Endocrine complications of immunotherapies: a review.

Use of immune checkpoint inhibitors in cancer treatment has increased vastly over the past decade, as both single and combination agent therapies. While having a positive impact on survival rates, adverse effects have been noted, with endocrine effects in around 10% of patients. Thyroid disease and hypophysitis are the most commonly encountered, with diabetes mellitus and primary adrenal insufficiency also reported, as well as more rare endocrinopathies. Patient and clinician education to raise awareness of these effects, as well as regular monitoring to enable early recognition, diagnosis and prompt treatment of the immune side effects, are key. In this review, we discuss the aetiology, presentation and management of the endocrine complications of immunotherapies that are relevant to the general physician, as well as highlighting important areas where further research is still needed.

Current perspectives on recurrent pituitary adenoma: The role and timing of surgery vs adjuvant treatment.

The clinical course of pituitary adenoma can be highly variable. Aggressive pituitary tumours may require multimodal therapy with multiple operations. Even standard pituitary adenomas exhibit relatively high long-term recurrence rates and delayed intervention is often required. The indications for revision surgery in the endoscopic era are expanding for both functioning and nonfunctioning tumours, including access to the cavernous sinus and intracranial compartments. Although revision surgery can be challenging, it has been demonstrated to be both safe and effective. The question of the use of early radiotherapy in pituitary adenoma remains controversial. Our increasing understanding of pituitary tumour biology facilitates individualized treatment and surveillance protocols, with early intervention in high-risk adenoma subtypes. In this review, we discuss the treatment options for recurring pituitary tumours and focus on the role of revision surgery.

Regional Cerebral Activation Accompanies Sympathoexcitation in Women With Polycystic Ovary Syndrome.

CONTEXT: Polycystic ovary syndrome (PCOS) is associated with increased sympathetic nervous system activation, but the cerebral pathways involved are unclear. OBJECTIVE: To compare cerebral [blood oxygen level-dependent (BOLD) functional MRI], pressor [blood pressure (BP), heart rate (HR], and muscle sympathetic nerve activity (MSNA) responses to isometric forearm contraction (IFC) in women with PCOS and matched control subjects. DESIGN: Case-control study. SETTING: Referral center. PARTICIPANTS: Patients with PCOS (n = 20; mean ± SD data: age, 29.8 ± 4.8 years; body mass index (BMI), 26.1 ± 4.9 kg/ m2) and 20 age- and BMI-matched control subjects (age, 29.7 ± 5.0 years; BMI, 26.1 ± 4.8 kg/ m2). MAIN OUTCOME MEASURES: BP, HR, catecholamine, and MSNA responses to 30% IFC. BOLD signal change was modeled for BP response to 30% IFC. RESULTS: Although HR and BP increased to a similar extent in both groups after IFC, MSNA burst frequency increased by 68% in the PCOS group compared with 11.9% in control subjects (n = 7 in both groups; P = 0.002). Brain activation indexed by the BOLD signal in response to IFC was significantly greater in the PCOS group (n = 15) compared with controls (n = 15) in the right orbitofrontal cortex (P < 0.0001). Adjustment for insulin sensitivity, but not hyperandrogenism, abolished these between-group differences. CONCLUSION: Our study confirms enhanced sympathoexcitation in women with PCOS and demonstrates increased regional brain activation in response to IFC. The right orbitofrontal cortex BOLD signal change in women with PCOS is associated with insulin sensitivity. Additional studies are warranted to clarify whether this may offer a novel target for cardiovascular risk reduction.

Effectiveness of Metyrapone in Treating Cushing's Syndrome: A Retrospective Multicenter Study in 195 Patients.

BACKGROUND: Cushing's syndrome (CS) is a severe condition with excess mortality and significant morbidity necessitating control of hypercortisolemia. There are few data documenting use of the steroidogenesis inhibitor metyrapone for this purpose. OBJECTIVE: The objective was to assess the effectiveness of metyrapone in controlling cortisol excess in a contemporary series of patients with CS. DESIGN: This was designed as a retrospective, multicenter study. SETTING: Thirteen University hospitals were studied. PATIENTS: We studied a total of 195 patients with proven CS: 115 Cushing's disease, 37 ectopic ACTH syndrome, 43 ACTH-independent disease (adrenocortical carcinoma 10, adrenal adenoma 30, and ACTH-independent adrenal hyperplasia 3). MEASUREMENTS: Measurements included biochemical parameters of activity of CS: mean serum cortisol "day-curve" (CDC) (target 150-300 nmol/L); 9 am serum cortisol; 24-hour urinary free cortisol (UFC). RESULTS: A total of 164/195 received metyrapone monotherapy. Mean age was 49.6 ± 15.7 years; mean duration of therapy 8 months (median 3 mo, range 3 d to 11.6 y). There were significant improvements on metyrapone, first evaluation to last review: CDC (91 patients, 722.9 nmol/L [26.2 µg/dL] vs 348.6 nmol/L [12.6 µg/dL]; P < .0001); 9 am cortisol (123 patients, 882.9 nmol/L [32.0 µg/dL] vs 491.1 nmol/L [17.8 µg/dL]; P < .0001); and UFC (37 patients, 1483 nmol/24 h [537 µg/24 h] vs 452.6 nmol/24 h [164 µg/24 h]; P = .003). Overall, control at last review: 55%, 43%, 46%, and 76% of patients who had CDCs, UFCs, 9 am cortisol less than 331 nmol/L (12.0 µg/dL), and 9 am cortisol less than upper limit of normal/600 nmol/L (21.7 µg/dL). Median final dose: Cushing's disease 1375 mg; ectopic ACTH syndrome 1500 mg; benign adrenal disease 750 mg; and adrenocortical carcinoma 1250 mg. Adverse events occurred in 25% of patients, mostly mild gastrointestinal upset and dizziness, usually within 2 weeks of initiation or dose increase, all reversible. CONCLUSIONS: Metyrapone is effective therapy for short- and long-term control of hypercortisolemia in CS.