Routine calcitonin measurement in nodular thyroid disease management: is it worthwhile?

PURPOSE: To evaluate the diagnostic accuracy of routine calcitonin measurement in patients with nodular thyroid disease. METHODS: Consecutive patients with nodular thyroid disease (n = 640) were studied. Serum calcitonin levels were measured under basal conditions, and when basal values were between 10–100 pg/mL, testing was repeated after pentagastrin (PG) stimulation. Patients with previously diagnosed or familial medullary thyroid cancer (MTC) were excluded. Patients were operated on when basal or stimulated calcitonin >100 pg/mL or when other surgical indications were present. RESULTS: Four cases of MTC were identified. MTC was diagnosed in 75% of patients with basal calcitonin >100 pg/mL. One out of 11 patients with basal calcitonin between 10–100 pg/mL was diagnosed with MTC. PG stimulation resulted in elevation in 4 cases, where 1 case was diagnosed with MTC. Positive predictive value for basal calcitonin levels in the preoperative diagnosis of MTC was 5% for values between 10–100 pg/mL and 100% for values >100 pg/mL. Possible reasons for false positivity were papillary thyroid cancer in 17%, renal insufficiency in 8.3%, Hashimoto thyroiditis in 17% and β-blocker use in 33%. Positive predictive value for the PG test (>100 pg/mL) was 25% in the entire series. The cost of adding calcitonin measurement (±PG stimulation) to the preoperative work-up, resulted in €912.68 per MTC patient to detect the disease. CONCLUSION: Basal calcitonin measurement together with PG stimulation in cases of basal calcitonin >10 pg/mL detects MTC in 0.62% of patients with nodular thyroid disease.

Effect of aqueous extract of neem (Azadirachta indica) leaves on offensive and diffensive gastric mucosal factors in rats.

Standardized aqueous extract of Neem (Azadirachta indica) leaves (AIE) has been reported to show both ulcer protective and ulcer healing effects in normal as well as in diabetic rats. To study the mechanism of its ulcer protective/healing actions, effects of AIE (500 mg/ kg) was studied on various parameters of offensive acid-pepsin secretion in 4 hr pylorus ligation, pentagastrin (PENTA, 5 microg/kg/hr)-stimulated acid secretion and gastric mucosal proton pump activity and defensive mucin secretion including life span of gastric mucosal cells in rats. AIE was found to inhibit acid-pepsin secretion in 4 hr pylorus ligated rats. Continuous infusion of PENTA significantly increased the acid secretion after 30 to 180 min or in the total 3 hr acid secretion in rat stomach perfusate while, AIE pretreatment significantly decreased them. AIE inhibited the rat gastric mucosal proton pump activity and the effect was comparable with that of omeprazole (OMZ). Further, AIE did not show any effect on mucin secretion though it enhanced life span of mucosal cells as evidenced by a decrease in cell shedding in the gastric juice. Thus, our present data suggest that the ulcer protective activity of AIE may be due to its anti-secretary and proton pump inhibitory activity rather than on defensive mucin secretion. Further, acute as well as sub acute toxicity studies have indicated no mortality with 2.5 g/kg dose of AIE in mice and no significant alterations in body or tissues weight, food and water intake, haematological profile and various liver and kidney function tests in rats when treated for 28 days with 1 g/kg dose of AIE.

effect of acute consumption of paraoxon on basal and Pentagastrin-Stimulated Gastric acid and pepsin secretion in rats

Paraoxon is an organophosphate. Organophosphate inhibit acetylcholinestrase enzyme and cause nicotinic and muscarinic sings. There is no study on our knowledge regarding the effect of these substances on gastric acid and pepsin secretion. In the present study, the effect of acute consumption of paraoxon on gastric acid and pepsin secretion has been investigated. In the present study 30 female N-mari rats weighing 200-250gr were used. The first group [paraoxon] received 0.5mg/kg paraoxon intraperitonealy. The second group [alcohol] received the dozes of ethyl alcohol [96%] and the third group [control] received no drug. Animals were anesthetized by intraperitoneal injection of 50mg/kg Sodium thiopental. After trachesotomy and laparatomy gastric secretions were collected with a tube via duodenum. Pentagastrin [25 micro g/kg. ip] was used as gastric stimulator. Acid and pepsin secretions were measured by titration and Anson methods respectively. Stages of measurement were basal, stimulated. and re-basal. The basal acid secretion in control, alcohol and paraoxon groups was 7.6 +/- 0.26, 7.46 +/- 0.4 and 7.03 +/- 0.28 micro mol/15min respectively that shows no significant difference among three groups. Although following pentagastrin-stimulation acid secretion was significantly more than basal stage in all groups, but there was significantly more secretion in control than alcohol subjects. But there was no difference between control and paraoxon or alcohol and paraoxon groups in this regard. Regarding pepsin secretion, there was significantly more secretion in alcohol subjects than others in all measured stages. In comparison to control group, acute paraoxon has no effect on basal acid pepsin secretion, while acute alcohol caused a significant increase in basal acid/pepsin secretion

[Effect of Heracleum persicum extract on acid and pepsin secretion level in both basic and stimulated conditions with pentagastrin in rat]

The Heraclleum persicum is widely used as an odorant in pickles around the world and particularly in Iran. As pickle is a gastric stimulator, the question is whether this plant which is used in making pickles, decreases gastric stimulation of this group of foods, or increases it, and in general, what is the cellular mechanism of this plant on acid and pepsin secretion. Therefore, in this study the effect of plant entrants on the secretion rate of acid and pepsin surveyed in the stomach in rats. This study involves two groups [12 in each group] of rats in experimental method [Control group and Heracleum group]. After anesthesia with nesdonal, 50 mg/kg IP, rats were gone under surgical process, tracheotomy, laparatomy and gasteroadeodenostomy and the Heraclleum extract [12.5 mg/kg] was send into the stomach from gasterodeodenostomy canula in Herculean group. The amount of both acid and pepsin in both basal and stimulated condition were significantly increased in heracleum group compared to control group [p<0.001]. Pentagastrin also increased acid and pepsin secretion in control group [p<0.001] and increased pepsin in heraclleum group [p<0.05] but did not significantly change in acid secretion in heraclleum group. The Heracleum persicum increases acid and pepsin secretion when is used in food regimen. Its extract also increases gastric acid secretion via blockage of gastric receptor. However, a different mechanism is involved in the increasing of pepsin secretion

Effect of thyriod hormones on basal and stimulated gastric acid secretion due to histamine, carbachol and pentagastrin in rats

Thyroid hormones affect gastric acid secretion. As the mechanism of this effect has not been fully known, in this experimental study the isolated gastric acid secretion of hypothyroid and hyperthyroid rats were compared with control group by the administration of different doses of pentagastrin, histamine and carbachol as gastric acid secretion stimulators. This study was carried out in Ahwaz University of Medical Sciences, Ahwaz, Iran in the year 2000. Each group were consisted of 8 rats [N-mari] of both sexes with a mean weight of 246 +/- 5 grams. Hypothyroid and hyperthyroid states were induced respectively by adding methimazole [500 mg/liter] for 20 days and thyroxin [500 ug/liter] for 35 days in animals drinking water. After general anesthesia, by intraperitoneal injection of sodium thiopental [50 mg/kg body weight], celiotomy was carried out quickly. The end of esophagus was tied and a silicon tube [2-2.5 mm] was entered into the stomach via duodenum and fasted in pylor region. The stomach was isolated by cutting the esophagus proximal to the tied region and the proximal part of duodenum and put into cold serous solution. After washing the serous and mucus surfaces by serous and mucus solutions, the stomach was transferred immediately to a tissue bath containing warm serous solution [V= 40 ml, T= 370C]. Gastric acid secretion in isolated stomach stimulated by pentagastrin, carbachol and histamine was measured by wash out technique and automatic titrator. Moreover, to study the effect of thyroid hormones on gastric acid secretion a number of dose-dependent experiments after the administration of different doses of histamine [50, 100, 150, 200 umol], carbachol [50, 100, 150, 200 umol], and pentagastrin [30, 60, 90, 120 ug/kg body weight] were performed. Both basal and histamine, carbachol, pentagastrin stimulated-acid secretion decreased and increased in hypothyroid and hyperthyroid groups compared with control group. It seems that thyroid hormones have not exert their effects by changing the cholinergic, gastrin and histamine receptors but probably by alerting the number or size of the secretory cells in stomach

Early Detection of Medullary Thyroid Cancer by Screening of the RET Proto-oncogene Germ Line Point Mutation in Family Members Affected with Hereditary Medullary Thyroid Cancer / 대한내분비학회지

BACKGROUND: Conventional biochemical screening for family members with hereditary medullary thyroid cancer (MTC) is associated with problems of sensitivity and, specificity and it frequently detects gene carriers only after disease progression. Molecular genetic screening tests that detect germ-line point mutations of the RET proto-oncogene has changed our approach to hereditary MTC. In this study we screened members of a large Korean family that had a history of hereditary MTC by a molecular genetic method and propose a therapeutic approach in managing the disorder. METHODS: Using DNA acquired from peripheral blood leukocytes of the index patient, we performed PCR and direct sequencing of exon 10 of the RET proto-oncogene. PCR-RFLP using an Mbo II restriction enzyme was performed on family members who were at risk of MTC according to the family pedigree. Basal serum calcitonin level was determined in family members who had a point mutation of the RET proto-oncogene and a pentagastrin stimulation test was performed in 3 members. RESULTS: Genetic analysis in the index case revealed a mutation in exon 10, codon 618 of the RET proto-oncogene (TGC to AGC). Out of 28 members who were at risk of MTC, 24 members participated in the screening test. 9 members tested positive for a mutation in the same chromosomal location as the index patient by PCR-RFLP. Basal serum calcitonins were above 100 pg/mL in 2 members. 3 members who had a RET point muatation but a normal basal serum calcitonin level participated in the pentagastrin stimulation test and the results were negative in all members. We found a small medullary thyroid carcinoma that had a diameter of 0.2 cm in a 16 years old boy according to a negative pentagastrin stimulation test and who had received a prophylactic total thyroidectomy. He had no evidence of a lymph node metastasis. CONCLUSION: We detected a germ-line mutation of the RET proto-oncogene in codon 618 of Exon 10 by a molecular genetic method in a family with a hereditary MTC and found 9 members that had a negative history of MTC but had a RET point mutation. There was a very small MTC found in a 16 years old boy who had a normal pentagastrin stimulation test result. Therefore, It is recommended that a prophylactic total thyroidectomy be performed as well as in members that have a mutation of the RET proto-oncogene because MTC can metastasize early in its disease course.'

Neoplasias endocrinas múltiples: un modelo clínico para aplicar técnicas de genética molecular / Multiple endocrine neoplasia: a clinical model for testing molecular genetic techniques

Multiple endocrine neoplasias (MEN) are syndromes inherited as autosomal dominant. The application of the techniques of molecular biology has made possible the identification of the genes causing MEN 1 and 2. The gene responsable for MEN 1 belongs to the family of tumor suppressor genes and encodes for a protein named MENIN whose function remains to be elucidated. The identification of mutant MEN 1 gene carriers who are at risk of developing this syndrome requires frequent biochemical screening for the development of endocrine tumors. MEN 2 is a consequence of mutations in the Ret proto- oncogene (c-Ret). This gene encodes for a tyrosine kinase receptor thought to play a role in the development of neural crest- derived tissue. Members of kindred with either MEN 2A or MEN 2B should be screened by direct DNA testing early in life for mutations in c-Ret. Those with the mutation should be advised to have thyroidectomy at five years of age in children with MEN 2A and earlier in children with MEN 2B . Some cases of sporadic MTC are actually MEN 2A or Familial MTC after c-Ret testing is done, therefore routine application of this test is recommended in all cases of apparent sporadic MTC

Routine Measurement of Serum Calcitonin Concentration is Useful in Early Detection of Medullary Thyroid Carcinoma Among Patients with Nodular Thyroid Disease / 대한내분비학회지

BACKGROUND: Serum calcitonin is a sensitive and specific marker for diagnosis of medullary thyroid carcinoma (MTC) and its determination leads to accurate preoperative diagnosis and gives chances of definite cure. However, since many non-MTC diseases are also associated with calcitonin elevation, its significance in patients with mild or moderately elevated basal serum calcitonin levels is not clear. Furthermore, the normal value of calcitonin using immunoradiometric assay (IRMA) kit has not so far been definitely ascertained. This study is aimed at assessing the clinical significance of routine measurement of serum basal calcitonin concentration in nodular thyroid disease patients and evaluating the pentagastrin stimulation test in case of mild or moderate elevation of basal calcitonin level. We also measured serum calcitonin value in 408 normal individuals. METHODS: The basal serum calcitonin concentrations using a commercial IRMA kit (Medgenix CT-U.S.-IRMA) were measured in 818 patients with nodular thyroid disease (average age 45 years with a range from 13 to 82 years; 125 males and 693 females) who visited thyroid clinics in Samsung Medical Center between June 1997 and December 1998. Serum concentrations of T3, T4, TSH and thyroid autoantibodies were measured and ultrasonography of thyroid and thyroid scan using 131I or 99mTc-pertechnetate were performed in all patients. We also studied 408 healthy subjects without any thyroid disease (average age 48 years with a range from 20 to 86 years; 224 females). RESULTS: The calcitonin value in normal subjects was found to range from 0 to 13 pg/mL, and it was shown that men had higher calcitonin level than women (p 10pg/mL) in nodular thyroid disease was 1.71% (14/818), and the incidence of MTC was 0.73% (6/818) in this study. MTC was found in all patients with basal serum calcitonin levels more than 100 pg/mL. Pentagastrin stimulation test was also required to diagnose MTC in patients with basal serum calcitonin levels between 30 and 100pg/mL. The calcitonin concentration stimulated by pentagastrin increased more than 400pg/mL or more than 3.8 times of basal concentration. It was possible to diagnose MTC with fine needle aspiration and cytology in only one case out of six patients with MTC. CONCLUSION: Fine needle aspiration and cytology in diagnosing MTC was not sensitive and not devoid of false positive results. We confirmed that serum calcitonin measurement was very useful means for the preoperative diagnosis of unsuspected MTC. Pentagastrin stimulation test may be a reliable means of evaluation in nodular thyroid disease patients with mild or moderate elevation of basal calcitonin level. We recommend routine measurement of serum calcitonin concentration in patients with nodular thyroid disease.

Small Medullary Thyroid Cancer Dectected by Genetic Mutation Screening in Men IIa Family / 대한내분비학회지

Multiple endocrine neoplasia (MEN) Ila is an inherited disease characterized by the development of medullary thyroid carcinoma, pheochromocytoma and hyperparathyroidism. It has been shown to be associated with germ-line mutatians in the RET proto-oncogene. Presymptomatic screening of medullary thyroid carcinoma in MEN IIa families enables the early diagnosis of this tumor with its significant morbidity, We describe a 19-year-old woman fmm a MEN IIa family who was founded by DNA analysis to be a gene carrier of MEN IIa and then was diagnosed, using a pentagastrin stimulation test, as having presymptomatie medullary thyroid carcinoma She underwent thyroidectomy and histologic examination confirmed medullary thyroid carcinoma. It is cancluded that direct genetic analysis for mutations in the RET proto-oncogene should be the diagnstlc test of choice for identifying family members at risk for MEN IIa and thyroidectomy on the basis of genetic analysis is a rational course of action.

Secretory, endoscopic and histophatologic changes and prevalence of Helicobacter pylori in the gastroduodenal mucosa in patients with chronic alcoholic pancreatitis

Com o intuito de determinar, em nosso meio, a prevalência de ulcera péptica em pancreatopatas crônicos de etiologia alcoólica, e sua eventual relaçäo com alteraçöes histopatológicas, endoscópicas e da produçäo ácida, bem como a ocorrência de colonizaçäo pelo Helibacter pylori na mucosa gastroduodenal desses pacientes, foram investigados prospectivamente 30 pancreatopatas crônicos (Grupo I) e dez controles (Grupo II). Todos os pacientes foram submetidos a avaliaçäo clinica, teste de secreçäo ácida, basal e estimulada por pentagastrina, dosagem de gastrinemia basal, esofagogastroduodenoscopia com biopsia de fundo, corpo e antro gastricos e de bulbo duodenal, para identificaçäo e gradaçäo da inflamaçäo e ocorrência do Helicobacter pylori

Effect of graded doses of methysergide on basal and pentagastrin stimulated gastric secretion in anaesthetised rats.

The effect of continuous infusion (iv) of graded doses of methysergide (0.1-50 microgram(s)/kg/hr) was studied on basal and pentagastrin (5 microgram(s)/kg/hr) stimulated gastric acid secretion in anaesthetised rats by the slow, continuous stomach perfusion method. Both basal and pentagastrin stimulated acid secretion indicated a biphasic response. Methysergide induced stimulation at a lower dose of 1 microgram(s)/kg/hr and inhibition at higher doses of 20-50 microgram(s)/kg/hr. The stimulatory effect may be due to postsynaptic receptor blockade while the inhibitory effect at higher dose may be due to blockade of presynaptic 5-HT autoreceptors, or due to a direct inhibitory effect of unknown basis.

Determinação do tempo da dilatação máxima do canalículo da célula parietal após injeção de pentagastrina em espaços de tempo fracionados / Timing of canalicular maximal dilation of the parietal cell after pentagastrin injection at fractionized spaces of time

Doze ratos da linhagem Wistar de 90 dias de idade, pesando aproximadamente 300g, foram mantidos em jejum, só com água, durante 48h, em regime circadiano. Três animais do grupo controle foram sacrificados após o período de jejum. Outros 9 ratos, pertencentes aos 3 grupos experimentais, receberam intraperitonealmente 250microgram/kg de pentagastrina e foram sacrificados respectivamente 3, 20 e 90 minutos depois da injeção. As observações histológicas das células parietais baseadas na histomorfometria comparativa seguida de citometria permitiu-nos confirmar a evidência da dilatação máxima dos canalículos aos 20 minutos, após injeção de pentagastrina

effect of gastric secretagogues during ontogenesis in rats

The effects of histamine, bethanechol and pentagastrin on gastric acid secretion were studied in rats of younger and older age groups. After 48 hours starvation, the pylorus was ligated and each of the secretagogues was administered subcutaneously to individual groups. Four hours later the animals were sacrified by chloroform-induced asphyxia and the stomach was removed after ligating the cardiac end. The stomach contents, obtained by flushing with 3 ml of distilled water, were used to determine the volume of gastric juice and its free and total acidity. Histamine and bethanechol produced a greater increase in the volume and acidity of gastric juice in older animals as compared to younger ones. Pentagastrin also produced greater increase in these parameters in older animals but it was not statistically significant. Possible explanation of these results include variable size of parietal cell mass and/or difference in the sensitivity of parietal cells to individual secretagogues in animals of different age groups

Effect of pentagastrin on gastric bicarbonate secretion in patients with duodenal ulcer & healthy controls.

We studied the gastric acid and bicarbonate secretion rates in 12 patients with duodenal ulcer and 6 age matched healthy controls. Measurements of gastric juice volume (nonparietal and parietal), acidity and osmolality were done. The ulcer patients secreted more acid, parietal and nonparietal fluid than controls under basal conditions and after subcutaneous pentagastrin injection (6 micrograms/kg body weight). However, the gastric bicarbonate secretion was similar in the duodenal ulcer patients and controls, both under basal state as well as after pentagastrin stimulation. The gastric acidity was similar in ulcer patients and control subjects under both the states (49.3 +2- 4.5 vs 50.0 +/- 6.0 mmol/l basally, 85.2 +/- 8.9 vs 63.4 +/- 6.6 mmol/l after pentagastrin injection respectively). Thus, gastric bicarbonate secretion was similar, whereas parietal and nonparietal volume secretions were increased in patients with duodenal ulcer as compared to controls.

Gastric acid secretion response in the Cebus apella: a monkey model of chronic Chagas' disease

The objective was to study the secretory pattern, both basal and stimulated either by histamine (0.1 mg/kg) or pentagastrin (64 micrograms/kg) in eighteen Cebus apella monkeys chronically infected with different T. cruzi strains (CA1, n = 10; Colombian, n = 4 and Tulahuen, n = 4) and to describe the morphological findings in the gastrointestinal tract in twelve infected (6 sacrificed and 6 spontaneously dead) and four healthy monkeys. All infected monkeys and 35 healthy ones were evaluated by contrast X-ray examination. No differences were observed in basal acid output between control and infected groups. Animals infected with the Tulahuen and Colombian strains showed significant lower values of peak acid output in response to histamine or pentagastrin (p < 0.01 and p < 0.05 respectively; t test) in comparison to the controls. Barium contrast studies showed enlargement and dilatation of the colon in three infected animals. Histopathological lesions were seen in 75% of the autopsied animals either in colon alone (33%) or both, in colon and esophagus (42%). The normal secretion observed in the CA1 infected group could be due to a lower virulence of the strain, a lower esophageal tropism or the necessity of a longer post-infection time to cause lesions

Molestia de Hansen e aparelho digestivo: estudo clinico e perfil secretorio do estomago em condicoes basais a apos estimulo maximo pela pentagastrina / ?

O numero reduzido de trabalhos sobre o comportamento do tubo digestivo na molestia de Hansen nos levou a estudar 100 pacientes com hanseniase em suas diveras formas clinicas, avaliando-se pormenorizadamente as queixas do aparelho digetivo, procurando-se relacionar a sintomatologia com o tempo de historia e o tempo de tratamento da molestia. Procurou-se, tambem, avaliar a existencia de um possivel comprometimento funcional do estomago em 30 desses pacientes pela determinacao da secrecao basal e pelo estudo da producao maxima de acido apos estimulo pela pentagastrina, comparando-se os resultados com os observados em 10 individuos com queixas digestivas altas, cujos exames endocopicos foram normais (grupo controle). Os resultados encontrados foram os seguintes:

Response of the lower esophageal sphincter to pentagastrin on patients with megaesophagus secondary to Chagas' disease

Em 12 pacientes com megaesôfago chagásico e 12 controles, a pressäo do esfincter inferior do esôfago foi determinada pelo método manomético em condiçöes basais e após infusäo i.v. de pentagastrina nas foses de 0,5, 1,0, 2,0 e 4,0 ug/Kg/h. A pressäo basal média (36,2 ñ 2,5 cm H2O) foi significativamente mais alta (p < 0,05) no grupo de megaesôfago do que no grupo de controle (27,4 ñ 1,8 cm H2O). Durante a infusäo de pentagastrina, os valores da pressäo do enfincter esogagiano inferior foram significativamente mais altos (p < 0,05) no grupo de doença de Chagas. O nível mais alto foi atingido com a dose de 0,5 ug/Kg/h no grupo controle e com 1,0 ug/Kg/h no grupo chagásico (p < 0,05). Os pacientes com megaesôfago necessitaram de doses maiores de epntagastrina para alcançar a contraçäo máxima

Effect of pirenzepine on basal gastric acid and pepsin secretion and on secretion stimulated with graded doses of pentagastrin in duodenal ulcer patients

1. The effect of pirenzepine, an antimuscarinic compound, on basal acid an pepsin secretion and on the kinetic characteristics (Vmax and ED50) of pentagastrin-stimulated gastric secretion was investigated in 11 duodenal ulcer male patients. 2. Each patient underwent two pentagastrin dose-response tests: one with placebo and the other with pirenzepine given as a 10-mg intravenous bolus followed by 2.5 mg/h continuous infusion. 3. Pirenzepine induced a marked reduction in basal acid secretion (4.4 vs 0.3 mEq/h) and pepsin secretion (76.3 vs 18.3 mPU/h). 4. The drug also caused a reduced response of parietal cells to pentagastrin, which resulted in an increase in ED50 (131 vs 299 ngKg-1h-1). The maximal acid secretory response (Vmax) was reduced (40.9 vs 32.3 mEq/h), but this effect was not demonstrable when the result was expressed as total output minus basal output. 5. Pentagastrin-induced pepsin secretion was not significantly affected by pirenzepine. 6. We conclude that the inhibitory action of pirenzepine on gastric acid secretion results from the effect of the drug on basal secretion and on parietal cell responsiveness to stimuli