities between patients with unilateral adrenal incidentalomas (UAI) and bilateral adrenal incidentalomas (BAI), as existing data are few and controversial. DESIGN Prospective observational study. METHODS Clinical examination, biochemical tests, and hormonal evaluation were performed in 298 consecutive patients with adrenal incidentalomas, unilateral in 224 patients (75.2%), bilateral in 74 patients (24.8%), with apparently benign masses based on imaging characteristics and after exclusion of overt endocrine disease. The diagnosis of SCS was based on a post-dexamethasone suppression test (2 mg dexamethasone/24 h for 48 h), with serum cortisol level ≥1.8 μg/dl combined with at least one abnormal result of the other hormonal measurements. RESULTS SCS was diagnosed in 66 out of 298 (22.1%) patients, being more frequent in patients with BAI (35.1 vs 17.9%, P=0.003, for BAI and UAI respectively). Hypertension, type 2 diabetes mellitus, impaired glucose tolerance, and dyslipidemia were of a similar frequency in both groups. SCS patients with UAI and BAI did not differ in age, gender, BMI, waist circumference, and mass size. Factors related to SCS were the presence of BAI (OR, 3.24; 95% CI, 2.31-4.54) and mass size (OR, 2.63; 95% CI, 1.31-5.26). CONCLUSION BAI patients present more often with SCS when compared with UAI patients; however, morbidities potentially related to subtle cortisol hypersecretion were of a similar frequency in both groups. Further studies are needed to clarify whether this difference in hormonal activity may be related to different pathophysiologies.

MECHANISMS IN ENDOCRINOLOGY: Metabolic syndrome through the female life cycle

The normal function of the female reproductive system is closely linked to energy homeostasis with the ultimate scope of fertility and human race perpetuation through the centuries. During a womans lifetime there are normal events such as puberty, pregnancy and menopause which are related to alterations in energy homeostasis and gonadal steroids levels followed by increase of body fat and insulin resistance, important components of metabolic syndrome (MetS). Pathological conditions such as premature adrenarche, polycystic ovary syndrome and gestational diabetes also present with shifts in gonadal steroid levels and reduced insulin sensitivity. The aim of this review is to discuss these conditions, both normal and pathological, analyzing the changes or abnormalities in ovarian function that coexist with metabolic abnormalities which resemble MetS in relationship with environmental, genetic and epigenetic factors.

Diabetic cardiomyopathy: a clinical entity or a cluster of molecular heart changes?

Although the increasing rate of cardiovascular mortality in patients with diabetes is thought to be due to the coronary atherosclerosis caused mainly by compounding factors such as dyslipidaemia and hypertension, it is now well documented that diabetes alone can lead to a vast array of molecular changes in the heart.

MECHANISMS IN ENDOCRINOLOGY: Aging and anti-aging: a Combo-Endocrinology overview

Aging and its underlying pathophysiological background has always attracted the attention of the scientific society. Defined as the gradual, time-dependent, heterogeneous decline of physiological functions, aging is orchestrated by a plethora of molecular mechanisms, which vividly interact to alter body homeostasis. The ability of an organism to adjust to these alterations, in conjunction with the dynamic effect of various environmental stimuli across lifespan, promotes longevity, frailty or disease. Endocrine function undergoes major changes during aging, as well. Specifically, alterations in hormonal networks and concomitant hormonal deficits/excess, augmented by poor sensitivity of tissues to their action, take place. As hypothalamic-pituitary unit is the central regulator of crucial body functions, these alterations can be translated in significant clinical sequelae that can impair the quality of life and promote frailty and disease. Delineating the hormonal signaling alterations that occur across lifespan and exploring possible remedial interventions could possibly help us improve the quality of life of the elderly and promote longevity.

Birth weight and polycystic ovary syndrome in adult life: is there a causal link?

Objectives Several studies have demonstrated associations of birth weight with metabolic and reproductive abnormalities in adults. The aim of this study was to investigate the birth weight in women with PCOS and its correlation with clinical and biochemical characteristics of the syndrome. Materials and Methods We studied 288 women with PCOS according to the NIH criteria and 166 women with normal cycle and without clinical hyperandrogenism. Birth weight and anthropometric characteristics were recorded, and levels of serum androgens, SHBG, insulin and fasting glucose were measured. Results Birth weight data were available for 243/288 women with PCOS and age- and BMI-matched 101/166 controls. No differences were found (p> 0.05) in birth weight among women with PCOS and normal controls. Birth weight of PCOS women was negatively correlated with DHEAS levels (p = 0.031, r = -0.143) and positively correlated with waist circumference (p <0.001, r = 0.297) and body mass index (BMI) (p = 0.040, r = 0.132). Birth weight of controls was negatively correlated with SHBG levels (p = 0.021, r = -0.234). Women from both groups were further divided in 6 categories according to birth weight (A. <2.500 gr, B. 2.501-3.000 gr, C. 3.001-3.500 gr, D. 3.501-4.000 gr, E. 4.001-4.500 gr, F. > 4.500 gr). No statistically significant differences were observed in the distribution percentages between PCOS women and controls. (A. 7% vs 7.9%, B. 26.8% vs 20.8%, C. 39.1% vs 48.5%, D. 21.4% vs 20.8%, E. 4.9% vs 2%, F. 0.8% vs 0%), (in all comparisons, p> 0.05). Conclusions Women with PCOS do not differ from controls in birth weight distribution. However, birth weight may contribute to subtypes of the syndrome that are characterized by adrenal hyperandrogenism and central obesity.

Type 2 Diabetes and Osteoporosis: A Guide to Optimal Management

Context Both type 2 diabetes (T2D) and osteoporosis are affected by aging and quite often coexist. Furthermore, the fracture risk in patients with T2D is increased. The aim of this article is to review updated information on osteoporosis and fracture risk in patients with T2D, to discuss the effects of diabetes treatment on bone metabolism, as well as the effect of antiosteoporotic medications on the incidence and control of T2D, and to provide a personalized guide to the optimal management. Evidence Acquisition A systematic literature search for human studies was conducted in three electronic databases (PubMed, Cochrane, and EMBASE) until March 2017. Regarding recommendations, we adopted the grading system introduced by the American College of Physicians. Evidence Synthesis The results are presented in systematic tables. Healthy diet and physical exercise are very important for the prevention and treatment of both entities. Metformin, sulfonylureas, dipeptidyl peptidase-4 inhibitors, and glucagon-like peptide-1 receptor agonists should be preferred for the treatment of T2D in these patients, whereas strict targets should be avoided for the fear of hypoglycemia, falls, and fractures. Insulin should be used with caution and with careful measures to avoid hypoglycemia. Thiazolidinediones and canagliflozin should be avoided, whereas other sodium-dependent glucose transporter 2 inhibitors are less well-validated options. Insulin therapy is the preferred method for achieving glycemic control in hospitalized patients with T2D and fractures. The treatment and monitoring of osteoporosis should be continued without important amendments because of the presence of T2D. Conclusions Patients with coexisting T2D and osteoporosis should be managed in an optimal way according to scientific evidence.

Changes in Thyroid Hormone Levels Within the Normal and/or Subclinical Hyper- or Hypothyroid Range Do Not Affect Circulating Irisin Levels in Humans

BACKGROUND Both thyroid hormones and irisin increase energy expenditure and induce browning of adipose tissue. However, irisin physiology and regulation remain largely unknown, and existing data are mainly derived from observational studies. In this study, we aimed to elucidate whether changes in thyroid-axis hormones alter circulating irisin levels in humans, thereby exerting a direct downstream effect on serum irisin. SUBJECTS AND METHODS Samples from a cross-sectional evaluation and two interventions were utilized, including patients who had previously undergone thyroidectomy. In the cross-sectional study, 96 consecutively enrolled subjects were divided into a euthyroid group and a subclinical hyperthyroid group, according to their serum thyrotropin (TSH) levels (TSH cutoff 0.3 mIU/L). In interventional study A, 34 patients who had undergone thyroidectomy due to thyroid cancer were withdrawn from their thyroxine replacement treatment for five weeks. In interventional study B, 13 patients underwent a recombinant human TSH stimulation protocol, and blood samples were drawn at baseline, day 3 (i.e., at least 24 hours after the second intramuscular injection), day 5, and day 10. RESULTS Irisin concentrations were not associated with thyroid-axis hormones (i.e., TSH, free thyroxine, and free triiodiothyronine) cross-sectionally in either the overall cohort or in the euthyroid and/or subclinical hyperthyroid subgroups (p > 0.05). There was no significant difference between euthyroid and subclinical hyperthyroid subjects (p = 0.60). Levothyroxine withdrawal did not result in any changes in irisin concentrations (p = 0.33). Recombinant human TSH stimulation did not induce any significant changes in circulating irisin (p = 0.60). CONCLUSIONS Changes in thyroid-axis hormone levels within the physiological or supraphysiological range do not affect circulating irisin levels in humans. Therefore, their metabolic effects are most likely independent of each other. Other regulators of irisin levels should be identified in the future.

Pituitary abscess: a case report and review of the literature

Summary Pituitary abscess is a rare life-threating entity that is usually misdiagnosed as a pituitary tumor with a definite diagnosis only made postoperatively. Over the last several decades, advances in healthcare have led to a significant decrease in morbidity and mortality due to pituitary abscess. We report a case of a 34-year-old woman who was admitted to our department for investigation of a pituitary mass and with symptoms of pituitary dysfunction, headaches and impaired vision. During her admission, she developed meningitis-like symptoms and was treated with antibiotics. She eventually underwent transsphenoidal surgery for excision of the pituitary mass. A significant amount of pus was evident intraoperatively; however, no pathogen was isolated. Six months later, the patient was well and had full recovery of the anterior pituitary function. Her menses returned, and she was only on treatment with desmopressin for diabetes insipidus that developed postoperatively. Learning points Pituitary abscess is a rare disease and the reported clinical features vary mimicking other pituitary lesions. The diagnosis of pituitary abscess is often very difficult to make and rarely included in the differential. The histological findings of acute inflammatory infiltration confirm the diagnosis of pituitary abscess. Medical and surgical treatment is usually recommended upon diagnosis of a pituitary abscess.

Pituitary incidentalomas: A guide to assessment, treatment and follow-up.

Pituitary incidentalomas are lesions which are detected incidentally in the pituitary gland during imaging procedures for unrelated causes, such as headache, trauma or symptoms involving the neck or central nervous system. The wide application of sensitive brain imaging techniques (CT, MRI) has led to an increasing recognition of such lesions. Although the etiology of pituitary incidentalomas covers a wide range of pathologies, most of them (∼90%) are benign adenomas; nonetheless, they may result in visual and/or neurologic abnormalities. By definition, micro-incidentalomas have maximum diameter of less than 1cm, while macro-incidentalomas are at least 1cm. Micro-incidentalomas have a reported mean prevalence in normal individuals of around 10%. The endocrinologist facing a pituitary incidentaloma has to solve two main diagnostic problems: (i) the nature and extent of the lesion, and (ii) whether hormonal excess or deficits result from the lesion. The former is achieved by the use of pituitary MRI and visual field (VF) examination and the latter by basal or dynamic hormonal assessments. The answers to these two questions will guide the treatment and follow-up. VF deficits or neurological disturbances due to compression of the optic chiasm or nerve by the incidentaloma are the strongest recommendations for surgery. Furthermore, hormonally active incidentalomas, with the exception of prolactinomas, should be treated by surgery. Most cases of pituitary incidentalomas do not meet criteria for surgical excision, but may require follow-up. The follow-up strategy consists of clinical evaluation, pituitary MRI, VF examination and hormonal assessments. Macro-incidentalomas require more extensive initial investigation, as well as closer MRI surveillance, than micro-incidentalomas. Diagnostic, treatment and follow-up strategies should be in alignment with the optimal personalized clinical benefit.

Hypertension in patients with type 2 diabetes mellitus: Targets and management

Two-thirds of patients with type 2 diabetes mellitus (T2DM) have arterial hypertension. Hypertension increases the incidence of both micro- and macrovascular complications in these patients, while the co-existence of these two major risk factors leads to a four-fold increased risk for cardiovascular disease (CVD) compared with normotensive non-diabetic controls. The aim of this article is to comprehensively review the literature and present updated information on targets for blood pressure (BP) and on the management of hypertension in patients with T2DM. A BP target of <140/90 mmHg applies to most patients, but individualization is always important. All classes of antihypertensive drugs can be used in the management of hypertension in patients with T2DM, as long as they are effective and safe and after taking co-morbidities into account. Angiotensin-converting-enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) are the ideal choice for initial or early treatment of hypertension in patients with T2DM and albuminuria. Combination of two or more drugs seems to be inevitable as most of these patients demonstrate resistant hypertension. The combination of ACE inhibitors with ARBs should be avoided. Thiazide and thiazide-like diuretics might be beneficial, alone or in a fixed-dose combination with ACE inhibitors or ARBs. Calcium channel blockers (CCBs) constitute an ideal option as a second- or third-line agent. Beta-blockers are not considered as first-line antihypertensive agents, except for those patients with heart failure or previous myocardial infarction. The addition of mineralocorticoid receptor antagonists to a triple-drug therapy seems the next ideal step. Gender-specific characteristics regarding BP, T2DM and CVD should be taken into consideration, even if different recommendations do not exist yet.