A moderate elevation of the daily excretion of free noradrenaline and adrenalin is observed in chronic circulatory insufficiency, beginning with Stage IIA. The catecholamines metabolism is elevated, as shown by the daily excretion of normethanpherine and methanpherine and of vanillyl-mandelic acid. The activity of renin and angiotensinases was growing along with the progressing cardiac insufficiency. The blood level of angiotensinogen was decreasing, especially in patients with Stage IIB and III of decompensation. The daily excretion of aldosterone was growing along with the development of cardiac insufficiency. The functional state of the glucocorticoid function of the adrenal cortex was of a phased nature in cases of circulatory insufficiency. The study of the functional state of the epiphysis was conducted by way of determining the blood level of melatonine and of its daily excretion. In Stages I and IIA the level of this hormone was clearly elevated, in Stages IIB and III -- decreased as compared with the initial and normal levels. The plasma level of the antidiuretic hormone was distinctly growing, beginning with Stage IIB, reaching its maximal values in Stage III.

The authors reported a twelve year and four-month old girl who had prolonged fever for 2 weeks. Physical examination revealed a painless enlarged thyroid gland with firm consistency. Hyperparathyroidism was suspected because of hypercalcemia, hypophosphatemia, high level of serum alkaline phosphatase, and decreased density of long bones. Thyroid scan showed a cold nodule of the left upper lobe which subsequently proved to be a medullary thyroid carcinoma by high serum thyrocalcitonin level and pathological examination. Her 24-hour urinary vanillyl mandelic acid was in the normal range, and abdominal ultrasonography demonstrated normal adrenal glands. Multiple endocrine neoplasia type IIa (MEN IIa) was diagnosed by medullary thyroid carcinoma and hyperparathyroidism. However, the fully developed syndrome is characterized by the combined occurrence of medullary thyroid carcinoma, primary hyperparathyroidism, and pheochromocytomas. This syndrome is a rare, complex, and potentially lethal disease so early recognition and family screening are very important.

The possibility of naturally occurring amnesia was examined in aging Fischer F254 rats. Animals 110 weeks old showed a loss of learning and memory in a passive avoidance responses (PAR) failure test. When 120 mg/kg/day of Shosaikoto extract was placed in the diet after 72 weeks of age to 110 weeks, it improved age-induced PAR failure in both the two-compartment avoidance box test and the step-down test. The responses of 110-week-old Shosaikoto-treated rats on both PAR failures were almost the same as those of non-treated 6-week-old rats. In these Shosaikoto-treated rats, dopamine was increased and norepinephrine and vanillyl mandelic acid were decreased in brain relative to those in non-treated aging rats.

The values of 17-ketosteroids (according toe Drekter, Pearson, Bartezak, modification of Kukuskina and Gurjeva), 5-hydroxyindole acetic acid (according to Sjoerdsma, Weisbach and Udenfriend) and 3-methoxy, 4-hydroxyvanillyl mandelic acid (according to Pisano et al, modification of Georges) were followed up in the 24-hour urine of 37 female-weavers (subdivided into two groups--healthy and neurotics) and 15 males--operators of control boards from the Chemical Combinate--Vratza. The urine was tested also according to the method of Wisser and Stamm, 1970, in mgr/2 hours. The comparison of the metabolite values before and after work revealed an increase of 17-ketosteroids and vanillyl-mandelic acid after neuro-sensory loading, especially in neurotics. Lower values, at the end of the working shift, were found for the 5-hydroyindole acetic acid, with the exception of those of the neurotics, that were elevated--an increased utilization of serotonin is relied on.

BACKGROUND

Hypertension is a major health issue worldwide. Calcium Channel Blockers (CCBs) are the most commonly used antihypertensive agents. CCBs act on voltage-dependent calcium channels and they were categorized into two subclasses, Dihydropyridine (DHP) and non-Dihydropyridine (non-DHP) derivative. Amlodipine is a third generation L-type of DHP and Cilnidipine is a novel L/N-type of DHP CCB, both drugs have excellent pharmacological profiles with the unique actions.

OBJECTIVE

To study the clinical and biochemical profile in Amlodipine and Cilnidipine treated mild to moderate hypertensive patients.

METHODS

The present study was a cross-sectional study. A total of 140 mild to moderate hypertensive patients (HTN classified according to Joint National Committee-8 (JNC-8) HTN guideline), 70 were in Amlodipine group (Group-A), and other 70 patients were in Cilnidipine group (Group-B). Group-A receiving Tab Amlodac 5 mg/day and Group-B receiving Tab Cilacar 10 mg/day, and both the group receiving respective medications since more than six months. Patients enrolled into the study with due consideration of eligibility criteria. Demographic, clinical and biochemical parameters were noted and compared.

RESULTS

Demographic parameters are matched, there was no significant difference seen between two study groups. Systolic and Diastolic Blood Pressure (SBP and DBP) showed a significant difference (p<0.001). There was no significant difference in pulse rate between the two groups, both QT/QTc showed statistically significant difference (p<0.001). The biochemical parameters like serum creatinine, albumin, globulin, total protein, serum Na+, fractional excretion of Na+, serum osmolality, vanillyl mandelic acid, were compared between two study groups, there was no significant difference seen between the two groups.

CONCLUSIONS

The Amlodipine and Cilnidipine both are equally effective antihypertensive drugs. Cilnidipine treated group showed more reduction in blood pressure than the Amlodipine treated group and there was no significant change in heart rate between the two groups. Cilnidipine group showed comparatively shortened QT/QTc interval than the Amlodipine group.

Alterations in metabolism of catecholamines were studied in sportsmen after development of acute fatigue as a result of the test physical loading. Three types of the alterations were characterized on the basis of differences in excretion with urine of free and sulphate-bound adrenaline, noradrenaline, of their precursors DOPA and dopamine as well as acid metabolites (vanillyl mandelic acid). The first type of the alterations in catecholamines metabolism comprized the cases, when excretion of catecholamines, their precursors and metabolites did not increase; this appears to relate to the partial exhaustion of hormones and peripheric mediators of sympathoadrenal system. The second type was characterized by decreased excretion of the substances studied, by development of the "perversed" reactions due to modifications in the regulatory system, which led to the inhibition of the system instead of its stimulation. The third type was manifested as the hyperfunction of the system. The increased synthesis of catecholamines during the hyperfunction suggests that this process serves as a compensatory reaction to their preceding elevated secretion; the phenomenon appears to depend on the increased secretion of the newly formed catecholamines. Excretion of catecholamines and their precursors was decreased for a long time after development of chronic fatigue in the resting state and the increase in excretion of the substances studied was not observed after physical loading.

This study examined 20 air traffic controllers from the Rome Regional Air Control Centre for three successive work shifts: afternoon (13:00-20:00), morning (07:00-13:00) and night (20:00-07:00). The number of aircraft under control per hour was recorded as index of workload. Recordings involved subjective ratings (mood, physical fitness, fatigue) and objective measures (heart rate, vanillyl mandelic acid excretion, reaction times, critical flicker fusion, oral temperature). In addition, the subjects filled out questionnaires for personality traits (extroversion, neuroticis, anxiety) and behavioural characteristics (morningness, rigidity of sleeping habits, vigourness to overcome drowsiness). The volume of air traffic varied greatly with peaks during the day and low levels at night. Nevertheless, the heart rates of the group members showed quite constant levels in all the three shifts, irrespective of the workload. The same pattern appeared in the controllers' excretion of VMA, which remained high during both day and night shifts, regardless of the reduced workload. The subjective mood and physical fitness decreased similarly, while feelings of fatigue increased on all three shifts, particularly on the night shift. The circadian rhythm of the oral temperature showed a slight modification of the nocturnal depression during the night shift, caused by the state of awakeness and activity. However, the rhythm was not altered in its normal circadian phase, due to the fast shift rotation adopted. The psychophysiological responses were affected by personal characteristics, in particular morningness and ability to overcome drowsiness.

A rare case of melanotic neuro-ectodermal tumour of infancy is presented. A 5-month-old child presented with rapidly progressing large swelling that almost filled up the opening of oral cavity. The vanillyl mandelic acid level was increased in the 24-hour urine sample of the child. Surgical excision was done and recovery was uneventful.

Headache and hypertension were the main clinical symptoms in this slim 77-year-old lady. Because the hypertension presented as paroxysmal and was combined with palpitations, dizziness, and sweating the suspicion of a phaeochromocytoma arouse. The vanillyl mandelic acid in the urine was elevated. As further investigation revealed that this elevation was due to medication with L-dopa because of Parkinson-syndrome. A proper history of the patients' medication or alternative laboratory tests prevent false conclusions.

In the Saitama prefecture in Japan, VMA (vanillyl mandelic acid) screening spot test for detection of neuroblastoma has been performed in 173,046 infants in the years 1981-1986 and 15 infants were found to have neuroblastoma. Two infants had mediastinal tumors and the remainder 13 had intraabdominal tumors. Only 7 infants had palpable masses. Although CT was documented to be the best imaging procedure to provide sufficient information for treatment, conventional radiographic examinations of the chest and abdomen, and abdominal ultrasonography were able, as initial imaging procedures, to detect reasonably small neuroblastomas in infants with a positive VMA screening test.

Pheochromocytoma is a catecholamine-secreting neoplasm of chromaffin tissue. The most common symptom is hypertension but there are incidentally discovered forms at imaging. From 1981 to 1998, the authors observed nine pheochromocytomas through three hospitals in Dakar. This study included seven male and two female patients. The average age was 31.61 years. Hypertension was present in 77% of the cases. Headache, palpitations and sweating were the authors most frequent symptoms, occuring in 55% of cases. Measurement of vanillyl mandelic acid level in six cases and urinary metanephrines in three cases made the diagnosis. There were six adrenal and three extra adrenal pheochromocytomas with two malignant tumors features. In our countries, measurement of urinary metanephrines and computed tomography processing may improve detection of pheochromocytomas.

Severe sustained hypertension occurs in only 0.1% of the paediatric population and only about 2% of these patients will have an underlying endocrine cause. Phaeochromocytoma as a catecholamine-secreting tumour causing severe hypertension is exceedingly rare in children. A high index of suspicion and an awareness of the clinical spectrum are therefore necessary to make the diagnosis. Phaeochromocytomas can have protean manifestations which may be mistaken for a variety of clinical conditions. We highlight the problems encountered in making the diagnosis in an 11-year-old Chinese girl who presented with sustained hypertension, heart failure and transient renal impairment with two normal 24-hour urinary vanillyl mandelic acid (VMA) results before a third produced the diagnosis. We emphasize that total reliance on a single biochemical urinary screening is not acceptable. The measurement of urinary catecholamines or their metabolites increases the sensitivity of diagnosis. We recommend that in situations where biochemical screening is doubtful, appropriate imaging should be undertaken to exclude the diagnosis.

OBJECTIVE

We describe a rare combination of pheochromocytoma and medullary thyroid carcinoma (MTC) during pregnancy.

METHODS

Twenty-three-years old lady, primigravida, was detected to be hypertensive at 12 weeks of gestation and was found to have left adrenal mass on routine obstetric scan. She had a goitre on examination which was proven to be MTC on fine needle aspiration cytology. Twenty-four hours urinary vanillyl mandelic acid and serum calcitonin levels were elevated. After adequate α and β blockade she underwent left adrenalectomy during second trimester of gestation with no significant perioperative complications. Twelve days later she underwent total thyroidectomy.

RESULTS

Adrenal mass was confirmed to be pheochromocytoma while MTC was confirmed in the thyroidectomy specimen. Post-operatively, she was normotensive and delivered a healthy female baby at term. Both mother and the baby tested positive for germline RET mutation (C634W) in exon 11.

CONCLUSIONS

We describe a rare case of pregnant multiple endocrine neoplasia-2A patient with pheochromocytoma and MTC.

Pheochromocytoma accounts for approximately 25% of incidentally discovered adrenal masses. Certain diagnostic procedures (e.g., adrenal arteriography, needle biopsy of an adrenal mass), anesthesia and abdominal surgery may cause a sudden release of catecholamines from a pheochromocytoma and induce paroxysmal attacks of hypertension. In addition, pheochromocytoma is well known to cause unsuspected operating room deaths. Therefore, we must carefully separate this functioning neoplasm from other types of adrenal masses. In this study, we compared the results of noninvasive tests including (1) assay of urinary catecholamines and their metabolites, (2) a provocative pharmacologic test using metoclopramide (MCP test), and (3) 131I-metaiodobenzylguanidine (MIBG) scintigraphy to screen for pheochromocytoma in 10 consecutive patients with an incidentally discovered adrenal mass (6 pheochromocytomas and 4 non-functioning adrenocortical adenomas). We measured the 24-hour urinary excretion of catecholamines, metanephrines and vanillyl mandelic acid in all 10 patients; 5 were positive, 4 were negative and 1 was false-negative (sensitivity = 83%, specificity = 100%). The MCP test was performed in 7 patients; 3 were positive, 3 were negative and 1 was false-negative (sensitivity = 75%, specificity = 100%). MIBG scintigraphy was performed in 7 patients; 4 were positive, 1 was negative and 2 were false-negative (sensitivity = 67%, specificity = 100%). According to these results, all patients with an incidentally discovered adrenal mass should undergo a determination of the 24-hour urinary excretion of catecholamines and their metabolites, including metanephrines. If this urine assay is negative, other noninvasive tests including the MCP test and MIBG scintigraphy should be considered in selected patients with radiographic characteristics of pheochromocytoma.

A 77-year-old man with a low grade fever persisting for 30 days consulted a local physician. A computed tomographic scan of the abdomen showed a mixed density mass on the left adrenal gland. He was referred to our hospital for further examination. Hormonal assay demonstrated a slightly high level of noradrenalin in the serum (18 pg/ml) and vanillyl mandelic acid in the urine (6.2 ng/ml). Magnetic resonance imaging revealed a heterogeneous mass lesion 3 cm in diameter with a high signal intensity on both T1 and T2 weighted images. Angiography showed a hypovascular mass in the supra-renal region suggesting an adrenal tumor or malignancy. Left adrenalectomy combined with en bloc nephrectomy was performed because of severe adhesion. Histologic evaluation showed hematoma without malignant cells due to idiopathic adrenal hemorrhage.

206 case records of the patients treated from 1985 to 1998 for various diseases of the adrenal glands were analyzed. In 39 (18.9%) patients tumors were chance finding at ultrasound examination or computer tomography of the abdominal cavity and retroabdominal space. 25 patients from this group were operated on, 14 patients were not operated and were followed up from 1 month to 7 years. All the patients underwent complex examination including analysis of the complaints, anamnesis and physical examination data, hormonal status examination (ACTH, hydrocortisone, 11-oxycorticosteroids, 17-ketosteroids, aldosterone, renin, adrenalin, noradrenalin, vanillyl-mandelic acid), device methods of examination USE, CT, MRT, superselective phlebography with separate catheterization of adrenal veins and blood intake per floor, fine needle aspiration biopsy under ultrasound control. Comparison of the results of complex clinical examination with morphological data of removed adrenal glands was carried out retrospectively. Arteriography and superselective phlebography with separate catheterization of adrenal veins and per floor taking of blood samples, performed in 36 patients, enabled not only to supplement and define more exactly the other methods of topical diagnosis, but also to asses objectively functional actively of the affected and contralateral adrenal. Despite the fact that during the study of hormonal level in peripheral blood of patients it was normal analysis of the data obtained by superselective phlebography of adrenal veins and per floor taking of blood samples showed significant increase in hormones level in blood of all operated patients. Comparison of the data of superselective phlebography with separate catheterization of adrenal veins and per floor taking of blood samples and clinical picture of the disease made it possible to suggest the presence of preclinical (subclinical) Cushing or Conn syndrome. Operative treatment was not indicated in the absence of hormonal activity of the tumor (i.e. preclinical syndromes by Icenko-Cushing, Conn, pheochromocytoma, the virilizing and feminizing tumors), tumors of small size (less than 3 cm), in absence of malignant growth features confirmed by complex instrumental examination (USE, CT, MRT, fine-needle aspiration biopsy under US control, superselective phlebography with per floor taking of blood samples). Such patients were reexamined in 6 months. During the follow up period no changes of tumor size, homogeneity, hormonal status were revealed.

The effect of pretreatment and simultaneous treatment with thiamine on therapeutic efficacy of calcium disodium edetate (CaNa2EDTA) in lead intoxication was investigated in rats. The animals exposed to Pb as Pb (CH3COO)2·3 H2O through drinking water (0.1%) for 8 wk were treated with either saline, thiamine-HCl (sc), CaNa2EDTA (ip), or thiamine-HCl plus CaNa2EDTA, for 3 d or thiamine-HCl for 3 d followed by thiamine, then HCl plus CaNa2EDTA for a further 3 d. The Pb exposure caused significant accumulation of Pb in liver, kideny, and brain, inhibition in the activity of blood δ-amino-levulinic acid dehydratase (δ-ALAD), and increase in levels of urinary δ-aminolevulinic acid, homovanillic acid (HVA), vanillyl mandelic acid (VMA), brain HVA and VMA. The brain δ-ALAD and lipomide dehydrogenase remained unaffected by Pb. Thiamine significantly enhanced the urinary excretion of Pb by CaNa2EDTA, but only marginally influenced the efficacy of CaNa2EDTA to either mobilize tissue Pb or reverse the biochemical alterations.

BACKGROUND

Catecholamine-producing neuroendocrine tumours are found in chromaffin cells of the adrenal medulla (phaeochromocytoma) or extra-adrenal paraganglia (paraganglioma), known collectively as PPGLs. In approximately a quarter or more of cases of PPGL, these rare tumours arise as a result of germline mutations of several tumour susceptibility genes. At the Crosshouse laboratory, urine tests include free metadrenalines (fMAs) (also known as free metanephrines) which demonstrate superior sensitivity over that obtained by urinary vanillyl mandelic acid, catecholamines or plasma catecholamines in the diagnosis of PPGL. This retrospective audit was to determine if urinary fMAs offered discrimination among the hereditary forms of PPGL.

METHODS

Retrospective biochemical and genetic data were gathered from 1997 to 2011. The identified urine specimens were those obtained at the time of first diagnosis or recurrence of PPGL. Results of catecholamines and metabolites were standardized as multiples of their respective relevant upper reference limits (URLs).

RESULTS

Results were available for 29 affected patients (15 females and 14 males), median age 26 (range 9-63) years, comprising three mutation groups: succinate dehydrogenase subunit B or D ([SDHB/D] 16 patients), multiple endocrine neoplasia type 2 ([MEN 2] 6 patients) and von Hippel-Lindau disease ([VHL] 7 patients). The parent catecholamines exhibited increased values for noradrenaline (NA) and/or adrenaline (AD) for 25/29 (86.2%) patients. Either or both free normetadrenaline (fNMA) and fMA were elevated in 29/29 (100%) patients.

CONCLUSIONS

The ratio of the multiples of URL for fMA/fNMA displayed a clearer separation of MEN 2 patients from those with SDHB/D or VHL than did the equivalent AD/NA ratio.

A short term course (8-11 days) of diethylpropion 50 mg a day was administered to 12 obese children of both sexes fed a mixed low calorie diet containing about 1000 calories/day. A group of 10 obese children received the same diet and no medication. The sex-distribution was similar in both groups as well as the degree of overweight (appreciated by the Quettelet index). The urinary excretion of some noradrenergic derivative (adrenaline-A, noradrenaline-NA, vanillyl-mandelic acid VMA, metanephrines NM and methoxy hydroxyphenyl glycol-MHPG) and of homovanillic acid (HVA) was measured in both groups before and after drug therapy or diet, respectively. After the diethylpropion course, the urinary mean value of MHPG decreased (2.17 +/- 0.30, mean +/- SE vs 1.47 +/- 0.21) but the significance was borderline. The mean level excretion of NA, VMA, MN and HVA were significantly lower following diethylpropion. No significant change was observed in the diet-only group of patients as regards the same determinations. These observations are not entirely explained by the previous pharmacologic knowledge on diethylpropion and other sympathomimetic amines.

A specific and practicable method is described for the quantitative determination of urinary phenol- and indole-carboxylic acids. High specificity is achieved by a preliminary separation of the free acids (extracted from the urine sample) with the aid of organophilic gel chromatography on Sephadex LH 20, followed by gas chromatographic analysis of the silyl derivatives of the acids. The organophilic gel chromatography of the free acids shows a high recovery rate in the micro- and submicrogram range. The difficulties encountered in other techniques in the derivatisation and gas chromatographic separation of the individual components are avoided by using the preliminary separation, and by using N-methyl-N-trimethylsilyl-trifluoroacetamide for the derivatisation. Use of this preparation technique with a direct read-out gas chromatograph with automatic sample introduction, gives high accuracy and precision, and a facility for the determination of a wide range of aromatic acids in urine.