Defining contralateral adrenal suppression in primary aldosteronism: implications for diagnosis and outcome.

OBJECTIVE: Unilateral primary aldosteronism (PA) should have a contralaterally normal and therefore suppressed adrenal zona glomerulosa. However, there is no validated definition of adrenal suppression. We created two biochemical hypotheses of adrenal suppression based upon measurements taken during adrenal vein sampling (AVS) to determine whether either proved useful for interpretation of AVS or prediction of hypertension outcome in operated cases. DESIGN: Retrospective database analysis. PATIENTS: Ninety-nine cases of PA from a tertiary hypertension unit. MEASUREMENTS: Hypothesis 1 was the proportional suppression of the uninvolved/lowest adrenal(aldo/cortisol) to IVC(aldo/cortisol) ratio pre- and post cosyntropin. Hypothesis 2 was the absolute decrease in the uninvolved adrenal(aldo/cortisol) ratio after cortrosyn injection. ROC analysis performed using lateralization and hypertension resolution as the outcomes of interest. RESULTS: Hypothesis 1 proved highly predictive of lateralization with a ROC AUC of 0.958, P < 0.0001, giving adrenal(aldo/cortisol):IVC(aldo/cortisol) <1.4 as the optimized criterion (sensitivity 90%, specificity 94%). For blood pressure outcomes in the surgical subgroup (n = 52), hypertension resolution was most commonly seen among subjects with adrenal suppression by both definitions although there was significant overlap with subjects requiring ongoing medication. CONCLUSIONS: Post cosyntropin suppression of the uninvolved adrenal-to-IVC ratio is a highly useful definition of adrenal suppression that accurately predicts unilateral PA. This may be particularly useful in a case where AVS fails to catheterize one of the adrenal veins but suppression is seen on the other side. Adrenal suppression may also predict blood pressure outcome, however, a much larger PA database is likely necessary to determine the relative contribution of this predictor.

Despite limited specificity, computed tomography predicts lateralization and clinical outcome in primary aldosteronism.

BACKGROUND: Computed tomography (CT) of the adrenals is a common first step for investigation of primary aldosteronism (PA). However, prior studies report poor specificity, necessitating adrenal vein sampling (AVS) prior to surgical consideration. METHODS: We examined our AVS database to determine whether CT adrenal findings could help select patients with a high likelihood of lateralization by AVS or high-value blood pressure (BP) outcomes. Subjects (N = 113) with validated outcomes were divided into groups of CT 'positive' or CT 'negative' according to the presence or absence of an adrenal mass and compared for the outcomes of lateralization by AVS or proportions achieving normotension off medications following surgery. RESULTS: For patients with CT adrenal masses, there was a significantly higher odds ratio (OR) for both outcomes (6.3 and 9.7, p < 0.01). In subgroup analysis, age <40 years carried particularly high odds for lateralization and cure when a CT mass was present (ORs 45 and 26, p < 0.01). Young individuals with normal CT adrenals rarely lateralized (10 %) and, in such patients, even factors like hypokalemia, body mass index (BMI), and plasma aldosterone level did not change the result on regression analysis. CONCLUSIONS: CT-imaged adrenal masses strongly predicted lateralization by AVS and normotension with surgical treatment of lateralized PA. In PA, CT-positive patients should indeed be offered AVS and/or surgery given the high chance of good outcomes; younger CT-negative patients should be advised of a low chance of finding surgical disease by AVS.

A marked proportional rise in IVC aldosterone following cosyntropin administration during AVS is a signal to the presence of adrenal hyperplasia in primary aldosteronism.

We hypothesized aldosteronoma responsiveness to cosyntropin may be a characterizing feature that could be determined in addition to standard adrenal vein sampling (AVS) data. We reviewed an AVS database from June 2005 to October 2011 including 65 patients with confirmed primary aldosteronism (PA) who underwent AVS and, if applicable, unilateral adrenalectomy. Patients were divided into confirmed lateralized and non-lateralized groups and subgrouped by histology. Plasma aldosterone in inferior vena cava (IVC) pre- and post-cosyntropin infusion during AVS was measured. Peak aldosterone and proportional change was compared between groups. Baseline and peak IVC aldosterone was higher in lateralized patients but incremental aldosterone rise was much greater in subjects with bilateral hyperplasia. From receiver operator characteristics (ROC) analysis, the optimized diagnostic cut point of peak IVC aldosterone of >649 pmol l(-1) would have a sensitivity of 94% for surgical disease although specificity of just 59%. A 250% increase in IVC aldosterone following cosyntropin would be specific enough to exclude 87% of surgical/lateralized disease. These diagnostic capabilities are similar to other results with non-AVS tests performed for diagnosis of lateralization. Although not specific enough to replace standard AVS interpretation, a marked IVC aldosterone increase after cosyntropin during AVS is a useful additional test to diagnose non-lateralizing forms of PA. Such a calculation requires no additional expense or tests.

Medical or surgical therapy for primary aldosteronism: post-treatment follow-up as a surrogate measure of comparative outcomes.

BACKGROUND: In primary aldosteronism (PA), lateralized aldosterone excess can be treated with aldosterone antagonists or surgery, which raises the question as to whether surgery or medications should be the preferred management. A difference in required patient follow-up/clinic resource utilization might provide a surrogate estimate of the comparative outcome efficacy of medical versus surgical therapy. METHODS: From a retrospective review of our adrenal vein sampling (AVS) database June 2005 to August 2011, we chose all patients with PA who were surgical candidates and investigated with AVS. There were 77 subjects; 38 (with aldosteronoma) had unilateral adrenalectomy, and 39 (7 aldosteronoma and 32 hyperplasia) were treated with primary medical therapy. After AVS, patients with nonsurgical disease immediately started mineralocorticoid antagonists and follow-up measured from the AVS date. Surgical patients were seen in the clinic immediately after hospital discharge and follow-up measured from the operative date. Target BP was <140/90 before discharge to the community. RESULTS: Total follow-up ranged from 1 to 55 months, and 4 subjects were lost to follow-up. Mean follow-up in the medical and surgical groups was 13.4 versus 6.5 months (p < 0.004). There was a trend toward more clinic visits for the medical group (7.0 vs 5.2, p = 0.17). CONCLUSIONS: Most PA patients can be managed by medical or surgical approaches. Medically treated patients require much longer-term follow-up to manage their condition, whereas most surgical patients can be successfully discharged shortly after surgery. When possible, surgical management may represent a more expeditious means of treating PA.

Long-term follow-up and cost benefit of adrenalectomy in patients with primary hyperaldosteronism.

BACKGROUND: The purpose of this study was to evaluate the long-term efficacy of adrenalectomy on blood pressure control in patients with primary hyperaldosteronism (HA), and to analyse the cost of adrenalectomy compared with non-surgical management of HA over the patient's lifetime. METHODS: All patients who underwent an adrenalectomy for HA were recalled to the endocrine surgical clinic. Data gathered included blood pressure, aldosterone : renin ratios and medication. Total costs for adrenalectomy and ongoing medications were compared with the estimated costs of lifelong medical therapy alone. RESULTS: Twenty-four adrenalectomies were performed for HA, with one death. The mean follow-up was 42 (range 13-97) months. Long term, there was a significant decrease in both the mean diastolic and systolic blood pressure. The aldosterone : renin ratio decreased in 21 patients. Of these patients, 20 were either off all antihypertensives (eight) or had a reduction in medication (12). An increased aldosterone : renin ratio occurred in two patients, both of whom required an increase in antihypertensive medication. Using the predicted life expectancy, the mean estimated cost savings over the lifetime of each patient undergoing adrenalectomy compared with medication alone was Canadian $31 132. CONCLUSION: Adrenalectomy for HA resulted in significant long-term reduction in blood pressure. Adrenalectomy for HA is a significantly less expensive than long-term medical therapy alone.

Carcinoid syndrome symposium on treatment modalities for gastrointestinal carcinoid tumours: symposium summary.

OBJECTIVE: To develop a collaborative approach for the treatment of gastrointestinal carcinoid tumours and carcinoid syndrome. PARTICIPANTS: Leaders in the medical, endocrine, radiologic and surgical treatment of carcinoid disease were selected to present papers at the Carcinoid Syndrome Symposium on Treatment Modalities for Gastrointestinal Carcinoid Tumours and participate in the workshop that followed. EVIDENCE: A multidisciplinary symposium with experts in the field of carcinoid syndrome was organized at the University of Calgary. Data presented, participation of the attendees and a review of the literature were used in the workshop to develop a collaborative approach to the management of carcinoid tumours. BENEFITS: Carcinoid tumours are rare and few centres have large experiences in their treatment. Before the development of this collaboration, patients with carcinoid tumours received a unidisciplinary approach depending on referral patterns. The development of a multidisciplinary neuroendocrine clinic helped to unify the approach to these patients, yet a consensus on the treatment of carcinoid tumours was lacking. The expertise at the symposium allowed for consensus and the development of treatment algorithms, including biochemical screening, radiographic localization and surgical intervention, for gastrointestinal carcinoid tumours. The role of medical and hormonal therapy after cytoreducion is presented. RECOMMENDATION: Patients with carcinoid tumours require a multidisciplinary approach to their care.

Feasibility of sentinel lymph node biopsy and lymphatic mapping in nodular thyroid neoplasms.

Although the prognostic significance of occult lymph node metastases in thyroid cancer remains controversial, identifying these patients may help direct therapy. The purpose of this study was to determine the feasibility and safety of sentinel lymph node biopsy (SLNBx) in thyroid nodular disease. Patients undergoing thyroid resection, with no evidence of clinical lymphadenopathy, were enrolled. The nodule was injected with isosulfan blue vital dye. Blue-stained lymphatic channels were traced within the central compartment to the SLN, which was excised. A total of 40 patients underwent SLNBx; lymphatics were seen in 31 patients, and SLNs were found in 26. In 11 patients the lymphatic vessels were traced through the central compartment into the lateral or mediastinal compartments, although a central SLN was retrieved in only 6. Of the 18 patients with benign neoplasms, 14 had benign SLNs, and no SLN was found in 4. A thyroid lymphoma patient had a true positive SLN. In the 12 patients with papillary thyroid cancer (PTC), 6 had true positive SLNs, and 2 had a true negative SLN. In one patient with metastatic PTC, the parathyroid stained blue. Another patient with PTC had lateral lymphatic channels, but no SLN was found. There were two false negatives, proven by a node dissection in one and lateral uptake on (131)I scanning in the other. There were no postoperative complications. SLNBx for thyroid disease is feasible and safe. Potential staining of the parathyroids makes their identification before injection mandatory. The variable lymphatic drainage patterns and the two false-negative nodes indicate that further investigation is required before the procedure can be recommended for patients with thyroid disease.

A prospective surgical outcome study assessing the impact of parathyroidectomy on symptoms in patients with secondary and tertiary hyperparathyroidism.

BACKGROUND: To assess the impact of surgery on preoperative symptoms in secondary (2 degrees ) and tertiary (3 degrees ) hyperparathyroidism (HPT) compared with primary (1 degrees ) HPT. METHODS: Twenty-two patients with 2 degrees HPT and 10 with 3 degrees HPT were enrolled. Age-matched patients, 32 with 1 degrees HPT and 32 with thyroid disease were enrolled for comparison. An outcome questionnaire documented symptoms expressed as the median symptom index score (MSIS) preoperatively and at days 7 and 3 and 12 months postoperatively. RESULTS: Preoperatively, the MSIS for the groups with 3 degrees, 2 degrees, and 1 degrees HPT and thyroid disease was 225, 572, 372, and 146, indicating that patients with HPT were more symptomatic than those in the thyroid group (P<.05). Patients with 1 degrees HPT had a decrease in their MSIS at day 7 (195, P<.05) and at 3 and 12 months (159 and 156). Patients with 3 degrees HPT also had a decrease in their MSIS over time. Patients with 2 degrees HPT had a decrease in their MSIS at day 7 (469, P<.05); however, they remained more symptomatic at 3 and 12 months (410 and 355). CONCLUSIONS: Parathyroidectomy reduces many of the preoperative symptoms in HPT. Patients with 1 degrees and 3 degrees HPT have a similar resolution of their symptoms. Patients with 2 degrees HPT have an improvement in many of their symptoms, although they remain more symptomatic at 1 year.

Hashimoto's disease and thyroid lymphoma: role of the surgeon.

With the turn of the century, the role of the surgeon in the treatment of diseases such as Hashimoto's and thyroid lymphoma has diminished. That is not to say that the surgeon must not have a thorough understanding of these diseases and the role he or she plays in their diagnosis and treatment. Hashimoto's disease is a common disease. Not infrequently the endocrine surgeon is faced with a thyroid nodule in a background of Hashimoto's disease. Interpretation of fine-needle aspiration (FNA) of a nodule in a patient with the background of Hashimoto's disease may be misleading if the surgeon fails to understand the limitations of FNA. The role of the surgeon in the treatment and diagnosis of thyroid lymphomas has evolved from surgical debulking to open biopsy. With the use of irradiation and chemotherapy, the need for surgical debulking has nearly disappeared. The recent development of ancillary techniques such as light chain restriction, flow cytometry, gene rearrangement, and immunohistochemical staining have enabled cytopathologists to diagnose thyroid lymphoma by FNA, further diminishing the surgeon's role in the diagnosis and treatment of this disease.

The surgeon as a prognostic factor in endocrine surgical diseases.

As with all subspecialties, the endocrine surgeon offers more than just improved technical expertise in the treatment of endocrine surgical disease. An understanding of the disease, and an ability to interpret investigations and surgically intervene with minimal morbidity allow for better patient care. Outcomes of endocrine surgical diseases are measured by the success of the operation at relieving the endocrinopathy and the ability of the surgeon to find the tumor, while at the same time minimizing the postoperative morbidity. Each of these factors has been considered when assessing the role of specialized expertise in endocrine surgical disease. The recurrence and survival data for these tumors, however, are not forthcoming and, therefore, the limitations of the existing literature must be acknowledged.

Short- and long-term outcome of total parathyroidectomy with immediate autografting versus subtotal parathyroidectomy in patients with end-stage renal disease.

A retrospective study was performed in 36 patients with end-stage renal disease (ESRD) comparing total parathyroidectomy followed by immediate autografting into the forearm (total PTX + IA) with parathyroidectomy (subtotal PTX) over a five-year period. Twenty-eight patients underwent subtotal PTX and 8 had total PTX + IA. The two surgical methods were evaluated with respect to preoperative severity of hyperparathyroidism, perioperative morbidity, and the incidence of recurrent hyperparathyroidism. Eleven patients in total (30.6%) developed recurrent hyperparathyroidism; 2/8 (25%) in the total PTX + IA group compared to 9/28 (32.1%) in the subtotal PTX group (p = 0.699). The median time to recurrence was longer in the total PTX + IA group (39 vs. 16 months), and the median long-term postoperative PTH value was lower (81 vs. 199 ng/l), but these differences did not reach statistical significance. In conclusion, the incidence of recurrent hyperparathyroidism is high regardless of surgical modality. However, total PTX + IA may produce more favorable results with respect to median postoperative PTH level and time to recurrence.

Pancreatic polypeptide hyperplasia causing watery diarrhea syndrome: a case report.

Neuroendocrine tumours of the pancreas can secrete numerous peptides, leading to various recognizable clinical syndromes. The secretion of pancreatic polypeptide has been used as a marker for neuroendocrine tumours but is considered to be a biologically inert peptide. A 37-year-old woman had watery diarrhea syndrome from pancreatic polypeptide hyperplasia. Only 2 other reported cases in the literature have described pancreatic polypeptide hyperplasia; however, this is the first reported case in which the patient was successfully treated by surgical resection, with a 2-year follow-up. This report and review of the literature illustrate that pancreatic polypeptide hypersecretion may present as a clinical endocrinopathy.

Hypopigmentation of a papillary carcinoma arising in a black thyroid.

We report a case of an unpigmented papillary carcinoma arising in a black thyroid induced by minocycline. Black thyroid syndrome is an unusual pigmented change seen almost exclusively in patients on minocycline, apparently resulting from an oxidative interaction between thyroid peroxidase and the drug. Twenty-six cases have previously been reported in the English literature, nine of which described an associated thyroid neoplasm. Four of these nine neoplasms were described as pale or hypopigmented. The nature of the lesion against the background of pigmentation suggests diminished function of the thyroid peroxidase in this clonal population.

Anaplastic cancer, lymphoma, and metastases of the thyroid gland.

Not all thyroid carcinomas behave in an indolent fashion. There is a rare group of thyroid neoplasms that is biologically aggressive and carries a poor prognosis. These tumors include poorly differentiated tumors, anaplastic, and thyroid lymphomas. Poorly differentiated tumors are important tumors to recognize because aggressive surgical intervention appears to offer the best chance for long-term survival. Until recently, anaplastic carcinoma was universally fatal. Preoperative chemotherapy and hyperfractionated radiation has led to better local control and a few long-term survivors. The role of the surgeon in the treatment of the thyroid lymphomas remains controversial, however, most would agree that the surgeons role is limited, because these tumors are radiosensitive and chemosensitive.

Prospective surgical outcome study of relief of symptoms following surgery in patients with primary hyperparathyroidism.

Many of the symptoms experienced by patients with primary hyperparathyroidism (HPT) develop insidiously and have often been misinterpreted as normal aging. The purpose of this study was to quantify HPT patients' preoperative symptoms prospectively and study the impact of successful surgical intervention on these symptoms. Altogether 63 consecutive patients with primary HPT and 54 comparison patients with nontoxic thyroid disease were prospectively enrolled in the study. An outcome questionnaire documenting symptoms with a visual analog scale (VAS) was used. The questionnaire was filled out preoperatively and at 7 to 10 days and 3 and 12 months postoperatively. At 1 year the questionnaire also included a general health assessment and quality of life index. Demographic data and follow-up blood work was obtained. Descriptive statistics, parametric comparisons (t-tests, ANOVA), and nonparametric comparisons (Mann-Whitney U-test) were calculated. The HPT group demonstrated a significant decrease in reported symptoms between the preoperatively assessment and 7 to 10 days after operation (p < 0.001). There were no further statistically significant decreases in the HPT group's symptoms at 3 and 12 months, but there was a trend for these symptoms to decrease over time. HPT patients perceived a 60% increase in their general health at 1 year; the comparison group perceived no increase. There was no significant change in the symptoms reported by the comparison group between each of the study intervals. Surgical intervention on HPT patients significantly reduces preoperative symptoms, and this reduction is most marked within the first 10 days after surgery.

Effect of pH modification by bicarbonate on pain after subcutaneous lidocaine injection.

OBJECTIVE: To quantify the pain experienced on subcutaneous injection of lidocaine, lidocaine with sodium bicarbonate (NaHCO3) and saline. DESIGN: A double-blind randomized prospective study. SETTING: A clinical research unit in a university-affiliated hospital. PARTICIPANTS: Forty-two healthy adult volunteers who did not have a history of adverse reaction to lidocaine or peripheral neuropathy and were not pregnant. The study was performed in two phases. In Phase 1, 1 mL each of three solutions (2 mL or 8.4% NaHCO3 in 20 mL 1% lidocaine, 2 mL saline in 20 mL lidocaine and saline alone) were injected by an investigator, blinded as to the identity of the solutions, in random order to five volunteers to measure onset and duration of anesthesia and the perceived pain on injection. In Phase 2, 37 volunteers were injected with the three solutions in random order, by an investigator blinded as to the identity of the solutions. MAIN OUTCOME MEASURE: Pain on injection measured with the visual analogue scale. RESULTS: There were no clinically significant differences between onset and duration of action of lidocaine with and without NaHCO3, as determined by Kruskal- Wallis one-way analysis of variance and the Wilcoxon signed-ranks test. Injection of lidocaine with NaHCO3 was significantly less painful than injection of plain lidocaine (p=0.041). Injection of saline was the most painful. CONCLUSION: The addition of NaHCO3 to lidocaine produces significant reduction in pain experienced on injection without significantly affecting the onset or duration of action.

Assessing the need for frozen sections: still a valuable tool in thyroid surgery.

BACKGROUND: Since the development of fine-needle aspiration (FNA) there has been a trend away from frozen sections (FS) in the assessment of thyroid neoplasms. The objective of this study was to determine the role of FS in the surgical management of thyroid nodules in the presence of an adequate FNA biopsy finding. METHODS: Charts of patients who presented within a 3-year period for thyroid surgery were reviewed. Inclusion criteria consisted of both an adequate FNA and FS. RESULTS: Eighty-five patients met the inclusion criteria. Three lesions were benign, 71 were suspicious, and 11 were malignant with FNA. There were 66 deferred and 19 malignant diagnoses with FS. The overall accuracy for FNA and FS was 40% and 86%, respectively. When the FNA report was positive for malignancy, it was correct in 91% (10 of 11) of the cases. When the FNA report was suspicious, only 30% (21 of 71) had a malignant lesions. FS confirmed malignancy in 19 patients and deferred more extensive surgery in 66 patients with suspicious lesions. However, 18% of the deferred FS were found to be malignant on final pathology report. CONCLUSIONS: This study showed that there is a role for FS in the surgical management of thyroid nodules. Frozen sections can be useful when the FNA report is suspicious for malignancy; however, FS may be eliminated when the FNA report is positive for malignancy.

Screening and surgical intervention in the multiple endocrine neoplasia patient.

Persons with multiple endocrine neoplasias (MEN) are a unique group of patients that present with various APUDomas. Screening of family members can lead to early detection of these tumors and possible cure of potentially fatal tumors. Screening for the MEN syndromes at present is limited to provocative and biochemical parameters. The gene(s) responsible for these syndromes have not, as of yet, been characterized but in the future will add greatly to the ability to identify these patients early. Early surgical intervention of these APUDomas, has lead to an improved prognosis for these tumors. The screening and the surgical approach to each syndrome are outlined.

Consensus conference on well-differentiated thyroid cancer: a summary.

OBJECTIVE: To update recommendations for the surgical treatment of well-differentiated thyroid cancer. DATA SOURCES: Literature reviews and personal files. STUDY SELECTION: Panelists selected relevant articles to make arguments for and against current recommendations for the surgical treatment of well-differentiated thyroid cancer. OUTCOMES: Four aspects of surgical treatment were considered: (a) the extent of surgical resection, (b) the definition and utilization of high- and low-risk patient groups, (c) who should perform thyroid surgery and (d) the use of radioactive iodine. RECOMMENDATIONS: Total thyroidectomy is not the treatment of choice for all well-differentiated thyroid cancers. The use of risk factors help select those patients in whom a total thyroidectomy would be of benefit. High-risk patients are those who are considered at high risk according to the AGES and AMES classifications or who have lymph-node metastases, aggressive variants of their disease, multifocal cancer or disease in the contralateral thyroid lobe and a history of radiation to the neck. Those at low-risk are those previously described as being at low risk according to the AGES and AMES classifications. General surgery training programs across Canada need to ensure that their residents obtain enough experience in thyroid surgery that as general surgeons they can perform this type of surgery with low morbidity. CONCLUSIONS: The findings of this consensus conference were supported by those of several review articles and by the arguments put forward by the panelists. These findings are only guidelines as to the surgical approach to well-differentiated thyroid cancer.