Viviane Canadas

ADRENAL INCIDENTALOMAS: DIAGNOSTIC EVALUATION AND LONG-TERM FOLLOW-UP

OBJECTIVE To evaluate the cause and the clinical and laboratory features of adrenal incidentalomas (AI) in 52 patients and to assess the evolution of nonsurgically treated lesions during long-term follow-up. METHODS We retrospectively analyzed the medical records of 52 patients with AI undergoing routine follow-up in 2 Brazilian endocrine centers. RESULTS In our study group, nonfunctioning adenomas were the most frequent cause of AI (42%), followed by cortisol-secreting adenomas (15%), metastatic disease (10%), pheochromocytomas (8%), myelolipomas (6%), cysts (6%), carcinomas (4%), lymphomas (4%), tuberculosis (4%), and aldosteronoma (2%). Only 13 lesions (25%) were functioning (8 cortisol-secreting adenomas, 4 pheochromocytomas, and 1 aldosteronoma). Carcinomas were the largest adrenal masses (mean diameter, 11.7 +/- 1.3 cm). With the exception of 1 pheochromocytoma, 1 cyst, and 1 myelolipoma, all AI larger than 6 cm were carcinomas. During follow-up of 21 patients with nonsurgically treated AI for 6 to 36 months (mean, 24.8 +/- 8.9), no patient had tumor reduction or disappearance. After 12 months of follow-up, however, a 45-year-old woman had adrenal mass enlargement from 3.2 cm to 4.4 cm; the excised lesion proved to be an adenoma. Moreover, evidence of cortisol hypersecretion developed after 24 months of follow-up in a 30-year-old man with a 3.5-cm adenoma in the left adrenal gland. CONCLUSION Our findings demonstrate that most AI are nonfunctioning benign lesions and emphasize the need for long-term follow-up of patients with conservatively managed lesions, in light of the potential for evolution to hormonal hypersecretion or tumor growth.

Prevalência da macroprolactinemia entre 115 pacientes com hiperprolactinemia

Macroprolactinemia is characterized by the predominance in the serum of macroprolactin, a prolactin (PRL) with high molecular mass and low biological activity that does not need treatment. The prevalence of macroprolactinemia was evaluated in 115 consecutive patients with hyperprolactinemia. Among them, 19 (16.5%) had solely macroprolactinemia, 4 (3.5%) polycystic ovary syndrome, 7 (6.1%) acromegaly, 8 (6.9%) idiopathic hyperprolactinemia, 10 (8.6%) primary hypothyroidism, 14 (12.2%) clinically non-functioning pituitary adenomas, 20 (17.4%) drug-induced hyperprolactinemia and 33 (28.7%) prolactinomas. The diagnosis of macroprolactinemia was established by the demonstration of a PRL recovery < 30% after treatment of sera with polyethylene glycol. Among the 19 patients with isolated macroprolactinemia, 16 (84.2%) were female and 12 (63.2%) were asymptomatic, while 4 (21%) presented with oligomenorrhea and 3 (15.8%) with galactorrhea. In contrast, only 11.5% of individuals with other causes of hyperprolactinemia were asymptomatic (p< 0.001). Prolactin levels in cases of macroprolactin ranged from 45.1 to 404 ng/mL (mean 113.3 +/- 94.5) but in 15 (78.9%) were < 100 ng/mL. Our findings demonstrate that macroprolactinemia is a common condition and, therefore, we suggest that it should be routinely screened in patients with hyperprolactinemia.

Tratamento medicamentoso dos tumores hipofisários. Parte I: prolactinomas e adenomas secretores de GH

The recent development of new drugs, particularly the somatostatin analogues (SRIFa), represents a great advance in the therapy of pituitary tumours. SRIFas are very effective in normalizing GH and IGF-1 levels in acromegaly and may be an effective alternative to transsphenoidal surgery. However, their usefulness as primary therapy for acromegaly is limited due to the small effect on tumour size. According to early data from clinical trials, pegvisomant, a GH receptor antagonist, seems to be a promising therapeutic tool in the management of acromegalic patients. This drug induces significant clinical improvement and normalization of IGF-1 levels in nearly all patients. However, it does not induce tumor shrinkage. Dopamine agonists (DA) are the preferred therapy for both symptomatic microprolactinomas and macroprolactinomas; their use result in normalization of prolactin levels and tumor shrinkage in most treated patients. They also may be useful in acromegaly, mainly in patients whose adenoma co-secrete prolactin and those with mild elevation of GH and IGF-1 levels. Due to its greater effectiveness and better tolerability, cabergoline represents the DA of choice for the management of prolactinomas and acromegaly.

Avaliação da radioiodoterapia com doses fixas de 10 e 15 mCi em pacientes com doença de graves

Evaluation of Radioiodine Therapy with Fixed Doses of 10 and 15 mCi in Patients with Graves’ Disease. The treatment options for the hyperthyroidism of Graves’ disease are antithyroid drugs, surgery and radioiodine, none of which is considered ideal, as they do not act directly on the etiopathogenesis of the disease. Radioiodine has been increasingly used as the treatment of choice because it is a safe and definitive therapy whose administration is very easy. Some authors prefer to administer higher doses in order to deliberately induce hypothyroidism, while others recommend lower doses that result in a lower incidence of hypothyroidism and a greater incidence of euthyroidism. There is no consensus for the optimal regimen of fixed doses to be used and this is the main focus of the present study, where doses of 10 and 15 mCi of 131I were compared. Among the 164 patients analyzed, 61 (37.2%) were submitted to 10 mCi and 103 (62.8%) to 15 mCi. In the longitudinal analysis it was observed that remission of the hyperthyroidism was statistically different in the sixth month (p < 0.001), being higher in the group that used the dose of 15 mCi, but similar in both groups at 12 and 24 months. It may be concluded that the administration of fixed doses of 10 and 15 mCi of 131 I brought about a similar remission of the hyperthyroidism after 12 months of treatment. Moreover, the remission rate of the hyperthyroidism had no association with age, sex or previous therapy with antithyroid drugs. (Arq Bras Endocrinol Metab 2007;51/7:1069-1076)

Comparison of metformin, gliclazide MR and rosiglitazone in monotherapy and in combination for type 2 diabetes

OBJECTIVE To compare the efficacy and tolerability of metformin, rosiglitazone and gliclazide MR as monotherapy and in combination in the treatment of type 2 diabetes. SUBJECTS AND METHODS 250 patients treated with oral antidiabetic agents for at least 24 weeks in monotherapy or in combination therapy were included in this retrospective study. RESULTS As monotherapy the reduction of fasting plasma glucose (FPG), postprandial glycemia (PPG) and HbA1c was similar with the three drugs after 24 weeks. Among patients on combination therapy, the reduction in HbA1c, FPG and PPG was significantly lower with rosiglitazone plus metformin, as compared to metformin plus gliclazide MR or gliclazide MR plus rosiglitazone. Patients treated with rosiglitazone achieved less favorable changes in lipid profile. CONCLUSION In monotherapy all drugs were equally effective in improving glycemic control, whereas the combination of metformin plus gliclazide MR provided the best results concerning the improvement of both, glycemic control and lipid profile.

Tratamento medicamentoso dos tumores hipofisários. parte II: adenomas secretores de ACTH, TSH e adenomas clinicamente não-funcionantes

This article reviews the potencial role of medical treatment for both ACTH and TSH secreting pituitary adenomas, as well as for clinically non-functionning pituitary adenomas (CNFPA). Metyrapone, mitotane and ketoconazole (preferable for causing less side-effects) are the most effective drugs for the control of hypercortisolism but none of them surpasses the efficacy of transsphenoidal surgery (TSA). Drug therapy in Cushings disease is therefore better indicated for patients waiting for the full effect of radiotherapy or, as an alternative to radiotherapy, for cases of TSA failure as well as patients that refuse or have clinical limitations to surgery. Other potential indications for medical treatment in Cushings disease include elderly patients with microadenomas or small macroadenomas, as well as cases associated to an empty sella. Concerning TSH-secreting adenomas, somatostatin analogues (SRIFa) lead to normalization of thyroid hormones in up to 95% of treated patients. Therefore they may represent an useful tool for long-term treatment of such rare tumors in case of surgery failure or as primary therapy for selected cases. Occasionaly, dopamine agonists (DA), especially cabergoline, may also be efficacious in normalizing hormone levels. In contrast, DA and SRIFa rarely induce significant tumor shrinkage in patients with CNFPA. Thus, these drugs should be considered particularly for patients who are poor candidates for surgery or in whom surgery and radiotherapy have failed to control the disease.

Effectiveness of adding vildagliptin to the treatment of diabetic patients nonresponsive to the combination of metformin and a sulphonylurea

OBJECTIVE To evaluate the effectiveness of adding vildagliptin to the treatment of patients with inadequately controlled type 2 diabetes mellitus (T2DM) treated with a combination of metformin and a sulphonylurea. SUBJECTS AND METHODS 37 T2DM patients with HbA1c ranging from 7.7% to 12.4% (mean of 9.30 ± 1.38), despite the use of metformin in combination with a sulphonylurea, were additionally treated with vildagliptin (100 mg/day) for at least 6 months. RESULTS During triple oral therapy (TOT) HbA1c levels < 7% were achieved in 11 patients (29.7%), whereas levels of fasting plasma glucose (FPG) < 120 mg/dL were observed in 12 patients (32.4%). Both findings were observed in 10 patients (27.0%). Compared to nonresponsive subjects, lower mean baseline HbA1c and FPG levels were seen in responsive patients, but the difference was only statistically significant for fasting plasma glucose (FPG). Moreover, there was considerable overlap between the two groups. CONCLUSION Our preliminary results suggest that TOT with metformin, a sulphonylurea and vildagliptin may be useful for some T2DM patients nonresponsive to combination therapy with metformin and sulphonylurea.