Diagnosis and Treatment > Signs and Symptoms > Bone pain
You are looking at 1 - 9 of 9 items
Faculty of Medicine, University of Sydney, Sydney, New South Wales, Australia
Department of Endocrinology and Diabetes, Royal North Shore Hospital, Sydney, New South Wales, Australia
Search for other papers by M L Gild in
Google Scholar
PubMed
Search for other papers by L Heath in
Google Scholar
PubMed
Search for other papers by J Y Paik in
Google Scholar
PubMed
Faculty of Medicine, University of Sydney, Sydney, New South Wales, Australia
Department of Endocrinology and Diabetes, Royal North Shore Hospital, Sydney, New South Wales, Australia
Search for other papers by R J Clifton-Bligh in
Google Scholar
PubMed
Faculty of Medicine, University of Sydney, Sydney, New South Wales, Australia
Department of Endocrinology and Diabetes, Royal North Shore Hospital, Sydney, New South Wales, Australia
Search for other papers by B G Robinson in
Google Scholar
PubMed
Summary
Struma ovarii is a rare, usually benign ovarian tumour with malignancy occurring in <5% of cases. Metastases, particularly seeding to bone, are extremely rare. Presentation is variable but often features local pain and/or ascites and hyperthyroidism may occur. It is not established how to best treat and follow patients with extensive disease. Case reports of radioiodine (I131) ablative therapy following thyroidectomy have shown reduced recurrence. We describe the case of a 33-year-old woman who presented with bone pain and was diagnosed with skeletal metastases with features of follicular thyroid carcinoma. However, thyroid pathology was benign. She recalled that 5 years prior, an ovarian teratoma was excised, classified at that time as a dermoid cyst. Retrospective review of this pathology confirmed struma ovarii without obvious malignant features. The patient was found to have widespread metastases to bone and viscera and her thyroglobulin was >3000 µg/L following recombinant TSH administration prior to her first dose of I131. At 25 months following radioiodine treatment, she is in remission with an undetectable thyroglobulin and clear I131 surveillance scans. This case demonstrates an unusual presentation of malignant struma ovarii together with challenges of predicting metastatic disease, and demonstrates a successful radioiodine regimen inducing remission.
Learning points:
-
Malignant transformation of struma ovarii (MSO) is extremely rare and even rarer are metastatic deposits in bone and viscera.
-
MSO can be difficult to predict by initial ovarian pathology, analogous to the difficulty in some cases of differentiating between follicular thyroid adenoma and carcinoma.
-
No consensus exists on the management for post operative treatment of MSO; however, in this case, three doses of 6Gbq radioiodine therapy over a short time period eliminated metastases to viscera and bone.
-
Patients should continue to have TSH suppression for ~5 years.
-
Monitoring thyroglobulin levels can predict recurrence.
Search for other papers by Marina Tsoli in
Google Scholar
PubMed
Search for other papers by Anna Angelousi in
Google Scholar
PubMed
Search for other papers by Dimitra Rontogianni in
Google Scholar
PubMed
Search for other papers by Constantine Stratakis in
Google Scholar
PubMed
Search for other papers by Gregory Kaltsas in
Google Scholar
PubMed
Summary
Parathyroid carcinoma is an extremely rare endocrine malignancy that accounts for less than 1% of cases of primary hyperparathyroidism. We report a 44-year-old woman who presented with fatigue and diffuse bone pain. Laboratory findings revealed highly elevated serum calcium and parathyroid hormone (PTH) levels and a 4.5 × 3 × 2.5 cm cystic lesion in the lower pole of the right thyroid lobe that was shown histologically to be a parathyroid carcinoma. Ten years later, the patient developed brain and pulmonary metastases and recurrence of PTH-related hypercalcemia. Treatment of hypercalcemia along with localized radiotherapy and various chemotherapy regimens failed to induce a biochemical or radiological response. In conclusion, parathyroid carcinoma is a rare neoplasia that may develop metastases even after prolonged follow-up, for which there is no evidence-based treatment besides surgery. Different chemotherapeutic schemes did not prove to be of any benefit in our case highlighting the need for registering such patients to better understand tumor biology and develop specific treatment.
Learning points:
-
Metastases can develop many years after parathyroid cancer diagnosis.
-
Surgery is the only curative treatment for parathyroid carcinoma.
-
Chemotherapy and radiotherapy prove to be ineffective in parathyroid cancer treatment.
-
Patient registering is required in order to delineate underlining pathology and offer specific treatment.
Search for other papers by Shintaro Kawai in
Google Scholar
PubMed
Search for other papers by Hiroyuki Ariyasu in
Google Scholar
PubMed
Search for other papers by Yasushi Furukawa in
Google Scholar
PubMed
Search for other papers by Reika Yamamoto in
Google Scholar
PubMed
Search for other papers by Shinsuke Uraki in
Google Scholar
PubMed
Search for other papers by Ken Takeshima in
Google Scholar
PubMed
Search for other papers by Kenji Warigaya in
Google Scholar
PubMed
Search for other papers by Yuji Nakamoto in
Google Scholar
PubMed
Search for other papers by Takashi Akamizu in
Google Scholar
PubMed
Summary
Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome characterized by renal phosphate wasting leading to hypophosphatemia due to excessive actions of fibroblast growth factor 23 (FGF23) produced by the tumors. Although the best way of curing TIO is complete resection, it is usually difficult to detect the culprit tumors by general radiological modalities owing to the size and location of the tumors. We report a case of TIO in which the identification of the tumor by conventional imaging studies was difficult. Nonetheless, a diagnosis was made possible by effective use of multiple modalities. We initially suspected that the tumor existed in the right dorsal aspect of the scapula by 68Ga-DOTATOC positron emission tomography/computed tomography (68Ga-DOTATOC-PET/CT) and supported the result by systemic venous sampling (SVS). The tumor could also be visualized by 3T-magnetic resonance imaging (MRI), although it was not detected by 1.5T-MRI, and eventually be resected completely. In cases of TIO, a stepwise approach of 68Ga-DOTATOC-PET/CT, SVS and 3T-MRI can be effective for confirmation of diagnosis.
Learning points:
-
TIO shows impaired bone metabolism due to excessive actions of FGF23 produced by the tumor. The causative tumors are seldom detected by physical examinations and conventional radiological modalities.
-
In TIO cases, in which the localization of the culprit tumors is difficult, 68Ga-DOTATOC-PET/CT should be performed as a screening of localization and thereafter SVS should be conducted to support the result of the somatostatin receptor (SSTR) imaging leading to increased diagnosability.
-
When the culprit tumors cannot be visualized by conventional imaging studies, using high-field MRI at 3T and comparing it to the opposite side are useful after the tumor site was determined.
Search for other papers by Christopher Muir in
Google Scholar
PubMed
Search for other papers by Anthony Dodds in
Google Scholar
PubMed
Garvan Institute of Medical Research, Sydney, Australia
Search for other papers by Katherine Samaras in
Google Scholar
PubMed
Summary
Diamond–Blackfan anaemia (DBA) is a rare cause of bone marrow failure. The incidence of malignancy and endocrine complications are increased in DBA, relative to other inherited bone marrow failure syndromes. We describe an adult woman with DBA who developed osteoporosis and avascular necrosis (AVN) of both distal femora. Such endocrine complications are not uncommon in DBA, but under-appreciated, especially in adulthood. Further, rectal adenocarcinoma was diagnosed at age 32 years, requiring hemi-colectomy and adjuvant chemotherapy. Elevated cancer risk may warrant disease-specific screening guidelines. Genetic predictors of extra-haematopoetic complications in DBA are yet to be established.
Learning points:
-
Endocrine complications are common in DBA.
-
Clinical vigilance is required in managing bone health of DBA patients treated with glucocorticoids.
-
There is currently no reliable way to predict which patients will develop complications of therapy or premature malignancy related to DBA.
-
Complaints of bone or joint pain should prompt screening with targeted magnetic resonance imaging. Osteoporosis screening should be performed routinely.
Search for other papers by Shamil D Cooray in
Google Scholar
PubMed
Department of Medicine, Monash University, Melbourne, Australia
Search for other papers by Duncan J Topliss in
Google Scholar
PubMed
Summary
A 58-year-old man with metastatic radioiodine-refractory differentiated thyroid cancer (DTC) presented with left thigh and right flank numbness. He had known progressive and widespread bony metastases, for which he received palliative radiotherapy, and multiple bilateral asymptomatic pulmonary metastases. CT scan and MRI of the spine revealed metastases at right T10–L1 vertebrae with extension into the central canal and epidural disease at T10 and T11 causing cord displacement and canal stenosis but retention of spinal cord signal. Spinal surgery was followed by palliative radiotherapy resulting in symptom resolution. Two months later, sorafenib received approval for use in Australia and was commenced and up-titrated with symptomatic management of mild adverse effects. Follow-up CT scan three months after commencement of sorafenib revealed regression of pulmonary metastases but no evident change in most bone metastases except for an advancing lesion eroding into the right acetabulum. The patient underwent a right total hip replacement, intra-lesional curettage and cementing. After six months of sorafenib therapy, CT scanning showed enlarging liver lesions with marked elevation of serum thyroglobulin. Lenvatinib was commenced and sorafenib was ceased. He now has stable disease with a falling thyroglobulin more than 5 years after metastatic radioiodine-refractory DTC was diagnosed.
In DTC, 5% of distant metastases become radioiodine-refractory, resulting in a median overall survival of 2.5–3.5 years. Tyrosine kinase inhibitor (TKI) therapy has recently been demonstrated to increase progression-free survival in these patients but poses some unique management issues and is best used as part of an integrated approach with directed therapy.
Learning points:
-
Directed therapies may have greater potential to control localised disease and related symptoms when compared to systemic therapies.
-
Consider TKI therapy in progressive disease where benefits outweigh risks.
-
Active surveillance and timely intervention are required for TKI-related adverse effects.
-
There is a need for further research on the clinical application of TKI therapy in advanced DTC, including comparative efficacy, sequencing and identifying responders.
Search for other papers by Nobuhiro Miyamura in
Google Scholar
PubMed
Search for other papers by Shuhei Nishida in
Google Scholar
PubMed
Search for other papers by Mina Itasaka in
Google Scholar
PubMed
Search for other papers by Hirofumi Matsuda in
Google Scholar
PubMed
Search for other papers by Takeshi Ohtou in
Google Scholar
PubMed
Search for other papers by Yasuhiro Yamaguchi in
Google Scholar
PubMed
Search for other papers by Daisuke Inaba in
Google Scholar
PubMed
Search for other papers by Sadahiro Tamiya in
Google Scholar
PubMed
Search for other papers by Tetsuo Nakano in
Google Scholar
PubMed
Summary
Hepatitis C-associated osteosclerosis (HCAO), a very rare disorder in which an extremely rapid bone turnover occurs and results in osteosclerosis, was acknowledged in 1990s as a new clinical entity with the unique bone disorder and definite link to chronic type C hepatitis, although the pathogenesis still remains unknown. Affected patients suffer from excruciating deep bone pains. We report the 19th case of HCAO with diagnosis confirmed by bone biopsy, and treated initially with a bisphosphonate, next with corticosteroids and finally with direct acting antivirals (DAA: sofosbuvir and ribavirin) for HCV infection. Risedronate, 17.5 mg/day for 38 days, did not improve the patient’s symptoms or extremely elevated levels of bone markers, which indicated hyper-bone-formation and coexisting hyper-bone-resorption in the patient. Next, intravenous methylprednisolone pulse therapy followed by high-dose oral administration of prednisolone evidently improved them. DAA therapy initiated after steroid therapy successfully achieved sustained virological response, but no additional therapeutic effect on them was observed. Our results strongly suggested that the underlying immunological alteration is the crucial key to clarify the pathogenesis of HCAO. Bone mineral density of lumbar vertebrae of the patient was increased by 14% in four-month period of observation. Clarification of the mechanisms that develop osteosclerosis in HCAO might lead to a new therapeutic perspective for osteoporosis.
Learning points:
-
HCAO is an extremely rare bone disorder, which occurs exclusively in patients affected with HCV, of which only 18 cases have been reported since 1992 and pathogenesis still remains unclear.
-
Pathophysiology of HCAO is highly accelerated rates of both bone formation and bone resorption, with higher rate of formation than that of resorption, which occur in general skeletal leading to the diffuse osteosclerosis with severe bone pains.
-
Steroid therapy including intravenous pulse administration in our patient evidently ameliorated his bone pains and reduced elevated values of bone markers. This was the first successful treatment for HCAO among cases reported so far and seemed to propose a key to solve the question for its pathogenesis.
-
The speed of increase in the bone mineral content of the patient was very high, suggesting that clarification of the mechanism(s) might lead to the development of a novel therapy for osteoporosis.
Search for other papers by Hanna Remde in
Google Scholar
PubMed
Search for other papers by Elke Kaminsky in
Google Scholar
PubMed
Search for other papers by Mathias Werner in
Google Scholar
PubMed
Search for other papers by Marcus Quinkler in
Google Scholar
PubMed
Summary
We report of a male patient aged 32 years who presented with primary hyperparathyroidism. Three parathyroid glands were resected. At the age of 46 years, nervus facialis irritation was noted, and an MRI scan incidentally revealed a non-functioning pituitary adenoma with affection of the chiasma opticum. The patient underwent transsphenoidal operation resulting in pituitary insufficiency postoperatively. At the same time, primary hyperparathyroidism reoccurred and a parathyroid adenoma located at the thymus was resected. The mother of the patient died early due to multiple tumors. The patient was suspected to have multiple endocrine neoplasia type 1 (MEN1) and genetic analysis was performed. In addition, on clinical examination, multiple exostoses were noticed and an additional genetic analysis was performed. His father was reported to have multiple osteochondromas too. MEN1 was diagnosed in the patient showing a novel heterozygote mutation c.2T>A in exon 2, codon 1 (start codon ATG>AAG;p.Met1?) of the MEN1 gene. In genetic mutational analysis of the EXT1 gene, another not yet known mutation c.1418-2A>C was found in intron 5 of the EXT1 gene (heterozygotic). In conclusion, we report novel mutations of the EXT1 and the MEN1 genes causing hereditary multiple osteochondromas and MEN1 in one patient.
Learning points
-
It is important to ask for the patient's family history in detail.
-
Patients with MEN1 are characterized by the occurrence of tumors in multiple endocrine tissues and nonendocrine tissues, most frequently parathyroid (95%), enteropancreatic neuroendocrine (50%), and anterior pituitary (40%) tissues.
-
Familiar MEN1 has a high degree of penetrance (80–95%) by the age over 50; however, combinations of the tumors may be different in members of the same family.
-
Patients with EXT1 gene mutations should be monitored for possible transformation of bone lesions into osteochondrosarcoma.
Search for other papers by K Nadarasa in
Google Scholar
PubMed
Search for other papers by M Bailey in
Google Scholar
PubMed
Search for other papers by H Chahal in
Google Scholar
PubMed
Search for other papers by O Raja in
Google Scholar
PubMed
Search for other papers by R Bhat in
Google Scholar
PubMed
Search for other papers by C Gayle in
Google Scholar
PubMed
Search for other papers by A B Grossman in
Google Scholar
PubMed
Search for other papers by M R Druce in
Google Scholar
PubMed
Summary
We present the case of a patient with metastatic parathyroid carcinoma whose hypercalcaemia was medically managed through two pregnancies. The diagnosis was made when the patient presented with chronic knee pain and radiological findings consistent with a brown tumour, at the age of 30. Her corrected calcium and parathyroid hormone (PTH) levels were significantly elevated. Following localisation studies, a right parathyroidectomy was performed with histology revealing parathyroid carcinoma, adherent to thyroid tissue. Aged 33, following biochemical recurrence of disease, the patient underwent a second operation. A subsequent CT and FDG–PET revealed bibasal pulmonary metastases. Aged 35, the patient was referred to our unit for treatment of persistent hypercalcaemia. The focus of treatment at this time was debulking metastatic disease using radiofrequency ablation. Despite advice to the contrary, the patient conceived twice while taking cinacalcet. Even though there are limited available data regarding the use of cinacalcet in pregnancy, both pregnancies continued to term with the delivery of healthy infants, using intensive medical management for persistent hypercalcaemia.
Learning points
-
Parathyroid carcinoma is a rare cause of primary hyperparathyroidism.
-
Hypercalcaemia during pregnancy can result in significant complications for both the mother and the foetus.
-
The use of high-dose cinacalcet in pregnancy has been shown, in this case, to aid in the management of resistant hypercalcaemia without teratogenicity.
Search for other papers by Anna Casteràs in
Google Scholar
PubMed
Search for other papers by Jürgen Kratzsch in
Google Scholar
PubMed
Search for other papers by Ángel Ferrández in
Google Scholar
PubMed
Search for other papers by Carles Zafón in
Google Scholar
PubMed
Search for other papers by Antonio Carrascosa in
Google Scholar
PubMed
Search for other papers by Jordi Mesa in
Google Scholar
PubMed
Summary
Isolated GH deficiency type IA (IGHDIA) is an infrequent cause of severe congenital GHD, often managed by pediatric endocrinologists, and hence few cases in adulthood have been reported. Herein, we describe the clinical status of a 56-year-old male with IGHDIA due to a 6.7 kb deletion in GH1 gene that encodes GH, located on chromosome 17. We also describe phenotypic and biochemical parameters, as well as characterization of anti-GH antibodies after a new attempt made to treat with GH. The height of the adult patient was 123 cm. He presented with type 2 diabetes mellitus, dyslipidemia, osteoporosis, and low physical and psychological performance, compatible with GHD symptomatology. Anti-GH antibodies in high titers and with binding activity (>101 IU/ml) were found 50 years after exposure to exogenous GH, and their levels increased significantly (>200 U/ml) after a 3-month course of 0.2 mg/day recombinant human GH (rhGH) treatment. Higher doses of rhGH (1 mg daily) did not overcome the blockade, and no change in undetectable IGF1 levels was observed (<25 ng/ml). IGHDIA patients need lifelong medical surveillance, focusing mainly on metabolic disturbances, bone status, cardiovascular disease, and psychological support. Multifactorial conventional therapy focusing on each issue is recommended, as anti-GH antibodies may inactivate specific treatment with exogenous GH. After consideration of potential adverse effects, rhIGF1 treatment, even theoretically indicated, has not been considered in our patient yet.
Learning points
-
Severe isolated GHD may be caused by mutations in GH1 gene, mainly a 6.7 kb deletion.
-
Appearance of neutralizing anti-GH antibodies upon recombinant GH treatment is a characteristic feature of IGHDIA.
-
Recombinant human IGF1 treatment has been tested in children with IGHDIA with variable results in height and secondary adverse effects, but any occurrence in adult patients has not been reported yet.
-
Metabolic disturbances (diabetes and hyperlipidemia) and osteoporosis should be monitored and properly treated to minimize cardiovascular disease and fracture risk.
-
Cerebral magnetic resonance imaging should be repeated in adulthood to detect morphological abnormalities that may have developed with time, as well as pituitary hormones periodically assessed.
