Background Immunotherapy is a firmly established pillar in the treatment of cancer, alongside the traditional approaches of surgery, radiotherapy, and chemotherapy. Like every treatment, also cancer immunotherapy causes a diverse spectrum of side effects, collectively referred to as immune-related adverse events. Objective This review will examine the main forms of immunotherapy, the proposed mechanism(s) of action, and the incidence of thyroid dysfunctions. Methods A comprehensive MEDLINE search was performed for articles published up to March 30, 2017. Results Following the pioneering efforts with administration of cytokines such as IL-2 and IFN-g, which caused a broad spectrum of thyroid dysfunctions (ranging in incidence from 1 to 50%), current cancer immunotherapy strategies comprise immune checkpoint inhibitors, oncolytic viruses, adoptive T-cell transfer, and cancer vaccines. Oncolytic viruses, adoptive T-cell transfer, and cancer vaccines cause thyroid dysfunctions only rarely. In contrast, immune checkpoint blockers (such as anti-CTLA-4, anti-PD-1, anti-PD-L1) are associated with a high risk of thyroid autoimmunity. This risk is highest for anti-PD-1 and increases further when a combination of checkpoint inhibitors is used. Conclusions Cancer patients treated with monoclonal antibodies that block immune checkpoint inhibitors are at risk of developing thyroid dysfunctions. Their thyroid status should be assessed at baseline and periodically after initiation of the immunotherapy.

The most known effects of endogenous Cushing’s syndrome are the phenotypic changes and metabolic consequences. However, hypercortisolism can exert important effects on other endocrine axes. The hypothalamus–pituitary–thyroid axis activity can be impaired by the inappropriate cortisol secretion, which determinates the clinical and biochemical features of the “central hypothyroidism”. These findings have been confirmed by several clinical studies, which also showed that the cure of hypercortisolism can determine the recovery of normal hypothalamus–pituitary–thyroid axis activity. During active Cushing’s syndrome, the “immunological tolerance” guaranteed by the hypercortisolism can mask, in predisposed patients, the development of autoimmune thyroid diseases, which increases in prevalence after the resolution of hypercortisolism. However, the immunological mechanism is not the only factor that contributes to this phenomenon, which probably includes also deiodinase-impaired activity. Cushing’s syndrome can also have an indirect impact on thyroid function, considering that some drugs used for the medical control of hypercortisolism are associated with alterations in the thyroid function test. These considerations suggest the utility to check the thyroid function in Cushing’s syndrome patients, both during the active disease and after its remission.

Background Walter E. Dandy (1886–1946) was an outstanding neurosurgeon who spent his entire career at the Johns Hopkins Hospital. After graduating from medical school in 1910, he completed a research fellowship in the Hunterian laboratory with Harvey Cushing and then joined the Department of Surgery as resident, rising to the rank professor in 1931. Dandy made several contributions that helped building the neurosurgical specialty, most famously the introduction of pneumo-ventriculography to image brain lesions for which he received a Nobel prize nomination. He also performed many pituitary surgeries, although his role in this area is less known and overshadowed by that of Cushing’s. Purpose This retrospective cohort study was designed to unveil Dandy’s pituitary work and place it in the context of the overall pituitary surgeries performed at the Johns Hopkins Hospital. Methods Pituitary surgery data were obtained by screening the paper and electronic surgical pathology records of the Department of Pathology, as well as the general operating room log books of the Johns Hopkins Hospital housed in the Chesney Medical Archives. Results A total of 3211 pituitary surgeries associated with a pathological specimen were performed between February 1902 and July 2017 in 2847 patients. Most of the surgeries (2875 of 3211 89%) were done by 21 neurosurgeons. Dandy ranks 4th as number of surgeries, with 287 pituitary operations in 35 years of activity. He averaged 8 pituitary surgeries per year, a rate that positions him 6th among all Hopkins neurosurgeons. With the exception of his first operation done in July 1912 while Cushing was still at Hopkins, Dandy approached the pituitary gland transcranially, rather than transphenoidally. The majority of Dandy’s pituitary patients had a pathological diagnosis of pituitary adenomas, followed by craniopharyngiomas and sellar cysts. In the decades Dandy operated, pituitary surgeries represented 0.56% of the total Johns Hopkins surgeries, a percentage significantly greater (p < 0.001) than the 0.1% observed in modern days. Dandy’s pituitary clinical work was matched by important experimental studies done in the early stages of his career. Conclusions This study highlights the role of Dandy as an important contributor to advance our understanding of pathophysiology and treatment of pituitary diseases.

Adrenocortical carcinoma (ACC) represents one of the most aggressive endocrine tumors. In spite of a correct therapeutic strategy based on a multidisciplinary approach between endocrinologist, surgeon and oncologist, the prognosis is often poor. Surgery is the mainstay treatment in ACC. Mitotane, a dichloro-diphenyl-trichloro-ethane derivate, represents the main medical treatment of ACC in consideration of its adrenocytolitic activity and it is mainly employed as adjuvant treatment after complete surgical resection and for the treatment of advanced ACC. However, the use of mitotane as adjuvant therapy is still controversial, also in consideration of the retrospective nature of several studies. The recurrence of disease is frequent, especially in advanced disease at the diagnosis. Therefore, in these contexts, conventional chemotherapy must be considered in association with mitotane, being the combination etoposide, doxorubicin and cisplatin (EDP) the standard of care in this setting. A more modern therapeutic approach, based on the need of a salvage therapy for advanced ACC that progresses through first-line EDP, is focused on molecular-targeted therapies. However, robust clinical trials are necessary to assess the real efficacy of these treatments.

Immune checkpoint inhibitors have improved the survival in patients affected by an increasing number of malignancies, but they may also trigger various autoimmune side-effects, including endocrinopathies. Very rarely, immune checkpoint inhibitors have been reported to cause central diabetes insipidus. However, with their expanding use, the likelihood that oncologists will face this endocrine adverse event is expected to increase. By reviewing the limited literature on central diabetes insipidus induced by immune checkpoint inhibitors, some inconsistencies emerge in the diagnosis and the management of patients presenting with this toxicity, together with difficulties related to classifying its severity. Until now, specific guidelines on the management of central diabetes insipidus induced by immune checkpoint inhibitors are lacking. In clinical practice, endocrinological consultation may relieve medical oncologists from difficulties in treating this side-effect; oncologists, however, remain responsible for its early diagnose and the management of the causative drugs. To this aim, some practical suggestions are advised for the multidisciplinary management of cancer patients presenting with central diabetes insipidus induced by immune checkpoint inhibitors.