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Taieb Ach Department of Endocrinology, University Hospital of Farhat Hached Sousse, Tunisia
University of Sousse, Faculty of Medicine of Sousse, Sousse, Tunisia

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Ben Yamna Hadami Department of Endocrinology, University Hospital of Farhat Hached Sousse, Tunisia
University of Tunis, Faculty of Medicine of Tunis, Tunis, Tunisia

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Nadia Ghariani Department of Endocrinology, University Hospital of Farhat Hached Sousse, Tunisia
University of Sousse, Faculty of Medicine of Sousse, Sousse, Tunisia
Department of Dermatology, University Hospital of Farhat Hached Sousse, Tunisia

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Randa Said ElMabrouk Department of Endocrinology, University Hospital of Farhat Hached Sousse, Tunisia
University of Sousse, Faculty of Medicine of Sousse, Sousse, Tunisia
Department of Dermatology, University Hospital of Farhat Hached Sousse, Tunisia

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Asma Ben Abdelkrim Department of Endocrinology, University Hospital of Farhat Hached Sousse, Tunisia
University of Sousse, Faculty of Medicine of Sousse, Sousse, Tunisia

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Maha Kacem Department of Endocrinology, University Hospital of Farhat Hached Sousse, Tunisia
University of Sousse, Faculty of Medicine of Sousse, Sousse, Tunisia

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Mohamed Denguezli Department of Endocrinology, University Hospital of Farhat Hached Sousse, Tunisia
University of Sousse, Faculty of Medicine of Sousse, Sousse, Tunisia
Department of Dermatology, University Hospital of Farhat Hached Sousse, Tunisia

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Koussay Ach Department of Endocrinology, University Hospital of Farhat Hached Sousse, Tunisia
University of Sousse, Faculty of Medicine of Sousse, Sousse, Tunisia

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Summary

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a rare autosomal recessive inherited syndrome caused by mutations in autoimmune regulator (AIRE) gene. The three clinical components of this syndrome are mucocutaneous candidiasis, hypoparathyroidism, and primary adrenal insufficiency. In addition to these frequent symptoms, many other components have been reported including gastrointestinal manifestations.We report a case of a 17-year-old Caucasian female patient diagnosed with APECED who presented with acute abdominal pain. Her medical history revealed chronic digestive discomfort without bowel movement disorders. The patient needed a significant increase in doses of calcium supplementation and hydrocortisone which appeared to be partially inefficient. Investigation with esophagogastroduodenoscopy and biopsy showed autoimmune atrophic gastritis. The patient eventually needed increasing doses of treatment received in order to achieve desired clinical and biological therapeutic goals.

Learning points

  • Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a rare autosomal recessive inherited syndrome caused by mutations in the autoimmune regulator (AIRE) gene.

  • The three clinical components of this syndrome that appear in early childhood are mucocutaneous candidiasis, hypoparathyroidism, and primary adrenal insufficiency.

  • In addition to these frequent symptoms, many other components have been reported including gastrointestinal manifestations like atrophic gastritis. They can be caused by many abnormalities including atrophic gastritis and the modification of intestinal biofilm and microbiota.

  • Early diagnosis and treatment of gastrointestinal manifestations associated with APECED prevent multiple life-threatening consequences like acute adrenal crisis and severe symptomatic hypocalcemia.

Open access
Ijaz S Jamall Risk-Based Decisions, Inc. 1540 River Park Drive, Suite 203, Sacramento, California, USA
Theodor-Billroth-Academy®, Munich – Sacramento, CA, Germany, USA
INCORE, International Consortium of Research Excellence of the Theodor-Billroth-Academy®, Germany, USA

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Michael C Ullery Primary Care Physician, Heart and Vascular Medical Associates, 500 University Avenue, Sacramento, California, USA

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Massimiliano Rocchietti March Internal Medicine Unit, Faculty of Medicine and Psychology, University of Rome "Sapienza", Sant'Andrea Hospital, Rome, Italy

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Elisa Pignatti Department of Surgery, Medicine Dentistry and Morphological Sciences with Interest in Transplant, University of Modena and Reggio Emilia, Modena, Italy

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Vincenzo Rochira Unit of Endocrinology, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy
UOC of Endocrinology, Department of Medical Specialties, Azienda Ospedaliero-Universitaria di Modena, Ospedale Civile di Baggiovara, Modena, Italy

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Björn L D M Brücher Theodor-Billroth-Academy®, Munich – Sacramento, CA, Germany, USA
INCORE, International Consortium of Research Excellence of the Theodor-Billroth-Academy®, Germany, USA
Department of Surgery, Carl-Thiem-Klinikum, Cottbus, Germany

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Summary

A 44-year-old athletic man presented in 2009 with severe low back pain. Dual-energy x-ray absorptiometry revealed severe osteoporosis; serum testosterone was 189 ng/dL while serum estradiol (E2) measured by liquid chromatography/mass spectrometry was 8 pg/mL. DNA was extracted and sequenced from a blood sample from the patient since his maternal first cousin also had low bone mass and both patients were screened for aromatase dysfunction by PCR analysis for the CYP19A1 gene, which encodes aromatase. No known pathologic mutations were observed in the coding exons, but novel single nucleotide polymorphisms were detected both in the proband and in his cousin. Treatment with topical testosterone started in August 2010. Over the next 8 years, testosterone dosage was varied and switched from topical gel to injections and maintained on depo-injections of testosterone at about 60 mg once per week. Re-examination in March 2012 included a brain MRI to exclude pituitary lesions; hyperparathyroidism was ruled out (normal serum parathyroid hormone, calcium, and calcium to phosphorous ratio) and celiac disease was excluded (negative transglutaminase antibodies). Follow-up in October 2018 showed improved bone mineral density of the lumbar spine by 29% and of the left femoral hip by 15% compared to baseline measurements. This reveals the importance of measuring serum E2 for making the correct diagnosis, as well as for monitoring a therapeutic effect. Herein, we propose treatment of male osteoporosis where serum E2 levels are below about 20 pg/mL with testosterone to reverse osteoporosis.

Learning points

  • Estrogen deficiency in the diagnosis of male idiopathic osteoporosis.

  • Importance of serum estradiol in male osteoporosis.

  • Role of polymorphisms in aromatase gene on bone health.

  • Reversal of osteoporosis.

  • Tailored testosterone treatment for bone health.

Open access
Tomoko Kobayashi Department of Endocrinology and Diabetes, Nagoya University Hospital, Nagoya, Japan

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Takuya Iwata Department of Endocrinology and Diabetes, Nagoya University Hospital, Nagoya, Japan

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Katsunari Handa Department of Endocrinology and Diabetes, Nagoya University Hospital, Nagoya, Japan

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Hiroshi Arima Department of Endocrinology and Diabetes, Nagoya University Hospital, Nagoya, Japan

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Summary

A 76-year-old female with type 2 diabetes mellitus presented with hematuria, low back pain, and intermittent fever for 7 days. She was admitted to our hospital and diagnosed with Streptococcus agalactiae (GBS) bacteremia. CT showed an air density within the right iliopsoas muscle, and an MRI of the spine revealed hyperintensity in the right half of the L1–L2 intervertebral disk, leading to the diagnosis of a paraspinal abscess and L1–L2 pyogenic spondylitis. Antibiotic therapy was started and the clinical symptoms, as well as serologic biomarkers and radiologic images of the paraspinal abscess, were improved. The therapy was stopped on day 72 despite vertebral destruction progression. Vertebral endplate ossification was observed on day 108, and further bone formation was noted on day 177. Our case study with radiologic findings over 6 months demonstrated how bone destruction with pyogenic spondylitis, which had been treated with antibiotic therapy, improved after cessation of antibiotics.

Learning points

  • Although GBS is a rare cause of spondylitis, diabetic mellitus is a risk factor for the development of invasive GBS infections, especially under poor glycemic control.

  • Bone destruction of pyogenic spondylitis can improve after discontinuation of antibiotic therapy.

  • It may be important to decide the period of antibiotic therapy based on clinical conditions, serologic biomarkers, and soft tissue findings rather than bone findings.

  • When elderly diabetic patients present with back pain and fever, spondylitis should be considered in the differential diagnosis to avoid potential diagnostic delays or misdiagnosis.

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Aneez Joseph Department of Endocrinology, Diabetes and Metabolism, Christian Medical College and Hospital, Vellore, India

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Kripa Elizabeth Cherian Department of Endocrinology, Diabetes and Metabolism, Christian Medical College and Hospital, Vellore, India

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Nitin Kapoor Department of Endocrinology, Diabetes and Metabolism, Christian Medical College and Hospital, Vellore, India

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Thomas V Paul Department of Endocrinology, Diabetes and Metabolism, Christian Medical College and Hospital, Vellore, India

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Summary

Tenofovir-induced osteomalacia secondary to proximal renal tubular dysfunction is not an uncommon complication known to occur. A 46-year-old woman was referred for the evaluation of osteoporosis which was diagnosed elsewhere. She had polyarthralgia, bony pains and proximal muscle weakness of 1 year duration. She was diagnosed to have HIV infection and was on antiretroviral therapy that consisted of tenofovir, lamivudine and efavirenz for the past 12 years. She had attained menopause 5 years back. On examination, she had bone tenderness, proximal myopathy and painful restriction of movement of her lower limbs. Investigations showed features of renal tubular acidosis, hypophosphatemia and raised alkaline phosphatase that were suggestive of osteomalacia. X-ray of the pelvis showed diffuse osteopenia and an MRI of the pelvis done showed multiple insufficiency fractures involving the head of femur on both sides. Following this, her tenofovir-based regimen was changed to abacavir, efavirenz and lamivudine with addition of neutral phosphate supplements and calcitriol. On follow-up after 6 months, she had significant improvement in her symptoms as well as in the bone mineral density at the lumbar spine (33.2%), femoral neck (27.6%), trabecular bone score (13.2%) and reduction in the buckling ratio at the narrow neck (6.3%), inter-trochanteric region (34%) and femoral shaft (28.8%). Tenofovir-induced osteomalacia is encountered in individuals on prolonged treatment with tenofovir. Treatment consists of changing to a non-tenofovir-based regimen, as well as supplementation of phosphate and calcitriol. Treatment results in remarkable improvement in symptoms and most densitometric indices.

Learning points

  • Tenofovir is a nucleotide reverse transcriptase inhibitor (NRTI) and is a major drug in the treatment of retroviral and hepatitis B infections.

  • Tenofovir-related hypophosphatemic osteomalacia is related to proximal tubulopathy and is not an uncommon occurrence.

  • Treatment mandates changing to a non-tenofovir-based regimen with supplementation of neutral phosphate and calcitriol.

  • Treatment results in a significant improvement in bone mineral density, trabecular bone score and hip geometric parameters.

Open access
L Aliberti Department of Medical Sciences, Section of Endocrinology and Internal Medicine, University of Ferrara, Ferrara, Italy

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I Gagliardi Department of Medical Sciences, Section of Endocrinology and Internal Medicine, University of Ferrara, Ferrara, Italy

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M Pontrelli Department of Medical Sciences, Section of Endocrinology and Internal Medicine, University of Ferrara, Ferrara, Italy

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M C Zatelli Department of Medical Sciences, Section of Endocrinology and Internal Medicine, University of Ferrara, Ferrara, Italy

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M R Ambrosio Department of Medical Sciences, Section of Endocrinology and Internal Medicine, University of Ferrara, Ferrara, Italy

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Summary

Tumour-induced osteomalacia (TIO) is due to an overproduction of fibroblast growth factor 23 (FGF23) by mesenchymal tumours, causing hypophosphatemia, osteomalacia and muscle weakness. TIO is usually cured by tumour resection, but neoplasms may be unidentifiable and unresectable or the patient may refuse surgery. In these cases, medical treatment with oral phosphate and calcitriol is mandatory, but it is not fully effective and it is associated with low compliance. Burosumab, a human MAB against FGF23 employed to treat X-linked hypophosphatemia (XLH), has recently been approved for TIO in the USA. Maximum burosumab dose in XLH is 90 mg administered for 2 weeks; there are no data on clinical efficacy and safety of this dose in TIO. We reported the case of a 73 years old male with multiple non-traumatic fractures, low bone mineral density, pain and reduced independence of activities of daily living. Biochemical evaluation showed hypophosphatemia, high alkaline phosphatase (ALP) and C-terminal telopeptide (CTX) and normal albumin-corrected total calcium and parathyroid hormone. Tubular phosphate reabsorption was low (80%), whereas C-terminal tail of FGF23 (cFGF23) was elevated. A 68Ga-DOTATOC PET was performed, identifying a lesion in the first left rib. The patient refused surgery; therefore, burosumab therapy was started. After 18 months of treatment (maximum dose: 60 mg administered for 2 weeks), plasma phosphate normalized and ALP levels improved (138 U/L). Patient clinical symptoms as well as pain severity and fatigue improved. Neither adverse events nor tumour progression was reported during follow-up except for a painless fracture of the second right rib.

Learning points

  • Our case shows efficacy and safety of burosumab treatment administered every 2 weeks in a tumour-induced osteomalacia (TIO) patient.

  • After 18 months of treatment at a maximum dose of 60 mg every 2 weeks, we found plasma phosphate normalization and ALP reduction as well as improvement in clinical symptoms and fatigue.

  • Neither adverse events nor tumour progression was reported during follow-up, except for a painless fracture of the second right rib.

Open access
Therese Adrian Department of Nephrology, Copenhagen University Hospital – Rigshospitalet, Copenhagen, Denmark
Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

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Mads Hornum Department of Nephrology, Copenhagen University Hospital – Rigshospitalet, Copenhagen, Denmark
Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

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Filip Krag Knop Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Center for Clinical Metabolic Research, Copenhagen University Hospital – Gentofte Hospital, Hellerup, Denmark
Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Science, University of Copenhagen, Copenhagen, Denmark
Copenhagen University Hospital – Steno Diabetes Center Copenhagen, Herlev, Denmark

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Lise Lotte Gluud Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Gastro Unit, Medical Division, Copenhagen University Hospital – Amager and Hvidovre Hospital, Hvidovre, Denmark

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Summary

A 72-year-old man with type 2 diabetes volunteered to participate in the control group of a clinical study. The study evaluated non-alcoholic fatty liver disease in patients with kidney disease. The patient was followed at a gastroenterology department due to Crohn’s disease and post-operative bile acid malabsorption. The patient had no symptoms or biochemical findings suggesting liver disease. Surprisingly, a transient elastography (FibroScan®) suggested advanced fibrosis with a median of 16.1 kPa. A liver biopsy showed non-alcoholic steatohepatitis (NASH)-cirrhosis. The diagnosis was only made incidentally and highlights how NASH-cirrhosis may be overlooked due to the lack of symptoms.

Learning points

  • Clinicians treating high-risk populations, including patients with type 2 diabetes and/or components of the metabolic syndrome, should be aware of the frequently occurring co-existence with non-alcoholic fatty liver disease (NAFLD) and especially non-alcoholic steatohepatitis (NASH).

  • Liver enzymes may be in the normal range even in people with steatosis, NASH, or even cirrhosis.

  • The diagnosis of NAFLD should include evaluation of hepatic fibrosis as this is the most important prognostic factor for liver-related complications and mortality.

  • Guidelines about systematic screening for NAFLD in patients with type 2 diabetes are incongruent.

Open access
Alyssa J Mancini Harvard Medical School, Boston, MA, USA Hospital Medicine Unit, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA

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Amin Sabet Boston University School of Medicine, Boston, Massachusetts Division of Endocrinology, Department of Medicine, St. Elizabeth’s Medical Center, Boston, Massachusetts, USA

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Gunnlaugur Petur Nielsen Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts, USA

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J Anthony Parker Department of Radiology, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA

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Joseph H Schwab Department of Orthopedic Surgery, Massachusetts General Hospital, Boston, Massachusetts, USA

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Ashley Ward Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts, USA

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Jim S Wu Department of Radiology, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA

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Alan O Malabanan Boston University School of Medicine, Boston, MA Section of Endocrinology, Diabetes and Nutrition, Boston Medical Center, Boston, Massachusetts, USA

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Summary

Tumor-induced osteomalacia (TIO) is a rare form of osteomalacia caused by fibroblast growth factor-23 (FGF23)-secreting tumors. Most of these tumors are phosphaturic mesenchymal tumors (PMTs) typically involving soft tissue in the extremities and bone of the appendicular skeleton and cranium. We report the case of a 60-year-old woman with about 3 years of persistent bone pain and multiple fractures, initially diagnosed as osteoporosis, who was found to have hypophosphatemia with low 1,25-dihydroxyvitamin D and elevated alkaline phosphatase and inappropriately normal FGF23 consistent with TIO. Her symptoms improved with phosphate supplementation, vitamin D and calcitriol. 68Ga-DOTATATE imaging revealed a T12 vertebral body lesion confirmed on biopsy to be a PMT. She underwent resection of the PMT with resolution of TIO and increased bone density. This rare case of TIO secondary to a PMT of the thoracic spine highlights some of the common features of PMT-associated TIO and draws attention to PMT-associated TIO as a possible cause of unexplained persistent bone pain, a disease entity that often goes undiagnosed and untreated for years.

Learning points

  • Tumor-induced osteomalacia (TIO) is typically caused by phosphaturic mesenchymal tumors (PMTs) that are usually found in the soft tissue of the extremities and bone of the appendicular skeleton/cranium and rarely in the spine.

  • TIO may be misdiagnosed as osteoporosis or spondyloarthritis, and the correct diagnosis is often delayed for years. However, osteoporosis, in the absence of fracture, is not associated with bone pain.

  • The hallmark of TIO is hypophosphatemia with inappropriately normal or low 1,25-dihydroxyvitamin D and elevated or inappropriately normal fibroblast growth factor-23 (FGF23) levels.

  • In patients with unexplained persistent bone pain, a serum phosphate should be measured. Consider PMT-associated TIO as a potential cause of unexplained persistent bone pain and hypophosphatemia.

  • PMTs express somatostatin receptors and may be identified with 68Ga-DOTATATE imaging.

  • Complete surgical resection is the preferred treatment for spinal PMTs associated with TIO.

Open access
Mike Lin Department of Endocrinology, Concord Repatriation General Hospital, Concord NSW, Australia

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Kirtan Ganda Department of Endocrinology, Concord Repatriation General Hospital, Concord NSW, Australia
The University of Sydney Concord Clinical School, Concord NSW, Australia.

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Summary

We present the case of a 60-year-old female who developed repeated atraumatic stress fractures. She was initially diagnosed with osteoporosis based on her dual-energy X-ray absorptiometry (DXA) scan bone mineral density (BMD) T-scores and started on denosumab therapy. Secondary osteoporosis screen revealed abnormal myeloma screen and low serum phosphate levels. It was thought that the patient had multiple myeloma with associated Fanconi-related tubular dysfunction. However, fibroblast growth factor-23 (FGF-23) levels were grossly elevated, making Fanconi syndrome unlikely. The patient was subsequently diagnosed with two separate conditions, namely cardiac amyloid light-chain (AL) amyloidosis and FGF-23-related hypophosphataemia, likely due to tumour-induced osteomalacia. This case highlights the importance of excluding osteomalacia as a cause of low BMD and checking FGF-23 levels in the workup for hypophosphataemia.

Learning Points

  • Tumour-induced osteomalacia is a difficult diagnosis as the tumour is often small and slow growing. Imaging may fail to identify a tumour, and treatment therefore consists of calcitriol and phosphate replacement.

  • Tumour-induced osteomalacia should be suspected in the adult presenting with new-onset hypophosphataemia, elevated FGF-23 levels and isolated renal phosphate wasting.

  • Serum phosphate is not part of the routine chemistry panels. Routinely checking phosphate levels prior to initiating antiresorptive therapy is warranted.

  • DXA cannot distinguish low bone mineral density due to osteoporosis from osteomalacia. Antiresorptive therapy should be avoided in osteomalacia due to the risk of clinical and radiographic deterioration.

Open access
Keerthana Haridas PGY2, Internal Medicine, Icahn School of Medicine, Mount Sinai St Luke’s/West, New York, New York, USA

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Summary

Human T-cell lymphotropic virus-1 (HTLV-1) causes adult T-cell leukemia and lymphoma (ATLL) and is a rare but important cause of hypercalcemia. A 53-year-old male with HTLV-1-associated myelopathy presented with acute on chronic bilateral lower extremity weakness and numbness. Initial blood work revealed hypercalcemia with corrected calcium of 16.2 mg/dL (8.5–11.5) with normal levels of phosphorus and alkaline phosphatase. Workup for hypercalcemia revealed parathyroid hormone (PTH) of 14 pg/mL (10–65), 25 hydroxy vitamin D at 19.6 ng/mL (30–100), 1,25 dihydroxy vitamin D at 6.7 pg/mL (19.9–79.3), thyroid-stimulating hormone of 1.265 μIU/mL (0.5–5), undetectable PTH-related protein (PTHrP) and lactate dehydrogenase of 433 U/L (100–220). The urine calcium creatinine ratio was 0.388. Reverse transcriptase PCR was positive for HTLV-1 and negative for HTLV-2. Peripheral blood flow cytometry and lymph node biopsy confirmed ATLL. He received treatment with fluids, calcitonin and denosumab after which serum calcium levels fell (nadir: 7.7 mg/dL) and then normalized. Humoral hypercalcemia in this setting is mediated by receptor activator of nuclear factor-kappa B ligand (RANKL), PTHrP and other cytokines. PTHrP levels depend on levels of the TAX gene product, cell type and lymphocyte-specific factors. Thus, a low level, like in our patient, does not rule out HTLV-1 infection/ATLL as the cause of hypercalcemia. Hypercalcemia is known to be responsive to monoclonal antibodies against RANKL given the compound’s role in mediating hypercalcemia in these cases.

Learning points

  • Human T-cell lymphotropic virus-1 infection and adult T-cell leukemia and lymphoma are associated with high rates of hypercalcemia and hypercalcemic crises.

  • Hypercalcemia in these cases is mediated by osteoclastic bone resorption carried out by several agents including receptor activator of nuclear factor-kappa B ligand, parathyroid hormone-related protein (PTHrP), macrophage inflammatory protein 1 alpha, interleukins, etc. A normal PTHRrP does not rule out humoral hypercalcemia of malignancy in this setting, as indicated by this case.

  • Hypercalcemia in such settings is highly responsive to monoclonal antibodies against RANKL given the role the ligand plays in resorptive hypercalcemia.

Open access
Mohammed Anwar Hussain Department of Endocrinology, Christian Medical College and Hospital, Vellore, India

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Aneez Joseph Department of Endocrinology, Christian Medical College and Hospital, Vellore, India

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Vinoo Mathew Cherian Department of Orthopaedics, Christian Medical College and Hospital, Vellore, India

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Alok Srivastava Department of Haematology, Christian Medical College and Hospital, Vellore, India

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Kripa Elizabeth Cherian Department of Endocrinology, Christian Medical College and Hospital, Vellore, India

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Nitin Kapoor Department of Endocrinology, Christian Medical College and Hospital, Vellore, India

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Thomas Vizhalil Paul Department of Endocrinology, Christian Medical College and Hospital, Vellore, India

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Summary

Although bisphosphonates (BPs) are mainly used for the treatment of osteoporosis and are generally safe, long-term use and more dosage as utilised in malignant conditions may be associated with the rare adverse event of an atypical femoral fracture (AFF). Occasionally, the risk of developing an AFF persists long after BPs are withdrawn. A 39-year-old woman who underwent chemotherapy and an autologous stem cell transplantation for multiple myeloma presented to us with history of pain in the left thigh. She had received multiple doses of oral and parenteral BPs for about 10 years in view of the underlying myeloma with osteoporosis. Her investigations showed a suppressed CTX of 192 pg/mL, and radiograph of pelvis displayed thickened cortices with beaking of the left femoral shaft, which was suggestive of an AFF. Following discontinuation of BPs, she underwent prophylactic intra-medullary nailing with which her symptoms improved. Five years later, she presented with similar complaints on the right side. Investigations showed that her bone turnover continued to be suppressed with Cross linked C- Telopeptide of type 1 collagen (CTX) of 165 pg/mL and an X-ray done showed AFF on the right side despite being off BPs. A second intra-medullary nailing was done and on follow-up, she has been symptom-free and independent in her daily activities. Discontinuation of BPs may not prevent the incident second AFF and, therefore, thus warranting long-term follow-up.

Learning points

  • Regular screening and follow-up of patients who receive long-term bisphosphonate (BP) therapy should be done.

  • Discontinuation of BPs does not preclude the possibility of repeated occurrence of a second AFF.

  • Long-term BP therapy warrants regular monitoring and follow-up should an AFF occur

Open access