Multiple Parathyroid Adenomas Research Articles

Multi-modality parathyroid imaging: A shifting paradigm.

The goal of parathyroid imaging in hyperparathyroidism is not diagnosis, rather it is the localization of the cause of hyperparathyroidism for planning the best therapeutic approach. Hence, the role of imaging to accurately and precisely localize the abnormal parathyroid tissue is more important than ever to facilitate minimally invasive parathyroidectomy over bilateral neck exploration. The common causes include solitary parathyroid adenoma, multiple parathyroid adenomas, parathyroid hyperplasia and parathyroid carcinoma. It is highly imperative for the radiologist to be cautious of the mimics of parathyroid lesions like thyroid nodules and lymph nodes and be able to differentiate them on imaging. The various imaging modalities available include high resolution ultrasound of the neck, nuclear imaging studies, four-dimensional computed tomography (4D CT) and magnetic resonance imaging. Contrast enhanced ultrasound is a novel technique which has been recently added to the armamentarium to differentiate between parathyroid adenomas and its mimics. Through this review article we wish to review the imaging features of parathyroid lesions on various imaging modalities and present an algorithm to guide their radiological differentiation from mimics.

ODP098 Hyperparathyroidism Caused by Two Large Water Clear Cell Adenomas

Abstract Background In ambulatory settings, primary hyperparathyroidism is the most prevalent cause of hypercalcemia. Approximately 85% of primary hyperparathyroidism cases are caused by a solitary parathyroid adenoma; other causes include diffuse parathyroid hyperplasia, multiple parathyroid adenomas, and parathyroid cancer. Chief cell adenomas are the most prevalent; adenomas can also consist of oxyphil cell adenomas, lipoadenomas, or mixed cell adenomas. Water clear cell adenoma (WCCA) is a rare tumor formed of large clear cells with foamy pink cytoplasm. Fewer than 30 cases have been recorded in the literature. Case A 52-year-old male with polyuria and polydipsia, diagnosed with hypercalcemia was referred to an endocrinologist. His calcium was 10.9 mg/dl, corresponding parathyroid hormone (PTH) 74 pg/ml, 24-hour urine calcium 818 mg/24hr, vitamin D 25–hydroxy 24.2 ng/ml. He was referred to an endocrine surgeon. A 4-dimensional CT scan revealed soft tissue masses posterior to the thyroid and in the tracheoesophageal groove, consistent with potential parathyroid masses. In the operating room, baseline intraoperative PTH (ioPTH) was 371 pg/ml. A large left superior gland was removed from its normal position, and the ioPTH dropped to 104 pg/ml at 10 minutes post-resection, followed by a rise to 525 pg/ml. A large descended (ectopic) right superior gland was then identified and resected, and the ioPTH decreased to 72, 44, and 57 pg/ml at 10, 15 and 20 minutes post-resection. The remaining parathyroid glands were not identified due to adipose tissue in the neck and likely gland suppression in the setting of high PTH. The pathology report of the two excised glands (left superior 3.2×1.7×0.5cm and 3.703g, right superior 3.4×1.3×0.4cm and 1.86g) demonstrated water clear cell tissue. Post-operatively, patient's polyuria and polydipsia resolved. Labs collected 3 months after surgery demonstrated normalization of the calcium and PTH. The patient was advised to continue follow up every six months. Conclusion Water clear cell parathyroid adenomas are extremely rare. Water clear-cell lesions are considered indolent because excised adenomas are markedly larger than conventional adenomas and grow to a considerable size before becoming biochemically active and diagnosed. Clinical presentation of water clear cell parathyroid lesion is like other causes of primary hyperparathyroidism. The only way to diagnose is via histopathological examination. In rare cases, clear cell renal carcinoma can metastasize to the parathyroid gland causing a similar presentation. Additionally, the rate of hypercalcemia recurrence is higher in WCCA as compared to chief cell adenoma. Therefore, closer follow up of these patients is recommended. Reporting additional cases will aid in our understanding of this uncommon entity, elucidating possible causes/associations, natural history, typical appearances, and post-treatment prognosis. Presentation: No date and time listed

Overview of the 2022 WHO Classification of Parathyroid Tumors.

The 2022 WHO classification reflects increases in the knowledge of the underlying pathogenesis of parathyroid disease. In addition to the classic characteristic features of parathyroid neoplasms, subtleties in histologic features which may indicate an underlying genetic abnormality reflect increased understanding of the clinical manifestations, histologic, and genetic correlation in parathyroid disease. The importance of underlying genetic aberrancies is emphasized due to their significance to the care of the patient. Traditionally, the term "parathyroid hyperplasia" has been applied to multiglandular parathyroid disease; however, the concept of hyperplasia is generally no longer supported in the context of primary hyperparathyroidism since affected glands are usually composed of multiple "clonal" neoplastic proliferations. In light of these findings and management implications for patient care, the 2022 WHO classification endorses primary hyperparathyroidism-related multiglandular parathyroid disease (multiglandular multiple parathyroid adenomas) as a germline susceptibility-driven multiglandular parathyroid neoplasia. From such a perspective, pathologists can provide additional value to genetic triaging by recognizing morphological and immunohistochemical harbingers of MEN1, CDKN1B, MAX, and CDC73-related manifestations. In the current WHO classification, the term "parathyroid hyperplasia" is now used primarily in the setting of secondary hyperplasia which is most often caused by chronic renal failure. In addition to expansion in the histological features, including those that may be suggestive of an underlying genetic abnormality, there are additional nomenclature changes in the 2022 WHO classification reflecting increased understanding of the underlying pathogenesis of parathyroid disease. The new classification no longer endorses the use of "atypical parathyroid adenoma". This entity is now being replaced with the term of "atypical parathyroid tumor" to reflect a parathyroid neoplasm of uncertain malignant potential. The differential diagnoses of atypical parathyroid tumor are discussed along with the details of worrisome clinical and laboratory findings, and also features that define atypical histological and immunohistochemical findings to qualify for this diagnosis. The histological definition of parathyroid carcinoma still requires one of the following findings: (i) angioinvasion (vascular invasion) characterized by tumor invading through a vessel wall and associated thrombus, or intravascular tumor cells admixed with thrombus, (ii) lymphatic invasion, (iii) perineural (intraneural) invasion, (iv) local malignant invasion into adjacent anatomic structures, or (v) histologically/cytologically documented metastatic disease. In parathyroid carcinomas, the documentation of mitotic activity (e.g., mitoses per 10mm2) and Ki67 labeling index is recommended. Furthermore, the importance of complete submission of parathyroidectomy specimens for microscopic examination, and the crucial role of multiple levels along with ancillary biomarkers have expanded the diagnostic workup of atypical parathyroid tumors and parathyroid carcinoma to ensure accurate characterization of parathyroid neoplasms. The concept of parafibromin deficiency has been expanded upon and term "parafibromin deficient parathyroid neoplasm" is applied to a parathyroid neoplasm showing complete absence of nuclear parafibromin immunoreactivity. Nucleolar loss is considered as abnormal finding that requires further molecular testing to confirm its biological significance. The 2022 WHO classification emphasizes the role of molecular immunohistochemistry in parathyroid disease. By adopting a question-answer framework, this review highlights advances in knowledge of histological features, ancillary studies, and associated genetic findings that increase the understanding of the underlying pathogenesis of parathyroid disease that are now reflected in the updated classification and new entities in the 2022 WHO classification.

Sporadic primary hyperparathyroidism with multiple parathyroid adenomas

Multiple lesions of the parathyroid glands (PTG) in primary hyperparathyroidism (PHPT) can be sporadic or develop as part of hereditary syndromes, manifesting at young age. There the description of a severe sporadic PHPT with big parathyroid neoplasms in the young patient is presented. Clinical data made it possible to suspect MEN-1 syndrome or parathyroid carcinomas; however, mutations CDKN, CDC73, MEN1 were excluded. The patient underwent removal of three identified tumors: benign adenomas of the left PTG and hyperplasia of the right one. Postoperative hypocalcemia and severe hungry bone syndrome required the administration of vitamin D and calcium carbonate preparations. However, a year after the operation, a «mild» recurrent disease was confirmed. Taking into account the patient's refusal to reoperation and a significant improvement of the target organs state, active observation was continued. The patient needs further careful dynamic monitoring by specialists in order to timely identify indications for repeated surgical treatment to improve the life quality and span.

Coexistence of multiple cystic parathyroid adenomas and thyroid carcinoma

Coexistence of multiple cystic parathyroid adenomas and thyroid carcinoma

Necrolytic migratory erythema: an important sign of glucagonoma

A 44-year-old male patient presented with a 1-month history of progressive pruritic skin rash on the face, scrotal region and lower extremities. His medical history included multiple parathyroid adenomas and...

MON-115 Inappropriate Ordering of Parathyroid Scintigraphy in an Academic Medical Center

Introduction: The diagnosis of primary hyperparathyroidism is a biochemical, not radiologic one. Unfortunately, many practitioners even in academic centers order parathyroid scintigraphy to “confirm a diagnosis of adenoma” or distinguish primary from secondary hyperparathyroidism. Knowing the location of single or multiple parathyroid adenomas is unnecessary unless parathyroidectomy is planned. The financial burden of nuclear imaging is substantial. The goals of this study were to determine the proportion of inappropriately ordered parathyroid scans and the cost to the health care system.Methods: We generated a database of patients who had consulted with at least one physician at our institution and underwent parathyroid scan between December 2012 and December 2017. We focused on the subset that did not undergo parathyroidectomy. “Slicer dicer” software in our EMR was used to generate the database. Chart review extracted data on diagnoses and reasons for parathyroid scintigraphy.Results: Over 5 years, a total of 325 parathyroid scans were performed. 171 of these did not have parathyroidectomy in our system. However, 18 underwent surgery elsewhere leaving 153 that received parathyroid scans but no surgery (47% of the total). Of the 91 cases so far analyzed of the 153 in our database, average age is 64, with 28 males and 63 females. 61 of the 91 scans (67%) were performed to confirm the diagnosis of parathyroid adenoma; 3 performed because of possible parathyroid adenoma seen on other imaging; and 24 (26%) were done supposedly to localize the adenoma for surgery. Ordering physicians were from primary care (41%), endocrinology (26%), nephrology (18%), and surgery (10%). Final diagnoses for these 91 patients were true primary hyperparathyroidism in 37 (41%), secondary hyperparathyroidism in 38 (42%), unclear in 10 and FHH in 4. In the primary hyperparathyroidism group, 19/37 met criteria for consideration of parathyroidectomy, but only 5/19 received surgical consultation. These 5 patients either refused surgery or surgeon decided against, usually because of high surgical risk.Conclusion: 47% of parathyroid scans at an academic institution were performed in patients who did not undergo parathyroidectomy. Many parathyroid scans were ordered inappropriately to “confirm” a diagnosis of primary hyperparathyroidism, leading to unnecessary charges and resource waste. Physician charges for sestamibi scans range from $237-$1942, depending on whether planar imaging, SPECT, or SPECT-CT is used; hospital charges are $1165-$3211. We propose to change the ordering system for parathyroid imaging to clarify that this is not a method to diagnose parathyroid adenoma, rather a tool to optimize surgical planning when the diagnosis is secure.

Parathyroid surgery for inherited endocrinopathies

Hyperparathyroidism presents as a component of selected familial endocrinopathies including multiple endocrine neoplasia types 1 and 2. These people develop multiple parathyroid adenomas that often present synchronously and can require operative intervention. The goals of the operation are to reduce the functional parathyroid mass to a point that normalizes the serum parathyroid hormone level, to avoid hypoparathyroidism, and to leave the residual parathyroid tissue in a place that can be safely accessed at the time of recurrent hyperparathyroidism. Recurrence is highly likely, as any residual parathyroid tissue has the propensity to develop subsequent adenomatous growth. The 2 main alternatives to accomplish these goals are to either remove all of the evident parathyroid tissue from the neck, and to move it to an accessible position, such as the forearm, as an autograft (total parathyroidectomy and autograft), or to remove nearly all of the parathyroid tissue from the neck, leaving a single focus of well-vascularized, carefully located tissue in the neck (subtotal parathyroidectomy).

Analysis of diagnosis and treatment of 89 patients with primary hyperparathyroidism

Objective To summarize the clinical manifestations, diagnosis and treatment of the primary hyperparathyroidism(PHPT). Methods The clinical data of 89 patients with PHPT admitted during 1991 to 2013 were retrospectively analyzed. Results The mean age of the 89 patients was(44.7±15.8)years(13-86 years), male to female ratio was 1∶2.1. 79% of the 89 patients were symptomatic. 62% of the 89 patients had been misdiagnosed. 52% had been misdiagnosed as kidney stones or bone diseases(fracture, tumor, and metabolic bone disease). The remaining subjects had been misdiagnosed as peptic ulcer, rheumatoid arthritis or pancreatitis. The median serum parathyroid hormone(PTH)level in 88 patients was 697.3 pg/ml(26.4-5 000.0 pg/ml, n=88), the mean serum calcium level was(3.03±0.56)mmol/L(n=88). The 24 h urine calcium was(10.02±4.73)mmol/24 h(n=36). The sensitivity of localization of the parathyroid lesions with technetium-99mmethoxy-isobutyl-isonitrile(99mTc-MIBI)was 96%, being higher than ultrasound(71%), CT(71%), and MRI(72%)(P<0.05, respectively). 79 cases had been treated surgically. The median serum PTH level was 748.2 pg/ml(46.1-5 000.0 pg/ml)before surgery, 79.9 pg/ml(11.35-838.0 pg/ml)15 minutes after surgical removal of the lesions(P<0.05 vs preoperative)and 22.9 pg/ml(2.3-1 203.0 pg/ml)on the first postoperative day(P<0.05 vs preoperative). Serum calcium was(3.03±0.56)mmol/L before surgery, (2.25±0.37)mmol/L on the first postoperative day(P<0.05 vs preoperative)and(2.08±0.36)mmol/L on the second postoperative day(P<0.05 vs preoperative). After the operation, 42 cases(53%)had perioral and limb numbness, 2 cases(3%)had hoarseness of voice and bucking while drinking, 1 case(1%) had tetany. All these symptoms were improved after calcium supplementation. 67 patients(85%)had been diagnosed as parathyroid adenoma pathologically, 7 patients(9%)as hyperplasia, 3 patients(4%)as cysts, and 2 patients(3%)as carcinoma. Among 67 cases of adenomas, 62 cases had a single parathyroid adenoma, 1 case with multiple parathyroid adenomas, and 4 cases with ectopic parathyroid adenomas. The ectopic lesions were located below the thyroid, in the rib cage, left mediastinum, and above the sternum. Conclusions The majority of domestic PHPT was symptomatic. Delayed diagnosis of PHPT is still very frequent. The clinical presentations of PHPT are variable, determination of serum calcium and PTH level simultaneously is the keypoint for early identification and diagnosis of PHPT. The clinician should be familiar with the various clinical manifestations of PHPT and thus enhance understanding of pathogenesis of the disease. 99mTc-MIBI scintigraphy remained the first choice of preoperative imaging localization of the parathyroid lesions, followed by ultrasound, CT, and MRI. Surgical removal of the lesions is effective and safe. (Chin J Endocrinol Metab, 2015, 31: 300-305) Key words: Primary hyperparathyroidism; Diagnosis; Treatment

Primary Hyperparathyroidism Focused on Molecular Pathogenesis.

Primary hyperparathyroidism (PHPT) is a common cause of hypercalcaemia. The most common lesion found in patients is the solitary benign parathyroid adenoma. Multiple parathyroid adenomas have also been reported. Parathyroid carcinomas are an uncommon cause of PHPT. In 15% of patients, all four parathyroid glands are involved and it may be associated with a familial hereditary syndrome, such as multiple endocrine neoplasia, types 1, 2A and 4. PHPT jaw tumour syndrome is associated with fibromas in the mandible and tumours can also be present in the kidneys and the uterus. No predisposing germline DNA variants in parathyroid adenomas have been demonstrated and only a few clonally altered genes that drive parathyroid tumorigenesis have been identified. Frequently parathyroid adenomas have HRPT2 gene mutations that are likely to be of pathogenetic importance. Mutations in the MEN1 gene (localised to 11q13) are responsible for multiple endocrine neoplasia 1. Multiple endocrine neoplasia 2A, which can be associated with medullary thyroid cancer, is due to a germline mutation of the RET proto-oncogene located on chromosome 10. In MEN1-like negative patients some of the germline mutations in this new susceptibility gene were due to gene CDKN1B (12p13). This new syndrome was classified as multiple endocrine neoplasia 4. In PHPT jaw tumour syndrome, HRPT2, the gene on the long arm of chromosome 1, is responsible for the syndrome. It is suggested to perform genetic testing in patients with PHPT below the age of 30 years, but at any age in patients presenting with multigland parathyroid disease.

Concerrent follicular adenoma and multiple ectopic parathyroid glands with an atypical parathyroid adenoma

Ectopic intrathyroid parathyroid glands may be the cause of primary hyperparathyroidism, parathyroid adenoma or carcinoma. Intrathyroid parathyroid tumors are not common lesions and are difficult to diagnose, both clinically and histologically; especially when the patient has no hyperparathyroid symptoms. A 45-year-old Thai woman was treated as having non-toxic goiter for 20 years. She was diagnosed with papillary carcinoma of the thyroid gland with lung metastases. During investigations of her hemoptysis and right lung atelectasis, incidental bilateral lobe enlargement was detected of her substernal thyroid gland, with multiple hypodense nodules on both lobes. Total thyroidectomy was performed after cytological studies failed to give a definite diagnosis. She did not have hyperparathyroid symptoms and her serum calcium level prior to surgery was normal (8.4mg/dL, normal 8.4-10.2 mg/dL). The surgical specimen revealed concurrent follicular adenoma with degenerative changes (left lobe, 5.5 × 7.0 cm), multiple ectopic parathyroid (right lobe, 0.5 × 0.7 cm) and atypical parathyroid adenoma (right lobe, 2.5 × 3.5 cm). The occurrence of ectopic lesions is explainable on an embryologie basis. Non-functioning parathyroid adenoma is uncommon and coexisting thyroid tumors are rare.

The role of ultrasound in the management of nodular thyroid disease and hyperparathyroidism

Thyroid Nodular Disease•. The incidence of sub-clinical thyroid nodules in the general population is high.•. Thyroid carcinoma is rare and has a good prognosis.•. Clinical criteria should be used to select patients for imaging.•. Ultrasound can depict the majority of neoplasms requiring treatment.•. Management strategies should minimise the risks, cost and anxiety of unnecessary surgery.Hyperparathyroidism•. Approximately 90% of primary hyperparathyroidism is due to a solitary parathyroid adenoma.•. Approximately 10% is due to parathyroid hyperplasia, multiple parathyroid adenomas and rarely to parathyroid carcinoma.•. Development of minimally invasive surgery means accurate pre-operative radiological localisation is essential.•. Ultrasound combined with scintigraphy has the greatest sensitivity for a single adenoma but is less effective at detecting multigland disease.•. CT, MRI and percutaneous venous sampling are reserved for cases with non-concordant ultrasound/scintigraphy or in the setting of previo...

Fenotipo de la mutación C634Y del protooncogén RET en el MEN2A: a propósito de una familia

Background and objectives Genetic testing of RET proto-oncogen allows an early diagnosis of Multiple Endocrine Neoplasia syndrome type 2 and establish a correlation between genotype and clinical manifestations. The purpose of this study was to demonstrate the benefits of an early diagnosis with genetic testing followed by prompt surgery on the cure of MTC versus a later diagnosis with serum calcitonin. Patients and method Retrospective descriptive study of 8 members of a MEN 2A family by C634Y mutation. We performed serum calcitonin screening until 1999 and subsequently RET genetic testing was obtained. Carriers underwent total thyroidectomy and periodic determination of calcitonin, urinary metanephrines, calcium, phosphorus and neck and abdominal imaging techniques. Results Five patients were diagnosed by calcitonin familial screening and all of them have high calcitonin by now. Three patients were diagnosed by genetic testing (an adult and two children) and they are free of disease. Calcitonin was closely monitored in children and they underwent surgery when it started to raise, at 6 and 10 years old respectively, finding nodular C-cell hyperplasia in both. Of 8 carriers 3 developed pheochromocytomas, bilateral and asynchronous, one-half had normal urinary metanephrines and two of them were simultaneous with MTC. No patient had biochemical data suggesting hyperparathyroidism although in one patient multiple parathyroid adenomas were found at thyroidectomy. Conclusions RET genetic analysis has achieved an early diagnosis and treatment with no development of MTC in our patients, adjusting the time and type of surgery and allowing a genotype-phenotype correlation. It demonstrates how a genetic alteration is associated with a pathology that we can prevent and manage improving the prognosis of our patients.

Phenotype of the C634Y mutation in the RET proto-oncogene in MEN2A: report of a family

Background and objectivesGenetic testing of the RET proto-oncogene allows for early diagnosis of multiple endocrine neoplasia syndrome type 2 and establishes a correlation between genotype and clinical manifestations. The purpose of this study was to demonstrate the benefits of early diagnosis with genetic testing followed by prompt surgery for curing medullary thyroid carcinoma (MTC) as compared to later diagnosis with serum calcitonin. Patients and methodA retrospective, descriptive study of 8 members of a family with MEN 2A due to C634Y mutation. We performed serum calcitonin screening until 1999, and subsequently RET genetic testing. The carriers underwent total thyroidectomy, periodic determination of calcitonin, urinary metanephrines, calcium, and phosphorus, and cervical and abdominal imaging techniques. ResultsFive patients were diagnosed by calcitonin familial screening and at the time of writing all of them had high calcitonin levels. Three patients were diagnosed by genetic testing (an adult and two children) and were free of disease. Calcitonin was closely monitored in the children, who underwent surgery when it started to rise at 6 and 10 years of age respectively, nodular C-cell hyperplasia having been found in both. Three of the eight carriers developed bilateral and asynchronous pheochromocytoma, half had normal urinary metanephrine levels and two also had MTC. No patient had biochemical data suggesting hyperparathyroidism although in one patient multiple parathyroid adenomas were found at thyroidectomy. ConclusionsRET genetic analysis allowed for early diagnosis and treatment with no development of MTC in our patients, gave early guidance about the type of surgery required, and allowed for genotype-phenotype correlation. It demonstrates how genetic change is associated with a pathology we can prevent and manage, thereby improving the prognosis of our patients.

Clinical utility of ultrasound and 99mTc sestamibi SPECT/CT for preoperative localization of parathyroid adenoma in patients with primary hyperparathyroidism

To evaluate the accuracy of ultrasound and parathyroid scintigraphy using single photon-emission computed tomography/computed tomography (SPECT/CT) for the preoperative localization of solitary parathyroid adenomas in patients with primary hyperparathyroidism who would be suitable for minimally invasive parathyroid surgery. Retrospective study of 63 consecutive patients with biochemical evidence of primary hyperparathyroidism referred for preoperative localization of parathyroid adenoma that proceeded to surgery in the same institution. All patients underwent high-resolution ultrasound and Technetium-99m sestamibi scintigraphy with planar and SPECT/CT imaging. The accuracy of preoperative imaging was compared to surgical and histological findings as the reference standard. Fifty-nine patients had solitary parathyroid adenomas, three patients had multiglandular hyperplasia, and one patient had multiple parathyroid adenomas confirmed at surgery and histology. Thirty-five solitary parathyroid adenomas were identified preoperatively with ultrasound (64%) and 53 with SPECT-CT (90%). Concordant ultrasound and SPECT/CT findings were found in 35 cases (59%). An additional three adenomas were found with ultrasound alone and 18 adenomas with SPECT/CT alone. Fifty-one of the 56 adenomas localized using combined ultrasound and SPECT/CT were found at the expected sites during surgery. Combined ultrasound and SPECT/CT has an overall sensitivity of 95% and accuracy of 91% for the preoperative localization of solitary parathyroid adenomas. The combination of ultrasound and SPECT/CT has incremental value in accurately localizing solitary parathyroid adenomas over either technique alone, and allows selection of patients with primary hyperparathyroidism who would be suitable for minimally invasive surgery.

Atypical clinical manifestations of multiple endocrine neoplasia type 1 syndrome

Multiple endocrine neoplasia type 1 (MEN1) is a hereditary tumor syndrome characterized by a genetic predisposition to develop a variety of neuroendocrine tumors and hormone excess syndromes. The major components of MEN1 are hyperparathyroidism due to multiple parathyroid adenomas or hyperplasia, duodenopancreatic neuroendocrine tumors and pituitary adenomas, most often producing prolactin. Physicians' inadequate knowledge of this clinical entity and sometimes its atypical presentation result in a probable significant underdiagnosis of MEN1. This describes the case of a 65-year-old female in whom primary hyperparathyroidism, limited to only one parathyroid gland, was preceded by acromegaly that was diagnosed 23 years earlier. This case shows that MEN1 manifests itself even in older groups and hyperparathyroidism may not be the first symptom of this syndrome. Therefore, we believe that all subjects who, regardless of age, gender and initial manifestation present with whichever the major symptom should be followed up regularly for the early detection of MEN1.

Multiple Endocrine Neoplasia Type 1 with Multiple Leiomyomas Linked to a Novel Mutation in the MEN1 Gene

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominantly inherited syndrome. MEN1 is characterized by the presence of functioning and nonfunctioning tumors or hyperplasia of the pituitary gland, parathyroid glands, and pancreatic islet cells. In addition, MEN1 carriers can have adrenal or thyroid tumors and non-endocrine tumors, such as lipomas, angiofibromas, and leiomyomas. Although leiomyoma is not a major component of MEN1, it is thought to occur more frequently than expected. However, there has been no report of a case of MEN1 with leiomyoma in Korea so far. This report describes a patient with multiple leiomyomas in MEN1. A 50-year-old woman was referred for further evaluation of elevated calcium levels and osteoporosis. Biochemical abnormalities included hypercalcemia with elevated parathyroid hormone. There was hyperprolactinemia with pituitary microadenoma in sella MRI. An abdominal MRI demonstrated adrenal nodules and leiomyomas in the bladder and uterus. Endoscopic ultrasonography demonstrated esophageal leiomyoma and pancreatic islet cell tumor. A subtotal parathyroidectomy with thymectomy was performed. Sequencing of the MEN1 gene in this patient revealed a novel missense mutation (D350V, exon 7). This is the first case of MEN1 accompanied with multiple leiomyomas, parathyroid adenoma, pituitary adenoma, pancreatic tumor, and adrenal tumor.

Interest of double phase technetium 99m-sestamibi scintigraphy in the exploration of multiple parathyroid adenomas

Technetium99m-sestamibi (Tc-sestamibi) scintigraphy using double phase technique is useful to detect and localize parathyroid adenomas by separating thyroid and parathyroid tissue. We report the case of 52 year old male patient with left kidney lithiasis and diffuse osteoaticular pain. Biological exam finds hypercalcemia with high level of parathormone. Double phase Tc-sestamibi scintigraphy allowed three hearths of high uptake corresponding to multiple parathyroid adenomas whereas ultrasonography and computed tomography showed only one hearth of adenoma. This case suggests that double phase Tc-sestamibi scintigraphy is very useful and more efficient as a functional exploration in the assessment of primary hyperparathyroidy, particulary to confirm the multiple character of parathyroid adenoma and also to improve the success of surgery.

Diagnosis of Birt-Hogg-Dube Syndrome in a Patient With Spontaneous Pneumothorax

Birt-Hogg-Dube syndrome refers to a dermatologic syndrome, consisting of small papular skins lesion distributed on the scalp, forehead, face and neck, which is autosomal dominantly inherited. Subsequently patients may develop concomitant renal and thoracic pathology. We report the case of a patient with Birt-Hogg-Dube syndrome diagnosed after spontaneous pneumothorax.

Multiple endocrine neoplasia type 1

Multiple endocrine neoplasia-1 (MEN-1) is an autosomal dominant inherited syndrome that occurs due to inactivating mutations of the MEN1 gene locus, coding for a tumor-suppressor protein, menin. The components of MEN-1 are hyperparathyroidism due to multiple parathyroid adenomas, pancreatic neuroendocrine tumors, and pituitary adenomas, in addition to some less common neoplastic manifestations. Care of people with MEN-1 requires knowledge of the problems that may arise, and the best approaches to detect and care for the manifestations of this incurable, but manageable, disease.