Use of fluorescence imaging and indocyanine green during thyroid and parathyroid surgery: Results of an intercontinental, multidisciplinary Delphi survey.

BACKGROUND: In recent years, fluorescence imaging-relying both on parathyroid gland autofluorescence under near-infrared light and angiography using the fluorescent dye indocyanine green-has been used to reduce risk of iatrogenic parathyroid injury during thyroid and parathyroid resections, but no published guidelines exist regarding its use. In this study, orchestrated by the International Society for Fluorescence Guided Surgery, areas of consensus and nonconsensus were examined among international experts to facilitate future drafting of such guidelines. METHODS: A 2-round, online Delphi survey was conducted of 10 international experts in fluorescence imaging use during endocrine surgery, asking them to vote on 75 statements divided into 5 modules: 1 = patient preparation and contraindications to fluorescence imaging (n = 11 statements); 2 = technical logistics (n = 16); 3 = indications (n = 21); 4 = potential advantages and disadvantages of fluorescence imaging (n = 20); and 5 = training and research (n = 7). Several methodological steps were taken to minimize voter bias. RESULTS: Overall, parathyroid autofluorescence was considered better than indocyanine green angiography for localizing parathyroid glands, whereas indocyanine green angiography was deemed superior assessing parathyroid perfusion. Additional surgical scenarios where indocyanine green angiography was thought to facilitate surgery are (1) when >1 parathyroid gland requires resection; (2) during redo surgeries, (3) facilitating parathyroid autoimplantation; and (4) for the predissection visualization of abnormal glands. Both parathyroid autofluorescence and indocyanine green angiography can be used during the same procedure and employing the same imaging equipment. However, further research is needed to optimize the dose and timing of indocyanine green administration. CONCLUSION: Though further research remains necessary, using fluorescence imaging appears to have uses during thyroid and parathyroid surgery.

Indocyanine green fluorescence imaging during partial adrenalectomy.

BACKGROUND: Indocyanine green (ICG) fluorescence imaging represents an emerging technology that facilitates the assessment of tissue vascularity, tissue distinction, and tumor localization during surgery. The aim of this study was to investigate the potential role of ICG imaging during laparoscopic partial adrenalectomy. METHODS: Indocyanine fluorescence imaging was carried out during laparoscopic partial adrenalectomy for bilateral pheochromocytoma and bilateral Cushing's syndrome. A first bolus of 5 mg ICG was applied intravenously upon exposure of the retroperitoneal plane to identify the adrenal borders. The fluorescence was visualized using a Storz® NIR/ICG endoscopic system. As the camera of this system detects NIR light as a blue signal, the well-vascularized adrenal tissue was expected to show a strong fluorescence in the blue color channel in contrast to the surrounding adipose tissue. Following partial adrenalectomy, a second bolus of 5 mg ICG was applied intravenously to evaluate the vascularity of the remaining adrenal tissue. RESULTS: We investigated six adrenal glands from three patients undergoing bilateral partial adrenalectomy. The indication for surgery was pheochromocytoma in two patients and Cushing's syndrome with bilateral adenomas in one patient. Regarding left adrenalectomies, ICG imaging was helpful in visualizing the adrenal borders and the adrenal vein. Further, it facilitated the identification of the hypofluorescent pheochromocytoma and to resect the entire tumor. On the right side, due to the more apparent anatomy, ICG imaging did not contribute to the conduct of the operation. Four adrenal remnants showed a strong vascularization and two remnants were only reasonably vascularized. CONCLUSION: ICG fluorescence may be helpful in guiding partial adrenalectomy and assessing the vascularity of remaining adrenal tissue.

Intraoperative Near-Infrared Autofluorescence and Indocyanine Green Imaging to Identify Parathyroid Glands: A Comparison.

OBJECTIVE: To investigate the feasibility of near-infrared autofluorescence (AF) and indocyanine green (ICG) fluorescence to identify parathyroid glands intraoperatively. METHODS: Fluorescence imaging was carried out during open parathyroid and thyroid surgery. After visual identification, parathyroid glands were exposed to near-infrared (NIR) light with a wavelength between 690 and 770 nm. The camera of the Storz® NIR/ICG endoscopic system used detects NIR light as a blue signal. Therefore, parathyroid AF was expected to be displayed in the blue color channel in contrast to the surrounding tissue. Following AF imaging, a bolus of 5 mg ICG was applied intravenously. ICG fluorescence was detected using the same NIR/ICG imaging system. Well-vascularized parathyroid glands were expected to show a strong fluorescence in contrast to surrounding lymphatic and adipose tissue. RESULTS: We investigated 78 parathyroid glands from 50 patients. 64 parathyroid glands (82%) displayed AF showing the typical bluish violet color. 63 parathyroid glands (81%) showed a strong and persistent fluorescence after application of ICG. The sensitivity of identifying a parathyroid gland by AF was 82% (64 true positive and 14 false negative results), while ICG imaging showed a sensitivity of 81% (63 true positive and 15 false negative results). The Fisher exact test revealed no significant difference between both groups at p < 0.05. Neither lymph nodes nor adipose tissue revealed substantial AF or ICG fluorescence. CONCLUSION: AF and ICG fluorescence reveal a high degree of sensitivity in identifying parathyroid glands. Further, ICG imaging facilitates the assessment of parathyroid perfusion. However, in the current setting both techniques are not suitable as screening tools to identify parathyroid glands at an early stage of the operation.

A pitfall of bilateral inferior petrosal sinus sampling in cyclic Cushing's syndrome.

BACKGROUND: Clinical care of patients with cyclic Cushing's syndrome (CS) is challenging. Classical pitfalls include incorrect subtyping, unnecessary surgical procedures and delayed definite treatment. CASE PRESENTATION: A 43-year-old female suffered from a rapidly cycling ectopic CS. She experienced six cycles of severe hypercortisolism within a 2 year period (maximum plasma cortisol 5316 nmol/L, normal range 124.2-662.4 nmol/L; maximum urinary free cortisol 79,469 nmol/24 h, normal range < 414 nmol/24 h) lasting 2-9 weeks. The episodes were associated with pronounced hypokalemia (lowest K+ value recorded 2.4 mmol/l) and progressive signs and symptoms of CS. A bilateral inferior petrosal sinus sampling (BIPSS) performed during a trough phase was false positive for pituitary ACTH overproduction resulting in unnecessary transsphenoidal surgery while a second BIPSS performed during an active phase was indicative for ectopic CS. The 18F-DOPA PET/CT showed a pancreatic lesion, which was subsequently partially removed. Surprisingly, the histopathology was conclusive for ACTH-positive lymph node metastasis located in the retro-duodenal tissue of an occult neuroendocrine tumor WHO grade II. The primary tumor has not been identified so far and, because of the persistent hypercortisolism, the patient underwent bilateral adrenalectomy. Two years later, ACTH levels started to increase progressively. Percutaneous biopsy of a newly identified suspected lesion in the fifth thoracic vertebra revealed a metastasis with positive staining for ACTH, synaptophysin and chromogranin A. Therapy with carboplatin and etoposide was started and, since then, the patient underwent 12 cycles of chemotherapy. CONCLUSIONS: We report the challenging case of a rapidly cycling CS secondary to ACTH-secreting neuroendocrine intestinal tumor of unknown primary. We highlight the importance of performing diagnostic tests only during the phases of active cortisol secretion and as soon as first symptoms appear to avoid pitfalls.

Parathyroid Autofluorescence-How Does It Affect Parathyroid and Thyroid Surgery? A 5 Year Experience.

Injury to parathyroid glands during thyroid and parathyroid surgery is common and postoperative hypoparathyroidism represents a serious complication. Parathyroid glands possess a unique autofluorescence in the near-infrared spectrum which could be used for their identification and protection at an early stage of the operation. In the present study parathyroid autofluorescence was visualized intraoperatively using a standard Storz laparoscopic near-infrared/indocyanine green (NIR/ICG) imaging system with minor modifications to the xenon light source (filtered to emit 690 nm to 790 nm light, less than 1% in the red and green above 470 nm and no blue light). During exposure to NIR light parathyroid tissue was expected to show autofluorescence at 820 nm, captured in the blue channel of the camera. Over a period of 5 years, we investigated 205 parathyroid glands from 117 patients. 179 (87.3%) glands were correctly identified by their autofluorescence. Surrounding structures such as thyroid, lymph nodes, muscle, or adipose tissue did not reveal substantial autofluorescence. We conclude that parathyroid glands can be identified by their unique autofluorescence at an early stage of the operation. This may help to preserve these fragile structures and their vascularization and lower the rate of postoperative hypocalcemia.

Liver rupture in a 28-year-old primigravida with superimposed pre-eclampsia and hemolysis, elevated liver enzyme levels, and low platelet count syndrome.

Serious hepatic complications, although rare, are one of the leading causes of maternofetal morbidity and mortality in hypertensive pregnancy disorders. A 28-year-old primigravida was transferred to our hospital complaining of refractory epigastric pain in the 29th week of pregnancy and was subsequently admitted due to superimposed pre-eclampsia and hemolysis, elevated liver enzyme levels, and low platelet count syndrome. Following a pathological cardiotocogram, a cesarean section was performed. The intra-abdominal situs presented with 1000 mL of blood and a bleeding rupture of the left lobe of the liver. The trauma to the liver was surgically repaired with a suture and the patient's state was stabilized. Following the surgical procedures and neonatal intensive care, mother and newborn both recovered without residues. In order to avoid unnecessary maternal morbidity, we therefore recommend an abdominal ultrasound, beyond an obstetric focus, as an additional and sensible means of diagnostic imaging in cases of hemolysis, elevated liver enzyme levels, and low platelet count syndrome.

Accuracy of adrenal imaging and adrenal venous sampling in diagnosing unilateral primary aldosteronism.

INTRODUCTION: The correct differentiation between unilateral and bilateral adrenal involvement in patients with primary aldosteronism (PA) is of utmost importance to justify surgical treatment. The aim of this study was to determine the accuracy of adrenal imaging compared to adrenal venous sampling (AVS), histopathology and postoperative outcome. METHODS: The data of all patients with unequivocal AVS who underwent unilateral laparoscopic adrenalectomy for primary aldosteronism between May 2004 and April 2015 were entered in this retrospective study. We compared computed tomography (CT) and magnetic resonance imaging (MRI) results with corresponding AVS data, histopathology findings and postoperative outcome. RESULTS: A total of 175 patients underwent unilateral laparoscopic adrenalectomy for primary aldosteronism. AVS was successful in 152 patients and postoperative outcome available in 148 patients. Despite unilateral disease according to AVS results, bilateral normal glands were seen in 15 MRI (17·2%) and 7 CT scans (8·5%), respectively. Unilateral enlargement of the nonhypersecreting adrenal gland was found in three MRI (3·5%) and 10 CT scans (12·2%) of patients who showed aldosterone hypersecretion deriving from the contralateral gland. Fifteen MRI (17·2%) and 18 CT scans (22·0%) revealed bilateral adrenal pathology despite unilateral aldosterone hypersecretion. CONCLUSION: The accuracy of CT and magnetic resonance imaging in predicting unilateral disease is poor. AVS appears to be an essential diagnostic step to identify those patients who may benefit from unilateral adrenalectomy.

Intraoperative near-infrared autofluorescence imaging of parathyroid glands.

OBJECTIVE: To identify parathyroid glands intraoperatively by exposing their autofluorescence using near-infrared light. METHODS: Fluorescence imaging was carried out during minimally invasive and open parathyroid and thyroid surgery. After identification, the parathyroid glands as well as the surrounding tissue were exposed to near-infrared (NIR) light with a wavelength of 690-770 nm using a modified Karl Storz near-infrared/indocyanine green (NIR/ICG) endoscopic system. Parathyroid tissue was expected to show near-infrared autofluorescence, captured in the blue channel of the camera. Whenever possible the visual identification of parathyroid tissue was confirmed histologically. RESULTS: In preliminary investigations, using the original NIR/ICG endoscopic system we noticed considerable interference of light in the blue channel overlying the autofluorescence. Therefore, we modified the light source by interposing additional filters. In a second series, we investigated 35 parathyroid glands from 25 patients. Twenty-seven glands were identified correctly based on NIR autofluorescence. Regarding the extent of autofluorescence, there were no noticeable differences between parathyroid adenomas, hyperplasia and normal parathyroid glands. In contrast, thyroid tissue, lymph nodes and adipose tissue revealed no substantial autofluorescence. CONCLUSION: Parathyroid tissue is characterized by showing autofluorescence in the near-infrared spectrum. This effect can be used to distinguish parathyroid glands from other cervical tissue entities.

Backscattering intensity measurements in optical coherence tomography as a method to identify parathyroid glands.

BACKGROUND AND OBJECTIVE: Previous studies have shown that the use of optical coherence tomography (OCT) permits the differentiation between parathyroid tissue, thyroid tissue, lymph nodes and adipose tissue. We investigated the backscattering intensity profiles of OCT images in order to determine whether significant differences between these tissue types exist. METHODS: Mean backscattering intensity profiles were obtained from OCT images of parathyroid glands, thyroid tissue, lymph nodes and adipose tissue. The profiles were analyzed employing Fisher's Linear Discriminant Analysis (LDA). The results were cross validated employing improved parameter estimation techniques. RESULTS: Mean backscattering intensity profiles from 300 OCT images of 34 patients undergoing thyroid or parathyroid surgery were analyzed. The overall rate of correct classifications was 96.15%. The cross validation employing improved parameter estimation techniques yielded results identical to those derived from Fisher's LDA. CONCLUSION: Besides the individual assessment of OCT images by interpreting morphological criteria, backscattering intensity measurements can reliably distinguish between different tissue entities.

A critical reappraisal of bilateral adrenalectomy for ACTH-dependent Cushing's syndrome.

OBJECTIVE: Our aim was to review short- and long-term outcomes of patients treated with bilateral adrenalectomy (BADx) in ACTH-dependent Cushing's syndrome. METHODS: We reviewed the literature and analysed our experience with 53 patients treated with BADx since 1990 in our institution. RESULTS: BADx is considered if ACTH-dependent Cushing's syndrome is refractory to other treatment modalities. In Cushing's disease (CD), BADx is mainly used as an ultima ratio after transsphenoidal surgery and medical therapies have failed. In these cases, the time span between the first diagnosis of CD and treatment with BADx is relatively long (median 44 months). In ectopic Cushing's syndrome, the time from diagnosis to BADx is shorter (median 2 months), and BADx is often performed as an emergency procedure because of life-threatening complications of severe hypercortisolism. In both situations, BADx is relatively safe (median surgical morbidity 15%; median surgical mortality 3%) and provides excellent control of hypercortisolism; Cushing's-associated signs and symptoms are rapidly corrected, and co-morbidities are stabilised. In CD, the quality of life following BADx is rapidly improving, and long-term mortality is low. Specific long-term complications include the development of adrenal crisis and Nelson's syndrome. In ectopic Cushing's syndrome, long-term mortality is high but is mostly dependent on the prognosis of the underlying malignant neuroendocrine tumour. CONCLUSION: BADx is a relatively safe and highly effective treatment, and it provides adequate control of long-term co-morbidities associated with hypercortisolism.

Laparoscopic adrenalectomy--10-year experience at a teaching hospital.

BACKGROUND: Minimally invasive adrenalectomy has been adopted as the treatment of choice for benign adrenal tumors. This study aimed to investigate the outcome of laparoscopic adrenalectomies performed over a 10-year period at a teaching hospital. METHODS: All laparoscopic adrenalectomies carried out between 1 April 2000 and 31 March 2010 were evaluated with respect to perioperative management, complications, conversion rate, learning curve, tumor size, and surgically relevant characteristics of different adrenal pathologies. RESULTS: Over a period of 10 years, 215 laparoscopic lateral transabdominal adrenalectomies were carried out for Conn's syndrome (n = 90), Cushing's syndrome (n = 72), pheochromocytoma (n = 30), metastatic disease (n = 8), incidentalomas (n = 10), and other rare adrenal pathologies (n = 5). Morbidity, mortality, and conversion rate were 7.0, 0.9, and 4.2 %, respectively. Patients with Cushing's disease and bilateral adrenalectomy showed a higher complication rate. In retrospect, the indication for a laparoscopic approach was at least questionable in five cases. During these 10 years, four surgeons unfamiliar with the technique received intensive training to a defined plan. CONCLUSIONS: Laparoscopic adrenalectomy represents a safe operating technique associated with few complications and a low conversion rate. Patients with severe Cushing's disease are prone to complications and require intensive monitoring postoperatively. Laparoscopic adrenalectomy is associated with a learning curve, and particular emphasis should be given to surgical training.

Time to recovery of adrenal function after curative surgery for Cushing's syndrome depends on etiology.

CONTEXT: Successful tumor resection in endogenous Cushing's syndrome (CS) results in tertiary adrenal insufficiency requiring hydrocortisone replacement therapy. OBJECTIVE: The aim was to analyze the postsurgical duration of adrenal insufficiency of patients with Cushing's disease (CD), adrenal CS, and ectopic CS. DESIGN: We performed a retrospective analysis based on the case records of 230 patients with CS in our tertiary referral center treated from 1983-2014. The mean follow-up time was 8 years. PATIENTS: We included 91 patients of the three subtypes of CS undergoing curative intended surgery and documented followup after excluding cases with persistent disease, pituitary radiation, concurrent adrenostatic or somatostatin analog treatment, and malignant adrenal disease. RESULTS: The probability of recovering adrenal function within a 5 years followup differed significantly between subtypes (P = .001). It was 82% in ectopic CS, 58% in CD and 38% in adrenal CS. In the total cohort with restored adrenal function (n = 52) the median time to recovery differed between subtypes: 0.6 years (interquartile range [IQR], 0.03-1.1 y) in ectopic CS, 1.4 years (IQR, 0.9-3.4 y) in CD, and 2.5 years (IQR, 1.6-5.4 y) in adrenal CS (P = .002). In CD the Cox proportional-hazards model showed that the probability of recovery was associated with younger age (hazard ratio, 0.896; 95% confidence interval, 0.822-0.976; P = .012), independently of sex, body mass index, duration of symptoms, and basal ACTH and cortisol levels. There was no correlation with length and extend of hypercortisolism or postoperative glucocorticoid replacement doses. CONCLUSIONS: Time to recovery of adrenal function is dependent on the underlying etiology of CS.

Intraoperative optical coherence tomography imaging to identify parathyroid glands.

OBJECTIVE: Optical coherence tomography (OCT) is a non-invasive high-resolution imaging technique that permits characterization of microarchitectural features in real time. Previous ex vivo studies have shown that the technique is capable of distinguishing between parathyroid tissue, thyroid tissue, lymph nodes, and adipose tissue. The purpose of this study was to evaluate the practicality of OCT during open and minimally invasive parathyroid and thyroid surgery. METHODS: During parathyroid and thyroid surgery, OCT images were generated from parathyroid glands, thyroid tissue, lymph nodes, and adipose tissue. The images were immediately assessed by the operating team using the previously defined criteria. Second, the OCT images were blinded with respect to their origin and analyzed by two investigators. Whenever possible the OCT findings were matched to the corresponding histology. RESULTS: A total of 227 OCT images from 27 patients undergoing open or minimally invasive thyroid or parathyroid surgery were analyzed. Parathyroid glands were correctly identified in 69.2%, thyroid tissue in 74.5%, lymph nodes in 37.5%, and adipose tissue in 69.2%. 43 OCT images (18.9%) could not be allocated to one of the tissue types (Table 2). Sensitivity and specificity in distinguishing parathyroid tissue from the other entities were 69% (63 true positive, 13 false negative findings, 15 images where an allocation was not possible) and 66%, respectively (71 true negative, 9 false positive, 28 images where an assessment was not possible). CONCLUSION: OCT is capable of distinguishing between parathyroid, thyroid, and adipose tissue. An accurate differentiation between parathyroid tissue and lymph nodes was not possible. The disappointing results compared to the previous ex vivo study are related to problems handling the endoscopic probe intraoperatively. However, further refinement of this new technology may lead to OCT systems with higher resolution and intraoperative probes that are easier to handle.

Favorable long-term outcomes of bilateral adrenalectomy in Cushing's disease.

OBJECTIVE: Bilateral adrenalectomy (BADX) is an important treatment option for patients with Cushing's syndrome (CS). Our aim is to analyze the long-term outcomes, surgical, biochemical, and clinical as well as morbidity and mortality, of patients who underwent BADX. DESIGN: A total of 50 patients who underwent BADX since 1990 in two German centers were identified. Of them, 34 patients had Cushing's disease (CD), nine ectopic CS (ECS), and seven ACTH-independent bilateral adrenal hyperplasia (BAH). METHODS: Standardized follow-up examination was performed in 36 patients with a minimum follow-up time of 6 months after BADX and a median follow-up time of 11 years. RESULTS: Surgical morbidity and mortality were 6 and 4% respectively. All patients were found to be in remission after BADX. Almost all Cushing's-specific comorbidities except for psychiatric diseases improved significantly. Health-related quality of life remained impaired in 45.0% of female and 16.7% of male patients compared with a healthy population. The median number of adrenal crises per 100 patient-years was four. Nelson tumor occurred in 24% of CD patients after a median time span of 51 months. Long-term mortality after 10 years was high in ECS (44%) compared with CD (3%) and BAH (14%). CONCLUSIONS: BADX is an effective and relatively safe treatment option especially in patients with CD. The majority of patients experience considerable improvement of Cushing's symptoms.

Optical coherence tomography as a method to identify parathyroid glands.

BACKGROUND AND OBJECTIVE: The identification of parathyroid glands can be a major problem in parathyroid surgery. The purpose of this study was to evaluate the feasibility of optical coherence tomography (OCT) in distinguishing between parathyroid tissue, thyroid tissue, lymph nodes, and adipose tissue. METHODS: Ex vivo OCT images as well as histological sections were generated from parathyroid glands, thyroid tissue, lymph nodes and fat in order to define significant morphologic differences between these entities. As a second step all OCT images were separately evaluated by two blinded investigators and later compared to the corresponding histology. Sensitivity and specificity of OCT in distinguishing between the different tissues were determined. To assess the interobserver agreement, κ coefficients were calculated from the ratings of each investigator for each OCT image seen. RESULTS: A total of 320 OCT images from 32 patients undergoing thyroid surgery, parathyroidectomy or lymphadenectomy were compared with the corresponding histology. The sensitivity and specificity in distinguishing parathyroid tissue from the other entities was 84% (second investigator: 82%) and 94% (93%) respectively. Unweighted κ using four diagnostic categories was 0.97 (95% CI, 0.94-0.99) showing substantial agreement between both investigators. CONCLUSION: OCT is highly sensitive in distinguishing between parathyroid tissue, thyroid tissue, lymph nodes and adipose tissue. These ex vivo results should be confirmed by using OCT imaging intraoperatively.

Lack of influence of somatic mutations on steroid gradients during adrenal vein sampling in aldosterone-producing adenoma patients.

OBJECTIVE: Adrenal vein sampling (AVS) is a technically demanding procedure required for the identification of suitable candidates for unilateral adrenalectomy in primary aldosteronism. Recently, somatic KCNJ5 K(+)-channel mutations in aldosterone-producing adenoma (APA) patients have been shown to influence steroid gradients during AVS. These and other recently identified genetic modifiers (ATP1A1 and ATP2B3) might affect the final diagnosis and treatment of the affected patients. DESIGN: Fifty-nine patients with APAS who had undergone successful AVS (adrenal vein cortisol:peripheral cortisol ratio 2) and had undergone a mutation analysis of their tumor tissue were studied. the mutation status of the APAS was as follows: 19 KCNJ5 mutations, eight ATPase mutations (five ATP1A1 and three ATP2B3), and 32 patients with none of these mutations. METHODS: The lateralization index (ratio of aldosterone:cortisol on the side of the adenoma to aldosterone to cortisol on the contralateral side) and the contralateral suppression index (ratio of aldosterone:cortisol on the contralateral side to aldosterone to cortisol in the periphery) were calculated for the KCNJ5-mutated, ATPase-mutated, and the KCNJ5/ATPase mutation-negative APA patients. RESULTS: The lateralization indices of the ATPase mutation carriers had a median of 19.9 compared with a median of 16.0 in the KCNJ5 mutation carriers and that of 20.5 in the KCNJ5/ATPase mutation-negative patients. The contralateral suppression indices of the ATPase-mutated patients had a median of 0.1 compared with a median of 0.4 in the KCNJ5 mutation carriers and that of 0.2 in the KCNJ5/ATPase mutation-negative patients. The differences between the genetic groups were not statistically significant. CONCLUSIONS: We did not find evidence for a clinically important impact of mutation status on steroid gradients during AVS.

Prolonged zona glomerulosa insufficiency causing hyperkalemia in primary aldosteronism after adrenalectomy.

CONTEXT: Unilateral adrenalectomy is the therapy of choice in aldosterone-producing adenoma (APA). Zona glomerulosa (ZG) insufficiency causing hyperkalemia after adrenalectomy has been described in case reports. OBJECTIVE: Our aim was to analyze the clinical relevance of ZG insufficiency causing hyperkalemia after adrenalectomy in a large series of patients with APA. DESIGN: This was a retrospective chart review. SETTING: The study was conducted at two tertiary university referral centers in Germany. PATIENTS: Data from 110 patients with confirmed APA adrenalectomized at the centers in Munich and Berlin between 2004 and 2012 were analyzed. MAIN OUTCOME MEASURES: The primary outcome was the incidence of ZG insufficiency causing hyperkalemia after adrenalectomy; the secondary outcome was the identification of risk factors predisposing for hyperkalemia. RESULTS: Eighteen of 110 patients (16%) developed postoperative hyperkalemia. The majority of these patients (n = 14) had undetectable plasma aldosterone levels after adrenalectomy; four had low aldosterone levels. In 12 of these patients, hyperkalemia was documented only once and resumed spontaneously. Prolonged hypoaldosteronism accompanied by hyperkalemia was observed in six patients (5% of total cohort). These patients needed continuous mineralocorticoid replacement therapy for 11-46 months. Mineralocorticoid antagonist treatment for 4 wk prior to surgery did not prevent hyperkalemia. In multivariate analysis, preoperatively decreased glomerular filtration rate and increased serum creatinine as well as increased postoperative creatinine and microalbuminuria remained significant predictors of hyperkalemia. CONCLUSION: Persistent postoperative hypoaldosteronism with hyperkalemia occurs in 5% of adrenalectomized PA patients through prolonged ZG insufficiency, requiring long-term fludrocortisone treatment. Potassium levels after adrenalectomy must be monitored to avoid life-threatening hyperkalemia.