A Brazilian multicentre study evaluating pregnancies induced by cabergoline in patients harboring prolactinomas.

OBJECTIVE: To evaluate the maternal-fetal outcomes of CAB-induced pregnancies in patients with prolactinoma in a large cohort. METHODS: The prevalence of tumor growth, miscarriage, preterm, low birth weight, congenital malformations and impairment in neuropsychological development in children among women treated with CAB were assessed in a Brazilian multicentre retrospective observational study, RESULTS: We included 194 women with a mean age of 31 (17-45) years, 43.6% presenting microadenomas and 56.4% macroadenomas, at prolactinoma diagnosis. In 233 pregnancies, CAB was withdrawn in 89%, after pregnancy confirmation. Symptoms related to tumor growth occurred in 25 cases, more frequently in macroadenomas. The overall miscarriage rate was 11%, although higher in the subgroup of patients with CAB maintainance after pregnancy confirmation (38% vs. 7.5%). Amongst the live-birth deliveries, preterm occurred in 12%, low birth weight in 6% and congenital malformations in 4.3%. Neuropsychological development impairment was reported in 7% of cases. CONCLUSIONS: Our findings confirm previous results of safety in maternal and fetal outcomes in CAB-induced pregnancies; nevertheless, CAB maintenance after pregnancy confirmation was associated with higher miscarriage rate; result that must be further confirmed.

Calcium and vitamin D intake and biochemical tests in short-stature children and adolescents.

BACKGROUND: Growth is highly dependent on the absorption of nutrients. Inadequate calcium and vitamin D intake may compromise bone mineralization and growth. There is a great deal of concern regarding calcium and vitamin D intake, as well as biochemical changes in children and adolescents, which led us to investigate calcium and vitamin D levels during growth. METHODS: Fifty-eight children and adolescents with short stature (z-score <3 s.d.) were evaluated from September 2005 to February 2007. Blood biochemical analyses and 24-h urine tests were performed and were used to evaluate calcium, phosphorus, creatinine, sodium, alkaline phosphatase, parathyroid hormone (PTH) and 25(OH)D levels. Dietary inquiries, repeated three times, were used to estimate the actual intake of these substances. RESULTS: A reduced calcium (608.6 mg/day) and vitamin D (72.5 IU/day) intake was observed. Calcium excretion in 24-h urine (56 mg/24 h) and calcium excretion by weight (2.0 mg/24 h/kg) showed scores that were below normal. A negative correlation between PTH and both dietary vitamin D (r=-0.46; P<0.01) and calcium intake (r =-0.41; P<0.001) was observed. CONCLUSIONS: The low calcium and vitamin D intake observed in short-stature children and adolescents was associated with biochemical results, and suggested that PTH and calcium excretion may be useful screening tests for evaluating dietary calcium and vitamin D.

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.

Ultrasonography: is it useful in the diagnosis of cancer in thyroid nodules?

The role of ultrasonography (US) in the diagnosis of cancer in thyroid nodules is not well-established. The aim of the present study was to evaluate US performance in predicting cancer in thyroid nodules using a novel approach. Two hundred and eighty-nine patients with thyroid nodular disease were evaluated with clinical, biochemical and cytopathological examinations. Eighty patients with palpable solitary thyroid nodules or multinodular goiters who were to undergo surgery were included, and had a US exam performed by one of us. Some US characteristics of thyroid nodules were associated to cancer: absent halo, hypoechogenicity and microcalcifications, with sensitivity, respectively, of 56, 44 and 56%, and specificity of, respectively, 80, 83 and 94%. These findings were considered positive and were studied in two different combinations: simultaneous, when two or more were positive, and parallel, when any positive finding was present. When positive findings were studied simultaneously, sensitivity ranged 25 to 38% and specificity ranged 89 to 97%. Microcalcifications, associated or not to other findings, were highly specific for thyroid cancer, but they were only present in half of the malignancies. When positive findings were studied in parallel, sensitivity ranged 69 to 81% and specificity ranged 70 to 81%. The parallel combination of hypoechogenicity or microcalcifications or absent halo improved US sensitivity to 81% with an acceptable specificity (70%). This method is potentially useful to help us select patients for surgery when fine-needle aspiration biopsy is repetitively non-diagnostic or select for biopsy incidentally discovered non-palpable nodules.

A prolactin-secreting tumor in a patient with Klinefelter's syndrome: a case report.

We report the case of a patient with Klinefelter's syndrome who developed a prolactin (PRL)-secreting tumor. The patient developed headaches, visual alterations and also symptoms of hypogonadism despite appropriate testosterone (T) replacement therapy. The diagnosis of hyperprolactinemia was then suspected. The laboratory findings confirmed the hypothesis, showing high levels of serum PRL. The patient was initially treated with oral bromocriptine, and afterwards with the injectable form. There was a marked decrease in PRL levels and in tumor size. Although some neoplasms, like breast carcinoma and germ cell tumors, are known to occur more frequently in patients with Klinefelter's syndrome, an association with PRL-secreting tumor has not been reported yet. In conclusion, symptoms of hypogonadism in patients with Klinefelter's syndrome receiving appropriate T replacement therapy can suggest the presence of hyperprolactinemia.

Riedel's thyroiditis associated with high titers of antimicrosomal and antithyroglobulin antibodies and hypothyroidism.

Riedel's thyroiditis is a rare, chronic inflammatory disease of the thyroid gland. The aggressive fibrosis with extension beyond the thyroid into adjacent tissues contrasts with the diffuse, but intracapsular fibrosis of Hashimoto's thyroiditis. Most current studies refute the possibility of progression from a highly fibrosing form of Hashimoto's thyroiditis to a Riedel's thyroiditis based on the distinct clinical and laboratory data, although an unknown immunological basis is suggested for both diseases. The authors describe a patient with Riedel's thyroiditis, probably associated with Hashimoto's thyroiditis, sent to surgery because her cytological examination suggested thyroid malignancy. This patient had clinical and laboratory features of hypothyroidism and very high titers of antimicrosomal and antithyroglobulin antibodies, which decreased after surgery. Pathology studies disclosed Riedel's thyroiditis with intense lymphocytic infiltration suggestive of Hashimoto's thyroiditis. Quantitative immunohistochemical studies were not able to distinguish between both diseases.

Giant aneurysms of the sellar region simulating pituitary adenomas: a diagnosis to be considered.

Aneurysms of the sellar region are commonly mistaken for pituitary adenomas, since they have similar clinical, endocrinological and neurological symptoms. The authors describe three patients with giant aneurysms of the internal carotid artery which were initially diagnosed as pituitary tumors. In all patients the clinical presentation was nonspecific, and consisted mainly of neurological symptoms such as headaches and visual field defects. Endocrine abnormalities were also found in the three cases. Patient no. 1 had short stature, lack of GH response to clonidine stimulation, low IGF-1 levels and blunted TSH response to TRH. Patient no. 2 had gonadotropin deficiency and patient no. 3 had hyperprolactinemia. CT scans showed a densely enhanced lesion in all patients, which was heterogeneous in one case and homogeneous in the remaining. Carotid angiography confirmed the diagnosis of aneurysm. Preoperative angiographic studies are necessary for the differential diagnosis of an aneurysm from a pituitary tumor. Furthermore, these studies could prevent the serious consequences of a transsphenoidal surgical approach in misdiagnosed cases.

Inhibitory effect of calcitonin on growth hormone response to growth hormone releasing hormone in acromegaly.

1. A neuroendocrine role for calcitonin (CT) has been suggested by the finding of CT receptors in the hypothalamus. We have recently shown that salmon calcitonin (sCT) inhibits growth hormone releasing hormone (GHRH)-induced GH secretion in man by a mechanism apparently independent of changes in peripheral cortisol, glucose, calcium or parathyroid hormone levels. 2. We have further investigated the inhibitory action of sCT on GH secretion by studying the effects of sCT (100 MRC units, im) or placebo on basal and GHRH (1-29) NH2 (50 micrograms, iv) stimulated GH secretion in 6 acromegalic patients with active disease. 3. Basal GH levels were not altered by sCT administration (placebo: 136 +/- 99 micrograms/l vs sCT: 99 +/- 53 micrograms/l). However, the GH response to GHRH was decreased by sCT. The area under the curve was significantly smaller when patients were treated with sCT compared to placebo controls (placebo: 77202 +/- 57036 vs sCT: 64828 +/- 51909 micrograms min-1 l-1; P less than 0.02). No changes in glucose or calcium levels were observed. 4. These results demonstrate that sCT decreases GHRH-induced GH secretion in acromegalic patients. Although the mechanism of action of sCT on GH secretion is unknown, our results indicate that the inhibitory effect of this peptide on GH secretion is also observed in patients harboring pituitary adenomas.

Metabolic factors for urolithiasis in acromegalic patients.

1. Acromegaly is associated with metabolic disturbances of calcium and phosphorus which can also contribute to renal lithogenesis. 2. In order to characterize these disturbances more precisely, an oral calcium load test was performed on 14 active acromegalic patients. Serum and urinary levels of calcium, phosphorus, uric acid, creatinine and urinary cyclic AMP were determined. 3. Of the 14 patients, 5 (36%) presented hypercalciuria, 5 (36%) presented intestinal calcium hyperabsorption, and 6 (43%) had uric acid hyperexcretion. Two patients (14%) presented nephrolithiasis. 4. The medical records of 32 additional acromegalic patients with or without active disease were reviewed for a history of previous stones, which was observed in three cases (9.5%). 5. The present data suggest that nephrolithiasis occurs more frequently among acromegalic patients because of the underlying metabolic disturbances of calcium presented by this population.

Metabolic factors for urolithiasis in acromegalic patients

Acromegaly is associated with metabolic disturbances of calcium and phosphorus which can also contribute to renal lithogenesis. In order to characterize these disturbances more precisely, an oral calcium load test was performed on 14 active acromegalic patients. Serum and urinary levels of calcium, phosphorus, uric acid, creatinine and urinary cyclic AMP were determined. Of the 14 patients, 5 (36%) presented hypercalciuria, 5 (36%) presented intestinal calciumhyperabsorption and 6 (43%) had uric acid hyperexcretion. Two patients (14%) presented nephrolithiasis. The medical records of 32 additional acromegalic patients with or without active disease were reviewed for a history of previous stones, which was observed in three cases (9.5%). The present data suggest that nephrolithiasis occurs more frequently among acromegalic patients because of the underlying metabolic disturbances of calcium presented by this population

Inhibitory effect of calcitonin on growth hormone response to growth hormone releasing hormone in acromegaly

1. A neuroendocrine role for calcitonin (CT) has been suggested by the finding of CT receptors in the hypothalamus. We have recently shown that salmon calcitonin (sCT) inhibits growth hormone releasing hormone (GHRH)-induced GH secretion in msn by a mechanism apparently independent of changes in peripheral cortisol, glucose, calcium or parathyroid levels. 2. We have further investigated the inhibitory action of sCT on GH secretion by studying the effects of sCT (100 MRC units, im) or placebo on basal and GHRH (1-29) NH2 (50µg, iv) stimulated GH secretion in 6 acromemgalic patients with active disease. 3. Basal GH lelvels were not altered by sCT administration (placebo: 136 ñ 99 µg/1 vs sCT: 99 ñ 53 µg/1). However, the GH response to GHRH was decreased by sCT. The area under the curve was signficantly smaller when patients were treated with sCT compared to placebo controls (placebo: 77202 ñ 57036 vs sCT: 64828 ñ 51909 µg min-1 1-1; P < 0.01). No changes in glucose or calcium levels were observed. 4 These results demonstrate that sCT decresases GHRH-induced GH secretion in acromegalic patients. Although the mechanism of action of sCT on GH secretion is unknown, our results indicate that the inhibitory effect of this peptide on GH secretion is also observed in patients harboring pituitary adenomas

Calcitonin suppresses growth hormone (GH) response to growth hormone-releasing hormone (GHRH) in man.

Calcitonin (CT) receptors have been found in the hypothalamus, suggesting a neuroendocrine role for this peptide. We have recently shown that, in the rat, central administration of salmon calcitonin (sCT) suppresses basal and GHRH-stimulated GH secretion. To further investigate how sCT alters GH secretion, we studied the effects of sCT (100U MRC, im) or placebo on basal and GHRH (50 micrograms, iv)-stimulated GH secretion in 6 normal men. GHRH was administered 1 h after sCT injection. Basal GH levels were not altered by sCT administration. However, GH response to GHRH was markedly suppressed by sCT (area under the curve - sCT: 574.6 +/- 69.7 vs placebo: 1057.2 +/- 284.8 micrograms. min/L; p less than 0.02). Cortisol levels were higher in sCT-treated subjects compared to controls, from 45 to 105 min after sCT injection (p less than 0.05). However, no correlation was found between GH response to GHRH and cortisol levels. No changes in glucose, calcium and PTH levels were seen. These results demonstrate that sCT inhibits GHRH-induced GH secretion in man by a mechanism apparently independent of changes in peripheral cortisol, glucose, calcium and PTH levels.