José Miguel Dora

Standards of Medical Care in Diabetes--2008: response to Hirsch, Inzucchi, and Kirkman.

The American Diabetes Association (ADA) has released a Standards of Medical Care in Diabetes Position Statement for 2008 (1). In this document, it is stated that aspirin therapy should be used as a primary prevention strategy in diabetic patients at increased cardiovascular (CV) risk, including those who are >40 years old or have additional risk factors. The recommendation is based on evidence graded “A,” which is defined by the ADA as “evidence from well-conducted, randomized controlled trials that are adequately powered or compelling nonexperimental evidence.” As this indication seemed very …

Hemoplasma infection in HIV-positive patient, Brazil.

Hemotrophic mycoplasmas infect a variety of mammals. Although infection in humans is rarely reported, an association with an immunocompromised state has been suggested. We report a case of a Mycoplasma haemofelis–like infection in an HIV-positive patient co-infected with Bartonella henselae.

Decreased type 1 iodothyronine deiodinase expression might be an early and discrete event in thyroid cell dedifferentation towards papillary carcinoma

Objective  Type I iodothyronine deiodinase (D1) catalyses the 5′ monodeiodination of T4 and is highly expressed in normal human thyroid gland. We have investigated D1 expression in a series of benign and malignant differentiated thyroid neoplasias.

A novel STAT5B mutation causing GH insensitivity syndrome associated with hyperprolactinemia and immune dysfunction in two male siblings.

BACKGROUND GH insensitivity (GHI) syndrome caused by STAT5B mutations was recently reported, and it is characterized by extreme short stature and immune dysfunction. Treatment with recombinant human IGF1 (rhIGF1) is approved for patients with GHI, but the growth response to this therapy in patients with STAT5B mutations has not been reported. OBJECTIVES To report the clinical features, molecular findings, and the short-term growth response to rhIGF1 therapy in patients with STAT5B mutation. SUBJECTS AND METHODS Hormonal and immunological evaluations were performed in two male siblings with GHI associated with atopic eczema, interstitial lung disease, and thrombocytopenic purpura. STAT5B genes were directly sequenced. The younger sibling was treated with rhIGF1 at a dose of 110 microg/kg BID. RESULTS Both siblings had laboratory findings compatible with GHI associated with hyperprolactinemia. Lymphopenia and reduced number of natural killer cells without immunoglobulin abnormalities were observed. STAT5B sequence revealed a homozygous frameshift mutation (p.L142fsX161) in both siblings. The younger sibling (9.9 years of age) was treated with rhIGF1 at appropriate dosage, and he did not present any significant change in his growth velocity (from 2.3 to 3.0 cm/year after 1.5 years of therapy). The presence of a chronic illness could possibly be responsible for the poor result of rhIGF1 treatment. Further studies in patients with STAT5B defects are necessary to define the response to rhIGF1 treatment in this disorder. CONCLUSION GHI associated with immune dysfunction, especially interstitial lung disease, and hyperprolactinemia is strongly suggestive of a mutation in STAT5B in both sexes.

Cutaneous Cryptococccosis Due to Cryptococcus gattii in Immunocompetent Hosts: Case Report and Review

Cutaneous cryptococcosis caused by C. gattii, in immunocompent patients is a rare manifestation of disease, and may be one of the first manifestations of disseminated cryptococcosis. We report a case of disseminated cryptococcosis caused by Cryptococcus gattii presenting as cutaneous lesions in an immunocompetent patient. Previously to our report, only five cases of cutaneous involvement by Cryptococcus gattii in immunocompetent patients have been reported in the literature. Risk factors for C. gattii infection included exposure to the eucalypt reservoirs in tropical and subtropical areas. Skin involvement corresponded to the disseminated form of cryptococcosis in the majority of patients, and commonly affected the face and neck with different morphologies including papules, pustules, plaques, ulcers, subcutaneous masses, cellulitis or acneiform lesions. Due to the severity of this infection and the life threatening condition that it represents, clinicians must be aware that cutaneous involvement may be one of the first manifestations of disseminated cryptococcosis caused by C. gattii especially in patients living and coming from endemic areas.

Lack of imatinib-induced thyroid dysfunction in a cohort of non-thyroidectomized patients.

Lack of imatinib-induced thyroid dysfunction in a cohort of non-thyroidectomized patients Jose Miguel Dora, Murilo Anderson Leie, Bruno Netto, Laura Maria Fogliatto, Lucia Silla, Felipe Torres and Ana Luiza Maia Endocrine Division, Thyroid Section, Hospital de Clinicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil, Hematology Division and Radiology Division, Hospital de Clinicas de Porto Alegre, Porto Alegre, Brazil

Toxic Cardiomyopathy leading to fatal acute cardiac failure related to vandetanib: a case report with histopathological analysis

CONTEXT Medullary thyroid carcinoma (MTC) accounts for 3-4% of all malignant thyroid neoplasias. Vandetanib, a tyrosine kinase inhibitor (TKI) targeting vascular endothelial growth factor receptor 2, epidermal growth factor receptor, and RET, has been approved by the FDA for the treatment of locally advanced or metastatic MTC. The heart seems to be particularly susceptible to adverse effects associated with TKI therapy, and virtually all TKIs have been associated with cardiovascular events. CLINICAL PRESENTATION We report the case of a patient with metastatic MTC who was enrolled in the Phase III clinical study (NCT00410761) and presented a favorable response to vandetanib therapy, displaying marked decrease in the level of serologic tumor markers and shrinkage of metastatic lesions. After 14 months of therapy, the patient developed a fatal cardiac failure. Myocardial infarction was excluded by serial measurements of specific cardiac markers (serial troponin-T measurements varied from 0.037 to 0.042 ng/ml) and serologic tests for Chagas disease were negative. Postmortem examination of the heart revealed cardiomyocyte hypertrophy and marked myocyte degeneration in the subendocardial zones and papillary muscles of the myocardium. These pathological changes are similar to those observed in TKI-treated rats and are suggestive of drug-induced cardiotoxicity. CONCLUSION This case illustrates a previously unreported serious vandetanib-related adverse effect and highlights the need for close monitoring of patients under TKI therapy in order to identify early signs of congestive heart failure or myocardium damage.

D2 Thr92Ala and PPARγ2 Pro12Ala polymorphisms interact in the modulation of insulin resistance in type 2 diabetic patients.

Type 2 deiodinase (D2) converts T4 into its active metabolite T3, an essential step in thyroid metabolism. A Thr92Ala polymorphism in the gene encoding D2 has been inconsistently associated with insulin resistance (IR). Recently, it was reported that the D2 Thr92Ala (rs225014) and the peroxisome proliferator‐activated receptor (PPAR) γ2 Pro12Ala (rs1801282) polymorphisms interact in the modulation of metabolic syndrome in nondiabetic subjects. Here, we investigated the effect of both polymorphisms, isolated or in combination, on IR in patients with type 2 diabetes mellitus (DM2). The D2 Thr92Ala and PPARγ2 Pro12Ala polymorphisms were genotyped in 721 DM2 patients. IR was evaluated using the homeostasis model assessment—IR (HOMAIR) index in a subgroup of 246 DM2 subjects. The frequencies of D2 Ala92 and PPARγ2 Ala12 variants were 0.390 and 0.074, respectively. Patients carrying D2 Ala/Ala genotype had a higher fasting plasma insulin and HOMAIR index as compared to patients carrying Thr/Ala or Thr/Thr genotypes (P = 0.022 and P = 0.001, respectively). A significant synergistic effect was observed between D2 Thr92Ala and PPARγ2 Pro12Ala polymorphisms on HOMAIR index, with carriers of both D2 Ala/Ala genotype and PPARγ2 Ala12 allele showing the highest HOMAIR values, after adjusting for age, gender, BMI, and use of medication for DM2 (P = 0.010). In conclusion, DM2 patients harboring both D2 Ala/Ala genotype and PPARγ2 Ala12 allele seem to present more severe IR than those with other D2/PPARγ2 genotype combinations. These findings suggest that these polymorphisms interact in the IR modulation, which may constitute a potential therapeutic target.

Type 2 Iodothyronine Deiodinase Is Highly Expressed in Medullary Thyroid Carcinoma

Type II deiodinase (D2) plays a critical role in controlling intracellular T3 concentration and early studies indicated a follicular but not a parafollicular C-cell origin of D2 activity in the thyroid gland. Here, we show that D2 is highly expressed in human medullary thyroid carcinoma (MTC), a tumor that arises from the C-cells. D2 transcripts were detected in all MTC samples obtained from 12 unselected MTC patients and the levels of D2 activity were comparable to those found in surrounding normal follicular tissue (0.41+/-0.10 fmol min mg protein vs. 0.43+/-0.41 fmol min mg protein, P=0.91). Additional analysis in the TT cells, a human MTC cell line, demonstrated that the D2 expression is downregulated by thyroid hormones and enhanced by cAMP analogs and dexamethasone. The thyroid hormone receptor alpha1 and beta isoforms were also detected in all MTC samples and in TT cells, thus suggesting a potential role of T3 locally produced by D2 in this neoplastic tissue.

Cerebral syphilitic gumma in HIV-infected patients: case report and review.

Neurosyphilis presenting as a cerebral gumma is an uncommon event. To date there are seven cases of cerebral gumma reported in human immunodeficiency virus (HIV)-infected patients. We describe a HIV-infected patient with neurosyphilis presenting as an expanding central nervous system lesion and unremarkable cerebrospinal fluid analysis. This case report illustrates the clinical and therapeutic aspects of syphilitic gumma in HIV-infected patients.