TM is a rare event, is more frequent in patients older than 60 years, and has the same impact on prognosis as nonthyroidal metastases. Although thyroidectomy may be useful to avoid further dissemination of the primary tumour in case of solitary TM, it does not contribute to prolonging patient's life.

Riedel thyroiditis (RT) is an uncommon form of chronic thyroiditis in which the thyroid gland is replaced by fibrous tissue. The etiologic mechanisms underlying RT are unclear: the prevailing view is that it is part of a generalized fibroinflammatory process also involving other organs. The clinical manifestations of RT are protean, often resembling malignancy owing to goiter of remarkably hard consistency. Physical examination, laboratory analysis, cytology, and imaging features are not useful for differentiating between RT and neoplastic diseases or the fibrous variant of Hashimoto thyroiditis in the presurgical evaluation of patients. Histologic examination is necessary to establish the final diagnosis of RT. The present article reviews the most recent concepts about etiologic mechanisms, pathogenesis, diagnosis, and management of RT

Chronic glucocorticoid (GC) treatment represents a widely-prescribed therapy for several diseases in consideration of both anti-inflammatory and immunosuppressive activity but, if used at high doses for prolonged periods, it can determine the systemic effects characteristic of Cushing’s syndrome. In addition to signs and symptoms of hypercortisolism, patients on chronic GC therapy are at risk to develop tertiary adrenal insufficiency after the reduction or the withdrawal of corticosteroids or during acute stress. This effect is mediated by the negative feedback loop on the hypothalamus-pituitary-adrenal (HPA) axis, which mainly involves corticotropin-release hormone (CRH), which represents the most important driver of adrenocorticotropic hormone (ACTH) release. In fact, after withdrawal of chronic GC treatment, reactivation of CRH secretion is a necessary prerequisite for the recovery of the HPA axis. In addition to the well-known factors which regulate the degree of inhibition of the HPA during synthetic GC therapy (type of compound, method of administration, cumulative dose, duration of the treatment, concomitant drugs which can increase the bioavailability of GCs), there is a considerable variation in individual physiology, probably related to different genetic profiles which regulate GC receptor activity. This may represent an interesting basis for possible future research fields.

Adrenocortical carcinoma (ACC) is a rare and aggressive endocrine tumour deriving from the adrenal cortex. A correct therapeutic strategy requires a multidisciplinary approach between endocrinologist, surgeon and oncologist. Surgery is the mainstay treatment in ACC while mitotane, deriving from the insecticide dichloro-diphenyl-trichloro-ethane, is the main base of the medical treatment of ACC in consideration of its adrenocytolitic activity. However, the use of mitotane as adjuvant therapy is still controversial, also in consideration of the retrospective nature of several studies. A prospective randomised trial (ADIUVO), recruiting patients with low-intermediate risk of recurrence, is evaluating the utility of adjuvant treatment with mitotane in this setting. The therapeutic response is observed with plasma levels of mitotane >14 mg/L. However, the major difficulty in the management of mitotane treatment is related to side effects and to the risk of toxicity, which is related to plasmatic levels >20 mg/L, that is considered the upper limit of the therapeutic window. Mitotane therapy results in adrenal insufficiency, and glucocorticoid replacement therapy has to be administered at higher doses than those used in other aetiologies of primary adrenal insufficiency. Furthermore, other endocrine side effects related to mitotane should be considered, in particular on thyroid hormone and testosterone metabolism. Waiting for new medical strategies on molecular targets, it will be mandatory to optimise the current knowledge by prospective trials and, in consideration of the rarity of the disease, collaborative studies between endocrinologists and oncologists are necessary.

Basal CT measurement detects elevated CT values in 1.6% of NTD patients. Although CT is not a specific marker of MTC, its routine measurement represents a useful tool in the pre-operative evaluation of NTD patients, particularly those >40 yr old presenting with nodules <10 mm, even when FNAC does not show malignant features. To our knowledge, this is the first trial using ILMA to assess the ability of pre-operative CT measurement to predict MTC in a large series of NTD patients.