Thyroid cancer in patients with acromegaly: a case-control study.

Several studies have associated acromegaly with an increased risk of benign and malignant tumors. While simple and multinodular goiters are common findings in acromegaly, the prevalence of thyroid cancer is uncertain. The objective of this study was to estimate the prevalence of thyroid cancer in a series of acromegalic patients from three hospitals in northeast of Brazil. The methodology used included morphological, cytological and histological thyroid analysis of acromegalic patients and volunteers over 18 years, matched for age and sex and with nodule (s) ≥1 cm. The subjects of this study were 124 acromegalic patients, including 76 females (61.3%) and 48 men (38.7%), with a mean age 45.1 years. Results of the study showed that thyroid ultrasonography was normal in 31 cases (25%), 25 had diffuse goiter (20.1%), 67 had nodules (54%) and one agenesis of the right lobe (0.8%). Thirty-six patients underwent fine needle aspiration biopsy (FNAB) of their nodules and 9 cases of papillary cancer were found (7.2%). The control group consisted of 263 subjects, 156 females (59.3%) and 107 males (40.7%), mean age 44.7 years. In ultrasound assessment, 96 had nodules (36.5%). Of these, 13 were punctured and 2 cases of papillary carcinoma were found (0.7%). These results gave an odds ratio of 10.21 (p = 0.0011, 95% CI 2.17 to 48.01). These findings demonstrate an increased prevalence of thyroid cancer, statistically significant when compared to our control group. Thus, it is suggested that acromegalic patients should be routinely submitted to thyroid ultrasound evaluation, followed by FNAB of nodules when indicated.

Management of prolactinomas in Brazil: an electronic survey.

Dopamine agonists are the treatment of choice for prolactinomas. However, there are still controversies concerning dose, treatment duration and criteria for drug withdrawal in different clinical situations. The aim of this study was to assess diagnostic and therapeutic approaches to prolactinomas among members of the Brazilian Society of Endocrinology and Metabolism (SBEM). SBEM members answered a questionnaire sent by e-mail that included 18 questions related to controversial issues about the management of prolactinomas. Among SBEM members, 721 (approximately 24% of total) answered the questionnaire. Concerning the diagnosis, 38% of the respondents stated that prolactin levels < 100 ng/ml would exclude the presence of a prolactinoma. Most of them favored the screening for macroprolactin in asymptomatic individuals instead of a routine screening (74% vs. 26%). Regarding the treatment, 70% of the respondents chose cabergoline as the drug of choice to treat macroprolactinomas whereas similar proportions advised cabergoline or bromocriptine as the best treatment for microprolactinomas (52% vs. 48%). Only 20% and 34% of respondents favored treatment withdrawal 2-3 years after prolactin normalization in patients with macroprolactinomas and microprolactinomas, respectively. In case of pregnancy, only 58 and 70% of respondents advocated discontinuation of treatment with dopamine agonists in patients with macroprolactinomas and microprolactinomas, respectively. Finally, only 36% would allow breast-feeding without restriction, 44% would restrict it to patients with microprolactinomas and 20% would not recommend it for women with prolactinomas There are several points of disagreement among SBEM members regarding the management of prolactinomas.

Novel Mutation in the Hemojuvelin Gene (HJV) in a Patient with Juvenile Hemochromatosis Presenting with Insulin-dependent Diabetes Mellitus, Secondary Hypothyroidism and Hypogonadism.

BACKGROUND Juvenile hemochromatosis is a rare genetic disease that leads to intense iron accumulation. The disease onset usually occurs before the third decade of life and causes severe dysfunction in various organs. The most classical clinical findings are hypogonadotropic hypogonadism, cardiomyopathy, liver fibrosis, glycemic changes, arthropathy and skin pigmentation. However, secondary hypothyroidism is not reported in these patients. Juvenile hemochromatosis has an autosomal recessive inheritance and might be type 2A or type 2B, due to mutation in either the hemojuvelin gene (HJV) or hepcidin antimicrobial peptide (HAMP) gene. CASE REPORT A 26-year-old female patient was admitted with a recent history of diabetic ketoacidosis. Three months after that admission, she presented with arthralgia, diffuse abdominal pain, adynamia, hair loss, darkening of the skin and amenorrhea. Severe iron overload was found and findings in the hepatic biopsy were compatible with hemochromatosis. An upper abdominal magnetic resonance imaging (MRI) showed iron deposition in the liver and pancreas and pituitary MRI exhibited accumulation on the anterior pituitary. After 16 months the patient presented with dyspnea and lower limb edema, and cardiac MRI indicated iron deposition in the myocardium. The patient was diagnosed with juvenile hemochromatosis presenting with hypogonadotropic hypogonadism, cardiomyopathy, insulin-dependent diabetes mellitus, and secondary hypothyroidism. A novel homozygous mutation, c.697delC, in the HJV gene was detected. CONCLUSIONS We describe for the first time a severe and atypical case of juvenile hemochromatosis type 2A presenting classical clinical features, as well as secondary hypothyroidism resulting from a novel mutation in the HJV gene.

Pituitary Metastasis of Thyroid Carcinoma: A Case Report.

BACKGROUND Pituitary metastasis of thyroid carcinoma is a rare entity. Differential diagnosis with other lesions in the sellar/parasellar region, through clinical, histopathological, immunohistochemical, and imaging is challenging but essential for adequate treatment. CASE REPORT This case report describes a 58-year-old patient with the previous diagnosis of follicular thyroid carcinoma, with metastasis to cervical lymph nodes, bone, and lung, initially evolving to left palpebral ptosis. In the investigation, laboratory tests showed hypopituitarism, and magnetic resonance imaging of the skull showed a suprasellar formation measuring 2.2×3.5×2.5 cm, which increased in size in a few months. The patient underwent transcranial neurosurgery and subsequent immunohistochemical analysis, which confirmed pituitary metastasis of follicular thyroid carcinoma. The patient underwent chemotherapy and radiotherapy but died 26 months after the onset of symptoms. CONCLUSIONS The differential diagnosis of pituitary metastasis from a benign lesion is difficult. Therefore, a careful analysis of the history and clinical evolution, use of complementary imaging tests, and, where possible, the histopathological and immunohistochemical analysis of the lesion for diagnostic elucidation are necessary.

Higher Income and Integration into the Workforce Are the Main Factors Associated with Quality of Life in Acromegalic Patients in Northeastern Brazil.

OBJECTIVE: To identify the factors associated with quality of life in patients with acromegaly with follow-up at the referral service in neuroendocrinology of the state of Maranhão, northeast Brazil. METHODS: The Acromegaly Quality of Life Questionnaire (Acro-QoL) was used. Factors independently associated with quality of life were identified using multivariate linear regression, with p values < 0.05 considered significant. RESULTS: The multivariate linear regression analysis indicated a positive association between being integrated into the job market and quality of life scores in the overall domain (ß = 0.288, p = 0.003), psychological domain (ß = 0.291, p = 0.032), and personal relationship domain (ß = 0.314, p = 0.019). We also observed a positive association with income and the quality of life scores in all domains as follows: overall domain (ß = 0.037, p = 0.003), physical domain (ß = 0.988, p = 0.001), psychological domain (ß = 0.342, p = 0.008), physical appearance domain (ß = 0.270, p = 0.049), and personal relationship domain (ß = 0.315, p = 0.012). CONCLUSION: For patients with acromegaly living in one of the least developed regions of Brazil, integration into the job market and a higher income were associated with a better quality of life.

Can we predict long-term remission after somatostatin analog withdrawal in patients with acromegaly? Results from a multicenter prospective trial.

Somatostatin analogs (SSAs) represent the mainstay of therapy in acromegaly. One of the potential disadvantages is the expected need to maintain therapy indefinitely in previously non-irradiated patients. The aim of this multicenter prospective open trial was to evaluate the likelihood of successful discontinuation of SSA therapy in well-controlled acromegalic patients who fulfilled very strict criteria: two or more years of treatment with the long-acting SSA octreotide LAR (OCT-LAR), a stable dose and injections interval every 4 weeks or longer for the previous year, GH levels <2.5 ng/ml and normal IGF-1 levels for age, a tumor remnant <10 mm, no history of radiotherapy, and no use of cabergoline or pegvisomant over the previous 6 months. Disease recurrence was defined as an increase of IGF-1 to levels above 1.2-fold the upper limit of normal (ULN). Out of 220 patients, 20 patients (12 women and 8 men; mean age, 48.1 ± 10.3 years; age range, 27-64) treated for 2.74 ± 0.64 years (range, 2.0-4.4) were included in this prospective study and OCT-LAR therapy was stopped. Four patients (20 %) remained without clinical and biochemical/neuroradiological evidence of disease recurrence after 12-18 months of follow-up. Sixteen patients (80 %) relapsed biochemically within 9 months after drug withdrawal and restarted OCT-LAR at the same previous dose. Compared to recurring subjects, non-recurring patients had significantly lower mean IGF-1 (× ULN) levels but there were some overlapping values in both groups. No other characteristic could be identified as a predictor of successful OCT-LAR discontinuation. Our findings demonstrated that OCT-LAR withdrawal, though rare, is possible in well-selected acromegalic patients treated for at least 2 years and considered optimally controlled in hormonal and neuroradiological terms.