Alice Helena Dutra Violante

Diagnosis and management of hyperprolactinemia: Results of a Brazilian multicenter study with 1234 patients

Objective: The aim of the study was to evaluate clinical and laboratorial features of 1234 patients with different etiologies of hyperprolactinemia, as well as the response of 388 patients with prolactinomas to dopamine agonists. Design, setting, and patients: A total of 1234 hyperprolactinemic patients from 10 Brazilian endocrine centers were enrolled in this retrospective study. Main outcome measure: PRL measurement, thyroid function tests, and screening for macroprolactin were conducted. Results: Patients were subdivided as follows: 56.2% had prolactinomas, 14.5% drug-induced hyperprolactinemia, 9.3% macroprolactinemia, 6.6% non-functioning pituitary adenomas, 6.3% primary hypothyroidism, 3.6% idiopathic hyperprolactinemia, and 3.2% acromegaly. Clinical manifestations were similar irrespective of the etiology of the hyperprolactinemia. The highest PRL levels were observed in patients with prolactinomas but there was a great overlap in PRL values between all groups. However, PRL>500 ng/ml allowed a clear distinction between prolactinomas and the other etiologies. Cabergoline (CAB) was more effective than bromocriptine (BCR) in normalizing PRL levels (81.9% vs 67.1%, p<0.0001) and in inducing significant tumor shrinkage and complete disappearance of tumor mass. Drug resistance was observed in 10% of patients treated with CAB and in 18.4% of those that used BCR (p=0.0006). Side-effects and intolerance were also more common in BCR-treated patients. Conclusion: Prolactinomas, drug-induced hyperprolactinemia, and macroprolactinemia were the 3 most common causes of hyperprolactinemia. Although PRL levels could not reliably define the etiology of hyperprolactinemia, PRL values >500 ng/ml were exclusively seen in patients with prolactinomas. CAB was significantly more effective than BCR in terms of prolactin normalization, tumor shrinkage, and tolerability.

Prevalence of osteopenia in men with prolactinoma

The aim of this cross-sectional study was to analyze bone mineral density (BMD) and prevalence of osteopenia and osteoporosis in 30 men with prolactinoma, and compare them to 22 control subjects. BMD of lumbar spine and femur was evaluated by dual-energy X-ray absorptiometry. PRL, testosterone, estradiol, sexual hormone-binding globulin and free androgen and estrogen indexes (FAI and FEI, respectively) were measured in all the subjects. In patients with prolactinoma, mean values of PRL and testosterone were calculated for the 12-month period that preceded the study. The mean T-score of the four sites analyzed by bone densitometry was lower in men with prolactinoma than in controls (p-values: lumbar spine=0.015, femoral neck >0.0001, trochanter=0.037, total femur=0.036), and 55.6% of the former presented osteopenia or osteoporosis at one or more sites (p = 0.035). The lumbar spine was the most seriously affected site, where 29.6% had osteopenia and 14.8% had osteoporosis. By the time of BMD determination, significant associations were found between BMD and PRL, testosterone, FAI, estradiol, FEI, and duration of hypogonadism. Considering the period of 12 months that preceded BMD evaluation, trochanter BMD was associated with mean PRL levels, while there was an association between lumbar spine BMD and mean testosterone levels. However, the multiple regression analysis showed that estradiol was the main determinant of BMD. In conclusion, men with prolactinoma have high prevalence of osteopenia and osteoporosis. Bone loss in such patients is associated with hyperprolactinemia and hypogonadism, and mainly influenced by estrogen.

Quality of life in women with microprolactinoma treated with dopamine agonists

Objectives To evaluate QOL in women with microprolactinomas treated with dopamine agonists, comparing the patients with normal versus those with elevated prolactin levels, and to identify clinical and biochemical influences on patients’ QOL. Material and methods A cross-sectional evaluation was performed in two University referral centers. Fifty women with microprolactinoma answered the SF-36 questionnaire by the time of their clinical evaluation. Their biochemical analysis included PRL, estradiol, testosterone, and SHBG. Fifty women of similar age distribution served as controls. Results Patients had lower scores than controls in all SF-36 categories: physical functioning, physical role, pain, general health, vitality, social functioning, emotional aspect, and mental health. Within the patients’ group, the ones with normal PRL levels had higher scores than those with high PRL levels in all categories but the physical role. The physical functioning score correlated with the free androgen index, while the pain, vitality, social functioning, emotional aspect, and mental health scores were associated with the prolactin levels obtained at study entry. Conclusions QOL is impaired in women with microprolactinoma treated with dopamine agonists, and was inversely associated with the PRL levels. This latter finding reinforces the importance of providing adequate disease control for these patients in order to avoid the adverse consequences of hyperprolactinemia on QOL.

Body fat in nonobese women with prolactinoma treated with dopamine agonists

Objectives  To evaluate body fat in nonobese women with prolactinoma treated with dopamine agonists, using whole body dual energy X‐ray absorptiometry (DXA) and to correlate DXA results with biochemical data and clinical aspects of the prolactinoma.

Bone density in women with prolactinoma treated with dopamine agonists

AbstractObjectives (1) to evaluate bone density in women with prolactinoma treated with dopamine agonists and healthy controls, using dual energy x-ray absorptiometry (DXA), (2) to classify the results according to the current International Society for Clinical Densitometry (ISCD) criteria, and (3) to correlate bone density with lean and fat masses, biochemical data and clinical aspects of prolactinomas. Materials and methods A cross-sectional study was performed in two University referral centers. Forty-five premenopausal women with prolactinoma were submitted to DXA and blood analysis (prolactin, estradiol, testosterone, SHBG, calcium, phosphorus, PTH, C-telopeptides of type 1 collagen, and osteocalcin) by the time of their clinical evaluation. They were compared with 25 control women of similar age and body mass index distribution. Results Women with prolactinoma had lower lumbar spine Z-score than controls. Femoral neck, trochanter, and total proximal femur Z-scores were similar in patients and controls. Twenty-two percent of the patients had Z-scores below the expected age range vs. 4% in the control group. Lumbar spine, femoral neck, and total proximal femur Z-scores were mainly correlated with the amenorrhea duration. The trochanter Z-score was associated with the gynoid lean/fat mass ratio. Conclusions Based on the current ISCD criteria, bone density evaluation in women with prolactinoma reveals bone loss, especially of trabecular type. Bone density in these patients was particularly associated with the duration of amenorrhea, which reinforces the importance of the adequate disease control in women with prolactinoma in order to avoid complications of this disease.

Body fat in men with prolactinoma.

Objective: (a) To evaluate body fat in men with prolactinoma and healthy controls, using whole body dual energy x-ray absorptiometry (DXA), and (b) to correlate DXA results with anthropometry and clinical aspects of male prolactinomas. Material and methods: A cross-sectional study was performed in two University referral centers. Eleven newly-diagnosed men with prolactinoma and 9 with normal PRL levels due to dopamine agonist treatment were submitted to DXA and blood analysis (PRL, testosterone, dihydrotestosterone, estradiol, and SHBG) by the time of their clinical evaluation. They were compared with 14 control men of similar age and body mass index distribution. Results: Newly-diagnosed men with prolactinoma had higher fat percentage in the arms and the total body, when compared with patients treated with dopamine agonists and controls. The former group also presented higher fat percentage in the legs than the controls. Truncal fat percentage of the newly-diagnosed patients was lower than the dopamine agonist treated group. The 3 groups had similar android and gynoid fat contents. Fat percentage of the 6 sites correlated with PRL, testosterone, and dihydrotestosterone levels. Conclusion: Newly-diagnosed men with prolactinomas had higher body fat content. Body fat was linked to disease control, especially to the PRL and androgen levels. Consequently, adequate control of hyperprolactinemia should be pursued in order to reduce the risk of obesity and its metabolic complications in men with prolactinoma.

Aspectos clínicos e terapêuticos de prolactinomas em homens

Macroprolactinomas predominate in males in comparison to microprolactinomas, with greater trend to invasiveness than in females. The clinical treatment has been the first option to prolactinomas, in both macro and microadenomas, irrespective the sex. We compared clinical presentation, prolactin levels, neuroradiologic invasiveness and prolactinemia response of 23 men with prolactinomas subjected to clinical therapy (group 1) with 19 who went also through surgical and/or radiotherapic treatment (group 2). The statistical analysis was done by the tests of chi-square or exact of Fisher, in order to compare proportions, and by t of Student or Mann-Whitney, in order to compare means. The level of significance adopted was 5% (p<0.05). The two groups were similar regarding age (p=0.23), period between start of the first symptom and diagnosis (p=0.82), prolactin levels before treatment (p=0.41) and invasive macroadenomas proportion (p=0.096). There was significantly greater percentage of headache (p=0.009) and visual deficit (p=0.025) in group 2, as well as the drug usage (p=0.007) and observation (p=0.0005) periods were superior in this group. The variations of prolactin levels before and after therapy (p=0.49) as well as the percentage of prolactin normalization (p=0.20) did not show any significant difference when comparing the two groups. We conclude, emphasizing the relevance of precocious prolactinoma diagnostic in men, because of the demonstrated morbidity. We strengthen the use of dopamine agonist as the first therapeutic option irrespective the adenoma size.

Prolactinomas e densidade mineral óssea em homens

Throughout the years evidence has been accumulated on the morbidity of hyperprolactinemia, particularly in terms of bone mineral density decrease. This complication of hyperprolactinemia affects both women and men. In this paper, we analyze aspects related to bone loss in men with hyperprolactinemia due to prolactinomas: prevalence, clinical relevance, physiopathology, diagnosis and the consequences of the treatment of hyperprolactinemia and hypogonadism on bone mineral density.

Pheochromocytomas and Paragangliomas: Clinical and Genetic Approaches

Pheochromocytomas (PCCs) and paragangliomas (PGLs) are neuroendocrine tumors derived from the chromaffin tissue. Diagnosis of these tumors is extremely important as they are linked to the hypertension syndrome with great cardiovascular morbidity and mortality. A great majority of PCCs and PGLs are sporadic and benign tumors; however, the classic idea of 10% exception of these features is changing. The description of new genes linked to familial forms of PCC/PGLs, such as succinate dehydrogenase (SDH) complex subunits, KIF1Bβ, EGLN1, TMEM127, and MAX, added to the well-known PCC familial syndrome (MEN2, VHL, and neurofibromatosis type 1) presents new challenges for diagnosis. In this review, we discuss the diversity of clinical and genetic approaches to this syndrome as well the diverse criteria that should guide genetic investigation.

Criptococose pulmonar pseudotumoral associada à síndrome de Cushing

Opportunistic infections in endogenous Cushings syndrome are associated with severe cortisol excess and carry a high mortality. Pulmonary cryptococcosis is one of these opportunistic infections and can mimic a lung neoplasm, therefore making its diagnosis difficult. We report a case of a young male with ACTH-dependent Cushings syndrome and severe hypercortisolism. The patient achieved cure after the transfenoidal surgery, but developed a febrile state. A chest computed tomography showed a pulmonary nodule that did not change in serial chest radiographs. Diagnosis of tuberculosis, fungal and bacterial infections were inconclusive, so the hypothesis of lung neoplasm became more probable. The necropsy, however, disclosed a pseudotumoral cryptococcosis. Opportunistic infections, like Cryptococcus neoformans, should be considered in patients with Cushings syndrome and a pulmonary infiltrate.