In this study we evaluated the motor co-ordination in Wistar strain albino rats that were maintained on a protein-restricted diet for a period of 1 year immediately after the weaning period, by substituting 75% of the normal diet with a carbohydrate-rich diet deficient in protein, for a period of 1 year immediately after the weaning period. This type of chronic protein restriction caused disturbances in motor co-ordination. It also caused a significant reduction in the basal levels of dopamine, norepinephrine, epinephrine and serotonin along with their metabolites homovanillic acid (HVA), vanillyl mandelic acid (VMA) and 5-hydroxy indoleacetic acid (5HIAA) and precursor L-dopa in the corpus striatum and cerebellum. Changes in these neurotransmitters could have caused altered co-ordination in the protein-restricted animals.

A 40-year-old woman was admitted because of abdominal pain and diarrhea. She sometimes experienced paroxysmal hypertension, sweating, headache, and palpitation. Sigmoidoscopic findings showed well-demarcated diffuse mucosal edema, hyperemia, and easy touch bleeding from distal descending colon up to the splenic flexure area. Barium x-ray showed loss of haustral marking, thumb printing appearance, and diffuse luminal stenosis in the transverse, descending, and sigmoid colon. On the abdominal computed tomogram, a 3.8-cm sized well-enhanced right adrenal mass was incidentally found. Twenty-four hour urinary excretion of vanillyl mandelic acid, norepinephrine, and normetanephrine were increased. Iodine131 metaiodobenzylguanidine scan showed hot uptake on the right adrenal gland compatible with pheochromocytoma. Exploratory laparotomy was done under the impression of ischemic colitis associated with pheochromocytoma. Adrenalectomy and resection of the stenotic left colon were performed. After surgery, pain subsided, blood pressure fell gradually, blood sugar and catecholamine level became normal, and bowel habit returned to normal.

Eighteen hypertensive patients with a clinical suspicion of pheochromocytoma and raised or borderline raised plasma catecholamine and urinary vanillyl mandelic acid (VMA) levels were studied by scintigraphy using 123I-labeled metaiodobenzylguanidine (MIBG). None of these patients had any scintigraphic evidence of pheochromocytoma at the time of study or on subsequent clinical follow-up. A quantitative approach was taken to calculate the adrenal medullary uptake of [123I]MIBG in these patients. Three different methods of quantitation were evaluated using data acquired from an anthropomorphic phantom and analysed by three independent observers. In the patient studies 34 out of 35 adrenal medullas were visualized with uptake in the range of 0.01-0.22% of the administered dose 22 hr postinjection which was calculated using the preferred quantitation method. This is an appropriate control group range for comparison with patients who have proven norepinephrine and epinephrine secreting tumors. A quantitative approach to [123I]MIBG imaging provides an important tool for studying adrenomedullary pathophysiology.

We have measured the concentrations of substance P, somatostatin, homovanillic acid (HVA), vanillyl mandelic acid (VMA) and 5-hydroxyindoleacetic acid (5-HIAA) in the cerebrospinal fluid (CSF) of six patients suffering from narcolepsy and 12 age- and gender-matched controls using high pressure liquid chromatography (HPLC) and radioimmunoassay (RIA). Substance P and somatostatin were significantly decreased in our patients compared to controls (36.9 +/- 9.1 fmol/ml versus 52.5 +/- 9.9 fmol/ml, P < 0.05 and 30.3 +/- 7.8 fmol/ml versus 43.9 +/- 9.8 fmol/ml, P < 0.05, respectively). 5-HIAA (P < 0.05) and VMA (P < 0.05) were also significantly decreased. HVA was significantly increased (P < 0.01). The CSF concentrations of substance P and somatostatin correlated with the clinical parameters duration of disease (r = -0.68, P < 0.05 and r = -0.72, P < 0.05, respectively) and severity of cataplectic symptoms (r = -0.71, P < 0.05 and r = -0.78, P < 0.01). In addition, substance P correlated with the intensity of sleepiness and the frequency of day-sleep attacks (r = -0.69, P < 0.05 and r = -0.68, P < 0.05, respectively). Substance P affects the amount of dopamine release in the nigra-striatal region, and decreased amounts could contribute to the pathogenesis of narcolepsy. Reduced levels of substance P, which affects serotonin release, may be responsible for diminished release of serotonin which in turn could affect sleep cycles. Because somatostatin affects motor behavior through dopaminergic mechanisms and since the levels of somatostatin correlate with the intensity of cataplectic symptoms, we speculate that an interaction between somatostatin and dopaminergic neurons plays a role in the pathogenesis of narcolepsy.

A primiparous, full-term, 28-year-old woman underwent an emergency lower segment Caesarean section under epidural anaesthesia for failure to progress in the first stage. Despite an uneventful pregnancy and delivery, she developed a hypertensive crisis in the postoperative period complicated by acute pulmonary oedema requiring ventilation for 48 h in the intensive care unit. Intravenous magnesium sulphate infusions and hydralazine boluses were used to control the blood pressure, which was associated with clonus, hyperreflexia, tachycardia and profuse sweating. The patient made a good recovery. Later measurement of urinary catecholamines in the recovery phase showed greatly elevated levels of norepinephrine, dopamine and vanillyl mandelic acid. Further investigations included a normal abdominal computed tomography scan and a I-123 meta-iodo-benzyl-guanidine scintigraphy scan which revealed a 3- to 4-cm irregular tumour located at the level of the lower pole of the right kidney and further liver hot spots. Intravenous magnesium sulphate infusion proved successful in controlling hypertension caused by a phaeochromocytoma in the postpartum period.

Capillary zone electrophoresis with photodiode array detection at 220 nm was used for analysis of catechol compounds in human urine. The method was optimized with reference compounds 3,4-dihydroxybenzylamine, adrenaline, noradrenaline, normetanephrine, dopamine, dopac (homogensitic acid), methanephrine, vanillyl-mandelic acid, 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid and 3-methoxytyramic acid at pH 4.0 and 8.0 for their electrophoretic separation. The UV spectra of the catechols were detected at a concentration of 20 microM. Repeatability of the method calculated using the absolute migration times of the catechols was below 1.5% and using the peak areas below 5%. The patient samples were hydrolyzed by 0.5 M acid or base solutions. In the studies, a few patient samples were analyzed using 3,4-dihydroxybenzylamine as an internal standard. In the hydrolysis steps needed for their detection in urine, all the other catecholamines, except 5-HIAA, did not decompose to detectable species at 220 or 254 nm. The concentrations of the catecholamines observed in real samples were at nM levels.

We analyzed a group of nine neonates diagnosed with adrenal gland hemorrhage in the years 2007-2011, to evaluate diagnostic methods. We assessed risk factors and factors predisposing to hemorrhage. Severe and moderate perinatal hypoxia was found in 5 cases, while sepsis in 4 cases. Three patients had bilateral adrenal hemorrhage. All patients underwent ultrasound examination and color Doppler US. Their levels of vanillyl-mandelic acid in 24-h urine collection were normal. A complete regression of changes without evidence of adrenal hemorrhage or vascular flow on color Doppler US was found in the period from the 20(th) to the 165(th) day of life.

CONCLUSIONS

1. Color Doppler ultrasound findings, observation of the evolution of changes and a lack of vascular flow in adrenal glands, are suggestive of bleeding. Color Doppler ultrasound seems to be the most important diagnostic method. 2. The level of urinary catecholamine metabolites (vanillyl-mandelic acid) does not fulfill the role of screening test for neuroblastoma. However, increased levels of these metabolites may suggest a diagnosis other than the adrenal hemorrhage.

BACKGROUND

Adrenal mature TMT is very rare. So far, only two cases have been reported.

METHODS

We report a rare case of malignant transformation of a mature teratoma in the right adrenal gland of a 36-year-old Chinese female. The patient had been asymptomatic until physical exam identified a palpable mass in the right abdomen. Abdominal non-enhanced computed tomography (CT) scan showed a huge tumor with mixed density in right adrenal region, which had cystic components, fat, calcifications, and separations. Contrast-enhanced CT showed significant enhancement of the cyst wall and septations as well as mural nodules. In addition, the patient had four abnormal laboratory results, including cortisol 773.58 mol/L ↑ (reference range 118.6 to 618 mol/L), adrenocorticotropic hormone (ACTH) 70.980 pg/ml ↑ (reference range 7.2 to 63.3 pg/ml), aldosterone 317.84 pg/ml ↑ (reference range prone: 49.3-175 pg/ml; Standing: 34.7-275 pg/ml; 24h urine 2.84-33.99 ug/d), and vanillyl mandelic acid (VMA) 22.38 mg / 24 h ↑ (reference range 0-13.6 mg / 24 h) which to our knowledge have not been reported by any adrenal mature teratoma's reference literature.

UNASSIGNED

It was initially diagnosed as a right adrenal hamartoma by the radiologist. Final pathology confirmed it as malignant transformation of a right adrenal mature teratoma, which is extremely rare.

METHODS

Laparoscopic resection is usually the treatment of choice for adrenal teratoma and our case report is no exception.

RESULTS

This article is a case report, no outcomes.

CONCLUSIONS

Non-enhanced CT findings of a mass with cystic change, fat, calcification and separation are suggestive of a teratoma. If there is significant enhancement of the cyst wall and septations as well as mural nodules in contrast-enhanced CT, then adrenal TMT should be considered. In addition, abnormal levels of hormones including cortisol, ACTH, aldosterone and VMA may also aid in the diagnosis of adrenal TMT.

BACKGROUND

Phaeochromocytomas are rare tumors of chromaffin cells of neural crest that classically present with symptoms of catecholamine excess such as palpitations, headache and sweating. They are diagnosed by measuring plasma or urinary levels of catecholamines or their metabolites. Anatomic localization is done by computed tomographic scan or magnetic resonance imaging, or meta-iodobenzyl guanidine scan in certain cases. Adequate preoperative catecholamine blockade prevents perioperative hemodynamic instability.

OBJECTIVE

To study the clinical spectrum and management of phaeochromocytomas in a tertiary care centre, Tribhuvan University Teaching Hospital, in Nepal.

METHODS

Retrospective review of case records of histologically proven cases of phaeochromocytomas from 2008 -2011 was done, and data collected on clinical spectrum, diagnostic modalities, perioperative management and follow-up.

RESULTS

Twelve cases of phaeochromocytomas were operated. The mean age was 36.41+/-14.07 years. There were 2 bilateral phaeochromocytomas and 1 extraadrenal paraganglioma. Apart from the common symptoms of catecholamine excess, patients had atypical presentations like psychiatric manifestations and blurred vision. A combination of urinary Vanillyl Mandelic Acid and computed tomographic scan was used for diagnosis, and open surgery was done in all cases. Pre-operative blood pressure control was achieved by prazocin or calcium channel blockers. Ten patients had intraoperative surge in blood pressure. There were no major morbidity or mortality. Three patients had high blood pressure postoperatively, but were effectively managed with antihypertensives.

CONCLUSIONS

Phaeochromocytomas can have variable presentation. Good preoperative preparation and perioperative management can result in an excellent outcome.

1. Plasma noradrenaline concentrations were similar in normotensive and hypertensive outpatients, but were significantly lower in laboratory control subjects. 2. Standing plasma noradrenaline concentrations were similar in all three groups. 3. Urinary vanillyl mandelic acid, catecholamines and metanephrines were also similar in the normotensive and hypertensive groups. 4. Laboratory controls, possibly because of familiarity with the techniques of sphygmomanometry and blood sampling, may attain a 'basal' resting level of sympathetic nervous discharge more readily and rapidly than subjects who are unfamiliar with such procedures. 5. After orthostatic stimulation by standing for 2 min, the activity of the sympathetic nervous system, as determined by pulse rate and plasma noradrenaline concentrations, was similar in the three groups, despite the lower starting values in the laboratory staff. 6. The absence of differences in plasma noradrenaline or urinary catecholamine and metabolite concentrations does not support the hypothesis of excessive sympathetic nervous activity in essential hypertension.

A high-performance liquid chromatographic method for the determination of catecholamines and their precursor and metabolites [amino compounds (norepinephrine, epinephrine, dopamine, normetanephrine, metanephrine, 3-methoxytyramine, and L-DOPA), acidic compounds (3,4-dihydroxyphenylacetic acid, vanillyl-mandelic acid, and homovanillic acid), and alcoholic compound [4-hydroxy-3-methoxyphenyl)ethylene glycol)] in human urine and plasma. Urine and plasma samples deproteinized with perchloric acid in the presence of isoproterenol and 3,4-dihydroxyphenylpropanoic acid (internal standards) are fractionated by solid-phase extraction on a strong cation-exchange resin cartridge (Toyopak IC-SP S) into two fractions (amine fraction and acid-alcohol fraction). The compounds in each fraction are separated by an ion-pair reversed-phase chromatography on a TSK gel ODS-80TM with isocratic elution and on-line derivatized by periodate oxidation followed by a fluorescence reaction using meso-1,2-diphenylethylenediamine. The detection limits (S/N = 5) vary from 0.5 to 95 pmol/ml, depending on the compounds.

The concentration of dopamine (DA), norepinephrine (NE), and its metabolites 3-methoxy-4-hydroxy-phenylethylene glycol (MHPG) and vanillyl mandelic acid (VMA), and prostaglandins E2, and F2a in amniotic fluid were measured at labor (1-3 cm of cervical dilatation), in uncomplicated and complicated pregnancies. The amniotic fluid concentration (mean +/- SD) of MHPG in maternal smoking (S) (30.6 +/- 11.9 nmol.mg creatinine-1) and intrauterine growth retardation (IUGR) (36.7 +/- 15.2 nmol.mg creatinine-1) groups is significantly higher than in uncomplicated pregnancies (C) (22.9 +/- 8.8 nmol.mg creatinine-1), or diabetes mellitus groups (D) (26.1 +/- 10.9 nmol.mg creatinine-1) groups; VMA presents similar differences between groups S (145.8 +/- 84.4 nmol.mg creatinine-1) and IUGR (173.0 +/- 135.4 nmol.mg creatinine-1) higher than C (58.3 +/- 26.1 nmol.mg creatinine-1) and D (76.8 +/- 49.0 nmol.mg creatinine-1) groups. NE levels differ between groups in a similar way, but DA does not present significant differences between groups. Prostaglandin levels are higher in the S than in the C group. Nicotine action and/or hypoxia are proposed as a possible cause of NE, MHPG, and VMA rise in amniotic fluid of S, and IUGR versus C or D groups.

For 15 years a now 70-year-old woman had been having occasional episodes of circulatory collapse which 7 years ago were diagnosed as being caused by severe idiopathic orthostatic hypotension. These episodes had recently become much more frequent and she was hardly able to be upright for more than one minute. In the Schellong test the blood pressure fell from 80/50 mm Hg when lying to 70/30 mm Hg on standing, the pulse rate remaining unchanged at 60/min. The standing test had to be abandoned after 90 seconds. Serum catecholamine concentrations (epinephrine 65 ng/l, norepinephrine 100 ng/l) did not rise on standing (epinephrine 25 ng/l, norepinephrine 105 ng/l). 24-hour urinary excretion of vanillyl mandelic acid was at the lower limit of normal (2.2 mg). The autonomic dysfunction of circulatory control suggested a Shy-Drager syndrome. Other signs of autonomic failure included gastroparesis, decreased tear and sweat secretion and transitory urinary incontinence. Symptomatic treatment with elastic stockings, fludrocortisone, etilefrine, dihydroergotamine, L-dopa, yohimbine and amezinium methylsulfate gave the patient greater mobility without achieving normal blood pressure responses.

This study was undertaken to clarify the relationship between mild transient hypertension and dilated cardiomyopathy. Fifty-five patients were studied: group 1--controls (12 patients), group 2--hypertensives without clinical evidence of heart failure (14 patients), group 3--patients with hypertensive heart failure and diastolic blood pressure above 100 mmHg (10 patients), group 4--patients with possible dilated cardiomyopathy with mild hypertension, i.e. diastolic blood pressure of 90-100 mmHg (8 patients), group 5--patients with dilated cardiomyopathy and normal blood pressure (11 patients). The haemodynamic status and cardiac contractility indices were measured in each patient on admission, using M-mode echocardiography. Serum sodium and potassium as well as the urinary sodium, potassium and vanillyl mandelic acid excretions were also measured. The stroke volume, cardiac output and cardiac index fell with heart failure, but much more remarkably in group 4. The peripheral vascular resistance was higher in groups 2, 3 and 4 than in groups 1 and 5; so also were the aortic diameter, left posterior wall thickness and left ventricular mass. The plasma volume, aldosterone and cortisol levels were higher and the urinary sodium and potassium excretion lower in patients with heart failure (groups 3, 4 and 5). It is concluded that the raised blood pressure found in some patients suspected to have dilated cardiomyopathy is not due to the haemodynamic and biochemical changes that occur in heart failure. Such patients are 'chronic' hypertensives with hypertensive heart failure. Their presenting blood pressure is low because of their markedly reduced cardiac output.

BACKGROUND

MDM2 SNP309, characterised by a T-to-G substitution in the MDM2 promoter, is associated with higher gene expression compared to wild type and was recently found to be a negative prognostic factor for patients with stage 4 neuroblastoma (NB), but not for children with localised disease. This polymorphism was not associated with any clinical or genetic tumour characteristics, including MYCN amplification and 1p chromosome deletion.

METHODS

To better define the involvement of MDM2 SNP309 in NB, we explored its association with the main biochemical tumour markers, namely urinary concentrations of vanillyl mandelic acid (VMA) and homovanillic acid (HVA) and blood concentrations of ferritin and lactate dehydrogenase (LDH). A cohort of 497 NB children, enrolled in the Italian Neuroblastoma Registry between January 1985 and December 2005 and previously investigated for the prognostic role of MDM2 SNP309, was considered for this study.

RESULTS

VMA and HVA concentrations as well as HVA/VMA ratio were not affected by the MDM2 SNP309 genotype. Ferritin and LDH concentrations were significantly lower in TT than in TG/GG only in patients with stage 4 disease (P = 0.007 and 0.015, respectively). No association emerged in patients with localised disease. These findings were not affected by confounding from clinical or biological characteristics.

CONCLUSIONS

The association between MDM2 SNP309 and both ferritin and LDH in patients with stage 4 disease confirms the prognostic role of this polymorphism. The results suggest that the MDM2 SNP309 genotype can impact on tumour responses to hypoxia and might play an important role in the alteration of energetic metabolism in NB cells.

We reported a 14-year-old boy who had had multiple thyroid nodules for 4 yrs. Physical examination revealed marfanoid habitus, coarse facies with thick lips and prominent jaw. Mucosal neuromas were present on the buccal mucosa, tongue and upper eyelids. Thyroid scan demonstrated multiple, cold nodules and medullary thyroid carcinoma was confirmed by pathological examination. He was normotensive and his 24 hrs urinary vanillyl mandelic acid was in the normal range. Computerized tomography demonstrated normal adrenal glands. Multiple endocrine neoplasia type IIb (MEN IIb) was diagnosed by the appearance of typical phenotypic features, multiple mucosal neuromas and medullary thyroid carcinoma. The scarcity of such reports in children and the importance of early recognition of this disorder prompted us to describe this patient.

A 49-year-old woman was diagnosed in 1985 as having pheochromocytoma because of hypertension with high levels of plasma catecholamine concentration and 24-hour urine excretion of vanillyl-mandelic acid and metanephrine together with a right adrenal mass. The excised tumor cells had fine granular basophilic cytoplasm with argyrophilic granules by Grimelius' method. Four years later, she was diagnosed as having a duodenal bulb ulcer. Serum gastrin showed an abnormally high level of 1900 pg/ml. Abdominal echogram and computed tomography revealed a hypoechoic lesion in the pancreas and intrahepatic multiple tumors. A needle biopsy specimen of the liver tumor was compatible with the histology of metastatic islet cell tumor. A diagnosis of Zollinger-Ellison syndrome was made due to malignant gastrinoma with multiple liver metastases. The patient had no family history of endocrinological or neoplastic disorders. The present case indicates the possibility that pheochromocytoma and gastrinoma, that is, endocrine tumors characteristic of multiple endocrine neoplasia (MEN) I and MEN II, may be coincident even in a person without MEN. A continued awareness of previously rare or undescribed manifestations is important in patients with islet cell tumors or pheochromocytoma.

Adrenocortical carcinoma (ACC) is a malignant tumour arising from the adrenal cortex, while pheochromocytoma is a catecholamine secreting tumour of the adrenal medulla or extra adrenal sites. Both conditions are very rare, with incidence of approximately 1-2 cases per million adults annually. Most adrenocortical tumours are functioning. ACC can be associated with clinical Cushing syndrome and virilisation due to excessive production of cortisol and androgens, respectively. However, it is rare for ACC to present clinically as pheochromocytoma. We report a case of a 28-year-old lady who presented with paroxysmal hypertension and palpitations associated with raised urinary vanillyl mandelic acid. On examination, there was postural hypotension and ballotable mass in right lumbar region with no obvious features suggestive of Cushing syndrome or virilisation. A huge right suprarenal mass with areas of necrosis and calcification was noted on the abdomen CT. A right adrenalectomy was done. The histology was consistent with ACC. There are reported cases of ACC presenting with clinical features of pheochromocytoma but limited in number, accounting for barely a dozen cases in the literature. This pseudopheochromocytoma may be due to the presence of neuroendocrine features in ACC.

Pheochromocytoma rarely extends locally into the vena cava or the right atrium. We report a case of malignant pheochromocytoma with growth into the inferior vena cava, extending into the right atrium, address clinical aspects of this tumour and review the literature on this malignancy. Pre-operative work-up of this tumour should include measurements of urinary vanillyl mandelic acid and cathecholamine excretion, MRI and spiral CT of the abdomen and thorax. After the diagnosis is made the patient should be treated with catecholamine alpha-receptor blockade and if necessary with subsequent beta-receptor blockade. An aggressive surgical approach is always warranted, even in cases with very large localized tumours, because surgery has been shown to lead to relief of symptoms and to prolong survival in cases otherwise deemed irresectable. The optimal surgical exposure is obtained via a transsternal midline thoraco-laparotomy. If feasible, a combination of cardiopulmonary bypass, hypothermia, cardiac arrest and exsanguination procedures should be used. In case of local of tumour remnants after surgery or distant metastases treatment options are secondary surgery, tumour embolization, or treatment with radioactive labelled drugs, including(131)I-MIBG.