Patient Demographics > Country of Treatment > Venezuela

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Ruth Mangupli Department of Neurosurgery, Section of Neuroendocrinology, Hospital Universitario de Caracas, Caracas, Venezuela

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Adrian F Daly Department of Endocrinology, Centre Hospitalier Universitaire de Liège, University of Liège, Liège, Belgium

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Elvia Cuauro Department of Neurosurgery, Section of Neuroendocrinology, Hospital Universitario de Caracas, Caracas, Venezuela

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Paul Camperos Department of Neurosurgery, Section of Neuroendocrinology, Hospital Universitario de Caracas, Caracas, Venezuela

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Jaime Krivoy Department of Neurosurgery, Section of Neuroendocrinology, Hospital Universitario de Caracas, Caracas, Venezuela

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Albert Beckers Department of Endocrinology, Centre Hospitalier Universitaire de Liège, University of Liège, Liège, Belgium

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Summary

A 20-year-old man with an 8-year history of progressive enlargement of his hands and feet, coarsening facial features, painful joints and thickened, oily skin was referred for investigation of acromegaly. On examination, the subject was of normal height and weight. He had markedly increased skin thickness around the forehead, eyelids and scalp with redundant skin folds. Bilateral painful knee swelling was accompanied by enlargement of the extremities, and his fingers were markedly clubbed. Routine hematological, biochemical and hormonal blood tests, including GH and IGF-1 were normal. The clinical picture suggested primary hypertrophic osteoarthropathy (PHOA) rather than acromegaly and radiological studies were supportive of this, demonstrating increased subperiosteal bone formation and increased bone density and cortical thickening. There was widespread joint disease, with narrowing of joint spaces, whereas the knees demonstrated effusions and calcification. A skull X-ray revealed calvarial hyperostosis and a normal sellar outline. Family history was negative. Genetic studies were performed on peripheral blood leukocyte DNA for mutations in the two genes associated with PHOA, 15-hydroxyprostaglandin dehydrogenase (HPGD; OMIM: 601688) and solute carrier organic anion transporter family member 2A1 (SLCO2A1; OMIM: 601460). The sequence of HPGD was normal, whereas the subject was homozygous for a novel pathological variant in SLCO2A1, c.830delT, that predicted a frameshift and early protein truncation (p.Phe277Serfs*8). PHOA, also known as pachydermoperiostosis, is a rare entity caused by abnormal prostaglandin E2 metabolism, and both HPGD and SLCO2A1 are necessary for normal prostaglandin E2 handling. High prostaglandin levels lead to bone formation and resorption and connective tissue inflammation causing arthropathy, in addition to soft tissue swelling.

Learning points:

  • The differential diagnosis of enlarged extremities, coarsened facial features, skin changes and increased sweating in suspected acromegaly is quite limited and primary hypertrophic osteoarthropathy (PHOA) is one of the few conditions that can mimic acromegaly at presentation.

  • PHOA is not associated with abnormalities in GH and IGF-1 secretion and can be readily differentiated from acromegaly by hormonal testing.

  • Clubbing in the setting of diffuse enlargement of joints and extremities in addition to skin changes should alert the physician to the possibility of PHOA, as clubbing is not a usual feature of acromegaly. Underlying causes of secondary hypertrophic osteoarthroapthy (e.g. bronchial neoplasia) should be considered.

  • PHOA is a very rare condition caused by abnormalities in prostaglandin metabolism and has two known genetic causes (HPGD and SLCO2A1 mutations).

  • SLCO2A1 gene mutations lead usually to autosomal recessive PHOA; fewer than 50 SLCO2A1 mutations have been described to date and the current case is only the second in a Hispanic patient.

  • Treatment of primary hypertrophic osteoarthropathy is focused on the management of joint pain usually in the form of non-steroidal anti-inflammatory drug therapy.

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Marcos M Lima-Martínez Departamento de Ciencias Fisiológicas, Universidad de Oriente, Ciudad Bolívar, Venezuela
Unidad de Endocrinología, Diabetes, Metabolismo y Nutrición, Anexo A. Centro Médico Orinoco, Avenida Siegart, Ciudad Bolívar 8001, Venezuela

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Ernesto Guerra-Alcalá Departamento de Medicina, Hospital Vargas, Caracas, Venezuela

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Miguel Contreras Centro Médico El Valle, Porlamar, Venezuela

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José Nastasi Servicio de Genética Médica, Universidad de Oriente, Ciudad Bolívar, Venezuela

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Janelle A Noble Children's Hospital Oakland Research Institute, Oakland, California, USA

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Constantin Polychronakos Departments of Paediatrics and Human Genetics, McGill University Health Centre, Montreal, Quebec, Canada

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Summary

Type 1 diabetes mellitus (T1DM) is a chronic disease characterized by the autoimmune destruction of pancreatic β-cells. This paper describes the case of a 19-year-old male patient who presented with glutamic acid decarboxylase (GAD) antibody positive and diabetic ketoacidosis, which mandated intensive insulin treatment. Once the ketoacidosis was controlled, an oral dose of 100 mg of sitagliptin was administered once a day. Ketoacidosis was managed by insulin and insulin daily requirement began to dwindle after one month, until its complete withdrawal at 8 weeks, when partial remission was reached. The patient has now remained on sitagliptin treatment alone for a year, without requiring insulin. The benefit observed with this medication is possibly associated with its immunological effects. Inhibition of dipeptidyl peptidase 4 in animal models deregulates the Th1 immune response, increases secretion of Th2 cytokines, activates CD4+CD25+FoxP3+ regulatory T-cells, and prevents IL17 production.

Learning points

  • The use of insulin-dose-adjusted HbA1c constitutes the best way to define partial remission in T1DM patients.

  • The use of sitagliptin in T1DM patients could help to decrease daily requirement of insulin by delaying β-cell loss and improving endogenous insulin production.

  • The determination of antibodies against insulin, islet cells, and GAD permits differentiation of T1DM patients from those with atypical or ketosis-prone diabetes.

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