Unravelling a hidden pathology of a vertebral fracture in a teenage girl.

BACKGROUND: Although the skeleton remains a common target of primary hyperparathyroidism, the classic bone disease "osteitis fibrosa cystica" is currently rare due to early diagnosis. This case represents severe classic bone manifestations of primary hyperparathyroidism due to delayed diagnosis and delayed medical attention. CASE PRESENTATION: A 19-year-old young female was symptomatically managed for chronic back pain and nonspecific bone pain in the small joints of both hands over 2 months by a general practitioner. The patient had delayed seeking for treatment for 3 months. Later, she was evaluated for tuberculosis, hematological malignancies and rheumatic disorders following a fractured T12 vertebra and underwent pedicle screw fixation. However, clinical examination and investigations, including biochemistry, imaging and histology, ruled out the above conditions. Unfortunately, serum calcium level was not performed at the initial presentation. Later, primary hyperparathyroidism was diagnosed on the basis of moderate hypercalcaemia and elevated intact PTH levels (2064 pg/ml). She had sufficient vitamin D levels and normal kidney function. Her DXA scan revealed severe secondary osteoporosis with the lowest Z score of -8 at the total lumbar spine. Ultrasonography of the thyroid revealed a hypo echoic mass in the left lower neck, and localization studies with technetium-99 m sestamibi and 4D-CT revealed a left inferior parathyroid adenoma (1.6 × 1.5 × 1.6 cm). CT scan also revealed brown tumors in the mandible and vertebrae and diffuse bony changes in the skull, sternum, humerus and vertebrae. Her radiographs revealed subperiosteal bone resorption on the radial aspects of the middle and distal phalanges and brown tumors in both the ulna and fibula. We excluded MEN and other hereditary syndromes in our patient with a personal and family history and with a normal pituitary hormone profile because of poor resources for genetic testing. She underwent parathyroid adenoma excision, and the postoperative period was complicated with hungry bone syndrome, requiring high doses of calcium and active vitamin D supplements. These supplements were gradually weaned off over 6 months, and she recovered with normal biochemical investigations. Histology revealed parathyroid adenoma without malignant features. CONCLUSION: In developing countries where routine calcium screening is not available, clinicians should be aware of various manifestations of primary hyperparathyroidism to allow diagnosis as soon as possible without delay to prevent further progression, as it is a treatable condition.

Brown tumors: Retrospective analysis of 26 cases.

INTRODUCTION: Brown tumors are reactive osteolytic lesions caused by hyperparathyroidism. These rare lesions are non-neoplastic processes that result from bone resorption. The purpose of this study was to retrospectively review a 34-year experience with brown tumors in our institution. MATERIALS AND METHODS: We retrospectively analyzed the records of 26 consecutive patients with brown tumor who were treated in our institution between May 1988 and October 2020, with a mean follow-up of 36,1 months. RESULTS: 17 male (65,4%) and 9 female (34,6%) patients with a mean age of 41,6 were included in the study. Localized bone pain was present in 13 cases (50,0%) as the first presenting symptom. 3 patients (11,5%) presented with diffuse bone pain. 7 patients (26,9%) were diagnosed with brown tumor while being investigated for pathological fractures. The other 3 patients (11,5%) were diagnosed while being evaluated for hypercalcemia symptoms. 7 patients (26,9%) had solitary lesions, while 19 patients (73,1%) had multiple lesions. Pelvis, femur, ribs, tibia, proximal humerus and mandible were the most common sites of localization. 23 patients (88,5%) were diagnosed with primary hyperparathyroidism, while the other 3 patients (11,5%) had secondary hyperparathyroidism. A total of the 65 lesions, 23 (35.4%) underwent orthopedic surgery, and 42 (64.6%) were followed up conservatively after parathyroidectomy. Orthopedic surgery was performed in 21 of 26 patients, the other 5 cases were followed up conservatively. Intralesional curettage was performed in 19 cases (82,6%). The resulting cavity was filled with bone cement in 11 cases (47,8%). Bone grafting was applied in 8 cases (34,8%). No recurrence was observed in any of the patients. CONCLUSION: The diagnosis of brown tumor begins with clinical suspicion. Endocrinology and general surgery consultation is important before surgery. Treatment of brown tumors requires a multidisciplinary approach.

Differentiating Brown Tumor From Bone Metastasis in Parathyroid Cancer Using 18 F-FDG PET and 99m Tc-MIBI SPECT.

ABSTRACT: A 69-year-old woman presented with a right clavicle pain. CT revealed a pathological fracture of the right clavicle, multiple osteolytic lesions, and a left cervical mass. 18 F-FDG PET/CT demonstrated a marked FDG uptake in the cervical mass and osteolytic lesions indicative of metastatic parathyroid cancer. 99m Tc-MIBI SPECT/CT revealed either faint or no uptake in the osteolytic lesions. However, a histopathological analysis after a parathyroidectomy and right clavicle biopsy confirmed the diagnosis of parathyroid cancer and the presence of benign brown tumors secondary to hyperparathyroidism. Postoperative imaging showed sclerotic change and a decreased FDG uptake in the bone lesions.

The refractory secondary hyperparathyroidism presenting with retro-orbital brown tumor: a case report.

BACKGROUND: Tertiary hyperparathyroidism describes the autonomous and excessive secretion of parathyroid hormone (PTH) by the parathyroid glands after longstanding secondary hyperparathyroidism in chronic kidney disease. Brown tumors are a sign of uncontrolled hyperparathyroidism. In this case, we have reported a refractory and destructive hyperparathyroidism storm. Also, it presented with atypical onset and unexpected adenoma location. CASE PRESENTATION: A 37-year-old man was diagnosed with end-stage kidney disease 22 years ago. He has been undergoing dialysis treatment since that time. Recently, he was admitted to the ophthalmology department due to the unilateral anterior bulging of the right eye and drooping of the eyelid. Magnetic resonance imaging exhibited an extraconal mass lesion located in the right orbital posterior superolateral position. Computerized tomography scans considered expansile bone lesion with peripheral calcification and originating from the sphenoid wing. The bone mass lesion was resected via craniotomy due to the compressive effect. The pathological findings were consistent with brown tumors. Plasma intact PTH level was 4557 pg/mL. The patient informed that he underwent parathyroidectomy and two leg fractures operation in a medical query. Parathyroid scintigraphy determined three distinct foci consistent with adenomas and one of them was in mediastenum. Second parathyroidectomy was recommended to the patient but the patient refused surgery. Despite his medication and dialysis regimen being revised, PTH levels were maintained at higher levels in follow-up. CONCLUSIONS: We presented a hyperparathyroidism case that was resistant to all treatments and exhibited all the severe complications in a long-term dialysis patient. Furthermore, this case has revealed the importance and difficulty of secondary hyperparathyroidism management.

Multiple brown tumors: a bone complication due to long-term untreated pseudohypoparathyroidism.

Bone lytic lesions are a possible complication of pseudohypoparathyroidism type 1B, in undertreated adult patients. Whole body [18F] F-fluorocholine PET/CT is a useful imaging tool to assess brown tumor progression in this context. We describe the case of a 33-year-old woman, referred for the diagnostic evaluation of lytic bone lesions of the lower limbs, in the context of asymptomatic pseudohypoparathyroidism. She had been treated with alfacalcidol and calcium during her childhood. Treatment was discontinued at the age of 18 years old because of the lack of symptoms. A femur biopsy revealed a lesion rich in giant cells, without malignancy, consistent with a brown tumor. Laboratory tests showed a parathyroid level at 1387 pg/ml (14-50). Whole-body Fluorocholine PET/CT revealed hypermetabolism of bone lesions. The final diagnosis was brown tumors related to hyperparathyroidism complicating an untreated pseudohypoparathyroidism. Genetic testing confirmed PHP type 1B. Pseudohypoparathyroidism with radiographic evidence of hyperparathyroid bone disease, is a very rare condition due to parathyroid hormone resistance in target organs, i.e., kidney resistance, but with conserved bone cell sensitivity. It has been reported in only a few cases of pseudohypoparathyroidism type Ib. Long-term vitamin D treatment was required to correct bone hyperparathyroidism. With this rationale, the patient was treated with calcium, alfacalcidol, and cholecalciferol. One-year follow-up showed complete resolution of pain, improvement in serum calcium, and regression of bone lesions on [18F]F-fluorocholine PET/CT. This case illustrates the usefulness of [18F]F-fluorocholine PET/CT for the imaging of brown tumors in pseudohypoparathyroidism type 1B, and emphasizes the importance of calcium and vitamin D treatment in adult patients, to avoid the deleterious effects of high parathyroid hormone on skeletal integrity.

Brown tumor due to primary hyperparathyroidism in a familial case: a case report.

BACKGROUND: Primary hyperparathyroidism (PHPT) is an uncommon disorder characterised by hypercalcemia with an increased parathyroid hormone level. We reported a PHPT familial case with two subjects, a father and a daughter, and both of them had suffered from the brown tumor. CASE PRESENTATION: The proband, a 43-year-old patient, developed parathyroid adenomas at the age of 15; a histologically confirmed right parathyroid adenoma was removed by parathyroidectomy; and after six months follow-up, the serum calcium level was normalised. At the age of thirty-three, a CT scan of his head and neck revealed a mass in the right maxilla, as well as PHPT (i.e., left inferior parathyroid adenoma). Then, he underwent a biopsy of an exophytic lesion in the right maxilla and was diagnosed by pathology as a brown tumor, with the serum calcium and PTH levels at 2.78 mmol/L and 221 pg/mL, respectively. Subsequently, the patient took a left inferior parathyroid microwave ablation with ultrasound guidance. After three months of follow-up, the serum calcium and PTH levels returned to normal, and the brown tumor was resolved. After three years, it mineralised as revealed in a CT scan. By the time he was 43 years old, during the 28-year follow-up period, the serum calcium and PTH levels were still within the normal range, and there was no discomfort reported. He has consistently taken calcium supplements throughout the 28 years. Since the initial diagnosis, his blood indicators of kidney function have been normal, and ultrasound showed renal calculus in the right kidney and a normal left kidney. The proband's daughter, a 15-year-old girl, experienced left upper extremity pain for ten months. CT scan revealed a mass in the distal left radius, and a giant cell tumor was suspected. A surgical internal fixation was performed, and the pathology showed a brown tumor. Laboratory tests revealed a serum parathyroid hormone (PTH) level of 1554pg/mL, calcium level of 3.14 mmol/L, phosphorus level of 0.72 mmol/L, and alkaline phosphatase level of 1892 U/L. Given the osteitic changes and elevated levels of calcium and PTH, ultrasonography was performed, after which a mass was detected measuring 19 × 9 × 7 mm mixed with solid components and cystic fluid in the right thyroid gland. The results of 99mTc-MIBI scintigraphy confirmed the abnormal accumulation of 99mTc-MIBI in the right thyroid gland but not seen in the bilateral parathyroid glands. The patient underwent thyroidectomy, and the postoperative pathology report indicated an intra-thyroid ectopic parathyroid adenoma. The serum calcium and PTH levels became normal at 4 h after surgery. One to three months after operation, the serum calcium level was low, while the serum PTH level was high. Then, the patient was advised to take calcium supplements. Until the sixth month after the operation, the serum calcium level and serum PTH level returned to normal, and the bone pain was relieved. The patient's blood tests for kidney function remained normal. There was no evidence of bilateral kidney disease (such as nephrolithiasis or nephrocalcinosis) detected by ultrasound scan. There were several similarities in the state of illness between these two subjects. Both the father and the daughter developed parathyroid adenomas at the age of 15, and there was no lesion in other endocrine glands. And genetic testing revealed mutations in the CDC73 genes in both father and daughter. On the other hand, there were also a few differences. The father's first signs of brown tumor were in the right maxilla, while the daughter's appeared in the distal left radius. The father presented pathological changes in the left and right parathyroid glands, whereas the daughter presented with an ectopic parathyroid adenoma in the right thyroid gland. CONCLUSION: We report a familial case in which father and daughter were diagnosed to have brown tumors due to parathyroid adenoma and ectopic parathyroid adenoma, and genetic testing revealed CDC73 gene mutations in both. Therefore, in the diagnostic and differential process of young patients having bone disease, clinicians should not only focus on the clinical manifestations of the skeleton, but also implement a comprehensive analysis of systemic symptoms, considering the possibility that the patient has familial PHPT.

Lytic Mastoid Lesion in a Patient with Otalgia.

The differential diagnosis for an isolated lytic mastoid lesion is broad, encompassing various conditions requiring careful consideration. These include granulomatous disorders such as Langerhans cell histiocytosis and sarcoidosis, neoplastic processes like multiple myeloma, leukemia, lymphoma, and metastases, primary bone diseases such as Paget's disease, fibrous dysplasia, and osteitis fibrosa cystica, as well as infectious causes like osteomyelitis. In this report, we present a patient with otalgia and an isolated lytic mastoid lesion.

Brown tumors of the jaw: an atypical manifestation of primary hyperparathyroidism.

Brown tumors represent the terminal stage of bone remodeling processes in primary hyperparathyroidism. Currently they are rare, and typically affect long bones, pelvis and ribs. Brown tumors may be not included in the initial differential diagnosis of bone disease, especially when they are present in atypical localizations. We reported two cases of oral brown tumors as the initial presentation of primary hyperparathyroidism. In the first case, a 44-year-old woman presented a painful and sessile lesion of 4 × 3 cm over the central body of the mandible which progressively increased in 4-month. The second case involved a 23-year-old woman who was referred with a 3-month history of a painful and ulcerated mass of 2 cm arising from left maxilla, episodes of gingival hemorrhage and difficulty of breathing. Both cases were solitary tumors with no evidence of palpable cervical lymphadenopathy. Incisional biopsy of oral tumors resulted in giant cell and primary hyperparathyroidism was confirmed by laboratory tests. After parathyroidectomy, histology confirmed adenoma in both cases. Although this type of clinical presentation has almost disappeared in the recent decades, brown tumors should be considered in the differential diagnosis of bone oral masses.

Los tumores pardos son raros y, por lo general, afectan huesos largos, pelvis y costillas. Pueden no estar incluidos en el diagnóstico diferencial inicial como manifestación de enfermedad esquelética, especialmente cuando se presentan en localizaciones atípicas. Comunicamos dos casos de tumores pardos orales como presentación inicial de hiperparatiroidismo primario. En el primer caso, una mujer de 44 años presentó una lesión dolorosa y sésil de 4 × 3 cm sobre el cuerpo central de la mandíbula que aumentó de tamaño progresivamente en 4 meses. El segundo caso corresponde a una mujer de 23 años que acudió por presentar una masa dolorosa y ulcerada de 2 cm en maxilar izquierdo de 3 meses de evolución, episodios de hemorragia gingival y dificultad para respirar. Todos fueron tumores solitarios sin evidencia de linfadenopatía cervical palpable. La biopsia incisional de los tumores orales resultó en células gigantes, y las pruebas de laboratorio confirmaron el hiperparatiroidismo primario. Tras la paratiroidectomía, la histología confirmó adenoma en ambos casos. Los tumores pardos representan la etapa terminal de los procesos de remodelación ósea en el hiperparatiroidismo primario. Aunque este tipo de presentación clínica casi ha desaparecido en las últimas décadas, los tumores pardos deben ser considerados en el diagnóstico diferencial de las masas óseas orales.

Localization of Brown Tumors With 18 F-Fluorocholine PET/CT Imaging in Severe Primary Hyperparathyroidism.

ABSTRACT: We present the case of a 68-year-old woman with a painful tibial tumor and fatigue. Histology and laboratory studies were consistent with a brown tumor secondary to initially unrecognized, severe primary hyperparathyroidism. 18 F-fluorocholine PET/CT revealed a large hypermetabolic parathyroid mass and multiple bone foci considered as brown tumors. Unilateral neck exploration confirmed a large parathyroid adenoma. Serum calcium and parathyroid hormone levels normalized quickly, and symptoms subsided gradually after parathyroidectomy. Brown tumors are a rare complication of severe hyperparathyroidism. 18 F-fluorocholine PET/CT allows the localization of parathyroid adenomas and brown tumors, and can be used as a single imaging modality.

Diffuse Calvarial Hyperstosis.

Calvarial hyperstosis can be an idiopathic benign finding or secondary to a metabolic pathology. We herein describe a case of diffuse calvarial hyperstosis. A 26-year-old man known to have end-stage renal disease on regular hemodialysis, tertiary hyperparathyroidism, extensive brown tumors, and severe developmental impairment with skeletal deformities was referred to us for macrocephaly. On examination, the patient was chairbound, with speech and motor developmental delay, and frontal bossing. Brain computed tomography revealed diffuse hyperstosis of the calvarium and facial bones expansion with multiple sclerotic and lytic areas, causing subsequent narrowing of the basilar skull foramina. Brain magnetic resonance imaging demonstrated an extensive expansile bone marrow abnormality in the calvarium and skull base. There was mild generalized prominence of cortical sulci and ventricular system. The findings were in keeping with his known hypermetabolic state and tertiary hyperparathyroidism. The patient was managed conservatively with regular follow-up in the clinic.

Large parathyroid adenomas: Potential mechanisms to reconcile adenoma size and disease phenotype.

Parathyroid adenomas weighing more than 3.5 g are reported variously as "atypical", "large" or "giant" parathyroid adenomas. All such adenomas are rare variants accounting for no more than 1.5% of all parathyroid adenomas. Large parathyroid adenomas are often associated with more severe form of the disease, including osteitis fibrosa cystica (OFC) and share many biochemical, histological, and molecular features of both benign and malignant parathyroid neoplasms, and are considered a distinct clinical entity. However, the pathogenesis of oversized parathyroid adenomas and the often-associated skeletal phenotype remains unclear. We present 5 cases of primary hyperparathyroidism (PHPT) with OFC, an uncommon manifestation of contemporary PHPT, associated with larger parathyroid adenomas, seen in the Bone and Mineral Disorders Clinic of the Henry Ford Health in the last 30 years to illustrate the critical role of vitamin D nutrition in the pathogenesis of both the OFC and adenoma size. The estimated prevalence of OFC was very low 0.2%, 5 of the >3000 surgically confirmed cases of PHPT seen during this time. The mean ± SD values were: age: 36.8 ± 22.1 years (4 of the 5 <36years), serum calcium 11.6 ± 1.1 mg/dl, alkaline phosphatase 799 ± 487 IU/L, PTH 1440 ± 477 pg/ml, 25-hydroxyvitamin D 13.0 ± 8.9 ng/ml, 1,25-dihyroxyvitamin D 26.5 ± 13.7 pg/ml, urine calcium 562 ± 274 mg/day, and parathyroid adenoma weight 4.53 ± 2.2 g. Parathyroidectomy led to the resolution of both the biochemical indices and OFC in each patient without recurrence over >10 years of follow-up. Because OFC is a very rare in the West, but very common areas of endemic vitamin D deficiency, we also examined the relationship between vitamin D nutrition, as assessed by serum 25-hydroxyvitamin D level, and parathyroid adenoma weight as well as prevalence of OFC in two large secularly diverse cohorts of patients with PHPT (Detroit, USA and Chandigarh, India). Based on this relationship and the relative prevalence of OFC in these two large cohorts, we propose that vitamin D nutrition (and perhaps calcium nutrition) best explains both the adenoma size and prevalence of OFC.

Brown tumor of the cervical spine with primary hyperparathyroidism: A case report and literature review.

RATIONALE: Brown tumor (BT), an uncommon focal lytic bone tumor, is a non-neoplastic and reactive process caused by increased osteoclastic activity and fibroblastic proliferation in primary or secondary hyperparathyroidism. Vertebral tumor causing neural compression is relatively rare, especially in the cervical spine. PATIENT CONCERNS: A 29-year-old man developed neck pain and arm radicular pain 4 months ago, with the level of serum calcium significantly higher than normal. Computed tomography scan of the cervical spine revealed an expansile lytic lesion occupying the C6 body, left pedicle, and left lamina of C5-6. DIAGNOSES: Osteoclastoma according to imaging and histopathological results. INTERVENTIONS: A laminectomy of C5-6 was performed. OUTCOMES: One month later, he was re-hospitalized due to nausea and vomiting and the serum calcium, was still, kept at a high level. Additionally, the parathormone (PTH) was greatly higher than normal. BT with primary hyperparathyroidism due to the parathyroid tumor was considered. After the surgery of the right parathyroid gland was performed, serum calcium and PTH both decreased, and computed tomography showed good recovery. LESSONS: BTs might be misdiagnosed as other giant cell tumors, thus when giant cell tumors are considered, serum calcium and PTH examination may be needed to exclude BTs.

Uncommon presentation of brown tumours revealing hyperparathyroidism: Three case reports.

Brown tumours (BTs) are focal bone lesions encountered in patients with uncontrolled hyperparathyroidism (HPT). They are due to a proliferation of multinucleated giant cells in osteolytic lesions. Because of early screening of bone metabolism disorders, BTs are rare bone manifestations. More importantly, they scarcely reveal the disease. We demonstrate through these two cases reports unusual locations of BT complicating the course of HPT due to parathyroid hyperplasia.

Pathological ankle fracture due to brown tumour: atypical presentation of low serum vitamin D with normal parathyroid hormone and bone profile.

Osteoclastomas or brown tumours are named as such due to increased vascularity, subsequent haemorrhage and haemosiderin deposition giving the lesion a reddish brown appearance under gross microscopic examination. It is due to an increase in parathyroid hormone activity from several causes, such as parathyroid adenomas, renal impairment and low vitamin D levels. The lesions increase the tendency of the bone to fracture. The challenging aspect of the diagnosis is that a histological diagnosis without immunohistochemistry is impossible to make. This is because, without special staining, brown tumours cannot be differentiated from giant cell tumours, which are also classed as benign but can be locally destructive and has potential for malignant transformation. Once tissue diagnosis is confirmed as a brown tumour, then aggressive forms of treatment are not needed, and they generally resolve once the underlying cause is treated. We describe a woman in her 80s who presented to the local Orthopaedic service with a pathological ankle fracture due to a brown tumour.

A patient with femoral osteitis fibrosa cystica mimicking bone neoplasm: a case report.

BACKGROUND: Osteitis fibrosa cystica is a rare, benign and osteolytic lesion attributed to hyperparathyroidism. The high level of parathyroid hormone cause rapid bone loss. CASE PRESENTATION: The patient is a 50-year-old male complaining of severe and persistent pain in the right knee joint. Imaging studies were suspicious for a benign tumor in the right distal femur. Biopsy under CT guidance showed numerous osteoclast aggregation and hemosiderin deposition around the bone trabeculae. Blood tests disclosed significantly elevated parathyroid hormone, serum calcium, serum alkaline phosphatase. Parathyroid ultrasonography and CT scan showed a solid mass in front of the trachea at the thoracic entrance plane. After resection of the mass, the clinical symptoms were relieved and the radiological results were significantly improved, which further confirmed the diagnosis. CONCLUSIONS: Metabolic diseases-associated bone lesions require a comprehensive diagnosis of multiple inspection items. An interprofessional team approach to the diagnosis and treatment of osteitis fibrosa cystica will provide the best outcome.