Surgical Approach of Synchronous Medullary Thyroid Carcinoma and Pheochromocytoma in MEN 2 Syndrome

In cases with concurrent medullary thyroid carcinoma (MTC) and pheochromocytoma, discussion regarding a one-stage versus two-stage treatment strategy approach remains open. From 1975 to 1990, 11 of 25 multiple endocrine neoplasia type 2 (MEN 2) patients presented with biendocrinopathies or triendocrinopathies synchronously. All patients were treated surgically and followed subsequently in our hospital. Of the group of nine patients with concurrent MTC and pheochromocytoma, five were treated in one-stage and four in two-stage procedures. No patient had major complications intraoperatively. For the two-stage group, the total hospital stay (preoperatively and postoperatively) averaged 35 days. For the one-stage group, the total hospital stay averaged 25 days. In patients with increased operative risks (patients with higher age and impaired physical condition or if neck surgery includes transstemal cervicomediastinal lymphadenectomy), two-stage procedures should be selected. However, in young patients with the MEN 2 syndrome or syndromes with small tumors detected by family screening, thyroidectomy, cervical lymphadenectomy, and adrenalectomy may be performed in a one-stage procedure without increasing surgically related morbidity

Long-Term Results after Treatment of Very Low-, Low-, and High-Risk Thyroid Cancers in a Combined Setting of Thyroidectomy and Radio Ablation Therapy in Euthyroidism

Introduction. Differentiated thyroid cancer treatment usually consists of thyroidectomy and radio ablation in hypothyroidism 4-6 weeks after surgery. Replacing hypothyroidism by recombinant human thyroid stimulating hormone can facilitate radio ablation in euthyroidism within one week after surgery. The outcome of this approach was investigated. Methods. This is a prospective randomized trial to compare thyroidectomy and radio ablation within a few days after preconditioning with recombinant human thyroid stimulating hormone versus thyroidectomy and radio ablation separated by four weeks of L-T4 withdrawal. Tumors were graded into very low-, low- , or high-risk tumors. Recurrence-free survival was confirmed at follow-up controls by neck ultrasound and serum thyroglobulin. Suspected tumor recurrence was treated by additional radio ablation or surgery. Quality-of-life questionnaires with additional evaluation of job performance and sick-leave time were used in all patients. Results. Radio ablation in euthyroidism in quick succession after thyroidectomy did not lead to higher tumor recurrence rates of differentiated thyroid cancers in any risk category and was significantly advantageous with respect to quality-of-life (P<0.001), sick-leave time (P<0.001), and job performance (P=0.002). Conclusion. Recombinant human thyroid stimulating hormone can be used safely and with good efficacy to allow radio ablation under sustained euthyroidism within one week after thyroidectomy

Adrenal Cortex Transplantation After Bilateral Total Adrenalectomy in the Rat

An experimental animal model with adrenal cortex transplantation was developed to study adrenal cortex replacement therapy in patients with multiple endocrine neoplasia type 2 who have had bilateral adrenalectomy for pheochromocytomas. Adrenal cortex of syngenetic rats was isolated from the medulla by collagenase digestion and a defined sedimentation. The cell suspension of the cortical cells was implanted under the kidney capsule of untreated syngenetic rats. After two weeks the recipients were bilaterally adrenalectomized. Serum corticosterone levels were measured as an estimate of function of the grafts. All recipients were healthy throughout the observation period, whereas all adrenalectomized controls died within 18 days. Vital cortex cells could be demonstrated in the explanted grafts by immunohistochemistry. Corticosterone levels of transplanted animals were nearly normal (9.5 ng/100 mL ± 0.4) compared to the controls (0.20 ng/mL ± 0.06). This animal model of adrenal cortex transplantation allows the separation of medullary from cortical cells. After transplantation, these cortical cells survived for eight weeks and were able to replace the adrenal cortex function

Risk-factors for nodular hyperplasia of parathyroid glands in sHPT patients

<div><p>Introduction</p><p>Nodular hyperplasia of parathyroid glands (PG) is the most probable cause of medical treatment failure in secondary hyperparathyroidism (sHPT). This prospective cohort study is located at the interface of medical and surgical consideration of sHPT treatment options and identifies risk-factors for nodular hyperplasia of PG.</p><p>Material and methods</p><p>One-hundred-eight resected PG of 27 patients with a broad spectrum of sHPT severity were classified according to the degree of hyperplasia by histopathology. Twenty routinely gathered parameters from medical history, ultrasound findings of PG and laboratory results were analyzed for their influence on nodular hyperplasia of PG by risk-adjusted multivariable binary regression. A prognostic model for non-invasive assessment of PG was developed and used to weight the individual impact of identified risk-factors on the probability of nodular hyperplasia of single PG.</p><p>Results</p><p>Independent risk-factors for nodular hyperplasia of single PG were duration of dialysis in years, PG volume in mm³ determined by ultrasound and serum level of parathyroid hormone in pg/mL. Multivariable analyses computed a model with an Area Under the Receiver Operative Curve of 0.857 (95%-CI:0.773–0.941) when predicting nodular hyperplasia of PG. Theoretical assessment of risk-factor interaction revealed that the duration of dialysis had the strongest influence on the probability of nodular hyperplasia of single PG.</p><p>Conclusions</p><p>The three identified risk-factors (duration of dialysis, PG volume determined by ultrasound and serum level of parathyroid hormone) can be easily gathered in daily routine and could be used to non-invasively assess the probability of nodular hyperplasia of PG. This assessment would benefit from periodically collected data sets of PG changes during the course of sHPT, so that the choice of medical or surgical sHPT treatment could be adjusted more to the naturally changing type of histological PG lesion on an individually adopted basis in the future.</p></div

Probability of nodular hyperplasia of PG depending on values of individual risk-factors.

<p>Values of the duration of dialysis (−∙−∙−), PG volume measured by US (---) and serum levels of PTH (−−−) were categorized and standard units for a 10-step alteration were defined. The duration of dialysis was prolonged from 1 to 10 years by steps of 1 year. The PG volume determined by US was increased from 100 to 1.000 mm³ by steps of 100 mm³. The units of the 10-step alteration are given at the x-axis. The serum level of PTH was decreased from 1.000 to 100 pg/mL by steps of 100 pg/mL. While altering each parameter separately, the others were set to a default reference level with duration of dialysis = 2 years, PG volume determined by US = 400 mm³, and PTH serum level = 600 pg/mL. The calculated probability for nodular hyperplasia of PG is given in percent at the y-axis.</p

Receiver operating characteristic—curve for the prediction of nodular hyperplasia in individual parathyroid glands by the use of the prognostic model.

<p>The AUROC is 0.857 with a binominal exact 95% confidence interval: 0.773–0.941. The best Youden index determined a predicted probability of 52.9% as the cut-off value with best sensitivity and specificity for prediction of nodular hyperplasia in individual (specificity 86.1%, sensitivity 70.6%, overall correctness 78.3%). Good model fit was demonstrated by use of Pearson (0.75), Deviance (0.49), and Hosmer-Lemeshow tests (0.16).</p

Characteristics of parathyroid glands.

<p>Characteristics of parathyroid glands.</p

Internal validation of the developed prognostic score using randomized bootstrapping.

<p>Internal validation of the developed prognostic score using randomized bootstrapping.</p

Topography and size of parathyroid glands at parathyroidectomy and ultrasound.

<p>Topography of the right-sided superior and inferior PG after luxation of the thyroid gland (A). Topography and measurement of corresponding PG by US: superior (B+C) and inferior (D+E). Volumes of PG were 479mm³ (PG superior) and 99mm³ (PG inferior) when calculated with US measurements. Documentation of PG size during surgery: superior (F+G) and inferior (H+I). Volumes of PG were 858mm³ (PG superior) and 293mm³ (PG inferior) when calculated with intra-operative measurements. PGs, superior parathyroid gland; PGi, inferior parathyroid gland.</p