Hyperfunctioning Glands Research Articles

Surgical Technique: Paratiroidectomia Minim Invazivă - Aspecte Tehnice, Experienţă Iniţială, Scurt Review al Literaturii

Primary hyperparathyroidism (pHPT) is a common disease, in the majority of cases determined by a single solitary parathyroid adenoma; it is more frequently encountered among older women, between 50-60 years. Due to advances in imaging, preoperative localization of the hyperfunctioning or enlarged gland is almost always possible. In this perspective the classic bilateral neck exploration shifted to limited (focused) surgical approaches i.e. minimally invasive parathyroidectomy (MIP). The aim of this study is to do a short literature review of MIP surgical techniques and to present the surgical procedure we have used, along with our initial experience, respectively.

Pharmacotherapy of Pathological States of Adrenal Glands (Review)

Recent advances in the pharmacological treatment of hormonal hyperfunction and insufficiency of adrenal glands were reviewed.

Minimally Invasive Resection for Mediastinal Ectopic Parathyroid Glands

We reviewed our experience with ectopic mediastinal parathyroidectomy. Between March 1980 and September 2010,mediastinal parathyroidectomy was performed in33 patients with hypercalcemia secondary to hyperparathyroidism. Primary hyperparathyroidism was the main diagnosis in 32 patients (97%). Technetium-sestamibi scan was used in 23 (70%) for preoperative localization. Minimally invasive resections were performed in 18 patients (55%), and 15 (45%) underwent open surgery. The most common minimally invasive surgery approach was video-assisted thoracoscopy in 9 patients (27%); the most common open approach was median sternotomy in 11 (33%). Intraoperative parathyroid hormone monitoring was used in 22 patients (67%). The ectopic glands were intrathymic in 15 patients (45%), in the aortopulmonary window in 7 (21%), and in other intrathoracic locations in the remaining 11 (33%). Parathyroid adenomas were identified in 21 patients (64%); parathyroid hyperplasia and carcinoma were identified in 9 (27%) and 3 (9%), respectively. No early mortality occurred in either group. Reoperation was required in 1 patient in the minimally invasive surgery group because of hemothorax. Morbidity occurred in 8 patients (24%), the most common of which was hypocalcemia in 4 (12%). The mean length of stay was significantly shorter in the minimally invasive surgery group (2 versus 6 days; p < 0.001) but mortality and morbidity were not statistically different between the two groups (p= 0.05). Mean follow-up was 3 ± 3.7 years. Minimally invasive mediastinal parathyroidectomy has similar outcomes to open surgery, with significantly shorter length of hospital stay.

Pitted keratolysis, erythromycin, and hyperhidrosis

Pitted keratolysis (PK) is a plantar skin disorder mainly caused by coryneform bacteria. A common treatment consists of the topical use of erythromycin. Hyperhidrosis is considered a predisposing factor for bacterial proliferation and, consequently, for the onset of PK. The aim of this study was to evaluate the relationship between PK erythromycin and hyperhidrosis. All patients with PK seen in Sant'Andrea Hospital, between January 2009 and December 2011, were collected. PK was clinically and microscopically diagnosed. All patients underwent only topical treatment with erythromycin 3% gel twice daily. At the beginning of the study and after 5 and 10 days of treatment, a clinical evaluation and a gravimetric measurement of plantar sweating were assessed. A total of 97 patients were diagnosed as PK and were included in the study. Gravimetric measurements showed that in 94 of 97 examined patients (96.90%) at the time of the diagnosis, there was a bilateral excessive sweating occurring specifically in the areas affected by PK. After 10 days of antibiotic therapy, hyperhidrosis regressed together with the clinical manifestations. According to these data, we hypothesize that hyperhidrosis is due to an eccrine sweat gland hyperfunction, probably secondary to bacterial infection.

Hansen′s disease with McCune-Albright syndrome

McCune–Albright syndrome (MAS) comprises a triad of fibrous dysplasia of bone, café-au-lait macule, and endocrinopathy. The disease is due to activating mutation of G protein-coupled receptor leading to hyperfunction of glands. Hansen's disease is caused by infection with Mycobacterium leprae and is seen with underlying immunosuppressed conditions in genetically predisposed individuals. We recently encountered a patient with Hansen's disease along with underlying MAS and report the same in this report.

Nonlocalizing Imaging Studies for Hyperparathyroidism: Where to Explore First?

For patients with primary hyperparathyroidism (pHPT), imaging studies are obtained to facilitate minimally invasive parathyroidectomy. If imaging studies are nonlocalizing, it is not known if exploration should begin on a particular side or gland location. A retrospective review of a prospective parathyroid database was performed. The cohort consists of pHPT patients who underwent initial parathyroidectomy between December 1999 and July 2010 and had all preoperative imaging studies reported as nonlocalizing (negative or indeterminate). Of 880 patients, 151 (17%) had nonlocalizing imaging studies. Reasons for starting exploration on a particular side were identified in 78 (52%) patients and included concomitant thyroid pathology (53%), suspicion on surgeon re-review of imaging (38%), or earlier thyroidectomy (9%). Exploration began on the right in 52%, the left in 42%, and was unknown in 6%. The surgeon had suspicion on imaging in 30 patients and correctly started on the side of pathology in 19 (63%). Hyperfunctioning glands were in eutopic locations in 144 patients (95%) and 3 had intrathyroidal glands. In 111 patients (74%) with single gland disease, median adenoma weight was 320 mg (range 80 to 8,210 mg). There was no difference in adenoma laterality (p = 0.7) or location (p = 0.8). Intraoperative parathyroid hormone criteria were met in 145 (96%) patients and 149 are eucalcemic at last follow-up; 2 (0.7%) patients have persistent disease. In pHPT patients with nonlocalizing imaging, hyperfunctioning glands are not more frequently located on a particular side or anatomic position. Eutopic location is common and intraoperative parathyroid hormone monitoring should be used to guide the extent of surgery.

The results of surgery for mediastinal parathyroid tumors: a comparative study of 63 patients

Parathyroidectomy for ectopic mediastinal hyperfunctioning glands could be performed by transcervical approach, sternotomy, thoracotomy, and recently by thoracoscopic and mediastinoscopic approaches. This study was aimed to analyze the results of traditional and video-assisted parathyroidectomy for mediastinal benign hyperfunctioning glands. Fifty-one upper mediastinal exploration by a conventional cervicotomy, 12 by video-assisted approaches (two thoracoscopy and 10 transcervical mediastinoscopy) and six by sternotomy were performed in 63 patients with primary hyperparathyroidism. Video-assisted and sternotomic parathyroid explorations achieved biochemical cure in all cases; following conventional transcervical mediastinal exploration, a persistent hyperparathyroidism occurred in 11.8% of patients, who were subsequently cured by sternotomic approach. No complications occurred after video-assisted parathyroidectomy, while an overall morbidity rate of 50% and 10% was found after sternotomic and conventional cervicotomic approaches. Postoperative pain and hospital stay were significantly increased following sternotomy; patient's subjective cosmetic satisfaction was significantly higher after video-assisted and conventional cervicotomic approaches. Conventional cervicotomic parathyroidectomy may achieve satisfactory results, especially for upper mediastinal glands. Sternotomic approaches are effective, but should be limited because of invasiveness and increased morbidity. In case of deep and lower hyperfunctioning mediastinal parathyroids, video-assisted approaches represent a less invasive, effective, and safe alternative and might be the technique of choice.

A Rising IoPTH Level Immediately After Parathyroid Resection

This study was designed to determine if a rising intraoperative parathyroid hormone (ioPTH) level following parathyroid resection indicates multiple hyperfunctioning glands and to determine the appropriate intraoperative management. IoPTH monitoring is commonly used to guide parathyroid surgery. A significant rise in the ioPTH immediately after resection of a single parathyroid is often perceived to be indicative of the presence of additional hyperfunctioning glands. A total of 797 consecutive patients underwent parathyroidectomy for primary hyperparathyroidism with ioPTH monitoring. Patients with an elevated 5 minute ioPTH were extensively studied. Operative success was defined as normocalcemia 6 months after surgery. Of the 797 patients, 108 (14%) had a rising ioPTH 5 minutes after resection of a single parathyroid. Of these 108 patients, 36 (33%) continued to have elevated ioPTH levels and further exploration revealed additional hyperfunctioning glands. Importantly, in the majority of patients (n = 72 or 67%), the ioPTH started to fall after an additional 5 minutes (10 minutes after resection). The ioPTH declined by more than 50% from the 5 minute elevated value in 30%, 89%, and 99% of patients at 10, 15, and 20 minutes after resection, respectively. Importantly, this fall correctly predicted operative success in 100% of patients after removal of a single abnormal gland. A rising ioPTH level immediately after parathyroidectomy is observed in 14% of patients. The majority of these patients do not have additional hyperfunctioning glands. Most of patients fell below 50% of the 5 minute elevated value within 20 minutes of gland resection and in all cases this fall correctly predicted operative success.

When Initial Postexcision PTH Level Does Not Fall Appropriately During Parathyroidectomy: What to Do Next?

Inadequate fall in the intraoperative parathyroid hormone (PTH) level after removing enlarged parathyroid gland(s) typically signifies additional hyperfunctioning gland(s), prompting further neck dissection, but it may also be a false negative result. We analyzed intraoperative management of patients with an inadequate fall on PTH after excision of enlarged parathyroid gland(s). Analysis involved a prospective database of 189 patients undergoing 193 procedures for primary hyperparathyroidism. The PTH level was determined before neck incision and 10-15 min after excision of enlarged parathyroid gland(s). A PTH decrease > 50% and into normal range was used as the criterion of successful parathyroidectomy. In 48 of 193 operations, initial postexcision PTH level did not fall appropriately. That inadequate fall in PTH level was a false negative result in 16 patients (33%) and cure was achieved without additional neck exploration in all but one patient, who had additional (negative) neck exploration after excision of a parathyroid adenoma. In all patients with false negative postexcision PTH assay, operative findings concurred with preoperative imaging tests. Inadequate fall in intraoperative PTH may be false negative, particularly after removal of an adenoma found in the location determined by preoperative imaging. Repeat PTH may confirm the initial assay as false negative, obviating the need for additional neck dissection. Importantly, if repeat PTH does not fall appropriately, additional neck exploration needs to be performed.

ES11 *10 YEAR HISTORY OF OVER 1000 CONSECUTIVE MINIMALLY INVASIVE PARATHYROIDECTOMIES (MIPS) WITHOUT INTRAOPERATIVE PTH AT A SINGLE INSTITUTION: LESSONS LEARNED

Purpose: Minimally invasive parathyroidectomy (MIP) has become the procedure of choice to treat primary hyperparathyroidism. The role for intra‐operative parathyroid hormone measurement (IOPTH) is controversial. Some experts indicate that IOPTH is a requirement for MIP while others feel it not needed. We reviewed a 10 year history of MIP at a single institution without use of IOPTH to determine reasons for failure.Methodology: This study is a retrospective review of the University of Sydney Endocrine Surgery Database from May of 1998 to August of 2008. The database was queried for MIPs performed as well as for failed operations. Patient record analysis was completed to determine the reason for failure of the operation.Results: 1020 MIPs were performed with 23 (2.2%) failures. 1 patient was found to have benign familial hypercalcaemia, 5 were lost to follow up. Of the remaining 17 patients, average age was 62, and 76% were female. Reasons for failure in these patients were: 10 patients (59%) found to have double adenomas, 3 (17%) patients with hyperplasia and 4 (24%) patients with single gland disease missed at initial operation. All 17 were cured on repeat exploration. Of these 11 (65%) had repeat Sestamibi scans that correctly localized remaining hyperfunctioning gland(s).Conclusion: MIP can be performed safely without the need for IOPTH. The most common cause of failure after MIP is an occult double adenoma. Given that repeat Sestamibi scan correctly identifies persistent disease consideration can be given to MIP as a choice of procedure for repeat operation.

Significance of Biochemical Parameters in Differentiating Uniglandular from Multiglandular Disease and Limiting Use of Intraoperative Parathormone Assay

We studied whether serum calcium and parathormone (PTH) levels are significantly different for uniglandular disease (UGD) and multiglandular disease (MGD) and whether intraoperative rapid intact parathormone (IOPTH) monitoring can be avoided in some cases of minimally invasive parathyroidectomy (MIP) without affecting cure rates, substantiating various previous published studies. This is a single-referral-center retrospective review of prospectively collected data for 281 patients with sporadic primary hyperparathyroidism (sPHPT) from January 1999 to February 2005. The calcium and PTH values were categorized using the following parameters: calcium > or = 3 mmol/l = 1, < 3 mmol/l = 0, PTH > or = 100 pg/ml = 1, PTH < 100 = 1. P values for serum calcium and PTH by ANOVA were 0.0547 and 0.3936, respectively, and by the Mann-Whitney test were 0.1606 and 0.6208, respectively. We had 118 patients with concordant technetium 99 m sestamibi scintigraphy (MIBI) and neck ultrasonography (US) and UGD was confirmed in 118 (100%) cases. No significant difference between serum calcium and PTH for UGD and MGD was found. IOPTH monitoring could be avoided when there is concordant positive MIBI and neck US for single, unilateral, hyperfunctioning gland without affecting cure rates.

Intraoperative assessment of parathyroid hormone

Technological developments have significantly contributed to the rapid evolution of the surgical management of parathyroid disorders. The ability to physiologically determine the intraoperative status of the patient is now possible through the assessment of changing levels of intact parathyroid hormone (PTH) during surgery. In most patients with primary hyperparathyroidism, this method provides biochemical confirmation of hyperfunctional gland removal, and is predictive of a eucalcemic state and surgical cure. Patients with renal-induced disease (excluding tertiary hyperparathyroidism) do not follow the same kinetic decline in PTH and are therefore less likely to benefit from this modality. An emerging population of patients with primary disease and lower baseline levels of intact PTH appear to demonstrate a greater likelihood of manifesting multiple gland disease and do not follow a consistently predictable kinetic degradation profile. Although this category of patients will require further investigation, potentially resulting in modification of the utility of intraoperative determination of PTH levels, it is clear that this modality represents a very powerful technique which has significantly enhanced the surgical treatment of parathyroid disease.

Targeted Parathyroidectomy: Effectiveness and Intraoperative Rapid‐Parathormone Dynamics

The objective of this study is to assess the effectiveness of selective parathyroid exploration, using preoperative image localization and intraoperative rapid-parathormone (rPTH) assay. The kinetics of intraoperative rPTH in parathyroid adenoma vs. multiglandular disease is assessed. This is a prospective noncontrolled study of a cohort of 100 patients with primary hyperparathyroidism, at a single academic institution. The patients underwent selective parathyroidectomy after preoperative localization, including sestamibi scan and ultrasonography. Intraoperative rPTH assay was used to determine the extent and success of parathyroidectomy. Frozen sections were used as additional confirmation. Follow-up serum calcium levels were used to assess the effectiveness of selective parathyroidedcomy. Mean preoperative serum calcium (Ca) and baseline intact-parathormone were 11.6 mg/dL and 136, respectively. Data were available in 96 cases: 87 single-gland adenoma with two in ectopic mediastinal position, two double adenoma and seven cases of hyperplasia. Ten percent of patients with adenoma needed bilateral exploration for nonlocalizing or false negative imaging, or for intraoperative rPTH failure to decay. All of the patients undergoing unilateral targeted exploration were normocalcemic on follow up. There were only one failed exploration and two cases of recurrent mild hypercalcemia, all three in bilateral exploration cases. Intraoperative rPTH reduction by standard curves was predictive of successful excision of all of the abnormal glands, as confirmed by postoperative serum calcium levels. More than one postexcision rPTH measurement was useful by showing failure of a decaying slope in multiglandular disease. Targeted parathyroidectomy, when appropriately selected and carried out, is an effective treatment of primary hyperparathyroidism in most cases. Intraoperative rPTH can correctly guide removal of hyperfunctioning glands. Targeted parathyroidectomy offers the advantage of less invasive surgery with less tissue dissection confined to one side and avoids surgically disturbing the remainder of the neck. This should reduce postoperative complications and allow for easier and safer re-exploration in the few cases with persistent or recurrent disease.

Preserving function and quality of life after thyroid and parathyroid surgery

Endocrine disease has been recognised for thousands of years, but surgical treatment of endocrine disorders has only been widely used in the past century. Surgery is an effective treatment for hyperfunctioning glands and benign and malignant tumours. Advances in surgical technique have led to the development of short and safe operations with a high cure rate, and recent studies have not only assessed the success of the operations but also have focused on how these diseases affect patient-reported quality of life before and after surgery. In this Review, we summarise current approaches to surgical treatment of thyroid and parathyroid disease, focusing on how these approaches both preserve function and improve quality of life after surgery.

Radioguided Reoperative Parathyroidectomy for Persistent Primary Hyperparathyroidism

We report a case of reoperative radioguided parathyroidectomy in a patient with primary hyperparathyroidism. A 58-year-old man presented to our center with persistent hypercalcemia and hyperparathyroidism after 2 previous parathyroid explorations at an outside facility. Despite the use of preoperative and intraoperative localization, identification of the hyperfunctioning gland was unsuccessful during the initial operations. Because of the continued presence of symptoms, the patient was referred to our center for reoperation. Repeat Tc-99m sestamibi parathyroid scan showed an inferior right parathyroid adenoma. With the intraoperative guidance of a hand-held gamma probe, an enlarged parathyroid gland was localized on the spine behind the esophagus on the right, and successfully removed. Intraoperative parathyroid hormone testing confirmed a surgical cure. The use of radioguidance and intraoperative parathyroid hormone testing were essential to the successful resection. The patient remained disease-free at follow-up.

Parathyroid Scintigraphy in Patients with Primary Hyperparathyroidism:99mTc Sestamibi SPECT and SPECT/CT

The clinical diagnosis of primary hyperparathyroidism is based largely on serum laboratory test results, as patients often are asymptomatic. Surgery, often with bilateral exploration of the neck, has been considered the definitive treatment for symptomatic disease. However, given that approximately 90% of cases are due to a single parathyroid adenoma, a better treatment may be the selective surgical excision of the hyperfunctioning parathyroid gland after its preoperative identification and localization at radiologic imaging. Scintigraphy and ultrasonography are the imaging modalities most often used for preoperative localization. Various scintigraphic protocols may be used in the clinical setting: Single-phase dual-isotope subtraction imaging, dual-phase single-isotope imaging, or a combination of the two may be used to obtain planar or tomographic views. Single photon emission computed tomography (SPECT) with the use of technetium-99m ((99m)Tc) sestamibi as the radiotracer, especially when combined with x-ray-based computed tomography (CT), is particularly helpful for preoperative localization: The three-dimensional functional information from SPECT is fused with the anatomic information obtained from CT. In addition, knowledge of the anatomy and embryologic development of the parathyroid glands and the pathophysiology of primary hyperparathyroidism aid in the identification and localization of hyperfunctioning glands.

Efficacy of 4D-CT Preoperative Localization in 2 Patients with MEN 2A

Multiple endocrine neoplasia type 2A (MEN2A) is an autosomal dominant syndrome that is associated with hyperparathyroidism in 20% to 30% of adult gene carriers. The appropriate surgical management of these patients remains in question. Approaches to this disease range from selective gland resection to a subtotal parathyroidectomy with or without autotransplantation. Despite surgical intervention, disease recurrence is problematic. Surgical management of patients found to have recurrence relies on localizing the anatomic location of the hyperfunctional gland(s). The primary imaging modality for localization of hyperfunctioning parathyroid glands is technetium 99m sestamibi single photon emission computed tomography (SPECT). Although sestamibi imaging has a sensitivity of 60% to 90%, specific anatomic detail is not always present by this imaging modality. Four-dimensional computed tomography (4D-CT) scans allow localization of ectopic parathyroid glands and autotransplanted parathyroid tissue, and they provide the anatomic detail necessary for decisions about appropriate surgical management. Another benefit of the 4D-CT scan is that enhancement characteristics, which are determined by contrast opacification of the hyperfunctional parathyroid tissue over 4 phases of the scan, correlate with metabolic activity. We recommend the use of 4D-CT scanning because of its capacity to identify hyperfunctional parathyroid glands and to provide anatomic information important in preoperative planning.

Use of Intraoperative Samples to Optimize Efficacy of Central Laboratory Parathyroid Hormone Analyses

Intact (1-84) parathyroid hormone (PTH) has a short half-life and can be monitored during surgery to confirm the removal of all hyperfunctioning parathyroid tissue, but exact criteria for timing of sample collection and number of samples that best indicate a surgical cure are still to be perfected (1). We report the degree of accuracy of our protocol of performing only 2 intraoperative PTH tests in patients undergoing parathyroidectomy. Sixty patients (43 women, 17 men; mean age 59.8 years, range 22–79 years), without renal failure, who underwent a minimally invasive surgical operation for sporadic primary hyperparathyroidism, participated in the study. Blood was collected from a peripheral vein before skin incision (basal or t-0) and 10 min after parathyroidectomy (t-10). The removal of the hyperfunctioning gland(s) was considered effective when the PTH decrease was ≥50% from the t-0 value (2). We measured the t-0 concentration before skin incision because physical manipulation …

Hyperfunctioning intrathyroid parathyroid gland: A potential cause of failure in parathyroidectomy

The surgical success rate of parathyroidectomy is 95%. However, in rare patients, ectopic hyperfunctioning parathyroid glands may be located in the thyroid but missed on imaging studies or during surgery. The aim of the present study was to evaluate the perioperative findings in 6 patients with intrathyroid parathyroid glands treated for hyperparathyroidism in our center over a 5-year period and to review the relevant literature. Of the 426 patients who underwent parathyroidectomy for hyperparathyroidism between 1998 and 2003 in our center, 6 (1.4%) were found to have intrathyroid glands. Their files were reviewed for clinical features, surgical approach, intraoperative findings, parathyroid gland location, and morphologic and histopathologic characteristics. The group included 2 men and 4 women of mean age 66 years. The diagnosis in all patients was based on an increase in serum calcium concentration (10.1-13 mg/100 mL) and parathyroid hormone level (102-320 pg/mL). The clinical symptoms were kidney stones, gastrointestinal complaints, hypertension, and osteopenia. Localization studies included ultrasonography in all patients and sestamibi in 4. When the parathyroid glands were not identified, bilateral neck and mediastinum were explored. Adenoma was diagnosed histologically in 4 patients; 2 had a double adenoma. Intrathyroid parathyroid gland is a rare condition in patients with hyperparathyroidism. In these patients, imaging may miss the pathologic gland. Despite its rarity, the possibility of an intrathyroid parathyroid should be kept in mind, and, when meticulous bilateral exploration of the neck fails to identity the hyperfunctioning gland, the surgeon should consider hemithyroidectomy.

Consequences of Targeted Parathyroidectomy Guided by Localization Studies Without Intraoperative Parathyroid Hormone Monitoring

After excision of an abnormal gland, the dynamics of intraoperative parathyroid hormone (PTH) levels signal whether or not more hypersecreting tissue is present. This quantitative assurance of operative success has led to targeted exploration of the hyperfunctioning gland(s). Some have questioned the need for intraoperative PTH monitoring (IPM) in the presence of positive nuclear scanning. The purpose of this study was to examine the accuracy of nuclear scans in correctly localizing and guiding the complete excision of all abnormal gland(s) in patients with sporadic primary hyperparathyroidism (SPHPT) and to demonstrate how IPM changed the operative management in these patients. Five hundred nineteen consecutive patients with sporadic primary hyperparathyroidism had technetium 99-m-sestamibi scans (MIBI) as localization studies obtained before undergoing parathyroidectomy guided exclusively by IPM. All patients were either followed for more than 6 months, or their procedures were identified as operative failures. MIBI reports were correlated with operative findings, hormone dynamics, and postoperative outcomes. Operative success was achieved in 506 of 519 patients (97%). MIBI correctly localized all involved glands in 411 patients (80%). Among the 105 patients (20%) with incorrect or negative scans, IPM changed the operative management in 86 of 105 (82%) by pointing out incomplete resection in patients with a single MIBI incorrect focus (21 of 28) or unrecognized multiglandular disease by scan (13 of 15); avoiding unnecessary exploration in patients with additional incorrect foci (20 of 21); and guiding the surgeon to successful excision or unilateral neck exploration in patients with negative MIBI (32 of 41). MIBI as a single adjunct missed 87% of patients with multiglandular disease. Including patients with negative (8%) and incorrect (12%) MIBI, IPM changed the operative management in 17% of patients and led to operative success in 97%. We suggest that IPM should be used to guide parathyroid excision in every patient with sporadic primary hyperparathyroidism.