Clinical Predictors of Malignancy in Patients with Pheochromocytoma and Paraganglioma.

BACKGROUND AND PURPOSE: Factors associated with malignancy in patients with pheochromocytoma (adrenal tumors, Pheo) and paraganglioma (extra-adrenal, PGL) are not well-defined and all patients require lifelong surveillance. The primary aim of our study was to determine genetic and clinical variables associated with malignancy in patients with Pheo/PGL. METHODS: Single institution retrospective review was performed of all patients who underwent surgery (1/95-1/15) for Pheo/PGL. Malignancy was defined as histology-confirmed distant metastasis, lymph nodal involvement, or tumor bed recurrence. RESULTS: A total of 157 Pheo/PGL patients (44 malignant, 113 benign) with mean follow-up of 87 months were included. Compared with patients with benign Pheo/PGL, patients with malignant Pheo/PGL were younger (median 42 vs 50 years, p = 0.014), had larger tumors (median 6.5 vs 4 cm, p < 0.001) and had PGL (63.6 vs 4.4%, p < 0.001). Genetic testing was performed in 60 patients and was positive in 38 (63%). Although positive genetic results were equally likely in malignant vs benign Pheo/PGL (76 vs 54%, p = 0.1), all 11 patients with germline SDHB mutations had malignant disease. In multivariable analysis, younger age, larger tumor size, and PGL were associated with malignancy (p < 0.05). Pheo patients with negative genetic testing and negative family history who developed metachronous metastases all had primary tumors ≥4 cm in size. CONCLUSIONS: Patients who are young, have larger tumors, positive genetic testing (especially SDHB) or have PGL require long-term follow-up. Patients with negative genetic testing or family history and Pheo <4 cm have a lower risk of malignancy, and de-escalated long-term surveillance may be appropriate follow-up.

Endoscopic Endonasal Approach for Adrenocorticotropic Hormone-Secreting Pituitary Adenomas: Outcomes and Analysis of Remission Rates and Tumor Biochemical Activity with Respect to Tumor Invasiveness.

OBJECTIVE: The purpose of this study was to analyze the outcomes and complications of the endoscopic endonasal approach (EEA) performed on patients with Cushing disease at our Pituitary Center during the past 11 years. METHODS: Clinical information and imaging in electronic medical records were reviewed for patients who underwent EEA. Statistical analysis was performed with χ2 testing and Student's t-test. RESULTS: Remission was achieved in 39 patients (79.6%) at initial evaluation within 2 weeks of surgery. At last follow-up, remission persisted in 70% of 50 patients with EEA alone (mean follow-up time, 37.5 ± 4.6 months; median, 26.2 months; range, 2.5-155.0 months). At last follow-up, remission rates were 80% among magnetic resonance imaging-negative adenomas, 70.6% among noninvasive or minimally invasive adenomas (Knosp 0, 1, 2), and 50% among invasive adenomas (Knosp 3, 4). There were no statistical differences in the remission rates among these categories (P = 0.444). Women had higher proportions of initial remission than men (P = 0.033) and patients who had no initial remission were older (P = 0.046). Higher preoperative normalized adrenocroticotropic hormone level was associated with a greater degree of invasiveness (P = 0.021). However, there was no association between preoperative normalized urine-free cortisol levels and degree of invasiveness (P = 0.582). Complications included panhypopituitarism (n = 3), hypothyroidism (n = 3), growth hormone deficiency (n = 1), hypogonadism (n = 1), postoperative cerebrospinal fluid leak (n = 2), and transient diabetes insipidus (n = 4). CONCLUSIONS: The EEA for Cushing disease resulted in remission and complication rates comparable with previous analyses of EEA, as well as microsurgical series. Preoperative adrenocorticotropic hormone levels were associated with invasiveness.

Discordance between growth hormone and insulin-like growth factor-1 after pituitary surgery for acromegaly: a stepwise approach and management.

INTRODUCTION: Follow-up management of patients with acromegaly after pituitary surgery is performed by conducting biochemical assays of growth hormone (GH) and insulin-like growth factor-1 (IGF1). Despite concordant results of these two tests in the majority of cases, there is increasing recognition of patients who show persistent or intermittent discordance between GH and IGF1 (normal GH and elevated IGF1 or vice versa). METHOD: In this narrative review, the last three decades materials on the issue of discrepancy between GH and IGF1 were thoroughly assessed. RESULTS: Various studies have obtained different discordance rates, ranging from 5.4 to 39.5%. At present, despite the use of current sensitive assays and more stringent criteria to define remission, the rate of discordance still remains high. A number of mechanisms have been proposed to explain the postoperative discordance of GH and IGF1 including; altered dynamics of the GH secretion after surgery, early postoperative hormone assay, inaccurate or less sensitive tests and laboratory errors, too high cut-off point for GH suppression in the GH assays, GH nadir values not adjusted to age, sex, and body mass index, the influence of concomitant medication, co-existing physiologic and pathologic conditions, and many other proposed reasons. Nevertheless, the underlying mechanisms are still far from clear, and the solution continues to evade complete elucidation. Similarly, the impacts of such a discrepancy over mortality and morbidity and the risk of biochemical and/or clinical recurrence are unclear. CONCLUSION: As a challenging clinical problem, a stepwise evaluation and management of these patients appears to be more rational.

A 23-year-old female with a mixed germ cell tumor of the pituitary infundibulum: the challenge of differentiating neoplasm from lymphocytic infundibuloneurohypophysitis-a case report and literature review.

The pathologic spectrum of diseases that infiltrate the pituitary infundibulum includes a broad variety of clinical entities. There are significant differences in the prevalence of these etiologies depending on the age of presentation. Lymphocytic infundibuloneurohypophysitis (LINH) predominates over other causes of infundibular disease in adults over age 21. Differentiating LINH from other causes of infundibular disease can be difficult because the various etiologies often have similar clinical presentations and radiologic imaging characteristics. We report the first case in an adult of a mixed germ cell tumor comprised of germinoma and embryonal cell carcinoma infiltrating the pituitary infundibulum. In our case, a 23-year-old female was initially misdiagnosed as having LINH. She presented with panhypopituitarism and diabetes insipidus, which is the most common initial presentation in both entities. The two diagnoses are difficult to distinguish based on MRI imaging, CSF findings, and histopathological examination. Our case demonstrates the need for close follow-up of patients with isolated lesions of the pituitary infundibulum and reinforces the need for biopsy of an infundibular lesion when progression of disease is demonstrated. In our case, biopsy with comprehensive immunohistochemical staining was the sole means of making a definitive diagnosis.

Endoscopic endonasal approach for growth hormone secreting pituitary adenomas: outcomes in 53 patients using 2010 consensus criteria for remission.

We report the outcomes of the endoscopic endonasal approach (EEA) for resection of growth hormone secreting pituitary adenomas using 2010 consensus criteria. We also assess outcomes with additional medical therapy and radiosurgery (RS) for patients not achieving remission with EEA alone. A retrospective review of 53 patients who had follow up endocrinologic data at least 3 months post-surgery was performed among patients who were treated by EEA between 1998 and 2012. Data were analyzed for remission using GH and IGF-I levels based on 2010 consensus criteria. We also analyzed the outcomes using 2000 consensus criteria for ease in comparison to prior studies of outcomes of surgery for acromegaly. In this series of mostly large (88.2% macroadenomas), invasive (46.9% Hardy-Wilson C, D, E) adenomas, there were 27 patients (50.9%) who achieved remission after EEA only. For patients who had no remission with EEA alone, RS and/or medical therapy were used and 37 patients (69.8 %) achieved remission overall. Statistical analysis showed larger tumor size, Hardy Stages C, D, E and Knosp Scores 3, 4 to be predictive against remission for EEA only and EEA with other modalities. The volume of residual tumor after EEA was not found to be predictive of remission with additional therapies. We used stringent consensus criteria from 2010 in a series which included a high proportion of invasive GH secreting adenomas to show that EEA alone or combined with other modalities results in comparable remission rates to earlier studies which used less strict criteria, while retaining low complication rates.

Imaging of the pituitary.

In the appropriate clinical setting of pituitary hyperfunction or hypofunction, visual field deficit, or cranial nerve palsy, imaging of the pituitary is necessary. This article reviews the normal appearance of the pituitary and its surroundings, emphasizing magnetic resonance imaging. Typical and variant appearances of pituitary pathology are discussed. Because growth of adenoma into surrounding structures is important to surgical management, cavernous sinus invasion and suprasellar spread as well as adenoma mimics are illustrated. Typical examples of pituitary dysfunction from other entities that secondarily affect the gland, hypophysis, or third ventricle are discussed. Some common errors of interpretation are listed.

Hyperthyroidism after parathyroid exploration.

BACKGROUND: We hypothesized that hyperthyroidism after parathyroid exploration may be an underreported phenomenon with a course more severe than recognized previously. METHODS: We examined pre- and postoperative thyroid function and outcomes in 199 consecutive patients who, since March 2000, had parathyroid exploration for primary sporadic hyperparathyroidism (HPTH). We excluded patients with prior thyroid or parathyroid surgery, preoperative thyroid medication, concurrent total thyroidectomy, or follow-up <5 months. RESULTS: Of 125 patients with normal preoperative serum thyroid-stimulating hormone levels, 39 (31.2%) were hyperthyroid postoperatively. Mean thyroid-stimulating hormone levels (mean +/- SD) dropped with operation from 2.0 +/- 1.1 microIU/mL to 1.2 +/- 1.4 microIU/mL (P < .0001). Nineteen patients (15%) reported symptoms 1 to 2 weeks after operation. The clinical course of hyperthyroidism typically was short, but 5 patients (4%) had symptomatic hyperthyroxinemia requiring medical therapy. Hyperthyroidism was independent of age, severity of HPTH, anatomic/pathologic features, operative time, and other measures of operative difficulty, but was associated with lithium therapy, bilateral exploration, and absence of concurrent thyroid lobectomy. CONCLUSIONS: Risk of hyperthyroidism may be underappreciated after routine parathyroid surgery for HPTH. Use of lithium and degree of dissection appear contributory. Patients undergoing parathyroid exploration need counseling and surveillance for hyperthyroidism, which may be reduced by minimizing the extent of parathyroid surgery.