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Fahad Al-Juraibah College of Medicine, King Saud bin Abdulaziz University for Health Science, Riyadh, Saudi Arabia
Ministry of National Guard – Health Affairs, Riyadh, Saudi Arabia

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Adnan Al Shaikh College of Medicine, King Saud bin Abdulaziz University for Health Science, Riyadh, Saudi Arabia
Department of Paediatrics, Endocrine Division, Jeddah, Saudi Arabia

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Afaf Al-Sagheir King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia

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Amir Babiker College of Medicine, King Saud bin Abdulaziz University for Health Science, Riyadh, Saudi Arabia
Ministry of National Guard – Health Affairs, Riyadh, Saudi Arabia

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Asma Al Nuaimi Department of Endocrinology and Diabetes, Sheikh Khalifa Medical City, Abu Dhabi, United Arab Emirates

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Ayed Al Enezi Al Jahra Hospital, Al Jahra, Kuwait

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George S Mikhail Al Jahra Hospital, Al Jahra, Kuwait

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Hassan A Mundi Dubai Hospital, Dubai, United Arab Emirates

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Hubert K Penninckx American Hospital, Dubai, United Arab Emirates

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Huda Mustafa Diabetes and Endocrinology Centre, HealthPlus Network, Abu Dhabi, United Arab Emirates

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Majid Al Ameri Department of Endocrinology and Diabetes, Sheikh Khalifa Medical City, Abu Dhabi, United Arab Emirates

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Mohamed Al-Dubayee College of Medicine, King Saud bin Abdulaziz University for Health Science, Riyadh, Saudi Arabia
Ministry of National Guard – Health Affairs, Riyadh, Saudi Arabia

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Nadia S Ali Dubai Hospital, Dubai, United Arab Emirates

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Nagla Fawzy Al Jahra Hospital, Al Jahra, Kuwait
Faculty of medicine, Sohag University, Egypt

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Sameer Al Shammari Al Jahra Hospital, Al Jahra, Kuwait

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Tarek Fiad Department of Endocrinology and Diabetes, Sheikh Khalifa Medical City, Abu Dhabi, United Arab Emirates

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Summary

X-linked hypophosphatemic rickets (XLH), the most prevalent form of inherited hypophosphatemic rickets, is caused by loss-of-function mutations in the gene encoding phosphate-regulating endopeptidase homolog, X-linked (PHEX). This case series presents 14 cases of XLH from Gulf Cooperation Council (GCC) countries. The patients’ medical history, biochemical and radiological investigative findings, as well as treatment responses and side effects from both conventional and burosumab therapy, are described. Cases were aged 2–40 years at diagnosis. There were two male cases and 12 female cases. All cases were treated with conventional therapy which resulted in a lack of improvement in or worsening of the clinical signs and symptoms of rickets or biochemical parameters. Side effects of conventional therapy included nausea, diarrhea, abdominal pain, nephrocalcinosis, and hyperparathyroidism, which affected the patients’ quality of life and adherence to treatment. In the 10 patients treated with burosumab, there was a marked improvement in the biochemical markers of rickets, with a mean increase in serum phosphate of +0.56 mmol/L and tubular maximum phosphate reabsorption (TmP) to glomerular filtration rate (GFR) ratio (TmP/GFR) of +0.39 mmol/L at 12 months compared to baseline. Furthermore, a mean decrease in serum alkaline phosphatase (ALP) of −80.80 IU/L and parathyroid hormone (PTH) of −63.61 pmol/L at 12 months compared to baseline was observed in these patients. Additionally, patients treated with burosumab reported reduced pain, muscle weakness, and fatigue as well as the ability to lead more physically active lives with no significant side effects of treatment.

Learning points

  • Conventional therapy resulted in a suboptimal response, with a lack of improvement of clinical signs and symptoms.

  • Side effects of conventional therapy included nausea, diarrhea, abdominal pain, nephrocalcinosis, and hyperparathyroidism, which affected the patients’ quality of life and adherence to treatment.

  • Burosumab demonstrated marked improvements in the biochemical markers of rickets, in addition to reducing pain, muscle weakness, and fatigue.

  • There were no significant side effects associated with burosumab therapy.

Open access
R K Dharmaputra Cairns and Hinterland Hospital and Health Service, Cairns, Queensland, Australia
Department of Endocrinolgy and Diabetes, Cairns Hospital, Cairns, Queensland, Australia
Cairns Diabetes Centre, Cairns, Queensland, Australia
Gold Coast Hospital and Health Service, Gold Coast, Cairns, Queensland, Australia

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C M Piesse Cairns and Hinterland Hospital and Health Service, Cairns, Queensland, Australia
Department of Endocrinolgy and Diabetes, Cairns Hospital, Cairns, Queensland, Australia
Cairns Diabetes Centre, Cairns, Queensland, Australia

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S Chaubey Cairns and Hinterland Hospital and Health Service, Cairns, Queensland, Australia
Department of Endocrinolgy and Diabetes, Cairns Hospital, Cairns, Queensland, Australia
Cairns Diabetes Centre, Cairns, Queensland, Australia

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A K Sinha Cairns and Hinterland Hospital and Health Service, Cairns, Queensland, Australia
Department of Endocrinolgy and Diabetes, Cairns Hospital, Cairns, Queensland, Australia
Cairns Diabetes Centre, Cairns, Queensland, Australia

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H C Chiam Cairns and Hinterland Hospital and Health Service, Cairns, Queensland, Australia
Department of Surgery, Cairns Hospital, Cairns, Queensland, Australia

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Summary

A 48-year-old Asian male, presented to the hospital for an elective total thyroidectomy in the context of 6.3 cm thyroid nodule. The fine needle aspiration cytology of the nodule confirmed papillary thyroid cancer (PTC) with some atypical histiocytes. He has a history of idiopathic arginine vasopressin deficiency (AVP-D) and has been taking oral DDAVP 100 µg daily, self-adjusting the dose based on thirst and polyuria. Additionally, he also has a history of recurrent spontaneous pneumothorax. His total thyroidectomy was aborted due to significant intraoperative bleeding, and his admission was further complicated by post-operative hyponatraemic seizure. Thyroid histology revealed the diagnosis of Langerhans cell histiocytosis (LCH), and further investigation with contrast CT demonstrated multi-organ involvement of the thyroid, lungs, and bones.

Learning points

  • Langerhans cell histiocytosis (LCH) is a condition that can affect one or more organ systems, including the pituitary, where it can present as AVP deficiency. Strict monitoring of fluid balance, as well as serial monitoring of serum sodium, is essential in all patients with AVP-D in the perioperative setting.

  • Iatrogenic hyponatraemic seizure is an uncommon but serious complication of DDAVP treatment in hospitalised patients with AVP-D. DDAVP dosing must be carefully monitored.

  • LCH with multisystem involvement is an important mimic for metastatic conditions, and histological diagnosis is essential to guide treatment and prognosis.

  • Although LCH without bone marrow involvement is unlikely to increase the risk of bleeding, its effect on tissue integrity may make surgery more challenging.

  • BRAF-V600E mutation is an important driver mutation and a potential therapeutic target in the treatment of LCH.

Open access
Albert Vu Division of Endocrinology & Metabolism, Faculty of Medicine & Dentistry, University of Alberta, Edmonton, Alberta, Canada

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Constance Chik Division of Endocrinology & Metabolism, Faculty of Medicine & Dentistry, University of Alberta, Edmonton, Alberta, Canada

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Sarah Kwong Division of Endocrinology & Metabolism, Faculty of Medicine & Dentistry, University of Alberta, Edmonton, Alberta, Canada

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Summary

Non-islet cell tumour hypoglycemia (NICTH), typically mediated by insulin-like growth factor 2 (IGF-2), is a rare but highly morbid paraneoplastic syndrome associated with tumours of mesenchymal or epithelial origin. Outside of dextrose administration and dietary modification which provide transient relief of hypoglycemia, resection of the underlying tumour is the only known cure for NICTH. Available medical therapies to manage hypoglycemia include glucocorticoids, recombinant growth hormone, and pasireotide. We report two cases of IGF-2 mediated hypoglycemia. The first was managed surgically to good effect, highlighting the importance of a timely diagnosis to maximise the likelihood of a surgical cure. The second patient had unresectable disease and was managed medically, adding to a growing number of cases supporting the efficacy of glucocorticoids and recombinant growth hormone in NICTH.

Learning points

  • Recurrent fasting hypoglycemia in the setting of a malignancy should raise suspicion of non-islet cell tumour hypoglycemia (NICTH), which is typically mediated by IGF-2.

  • The initial workup for NICTH should include a serum glucose, C-peptide, insulin, insulin antibodies, beta-hydroxybutyrate, IGF-2, IGF-1, and sulphonylurea screen during a spontaneous or induced hypoglycemic episode.

  • An IGF-2/IGF-1 ratio above 10 is highly suggestive of IGF-2-mediated hypoglycemia if the IGF-2 level is normal or elevated. False positives may be seen with sepsis and cachexia as both IGF-2 and IGF-1 are subnormal in these cases. A low IGF binding protein 3 (IGFBP3), such as in renal failure, may also result in a falsely normal or low IGF-2/IGF-1 ratio.

  • Surgical resection of the associated tumour is curative in most NICTH cases.

  • When the tumour is unresectable, moderate-dose glucocorticoids, low-dose glucocorticoids in combination with recombinant growth hormone, and pasireotide are medical therapies with promising results in controlling NICTH.

Open access
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.

Open access
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