Ekaterina Manuylova

MORNING SERUM CORTISOL LEVEL AFTER TRANSSPHENOIDAL SURGERY FOR PITUITARY ADENOMA PREDICTS HYPOTHALAMIC-PITUITARY-ADRENAL FUNCTION DESPITE INTRAOPERATIVE DEXAMETHASONE USE

OBJECTIVE Perioperative glucocorticoid (GC) is rarely needed in patients undergoing transsphenoidal surgery (TSS). We instituted a steroid-sparing protocol in the settings of intraoperative dexamethasone use. We evaluated the safety of using a cut off cortisol level of 14 μg/dL on postoperative day (POD)-1 and -6 after dexamethasone use during the surgery. We also analyzed the efficacy of serial morning cortisol levels for weaning GC replacement. METHODS The charts of 48 adult patients who received dexamethasone 4 mg intraoperatively were reviewed. Morning cortisol levels were measured on POD-1. Patients with cortisol ≥14 μg/dL were discharged without CG replacement. Morning cortisol level was checked routinely on POD-6, and GC replacement was initiated when the level was <14 μg/dL. Serial cortisol levels were measured in patients requiring GC after the first postoperative week. RESULTS Overall, 67% patients had POD-1 cortisol ≥14 μg/dL and did not require GC on discharge. After POD-6, 83% of patients were not on GC replacement. A cosyntropin stimulation testing (CST) was only performed in 3 patients. There were no hospital admissions for adrenal crisis during the postoperative period. CONCLUSION A steroid-sparing protocol with POD-1 and -6 morning cortisol levels can be safely and effectively used in the settings of intraoperative dexamethasone administration. It leads to avoidance of GC in more than two-thirds of patients on discharge and more than 80% of patients after the first postoperative week. We found that dynamic adrenal testing could be omitted in the majority of patients by using serial morning cortisol levels to assess the hypothalamic-pituitary-adrenal (HPA) axis.

BIOCHEMICAL CONTROL DURING LONG-TERM FOLLOW-UP OF 230 ADULT PATIENTS WITH CUSHING DISEASE: A MULTICENTER RETROSPECTIVE STUDY

OBJECTIVE Cushing disease (CD) results from excessive exposure to glucocorticoids caused by an adrenocorticotropic hormone-secreting pituitary tumor. Inadequately treated CD is associated with significant morbidity and elevated mortality. Multicenter data on CD patients treated in routine clinical practice are needed to assess treatment outcomes in this rare disorder. The study purpose was to describe the burden of illness and treatment outcomes for CD patients. METHODS Eight pituitary centers in four U.S. regions participated in this multicenter retrospective chart review study. Subjects were CD patients diagnosed at ≥18 years of age within the past 20 years. Descriptive statistical analyses were conducted to examine presenting signs, symptoms, comorbidities, and treatment outcomes. RESULTS Of 230 patients, 79% were female (median age at diagnosis, 39 years; range, 18 to 78 years). Length of follow-up was 0 to 27.5 years (median, 1.9 years). Pituitary adenomas were 0 to 51 mm. The most common presenting comorbidities included hypertension (67.3%), polycystic ovary syndrome (43.5%), and hyperlipidemia (41.5%). Biochemical control was achieved with initial pituitary surgery in 41.4% patients (91 of 220), not achieved in 50.0% of patients (110 of 220), and undetermined in 8.6% of patients (19 of 220). At the end of follow-up, control had been achieved with a variety of treatment methods in 49.1% of patients (110 of 224), not achieved in 29.9% of patients (67 of 224), and undetermined in 21.0% of patients (47 of 224). CONCLUSION Despite multiple treatments, at the end of follow-up, biochemical control was still not achieved in up to 30% of patients. These multicenter data demonstrate that in routine clinical practice, initial and long-term control is not achieved in a substantial number of patients with CD. ABBREVIATIONS BLA = bilateral adrenalectomy CD = Cushing disease CS = Cushing syndrome eCRF = electronic case report form MRI = magnetic resonance imaging PCOS = polycystic ovary syndrome.

Ventricular Tachycardias: Characteristics and Management

Ventricular tachycardias include ventricular tachycardia, ventricular fibrillation, and torsades de pointes; although these rhythms may be benign and asymptomatic, others may be life threatening and lead to increased morbidity and mortality. To optimize patient outcomes, ventricular tachycardias need to be rapidly diagnosed and managed, and often the electrocardiogram (ECG) is the first and only manifestation of a cardiac defect. Understanding of the initial electrocardiographic pattern and subsequent changes can lead to early intervention and an improved outcome. This article describes mechanisms, ECG characteristics, and management of ventricular tachycardias.

Late presentation of acromegaly in medically controlled prolactinoma patients.

Summary Co-secretion of growth hormone (GH) and prolactin (PRL) from a single pituitary adenoma is common. In fact, up to 25% of patients with acromegaly may have PRL co-secretion. The prevalence of acromegaly among patients with a newly diagnosed prolactinoma is unknown. Given the possibility of mixed GH and PRL co-secretion, the current recommendation is to obtain an insulin-like growth factor-1 (IGF-1) in patients with prolactinoma at the initial diagnosis. Long-term follow-up of IGF-1 is not routinely done. Here, we report two cases of well-controlled prolactinoma on dopamine agonists with the development of acromegaly 10–20 years after the initial diagnoses. In both patients, a mixed PRL/GH-cosecreting adenoma was confirmed on the pathology examination after transsphenoidal surgery (TSS). Therefore, periodic routine measurements of IGF-1 should be considered regardless of the duration and biochemical control of prolactinoma. Learning points: Acromegaly can develop in patients with well-controlled prolactinoma on dopamine agonists. The interval between prolactinoma and acromegaly diagnoses can be several decades. Periodic screening of patients with prolactinoma for growth hormone excess should be considered and can 
lead to an early diagnosis of acromegaly before the development of complications.

Transsphenoidal Surgery for Craniopharyngiomas

Complication avoidance and management with craniopharyngioma patients should focus more on avoidance; these complex lesions demand multidisciplinary evaluation and management long before knife is put to skin except if a patient presents in extremis. Although benign histologically, the invasiveness and location of these tumors makes their management difficult over the long term. Expertise in endocrinology, neurosurgery, radiation oncology, ophthalmology, reproductive medicine, and, frequently, pediatric medicine are required to deliver the best possible care. In our practice, these patients are managed by a multidisciplinary team that is intimately involved in all phases of care.

Antibody Response to Serpin B13 Induces Adaptive Changes in Mouse Pancreatic Islets and Slows Down the Decline in the Residual Beta Cell Function in Children with Recent Onset of Type 1 Diabetes Mellitus

Type 1 diabetes mellitus (T1D) is characterized by a heightened antibody (Ab) response to pancreatic islet self-antigens, which is a biomarker of progressive islet pathology. We recently identified a novel antibody to clade B serpin that reduces islet-associated T cell accumulation and is linked to the delayed onset of T1D. As natural immunity to clade B arises early in life, we hypothesized that it may influence islet development during that time. To test this possibility healthy young Balb/c male mice were injected with serpin B13 mAb or IgG control and examined for the number and cellularity of pancreatic islets by immunofluorescence and FACS. Beta cell proliferation was assessed by measuring nucleotide analog 5-ethynyl-2′-deoxyuridine (5-EdU) incorporation into the DNA and islet Reg gene expression was measured by real time PCR. Human studies involved measuring anti-serpin B13 autoantibodies by Luminex. We found that injecting anti-serpin B13 monoclonal Ab enhanced beta cell proliferation and Reg gene expression, induced the generation of ∼80 pancreatic islets per animal, and ultimately led to increase in the beta cell mass. These findings are relevant to human T1D because our analysis of subjects just diagnosed with T1D revealed an association between baseline anti-serpin activity and slower residual beta cell function decline in the first year after the onset of diabetes. Our findings reveal a new role for the anti-serpin immunological response in promoting adaptive changes in the endocrine pancreas and suggests that enhancement of this response could potentially help impede the progression of T1D in humans.

Orbital Pseudotumor in a Patient Treated With Zoledronic Acid: A Case Report and Pertinent Literature Review

ABSTRACT Objective: To enhance recognition of ocular inflammation as a rare side effect of zoledronic acid. Methods: A case report of bisphosphonate-induced orbital inflammation with permanent visual deterioration and pertinent literature review. Results: A 66-year-old man with newly diagnosed osteoporosis and concomitant hypertension, hyperlipidemia, and gastroesophageal reflux disease was treated with intravenous zoledronic acid. He developed acute anterior uveitis on day 4 after treatment, manifested by orbital erythema, swelling, and decreased visual acuity. His symptoms resolved after a course of systemic glucocorticoid. However, he developed blurred vision 3 months after treatment with zoledronic acid and was diagnosed with cystoid macular edema and wrinkling retinopathy, thought to be related to prior history of uveitis. He underwent intravitreal steroid injection, with a partial response 6 months after use of zoledronic acid, later followed by retinal surgery. At 24 months after zoledronic acid in...