Wouter P. Kluijfhout

Long-Term Natural Course of Pituitary Tumors in Patients With MEN1: Results From the DutchMEN1 Study Group (DMSG).

CONTEXT Guidelines advise lifelong radiological followup for asymptomatic pituitary adenomas (PITs) because of the risk for growth and subsequent visual field defects. In the context of multiple endocrine neoplasia type 1 (MEN1) an even more comprehensive screening is advised because PITs are presumed to manifest more aggressive behavior. We studied the long-term course of MEN1-related PITs, which may be used as a model for sporadically occurring PITs. OBJECTIVE The aim of our study is to assess the results of systematic pre-symptomatic PIT screening and subsequent long-term followup of PITs with emphasis on nonfunctioning microadenomas diagnosed by screening. PATIENTS AND METHODS A cohort study was performed using the Dutch national MEN1 database, including greater than 90% of the Dutch MEN1 population older than 16 years (n = 323). MAIN OUTCOME MEASURES Screening results, natural course, and effects of treatment of PIT were assessed. RESULTS PIT was diagnosed in 123 patients with MEN1 (38.1 %), of whom 66 were diagnosed by MEN1-related screening. Ninety-one percent of the nonfunctioning PIT detected during screening (n = 35), did not require intervention during followup (median, 6.0 y). Three microadenomas showed limited growth but did not progress toward macroadenomas. Both screening-detected and prevalent prolactinomas (n = 52) responded well to treatment with dopamine agonists. CONCLUSION Systematic presymptomatic screening for PIT in patients with MEN1 predominantly results in detection of nonfunctioning microadenomas. Prolactinoma in patients with MEN1 responded well to medical treatment. Microadenomas grew only occasionally and after many years without clinical consequences. Frequent magnetic resonance imaging followup of nonfunctioning microadenomas in the context of MEN1 and sporadically occurring PITs therefore seems debatable.

Enabling minimal invasive parathyroidectomy for patients with primary hyperparathyroidism using Tc-99m-sestamibi SPECT–CT, ultrasound and first results of 18F-fluorocholine PET–CT

OBJECTIVE Assessment of the diagnostic value of ultrasound (US), single photon-emission computed tomography-computed tomography (SPECT-CT) and (18)F-fluorocholine (FCH) PET-CT for preoperative localization of hyper-functioning parathyroid(s) in order to create a more efficient diagnostic pathway and enable minimal invasive parathyroidectomy (MIP) in patients with biochemical proven non-familial primary hyperparathyroidism (pHPT). METHODS A single-institution retrospective study of 63 consecutive patients with a biochemical diagnosis of non-familial pHPT who received a Tc-99m-sestamibi SPECT-CT and neck ultrasound. Surgical findings were used in calculating the sensitivity and the positive predictive value (PPV) of both imaging modalities. Furthermore we present 5 cases who received additional FCH PET-CT. RESULTS A total of 42 (66.7%) patients underwent MIP. The PPV and sensitivity of SPECT-CT, 93.0% and 80.3%, were significantly higher than those of US with 78.3% and 63.2%, respectively. Adding US to SPECT-CT for initial pre-operative localization did not significantly increase sensitivity but did significantly decrease PPV. Performance of US was significantly better when performed after SPECT-CT. (18)F-fluorocholine PET-CT localized the hyper-functioning parathyroid gland in 4/5 cases with discordant conventional imaging, enabling MIP. CONCLUSION SPECT-CT is the imaging modality of choice for initial pre-operative localization of hyper-functioning parathyroid gland(s) in patients with biochemical pHPT. Ultrasound should be performed after SPECT-CT for confirmation of positive SPECT-CT findings and for pre-operative marking allowing MIP. In cases with negative or discordant imaging additional FCH PET-CT should be considered since this might enable the surgeon to perform MIP.

Low-level laser therapy as a treatment for androgenetic alopecia.

Androgenetic alopecia (AGA) affects 50% of males by age 50 and 50% of females by age 80. Recently, the use of low‐level laser therapy (LLLT) has been proposed as a treatment for hair loss and to stimulate hair regrowth in AGA. This paper aims to review the existing research studies to determine whether LLLT is an effective therapy for AGA based on objective measurements and patient satisfaction.

No evidence for distinguishing bacterial from viral acute rhinosinusitis using symptom duration and purulent rhinorrhea: a systematic review of the evidence base

Objective To evaluate the diagnostic value of symptom duration and purulent rhinorrhea in adults suspected of having acute bacterial rhinosinusitis. Data Sources PubMed, EMBASE, and the Cochrane Library. Review Methods We performed a comprehensive systematic search on March 28, 2013. We included studies on the diagnostic value of duration of symptoms and purulent rhinorrhea in patients suspected of having acute bacterial rhinosinusitis. We assessed study design of included articles for directness of evidence and risk of bias. We extracted prevalence and positive and negative predictive values. Results Of 4173 unique publications, we included 1 study with high directness of evidence and moderate risk of bias. The prior probability of bacterial rhinosinusitis was 0.29 (95% confidence interval [CI], 0.24-0.35); we could not extract posterior probabilities. Odds ratios (95% CI) from univariate analysis were 1.03 (0.78-1.36) for duration of symptoms and 2.69 (1.39-5.18) for colored discharge on the floor of the nasal cavity. Conclusion and Recommendation We included 1 study with moderate risk of bias, reporting data in such a manner that we could not assess the value of symptom duration and purulent rhinorrhea in adults suspected of having acute bacterial rhinosinusitis. Recommendations to distinguish between a viral and a bacterial source based on purulent rhinorrhea are not supported by evidence, and the decision to prescribe antibiotic treatment should not depend on its presence. Based on judgment driven by theory and subsidiary evidence of a greater likelihood of bacterial rhinosinusitis after 10 days, antibiotic therapy may seem a reasonable empirical option.

Fluorine-18 fluorocholine PET-CT localizes hyperparathyroidism in patients with inconclusive conventional imaging : a multicenter study from the Netherlands

BackgroundSeveral reports have shown good performance of fluorine-18 fluorocholine (18F-FCH) PET-computed tomography (CT) for parathyroid localization, although overall evidence remains scarce. We collected data from three institutions in the Netherlands and investigated the performance of 18F-FCH PET-CT as a second-line imaging modality. Materials and methodsWe performed a retrospective review of all patients at least 18 years who underwent 18F-FCH PET-CT for biochemically proven hyperparathyroidism (HPT) and inconclusive ultrasound and sestamibi scintigraphy. Acquisition of PET images was performed 30 min after the administration of 2 MBq/kg 18F-FCH, together with a low-dose CT. ResultsPET-CT scans were performed in 33 (75%) women and 11 (25%) men with a mean age of 58.9 (range 31–80 years). Three patients had multiple endocrine neoplasia type 1, one patient had tertiary HPT because of Alport syndrome and the remaining patients had sporadic primary HPT. 18F-FCH PET-CT was positive in 34/44 (77.3%) cases. Of the 35 abnormal glands resected in 33 patients, 18F-FCH PET-CT could successfully localize 33/35 (94.3%), with only one false-positive result [positive predictive value (PPV)=97.1%]. Comparison of the 10 patients with negative PET-CT with the 34 patients with positive PET-CT showed no significant differences in age, sex, ratio of preoperative calcium, use of cinacalcet, history of neck surgery, and concomitant multinodular goiter. ConclusionOur study shows excellent performance of 18F-FCH PET-CT in patients with HPT and inconclusive conventional imaging. Because of its favorable characteristics with high performance, prospective studies should be initiated to determine whether this new technique may replace conventional sestamibi scintigraphy as a first-line imaging modality.

Postoperative Complications After Prophylactic Thyroidectomy for Very Young Patients With Multiple Endocrine Neoplasia Type 2: Retrospective Cohort Analysis.

Abstract The aim of this study was to investigate whether younger age at surgery is associated with the increased incidence of postoperative complications after prophylactic thyroidectomy in pediatric patients with multiple endocrine neoplasia (MEN) 2. The shift toward earlier thyroidectomy has resulted in significantly less medullary thyroid carcinoma (MTC)-related morbidity and mortality. However, very young pediatric patients might have a higher morbidity rate compared with older patients. Hardly any literature exists on complications in the very young. A retrospective single-center analysis was performed on the outcomes of MEN2 patients undergoing a prophylactic total thyroidectomy at the age of 17 or younger. Forty-one MEN2A and 3 MEN2B patients with thyroidectomy after January 1993 and at least 6 months of follow-up were included, subdivided in 9 patients younger than 3 years, 15 patients 3 to 6 years, and 20 patients older than 6 years. Postoperative hypocalcemia and other complications were registered. Twelve (27%) patients developed transient hypocalcemia and 9 (20%) patients suffered from permanent hypocalcemia, with a nonsignificant trend toward higher incidence with decreasing age. Three (7%) patients had other complications, of whom 2 were younger than 3 years. For patients younger than 3 years, the average length of stay (LOS) was 6.7 days, versus 1.7 and 3.5 days, respectively, for the older patient groups (P < 0.05). Patients with complications had a longer LOS compared with patients without (5.0 vs 2.0, P < 0.01). None of the patients had clinical signs of recurrent MTC after a mean follow-up of 10.5 years. Prophylactic thyroidectomy in very young children is associated with a higher rate of complications, causing a significant increased LOS. Irrespective age of surgery, MTC did not recur in any patient. In planning optimal timing of surgery, clinicians should take the risk of complications into account. We advise not to perform total thyroidectomy before the age of 3 for patients defined high risk by the American Thyroid Association guideline.

18F Fluorocholine PET/MR Imaging in Patients with Primary Hyperparathyroidism and Inconclusive Conventional Imaging: A Prospective Pilot Study

Purpose To investigate the performance of flourine 18 (18F) fluorocholine (FCH) positron emission tomography (PET)/magnetic resonance (MR) imaging in patients with hyperparathyroidism and nonlocalized disease who have negative or inconclusive results at ultrasonography (US) and technetium 99m (99mTc) sestamibi scintigraphy. Materials and Methods This study was approved by the institutional review board. Between May and December 2015, 10 patients (mean age, 70.4 years; range, 58-82 years) with biochemical primary hyperparathyroidism and inconclusive results at US and 99mTc sestamibi scintigraphy were prospectively enrolled. All patients gave informed consent. Directly after administration of 3 MBq/kg of FCH, PET imaging was performed, followed by T1- and T2-weighted MR imaging before and after gadolinium enhancement. Intraoperative localization and histologic results were the reference standard for calculating sensitivity and positive predictive value. The Wilcoxon rank test was used to calculate the mean difference in maximum standardized uptake value (SUVmax) between abnormal parathyroid uptake and physiologic thyroid uptake. The Wilcoxon rank-sum test was performed. Results MR imaging alone showed true-positive lesions in five patients and a false-positive lesion in one patient. FCH PET/MR imaging allowed correct localization of nine of 10 adenomas (90% sensitivity), without any false-positive results (100% positive predictive value). One patient had four-gland hyperplasia, of which three hyperplastic glands were not localized. The median SUVmax of the nine preoperatively identified adenomas was 4.9 (interquartile range, 2.45-7.35), which was significantly higher than the SUV, 2.7 (interquartile range, 1.6-3.8), of the thyroid (P = .008). Conclusion FCH PET/MR imaging allowed localization of adenomas with high accuracy when conventional imaging results were inconclusive and provided detailed anatomic information. More patients must be examined to confirm our initial results, and the accuracy of FCH PET/MR imaging for localization of glands in patients with four-gland hyperplasia remains to be investigated.

Diagnostic performance of computed tomography for parathyroid adenoma localization; a systematic review and meta-analysis

PURPOSE To perform a systematic review and meta-analysis of the sensitivity and positive predictive value (PPV) of CT for preoperative parathyroid localization in patients with primary hyperparathyroidism (pHPT), and subsequently compare the different protocols and their performance in different patient groups. MATERIALS AND METHODS We performed a search of the Embase, Pubmed and Cochrane Library databases to identify studies published between January 1, 2000 and March 31, 2016 investigating the diagnostic value of CT for parathyroid localization in patients with biochemical diagnosis of pHPT. Performance of CT was expressed in sensitivity and PPV with pooled proportion using a random-effects model. Factors that could have affected the diagnostic performance were investigated by subgroup analysis. RESULTS Thirty-four studies evaluating a total of 2563 patients with non-familial pHPT who underwent CT localization and surgical resection were included. Overall pooled sensitivity of CT for localization of the pathological parathyroid(s) to the correct quadrant was 73% (95% CI: 69-78%), which increased to 81% (95% CI: 75-87%) for lateralization to the correct side. Subgroup analysis based on the number of contrast phases showed that adding a second contrast phase raises sensitivity from 71% (95% CI: 61-80%) to 76% (95% CI: 71-87%), and that adding a third phase resulted in a more modest additional increase in performance with a sensitivity of 80% (95% CI: 74-86%). CONCLUSION CT performs well in localizing pathological glands in patients with pHPT. A protocol with two contrast phases seems to offer a good balance of acceptable performance with limitation of radiation exposure.

Application of the new American Thyroid Association guidelines leads to a substantial rate of completion total thyroidectomy to enable adjuvant radioactive iodine

Background. The recently published 2015 American Thyroid Association guidelines recognize lobectomy as a viable alternative for low‐risk cancers and advise more conservative use of radioactive iodine. Some factors indicating adjuvant treatment with radioactive iodine (and therefore completion total thyroidectomy), however, only can be found upon pathologic investigation. Methods. We performed a retrospective analysis including patients with American Thyroid Association low‐ and low‐to‐intermediate risk well‐differentiated thyroid cancer 1–4 cm. We evaluated how often radioactive iodine would be indicated and compared this with our historic rate. A subanalysis was performed to determine the rate of completion total thyroidectomy necessary, based on the indications for adjuvant radioactive iodine therapy. Results. A total of 394/1,000 (39.4%) patients were included for final analysis. Adjuvant radioactive iodine would have been favored in 101/394 (25.6%) of patients, which is 2.5 times less than was given in our historic cohort. Completion total thyroidectomy to enable adjuvant radioactive iodine would have been recommended in 29/149 (19.5%) patients preoperatively eligible for lobectomy. Conclusion. Despite the tightened regulations for radioactive iodine, about 20% of patients with apparently “low‐risk” well‐differentiated thyroid cancer who are eligible for lobectomy may need completion total thyroidectomy because of pathologic findings for which radioactive iodine use is listed as considered or favored by the current guidelines.

18 F-Fluorocholine PET-CT enables minimal invasive parathyroidectomy in patients with negative sestamibi SPECT-CT and ultrasound: A case report

Highlights • Preoperative imaging is essential for minimal invasive parathyroidectomy.• Conventional imaging is often negative or inconclusive.• 18F-Fluorocholine PET–CT might be a solution.• We describe a patient with negative SPECT–CT and ultrasound.• Patient underwent successful surgery after positive PET–CT.