Malebranche Berardo Carneiro da Cunha Neto

Impact of recombinant human growth hormone (rh-GH) treatment on psychiatric, neuropsychological and clinical profiles of GH deficient adults: a placebo - controlled trial

BACKGROUND Untreated GH-deficient adults have a diversity of dysfunctions (e.g. reduced muscle strength, emotional instability during stress, depressive symptoms) that may cause deleterious effects on quality of life, and may be positively influenced by recombinant human growth hormone (rh-GH) therapy. AIM To evaluate the impact of a clinical intervention with rh-GH therapy on GH- deficient adults. METHOD The physical, psychiatric and neuropsychological status of 9 GH-deficient adults was determined before and after the administration of rh-GH (0.250 IU/Kg/week) in a double blind placebo-controlled trial for six months. Patients then received rh-GH for a further period of 6 months and their status was re-evaluated. RESULTS Rh-GH was significant better than placebo at 6th month (p < 0.05), producing increased serum Insulin like growth factor-I (IGF-I) levels, reduced body mass index (BMI) and body fat, increased lean body mass and water, reduced waist/hip ratio and increased energy expenditure. The rh-GH therapy was also significantly better than placebo on depressive features as measured by the Hamilton Depression Scale (17-items) (p = 0.0431) and the Beck Depression Inventory (p = 0.0431). Neuropsychological evaluations showed significant improvements in measures of Attention: Digit Backward (p = 0.035), Verbal Fluency (FAS) (p = 0.02) and Cognitive Efficiency (WAIS-R tests): Vocabulary (p = 0.027), Picture Arrangements (p = 0.017), and Comprehension (p = 0.01) following rh-GH therapy. CONCLUSION The clinical, psychiatric, and neuropsychological impairments of untreated GH-deficient adults can be decreased by rh-GH therapy.

Role for postoperative cortisol response to desmopressin in predicting the risk for recurrent Cushing's disease

In the early postoperative period of Cushings disease patients, desmopressin may stimulate ACTH secretion in the remnant corticotrophic tumour, but not in nontumour suppressed cells.

ALTERACOES SEXUAIS NA EPILEPSIA: RESULTADOS DE UMA AVALIACAO MULTIDISCIPLINAR

Eleven epileptic men who complained of epilepsy and sexual dysfunction were submitted to a multidisciplinary evaluation. Mean age was 27 years (20-34), mean epilepsy duration was 19 years (0,5-32) and the mean seizure frequency was two by week (0-7). Ten patients had partial seizures and one other had myoclonic epilepsy. Ten patients were treated with antiepileptic drugs (phenytoin - 1, carbamazepine - 8, clonazepam - 3, clobazam - 2, valproic acid - 3, vigabatrin - 1). As defined in the DSM III-R, the complaints were: erectile disorder (9), hypoactive sexual desire disorder (4), frotteurism (4), inhibited orgasm (3), premature ejaculation (3), fetishism (2), voyeurism (2), exhibitionism (2), pedophilia (1) and sexual aversion disorder (1). Two patients showed hypogonadotropic hypogonadism on endocrinologic screening. Urological evaluation disclosed organic erectile dysfunction in other two. One patient had a diagnosis of psychogenic sexual disorder. In six patients a conclusive etiologic diagnosis was not reached This report shows the multifactorial nature of sexual disorder in epilepsy and underlies the need of a multidisciplinar evaluation.

Cabergolina como alternativa no tratamento clínico de prolactinomas. experiência na intolerância/resistência à bromocriptina

Cabergoline (CAB, Pharmacia) is a long-acting ergoline dopaminergic agonist for oral administration, already described as a useful drug for hyperprolactinemia therapy. Forty-five patients (36 women, 9 men) with prolactinomas (27 micro, 18 macro) with persistent intolerance and/or resistance to bromocriptine (BRC) were treated with a weekly CAB dose of 0.25-7.0mg (median: 1mg) divided in one to seven administrations along the week. The treatment, in compassionate basis, lasted from 1 to 38 months (median: 12 mo). Among the 38 BRC intolerant patients (digestive symptoms, n=27; orthostatic hypotension, n=13; nasal stuffiness, n=5; psychiatric manifestations, n=4; urinary retention, n=1) only 5 remained persistently intolerant to CAB (digestive symptoms, n=2; arterial hypotension, n=2; nasal stuffiness, n=1). All BRC tolerant patients accepted CAB well. Eleven cases had serum prolactin levels normalized with BRC. These patients and other 19 also reached normal prolactin levels with CAB. However, only 3 out of the 7 BRC resistant patients (daily dose: 10-25mg) had their serum prolactin levels normalized with CAB. Tumor shrinkage was documented by magnetic resonance imaging or computed tomography scanning in 7 macroprolactinoma patients during CAB treatment. Thus, due to its excellent efficacy, tolerability and low frequency administration, CAB can be very useful for medicai management of prolactinomas.

Progression of an Invasive ACTH Pituitary Macroadenoma with Cushing's Disease to Pituitary Carcinoma.

Pituitary carcinomas are very rare tumors that in most cases produce prolactin and adrenocorticotropic hormone (ACTH). It is a challenge to diagnosis of a pituitary carcinoma before disclosed symptomatic metastasis. We report the case of a female patient with Cushings disease who underwent three transsphenoidal surgeries, with pathological findings of common ACTH pituitary adenoma including Ki-67 expression <3%. She achieved hypocortisolism after the 3rd surgery although ACTH levels remained slightly elevated. The patient returned some time later with fast worsening of hypercortisolism. Magnetic resonance imaging showed clivus invasion, which led to a fourth surgery and radiation. This time, immunohistochemistry revealed strong Ki-67 (10% to 15%) and p53 expression. Liver and lumbar spine metastases were found on workup. The patient died after few months due to lung infection. Pituitary carcinomas are rare, and the transformation of an ACTH-secreting pituitary adenoma into a carcinoma is exceptional. The difficulty of defining markers for the diagnosis of carcinoma, before metastasis diagnosis, in order to change the management of the disease, is a challenge.

Diagnosis and Treatment of Hypothalamic Disease

Anatomo-functional studies on the hypothalamus have faced major difficulties, because this organ cannot, as far as function is concerned, be considered like the cerebral cortex, where the homunculus could be mapped, with usually well-determined brain regions corresponding to somatic or visceral afferent or efferent projections, according to an established map. This may be because of the proximity of the hypothalamic nuclei to afferent and efferent paths of the cortex, thalamus, limbic system, and spinal cord; all occurring in a rather limited region, measuring 1.5 × 1.5 × 1.3 cm, weighing approximately 2.5 g and divided into three zones (periventricular, medial and lateral) and four regions (preoptic, supraoptic, tuberal, and mamillary.) In Table 1, we describe the several hypothalamic regions or nuclei involved in different functions, according to studies conducted both in human beings and other animals.

Hypopituitarism due to Hydrocephalus: Case Report and Review of the Literature

Introduction: Although rare, chronic hydrocephalus may cause amenorrhea and delayed puberty associated with obesity as the main endocrine manifestations. Since the first operation carried out in 1950 on a patient with amenorrhea and hydrocephalus, fewer than 30 patients with these features have been reported. Case Report: Our patient represents a teenage case of primary amenorrhea, partial adrenal insufficiency and adult growth hormone deficiency caused by hydrocephalus due to aqueductal stenosis. Our English-language literature search for similar well-documented cases yielded less than 30 cases. Our management consisted of endoscopic third ventriculostomy, which resulted in regular menstrual cycles and normalization of somato- and adrenocorticotropic axes. Discussion: This is a rare case of a 20-year-old woman with primary amenorrhea caused by hydrocephalus due to aqueductal stenosis. Neurosurgical treatment produced relief in hypothalamic hydrodynamics tension, allowing recovery of hormonal function and restoring normal menstrual cycles.

Topiramate Overcoming Dopamine Agonist‐Induced Migraine Exacerbation and Avoiding Transsphenoidal Surgery in a Young Boy With a Macroprolactinoma

A 10-year-old boy was referred to our clinic with a 2-year history of headaches, which had become worse in the 6 months prior to presentation. The headache was described as a pulsatile pain of moderate intensity in the bilateral orbital, periorbital and temporal regions, aggravated by routine physical activity, associated with blurred vision, phonophobia, photophobia and dizziness, during most part of the day, and with almost daily frequency. No visual disturbances were reported outside the pain episodes and the patient also denied associated autonomic symptoms such as conjunctival injection, lacrimation, nasal congestion, eyelid edema, ptosis, facial flushing or sweating, and sensation of fullness in the ear. Therefore, the patient met the ICHD-3 criteria for migraine. His mother also had a history of migraine with no other comorbidities. Growth and weight development were normal in reference to sex and age (weight 43 kg, height 1.42 m; BMI 21.3 kg/m). On initial evaluation, bilateral gynecomastia (Tanner stage 2) and galactorrhea on expression were noted. Testicles were on the early pubertal range (5 cm) and pubic hair was stage 3. Due to the association of refractory headache and galactorrhea, laboratory evaluation was performed, which revealed a serum prolactin of 428 ng/mL and normal thyroid, gonadal, somatotrophic, and corticotrophic function (Table 1). Sellar MRI showed the presence of a pituitary macroadenoma measuring 2.1 3 1.7 3 1.3 cm occupying the central and left portion of the sellar and suprasellar region with heterogeneous signal intensity, presenting a central necrotic area and showing proximity to the left cavernous sinus without definitive signs of invasion (Fig. 1). Neurophtalmologic examination showed no visual field disturbances. A diagnosis of macroprolactinoma was established and the patient was started on cabergoline 0.25 mg once a week. After 6 days of treatment initiation, the prolactin level was 253 ng/mL. Right after starting cabergoline, the patient experienced considerable worsening of the frequency and intensity of his headaches but maintaining the same characteristics as described previously, no more tolerating its use after 23 days. He was then switched to bromocriptine 1.25 mg qd, but symptoms persisted on this dopamine agonist as well, preventing its use after 2 weeks. After drug withdrawal, prolactin levels rose significantly, reaching a peak of 625 ng/mL 1 month later. At this time, considering the patient developed intolerance to two different dopamine agonists, surgical treatment remained a major possibility. However, since the patient exhibited a headache with migraine characteristics, we decided to give him a trial of topiramate as a prophylaxis drug, in conjunction with cabergoline, aiming to avoid surgical treatment. Cabergoline 0.25 mg was then started twice a week in association with topiramate 25 mg qd. One month later, the patient reported expressive improvement of the frequency and intensity of the headache episodes, which allowed increasing cabergoline to 0.5 mg four times a week, maintaining the same topiramate dose. Five months after increasing the cabergoline dose, the patient reported complete resolution of the pain crises and galactorrhea also had subsided. Prolactin levels at this time This article originally published online as a Brief Communication. It was changed to a Letter to the Editor on October 4, 2016.

Clinically nonfunctioning pituitary adenoma growth after radiosurgery

provoked by gastric atrophy is the commonest cause of VBD. Autoimmune atrophic gastritis (AAG) is a special type of gas-tric atrophy characterized by serum antibodies antiparietal cells and/or anti-intrinsic factor. AAG was an unexpected di-agnosis since it is a relatively rare disease and the peak age of onset is 60 years, with only 10% of patients being <40 years of age. Myelopathy alone as clinical presentation is also a rare situation, occurring in about 12% of patients