Follow-up of patients treated with retinoic acid for the control of radioiodine non-responsive advanced thyroid carcinoma

During thyroid tumor progression, cellular de-differentiation may occur and it is commonly accompanied by metastatic spread and loss of iodine uptake. Retinoic acid (RA) administration might increase iodine uptake in about 40 percent of patients, suggesting that RA could be a promising therapeutic option for radioiodine non-responsive thyroid carcinoma, although a prospective study with a long-term follow-up has not been reported. This was a clinical prospective study assessing the value of 13-cis-RA in patients with advanced thyroid carcinoma and its impact on major outcomes such as tumor regression and cancer-related death with a long-term follow-up of patients submitted to radioiodine (131I) therapy after RA administration. Sixteen patients with inoperable disease and no significant radioiodine uptake on post-therapy scan were selected. Patients were treated orally with 13-cis-RA at a dose of 1.0 to 1.5 mg·kg-1·day-1 for 5 weeks and then submitted to radioiodine therapy (150 mCi) after thyroxine withdrawal. A whole body scan was obtained 5 to 7 days after the radioactive iodine therapy. RECIST criteria were used to evaluate the response. An objective partial response rate was observed in 18.8 percent, a stable disease rate in 25 percent and a progression disease rate in 56.2 percent. Five patients died (62.5 percent) in the group classified as progression of disease. Progression-free survival rate (PFS) ranged from 72 to 12 months, with a median PFS of 26.5 months. RA may be an option for advanced de-differentiated thyroid cancer, due to the low rate of side effects.

Follow-up of patients treated with retinoic acid for the control of radioiodine non-responsive advanced thyroid carcinoma.

During thyroid tumor progression, cellular de-differentiation may occur and it is commonly accompanied by metastatic spread and loss of iodine uptake. Retinoic acid (RA) administration might increase iodine uptake in about 40% of patients, suggesting that RA could be a promising therapeutic option for radioiodine non-responsive thyroid carcinoma, although a prospective study with a long-term follow-up has not been reported. This was a clinical prospective study assessing the value of 13-cis-RA in patients with advanced thyroid carcinoma and its impact on major outcomes such as tumor regression and cancer-related death with a long-term follow-up of patients submitted to radioiodine (¹³¹I) therapy after RA administration. Sixteen patients with inoperable disease and no significant radioiodine uptake on post-therapy scan were selected. Patients were treated orally with 13-cis-RA at a dose of 1.0 to 1.5 mg·kg⁻¹·day⁻¹ for 5 weeks and then submitted to radioiodine therapy (150 mCi) after thyroxine withdrawal. A whole body scan was obtained 5 to 7 days after the radioactive iodine therapy. RECIST criteria were used to evaluate the response. An objective partial response rate was observed in 18.8%, a stable disease rate in 25% and a progression disease rate in 56.2%. Five patients died (62.5%) in the group classified as progression of disease. Progression-free survival rate (PFS) ranged from 72 to 12 months, with a median PFS of 26.5 months. RA may be an option for advanced de-differentiated thyroid cancer, due to the low rate of side effects.

Treatment of subclinical hypothyroidism reduces atherogenic lipid levels in a placebo-controlled double-blind clinical trial.

Many studies have found clinical and metabolic alterations in subclinical hypothyroidism, however, there are disagreements about the benefits of levothyroxine therapy. The objective of the present study was to analyze the effects of 6 months of treatment on the lipid profile of patients with subclinical hypothyroidism. A randomized double blind, placebo-controlled clinical assay was conducted. Sixty patients were enrolled in stratified random allocation by TSH levels that generated similar groups in average: free thyroxine levels, lipid levels, age, clinical score, and sedentary. At 6 months, 18 patients in the levothyroxine and 20 in the placebo group were reevaluated and a fall in all atherogenic lipid variables was observed with treatment. The TC and LDL-c variations (-22.6+/-37.2 and -18.5+/-34.6 mg/dl, respectively) in the group that received LT4 were statistically different (p=0.023 and p=0.012) from those occurring in the placebo group (+7.3+/-37.1 and +14.7+/-40.6 mg/dl). Baseline characteristics associated with better improvement in the levels of TC and LDL-c were the presence of TPO-Ab, TSH levels >8.0 microUI/ml, Body Mass Index >or=25 kg/m2, and the presence of menopause. We concluded that treatment with dose-adjusted levothyroxine reduced atherogenic lipid levels in some patients. Further studies to determine the effects of LT4 replacement in specific subgroups of SH patients are still necessary, especially in patients with TSH <8.0 microUI/ml.

Insulin-like growth factor I levels during growth hormone (GH) replacement in GH-deficient adults: a gender difference.

To evaluate the variation of serum IGF-1 levels during GH replacement and observe gender differences, 29 adults with GH deficiency (mean age 42.5 +/- 10.1 year), were studied. Serum IGF-1 was assessed every 4 weeks during the titration period and afterwards every 3 months of GH therapy. At baseline 77.7% of women and 45.4% of men had serum baseline IGF-1 levels below the lower limit of normal age-related reference range. The time to reach the maintenance dose was lower in men than women (p < 0.05). There was an increase in IGF-1 levels after one year of GH therapy, significant only in men (p < 0.01). IGF-1 concentrations were higher in men than women (p < 0.05), at the 12th and 18th months of GH therapy. GH dose was reduced by 25% in men (p < 0.01). At the end of the study the mean GH dose was lower in men than in women (p < 0.05). The factor responsible for these findings is not known, however a possible role of androgens has been suggested.

Retinoic acid in patients with radioiodine non-responsive thyroid carcinoma.

De-differentiated thyroid carcinoma is characterized by loss of thyroid-specific functions and properties. The therapeutic options for this type of thyroid cancer are limited and generally not efficient. Recent studies with retinoic acid (RA) have shown that this drug can induce re-differentiation of the thyrocyte and tumor regression after 131I therapy. The aim of the present study was to assess the effects of RA therapy in patients with extensive thyroid tumor involvement, which lost radioiodine uptake ability. A total of 5 patients (1 follicular carcinoma, 3 papillary carcinomas and 1 poorly differentiated carcinoma) were treated with isotretinoin (1.0 to 1.5 mg/kg/day) for 5 weeks and then submitted to radioiodine therapy. Three parameters for assessment of RA effects were established: a) reduction of serum thyroglobulin levels; b) increment of the post-therapeutic dose radioiodine uptake; c) tumor size regression after therapy. All patients completed the treatment and the most frequent side effects were dry skin and lips and hypertriglyceridemia. One patient showed satisfactory response (2 or more of the 3 criteria were reached) and a new cycle of RA was given. In two, just a partial response (1 criterion) was seen and the other patients did not respond. Based on these results, isotretinoin might be an option for de-differentiated thyroid cancer, with low rate of severe side effects, especially when compared with cytotoxic drugs. Aggressive thyroid cancer frequently needs multimodal adjuvant therapy.

Orbital lymphoma misdiagnosed as Graves' ophthalmopathy.

OBJECTIVE: To describe a case of bilateral orbital lymphoma mistakenly diagnosed as Graves' ophthalmopathy. METHODS: We present a case report, with laboratory data and photographic documentation, and discuss the differential diagnosis in patients with orbital masses. RESULTS: A 65-year-old man with bilateral exophthalmos and substantial weight loss was referred to the Endocrine Clinic for evaluation of possible Graves' disease. A 6-cm mass was detected in the left axilla. Biopsy of this mass revealed the histopathologic diagnosis of anaplastic B-cell lymphoma. Treatment with intrathecally administered methotrexate and orally administered dexamethasone promptly resulted in decreased proptosis. CONCLUSION: The most frequent cause of bilateral proptosis is Graves' ophthalmopathy, and when it is associated with weight loss in an elderly patient, the initial diagnostic consideration is thyrotoxic Graves' disease. This case should remind physicians that bilateral orbital lymphoma, although uncommon, may mimic Graves' ophthalmopathy.

A case of laryngeal carcinoma appearing as a goiter.

We describe the case of a 41-year-old man with hoarseness and a hard, fixed mass in the anterior cervical region. He was referred to our endocrinology service for evaluation of possible thyroid cancer. The results of laboratory tests of thyroid function were normal. Indirect laryngoscopy revealed paralysis of the left hemilarynx and the presence of a large vegetating lesion. Computed tomography of the neck disclosed the presence of a mass in the anterior region, along with invasion and destruction of the adjacent structures. The cytologic diagnosis was established by analysis of a fine-needle aspiration biopsy specimen, which revealed a squamous cell carcinoma. The final diagnosis was carcinoma of the larynx.

Hipoglicemia associada a tumor extrapancreático / Hypoglycemya associated with extra-pancreatic tumor

Os autores descrevem o caso de uma mulher de 51 anos, portadora de massa torácica extrapulmonar, que apresentou episódios de hipoglicemia sintomática dejejum. Esse quadro reverteu após a retirada cirúrgica de um mesotelioma pleural benigno, que pesava 1.800g. Sao discutidos os mecanismos de hipoglicemia tumoral extrapancreática em face de níveis indetectáveis de insulina, como em nosso caso.

Abnormal proteins in the cerebrospinal fluid of a patient with Creutzfeldt-Jakob disease following administration of human pituitary growth hormone.

A Brazilian case of Creutzfeldt-Jakob disease in a hypopituitary patient who had received cadaver-derived human pituitary growth hormone between 1968 and 1977 is reported. The clinical diagnosis was confirmed during his lifetime by the demonstration of two abnormal 30-kDa proteins in the cerebrospinal fluid by two-dimensional gel electrophoresis. These proteins, characteristic of Creutzfeldt-Jakob disease, present isoelectric points of 5.1 and 5.2. Furthermore, both proteins migrate as doublets, each one displaying a molecular weight variant of about 29-kDa. This is one of 16 cases of the disease associated to therapy with cadaver-derived human growth hormone and one of the few examples among such cases of confirmation of the clinical diagnosis by biochemical characterization of abnormal proteins in the cerebrospinal fluid.

Abnormal proteins in the cerebrospinal fluid of a patient with Creutzfeldt-Jakob disease following administration of human pituitary growth hormone

A Brazilian case of Creutzfeldt-Jakob disease in a hypopituitary patient who had received cadaver-derived human pituitary growth hormone between 1968 and 1977 is reported. The clinical diagnosis was confirmed during his lifetime by the demonstration of two abnormal 30-kDa proteins in the cerebrospinal fluid by two-dimensional gel electrophoresis. These proteins, characteristic of Creutzfeldt-Jakob disease, present isoelectric points of 5.1 and 5.2. Furthermore, both proteins migrate as doublets, each one displaying a molecular weight variant of about 29-kDa. This is one of 16 cases of the disease associated to therapy with cadaver-derived human growth hormone and one of the few examples among such cases of confirmation of the clinical diagnosis by biochemical characterization of abnormal proteins in the cerebrospinal fluid

Computed tomography and ultrasonography of the adrenal glands in paracoccidioidomycosis. Comparison with cortisol and aldosterone responses to ACTH stimulation.

Fifteen patients with proven disseminated paracoccidioidomycosis (PCM) had computed tomography (CT) and ultrasonography (US) performed to evaluate the form, shape, density and size of their adrenal glands. Plasma and urinary cortisol were determined and adrenal reserve assessed by measuring the cortisol and aldosterone responses to synthetic ACTH. The adrenal CT showed unilateral lesions in two cases and bilateral in another four. The US study showed more frequent alterations, unilateral in seven and bilateral in three subjects. Combining both methods increased the sensitivity to 85% of the cases. All patients had normal plasma cortisol concentrations and normal or increased urinary cortisol excretion. Plasma aldosterone concentration was also normal except in one patient with hypokalemia. Seven patients showed diminished cortisol responses, five had subnormal aldosterone responses and in five plasma aldosterone concentration increased more than normally after stimulation by ACTH. There was an incidence of limited adrenal reserve in 53% of the patients on ACTH stimulation. No correlation was evident between the disorders in adrenal steroid responses to ACTH and changes in morphology revealed by CT and/or US.