Predictive value of pentagastrin test for preoperative differential diagnosis between C‐cell hyperplasia and medullary thyroid carcinoma in patients with moderately elevated basal calcitonin levels

Background and Objectives Medullary thyroid carcinoma (MTC) is a calcitonin (CT)‐secreting neuroendocrine tumour originating from thyroid C cells. Serum CT concentrations are helpful in the early detection of MTC, while it is still unclear whether they can be used also for the differential diagnosis between MTC and C‐cell hyperplasia (CCH), a precancerous condition in familial MTCs but with unclear clinical significance in sporadic MTCs. Nowadays, surgery is recommended in all patients with basal or pentagastrin (PG)‐stimulated CT value of 100 pg/ml or more, without discriminating if they are affected with MTC or CCH only. The objective of this study was to investigate the utility of the PG test for CT in distinguishing CCH from MTC before surgery. Patients and Methods Sixteen of 20 patients with thyroid nodules and basal CT levels between 15 and 100 ng/l had a positive PG test (>100 ng/l PG CT peak) and form the basis of the data analysis. A diagnosis of MTC was histologically proved on surgical samples in seven patients and of CCH in nine other patients. Four patients with neither FNAB nor PG test consistent with a diagnosis of MTC did not undergo thyroidectomy. Results A peak of CT of 275 ng/l after PG was able to significantly distinguish patients with MTC from patients with CCH, with 100% sensitivity and 89% specificity (P = 0·002). PG‐stimulated calcitonin levels >275 ng/l had a positive predictive value (PPV) value for diagnosis of MTC of 100%, and PG‐stimulated calcitonin levels <275 had a PPV for the diagnosis of CCH of 89%. Conclusions A CT cut‐off after PG of 275 ng/l is suggested to be highly predictive in distinguishing CCH from MTC before surgery, and this may be helpful in selecting patients for thyroid surgery.     

老龄大鼠慢性脑灌注不足与认知功能障碍的研究

目的　探讨老龄大鼠慢性脑灌注脑损害和认知功能障碍及其机制。方法　 5 0只老龄大鼠用于实验 ,其中 2 0只接受环孢菌素A(CsA)胃灌治疗。用光镜和电镜观察组织学改变 ,免疫组织化学法检测免疫细胞的活动 ,采用微机控制穿梭箱双向主动回避反应实验系统检测大鼠认知功能。结果　大鼠持久性双侧颈总动脉结扎 (2VO)诱导的慢性脑灌注不足造成了脑组织广泛免疫细胞活动和进行性脑损害 ,导致了大鼠进行性学习和记忆能力下降。CsA治疗组大鼠脑内免疫细胞的活动明显减少 ,脑损害明显减轻 ,学习和记忆能力显著提高。结论　脑组织免疫细胞的活动贯穿于大鼠慢性脑灌注不足脑损害的病理过程 ,在脑损害和认知功能障碍的发生和发展中起重要作用 ;CsA可明显减轻脑内免疫细胞的活动 ,防治了大鼠的脑损害和认知功能障碍。     

C-cell hyperplasia

Routine calcitonin assay programs and recent studies on the natural history of familial medullary thyroid carcinoma (MTC) have greatly added to our understanding of C-cell hyperplasia (CCH) and refined its classification. This article is an update on CCH physiopathology related to clinical presentation. With this combined approach, two types of CCH that differ by their physiological characteristics can be identified: neoplastic CCH and reactive (also called physiological) CCH. Neoplastic CCH is caused by a germline mutation of the RET protooncogene in a multiple endocrine neoplasia type 2 (MEN 2) syndrome. It progresses to MTC following a time line that depends on the RET mutation involved. CCH may actually be a misnomer for a neoplastic condition that some authors have proposed to call "in situ-MTC". Reactive CCH is considered to be caused by a stimulus that is external to the C-cell, and its premalignant potential is not documented. Many situations such as hypercalcemia, hyperparathyroidy, chronic lymphocytic thyroiditis or follicular tumors have been associated with reactive CCH, the pathogenesis of which remains unclear. But C-cell density in normal patients is subject to important variability, and several studies have demonstrated the dramatic male predominance in physiological CCH when hypercalcitoninemia was a random discovery. These data suggest that a number of conditions which were previously associated with reactive CCH might be purely fortuitous. Our clinical/pathological confrontation contributes to appropriately distinguishing between various CCH types, and in turn to identify the best way of managing patients.     

Differential effects of chronic intermittent and chronic constant hypoxia on postnatal growth and development

Exposure to chronic constant or intermittent hypoxia (CCH or CIH) may have different effects on growth and development in early life. In this work, we exposed postnatal day 2 (P2) CD1 mice to CCH or CIH (11% O2) for 4 weeks and examined the effect of hypoxia on body and organ growth until P30. Regression analysis showed that weight increased in control, CCH and CIH cohorts with age with r2 values of 0.99, 0.97, and 0.94, respectively. Between days 2 and 30, slopes were 0.93+/-0.057, 0.76+/-0.108, and 0.63+/-0.061 (g/day, means+/-SEM) for control, CIH, and CCH, respectively and significantly different from each other (P<0.001). The slopes between P2 and P16 were 0.78+/-0.012, 0.46+/-0.002, and 0.47+/-0.019 for control, CCH and CIH, respectively. From P16 to 30, slopes were 1.12+/-0.033, 1.09+/-0.143, and 0.82+/-0.08 for control, CIH, and CCH, respectively with no significant difference from each other, suggesting a catch-up growth in the latter part of the hypoxic period. Slower weight gain resulted in a 12% and 23% lower body weight in CIH and CCH mice (P<0.001) by P30. Lung/body ratios were 0.010, 0.015, 0.015 for control, CIH, and CCH at P30, respectively. The decrease in liver, kidney, and brain weight were greater in CCH than CIH. Smaller liver weight was shown to be due to a reduction in cell size and cell number. Liver in CIH and CCH mice showed a 5% and 10% reduction in cell size (P<0.05) and a reduction of 28% in cell number (P<0.001) at P30. In contrast, CCH and CIH heart weight was 13% and 33% greater than control at P30 (P<0.05), respectively. This increase in the heart weight was due to an increase in the size of cardiomyocytes which showed an increase of 12% and 14% (P<0.001) for CIH and CCH, respectively as compared to control. Brain weight was 0.48 and 0.46 g for CIH and CCH, respectively (95% and 92% of normal). We concluded that (a) CIH and CCH follow different body and organ growth patterns; (b) mostly with CCH, the liver and kidneys are reduced in size in a proportionate way to body size but heart, lung, and brain are either spared or increased in size compared to body weight; and (c) the decrease in liver is secondary mostly to a decrease in cell number.     

Prevalence of C-cell hyperplasia in patients with normal basal and pentagastrin-stimulated calcitonin.

The prevalence of thyroid C-cell hyperplasia (CCH) was investigated prospectively in 57 patients with normal preoperative pentagastrin-stimulated plasma concentrations of calcitonin (hCT, range, 1-60 pg/mL; normal, 100 pg/mL) who subsequently underwent total thyroidectomy due to thyrotoxicosis (n = 18) or to nodular thyroid disease in the presence (n = 9) or absence (n = 30) of cytological follicular neoplasia. CCH was seen in 28 of 57 (49%) of all patients. CCH was more common in hyperthyroid (12/18 [66%]) than in euthyroid (16/39 [41%] patients. No age- or gender-related differences in the occurrence of CCH was seen. There was no histological evidence of medullary thyroid carcinoma (MTC) in any patient. CCH classified histologically as neoplastic was encountered in two instances. It was concluded that CCH may be expected in almost 50% of normocalcitonemic patients with various thyroid disorders. Although the potential clinical importance of this histological finding and specifically its neoplastic variety remains unknown, these results are in keeping with the assumption that pentagastrin-stimulated plasma concentrations of hCT within the normal range do not exclude the presence of CCH.     

Nifedipine therapy for Prinzmetal's angina.

A case is described in which nifedipine, a new coronary vasodilator, was effective in relieving attacks of Prinzmetal's angina unresponsive to conventional therapy. The extreme frequency of the anginal attacks provided evidence that lower doses of nifedipine lost their effectiveness approximately 4 hours after administration. A month after initiation of nifedipine, nitrates were withdrawn since they had been ineffective in controlling the attacks. A myocardial infarction occurred immediately, presumably due to coronary spasm.     

Obstructive sleep apnoea is improved by a prolonged treatment of gastrooesophageal reflux with omeprazole

BACKGROUND: Obstructive sleep apnoea has been demonstrated to induce gastrooesophageal reflux through highly negative intrathoracic pressure during the attacks. However, we believe that gastrooesophageal reflux on its part may favour or aggravate the apnoea attacks. AIMS: We investigated whether the treatment of gastrooesophageal reflux with omeprazole is able to decrease apnoea attacks. PATIENTS AND METHODS: Twenty patients (mean age 55.4 years, range 49-73 years; 17 males) with confirmed obstructive sleep apnoea at overnight polysomnography and pathological gastrooesophageal reflux at ambulatory 24-h oesophageal pHmetry were asked to note in a diary the occurrence of apnoea attacks for a basal period of 4 weeks. Subsequently, the patients were randomly and in a double-blind manner treated with omeprazole 20mg (10 patients, group A) or placebo (10 patients, group B) by giving 1 cp 30 min before breakfast and 1 cp 30 min before dinner for another 6 weeks with a diary documentation. The results were averaged weekly and over the entire treatment duration and a statistical comparison was made between the groups and within each group before and after treatment. RESULTS: The mean weekly frequency of apnoea attacks of group A during the entire period of treatment with omeprazole was significantly decreased with respect to the basal period and was significantly lower than that of group B. The weekly frequency of apnoea attacks in group A started to be significantly lower from the third week than the corresponding values of both group B and the basal period, reaching a decrease of about 73% in the sixth week. CONCLUSION: The occurrence of apnoea attacks progressively decreased during the treatment of gastrooesophageal reflux with omeprazole. This fact suggests that gastrooesophageal reflux may play a role in triggering and/or worsening obstructive sleep apnoea.     

Recurrent supraventricular tachycardia. The efficacy of a radio frequency system inserted into the coronary sinus]

The case is reported of a man of 66 with attacks of recurrent supraventricular tachycardia (SVT) which failed to respond to the standard medical treatment and which, because of their frequency, led to mental disturbances. The electrophysiological features of SVT are discussed, and the possibilities of recording potentials from the SA node. A definitive pacemaker was placed in the coronary sinus, and linked to a simple stimulator working at radio frequency (and activated by the patient himself); this led to an almost immediate reduction in the attacks of SVT.     

Uncommon association of germline mutations of RET proto-oncogene and CDKN2A gene

INTRODUCTION: Calcitonin measurement is advised in the diagnosis of thyroid nodules, as it is an accurate marker of medullary thyroid carcinoma (MTC). C-cell hyperplasia (CCH)-induced hypercalcitoninemia cannot be distinguished from that induced by MTC, unless surgery is performed. CASE: We report the clinical and biological features of a patient with a family history of cancer, including melanoma and pancreatic cancer, who had previously undergone surgery for melanoma. He presented the unusual association of papillary thyroid carcinoma (PTC), normocalcemic hyperparathyroidism, and hypercalcitoninemia with a pathological response to pentagastrin, which was histologically deemed secondary to CCH. Multiple endocrine neoplasia (MEN) 2A was diagnosed. RET gene analysis showed a p.V804M missense mutation in exon 14, a low- but variably penetrant defect found in both sporadic and MEN2A-associated MTC/CCH, and a p.G691S polymorphism in exon 11. Furthermore, the germline P48T mutation was found in the CDKN2A gene exon 1, which is known to be associated with melanoma and pancreatic cancer. The patient showed the uncommon coexistence of a germline mutation in two suppressor genes, RET and CDKN2A; this finding, deemed to be a mere coincidence, did not modify the phenotype expected by each single mutation. CCH associated with V804M RET mutation is a precancerous condition and surgery is recommended. In order to exclude MTC, surgery is advised in patients with a pathological calcitonin response to pentagastrin, in the absence of thyroid autoimmunity. CCH-induced hypercalcitoninemia can be associated with thyroid cancers other than MTC (e.g., PTC). Family history is important in scheduling specific genetic screening in high-risk patients and their relatives.     

Criss-cross heart: Transthoracic echocardiographic features

ObjectiveTo study the echocardiographic features of criss-cross heart (CCH), a congenital cardiac anomaly characterized by crossed ventricular inflow streams, in Indian patients.MethodsIn this retrospective observational study, all pediatric echocardiograms performed in a single tertiary care institution in South India over a three-year period were scrutinized for a diagnosis of CCH. Demographic, clinical and echocardiographic data were collected from patients’ medical records and echocardiographic database. Crossed ventricular inflow streams was identified when there was inability to visualize both atrio-ventricular valves in a single imaging plane in cardiac four chamber view.ResultsCCH was diagnosed in five patients from 10,500 pediatric echocardiographic studies. The age at diagnosis ranged from one month to 8 years. Cyanosis was present in all but one of the five cases. Crossed ventricular inflow streams was present by definition in all cases, whereas superior-inferior ventricular relationship was present in only three cases. All cases were associated with ventricular septal defects. Atrio-ventricular discordance was seen in three cases and concordance in two. Ventriculo-arterial discordance was seen in three cases, concordance in one and double outlet right ventricle in one. Three cases had pulmonary stenosis and the other two had pulmonary arterial hypertension. Straddling of AV valve was observed in four cases and hypoplastic aortic arch in one case.ConclusionCCH is an extremely rare congenital cardiac anomaly. Superior-inferior ventricular relationship often co-exists with CCH, but is not necessarily present in all cases. CCH requires early diagnosis because of its common association with diverse cardiac anomalies.     

Central congenital hypothyroidism due to gestational hyperthyroidism: detection where prevention failed

Much worldwide attention is given to the adverse effects of maternal Graves' disease on the fetal and neonatal thyroid and its function. However, reports concerning the adverse effects of maternal Graves' disease on the pituitary function, illustrated by the development of central congenital hypothyroidism (CCH) in the offspring of these mothers, are scarce. We studied thyroid hormone determinants of 18 children with CCH born to mothers with Graves' disease. Nine mothers were diagnosed after pregnancy, the majority after their children were detected with CCH by neonatal screening. Four mothers were diagnosed during pregnancy and treated with antithyroid drugs since diagnosis. Another four mothers were diagnosed before pregnancy, but they used antithyroid drugs irregularly; free T(4) concentrations less than 1.7 ng/dl (<22 pmol/liter) were not encountered during pregnancy. All neonates had decreased plasma free T(4) concentrations (range 0.3-0.9 ng/dl, 3.9-11.5 pmol/liter); plasma TSH ranged between 0.1 and 6.6 mU/liter. TRH tests showed pituitary dysfunction. Seventeen children needed T(4) supplementation. Because all mothers were insufficiently treated during pregnancy, it is hypothesized that a hyperthyroid fetal environment impaired maturation of the fetal hypothalamic-pituitary-thyroid system. The frequent occurrence of this type of CCH (estimated incidence 1:35000) warrants early detection and treatment to minimize the risk of cerebral damage. A T(4)-based screening program appears useful in detecting this type of CCH. However, the preferential and presumably best strategy to prevent CCH caused by maternal Graves' disease is preserving euthyroidism throughout pregnancy.     

Hereditary Angioedema: Increased Number of Attacks after Frequent Treatments with C1 Inhibitor Concentrate

Objective

C1 inhibitor concentrate is regarded as effective and safe in treating acute attacks of hereditary angioedema caused by C1 inhibitor deficiency. This study investigated the course of disease in 3 women treated frequently with C1 inhibitor concentrate.

Methods

Three women are described who received C1 inhibitor concentrate for the treatment of acute attacks of hereditary angioedema and experienced an increase in the frequency of attacks during that treatment period. In a control group of 24 patients aged more than 60 years with hereditary angioedema, the natural course of disease was determined.

Results

The 3 women (ages 50, 69, and 72 years) had received C1 inhibitor concentrate for 27, 18, and 22 years, respectively, for acute abdominal and skin attacks. Before this treatment, all attacks were severe. The treatment was always effective: The attacks were mild, and the duration of the attacks was shortened. During the treatment period, the number of attacks increased slowly but continuously, starting at the onset of treatment and paralleling the course of treatment. At the end of the observation period, the number of attacks increased by 4-fold, 12-fold, and 5-fold in the 3 women, respectively. No factors known to increase the frequency of attacks in hereditary angioedema were found in these patients. The control group did not show a similar increase in attacks during a comparable period of time.

Conclusion

A possible explanation for the increase in the frequency of attacks may lie in the large number of injections of C1 inhibitor concentrate.     

Feasibility of controlling lymphatic filarial diseases through primary health care system

A study was undertaken to explore the feasibility of treatment of clinical cases of filariasis by the Village Health Guides (VHG) and to assess the impact of different dose schedules by Diethylcarbamazine (DEC) on the frequency of acute attacks. It was observed that six days treatment with DEC at a dose of 500 mg daily was the most effective regimen in controlling recurrence of filarial attacks. The VHGs can serve the community in treating filarial cases with DEC.     

Nifedipine in the treatment of idiopathic Raynaud's syndrome

Thirty-nine patients with idiopathic Raynaud's syndrome were randomized into a double-blind controlled trial comparing nifedipine 10 mg TID to placebo during the winter months between November, 1981 and March, 1983. The pills were doubled at 5 weeks in the absence of subjective improvement. Frequency and severity of vasospastic attacks were recorded in a diary. Over the 10-week treatment period, there was a 48.2% reduction in frequency of attacks in the nifedipine group compared to a 24.6% reduction in the placebo group (p less than 0.05). Treatment reduced the frequency of attacks by at least 30% in 10 of 15 patients. The severity of attacks was also significantly improved. Further, analysis suggests a trend towards diminished effectiveness over time. Side effects occurred in all patients taking nifedipine but were usually mild and well tolerated. Nifedipine is effective in reducing the frequency and severity of vasospastic attacks in idiopathic Raynaud's syndrome over a 10-week period.     

Anti-interleukin-1 treatment in 26 patients with refractory familial mediterranean fever

Objective: To investigate the effect of anti-interleukin-1 (anti-IL-1) treatment on the frequency and severity of attacks and other disease-related clinical parameters and to evaluate the adverse effects associated with anti-IL-1 treatment in 26 patients with refractory familial mediterranean fever (FMF).

Methods: The study included 26 FMF patients followed up in our centre using colchicine for 4 months to 30 years. The treatment was switched to anti-IL-1 treatment for various reasons; 20 cases were resistant to colchicine, 8 were intolerant to colchicine, and 3 had prolonged arthritis under colchicine. Clinical response was monitored through the number of attacks, and laboratory inflammation was monitored through erythrocyte sedimentation rate, C-reactive protein, and serum amyloid A concentrations. Colchicine resistance was defined as at least two attacks/month together with C-reactive protein and serum amyloid A levels above the normal range between attacks. The colchicine dose was increased to 2?mg/day before they were considered colchicine-resistant.

Results: 24 patients used anakinra (100?mg/day), and 2 used canakinumab (150?mg/month), for –36 months. Sixteen patients with colchicine resistance had no attacks under anti-IL-1 treatment, and 4 had decreased frequency and duration of attacks. Seven of 8 patients intolerant to colchicine used anakinra, and 6 were attack-free under treatment, while 1 using canakinumab had attacks under treatment. One patient with prolonged arthritis used canakinumab but arthritis showed progression and the treatment was changed to IL-6 inhibitor. Three patients had injection site erythema and one had fatigue with anti-IL-1 treatment. Topical steroids with systemic antihistaminics were sufficient for symptom control in two cases, but canakinumab treatment was given due to severe injection site erythema in one case.

Conclusion: Anti-IL-1 agents are rational treatment modalities in patients resistant or intolerant to colchicine. Anti-IL-1 agents can control FMF attacks quite effectively and they have a promising role in the treatment of FMF.     

Succinate dehydrogenase D variants do not constitute a risk factor for developing C cell hyperplasia or sporadic medullary thyroid carcinoma

Medullary thyroid carcinoma (MTC) is a tumor that arises from parafollicular cells of the thyroid gland. MTC can occur sporadically (75%) or as part of inherited cancer syndromes (25%). In most cases, hereditary MTC evolves from preneoplastic C cell hyperplasia (CCH), so early detection of this pathology would evidently be critical. A recent study reports that alterations in succinate dehydrogenase (SDH) D are responsible for familial non-RET CCH. First, we studied SDHD in two families with hereditary non-RET CCH and found no alterations related to the inheritance of this disease. Then, we investigated whether the H50R variant could be a risk factor in the sporadic development of MTC in both Spanish and English patients. We found no evidence that the presence of the H50R is strongly associated with the risk of sporadic MTC, although we did observe an association with age at diagnosis of MTC in Spanish H50R carriers that we did not find in English patients. Finally, we looked for evidence of CCH or any other thyroid disease in a panel of germ-line SDH (B or D) mutation carriers and found none. We conclude that SDHD variants do not constitute a risk factor for developing CCH or sporadic MTC.     

Primary Headache and Helicobacter Pylori

H. pylori infection has recently been associated with various vascular disorders. The aim of this study was to investigate its role in primary headache, a pathology strictly associated with vascular alterations. A total of 200 subjects affected by primary headache were evaluated. H. pylori infection was diagnosed by the 13C urea breath test. Headache was classified in tension-type headache, cluster headache, and migraine with or without aura. Prevalence of H. pylori infection and gastrointestinal (GI) symptoms were evaluated. H. pylori infection was found in 40% of the patients; prevalence of migraine without aura was found to be significantly greater in infected patients. The positive group showed no significant differences in the prevalence of the GI symptoms evaluated. In 30 infected patients, it was assessed whether the eradication of the bacterium was able to reduce frequency, intensity, and duration of clinical attacks of headache. After eradication, clinical attacks of headache completely disappeared in 17% of patients. Moreover, intensity, duration, and frequency of headache attacks were reduced in 69% of the remaining subjects. In conclusion, H. pylori infection is common in primary headache; bacterium eradication appears to be related to a significant reduction in clinical attacks of the disease.     

Histopathological and molecular studies in patients with goiter and hypercalcitoninemia: reactive or neoplastic C-cell hyperplasia?

The cut-off values able to differentiate between reactive or neoplastic C-cell hyperplasia (CCH) or to predict sporadic medullary thyroid cancer (MTC) are still debated both for basal and stimulated calcitonin (bCT and sCT). In the present study, the prevalence and the histological patterns of CCH in 15 patients with multinodular goiter (MNG), bCT>10 pg/ml and sCT levels >50 pg/ml were studied. As controls, 16 patients with MNG and bCT levels <10 pg/ml and 4 patients with familial (FMTC) were included. For each case, calcitonin (CT) immunoreactive cells were counted in 60 consecutive high-power fields (400x) and CCH classified as focal, diffuse, nodular, or neoplastic. RET genetic analyses were performed at the germline and tissue levels in MTC and CCH cases. In patients with MNG, sCT levels >50 pg/ml were associated with CCH or MTC, being the total number of C-cells/60 fields significantly higher than that found in MNG with normal bCT (P = 0.0008) and comparable with that detected in FMTCs. In the group with sCT>50 pg/ml, the C-cells displayed a neoplastic phenotype. Neither germline nor somatic RET mutations were found. In conclusion, sCT levels >50 pg/ml were always associated with CCH, without correlation between CT levels and the number of C-cells or the final diagnosis. The C-cells had a morphology and distribution pattern similar to those observed in FMTC. Thus, sCT levels >50 pg/ml indicate the presence of CCH with a possible preneoplastic potential, suggesting the opportunity to perform a prophylactic surgical treatment.     

Evaluation of provocative tests in suspected medullary carcinoma of the thyroid:heterogeneity of calcitonin responses to calcium and pentagastrin

Abnormal calcitonin secretion provides a reliable marker for the presence of medullary carcinoma of the thyroid (MCT) and its precursor form, C-cell hyperplasia (CCH). Since this tumor may be transmitted by a dominant autosomal gene, the coincidence of a sensitive marker and an easily identified "at risk" population affords an unusual opportunity for cancer prophylaxis. To evaluate the specificity and sensitivity of provocative tests used for detection of C-cell disease, we have compared the calcitonin (hCT) responses to calcium (3 mg/kg body weight over 10 minutes intravenously), pentagastrin (0.5 microgram/kg body weight), and injection of calcium (1.0 mg/kg body weight) plus pentagastrin (0.25 microgram/kg body weight) over 60 seconds in 13 patients with subsequently proven MCT or CCH and in 31 normal volunteers. The ranges of hCT observed in normals after injection of pentagastrin and combined calcium and pentagastrin were lower than those seen in all nine patients with MCT. One subject, the only MCT patient with normal basal hCT values, had a normal response to calcium whereas all others achieved supranormal levels. Basal hCT levels were normal in the four patients with CCH but the hCT response to calcium was to a value in excess of 300 pg/mL, a level exceeded by only 3 of 31 normal subjects; the hCT response to pentagastrin in CCH and in normal subjects was indistinguishable. Combined calcium and pentagastrin administration was associated with abnormal hCT responses in two of the CCH patients and in the MCT patient with a normal response to calcium.(ABSTRACT TRUNCATED AT 250 WORDS)