The role of thyroidectomy in metastatic disease to the thyroid gland.

BACKGROUND: Whether thyroidectomy for metastases to the thyroid is associated with a survival benefit remains debatable; in general, palliation and disease control are accepted goals in this setting. We evaluated the clinical features and overall survival of patients with thyroid metastasis treated by thyroid resection or nonoperatively. METHODS: This retrospective analysis included 90 patients identified with metastasis to the thyroid confirmed pathologically via thyroidectomy (n = 31) or fine-needle aspiration biopsy (n = 59). Overall survival was calculated by the Kaplan-Meier method, and differences between groups were calculated by Pearson's χ (2) coefficient. RESULTS: The most common primary malignancies were renal cell (20%), head and neck (19%), and lung (18%). The median time from primary tumor diagnosis to thyroid metastasis diagnosis was 37.4 months (range 0-210 months). Most metastases (69%) were metachronous, and 12% were isolated. The median follow-up after diagnosis of thyroid metastasis was 11.5 months (range 0-112 months). Median overall survival was longer in thyroidectomy patients compared to the fine-needle aspiration group (34 vs. 11 months, P < 0.0001). Patients with renal cell primary tumors were more likely to undergo thyroidectomy than patients with other primary tumors (78 vs. 24%, P < 0.0001). Nearly all patients with lung primary tumors died within 24 months of thyroid metastasis diagnosis, and thyroidectomy was only offered to three patients. CONCLUSIONS: Thyroidectomy was safe for selected patients with metastatic disease to the thyroid. Patients with metachronous or renal cell metastasis to the thyroid and whose primary tumor is/was treatable may be appropriate candidates for resection. Lung cancer metastasis to the thyroid is generally an ominous sign.

Operative failure in minimally invasive parathyroidectomy utilizing an intraoperative parathyroid hormone assay.

BACKGROUND: Minimally invasive parathyroidectomy (MIP) is a targeted operation to cure primary hyperparathyroidism utilizing intraoperative parathyroid hormone monitoring (IOPTH). The purpose of this study was to quantify the operative failure of MIP. METHODS: Utilizing institutional parathyroid surgery database, demographic, operative, and biochemical data were analyzed for successful and failed MIP. Operative failure was defined as <6 months of eucalcemia after operation. RESULTS: Five hundred thirty-eight patients (96.6 %) had successful MIP with mean follow-up of 13 months, and 19 (3.4 %) had operative failure. The major cause of operative failure (11 of 19) was the result of surgeons' inability to identify all abnormal parathyroid glands. The remaining eight operative failures were the result of falsely positive IOPTH results. Eleven of 19 patients whose MIP had failed underwent a second parathyroid surgery. All but one of these patients achieved operative success, and 9 patients had missed multigland disease. Only 46 (8.3 %) of 557 patients had conversion to bilateral cervical exploration (BCE). Eighty percent of patients had more than 70 % IOPTH decrease, and all had successful operations. Patients with a marginal IOPTH decrease (50-59 %) had a treatment failure rate of 20 %. CONCLUSIONS: The most common cause of operative failure in MIP utilizing IOPTH was the result of surgeons' failure to identify all abnormal parathyroid glands. Falsely positive IOPTH is rare, and a targeted MIP utilizing IOPTH can achieve an excellent operative success rate without routine BCE. Selective BCE on patients with marginal IOPTH decrease may improve surgical outcome.

Ultrasonography should not guide the timing of thyroidectomy in pediatric patients diagnosed with multiple endocrine neoplasia syndrome 2A through genetic screening.

BACKGROUND: American Thyroid Association (ATA) guidelines suggest that thyroidectomy can be delayed in some children with multiple endocrine neoplasia syndrome 2A (MEN2A) if serum calcitonin (Ct) and neck ultrasonography (US) are normal. We hypothesized that normal US would not exclude a final pathology diagnosis of medullary thyroid cancer (MTC). METHODS: We retrospectively queried a MEN2A database for patients aged<18 years, diagnosed through genetic screening, who underwent preoperative US and thyroidectomy at our institution, comparing preoperative US and Ct results with pathologic findings. RESULTS: 35 eligible patients underwent surgery at median age of 6.3 (range 3.0-13.8) years. Mean MTC size was 2.9 (range 0.5-6.0) mm. The sensitivity of a US lesion≥5 mm in predicting MTC was 13% [95% confidence interval (CI) 2%, 40%], and the specificity was 95% [95% CI 75%, 100%]. Elevated Ct predicted MTC in 13/15 patients (sensitivity 87% [95% CI 60%, 98%], specificity 35% [95% CI 15%, 59%]). The area under the receiver operating characteristic curve (AUC) for using US lesion of any size to predict MTC was 0.50 [95% CI 0.33, 0.66], suggesting that US size has poor ability to discriminate MTC from non-MTC cases. The AUC for Ct level at 0.65 [95% CI 0.46, 0.85] was better than that of US but not age [AUC 0.62, 95% CI 0.42, 0.82]. CONCLUSIONS: In asymptomatic children with MEN2A diagnosed by genetic screening, preoperative thyroid US was not sensitive in identifying MTC of any size and, when determining the age for surgery, should not be used to predict microscopic MTC.

Advances in robotic adrenalectomy.

PURPOSE OF REVIEW: We review the development of robotic adrenalectomy over the last decade, focusing on specific technical advances in the last 18 months. RECENT FINDINGS: The learning curve for robotic adrenalectomy, after which conversion rates and operative times significantly decrease, is more than 20 cases even in surgeons with extensive laparoscopic experience. Two new uses of the robot to extend traditional laparoscopic adrenalectomy have been highlighted in recent studies. Posterior retroperitoneoscopic adrenalectomy can be aided by robotic assistance, particularly in patients whose adrenal gland is located well superior to the 12th rib, on the anterior surface of the kidney, or in the renal hilum. Robotic assistance has also enabled cortical-sparing adrenalectomy which may obviate the need for steroid hormone replacement in patients with multiple or bilateral tumors. SUMMARY: Robot-assisted adrenalectomy can extend the capabilities of traditional laparoscopy, particularly in regard to performing posterior retroperitoneal and subtotal adrenalectomies.

T cell receptor (TCR)-transgenic CD8 lymphocytes rendered insensitive to transforming growth factor beta (TGFß) signaling mediate superior tumor regression in an animal model of adoptive cell therapy.

Tumor antigen-reactive T cells must enter into an immunosuppressive tumor microenvironment, continue to produce cytokine and deliver apoptotic death signals to affect tumor regression. Many tumors produce transforming growth factor beta (TGFß), which inhibits T cell activation, proliferation and cytotoxicity. In a murine model of adoptive cell therapy, we demonstrate that transgenic Pmel-1 CD8 T cells, rendered insensitive to TGFß by transduction with a TGFß dominant negative receptor II (DN), were more effective in mediating regression of established B16 melanoma. Smaller numbers of DN Pmel-1 T cells effectively mediated tumor regression and retained the ability to produce interferon-γ in the tumor microenvironment. These results support efforts to incorporate this DN receptor in clinical trials of adoptive cell therapy for cancer.

Non-super-selective venous sampling for persistent hyperparathyroidism using a systemic hypocalcemic challenge.

PURPOSE: To describe a new protocol employing an acute systemic hypocalcemic challenge (SHC) aimed at augmenting the parathyroid hormone (PTH) gradient to enable non-super-selective venous sampling (VS) in patients with persistent primary hyperparathyroidism (PHPT). MATERIALS AND METHODS: In a retrospective study, 37 patients (39 studies-20 SHC, 19 super-selective VS) who underwent VS for persistent or recurrent PHPT were examined. Study patients were pretreated with intravenous hydration, diuretics, and bicarbonate to induce temporary relative hypocalcemia and then underwent non-super-selective VS targeted at large vessels within the neck and chest with rapid PTH testing. The traditional VS protocol involved super-selective VS with arteriography. RESULTS: SHC decreased ionized calcium by 0.098 mmol/L ± 0.18 (P = .07) and increased peripheral PTH by 10.2 pg/mL (P = .58). Positive VS gradients, defined as a ≥ 1.4-fold difference from baseline to after SHC, were detected in 95% of patients. VS findings guided successful surgery in 77% of SHC cases and 90% of super-selective VS cases; the peak gradient site was concordant with operative findings in 46% of SHC cases and 80% of super-selective VS cases. Avoidance of super-selective sampling decreased mean fluoroscopy time from 91 minutes to 33 minutes and decreased contrast material administered from 204 mL to 63 mL (both P < .0001). CONCLUSIONS: The SHC protocol to enable non-super-selective VS in patients with persistent PHPT had the same ability as super-selective VS to detect a positive (≥ 1.4-fold) PTH gradient, was associated with decreased accuracy in identifying the site of the adenoma compared with super-selective VS, and significantly decreased contrast material used and fluoroscopy time.

A selective, Bayesian approach to intraoperative PTH monitoring.

OBJECTIVE: To determine if the performance of intraoperative parathyroid hormone monitoring (IPM) can be optimized by limiting its application to patients with weak preoperative localization. BACKGROUND: The value of IPM during minimally invasive parathyroidectomy (MIP) has been questioned, particularly in cases with strong preoperative localization. We describe a novel, Bayesian strategy employing IPM in select patients with a high pretest probability of multiple gland disease (MGD). METHODS: We prospectively examined 361 consecutive patients undergoing surgery for primary hyperparathyroidism. All patients underwent sestamibi (MIBI) scanning and surgeon-performed ultrasound. Intraoperative PTH levels were only used for surgical decision-making in the MIBI-negative, ultrasound-positive patient subset. The following outcomes were analyzed: MGD rate, test performance, success rate, and operative time. RESULTS: Patients with any positive localization study (91%) were offered MIP. The success rate was 99%. The MGD rate was 3% in MIBI-positive patients and 36% in MIBI-negative patients (10% overall, P < 0.0001). MIBI and surgeon-performed ultrasound were equally sensitive (80% vs. 85%, NS). Among MIBI-negative patients, 71% of whom underwent MIP with IPM, an inadequate fall in the 10-minute postexcision PTH level was highly predictive of MGD, saving 10 failures while causing 1 inappropriate conversion to bilateral exploration (negative likelihood ratio, NLR 28.0). In contrast, among MIBI-positive patients, IPM could have saved 3 failures at the expense of 18 inappropriate conversions (NLR 9.9). IPM increased operative time from 34 to 60 minutes (P < 0.0001). CONCLUSION: IPM is more likely to guide the surgeon correctly when used only in MIBI-negative patients, who have a high pretest probability of MGD. This selective strategy maintains high success rates while limiting the frequently adverse impact that IPM carries when used indiscriminately.

Parathyroid surgery in the elderly.

INTRODUCTION: The prevalence of primary hyperparathyroidism (PHPT) is expected to increase in developed nations as the aged population grows. This review discusses issues related to PHPT in the elderly population with a focus on differences in disease presentation, medical and surgical management, and outcomes. METHODS: Literature review of English-language studies of PHPT or parathyroidectomy (PTx) in the elderly was performed. Surgical literature reviewed included original clinical studies published after 1990. Priority was given to studies with >30 patients where institutional practice and outcomes have not changed significantly over time. RESULTS: Elderly patients primarily present with nonclassic symptoms of PHPT that can sometimes be missed in favor of other diagnoses. They have equivalent surgical outcomes, including morbidity, mortality, and cure rates, compared with younger patients, although their length of hospital stay is significantly longer. Several recent studies demonstrate the safety and efficacy of outpatient, minimally invasive parathyroidectomy in an elderly population. Patients are referred for PTx less frequently with each advancing decade, although surgical referral patterns have increased over time in centers that offer minimally invasive parathyroidectomy. Elderly patients experience increased fracture-free survival after PTx. The majority of elderly patients report symptomatic relief postoperatively. CONCLUSION: PTx can offer elderly patients with PHPT improved quality of life. PTx is safe and effective in elderly patients, and advanced age alone should not deter surgical referral.

The value of intraoperative parathyroid hormone monitoring in localized primary hyperparathyroidism: a cost analysis.

BACKGROUND: Minimally invasive parathyroidectomy (MIP) is the preferred approach to primary hyperparathyroidism (PHPT) when a single adenoma can be localized preoperatively. The added value of intraoperative parathyroid hormone (IOPTH) monitoring remains debated because its ability to prevent failed parathyroidectomy due to unrecognized multiple gland disease (MGD) must be balanced against assay-related costs. We used a decision tree and cost analysis model to examine IOPTH monitoring in localized PHPT. METHODS: Literature review identified 17 studies involving 4,280 unique patients, permitting estimation of base case costs and probabilities. Sensitivity analyses were performed to evaluate the uncertainty of the assumptions associated with IOPTH monitoring and surgical outcomes. IOPTH cost, MGD rate, and reoperation cost were varied to evaluate potential cost savings from IOPTH. RESULTS: The base case assumption was that in well-localized PHPT, IOPTH monitoring would increase the success rate of MIP from 96.3 to 98.8%. The cost of IOPTH varied with operating room time used. IOPTH reduced overall treatment costs only when total assay-related costs fell below $110 per case. Inaccurate localization and high reoperation cost both independently increased the value of IOPTH monitoring. The IOPTH strategy was cost saving when the rate of unrecognized MGD exceeded 6% or if the cost of reoperation exceeded $12,000 (compared with initial MIP cost of $3733). Setting the positive predictive value of IOPTH at 100% and reducing the false-negative rate to 0% did not substantially alter these findings. CONCLUSIONS: Institution-specific factors influence the value of IOPTH. In this model, IOPTH increased the cure rate marginally while incurring approximately 4% additional cost.

Intratumoral immune cell infiltrates, FoxP3, and indoleamine 2,3-dioxygenase in patients with melanoma undergoing CTLA4 blockade.

PURPOSE: CTL-associated antigen 4 (CTLA4)-blocking monoclonal antibodies induce long-term regression of metastatic melanoma in some patients, but the exact mechanism is unknown. In this study, biopsies of selected accessible tumor lesions from patients treated with tremelimumab were examined to further elucidate the mechanism of its antitumor activity. EXPERIMENTAL DESIGN: Fifteen tumor biopsies from 7 patients who had been treated with tremelimumab (CP-675,206) were collected. Samples were analyzed for melanoma markers, immune cell subset markers, the presence of the T regulatory-specific transcription factor FoxP3 and the immunosuppressive enzyme indoleamine 2,3-dioxygenase (IDO). RESULTS: Clinically responding lesions had diffuse intratumoral infiltrates of CD8(+) T cells that were markedly increased in cases where comparison with a baseline biopsy was available. Nonregressing lesions had sparse, patchy CD8(+) intratumoral infiltrates. Patients with regressing lesions had an increased frequency of CD8(+) cells with or without a concomitant increase in CD4(+) cells. Two of 3 responding patients with paired samples showed a slight increase in the number of FoxP3(+) cells in the postdosing biopsies. In patients with regressing lesions who had paired samples, the intensity of IDO staining in macrophages and/or melanoma cells showed no clear pattern of change postdosing. CONCLUSIONS: Administration of tremelimumab was associated with massive intratumoral infiltrates of CD8(+) CTLs in patients with regressing tumors but had varying effects on intratumoral infiltrates of CD4(+) and FoxP3(+) cells or intratumoral expression of IDO.

Immunosensitization with a Bcl-2 small molecule inhibitor.

Several tumor immunotherapy approaches result in a low percentage of durable responses in selected cancers. We hypothesized that the insensitivity of cancer cells to immunotherapy may be related to an anti-apoptotic cancer cell milieu, which could be pharmacologically reverted through the inhibition of antiapoptotic Bcl-2 family proteins in cancer cells. ABT-737, a small molecule inhibitor of the antiapoptotic proteins Bcl-2, Bcl-w and Bcl-x(L), was tested for the ability to increase antitumor immune responses in two tumor immunotherapy animal models. The addition of systemic therapy with ABT-737 to the immunization of BALB/c mice with tumor antigen peptide-pulsed dendritic cells (DC) resulted in a significant delay in CT26 murine colon carcinoma tumor growth and improvement in survival. However, the addition of ABT-737 to either a vaccine strategy involving priming with TRP-2 melanoma antigen peptide-pulsed DC and boosting with recombinant Listeria monocytogenes expressing the same melanoma antigen, or the adoptive transfer of TCR transgenic cells, did not result in superior antitumor activity against B16 murine melanoma. In vitro studies failed to demonstrate increased cytotoxic lytic activity when testing the combination of ABT-737 with lymphokine activated killer (LAK) cells, or the death receptor agonists Fas, TRAIL-ligand or TNF-alpha against the CT26 and B16 cell lines. In conclusion, the Bcl-2 inhibitor ABT-737 sensitized cancer cells to the antitumor effect of antigen-specific immunotherapy in a vaccine model for the CT26 colon carcinoma in vivo but not in two immunotherapy strategies against B16 melanoma.

Therapeutic cancer vaccines.

Therapeutic cancer vaccines target the cellular arm of the immune system to initiate a cytotoxic T-lymphocyte response against tumor-associated antigens. Immunotherapy offers one of the few therapeutic options that reproducibly leads to a subset of patients with long-term remissions (seemingly cures) of widely metastatic disease. Therapeutic cancer vaccines tested in clinical trials have included inactivated tumor cells administered in immunological adjuvants or after genetic modification to increase their immunogenicity. Other forms are heat shock protein vaccines and anti-ganglioside antibodies. Tumor-associated antigenic peptides have been fully characterized for some cancers. Finally, strategies to directly expand antitumor T lymphocytes and adoptively transfer them to patients with cancer have been developed and shown to induce objective tumor regressions.

Thyroid stunning.

Debates regarding thyroid stunning-a phenomenon whereby a diagnostic dose of radioiodine decreases uptake of a subsequent therapeutic dose by remnant thyroid tissue or by functioning metastases-have been fueled by inconsistent research findings. Quantitative studies evaluating radioiodine uptake and qualitative studies using visual observations both compare thyroid function on the diagnostic scan (DxSCAN) versus the posttreatment whole-body scan (RxWBS). The variability of findings may be the result of a lack of consensus in clinical nuclear medicine regarding many parameters of radioiodine usage including the need to obtain a pretreatment diagnostic scan, appropriate therapeutic dose, time between therapy dose administration and DxSCAN, and how successful ablation is measured. In the studies considered in this review, those that used (123)I rather than (131)I for DxSCAN, allowed less time to elapse between diagnostic and therapy dose, and more time between therapy dose and RxWBS (at least 1 week), did not observe stunning. However, groups that recognized stunning did not demonstrate any difference in outcomes (determined by successful first-time ablation). Whether stunning is a temporary phenomenon whereby stunned tissue eventually rejuvenates, or whether observed stunning actually constitutes "partial ablation," is yet to be delineated.

Preoperative multiple endocrine neoplasia type 1 diagnosis improves the surgical outcomes of pediatric patients with primary hyperparathyroidism.

BACKGROUND: Primary hyperparathyroidism (PHPT) is uncommon in children. The surgical management of PHPT in children has evolved over the past two decades. METHODS: A retrospective study of patients who underwent parathyroidectomy for PHPT diagnosed at age < 18 years and managed at a tertiary referral center for endocrine and familial disorders. RESULTS: Thirty-eight patients met eligibility criteria (1981-2012). Median age at PHPT diagnosis was 15 years. Two-thirds of patients were symptomatic (68%, n=26), most commonly from nephrolithiasis. Twenty-six (68%) patients underwent a standard cervical exploration while 32% underwent a focused unilateral parathyroidectomy. Multiple endocrine neoplasia type 1 (MEN1) was diagnosed preoperatively in 22/26 patients. Patients with a preoperative diagnosis of MEN1 were more likely to undergo a complete initial operation (≥ 3 gland parathyroidectomy with transcervical thymectomy, 13/22, 59% vs. 0/4, 0%; P=0.03) and less likely to have recurrent disease (10/22, 45% vs. 3/4, 75%; P<0.001) during follow up than patients diagnosed postoperatively. CONCLUSIONS: Children with PHPT should raise suspicion for MEN1. Preoperative MEN1 evaluation helped guide the extent of initial parathyroidectomy and was associated with lower rates of recurrence in sporadic and familial PHPT in pediatric patients. Management should occur at a high volume center with experienced clinicians and genetic counseling services.

Fewer adverse events after reoperative parathyroidectomy associated with initial minimally invasive parathyroidectomy.

BACKGROUND: This study compared reoperative complication rates after initial minimally invasive parathyroidectomy and standard cervical exploration. METHODS: Records from patients who underwent 1 reoperative parathyroidectomy at a single institution (1998 to 2012) were retrospectively reviewed. RESULTS: Seventy-seven patients were included; 74% underwent initial standard cervical exploration. Preoperative and operative characteristics were similar between groups; 74% underwent focused, unilateral reoperation. A significantly higher rate of postoperative complications occurred in the initial standard cervical exploration group (42% vs 15%, P = .03) that could not be explained by differences in the rates of symptomatic hypocalcemia (P = .5). The type of prior parathyroidectomy was significantly associated with postoperative complications (odds ratio 4.1, 95% confidence interval 1.1 to 15.7, P = .04). In a multivariable logistic regression model that included body mass index, type of operation (for initial and reoperation), and initial operation performed prereferral as covariates, type of prior parathyroidectomy remained a significant predictor of postoperative complications. CONCLUSION: Higher rates of postoperative sequelae after initial standard cervical exploration should be considered before performing routine 4-gland exploration.

Streamlining variability in hospital charges for standard thyroidectomy: Developing a strategy to decrease waste.

BACKGROUND: We assessed the efficiency, consistency, and appropriateness of perioperative processes for standard (total) thyroidectomy and devised a valuable strategy to decrease variability and waste. METHODS: Our multidisciplinary team evaluated <23-hour stay standard thyroidectomy performed by 3 surgical endocrinologists. We used the nominal group technique, process flowcharts, and root cause analysis to evaluate 6 perioperative processes. Anticipated decreases in costs, charges, and resources from improvements were calculated. RESULTS: Median total charge for standard thyroidectomy was $27,363 (n = 80; $48,727 variation). Perioperative coordination between surgery and anesthesia clinics could eliminate unnecessary testing (potential decrease in charges of $1,505). Nonoperating room time was less in the outpatient operating room (43 vs 52 minutes; P < .001). Consistent scheduling could decrease charges by $585.49 per case. By decreasing 20% of nondisposable instruments on the surgical tray, we could decrease sterile processing costs by $13.30 per case. Modification of postoperative orders could decrease charges by $643 per patient. Overall, this comprehensive analysis identified an anticipated decrease in cost/charge of >$200,000 annually. CONCLUSION: Perioperative process analyses revealed wide variability for a single, presumed uniform procedure. Systematic assessment helped to identify opportunities to improve efficiency, decrease unnecessary waste and procedures/instrument usage, and focus on patient-centered, quality care. This multidisciplinary strategy could substantially decrease costs/charges for common operative procedures.

Pre-operative ultrasound identification of thyroiditis helps predict the need for thyroid hormone replacement after thyroid lobectomy.

OBJECTIVE: To evaluate whether pre-operative thyroiditis identified by ultrasound (US) could help predict the need for thyroid hormone replacement (THR) following thyroid lobectomy. METHODS: Data from patients who underwent thyroid lobectomy in 2006-2011, were not taking THR pre-operatively, and had ≥1 month of follow-up were reviewed retrospectively. THR was prescribed for relatively elevated thyroid-stimulating hormone (TSH) and hypothyroid symptoms. The Kaplan-Meier method was used to estimate the percentage of patients who required THR at 6, 12, 18, and 24 months postoperatively, and Cox proportional hazards regression models were used to evaluate prognostic factors for requiring post-thyroid lobectomy THR. RESULTS: During follow-up, 45 of 98 patients required THR. Median follow-up among patients not requiring THR was 11.6 months (range, 1.2 to 51.3 months). Six months after thyroid lobectomy, 22% of patients were taking THR (95% confidence interval [CI], 15-32%); the proportion increased to 46% at 12 months (95% CI, 36-57%) and 55% at 18 months (95% CI, 43-67%). On univariate analysis, significant prognostic factors for postoperative THR included a pre-operative TSH level >2.5 µ international units [IU]/mL (hazard ratio [HR], 2.8; 95% CI, 1.4-5.5; P = .004) and pathology-identified thyroiditis (HR, 2.4; 95% CI, 1.3-4.3; P = .005). Patients with both pre-operative TSH >2.5 µIU/mL and US-identified thyroiditis had a 5.8-fold increased risk of requiring postoperative THR (95% CI, 2.4-13.9; P<.0001). CONCLUSION: A pre-operative TSH level >2.5 µIU/mL significantly increases the risk of requiring THR after thyroid lobectomy. Thyroiditis can add to that prediction and guide pre-operative patient counseling and surgical decision making. US-identified thyroiditis should be reported and post-thyroid lobectomy patients followed long-term (≥18 months).

Impact and timing of bilateral adrenalectomy for refractory adrenocorticotropic hormone-dependent Cushing's syndrome.

INTRODUCTION: In patients with refractory adrenocorticotropic hormone-dependent Cushing's syndrome,we evaluated steroidogenesis inhibition (SI) and bilateral adrenalectomy (BA) to predict which patients might benefit most from each treatment modality. METHODS: Clinical data from patients treated 1970-2012 were reviewed retrospectively by treatment group (SI or SI+BA). Validated severity scales were used to calculate metabolic (M) score (hypokalemia, hyperglycemia, hypertension, proximal muscle weakness) and adverse events (AE) score (thrombosis, fracture, infection). RESULTS: A total of 65 patients (16 pituitary, 49 ectopic) were treated with SI+BA (n = 21,32%) or SI alone (n = 44,68%). Presenting M scores and source of adrenocorticotropic hormone excess (ectopic versus pituitary) were similar. Both groups improved metabolically after treatment. Over one-third of AEs in the SI+BA group occurred within 12 months of presentation. Half (n = 24, 55%) of the patients treated with SI died (median survival, 24.0 months). Steroid excess contributed to 71% of complications. Six SI+BA patients died (29%), including all 3 patients with recurrent Cushing's syndrome after BA. Minor perioperative complications occurred in 7 patients (33%). CONCLUSION: Posttreatment M and AE scores improved for all patients and 70% of AEs occurred in SI+BA patients within 12 months of presentation, emphasizing the importance of early operative intervention. These data argue for the safety and efficacy of early BA in selected patients with uncontrollable Cushing's syndrome.

Long-term follow-up data may help manage patient and parent expectations for pediatric patients undergoing thyroidectomy.

BACKGROUND: We investigated the incidence and impact of postoperative complications in children who underwent total thyroidectomy (TTx). METHODS: The records of all pediatric patients undergoing TTx (2001-2011) at our institution were retrospectively reviewed for the occurrence of biochemical hypothyroidism (thyroid-stimulating hormone >10 mIU/mL), laboratory assessments, and medication nonadherence. RESULTS: The 74 patients (median age, 12.5 years) had thyroid cancer (differentiated, n = 39; medullary, n = 16) or benign pathology (n = 19; 16 with multiple endocrine neoplasia type 2A). The median postoperative follow-up was 3.2 years; 46 patients (62%) had ≥ 1 year follow-up. Forty-one percent had ≥ 1 period of medication nonadherence; this was not associated with age at TTx (P = .30). Non-treatment-related hypothyroidism occurred in 33% of patients during postoperative year (POY) 1. The number of POY1 laboratory assessments among the 30% of patients with parathyroid dysfunction was more than twice that among patients with normal parathyroid function (median assessments per year 8 vs 3; P < .0001). Forty-four percent of patients/families reported behavioral or physiologic changes; 40% were concomitant with abnormal thyroid function. CONCLUSION: More than 40% of pediatric patients were unable to fully adhere to postoperative medication regimens, and non-treatment-related hypothyroidism was common. Postoperative hypoparathyroidism doubled the number of laboratory assessments obtained. These data may help families better prepare for TTx sequelae.