Primary Aldosteronism: Cardiovascular Risk, Diagnosis, and Management.

Primary aldosteronism remains a leading cause of secondary hypertension, and its diagnosis and management continue to pose a challenge for clinicians. In this article, we review the diagnosis of primary aldosteronism along with its cardiovascular manifestations. Treatment is described depending on the diagnostic outcome, focusing on medical management with mineralocorticoid receptor antagonists and unilateral adrenalectomy. Although screening and diagnosing hyperaldosteronism follows well-known algorithms, in practice, physicians may find difficulty establishing the best course of action due to complexity in testing and confirming laterality of aldosterone production by the adrenals. Recognizing and treating primary aldosteronism requires a multidisciplinary approach with primary care physicians, cardiologists, endocrinologists, and radiologists working collaboratively.

Cardiovascular Manifestations of Pheochromocytoma.

Pheochromocytomas are rare endocrine tumors that can have a significant impact on a variety of organ systems, including the cardiovascular system. Although the pathophysiology is not completely understood, pheochromocytomas exert their effects through high levels of catecholamines, mainly epinephrine and norepinephrine, which stimulate adrenergic receptors, including those within the cardiovascular system. Although the most common cardiovascular manifestation is hypertension, patients with pheochromocytoma can present with arrhythmia, hypotension, shock, myocardial ischemia, cardiomyopathy, aortic dissection, and peripheral ischemia. The medical management of the cardiovascular effects of pheochromocytoma is via blockade of adrenergic receptors, usually through the use of alpha blockers, with the addition of beta blockers if needed. However, only surgical resection of the pheochromocytoma is potentially curative, and this tumor requires unique management perioperatively. Because of the variability of presentation and the significant morbidity and mortality of patients with an undiagnosed pheochromocytoma, this entity should not be overlooked in the evaluation of patients with a wide variety of cardiovascular disorders.

Nilotinib-Associated Destructive Thyroiditis.

Protein tyrosine kinase inhibitors are currently an important drug class in the treatment of leukemia. They represent targeted cancer therapy and have become the treatment of choice in chronic myeloid leukemia. Tyrosine kinases are enzymes expressed in multiple tissues and are involved in several signaling pathways influencing cellular growth. Below we describe a patient who developed an unusual complication of tyrosine kinase inhibitor therapy: thyrotoxicosis due to destructive thyroiditis. We review the pathophysiology of tyrosine kinase inhibitor-induced thyroid dysfunction particularly with regard to new second-generation tyrosine kinase inhibitors.

Megace Mystery: A Case of Central Adrenal Insufficiency.

Megestrol acetate (MA) is a synthetic progestin with both antineoplastic and orexigenic properties. In addition to its effects on the progesterone receptor, MA also binds the glucocorticoid receptor. Some patients receiving MA therapy have been reported to develop clinical features of glucocorticoid excess, while others have experienced the clinical syndrome of cortisol deficiency-either following withdrawal of MA therapy or during active treatment. We describe a patient who presented with clinical and biochemical features of central adrenal insufficiency. Pituitary function was otherwise essentially normal, and the etiology of the isolated ACTH suppression was initially unclear. The use of an exogenous glucocorticoid was suspected but was initially denied by the patient; ultimately, the culprit medication was uncovered when a synthetic steroid screen revealed the presence of MA. The patient's symptoms improved after she was switched to hydrocortisone. Clinicians should be aware of the potential effects of MA on the hypothalamic-pituitary-adrenal (HPA) axis.

Subclinical hyperthyroidism and cardiovascular risk: recommendations for treatment.

Subclinical hyperthyroidism (SHy), the mildest form of hyperthyroidism, is diagnosed in patients having a persistently low or undetectable serum concentration of thyroid-stimulating hormone (TSH) with normal free T4 and T3 concentrations. Although overt hyperthyroidism is associated with an increased risk of adverse cardiovascular outcomes, the cardiovascular risk of SHy is controversial. Multiple studies have demonstrated an increased risk of atrial fibrillation, especially in older individuals with TSH levels <0.1 mU/L. The effects of SHy on all-cause and cardiovascular mortality are not clear, but recent meta-analyses suggest a modest increase in mortality, with the risk increasing with age and associated with the lowest TSH levels. The long-term consequences of SHy in young- and middle-aged adults, and in those with TSH levels are mildly low, are uncertain. For these reasons, guidelines for treatment are based on patient age, the degree of TSH suppression, symptoms consistent with hyperthyroidism, and overall cardiovascular and osteoporotic fracture risks.

Vitamin D and retinopathy in adults with diabetes mellitus.

OBJECTIVE To explore a hypothesized association between vitamin D inadequacy and diabetic retinopathy. METHODS This cross-sectional study analyzed data from individuals aged 40 years and older with diabetes mellitus who participated in the interview and medical examination components of the Third National Health and Nutrition Examination Survey conducted from October 1, 1988, through September 30, 1994. The relationship between diabetic retinopathy and serum 25-hydroxyvitamin D concentration was evaluated using regression analysis in the presence of demographic and clinical covariates, such as age, race, obesity, and persistent hyperglycemia. RESULTS On the basis of the 1790 adults with diabetes who met the study's inclusion criteria, the percentage of individuals with vitamin D deficiency increased with severity of retinopathy: no retinopathy, 27.9%; mild, 28.2%; moderate to severe, 43.2%; and proliferative, 64.6% (P = .01). Regression analysis of retinopathy severity vs serum 25-hydroxyvitamin D concentration did not demonstrate a statistically significant relationship between the two variables (P = .07). CONCLUSIONS This study found an association between severity of diabetic retinopathy and prevalence of vitamin D deficiency, but the findings were inconclusive about the existence of a relationship between retinopathy severity and serum 25-hydroxyvitamin D concentration. Given previous research indicating possible anti-inflammatory and antiangiogenic properties of vitamin D, the connection between vitamin D and diabetic retinopathy warrants further study.

Growth hormone and the cardiovascular system.

Growth hormone (GH) exerts its effects through insulin-like growth factor-1, and although ubiquitous in human tissues, it has a significant role in cardiovascular function. In recent years, there has been a great deal of interest in GH as an etiologic factor in many cardiovascular disease states. Acromegaly, a state of endogenous GH excess, results in myocardial hypertrophy and decreased cardiac performance with increased cardiovascular mortality. Additional insight into the role of excess GH on the cardiovascular system has been gained from data collected in athletes doping with GH. Likewise, GH deficiency is associated with increased mortality, possibly from the associated increase in atherosclerosis, lipid abnormalities, and endothelial dysfunction. However, further research is required to clarify the benefit of GH treatment in both deficient states and in heart failure patients.

Subclinical hypothyroidism and cardiovascular risk: recommendations for treatment.

The definition of subclinical hypothyroidism (SCH) is solely biochemical: a serum free T4 level within the reference range in the presence of an elevated serum thyroid-stimulating hormone (TSH) level. While overt hypothyroidism is associated with an increased cardiovascular disease risk, SCH, the mildest form of hypothyroidism, may also be associated with an increased cardiovascular disease risk, but to a lesser degree. Recent evidence points to a significant trend toward an increase in cardiovascular risk at higher TSH levels, with TSH levels ≥10 mIU/L associated with increased cardiovascular morbidity and mortality. It is generally recommended to treat with thyroid hormone those individuals with SCH and TSH values ≥10 mIU/L. Treatment of patients with SCH and TSH values <10 is controversial but may be considered in selected patients.

Impact of glycemic treatment choices on cardiovascular complications in type 2 diabetes.

As the diabetic population has significant morbidity and mortality from cardiovascular disease (CVD), much of its medical care focuses on CVD prevention and treatment. Some medications used to treat hyperglycemia may have beneficial effects on CV outcomes, others may have negative effects, while still others seem to have no direct effect. Although past epidemiological studies have shown a relationship between glycated hemoglobin levels and CV events in patients with type 2 diabetes, recent large randomized clinical trials (ACCORD, ADVANCE, and VADT) lasting 3.5 to 5.6 years have found that intensive glycemic control either has no impact on CV outcomes or even worsens them. Results of the 10-year follow-up of the UKPDS suggest that tight glycemic control of younger, newly diagnosed patients with type 2 diabetes may have CV benefits many years later. Because the pathogenesis of atherosclerosis spans decades, it may be that beneficial effects of tight glycemic control on CV outcomes are mainly in younger patients without established macrovascular disease. There is an emerging notion that tight glycemic control may be beneficial in primary prevention of CVD in younger patients with diabetes, but may become deleterious in older patients with established or subclinical CVD. Thus, while tight control may lessen microvascular disease, it may increase the risk of hypoglycemia and possibly of adverse CV events. In each patient, the goals of glycemic control need to be individualized based on age, overall prognosis, presence of macrovascular disease, and risk of hypoglycemia.