Manifestation Of Primary Hyperparathyroidism Research Articles

Expect the unexpected: Brown tumor of the mandible as the first manifestation of primary hyperparathyroidism.

Hyperparathyroidism (HPT) is a condition in which one or more parathyroid glands produce increased levels of parathyroid hormone (PTH), causing disturbances in calcium homeostasis. Most commonly HPT presents with asymptomatic hypercalcemia but the clinical spectrum may include disturbances reflecting the combined effects of increased PTH secretion and hypercalcemia. Brown tumors are rare, benign, tumor-like bone lesions, occurring in 1.5% to 4.5% of patients with HPT, as a complication of an uncontrolled disease pathway, and are nowadays rarely seen in clinical practice. The tumor can appear either as a solitary or multifocal lesion and usually presents as an asymptomatic swelling or a painful exophytic mass. Furthermore, it can cause a pathological fracture or skeletal pain and be radiologically described as a lytic bone lesion. The diagnosis of a brown tumor in HPT is typically confirmed by assessing the levels of serum calcium, phosphorus, and PTH. Although when present, brown tumor is quite pathognomonic for HPT, the histologic finding often suggests a giant cell tumor, while clinical presentation might suggest other more frequent pathologies such as metastatic tumors. Treatment of brown tumors frequently focuses on managing the underlying HPT, which can often lead to regression and resolution of the lesion, without the need for surgical intervention. However, in refractory cases or when dealing with large symptomatic lesions, surgical treatment may be necessary.

Brown tumor of the mandible - a possible clinical manifestation of primary hyperparathyreoidism

Introduction. One of the possible manifestations of primary hyperparathyroidism (PHPT) is the appearance of a benign bone tumor. We hereby present a case of a young woman whose first clinical manifestation of PHPT was a brown tumor of the mandible. Case report. A 27-year-old female patient was hospitalized at the Clinic for Endocrinology, Diabetes, and Metabolic Diseases due to problems occurring in the form of nausea, exhaustion, the feeling of suffocation, dysphagia, pain in the right ear and the right half of the cheeks, with suspected PHPT. Initial laboratory findings pointed out the high levels of parathyroid (PT) hormone (PTH) and calcium (Ca2+) ions, low levels of vitamin D, and increased parameters of bone metabolism with signs of osteopenia. Cone beam computed tomography revealed the presence of bilateral radiolucent lesions of the mandible. Scintigraphy verified a retrosternal hot focus consistent with PT adenoma. After parathyroidectomy was performed, there was a normalization of PTH values, bone metabolism parameters, and the Ca2+ values. Four months after parathyroidectomy, a significant regression of the mandibular tumefaction was confirmed, clinically and radiologically. Conclusion. Brown tumors are rare first clinical manifestations of PHPT. Owing to their histological similarities with other giant-cell lesions (GCLs), definitive diagnosis is sometimes difficult and is based on a correlation of pathohistological, radiological, and laboratory findings. Due to the spontaneous regression of bone lesions after treatment of the basic cause of PHPT, brown tumors should be considered in the differential diagnosis of any GCLs in order to avoid unnecessary surgical procedures.

Rare Case of a Peripheral Giant Cell Granuloma of the Jaw as First Manifestation of Primary Hyperparathyroidism.

Giant cell granulomas (GCG) are uncommon benign tumor-like lesions mostly arising in the oro-facial area. They are more common in women and occur in patients younger than 30 years. Lesions restricted to the bone are referred to as central giant cell granulomas (CGCG), and those developing primarily on soft tissues are termed peripheral giant cell granulomas (PGCG). Both types are histologically identical. The combination of both clinical examination and radiography allows for the differentiation of those two variants. On rare occasions GCG, and especially CGCG, may develop in relation to hypercalcemia linked to hyperparathyroidism (HPT). In those cases, the GCG treatment prognosis is closely linked to the HPT management. Therefore, patients diagnosed with a GCG must be investigated to search for an HPT. Reported herein is a rare clinical case of a mandibular PGCG which led to the diagnosis of primary HPT.

Brown tumour of the mandible as the first manifestation of primary hyperparathyroidism: a case report

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Primary Hyperparathyroidism Masquerading as Acute Pancreatitis.

Acute pancreatitis as an initial manifestation of primary hyperparathyroidism (PHPT) is a rare occurrence and timely diagnosis of PHPT is crucial in preventing repeat attack of pancreatitis. The study aimed at evaluating the clinico-radiological profile of patients admitted with acute pancreatitis as the index presentation of PHPT and to determine the factors associated with development of severe pancreatitis. This series included retrospective analysis of medical records of 30 patients admitted with acute pancreatitis as initial manifestation of PHPT. Additionally, we analyzed the data of another 30 patients admitted with PHPT but without any evidence of pancreatitis, to serve as control group. The mean age of the subjects was 44.9±13.9 years with male to female ratio of 1.30. The mean serum calcium level was 12.24±2.79 mg/dl and five (16.6%) patients had normocalcemia at time of presentation. Presence of nephrolithiasis was significantly associated with severe pancreatitis. One patient had refractory hypercalcemia associated with renal failure and was successfully managed with denosumab. Patients with PHPT associated with acute pancreatitis had significantly higher calcium levels and lower frequency of skeletal involvement as compared to PHPT patients without pancreatitis. PHPT masquerading as acute pancreatitis is rare and high index of suspicion is required to diagnose this condition especially in the presence of normocalcemia at presentation. Patients with PHPT associated pancreatitis had male preponderance, higher calcium levels, and lower frequency of skeletal involvement as compared to PHPT patients without pancreatitis.

Osteitis Fibrosa Cystica and pathological fractures\u2014the classic but neglected skeletal manifestation of primary hyperparathyroidism: a case report

BackgroundOsteitis fibrosa cystica is the classic manifestation of primary hyperparathyroidism (PHPT), occurs after prolonged exposure of bone to high serum parathyroid hormone (PTH) level. It has become increasingly rare due to early detection of PHPT.Case presentationA 37-year-old woman was referred to our institution for fixation of multiple fractures of upper and lower extremities that had been reoccurring in the past 5 years. Her medical history showed right-shoulder, left-elbow, and right-femur fractures after a fall 5 years previously. One month ago, she sustained fractures of the right distal humerus, left tibia, and left femur without history of trauma. Upon arrival to our hospital, a thorough review of her plain radiographs demonstrated brown tumors at multiple sites, along with a salt-and-pepper appearance of the skull and a rugger-jersey spine, compatible with osteitis fibrosa cystica. Patient was diagnosed with PHPT, confirmed by high-corrected serum calcium (13.6 [8.6–10.0] mg/dl), low serum phosphate (2.2 [2.5–4.5] mg/dL), high serum alkaline phosphatase (1482 [35–105] U/L), and significantly elevated parathyroid hormone (PTH 3850 [15–65] pg/mL). A histologically confirmed, 2.5-cm parathyroid adenoma was removed by parathyroidectomy. Ten days later, closed reduction and internal fixation of the left proximal femoral shaft was performed. Pain and ambulation were significantly improved 6 months postoperatively. At the 1.5-year follow-up, fracture unions and complete mineralization of brown tumors were noted; the patient could ambulate with neither pain nor an assistive device.ConclusionsPHPT has become more asymptomatic in countries where routine calcium screening is performed. Nevertheless, the classic skeletal involvement, osteitis fibrosa cystica, should not be overlooked, particularly in young patients who present with a low-energy fracture.

Primary Hyperparathyroidism: Modern Conception and Clinical Observation

The article is devoted to one of the actual medical and social problems — primary hyperparathyroidism, the late diagnosis of which leads to the development of severe complications and an increased risk of premature death. Unlike developed countries, where 80% of cases are represented by mild forms of the disease, in the Russian Federation this indicator does not exceed 30%, while 70% are manifest forms. Widespread awareness of doctors of various specialties in the diagnosis of parathyroid adenoma is necessary for the timely detection of the disease. The article reflects the main stages of the study of the disease, the pathogenesis of the clinical manifestations of primary hyperparathyroidism, the classic symptoms of which are changes in the target organs of the parathyroid hormone — bone tissue, urinary system and gastrointestinal tract, is considered. Bone disorders are the most common manifestation of hyperparathyroidism and are characterized by increased bone metabolism with a progressive decrease in bone mineral density. Typical changes in the kidneys include nephrolithiasis and nephrocalcinosis, causing the formation of renal failure. Gastrointestinal signs of hyperparathyroidism are erosion and ulcers of the stomach and duodenum, prone to bleeding, recurrent pancreatitis. Diagnosis of the disease is based on laboratory results, characterized by elevated levels of calcium and parathyroid hormone in the blood. Visualization of the paradenomas in most cases is provided by ultrasound and scintigraphy. Removal of parathyroid adenoma is the most effective treatment. A clinical case of a severe form of the disease is presented, indicating an urgent need to take measures to solve the problem of primary hyperparathyroidism.

Primary Hyperparathyroidism: Modern Conception and Clinical Observation

The article is devoted to one of the actual medical and social problems — primary hyperparathyroidism, the late diagnosis of which leads to the development of severe complications and an increased risk of premature death. Unlike developed countries, where 80% of cases are represented by mild forms of the disease, in the Russian Federation this indicator does not exceed 30%, while 70% are manifest forms. Widespread awareness of doctors of various specialties in the diagnosis of parathyroid adenoma is necessary for the timely detection of the disease. The article reflects the main stages of the study of the disease, the pathogenesis of the clinical manifestations of primary hyperparathyroidism, the classic symptoms of which are changes in the target organs of the parathyroid hormone — bone tissue, urinary system and gastrointestinal tract, is considered. Bone disorders are the most common manifestation of hyperparathyroidism and are characterized by increased bone metabolism with a progressive decrease in bone mineral density. Typical changes in the kidneys include nephrolithiasis and nephrocalcinosis, causing the formation of renal failure. Gastrointestinal signs of hyperparathyroidism are erosion and ulcers of the stomach and duodenum, prone to bleeding, recurrent pancreatitis. Diagnosis of the disease is based on laboratory results, characterized by elevated levels of calcium and parathyroid hormone in the blood. Visualization of the paradenomas in most cases is provided by ultrasound and scintigraphy. Removal of parathyroid adenoma is the most effective treatment. A clinical case of a severe form of the disease is presented, indicating an urgent need to take measures to solve the problem of primary hyperparathyroidism.

BROWN TUMORS OF GNATHIC BONES AS THE FIRST MANIFESTATION OF PRIMARY HYPERPARATHYROIDISM

We report a case of exuberant brown tumors affecting the gnathic bones as the first manifestation of primary hyperparathyroidism (PHPT). A 34-year-old female patient presented with midfacial asymmetry caused by an 8- × 4-cm painful and bleeding swelling in the left posterior maxilla, showing progressive growth for the last 2 months. A 4- x 2-cm normal-colored swelling was also detected in the right body of the mandible. Medical history included hypertension, fever, and weight loss. Panoramic radiography showed multilocular radiolucencies, overall thinning of the inferior border of the mandible, and loss of the lamina dura. Incisional biopsy revealed central giant cell lesions, which were diagnosed as brown tumors of PHPT. High values of parathormone and alkaline phosphate were detected and microscopic diagnosis of parathyroid adenoma was established after parathyroidectomy. The patient received calcium and calcitriol supplementation. Both lesions decreased partially after 2 years of follow-up, with aesthetic surgery being planned. We report a case of exuberant brown tumors affecting the gnathic bones as the first manifestation of primary hyperparathyroidism (PHPT). A 34-year-old female patient presented with midfacial asymmetry caused by an 8- × 4-cm painful and bleeding swelling in the left posterior maxilla, showing progressive growth for the last 2 months. A 4- x 2-cm normal-colored swelling was also detected in the right body of the mandible. Medical history included hypertension, fever, and weight loss. Panoramic radiography showed multilocular radiolucencies, overall thinning of the inferior border of the mandible, and loss of the lamina dura. Incisional biopsy revealed central giant cell lesions, which were diagnosed as brown tumors of PHPT. High values of parathormone and alkaline phosphate were detected and microscopic diagnosis of parathyroid adenoma was established after parathyroidectomy. The patient received calcium and calcitriol supplementation. Both lesions decreased partially after 2 years of follow-up, with aesthetic surgery being planned.

Uncommon cutaneous manifestation of primary hyperparathyroidism

Uncommon cutaneous manifestation of primary hyperparathyroidism

Giant mediastinal parathyroid adenoma presenting as bilateral brown tumour of mandible: a rare presentation of primary hyperparathyroidism

Hyperparathyroidism (HPT) is becoming increasingly common endocrinopathy in clinical practice. Nowadays, it is mostly diagnosed in subclinical or early clinical stage. Bony involvement in HPT has seen significant fall in...

Expression of transcription factors in MEN1-associated pancreatic neuroendocrine tumors.

MEN1-associated pancreatic neuroendocrine tumors (pNETs) may potentially express distinct hormones, but the mechanism has not been elucidated. Transcription factors such as MafA and Pdx1 have been identified to lead to beta cell differentiation, while Arx and Brn4 to alpha cell differentiation in developing pancreas. We hypothesized those transcription factors are important to produce specific hormones in pNETs, similarly to developing pancreas, and examined the expression of transcription factors in a case of MEN1 who showed immunohistological coexistence of several hormone-producing pNETs including insulinoma. A 70-year-old woman was found to manifest hypoglycemia with non-suppressed insulinemia and hypercalcemia with elevated PTH level. She was diagnosed as MEN1 based on the manifestation of primary hyperparathyroidism, pituitary adenoma and insulinoma, with genetic variation of MEN1 gene. She had pylorus-preserving pancreaticoduodenectomy because CT scan and SACI test indicated that insulinoma was localized in the head of the pancreas. Histopathological finding was MEN1-associated NET, G1. Interestingly, immunohistological examination of the resected pancreas revealed that two insulinomas, a glucagon-positive NET and a multiple hormone-positive NET coexisted. Hence, we examined the expression of transcription factors immunohistochemically to elucidate the role of the transcription factors in MEN1-associated hormone-producing pNETs. We observed homogeneous expressions of MafA and Pdx1 in insulinomas and Arx in glucagon-positive NET, respectively. Moreover, multiple hormone-positive NETs expressed several transcription factors heterogeneously. Collectively, our results suggested that transcription factors could play important roles in the production of specific hormones in MEN1-associated pNETs, similar to islet differentiation.Learning points:To date, it has been shown that different hormone-producing tumors coexist in MEN1-associated pNETs; however, the underlying mechanism of the hormone production in MEN1-associated pNETs has not been well elucidated.Although this case presented symptomatic hypoglycemia, several hormone-producing pNETs other than insulinoma also coexisted in the pancreas.Immunohistochemical analysis showed MafA and Pdx1 expressions distinctly in insulinoma, and Arx expression particularly in a glucagon-positive NET, while a multiple hormone-positive NET expressed MafA, Pdx1 and Arx.Collectively, clinicians should consider that several hormone-producing pNETs may coexist in a MEN1 case and examine both endocrinological and histopathological analysis of pNETs, regardless of whether symptoms related to the excess of hormones are observed or not.

Abstract #602: Chondrocalcinosis: Common and Important Manifestation of Primary Hyperparathyroidism

Abstract #602: Chondrocalcinosis: Common and Important Manifestation of Primary Hyperparathyroidism

Molecular and genetic features of primary hyperparathyroidism in young patients

When primary hyperparathyroidism (PHPT) is diagnosed in a young patient in the absence of other clinical manifestations differential diagnosis between a sporadic form of PHPT and PHPT as the first manifestation of one of hereditary syndromes may be challenging. Diagnosis of sporadic or hereditary PHPT determines the extent of surgical intervention, a strategy for further observation and treatment, and the need for examination and treatment of first-degree relatives. Aim of the study — to determine genetic characteristics of PHPT with manifestation at a young age (<40 years old) with clinically sporadic PHPT and familial isolated hyperparathyroidism (FIHP).Material and methods. 40 patients with manifestation of PHPT at the age younger than 40 years, 4 of which with FIHP, were included in the study. In 11 patients Sanger sequencing of MEN1 gene was performed (ABI 3130 Genetic Analyser, «Applied Biosystems», USA). 37 patients underwent next-generation sequencing (NGS) (Ion Torrent PGM, Thermo Fisher Scientific — Life Technologies, USA) using a panel of candidate genes (MEN1, CASR, CDC73, CDKN1A, CDKN1B, CDKN1C, CDKN2A, CDKN2C, CDKN2D). Results. In 3 (7,5%) patients (1 of which with FIHP) we revealed germline heterozygous mutations in MEN1 gene: in exon 9 p.D418N, exon 3 p.R176Q, intron 3 с.654+1G>A. In 4 (4/40, 10%) patients we revealed germline heterozygous mutations in CDC73 gene: 3 nonsense mutations in patients with parathyroid carcinoma — in exon 3 p.R91X, exon 6 p.Q166X, exon 7 p.R229X, and 1 missense mutation in a patient with parathyroid hyperplasia in exon 8 p.R263C. Conclusions. In the majority of cases (75%) PHPT in young patients without positive family history is sporadic. Search for germline mutations in the genes, leading to development of hereditary forms of PHPT (first of all in MEN1 and CDC73), is appropriate in young patients with positive family history, or when positive family history may be suspected, and in patients with parathyroid carcinoma. In the majority (75%) of FIHP cases search for other, probably yet unknown, genes is necessary.

BROWN TUMOR OF BONE AS INITIAL MANIFESTATION OF PRIMARY HYPERPARATHYROIDISM

Primary hyperparathyroidism (PHPT) is characterized with primary hyperproduction of parathyroid hormone (PTH) by affected parathyroid glands and with a corresponding increase in concentration of extracellular calcium. Long-term development of PHPT through decades leads to calcium-related symptoms and distinct changes in the skeleton, kidneys, digestive tract and other organs. In the clinical picture of PHPT, granulomatous pseudo-tumors in bones are observed as a rare manifestation of the disease – these lesions, which could imitate malignancy, are called «brown tumors». The present publication that goes into details about a clinical diagnosis, in which a brown tumor became the primary manifestation of PHPT, may be useful for physicians across various fields.

Peripheral giant cell granuloma as an oral manifestation of primary hyperparathyroidism on a pediatric patient: A case report

Peripheral giant cell granuloma as an oral manifestation of primary hyperparathyroidism on a pediatric patient: A case report

Calcium metabolism and the clinical manifestations of primary hyperparathyroidism

Calcium metabolism and the clinical manifestations of primary hyperparathyroidism

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

Acute necrotizing pancreatitis as first manifestation of primary hyperparathyroidism

Acute necrotizing pancreatitis as first manifestation of primary hyperparathyroidism

A Rare Case of Parathyroid Adenoma Presenting As Acute Pancreatitis

Acute pancreatitis as a first manifestation of primary hyperparathyroidism (PHPT) caused by parathyroid adenoma is exceptionally rare. A 24 year old female presented with pain in the left side of chest , upper abdomen and breathlessness. Laboratory studies showed elevated levels of calcium, amylase, lipase and parathormone. She was found to have associated gall stones, pancreatic and renal medullary calcifications and also left sided pleural effusion. Tc 99m scan showed increased activity of right inferior parathyroid gland. The patient underwent surgical resection of the functioning parathyroid adenoma. Although the actual causal relationship between hypercalcemia and pancreatitis has been a persistent topic of debate, detection of hypercalcemia may be a clue to diagnose PHPT due to parathyroid adenoma.