Insulin autoimmune syndrome (IAS), also named Hirata's disease, is a rare condition characterized by hypoglycemic episodes due to the presence of high titers of insulin autoantibodies (IAA). IAS is a form of immune-mediated hypoglycemia, which develops when a triggering factor (ie, a medication or a viral infection) acts on an underlying predisposing genetic background. IAS pathogenesis involves the formation of insulin-IAA complexes that induce glycemic alterations with a double-phase mechanism: IAA prevent insulin to bind its receptor in the postprandial phase, possibly resulting in mild hyperglycemia; thereafter, insulin is released from the complexes irrespective of blood glucose concentrations, thus inducing hypoglycemia. The diagnosis of IAS is challenging, requiring a careful workup aimed at excluding other causes of hyperinsulinemic hypoglycemia. The gold standard for the definitive diagnosis is the finding of IAA in a blood sample. Because IAS is frequently a self-remitting disease, its management mostly consists of supportive measures, such as dietary modifications, aimed at preventing the development of hypoglycemia. Pharmacological therapies may occasionally be necessary for patients presenting with severe manifestations of IAS. Available therapies may include drugs that reduce pancreatic insulin secretion (somatostatin analogues and diazoxide, for instance) and immunosuppressive agents (glucocorticoids, azathioprine and rituximab). The purpose of this review is to provide a comprehensive analysis of the disease, by describing the burden of knowledge that has been obtained in the 50 years following its first description, took in 1970, and by highlighting the points that are still unclear in its pathogenesis and management.

We report the incidence of thyroid cancer in a series of 1832 consecutive patients seen for thyrotoxicosis of any etiology during 1970 and 1985 in our department. Surgical treatment for thyrotoxicosis was selected as the treatment of choice in 179 patients (9.8%), 86 with toxic diffuse goiter (TDG), 21 with toxic nodular goiter (TNG) and 40 with toxic adenoma (TA). The presence of thyroid cancer was found in 11 patients for a total incidence of 6.1%. Six patients had TDG (percent incidence in this group 6.9%), 4 patients had TNG (7.5%) and 1 had TA (2.5%). While the presence of thyroid cancer was totally unsuspected in TNG and TA, in TDG 4 out of 6 patients found to have a cancer, had been suspected before surgery. When a thyroid nodule was present in a toxic diffuse goiter the possibility to face with a malignant lesion reached 22.2% of the cases (4 out of 18 cases), while only 2 out of 68 patients (2.9%) with TDG and no nodule had thyroid cancer. These results confirm recent other series reporting the frequent association of hyperthyroidism and thyroid cancer and suggest that in thyrotoxic patients any nodule must be screened carefully to rule out malignancy.

Over a 27-year period, the epidemiology of AIT changed, as the prevalence of type 2 AIT progressively increased and that of type 1 remained constant. Thus, under most circumstances, endocrinologists nowadays deal with type 2 AIT, which is a destructive thyroiditis, generally treated successfully with glucocorticoids. Although no additional treatment is usually required after the destructive process subsides, periodic assessment of thyroid function is warranted, because of the occurrence of hypothyroidism (up to 17%) during long-term follow-up of these patients.

Summary Objective  Polymorphism of the androgen receptor (AR) has been related to various pathophysiological conditions, such as osteoporosis and infertility. The objectives of this study were to evaluate the frequency of distribution in a normal Italian population and to assess CAG repeats (CAGr) in other conditions, such as hypoandrogenism, potentially influenced by AR polymorphism. Patients and measurements  CAGr polymorphism was determined in a group of 91 healthy normoandrogenized subjects, 29 hypoandrogenized patients (hypoplasia of prostate and seminal vesicles, reduced beard or body hair, etc.) and 29 infertile patients by direct sequencing. Results  The mean (± SD) number of CAG repeats [(CAGr)n] was 21·5 (± 1·7) in the control group, 21·4 (± 2·0) in the infertile patients and 24·0 (± 2·9) in the hypoandrogenic males. The difference was statistically significant between this last group and the other two (P < 0·0001), while there was no difference between normal controls and infertile patients. The frequency distribution showed a shift towards higher CAG length in hypoandrogenized patients compared to controls and infertile patients. If we used a cut‐off point of 24·9 (2 SD above the mean), the percentage of patients with 25 or more CAGr repeats was 38% among hypoandrogenized patients, 7% among infertile patients and 5% among the control group. In hypoandrogenized subjects (CAGr)n correlated slightly with testis and prostate volume. The number of CAG repeats was not associated with any of the hormonal parameters, including testosterone, evaluated in the three groups. Conclusions  Our normal population, representing subjects from Central Italy, is superimposable on other European populations with regard to (CAGr)n distribution. Hypoandrogenic males have a shift in the frequency distribution towards longer (CAGr)n. Infertile patients are not statistically different from the control group. These findings suggest that, given the same amount of circulating testosterone, as in our hypoandrogenized and control group, the final net androgenic phenotypical effect is due to AR polymorphism.

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