Shelby Holt

Surgical Approach and Perioperative Complications Determine Short-Term Outcomes in Patients with Insulinoma: Results of a Bi-Institutional Study

BackgroundDespite advancements in radiologic imaging and minimally invasive surgery, the evaluation and management of insulinomas is institution and surgeon dependent. Therefore, the reported surgical outcomes are highly variable. We compared the surgical management and outcomes of insulinomas between two international tertiary-care surgical units to better identify the best management as determined by short-term outcomes.MethodsWe performed a retrospective review of patients who underwent surgery for insulinomas over a 117-month period at UT Southwestern Medical Center in Dallas (UTSW) and Queen Mary Hospital in Hong Kong (QMHK). Data collected included imaging studies, operative procedure, complications, and outcomes.ResultsThirty-seven patients were identified. Preoperative localization by computed tomography (CT) scan was successful in 21 patients (63.9%). In Hong Kong, 16 patients underwent selective arterial cannulation and calcium stimulation (SACST) with a success rate of 87.5%. Surgical management consisted of enucleation in 24 patients and distal pancreatectomy in 13 patients. Thirty patients underwent a concurrent intraoperative ultrasound, with localization in 96.7%. Laparoscopic procedures were accomplished in 20 patients. Nine postoperative complications were identified, four occurring in the laparoscopic group. Patients undergoing laparoscopic procedures had a decreased length-of-stay (LOS) compared with patients undergoing an open procedure and patients who had uncomplicated surgery had a trend toward decreased LOS.ConclusionThough the accuracy of CT scans for localizing insulinomas is only 64%, the addition of SACST or intraoperative ultrasound and pancreatic palpation increases accuracy to 97.1%. Compared with open procedures, laparoscopic resection is associated with comparable complication rates and shorter hospital length of stay.

Papillary thyroid carcinoma shows elevated levels of 2-hydroxyglutarate

Elevated levels of d-2-hydroxyglutarate (d-2-HG) occur in gliomas and myeloid leukemias associated with mutations of IDH1 and IDH2. l-2-Hydroxyglutaric aciduria, an inherited metabolic disorder, predisposes to brain tumors. Therefore, we asked whether sporadic cancers, without IDH1 or IDH2 hot-spot mutations, show elevated 2-hydroxyglutarate levels. We retrieved 15 pairs of frozen papillary thyroid carcinoma (PTC) and adjacent non-neoplastic thyroid, and 14 pairs of hyperplastic nodule (HN) and adjacent non-hyperplastic thyroid. In all lesions, exon 4 sequencing confirmed the absence of known mutations of IDH1 and IDH2. We measured 2-hydroxyglutarate by liquid chromatography-tandem mass spectrometry. Compared to normal thyroid, PTCs had significantly higher d-2-HG and l-2-hydroxyglutarate (l-2-HG) levels, and compared to HNs, PTCs had significantly higher d-2-HG levels. d-2-HG/l-2-HG levels were not significantly different between HNs and normal thyroid. Further studies should clarify if elevated 2-hydroxyglutarate in PTC may be useful as cancer biomarker and evaluate the role of 2-hydroxyglutarate in cancer biology.

Significance of elevated parathyroid hormone after parathyroidectomy for primary hyperparathyroidism.

OBJECTIVE To provide a clinical update on persistent parathyroid hormone (PTH) elevation after surgical resection for primary hyperparathyroidism (PHPT) and to suggest a schedule for follow-up monitoring and strategies for future study. METHODS We reviewed the literature targeting studies with detailed analysis of biochemical parameters before and after parathyroidectomy for PHPT. We focused on potential etiologies and currently available outcome data. RESULTS PTH elevation with eucalcemia after parathyroidectomy for PHPT occurs in 12% to 43% of patients. Underlying etiology is probably multifactorial, and possible causes include bone hunger, vitamin D deficiency, inadequate calcium intake or absorption, reduced peripheral sensitivity to PTH, underlying chronic kidney disease, and/or a renal leak of calcium. No consensus exists on how to follow-up and treat these patients. CONCLUSIONS Although most patients with PTH elevation after parathyroidectomy will have normalization of PTH levels with time and/or calcium and vitamin D supplementation, this finding may be an early indicator of autonomous parathyroid secretion in a small number of patients. Patients with persistent PTH elevation should be monitored over time for recurrence of PHPT and other possible complications. A standardized follow-up protocol is needed to better study and elucidate the clinical significance of elevated PTH after parathyroidectomy.

The Impact of Obesity on the Presentation of Primary Hyperparathyroidism

CONTEXT Obesity has been associated with elevated serum PTH (sPTH) in the general population. Obesity may also alter the clinical presentation in patients with primary hyperparathyroidism (PHPT). OBJECTIVES The objectives of the study were to compare the clinical presentation of obese (OB) vs nonobese (NO) PHPT patients and to assess the impact of obesity on the presentation of PHPT independent of serum calcium and PTH. PATIENTS Consecutive PHPT patients who underwent parathyroidectomy between 2003 and 2012 by a single surgical group participated in the study. SETTING The study was conducted at an academic medical center. DESIGN Cross-sectional review of records of preoperative demographic, historical, laboratory, and densitometry findings and intraoperative pathological findings were compared in OB vs NO patients. MAIN OUTCOME MEASURES The prevalence of nephrolithiasis and osteoporosis was measured. RESULTS Two hundred forty-seven PHPT patients were included in this analysis. Fifty percent were OB and 79% were women. Mean body mass index was 25.3 ± 3.3 and 36.0 ± 5.2 kg/m(2) in the NO and OB groups, respectively. Age, gender, and race distribution was similar between the two groups. Serum calcium was similar between the groups (11.0 ± 0.7 mg/dL in NO vs 11.1 ± 0.9 mg/dL in OB, P = .13), whereas sPTH was higher in OB (151 ± 70 vs 136 ± 69 pg/mL, P = .03). The OB group exhibited higher prevalence of hypercalciuria (urine calcium > 400 mg per 24 h) (41% vs 23% in NO, P = .01) and nephrolithiasis (36% vs 21% in NO, P = .03). Despite higher sPTH, OB patients showed higher bone mineral density and a lower rate of osteoporosis (21% vs 35%, P = .05). Differences in the prevalence of hypercalciuria and osteoporosis between the groups persisted after adjustment for age, race, estimated glomerular filtration rate, gender, sPTH, and calcium. CONCLUSIONS In PHPT patients, obesity is a risk factor for hypercalciuria and nephrolithiasis and is protective against osteoporosis. The impact of parathyroidectomy on the clinical features of obese PHPT patients merits further evaluation.

The many faces of pheochromocytoma

Objective: To recognize and manage pheochromocytomas in unusual settings. Methods: Three case reports are presented with clinical, biochemical, imaging, and operative findings. The pitfalls in diagnosis of pheochromocytomas and management are addressed. Results: We begin with a 27-yr-old gravida 2, para 1 Caucasian woman with unexplained tachycardia and hypertension during a routine pre-natal visit at 30 weeks estimated gestational age. Urinary studies revealed elevated catecholamines. Magnetic resonance imaging localized a 6.6-cm right adrenal mass with features consistent with a pheochromocytoma. She was medically managed with phenoxybenzamine and propranolol until 35 weeks, after which she underwent a combined Cesarean section, and open right adrenalectomy. Another patient, a 36-yr-old African-American woman presented to a hospital in cardiac arrest, with elevated serum troponins, and underwent cardiac catheterization, which revealed normal coronary arteries. A computed tomography (CT) scan revealed a left adrenal mass and CT-guided biopsy was consistent with a pheochromocytoma, although prior studies were negative. Finally, we present a 49-yr-old Caucasian woman who had a right adrenalectemy 10 yr prior and presented to the clinic with fluctuating blood pressures, headaches, and palpitations. Further testing revealed she had a recurrent metastatic pheochromocytoma. The challenges behind treating these patients are further explored. Conclusion: Antenatal diagnosis of pheochromocytoma, though challenging, is associated with lower maternal and fetal morbidity and mortality. The differential diagnosis for cardiac arrest in the presence of normal coronary arteries should include a pheochromocytoma. Finally, treatment with iodinated metaiodobenzylguanidine may be a therapeutic option for those patients with metastatic pheochromocytomas.

How do we improve patient access to high-volume thyroid surgeons?

THE IMPACT OF BOTH SURGEON AND HOSPITAL VOLUME ON PATIENT OUTCOMES is not a new concept. The everincreasing demand for high-quality medical care, however, has drawn further attention to factors influencing patient outcomes. Greater surgeon volumes have been associated consistently with better outcomes across multiple surgery specialties. Although recognizing this well-studied, reproducible association, it is imperative to emphasize that volume is only one of multiple factors influencing operative quality and outcome. This article, like other preceding studies, affectively illustrates how high volume contributes to lesser complication rates in endocrine surgery. In addition, the authors of ‘‘Surgeon Volume and Adequacy of Thyroidectomy for Differentiated Thyroid Cancer’’ demonstrate how increasing operative volume can optimize the care of patients with differentiated thyroid cancer. Adkisson et al evaluated a single health care system experience with thyroid surgery for differentiated thyroid cancer. Primary outcome measures included complication rates and selected surrogate markers for completeness of oncologic resection. They found that high-volume surgeons (HVS) experienced fewer complications and performed fewer 2-stage thyroidectomies. In addition, resection by HVS resulted in lower iodine uptake values on pretreatment scans as well as lower initial stimulated thyroglobulin levels, both suggestive of a more complete surgical resection. Although these findings did not equate to differences in recurrence rates or disease-free survival in the present study, an association between lesser iodine

High-Risk and Poorly Differentiated Thyroid Cancer

Follicular cell-derived thyroid carcinomas are classified based on their histology and cellular architecture, as well differentiated (papillary carcinoma and follicular carcinoma), poorly differentiated, and undifferentiated thyroid carcinomas (Pathology and genetics of tumors of endocrine organs. Lyon: IARC Press, 2004). Although the majority of clinically diagnosed thyroid cancers today are of the well-differentiated variety arising from follicular thyroid cells, dedifferentiation results in an aggressive phenotype which is responsible for an inordinate number of deaths from thyroid cancer.

Glucocorticoid-responsive lymphocytic parathyroiditis and hypocalciuric hypercalcemia due to autoantibodies against the calcium-sensing receptor: a case report and literature review

OBJECTIVE Autoimmune lymphocytic parathyroiditis and acquired hypocalciuric hypercalcemia associated with autoantibodies against the calcium-sensing receptor (anti-CaSR) are rare and poorly understood conditions. Here, we describe a patient with acquired parathyroid hormone (PTH)-dependent hypercalcemia with associated hypocalciuria, found to have true lymphocytic parathyroiditis on histopathology, and circulating anti-CaSR antibodies in serum. DESIGN AND METHODS A 64-year-old woman was referred to our clinic for persistent hypercalcemia after a subtotal parathyroidectomy. She was normocalcemic until the age of 63 years when she was diagnosed with primary hyperparathyroidism. She underwent subtotal parathyroidectomy with appropriate intraoperative PTH decline. Two weeks post-parathyroidectomy, she presented with persistent hypercalcemia and hyperparathyroidism. Urine studies revealed an inappropriately low 24-h urine calcium (Ca)/creatinine clearance ratio. Surgical pathology was consistent with true lymphocytic parathyroiditis with lymphoid follicles. The presence of circulating anti-CaSR antibodies was detected by immunoprecipitation of CaSR by the patients serum. After a 4-week course of prednisone, serum Ca and PTH normalized, and her anti-CaSR titers declined. She remains normocalcemic 10 months after the discontinuation of glucocorticoid therapy. We present this patient in the context of the relevant published literature on lymphocytic parathyroiditis and acquired hypocalciuric hypercalcemia related to anti-CaSR antibodies. CONCLUSIONS Autoimmune lymphocytic parathyroiditis and acquired hypocalciuric hypercalcemia associated with anti-CaSR antibodies is a very rare yet important condition to be considered in a patient with acquired PTH-dependent hypercalcemia with inappropriate hypocalciuria. Although subtotal parathyroidectomy is unlikely to correct the hypercalcemia, this entity may respond to a short course of prednisone therapy.