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Adrenal insufficiency is the clinical manifestation of deficient production or action of glucocorticoids, with or without deficiency also in mineralocorticoids and adrenal androgens. It is a life-threatening disorder that can result from primary adrenal failure or secondary adrenal disease due to impairment of the hypothalamic–pituitary axis. Prompt diagnosis and management are essential. The clinical manifestations of primary adrenal insufficiency result from deficiency of all adrenocortical hormones, but they can also include signs of other concurrent autoimmune conditions. In secondary or tertiary adrenal insufficiency, the clinical picture results from glucocorticoid deficiency only, but manifestations of the primary pathological disorder can also be present. The diagnostic investigation, although well established, can be challenging, especially in patients with secondary or tertiary adrenal insufficiency. We summarise knowledge at this time on the epidemiology, causal mechanisms, pathophysiology, clinical manifestations, diagnosis, and management of this disorder.

Substantial developments have occurred in the past 5–10 years in clinical translational research of thyroid cancer. Diagnostic molecular markers, such as RET-PTC, RAS, and BRAFV600E mutations; galectin 3; and a new gene expression classifier, are outstanding examples that have improved diagnosis of thyroid nodules. BRAF mutation is a prognostic genetic marker that has improved risk stratification and hence tailored management of patients with thyroid cancer, including those with conventionally low risks. Novel molecular-targeted treatments hold great promise for radioiodine-refractory and surgically inoperable thyroid cancers as shown in clinical trials; such treatments are likely to become a component of the standard treatment regimen for patients with thyroid cancer in the near future. These novel molecular-based management strategies for thyroid nodules and thyroid cancer are the most exciting developments in this unprecedented era of molecular thyroid-cancer medicine.

After a prolonged response, an anaplastic thyroid cancer developed resistance to mammalian target of rapamycin (mTOR) inhibition by somatic mutation of mTOR at the everolimus binding site. The mutant enzyme retained in vitro responsiveness to an mTOR kinase inhibitor. A better understanding of the mechanisms of sensitivity and resistance to anticancer therapies may improve patient selection and allow the development of rational treatment designs. One approach involves studying paired biopsy samples of pretreatment and drug-resistant tumors obtained from patients with exquisite sensitivity or unusually durable responses to therapy. Everolimus is a Food and Drug Administration–approved oral allosteric inhibitor of mTOR. Tumors that exhibit a dependency on the mTOR pathway might have enhanced sensitivity to mTOR inhibition. Inactivating mutations in the tumor-suppressor genes TSC1, TSC2, and STK11 result in mTOR-pathway activation and are targetable by TOR inhibitors in hamartoma syndromes . . .

Inhibition of mitogen-activated protein kinase resulted in an increase in expression of the sodium–iodide symporter in 12 of 20 patients, 8 of whom had sufficient uptake to warrant treatment with radioiodine. Five patients had a response, and 3 had stable disease. Metastatic disease is the most frequent cause of death related to thyroid cancer. 1 Radioiodine (iodine-131) remains a mainstay of therapy for patients with metastatic thyroid cancer of follicular origin (i.e., papillary thyroid cancer or follicular thyroid cancer). Unfortunately, many patients have tumors that do not concentrate iodine, resulting in radioiodine resistance and a poor prognosis (the 10-year survival rate among patients with metastatic thyroid cancer that retains radioiodine avidity is approximately 60%, whereas it is only 10% if the metastases are refractory to radioiodine therapy). 2 Several trials have evaluated strategies to “redifferentiate” metastatic thyroid cancers and render them responsive to . . .

Corticotropin-independent Cushing's syndrome occurs with adrenocortical tumors or hyperplasia. The authors report that germline duplications of PRKACA lead to bilateral adrenal hyperplasia, whereas somatic mutations lead to unilateral cortisol-producing adrenal adenomas. Endogenous hypercortisolism, referred to as Cushing's syndrome, is associated with substantial morbidity and mortality. 1 When Cushing's syndrome is severe, patients have catabolic symptoms such as muscle weakness, skin fragility, osteoporosis, and severe metabolic sequelae. 2 Hypersecretion of cortisol can be driven by an excess of pituitary or ectopic corticotropin or can be due to adrenocortical tumors or hyperplasias with corticotropin-independent cortisol production. Adrenal adenomas are common, with a prevalence of at least 3% among persons older than 50 years of age. 3 Whereas only a subset of these tumors is associated with overt Cushing's syndrome, some degree of cortisol excess is present, . . .

A significant fraction of fine-needle aspirates obtained from thyroid nodules are read as indeterminate. A new molecular test accurately predicts whether a cytologically indeterminate nodule is benign 93% of the time, permitting a conservative approach to management. Thyroid nodules are common and are usually benign. 1 However, 5 to 15% prove to be malignant; accordingly, identification of a nodule 1 cm or larger in diameter often prompts a diagnostic evaluation. 2 , 3 The cornerstone of thyroid-nodule evaluation is fine-needle aspiration, 4 which enables the assessment of cellular morphologic features that could not be identified by means of clinical assessment or imaging. Preoperative, ultrasonographically guided fine-needle aspiration has been shown to accurately classify 62 to 85% of thyroid nodules as benign, thereby avoiding diagnostic surgery. 5 However, 15 to 30% of aspirations yield indeterminate cytologic findings, 4 which include three subtypes: “atypia (or . . .

This article reviews the mechanisms that lead to the development of Graves' ophthalmopathy. A central feature in its development is autoimmunity that involves not only T cells, B cells, and macrophages but also fibroblasts and adipose tissue within the orbit. Intraorbital cytokine-mediated inflammation also has a prominent role. These recent findings suggest new ways of treating this debilitating disease. This article reviews the mechanisms that lead to the development of Graves' ophthalmopathy. Recent findings suggest new ways of treating this debilitating disease. Graves' ophthalmopathy, also called Graves' orbitopathy, is a potentially sight-threatening ocular disease that has puzzled physicians and scientists for nearly two centuries. 1 – 3 Generally occurring in patients with hyperthyroidism or a history of hyperthyroidism due to Graves' disease, Graves' ophthalmopathy is also known as thyroid-associated ophthalmopathy or thyroid eye disease, because it sometimes occurs in patients with euthyroid or hypothyroid chronic autoimmune thyroiditis. The condition has an annual adjusted incidence rate of 16 women and 3 men per 100,000 population. 4 This review explores the perplexing relationship between Graves' ophthalmopathy, hyperthyroidism, and thyroid dermopathy, the associated skin condition. I examine clinical . . .

Pituitary tumors account for about 15% of primary intracranial neoplasms. Proliferation of pituitary cells, which secrete hormones, may result in a spectrum of endocrine symptoms. Tumors that originate from pituitary somatotroph cells lead to aberrant secretion of growth hormone and the distinctive features of acromegaly. This review discusses advances in the understanding and treatment of acromegaly. Tumors that originate from pituitary somatotroph cells lead to aberrant secretion of growth hormone and the distinctive features of acromegaly. This review discusses advances in the understanding and treatment of acromegaly. Pituitary tumors account for about 15% of primary intracranial neoplasms. 1 Given the critical location of the gland, expanding tumors cause compressive symptoms. Furthermore, as pituitary cells secrete hormones, the proliferation of these cells may lead to a spectrum of endocrine symptoms. When tumors arise in pituitary somatotroph cells, aberrant secretion of growth hormone leads to the distinctive features of acromegaly. Understanding the development, function, and regulation of somatotroph cells provides insight into the cellular origin of this tumor, as well as approaches to the treatment of acromegaly. This review discusses advances in the understanding and treatment of acromegaly that have . . .

This trial compared two thyrotropin-stimulation methods and two 131I doses for postoperative ablation in patients with low-risk thyroid cancer. Rates of ablation were similar in all treatment groups. Doses lower than those currently recommended may be adequate for this condition. Radioiodine ( 131 i) is administered to patients with thyroid cancer after total thyroidectomy for three reasons 1 – 3 : first, to eradicate normal-thyroid remnants (ablation) in order to achieve an undetectable serum thyroglobulin level; second, to irradiate any neoplastic focus in order to decrease the risk of recurrence; and third, to perform 131 I total-body scanning for persistent carcinoma. Successful ablation is defined by the combination of undetectable serum thyroglobulin levels after thyrotropin stimulation and normal results on neck ultrasonography 6 to 12 months after 131 I administration. 2 , 3 When these criteria are met, approximately 1% of patients have a recurrence. 4 – 6 In . . .