Acute Charcot neuropathic osteoarthropathy (CN) is a clinical entity which can easily go unrecognized in its acute early stages due to lack of awareness and unspecific presentation. However, missing early diagnosis can lead to severe complications. We present the case of a 72-year-old male patient who went through the natural course of the disease unnoticed before the very eyes of his physicians leading to a tragic end. We aim to raise awareness for this rare diabetic complication, emphasizing the necessity of early diagnosis and adequate, interdisciplinary treatment.
Clinical signs and symptoms of acute Charcot neuropathic osteoarthropathy (CN).
Importance of early diagnosis and correct treatment.
Central diabetes insipidus (CDI) and several endocrine disorders previously classified as idiopathic are now considered to be of an autoimmune etiology. Dermatomyositis (DM), a rare autoimmune condition characterized by inflammatory myopathy and skin rashes, is also known to affect the gastrointestinal, pulmonary, and rarely the cardiac systems and the joints. The association of CDI and DM is extremely rare. After an extensive literature search and to the best of our knowledge this is the first reported case in literature, we report the case of a 36-year-old male with a history of CDI, who presented to the hospital’s endocrine outpatient clinic for evaluation of a 3-week history of progressive facial rash accompanied by weakness and aching of the muscles.
Accurate biochemical diagnosis should always be followed by etiological investigation.
This clinical entity usually constitutes a therapeutic challenge, often requiring a multidisciplinary approach for optimal outcome.
Dermatomyositis is an important differential diagnosis in patients presenting with proximal muscle weakness.
Associated autoimmune conditions should be considered while evaluating patients with dermatomyositis.
Dermatomyositis can relapse at any stage, even following a very long period of remission.
Maintenance immunosuppressive therapy should be carefully considered in these patients.
Congenital hyperinsulinism (CHI) is an important cause of severe hypoglycaemia in infancy. To correct hypoglycaemia, high concentrations of dextrose are often required through a central venous catheter (CVC) with consequent risk of thrombosis. We describe a series of six cases of CHI due to varying aetiologies from our centre requiring CVC for the management of hypoglycaemia, who developed thrombosis in association with CVC. We subsequently analysed the incidence and risk factors for CVC-associated thrombosis, as well as the outcomes of enoxaparin prophylaxis. The six cases occurred over a 3-year period; we identified an additional 27 patients with CHI who required CVC insertion during this period (n = 33 total), and a separate cohort of patients with CHI and CVC who received enoxaparin prophylaxis (n = 7). The incidence of CVC-associated thrombosis was 18% (6/33) over the 3 years, a rate of 4.2 thromboses/1000 CVC days. There was no difference in the frequency of genetic mutations or focal CHI in those that developed thromboses. However, compound heterozygous/homozygous potassium ATP channel mutations correlated with thrombosis (R2 = 0.40, P = 0.001). No difference was observed in CVC duration, high concentration dextrose or glucagon infused through the CVC. In patients receiving enoxaparin prophylaxis, none developed thrombosis or bleeding complications. The characteristics of these patients did not differ significantly from those with thrombosis not on prophylaxis. We therefore conclude that CVC-associated thrombosis can occur in a significant proportion (18%) of patients with CHI, particularly in severe CHI, for which anticoagulant prophylaxis may be indicated.
CVC insertion is one of the most significant risk factors for thrombosis in the paediatric population.
Risk factors for CVC-associated thrombosis include increased duration of CVC placement, malpositioning and infusion of blood products.
To our knowledge, this is the first study to evaluate CVC-associated thrombosis in patients with congenital hyperinsulinism (CHI).
The incidence of CVC-associated thrombosis development is significant (18%) in CHI patients and higher compared to other neonates with CVC. CHI severity may be a risk factor for thrombosis development.
Although effective prophylaxis for CVC-associated thrombosis in infancy is yet to be established, our preliminary experience suggests the safety and efficacy of enoxoaparin prophylaxis in this population and requires on-going evaluation.
Necrobiosis lipoidica diabeticorum (NLD) is a chronic granulomatous dermatitis generally involving the anterior aspect of the shin, that arises in 0.3–1.2% of patients with diabetes mellitus (). The lesions are often yellow or brown with telangiectatic plaque, a central area of atrophy and raised violaceous borders (). Similar to other conditions with a high risk of scarring including burns, stasis ulcers and lupus vulgaris, NLD provides a favourable environment for squamous cell carcinoma (SCC) formation (). A number of cases of SCC from NLD have been recorded (, , ); however, our search of the literature failed to identify any cases of either metastatic or fatal SCC which developed within an area of NLD. This article describes a patient with established type 1 diabetes mellitus who died from SCC which developed from an area of NLD present for over 10 years. Currently, there are a paucity of recommendations in the medical literature for screening people with NLD for the early diagnosis of SCC. We believe that clinicians should regard non-healing ulcers in the setting of NLD with a high index of clinical suspicion for SCC, and an early biopsy of such lesions should be recommended.
Non-healing, recalcitrant ulcers arising from necrobiosis lipoidica diabeticorum, which fail to heal by conservative measures, should be regarded with a high index of clinical suspicion for malignancy.
If squamous cell carcinoma is suspected, a biopsy should be performed as soon as possible to prevent metastatic spread, amputation or even death.
Our literature search failed to reveal specific recommendations for screening and follow-up of non-healing recalcitrant ulcers in the setting of necrobiosis lipoidica diabeticorum.
A 71-year-old woman with severe right lower leg pain, edema and erythema was presented to the Emergency Department and was found to have an extensive deep vein thrombosis (DVT) confirmed by ultrasound. She underwent an extensive evaluation due to her prior history of malignancy and new hypercoagulable state, but no evidence of recurrent disease was detected. Further investigation revealed pernicious anemia (PA), confirmed by the presence of a macrocytic anemia (MCV=115.8fL/red cell, Hgb=9.0g/dL), decreased serum B12 levels (56pg/mL), with resultant increased methylmalonic acid (5303nmol/L) and hyperhomocysteinemia (131μmol/L), the presumed etiology of the DVT. The patient also suffered from autoimmune thyroid disease (AITD), and both antithyroglobulin and anti-intrinsic factor antibodies were detected. She responded briskly to anticoagulation with heparin and coumadin and treatment of PA with intramuscular vitamin B12 injections. Our case suggests that a DVT secondary to hyperhomocystenemia may represent the first sign of polyglandular autoimmune syndrome III-B (PAS III-B), defined as the coexistent autoimmune conditions AITD and PA. It is important to recognize this clinical entity, as patients may not only require acute treatment with vitamin B12 supplementation and prolonged anticoagulation, as in this patient, but may also harbor other autoimmune diseases.
A DVT can be the first physical manifestation of a polyglandular autoimmune syndrome.
Hyperhomocysteinemia secondary to pernicious anemia should be considered as an etiology of an unprovoked DVT in a euthyroid patient with autoimmune thyroid disease.
Patients with DVT secondary to hyperhomocysteinemia should undergo screening for the presence of co-existent autoimmune diseases in addition to treatment with B12 supplementation and anticoagulation to prevent recurrent thromboembolism.
Peter TaylorDepartment of Diabetes and Endocrinology, Prince Charles Hospital, Cwm Taf Health Board, Merthyr Tydfil, UK Thyroid Research Group, Institute of Molecular and Experimental Medicine, Cardiff University School of Medicine, Cardiff, UK
Onyebuchi E OkosiemeDepartment of Diabetes and Endocrinology, Prince Charles Hospital, Cwm Taf Health Board, Merthyr Tydfil, UK Thyroid Research Group, Institute of Molecular and Experimental Medicine, Cardiff University School of Medicine, Cardiff, UK
TSH receptor antibodies (TRAbs) are the pathological hallmark of Graves’ disease, present in nearly all patients with the disease. Euthyroid Graves’ ophthalmopathy (EGO) is a well-recognized clinical entity, but its occurrence in patients with negative TRAbs is a potential source of diagnostic confusion. A 66-year-old female presented to our endocrinology clinic with right eye pain and diplopia in the absence of thyroid dysfunction. TRAbs were negative, as measured with a highly sensitive third-generation thyrotropin-binding inhibitory immunoglobulin (TBII) ELISA assay. CT and MRI scans of the orbit showed asymmetrical thickening of the inferior rectus muscles but no other inflammatory or malignant orbital pathology. Graves’ ophthalmopathy (GO) was diagnosed on the basis of the clinical and radiological features, and she underwent surgical recession of the inferior rectus muscle with complete resolution of the diplopia and orbital pain. She remained euthyroid over the course of follow-up but ultimately developed overt clinical and biochemical hyperthyroidism, 24 months after the initial presentation. By this time, she had developed positive TRAb as well as thyroid peroxidase antibodies. She responded to treatment with thionamides and remains euthyroid. This case highlights the potential for negative thyroid-specific autoantibodies in the presentation of EGO and underscores the variable temporal relationship between the clinical expression of thyroid dysfunction and orbital disease in the natural evolution of Graves’ disease.
Euthyroid Graves’ ophthalmopathy can present initially with negative thyroid-specific autoantibodies.
Patients with suggestive symptoms of ophthalmopathy should be carefully evaluated for GO with imaging studies even when thyroid function and autoantibodies are normal.
Patients with EGO can develop thyroid dysfunction within 4 years of follow-up underpinning the need for long-term follow-up and continued patient and physician vigilance in patients who have been treated for EGO.
Vertebral osteomyelitis (or spondylodiscitis) is steadily increasing in Western countries and often results from hematogenous seeding, direct inoculation during spinal surgery, or contiguous spread from an infection in the adjacent soft tissue. We present the case of a 67-year-old white patient with type 2 diabetes who went to Hospital for high fever, back pain, and worsening of known infected ulcers in the left foot. Despite intravenous antibiotic treatment and surgical debridement of the foot infection, high fever and lower back pain continued. Bone biopsy and two consecutive blood cultures were positive for Staphylococcus aureus. A spinal magnetic resonance imaging (MRI) was performed, revealing serious osteomyelitis in L4 and L5 complicated by an epidural abscess. Contiguous or other distant focuses of infection were not identified. In this case, diabetic foot could be considered as a primary distant focus for vertebral osteomyelitis. Clinicians should consider vertebral osteomyelitis as a ‘possible’ diagnosis in patients with type 2 diabetes complicated by foot infection that is associated with fever and lower back pain.
Vertebral osteomyelitis is increasing in Western countries, especially in patients with type 2 diabetes.
The primary focus of infection is the genitourinary tract followed by skin, soft tissue, endocarditis, bursitis, septic arthritis, and intravascular access.
Diabetic foot could be a rare primary focus of infection for vertebral osteomyelitis, and, however, vertebral osteomyelitis could be a serious, albeit rare, complication of diabetic foot.
Clinicians should keep in mind the many potential complications of diabetic foot ulcerations and consider vertebral osteomyelitis as a “possible” diagnosis in patients with type 2 diabetes and foot ulcers associated with nonspecific symptoms such as lower back pain.
Early diagnosis and correct management of vertebral osteomyelitis are crucial to improve clinical outcomes.
Functional parathyroid cysts are a rare cause of primary hyperparathyroidism and are often mistaken for thyroid cysts. Systemic lupus erythematosus (SLE) is also a very rare cause of hypercalcemia. We report the case of a 62-year-old woman, who was diagnosed with SLE 30 years ago, presenting with clinical and biochemical features of primary hyperparathyroidism. Laboratory investigation revealed increased serum calcium and parathyroid hormone (PTH) levels; neck ultrasonography (USG) revealed 40×34×26 mm cystic mass in the left lobe of thyroid gland. PTH level in the cysts was >2500 pg/ml, determined by USG-guided fine-needle aspiration (FNA). In this case, no evidence for potential pathogenic association between parathyroid cyst and SLE was uncovered. However, the recognition of this association is very important because the therapeutical strategy is completely different. Operative management is usually straightforward and alleviates symptoms and any biochemical abnormalities caused by the cyst.
Functional parathyroid cysts are the rare cause of primary hyperparathyroidism and are often mistaken for thyroid cysts.
SLE is also a very rare cause of hypercalcemia.
Ultrasound-guided FNA of cystic fluid with assay for PTH level is an accurate method of differentiating parathyroid cyst from thyroid cyst.
Appropriate management of functional parathyroid cysts is surgical excision.