A case of von Recklinghausen's disease associated with pheochromocytoma and papillary carcinoma of the thyroid gland

A 58-year-old woman was admitted to our hospital complaining of headache, dizziness and intermittent elevation of blood pressure. Multiple café-au-lait spots and neurofibromas had appeared on the back and the limbs since the age of 30 years. At the age of 54 years she underwent total thyroidectomy because of papillary carcinoma of the thyroid gland. On admission, the levels of plasma norepinephrine and epinephrine, urinary norepinephrine and normetanephrine were all within the normal range. However, urinary excretion of metanephrine was markedly increased to 1.49 +/- 0.45 (Mean +/- SD) mg/day and that of epinephrine was also slightly increased. The computed tomographic scans of the abdomen and the scintigraphy with 131I-metaiodobenzylguanidine revealed a tumor mass in the region of the right adrenal gland. The tumor was histologically confirmed to be pheochromocytoma at the operation. In her family history, her mother and one of her two sisters had von Recklinghausen's disease and another sister suffered from follicular carcinoma of the thyroid gland. As far as we know, this paper is the first report of a patient with von Recklinghausen's disease associated with both pheochromocytoma and non-medullary carcinoma of the thyroid gland, and her family.     

Endocrine-disrupting effects of nonylphenol in the newt, Triturus carnifex (Amphibia, Urodela)

The aim of our study was to verify whether environmental concentrations of nonylphenol influenced the adrenal gland of Triturus carnifex. Newts were exposed to 19 μg/L nominal concentration of nonylphenol throughout the periods of December-January and March-April, corresponding to different stages of the chromaffin cell functional cycle. The morphological features of the steroidogenic and chromaffin tissues, and the serum levels of ACTH, aldosterone, corticosterone, norepinephrine and epinephrine were evaluated. Nonylphenol did not influence ACTH serum levels. During the two periods examined, the steroidogenic tissue had the same reaction: the quantity of cytoplasmic lipids, and the corticosteroid serum levels, decreased, suggesting the inhibition of synthesis and release of corticosteroids. During the two periods examined, the chromaffin tissue reacted differently to nonylphenol. During December-January, the numeric ratio of norepinephrine granules to epinephrine granules, and the epinephrine serum levels, increased, suggesting the stimulation of epinephrine release. During March-April, the numeric ratio of norepinephrine granules to epinephrine granules did not change, and the norepinephrine serum levels decreased, suggesting the inhibition of norepinephrine release. Our results show that nonylphenol influences the activity of the newt adrenal gland; considering the physiological role of this gland, our results suggest that nonylphenol may contribute to amphibian decline.     

Pheochromocytoma associated with adrenocortical adenoma: case report and literature review

The case of a 60-year-old woman with pheochromocytoma and concomitant adrenocortical adenoma in the same gland is presented. She complained of episodic headache, palpitation, nausea, vomiting and sweating. Physical examination revealed that the patient has generalized obesity, wet skin and paroxysmal hypertension, but no signs of Cushing's syndrome. Elevated levels of urinary noradrenaline, adrenaline and total metanephrine were sequentially observed. In addition, urinary 17-OHCS was also slightly elevated, but plasma cortisol was normal and suppressed after oral administration of 0.5 mg of dexamethasone. Abdominal echography and CT scanning demonstrated a left adrenal tumor, which took up both 131I-meta-iodobenzylguanidine and 75Se-scintadoren in the same region. A left adrenalectomy was performed and the tumor was found to consist of two parts, pheochromocytoma (2.5 X 2.5 X 2.5 cm) and cortical adenoma (2.5 X 3 X 5 cm). A total of 23 reported cases showing evidence of hyperfunction of the adrenal cortex and the medulla were noted. So far as we know, this patient was the second case of pheochromocytoma with adrenocortical adenoma in Japan.     

The Effects of Intra-Abdominal Hypertension on the Secretory Function of Canine Adrenal Glands

Intra-abdominal hypertension (IAH) can damage multiple organ systems, but the explicit impact on the adrenal gland is unclear. To evaluate the effects of intra-abdominal pressure (IAP) on the secretory function of the adrenal glands, we established canine models of IAH. By comparing morphology; hemodynamics; plasma cortisol, aldosterone, epinephrine, and norepinephrine concentrations; and the expression of IL-1, IL-6, and TNF-α in adrenal gland tissue from these dogs, we found that hemodynamic instability occurred after IAH and that IAH increased the plasma cortisol, aldosterone, epinephrine, and norepinephrine concentrations. Higher IAPs resulted in more significant changes, and the above indicators gradually returned to normal 2 h after decompression. Compared with the sham-operated group, IAH significantly increased IL-1, IL-6, and TNF-α levels in adrenal tissue, with larger increases in the presence of higher IAPs. However, the concentrations of these markers remained higher than those in the sham-operated group despite their decrease after 2 h of decompression. Histopathological examination revealed congestion, red blood cell exudation, and neutrophil infiltration in the adrenal glands when IAP was elevated; these conditions became more significant with more severe IAH. These results suggest that the secretion of adrenal hormones and adrenal gland inflammation are positively correlated with IAP and that abdominal decompression effectively corrects adrenal gland function.     

Association of Pheochromocytoma and Ganglioneuroma: Unusual Finding in Neurofibromatosis Type 1

ObjectiveTo report a rare case of association of pheochromocytoma and ganglioneuroma in an asymptomatic patient with neurofibromatosis type 1 (NF1) and to discuss the importance of annual biochemical and imaging studies.MethodsWe present the clinical, laboratory, and pathology findings in a 41-year-old woman with NF1 and review the pertinent literature.ResultsA 41-year-old woman with NF1 presented for a routine gynecologic examination, at which time a right adrenal mass (4 by 3 cm) was discovered by abdominal ultrasonography and confirmed by abdominal computed tomographic scans and magnetic resonance imaging. The patient was normotensive and complained only of discrete essential tremors. Biochemical studies showed a serum epinephrine level of 195 pg/mL (normal,<100) and a 24-hour urine epinephrine excretion of 55 μg (normal,<20), findings consistent with pheochromocytoma. Metaiodobenzylguanidine scintigraphy revealed uptake in the right adrenal gland, with no evidence of metastatic lesions. Before surgical treatment, the patient received an α-adrenergic antagonist for 30 days. Laparoscopic excision of the right adrenal gland yielded excellent postoperative results. Surgical pathology revealed a multinodular mass composed of pheochromocytoma and ganglioneuroma. In patients with NF1 (von Recklinghausen’s disease), a tumor consisting of pheochromocytoma and ganglioneuroma is rare and may be more aggressive than pheochromocytoma alone. An asymptomatic catecholamine-producing tumor may cause substantial morbidity and mortality, especially in patients who are undergoing surgical intervention or are under other stressors.ConclusionThe current guidelines for managing patients with NF1 are an annual history and physical examination. Because of the increased prevalence of pheochromocytoma and ganglioneuroma in patients with NF1, and the potential associated adverse effects, we emphasize the importance of periodic clinical evaluation with biochemical testing and imaging studies. (Endocr Pract. 2007;13:647-651)     

A case of extraadrenal pheochromocytoma with papillary thyroid carcinoma.

A 63-year-old housewife with a history of partial thyroidectomy was referred to our hospital because of a neck mass and abdominal tumor. Aspiration biopsy of the neck tumor revealed the recurrence of papillary thyroid carcinoma. Magnetic resonance imaging (MRI) of the abdomen and urinary and plasma catecholamine levels indicated that the tumor beside the abdominal aorta was an extraadrenal pheochromocytoma. Two tumors were excised and histologic studies confirmed the diagnosis. So far two cases of extraadrenal pheochromocytoma with papillary thyroid carcinoma have been reported. The present case indicates that the presence of papillary thyroid carcinoma should be considered in patients with extraadrenal pheochromocytoma.     

Human follicle-stimulating hormone modulation of adrenal gland activity in the Italian crested newt, Triturus carnifex (Amphibia, Urodela)

The aim of the present study was to verify if human FSH influences the adrenal gland of the newt, Triturus carnifex. Newts were given intraperitoneal injections of human FSH throughout the periods of February-March, and December-January; periods in which newt FSH levels are normally very low. The effects of human FSH on adrenal gland activity were observed in the morphological features of the steroidogenic and chromaffin adrenal cells, and in the serum levels of aldosterone, corticosterone, norepinephrine and epinephrine. The effect of human FSH on the steroidogenic cells was significant during the February-March period; the quantity of cytoplasmic lipids decreased, and the corticosteroid serum levels increased. During the December-January period, the human FSH effects were negligible. The effect of human FSH on the chromaffin cells was significant during both the February-March, and the December-January periods. During February-March, the human FSH increased the numeric ratio of norepinephrine granules to epinephrine granules, and increased the epinephrine serum levels. During December-January, the human FSH decreased the numeric ratio of norepinephrine granules to epinephrine granules, and increased the norepinephrine serum levels. The results of the present study show that human follicle-stimulating hormone influences the activity of the newt adrenal gland, thus indicating a relationship between the annual sexual cycle and the annual adrenal cycle of the newt.     

Effect of denervation and/or reserpine-induced changes on adrenomedullary catecholamines in pigeon: a fluorescence histochemical study

Splanchnic denervation of the left adrenal gland was made in adult pigeons of both sexes. Denervation of the adrenal medulla alone did not produce any appreciable change in adrenomedullary catecholamine fluorescence in pigeon. Reserpine, at the doses of 0.05 mg, 0.2 mg and 0.8 mg/100 gm body weight was injected in both innervated and denervated pigeons. Reserpine, at all doses, induced catecholamine fluorescence depletion from the innervated pigeon adrenal medulla. Denervation failed to affect reserpine-induced epinephrine depletion while it prevented reserpine-induced norepinephrine depletion only at a low dose of reserpine.     

A close correlation between the amount of met-enkephalin-immunoreactivity and epinephrine in adrenal pheochromocytoma tissue from patients with Sipple's syndrome

The concentration of epinephrine, norepinephrine, dopamine, met-enkephalin-, ACTH-, calcitonin- and somatostatin-like immunoreactivity (IR) were determined in the extracts of 9 adrenal pheochromocytomas from 7 patients. Six of these patients had Sipple's syndrome. There was a close correlation between the amounts of met-enkephalin-IR and of epinephrine present in the tumor tissue (p less than 0.01). Such a correlation was not found between catecholamines and the other polypeptide hormones investigated. The relevance of the close parallel in the occurrence of met-enkephalin-IR and epinephrine in human adrenal pheochromocytoma tissue is unknown, but it underlines earlier observations in the normal bovine and rat adrenal medulla on a co-storage and co-release of these substances in normal circumstances.     

Aspiration cytology of the oncocytic variant of papillary adenocarcinoma of the thyroid gland

OBJECTIVE: To study the cytologic features of the oncocytic variant of papillary adenocarcinoma of the thyroid gland to distinguish this subtype from other oncocytic lesions of the thyroid. STUDY DESIGN: We reviewed the smears from aspiration biopsies of 6 proven cases of oncocytic variant of papillary adenocarcinoma and compared their cytologic features with smears from 19 oncocytic follicular neoplasms (11 adenocarcinomas and 8 adenomas). Smears were stained with a modified Giemsa stain (Diff-Quik). RESULTS: All smears were cellular. Colloid was variable but more abundant in cases of the oncocytic variant of papillary adenocarcinoma. The cells in papillary adenocarcinoma had round to ovoid, overlapped nuclei; prominent intranuclear inclusions; and "grooves." Nucleoli were generally absent. In oncocytic follicular neoplasms, the cells had round nuclei and prominent nucleoli. Nuclear inclusions and grooves were seen but were not as prevalent as in papillary adenocarcinomas. CONCLUSION: The oncocytic variant of papillary adenocarcinoma of the thyroid gland can be distinguished from other oncocytic lesions by fine needle aspiration biopsy, whereas the absence of prominent nucleoli in oncocytes favors the diagnosis of an oncocytic papillary adenocarcinoma.     

In vivo evidence of regulation by pituitary-adrenal axis of urinary epinephrine excretion in men

The effect of the pituitary-adrenal axis on epinephrine synthesis in the human adrenal medulla was examined by the estimation of the 24-h urinary epinephrine level after treatment with glucocorticoids in four patients with systemic lupus erythematodes (SLE), one patient with rheumatoid arthritis (RA) and one patient with adrenal pheochromocytoma. 24-h urinary catecholamines (CAs) were measured by HPLC before and after glucocorticoid treatment, dexamethasone or prednisolone was orally given for more than seven days to patients with SLE, RA or isolated ACTH deficiency and five days to a patient with adrenal pheochromocytoma. In patients with isolated ACTH deficiency, the 24-h urinary epinephrine level was significantly lower than the normal range. In patients with SLE or RA, the 24-h urinary epinephrine level was normal and it was significantly suppressed by therapeutic doses of prednisolone 30-40 mg/day. In a patient with adrenal pheochromocytoma, 24-h urinary epinephrine was extremely high and it was significantly increased after dexamethasone 0.5 mg/day. These results suggest that epinephrine synthesis in the human adrenal medulla may be dependent on the pituitary-adrenal axis. But the increase in epinephrine synthesis due to dexamethasone in a patient with pheochromocytoma may reflect the direct effect via the feeding artery to the tumor, as previously shown in an in vitro culture system.     

Adrenal pheochromocytoma with contralateral cortisol-producing adrenal adenoma: diagnostic and therapeutic management.

There is evidence for a close interrelation between the adrenomedullary and adrenocortical tissues, and there are well-characterized models of their paracrine interaction. To contribute to the studies of systemic interactions between these tissues, we studied a 52-year-old female patient with a pheochromocytoma and a contralateral cortisol-producing adenoma. Due to a misunderstanding, she presented to her family doctor to have an inherited kidney disease ruled out. An adrenal mass was discovered incidentally by ultrasound. A computerized tomography of the abdomen revealed bilateral adrenal masses. Due to excess catecholamine secretion, bilateral pheochromocytomas based on multiple endocrine neoplasia syndrome were suspected. Laboratory work-up, selective adrenal venous sampling and magnetic resonance imaging studies established the diagnosis of a pheochromocytoma in the right-hand adrenal gland and a cortisol-producing adenoma on the left. Simultaneous bilateral laparoscopic subtotal adrenalectomy was performed. Immunohistochemistry showed positive staining against chromogranin A in a histological specimen obtained from the right-hand adrenal gland, while the left was negative; the left-hand adrenal gland stained positive against the ACTH receptor (MC2R) while the right was negative. Genetically, the patient was negative for MEN2, von Hippel-Lindau disease, and mutations in subunits B, C, and D of the succinate dehydrogenase gene. Although presence of bilateral adrenal adenomas or bilateral adrenal pheochromocytomas in certain inherited disorders are possible, this rare case of an adrenal pheochromocytoma combined with a contralateral cortisol-producing adrenal adenoma may further underline the wide range of complex interactions between the two endocrine systems.     

Urinary cystic calculi in a cynomolgus monkey (Macaca fascicularis): a case report.

An adult female Macaca fascicularis monkey became acutely anorexic and depressed and was found dead approximately 24 hours later. Necropsy revealed three hard brownish-yellow stones within the urinary bladder and urethra, a moderately shrunken left kidney, hemorrhage of the medulla of the left adrenal gland and a yellow liver. The stones, one of which was lodged in the urethra, were 1-2.5 cm in diameter, and their surfaces were rough and covered with spines. Chemical analysis of the stones revealed oxalates, phosphates, carbonates, ammonium salts, magnesium and calcium. Microscopic examination revealed chronic interstitial and glomerular nephritis and papillary hyperplasia of the transitional epithelium of the bladder.     

Differential control of adrenal and sympathetic catecholamine release by alpha 2-adrenoceptor subtypes

In the adrenergic system, release of the neurotransmitter norepinephrine from sympathetic nerves is regulated by presynaptic inhibitory alpha2-adrenoceptors, but it is unknown whether release of epinephrine from the adrenal gland is controlled by a similar short feedback loop. Using gene-targeted mice we demonstrate that two distinct subtypes of alpha2-adrenoceptors control release of catecholamines from sympathetic nerves (alpha 2A) and from the adrenal medulla (alpha 2C). In isolated mouse chromaffin cells, alpha2-receptor activation inhibited the electrically stimulated increase in cell capacitance (a correlate of exocytosis), voltage-activated Ca2+ current, as well as secretion of epinephrine and norepinephrine. The inhibitory effects of alpha2-agonists on cell capacitance, voltage-activated Ca2+ currents, and on catecholamine secretion were completely abolished in chromaffin cells isolated from alpha 2C-receptor-deficient mice. In vivo, deletion of sympathetic or adrenal feedback control led to increased plasma and urine norepinephrine (alpha 2A-knockout) and epinephrine levels (alpha 2C-knockout), respectively. Loss of feedback inhibition was compensated by increased tyrosine hydroxylase activity, as detected by elevated tissue dihydroxyphenylalanine levels. Thus, receptor subtype diversity in the adrenergic system has emerged to selectively control sympathetic and adrenal catecholamine secretion via distinct alpha2-adrenoceptor subtypes. Short-loop feedback inhibition of epinephrine release from the adrenal gland may represent a novel therapeutic target for diseases that arise from enhanced adrenergic stimulation.     

Glucagon-Induced Pheochromocytoma Crisis

ObjectiveTo describe a previously asymptomatic woman who developed a glucagon-induced pheochromocytoma crisis during preparation for screening colonoscopy.MethodsWe present the patient’s clinical features, laboratory and imaging findings, and outcome and review the related literature.ResultsA 76-year-old woman received glucagon to inhibit intestinal motility before routine colonoscopy. She immediately developed severe hypertension, cardiac arrhythmia, and altered mental status. Her hospital course was complicated by encephalopathy and cardiac, respiratory, renal, and hepatic failure. Computed tomography of the abdomen showed a 6.5 × 4.8-cm mass in the left adrenal gland. Biochemical testing for pheochromocytoma revealed markedly elevated plasma catecholamines and metanephrines and urinary vanillylmandelic acid and metanephrine. She underwent a successful laparoscopic left adrenalectomy. Findings from histopathologic and immunohistochemical examination of the adrenal mass were diagnostic of pheochromocytoma.ConclusionsGlucagon administration induced catecholamine release from an occult pheochromocytoma, which caused multiorgan injury. Health care providers using glucagon must consider this rare, but life-threatening, complication. (Endocr Pract. 2011;17:e51-e54)     

Basement membrane-like substance in cytologic diagnosis in clear cell adenocarcinoma of the minor salivary gland of the palate. A case report

BACKGROUND: Clear cell adenocarcinoma (CCA) of the minor salivary gland accounts for < 1% of all tumors of the salivary gland. CASE: A 32-year-old woman with a history of papillary carcinoma of the thyroid 1 year earlier complained of pain on the left side of the neck. After a detailed examination, the patient underwent the resection of a tumor located at the palate. Imprint cytology of the tumor revealed cohesive tumor cells of uniform size containing an abundant clear cytoplasm and round nuclei with extra but fine granular chromatin and conspicuous nucleoli. A basement membrane-like substance (BMS) was stained in light green with Papanicolaou staining and was positive for laminin with immunohistochemical staining. Histopathologic analysis confirmed the trabecular or nest-like arrangement of the cells with the clear cytoplasm and BMS substance surrounded by tumor cells, which were positive for laminin and AE1 immunohistochemically. CONCLUSION: Although CCA of the palate is extremely rare, an accurate cytologic diagnosis can be made if the characteristic findings of CCA, including BMS, are imaged.     

A nonisotopic method for determination of the in vivo activities of tyrosine hydroxylase in the rat adrenal gland

A rapid and reliable method for determination of in vivo activities of tyrosine hydroxylase in the rat adrenal gland is presented. This method involves determining the rate of accumulation of 3,4-dihydroxyphenylalanine (Dopa) in the adrenal gland after decarboxylase inhibition by NSD 1015, using HPLC with electrochemical detection after purification of the acid-deproteinized tissue extract with Bio-Rex 70 columns followed by alumina batch method. Purification of the sample with alumina adsorption alone, a method usually used for purification of catecholamines and Dopa, was ineffective: epinephrine and norepinephrine, which are present in high concentrations, interfered with an accurate determination of Dopa, and dopamine, which is retained strongly on the reverse-phase column, interfered with a rapid analysis. Purification with Sephadex G-10 columns followed by alumina adsorption was also ineffective. After purification with columns of weak cation-exchange resins such as Bio-Rex 70 or Amberlite CG-50 followed by alumina adsorption, most of the epinephrine and norepinephrine was removed and dopamine was eliminated. Thus a rapid and accurate determination of Dopa could be made. Of the two cation exchangers, Bio-Rex 70 was more effective. Accumulation of Dopa in the adrenal gland was linear up to 30 min after administration of NSD 1015 and a plateau was reached with doses over 10 mg/kg. Using this method, we investigated the effects of immobilization stress, reserpine, and hypoxia on in vivo activities of tyrosine hydroxylase in the adrenal gland.     

Evaluation of plasma norepinephrine as an index of sympathetic neuron function in the conscious, unrestrained rat.

Measurement of plasma norepinephrine and epinephrine concentrations in the conscious, unrestrained rat yielded values of 138±10 and 55±8 pg/ml, respectively. Ganglionic blockade reduced basal norepinephrine levels without affecting plasma epinephrine levels. Adrenal demedullation reduced plasma epinephrine to undetectable levels (<20 pg/ml) and gave rise to an apparent compensatory increase in plasma norepinephrine levels. Adrenal demedullation in combination with ganglionic blockade reduced plasma norepinephrine to the same level as did ganglionic blockade alone. These observations indicated that the plasma epinephrine was of adrenal origin. Furthermore, under these experimental conditions, the results suggested that the major portion of the plasma norepinephrine was of neuronal origin. When specific destruction of the sympathetic nerve terminals without alteration of adrenal medullary function was accomplished with 6-hydroxydopamine, a fivefold increase in plasma epinephrine concentration was observed at 24 hours. Plasma norepinephrine levels at 24 hours were not significantly altered from the control levels by the 6-hydroxydopamine suggesting that the rodent adrenal medulla was capable of secreting substantial amounts of norepinephrine under these conditions. It was concluded that plasma norepinephrine concentrations reflect both sympathetic neuronal and adrenomedullary activity. However, in the absence of changes in plasma epinephrine, plasma norepinephrine appears to be an index of sympathetic neuron function.     

Cellular localization of orexin receptors in human adrenal gland, adrenocortical adenomas and pheochromocytomas

Orexin-A and -B are hypothalamic peptides derived from a precursor called prepro-orexin and related with the regulation of the energy balance and arousal. They act on G protein receptors named orexin receptor 1 (OX1R) and orexin receptor 2 (OX2R). In the present study, we used immunohistochemical techniques to detect the distribution of OXR in normal human adrenal gland and adrenal tumours (adrenocortical adenomas and pheochromocytomas). OX1R was expressed in the cortex of the normal human adrenal gland (glomerulosa, fasciculata and reticular zones) and OX2R was located in the medulla (epinephrine and norepinephrine cells). By the double immunofluorescence techniques, we demonstrated that virtually all medullar cells (epinephrine and norepinephrine cells) expressed OX2R. As was expected, according to the results obtained in normal tissues, cortical tumours (adrenocortical adenomas) were positive for OX1R but not for OX2R and conversely, medullar tumours (pheochromocytomas) expressed only OX2R.