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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Clinical efficacy of enalapril, a drug belonging to a group of angiotensin-converting enzyme inhibitors, was studied in patients with pubertal juvenile dyspituitarism (juvenile obesity) coursing with arterial hypertension. A reactive increase of plasma renin activity and reduced concentration of plasma aldosterone were revealed. The drug was characterized by a pronounced hypotensive effect. No negative effects on the blood lipid spectrum or carbohydrate metabolism were observed. The study showed that enalapril may be a drug of choice in the treatment of the hypertensive syndrome in patients with juvenile obesity.
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PMID:[An attempt to use enalapril in arterial hypertension in patients with juvenile obesity]. 774 32

Red cell membrane permeability was studied in 46 patients with pubertal juvenile dyspituitarism by measuring the rates of Na+/H,-Na+/Li(+)-metabolism, Na(+)-K(+)-contra-transport. The reference group consisted of 25 healthy adolescents and youths whose heredity was not aggravated for essential hypertension. No significant differences in the membrane permeability for monovalent cations in the reference subjects and the patients with the pubertal juvenile dyspituitarism were revealed. Thus analysis of the membrane characteristics may be helpful in the differential diagnosis of hypertension.
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PMID:[Erythrocyte membrane permeability for monovalent ions in pubertal juvenile dyspituitarism]. 805 74

Pituitary tumours result in hypersecretion of different hormones which can be used in diagnosis. Prolactinomas can be diagnosed by measurement of prolactin serum concentration. Prolactin concentrations of > 150 to 200 micrograms/l are invariably due to macroprolactinoma. Lower levels may indicate microprolactinoma or a peripituitary tumour. Computed tomography scans visualize (micro)prolactinomas of 3 mm. Diagnosis of acromegaly is now based on measurement of serum IGF-I concentration. IGF-I levels correlate with the old test which measured insufficient suppression of GH levels to < 2 micrograms/l in response to oral glucose load. Most endocrine tumours have somatostatin receptors, allowing visualization with radiolabelled somatostatin analogues. 111In-diethylenetriaminopentaacetic acid-octreotide allows normal pituitary and somatostatin positive tumours to be visualized. A positive scan is predictive of good response to octreotide therapy. Cushing's syndrome is diagnosed by ecchymoses, myopathy, hypertension, and by measurement of the overnight 1 mg dexamethasone suppression test, urine cortisol levels and the diurnal cortisol rhythm. Clinically nonfunctioning macroadenomas in post-menopausal women often do not immunostain for gonadotropins. Serum gonadotropin levels are not elevated, although they do release gonadotropins or subunits in vitro. Diagnosis is assisted by TRH administration which increases serum gonadotropins or subunits, especially LH-beta.
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PMID:Current tools in the diagnosis of pituitary tumours. 837 8

Pituitary adenomas are the most common pituitary disorder affecting pregnancy, and prolactinomas are the most common of the hormone-secreting pituitary adenomas. Hyperprolactinemia must be corrected to allow ovulation and fertility. Bromocriptine has been shown to be safe for use during early gestation. There is less than a 2% risk of microprolactinoma enlargement during pregnancy but a greater than 15% risk of symptomatic enlargement of a macroprolactinoma. Treatment options for patients with macroadenomas include stopping bromocriptine when pregnancy is diagnosed and reinstituting with tumor enlargement, continuous bromocriptine throughout pregnancy, and prepregnancy tumor debulking by surgery. The diagnosis of acromegaly may be difficult to make during pregnancy and relies, in part, on the persistence of the normal pulsatile secretion of growth hormone and loss of this secretory characteristic with a tumor. The growth hormone oversecretion may exacerbate tendencies to gestational diabetes, fluid retention, and hypertension. Treatment for acromegaly and other tumors generally may be deferred until after delivery. There are rare reports of enlargement of clinically nonfunctioning and growth hormone secreting tumors during pregnancy, and surveillance is needed. Tumors may need to be differentiated from lymphocytic hypophysitis. Patients with chronic hypopituitarism usually will need treatment with gonadotropins or pulsatile GnRH to become pregnant and may need increased steroid coverage during labor and delivery. Hypopituitarism developing during pregnancy is usually caused by lymphocytic hypophysitis and usually also will require steroid replacement therapy. Hypopituitarism arising postpartum may be caused by either lymphocytic hypophysitis or Sheehan's syndrome, and the latter may present as an acute or chronic syndrome. Borderline diabetes insipidus may manifest during pregnancy because of increased vasopressin degradation caused by markedly increased levels of placental vasopressinase. Treatment with desmopressin usually is satisfactory. Patients presenting with either anterior or posterior pituitary insufficiency in the peripartum period should always be evaluated for function of the other portion of the pituitary.
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PMID:Pituitary diseases in pregnancy. 988 Jan 16

Pituitary adenylyl cyclase-activating polypeptide (PACAP) is a potent endogenous secretagogue for chromaffin cells. We previously reported that PACAP coupled to the PAC1 receptor to evoke dihydropyridine-sensitive early (15 to 20 minutes) catecholamine secretion and cAMP response element binding protein-mediated trans-activation of the secretory protein chromogranin A promoter in PC12 pheochromocytoma cells. In this report, we studied whether the secretory and transcriptional responses elicited by PACAP were subject to desensitization. We found that PACAP evoked distinct immediate (initial, 0 to 20 minutes) and long-lasting (20 to 180 minutes) effects on catecholamine secretion. Initial secretory and chromogranin A trans-activation responses induced by PACAP were desensitized in a dose-dependent fashion after preexposure of cells to PACAP, and the IC(50) doses of PACAP for desensitization were approximately 18- to approximately 32-fold lower than the EC(50) activating doses for secretion or transcription. Desensitization of the initial secretion response was associated with decreased Ca(2+) influx through L-type voltage-operated Ca(2+) channels. Acute exposure to PACAP also triggered long-lasting (up to 3 hours), extracellular Ca(2+)-dependent, pertussis toxin-insensitive catecholamine secretion; indeed, even after short-term (20 minutes) exposure to PACAP and removal of the secretagogue, PC12 cells continued to secrete norepinephrine up to 76.9+/-0.22% of cellular norepinephrine content after 3 hours. A phospholipase C-beta inhibitor (U-73122) blocked this extended secretory response, which was dependent on low-magnitude Ca(2+) influx resistant to several L-, N-, P/Q-, or T-type Ca(2+) channel antagonists, but sensitive to Zn(2+), Ni(2+), Cd(2+), or to the store-operated Ca(2+) channel blocker SKF96365. A less than additive effect of the sarco-endoplasmic reticulum Ca(2+)-ATPase inhibitor thapsigargin plus PACAP on this sustained secretion also supported a contribution of store-operated Ca(2+) entry to the sustained secretory response. We propose that PACAP-evoked secretion and transcription are subject to homologous desensitization in PC12 cells; however, PACAP also induces long-lasting secretion, even under dose and time circumstances in which acute, dihydropyridine-sensitive secretion has been desensitized. Although initial secretion is mediated by an L-type voltage-operated Ca(2+) channel, extended secretion may involve a store-operated Ca(2+) channel that is activated through a G(q/11)/phospholipase C-beta/phosphoinositide signaling pathway.
Hypertension 1999 Nov
PMID:Time-dependent effects of the neuropeptide PACAP on catecholamine secretion : stimulation and desensitization. 1056 98

Acromegaly is a consequence of chronic growth hormone (GH) excess, due in the majority of cases to a GH-secreting pituitary adenoma, and occurring with a population prevalence of 60 per million and an incidence of 3-4 per million per year. Males and females appear to be equally affected with an average age of presentation of 44 years. Younger patients may have more aggressive tumours and higher GH concentrations. There is co-existent hyperprolactinaemia in about one third of cases, and a variable proportion of [figure: see text] tumours appear to have activating mutations of the gsp gene or other genetic abnormalities. Acute complications such as carpal tunnel syndrome, sweating and obstructive sleep apnoea are usually readily reversible with treatment of the condition, but chronic complications such as hypertension, diabetes and heart disease are less readily corrected and post-treatment GH levels of < 2.5 ug/L (5 mU/L) are needed to achieve the prevalence found in the general community. Such 'curative' levels of GH are achieved in only about 50% of patients with current therapies, and as a result there is an ongoing excess of patients with chronic complications of acromegaly leading to increased morbidity and mortality from the disorder, with observed-to-expected mortality ratios ranging from 1.6-3.3 and only approaching unity in those with growth hormone levels < 2.5 ug/L following treatment. Prognostic factors include in some studies the presence of diabetes and [table: see text] hypertension prior to diagnosis as well as measures of exposure to excessive growth hormone derived from the product of preoperative serum GH and the time from first symptoms to treatment. Overall, however, the most important prognostic variable appears to be the serum GH concentration achieved by treatment, with an increasing consensus that this needs to be < 2.5 ug/L (5 mU/L) to achieve cure of the condition.
Pituitary 1999 Jun
PMID:Epidemiology of acromegaly. 1108 Nov 70

Double pituitary adenomas are rare in surgical specimens and the most common clinical feature in reported patients has been acromegaly. We report 3 cases of double pituitary lesions in patients who presented with Cushing's disease. In a 22-year-old man (case 1) with delayed puberty and low testosterone levels, mild hyperprolactinemia was diagnosed and treated with dopamine agonist therapy that reduced the prolactin (PRL) levels to normal. Over a 1-year period Cushing's disease developed gradually and was confirmed with classical endocrine testing. In a 27-year-old woman (case 2) who initially presented with severe depression and morbid obesity there was a gradual onset of Cushing's disease; initially she had minimally elevated serum PRL. In a 33-year-old woman (case 3) there was a 2-year history of Cushing's disease characterized by hirsutism, hypertension and weight gain; serum PRL was normal. Magnetic resonance imaging in all 3 patients revealed a microadenoma that was successfully removed by transsphenoidal pituitary surgery. Histology and immunocytochemistry in case 1 and case 3 revealed a corticotroph cell adenoma and a PRL cell adenoma in separate areas of the pituitary. In case 3 the PRL cell adenoma was "silent" but in case 1 the PRL cell adenoma may have been the cause of the mild hyperprolactinemia. In case 2 nodular corticotroph hyperplasia was the cause of Cushing's disease and a "silent" PRL cell adenoma was also identified. We conclude from these cases and a literature review that double pituitary lesions may occur in patients with Cushing's disease. The corticotroph part of the double lesion may consist of a corticotroph cell adenoma or, as reported in this study, of corticotroph nodular hyperplasia. The counterpart of the double lesion may consist either of a "silent" PRL cell adenoma or a functional PRL cell adenoma causing hyperprolactinemia.
Pituitary 2000 Nov
PMID:Double pituitary lesions in three patients with Cushing's disease. 1138 80

Seventeen patients with Cushing's disease (CD) were treated from 1978 to 2000. There were 11 males and 6 females aged 6.8-18.8 years (mean age 13.0 +/- 5.9 years). Presenting features were: weight gain (100%); growth failure (71%); hirsutism (53%); striae (53%); hypertension (47%). Mean age of patients with striae was 15.2 +/- 2.3 years, without striae 10.3 +/- 3.3 years. Median height SDS was -1.81 (range -0.28 to -4.17), 53% having height SDS < -1.8. The height velocity in 6 subjects was subnormal (0.9-3.8 cm/year). Median BMI SDS was 2.29 (range 1.72-5.06). Cushing's disease was confirmed by detectable serum ACTH, median 28 ng/l (range 12-99, NR <10-50) (n = 15); loss of cortisol circadian rhythm values at midnight ranging from 216 to 1,080 nmol/l (NR <50) (n = 15); lack of cortisol suppression (NV < 50 nmol/l) during low-dose dexamethasone suppression test (LDDST) (0.5 mg 6-hourly x 8) (n = 14); and >50% suppression of cortisol compared with the basal value during high-dose dexamethasone suppression test (HDDST) (2 mg 6-hourly x 8) (n = 14). A CRH test (1 microg/kg i.v.) showed an increase of cortisol from 12 to 217% (median 73.5%) (n = 16). Pituitary imaging (CT/MRI) showed an image consistent with microadenoma in 6/17 patients, but there was concordance between pituitary imaging and surgical findings in 1/11 patients (9%). Inferior petrosal sinus sampling (IPSS) for ACTH after CRH was performed in 11 subjects (age 10.7-18.8 years). Central to peripheral ACTH ratios were >2 (2.5-157.2) in 10/11 patients. The inter-petrosal sinus ACTH gradient was >1.4 in 10 patients (2.1-20.8), indicating lateralization of ACTH secretion. In 10 patients (91%), the side of the tumour on IPSS was predictive of findings at surgery. Therapy consisted of transsphenoidal microadenomectomy (TSS) in 16 patients and bilateral adrenalectomy (1978) in 1. Following TSS alone, 7 patients were cured (cortisol <50 nmol/l) and 2 were in remission (cortisol <300 nmol/l), i.e. 56%. Seven had persisting hypercortisolaemia and underwent pituitary irradiation (4,500 cGy). Therapeutic outcome for a median of 8 years (0.5-24 years) resulted in cure of CD in 14/17 patients (82%) and remission in 1. Linear growth after TSS +/- pituitary irradiation in 10 subjects showed no short-term catch-up growth, with peak growth hormone (GH) 0.5-20.9 mU/l to insulin tolerance test (ITT)/glucagon. Eight patients were treated with human growth hormone (hGH) (14 U/m(2)/week) combined in 3 with GnRH analogue. The mean final (n = 6) or latest (n = 4) height SDS was -1.36. The difference between final/latest height SDS and target height SDS was 0.93 +/- 1.13, i.e. less (p = 0.005) than the difference between height SDS and target height SDS at presentation, i.e. 1.72 +/- 1.26, indicating long-term catch-up growth.
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PMID:Cushing's disease in childhood: presentation, investigation, treatment and long-term outcome. 1140 58

Cushing's syndrome invariably presents with a classical phenotype comprising central adiposity, prominence of dorsal, supraclavicular and temporal fat pads, bruising, abdominal striae, proximal myopathy, and hypertension. We report the case of a 20-yr-old student with pituitary-dependent Cushing's syndrome who was spared this classical phenotype because of a defect in the peripheral conversion of cortisone to cortisol. She presented to her general practitioner with secondary amenorrhea. Clinical examination revealed normal fat distribution (body mass index, 20.9 kg/m(2)), absence of hirsutism, myopathy, or bruising; her blood pressure ranged from 115/70 to 122/82 mm Hg. She was investigated for biochemical hypercortisolemia because of a mildly elevated random circulating cortisol (serum cortisol, 661 nmol/liter). Cushing's syndrome was confirmed on the basis of repeatedly elevated urinary free cortisols (831-1049; reference range, <350 nmol/24 h), failure of low-dose dexamethasone suppression (611 nmol/liter) and loss of circadian cortisol secretion. Investigations suggested Cushing's disease; there was suppression after high-dose dexamethasone (<20 nmol/liter) and a 950% increase in ACTH after stimulation with CRH. Pituitary magnetic resonance imaging revealed a 3-mm adenoma within the pituitary gland. Urinary corticosteroid metabolites were analyzed by gas chromatography-mass spectrometry and demonstrated a decreased THF+allo-THF/THE ratio of 0.66 (mean +/- SE in Cushing's disease, 1.74 +/- 0.24) suggesting a defect in 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1), an enzyme that converts the inactive glucocorticoid cortisone to active cortisol. Transphenoidal microadenomectomy was performed, and histology confirmed the diagnosis of a corticotroph adenoma. Postoperatively, serum cortisol was undetectable and replacement therapy was commenced. Subsequent investigations revealed a significantly impaired ability to convert an oral dose of cortisone acetate (25 mg) to cortisol, reduced serum cortisol to cortisone ratios, and a reduced serum half-life for cortisol (57.3 min). These results provide strong evidence for a partial defect in 11beta-HSD1 activity and concomitant increase in cortisol clearance rate. We have described a case of Cushing's disease that failed to present with a classical phenotype, and we postulate that this is due to a partial defect of 11beta-HSD1 activity, the defect in cortisone to cortisol conversion increasing cortisol clearance and thus protecting the patient from the effects of cortisol excess. This observation may help to explain individual susceptibility to the adverse effects of glucocorticoids.
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PMID:Absence of Cushingoid phenotype in a patient with Cushing's disease due to defective cortisone to cortisol conversion. 1178 23

Obesity is a major health problem that contributes to the development of type 2 diabetes, hypertension, dyslipidemia, and cardiovascular disease. The current pharmacological therapies for obesity are limited and may have significant side effects. Leptin therapy was shown to effectively cause weight loss in obese rats, however its effectiveness in humans is still under investigation. Obese humans have significantly elevated plasma leptin concentrations compared with lean individuals. Plasma leptin concentrations strongly correlated with percentage of body fat. Leptin concentration in the cerebrospinal fluid (CSF) is correlated, in a nonlinear manner, with plasma leptin levels and body mass index (BMI). The ratio of CSF leptin levels to serum leptin levels was 4 times greater in lean individuals than in obese individuals. One interpretation of this finding is that human obesity could be secondary to a central resistance to leptin action, causing a relative leptin deficiency in the CNS. Six years after the discovery of leptin we still do not have a clear understanding of how leptin accesses its targets in the brain, or whether there is defect in this process in the brain of obese individuals. In this manuscript we will review the different leptin gateways to the brain and the potential sites where a defect in leptin action may be present, as well as some potential clinical implications of leptin. A better understanding of how leptin reaches the brain and how it modulates the release of hypothalamic neuropeptides will be important in understanding the role that leptin plays in the pathophysiology of obesity.
Pituitary
PMID:Limited brain access for leptin in obesity. 1182 2


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