Faculty Bibliography

OBJECTIVE:Prolactin secreting tumors respond well to medical management with a small fraction of patients requiring surgery. We conducted a systematic review and meta-analysis to study the determinants of surgical remission in these tumors. METHODS:We searched PubMed to identify eligible studies reporting postoperative remission in patients treated with transsphenoidal surgery for prolactinoma. Primary outcomes included postoperative remission, follow-up remission, and recurrence. Postoperative and follow-up remission were defined as normoprolactinemia at less than and greater than one-year post-operation respectively. Recurrence was defined as hyperprolactinemia after initial normalization of prolactin levels. Odds ratios (OR) were calculated, stratified by radiological size, tumor extension, and tumor invasion, and analyzed using a random-effects model meta-analysis. RESULTS:Thirty-five studies were included. Macroadenomas were associated with lower rates of postoperative remission OR 0.20, 95% confidence interval [CI] 0.16-0.24) and lower rates of remission at follow-up (OR 0.11, 95% CI 0.053-0.22). Postoperative remission was less likely in tumors with extra- or suprasellar extension (OR 0.16, 95% CI 0.06-0.43) and tumors with cavernous sinus invasion (OR 0.03, 95% CI 0.01-0.13). Female gender and absence of preoperative dopamine agonist (DA) treatment were also associated with higher remission rates. Across the included studies, there was considerable heterogeneity in each primary outcome (postoperative remission I2=94%, follow-up remission I2=86%, recurrence I2=68%). CONCLUSIONS:Transsphenoidal surgery for prolactinomas may be particularly effective in small, non-invasive, treatment naive tumors and may provide a viable first-line alternative to dopamine agonist therapy in such patients.

PURPOSE/OBJECTIVE:Both prolactinomas and nonfunctioning adenomas (NFAs) can present with hyperprolactinemia. Distinguishing them is critical because prolactinomas are effectively managed with dopamine agonists, whereas compressive NFAs are treated surgically. Current guidelines rely only on serum prolactin (PRL) levels, which are neither sensitive nor specific enough. Recent studies suggest that accounting for tumor volume may improve diagnosis. The objective of this study is to investigate the diagnostic utility of PRL, tumor volume, and imaging features in differentiating prolactinoma and NFA. METHODS:Adult patients with pathologically confirmed prolactinoma (n = 21) or NFA with hyperprolactinemia (n = 58) between 2013 and 2020 were retrospectively identified. Diagnostic performance of clinical and imaging variables was analyzed using receiver-operating characteristic curves to calculate area under the curve (AUC). RESULTS:with sensitivity of 100% and specificity of 82.76%. Binary logistic regression found that PRL was a significant positive predictor of prolactinoma diagnosis, whereas tumor volume, presence of CSI not previously defined, and T2 hyperintensity were significant negative predictors. The regression model had an AUC of 0.9915 (p < 0.0001). CONCLUSIONS:Consideration of tumor volume improves differentiation between prolactinomas and NFAs, which in turn leads to effective management.

PURPOSE/OBJECTIVE:Biochemical control is the main determinant of survival, clinical manifestations and comorbidities in acromegaly. Transsphenoidal selective adenomectomy (TSA) is the initial treatment of choice with reported biochemical remission rates varying between 32 and 85%. Understanding the limiting factors is essential for identification of patients who require medical treatment. METHODS:We reviewed the English literature published in Medline/Pubmed until Dec 31, 2019 to identify eligible studies that described outcomes of TSA as primary therapy and performed analyses to determine the main predictors of remission. RESULTS:Most publications reported single-institution, retrospective studies. The following preoperative parameters were consistently associated with lower remission rates: cavernous sinus invasion by imaging, larger tumor size and higher GH levels. Young age and preoperative IGF-1 levels were predictive in some studies. When controlled for covariates, the best single preoperative predictor was cavernous sinus invasion, followed by preoperative GH levels. Conversely, low GH level in the first few days postoperatively was a robust predictor of durable remission. The influence of tumor histology (sparsely granular pattern, co-expression of prolactin and proliferation markers) on surgical remission remains to be established. Few studies developed predictive models that yielded much higher predictive values than individual parameters. CONCLUSION/CONCLUSIONS:Surgical outcome prognostication systems could be further generated by machine learning algorithms in order to support development and implementation of personalized care in patients with acromegaly.

Hypophosphatasia should be considered for any patient who presents with multiple metatarsal stress fractures and a low alkaline phosphatase.

Parathyromatosis is a rare but recognized cause of recurrent primary hyperparathyroidism. Initially described in 1975 by Palmer et al.(1), about 40 cases have been described in the literature. Most patients are middle-aged females. A small majority of the cases arise in the context of secondary hyperplasia due to end-stage renal disease.(2) The nature of parathyromatosis is unknown. It may be a low-grade carcinoma, seeding of a prior adenoma, or overgrowths of embryologic rests. Several oncogenes of interest have been identified in parathyroid neoplasms (PRAD1, MEN1, HRPT2, CaSR). (3) A biallelic CDC73/HRPT2 inactivating mutation is known to be present in about 75% of sporadic parathyroid carcinomas and absent in most adenomas. (4) Their possible relationship to parathyromatosis has not been studied. As such, differentiating parathyromatosis from other parathyroid neoplasms is challenging.(5-10) This article is protected by copyright. All rights reserved.

Purpose Abnormalities of water and sodium balance, including diabetes insipidus (DI) and the syndrome of inappropriate anti-diuretic hormone (SIADH) are common complications of transsphenoidal surgery. Postoperative practice patterns vary among clinicians and no consensus guidelines exist to direct their monitoring and management. We aimed to identify and compare practice patterns regarding the evaluation and management to these postoperative complications. Methods. A questionnaire was utilized to capture demographic data and practice habits in the postoperative setting. Respondents were members of the Pituitary Society, an international organization comprised of clinicians and researchers dedicated to the study of pituitary disease. Results. Eighty-six respondents completed at least part of the survey. The geographic distribution of respondents was roughly even between American and non-American practitioners. The majority of respondents practiced at academic institutions (67.4%), worked in multidisciplinary teams (88.4%), and possessed significant greater than 10 years of clinical experience (71%). Compared to non-American practitioners, American practitioners describe a shorter length of stay post-operatively (p<0.001) and prescribe more restrictive volume recommendations for post-operative SIADH (p=0.0035). Early career clinicians (less than 10 years in practice) checked first post-operative sodium level earlier than later career clinicians (p=0.010). Conclusion. Water and sodium dysregulation are common following transsphenoidal surgery, but their management is not well-standardized in clinical practice. We created a questionnaire to define and compare practice patterns. Most respondents practice in academic settings in multidisciplinary teams. The length of clinical experience did not significantly impact practice habits. Practice location influenced length of stay postoperatively and fluid-restriction in SIADH.

Objective/UNASSIGNED:To describe an unusual presentation of a follicle-stimulating hormone-secreting pituitary adenoma leading to ovarian hyperstimulation syndrome. We also discuss the pathophysiology and subsequent management of these tumors. Methods/UNASSIGNED:This is a case report and review of the literature. A 37-year-old female with menorrhagia was found to have bilateral multilocular adnexal cysts with concern for ovarian hyperstimulation syndrome. Results/UNASSIGNED:Labs revealed elevated follicle-stimulating hormone, and an eminent estradiol level. Pituitary magnetic resonance imaging revealed a macroadenoma with cavernous sinus invasion. The patient went on to have a successful transsphenoidal resection with normalization of hormones and subsequent resumption of menstrual cycles. Conclusion/UNASSIGNED:With the help of this case report, we illustrate the pathogenesis of functioning gonadotroph adenomas as well as the management challenges associated with these tumors. Our case is unique in its presentation with severe hyperestrogenemia and cavernous sinus invasion pointing towards a clinically aggressive adenoma. It is important to increase awareness of these tumors to ensure timely and effective management of their complications.

OBJECTIVES/OBJECTIVE:Biotin is a component of the vitamin B complex used in standard immunoassays to detect serum levels of various hormones and non-hormones, including thyrotropin (TSH) and thyroxine. These assays involve a strong bond between streptavidin and biotin, which serves as an anchor for measured analytes. Large doses of exogenous biotin for the treatment of certain medical conditions have resulted in assay interference, causing TSH to be spuriously lowered. Smaller doses of biotin found in dietary supplements also have caused assay interference. METHODS:We describe four cases in which over-the-counter (OTC) biotin caused erroneous thyroid diagnosis and clinical confusion in patients with preexisting thyroid disease. Serum TSH and thyroxine were measured by the Vitros 5600 assay. CONCLUSIONS:Although the biotin-streptavidin interaction is sensitive for detecting serum levels of TSH, it is subject to interference by exogenous biotin at levels found in OTC products. The widespread use of OTC biotin for cosmetic purposes can adversely affect the diagnosis of the entire spectrum of functional thyroid disorders. Physicians must carefully and routinely question for the use of biotin before thyroid function testing.