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Supplementary Table 1. Clinico-Pathologic Features of Patients with Pancreatic Neuroendocrine Tumors Associated with Cushing’S Syndrome

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Supplementary Table 1. Clinico-pathologic features of patients with pancreatic neuroendocrine tumors associated with Cushing’s syndrome. Review of the English/Spanish literature. Other hormones Age of Cortisol Other hormones Other ACTH Size (ICH or assay) ENETS Follow- Time Year Author Sex CS onset level (Blood syndromes or Site MET Type AH level (cm) corticotrophic Stage up (months) (years) (µg/dl) detection) NF other differentiation 1 1 1946 Crooke F 28 uk uk none no 4.5 H liver/peritoneum NET uk uk yes IV DOD 6 2 1956 Rosenberg 2 F 40 uk 92 none no 10 B liver NET uk uk yes IV PD 3 & p 3 1959 Balls F 36 uk elevated insulin Insulinoma 20 B liver/LNl/lung NET uk uk yes IV DOD 1 4 & 4 1962 Meador F 47 13~ elevated none no uk T liver/spleen NET ACTH uk yes IV uk 5 1963 Liddle5 uk uk uk elevated uk uk uk uk uk NET ACTH uk uk uk uk 6 1964 Hallwright6 F 32 uk uk none no large H LN/liver NET ACTH, MSH uk yes IV DOD 24 7 1965 Marks7 M 43 uk elevated insulin insulinomas 1.8 T liver NET uk uk yes IV DOD 7 8 1965 Sayle8 F 62 uk uk none carcinoidb 4 H LN/liver NET uk uk yes IV DOD 6 9 1965 Sayle8 F 15 uk uk none no 4 T no NET ACTH uk yes IIa DOD 5 9 b mesentery/ 10 1965 Geokas M 59 uk uk gastrin ZES large T NET uk uk yes IV DOD 2 LN/pleural/bone 11 1965 Law10 F 35 1.2 ∞ 91 gastrin ZESs uk B LN/liver NET ACTH, MSH gastrin yes IV PD 12 1967 Burkinshaw11 M 2 uk 72 none no large T no NET uk uk no uk AFD 12 13 1968 Uei12 F 9 uk uk none ZESs 7 T liver NET ACTH uk yes IV DOD 8 13 PTH, ADH, b gastrin, 14 1968 O'Neal F 52 13~ uk ZES uk T LN/liver/bone NET ACTH, MSH yes IV DOD 36 gastrin glucagon 15 1969 Vieweg14 M 24.5 1.2~ 71 Insulin, MSH insulinomab 6 B LN/liver/lung NET uk uk yes IV DOD 3 16 1972 Frederick15 M 21 uk 115 none no 2.5 T no NET uk uk uk IIa AFD 12 17 1973 Rawlinson16 M 67 14.5~ 74.3 none no 5 B LN/liver/lung NET ACTH uk yes IV DOD 1 18 1973 Corrin17 F 50 uk 180 none no 4 T LN/liver NEC uk uk yes IV DOD 1 18 b gastrin, 19 1973 Belchetz M 44 625-1740 ^ 145 gastrin, glucagon ZES large T LN/liver NET ACTH uk IV DOD 78 glucagon 20 1973 Walter19 F 45 160 - 1068^ 106 insulin insulinomab 5 B liver NET ACTH uk yes IV DOD 10 21 1975 Sadoff20 F 56 80 ^ 46.7 insulin insulinomab large uk liver NET uk uk yes IV DOD 84 22 1975 Craig21 M 59 uk 49 none no large T no NET ACTH uk yes uk PD 23 1975 Imura22 F 9 uk uk uk uk uk uk uk NET ACTH none uk uk uk 24 1975 Imura22 F 33 uk uk uk uk uk uk liver NET ACTH, MSH, CRF uk uk IV uk 25 1977 Kovacs23 M 54 285^ 81 none no 3 T liver NET ACTH SOM yes IV PD 26 1977 Kawaoi24 M 58 2220 ^ 71-136 none no uk H/T LN/liver NET ACTH uk yes IV DOD 8 27 1978 Joffe25 M 29 470-6014 ^ 29.7 gastrin, MSH no 6.00 B liver NET ACTH, MSH gastrin yes IV DOD 15 26 s gastrin, 28 1979 Kyriakides M 41 200-356 ^ 14.9 gastrin ZES uk H liver/lung NET uk yes IV DOD 33 secretin 27 b CAL, SOM, 29 1980 Asa F 68.5 115 ^ 29.8 gastrin ZES 1.5 T Liver/LN NEC ACTH, end yes IV DOD 20 gastrin 30 1981 Daniels28 F 47 89 ^ 52 calcitonin no uk T liver NET uk uk yes IV uk Other hormones Age of Cortisol Other hormones Other ACTH Size (ICH or assay) ENETS Follow- Time Year Author Sex CS onset level (Blood syndromes or Site MET Type AH level (cm) corticotrophic Stage up (months) (years) (µg/dl) detection) NF other differentiation 31 1981 Heitz29 F 46 uk uk uk uk 3 H no NET ACTH, LPH insulin, glucagon yes IIa DOC 6 32 1981 Heitz29 M 29 468-7732 ^ 29.7 gastrin no uk uk liver NET ACTHLPH gastrin yes IV PD 33 1981 Heitz29 M 48 uk uk uk uk uk uk liver NET none none uk IV DOD uk liver/bone/heart/ 34 1981 Kitchens30 M 34 355-1550 ^ 174 - 225 glucagon no large H/B/T LN/lung/ NEC uk uk yes IV DOD 48 kidney/brain 35 1982 Davies31 M 29 557 ^ 51 gastrin, MSH no uk uk liver NET ACTH, -end gastrin yes IV Lost 36 1982 Drury32 M 34 41-120 ^ uk none no 5 uk uk uk uk uk uk uk uk 37 1983 Santelices33 M 30 680 ^ 50 none no uk H liver NET uk uk yes IV Lost 38 1983 Styne34 F 7 uk uk none no large H no NET uk uk yes uk DOC 24 34 LPH, CAL, 39 1983 Styne § M 8 500-1520 ^ 112 no 10 T omentum NET ACTH insulin yes IIb DOD 18 glucagon, AFP 40 1984 Lyons35 F 19 64-136 ^ 36.2 gastrin ZESs 6 H no NET ACTH gastrin yes IIb PD insulin, 41 1984 Clark36 F 55 35-180 ^ 39 NF no uk uk LN NET ACTH glucagon, uk IIIb DOD 49 gastrin,SOM 42 1984 Clark36 F 45 580-1160 ^ 39 gastrin no uk uk liver NET ACTH none uk IV DOD 33 43 1984 Clark36 F 31 uk 80 none no uk uk liver NET ACTH none uk IV DOD 20 44 1984 Clark36 F 22 480 ^ 17 none no uk uk liver NET ACTH none uk IIIb AWD 240 insulin, 45 1984 Clark36 F 52 uk 21.5 none no uk uk liver NET ACTH glucagon, uk IV DOD 228 gastrin, SOM 46 1984 Clark36 F 16 uk 37.9 NF uk uk uk liver NET none insulin uk IV DOD 20 47 1984 Clark36 F 61 uk 27.8 uk uk uk uk liver NET none gastrin uk IV PD 48 1985 Allison37 M 67 447 ^ 54.3 gastrin ZESb 3 H liver NET ACTH gastrin,hCG yes IV DOD 4 49 1986 Jex38 F uk elevated elevated uk uk uk uk yes NET ACTH none yes uk DOD uk 50 1986 Jex38 F uk elevated elevated uk uk uk uk yes NET uk none yes uk DOD uk 51 1986 Jex38 F uk No elevated uk uk uk uk yes NET uk PTH yes uk DOD uk 52 1986 Jex38 F uk No elevated uk uk uk uk yes NET uk gastrin, CAL yes uk DOD uk 53 1986 Howlett39 M 37 907 ^ 132.3 none no uk uk liver NET none hCG uk IV DOD 1 54 1986 Howlett39 M 34 134 ^ 87 none no uk uk no NET POMC hCG, CAL uk uk alive 96 40 55 1986 Maton uk 32 11 ^ 47000 gastrin ZESp >7 H liver NET uk uk yes IV DOD 36 40 56 1986 Maton uk 50 56 ^ 31000 gastrin ZESb >7 H liver NET uk uk yes IV DOD 36 40 57 1986 Maton uk 48 2.548 ^ 27000 gastrin ZESb >7 H liver NET uk uk yes IV DOD 36 41 & 58 1986 Findling F 39 476 ^ elevated uk uk large uk LN/liver NET uk uk yes IV uk 59 1987 Long42 F 31 uk elevated uk uk uk B/T liver NET ACTH uk uk IV uk 43 & b 60 1987 Souquet M 29 elevated elevated gastrin ZES uk uk bone/liver NET ACTH uk uk IV uk 44 ACTHend, 61 1987 Melmed M 60 206-307 ^ 78 none no large uk no NET none uk uk AWD 3 POMC gastrin, 45 b glucagon, 62 1987 Lokich F 23 163 ^ 86 gastrin, glucagon ZES 15 B/T liver NET none yes IV AWD 10 insulin,PP,VIP, serotonin 63 1988 Ruszniewski46 F 54 138 ^ 16.5 LPH, gastrin ZESb uk B/T liver NET uk uk uk IV AWD 9 64 1988 Garg47 M 12 uk 74.3 none no uk uk LN/pelvis NET uk uk uk IV DOD 2 65 1988 Lamberts48 M 37 51.8-68.1 ^ 32 gastrin ZESb 5 H LN NET ACTH gastrin uk IIIb AWD 12 Other hormones Age of Cortisol Other hormones Other ACTH Size (ICH or assay) ENETS Follow- Time Year Author Sex CS onset level (Blood syndromes or Site MET Type AH level (cm) corticotrophic Stage up (months) (years) (µg/dl) detection) NF other differentiation 66 1989 Torriani49 F 45 106 ^ 71.8 none no 3 H no NET ACTH gastrin, VIP yes IIa DOD 60 67 1989 Bertagna50 F 37 218 ^ 26 LPH, gastrin no large uk LN/liver NET uk uk uk IV DOD 10 68 1989 Doppman51 F 60 uk uk none no uk uk widely NET ACTH uk no IV DOD 6 69 1989 Doppman51 F 57 uk uk none ZES uk uk liver NET ACTH uk yes IV uk 70 1989 Doppman51 F 55 uk uk gastrin no uk H widely NET ACTH uk yes IV DOD uk van 71 1990 52 F 72 135-250 ^ 46.5 none no 3 T liver NET ACTHMSH HCG yes IV DOD 10 Coevorden 72 1992 Gullo53 M 47 199-340 ^ 60-69 none no uk B liver MANEC ACTH none uk IV DOD <1 73 1994 Doppman54 F 37 uk elevated gastrin ZESb 3,5 B liver NET ACTH gastrin uk IV AWD uk 74 1994 Doppman54 F 39 uk elevated gastrin ZESb 4 H liver NET ACTH gastrin uk IV DOD 48 54 gastrin, 5HT, b 75 1994 Doppman F 46 uk elevated ZES 6 H liver NET ACTH, MSH gastrin, 5HT uk IV DOD 48 MSH 54 b adrenal/ liver/ 76 1994 Doppman F 45 uk elevated gastrin ZES 2.5 T NET ACTH gastrin uk IV DOD uk spine 77 1994 Doppman54 M 33 uk elevated gastrin ZESb 7 H liver NET ACTH gastrin uk IV DOD uk 78 1994 Doppman54 F 38 uk elevated gastrin ZESb 4 T liver NET ACTH gastrin uk IV AWD uk 79 1994 Doppman54 F 57 uk elevated none no 3.2 T liver NET ACTH none uk IV AWD 24 80 1994 Doppman54 M 36 uk elevated none no 3.8 B liver NET ACTH none uk IV AWD 12 81 1994 Doppman54 F 65 uk elevated glucagon no 7 H liver NET ACTH glucagon uk IV DOD uk 82 1994 Ishido55 F 64 112-900 ^ 25.7 gastrin ZESs 9 H/B liver NET ACTH gastrin no IV DOD 68 83 1995 Amikura56 uk uk elevated elevated uk uk uk T uk NET ACTH uk uk uk AWD 12 84 1995 Amikura56 F uk elevated elevated uk uk 7 H uk NET ACTH uk uk uk DOD 6 85 1995 Amikura56 uk uk elevated elevated uk uk uk uk liver NET ACTH uk uk IV AWD 40 86 1995 Amikura56 uk uk elevated elevated gastrin no uk uk liver NET ACTH gastrin uk IV AWD 32 87 1995 Amikura56 uk uk elevated elevated gastrin ZESb uk uk LN/liver/bone NET ACTH gastrin uk IV DOD 2 88 1995 Amikura56 uk uk elevated elevated gastrin ZESs uk uk LN/liver NET ACTH gastrin uk IV AWD 43 89 1995 Amikura56 uk uk elevated elevated gastrin ZESb uk uk liver NET ACTH gastrin uk IV DOD 27 90 1995 Amikura56 uk uk elevated elevated gastrin ZESp uk uk liver NET ACTH gastrin uk IV AWD 59 91 1995 Amikura56 uk uk elevated elevated gastrin ZESb uk uk liver NET ACTH gastrin uk IV DOD 24 92 1995 Amikura56 uk uk elevated elevated gastrin ZESb uk uk liver NET ACTH gastrin uk IV AWD 19 93 1995 Amikura56 uk uk elevated elevated gastrin ZESp uk uk liver NET ACTH gastrin uk IV DOD 17 94 1995 Amikura56 uk uk elevated elevated gastrin ZESb uk uk liver NET ACTH gastrin uk IV DOD 14 95 1995 Kelekis57 M 33 422 ^ 52.8 none no 6 T liver NET ACTH none uk IV uk 96 1996 Zhu58 M 51 522 ^ 71.4 none NFb 3.2 H liver NET ACTH (MET) gastrin, 5HT no IV AFD 21 97 1998 Sundaram59 # M 24 52.2 ^ 15.5 none no 3.00 H no NET CRH uk no IIa AFD 12 98 1998 Phan59 uk uk uk uk uk uk uk T uk NET uk uk uk uk DOC uk 99 1998 Young60 M 60 1036.4 ^ 35.2 none no 3 uk LN NET ACTH, CRH uk yes IIIb uk 100 1998 Raddatz61 F 69 250 ^ 50 gastrin
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  • Maternal Smoking and Infantile Gastrointestinal Dysregulation: the Case of Colic

    Maternal Smoking and Infantile Gastrointestinal Dysregulation: the Case of Colic

    Maternal Smoking and Infantile Gastrointestinal Dysregulation: The Case of Colic Edmond D. Shenassa, ScD*‡, and Mary-Jean Brown, ScD, RN§ ABSTRACT. Background. Infants’ healthy growth intestinal motilin levels and (2) higher-than-average lev- and development are predicated, in part, on regular func- els of motilin are linked to elevated risks of IC. Although tioning of the gastrointestinal (GI) tract. In the first 6 these findings from disparate fields suggest a physio- months of life, infants typically double their birth logic mechanism linking maternal smoking with IC, the weights. During this period of intense growth, the GI entire chain of events has not been examined in a single tract needs to be highly active and to function optimally. cohort. A prospective study, begun in pregnancy and Identifying modifiable causes of GI tract dysregulation continuing through the first 4 months of life, could pro- is important for understanding the pathophysiologic pro- vide definitive evidence linking these disparate lines of cesses of such dysregulation, for identifying effective research. Key points for such a study are considered. and efficient interventions, and for developing early pre- Conclusions. New epidemiologic evidence suggests vention and health promotion strategies. One such mod- that exposure to cigarette smoke and its metabolites may ifiable cause seems to be maternal smoking, both during be linked to IC. Moreover, studies of the GI system and after pregnancy. provide corroborating evidence that suggests that (1) Purpose. This article brings together information that smoking is linked to increased plasma and intestinal strongly suggests that infants’ exposure to tobacco smoke motilin levels and (2) higher-than-average intestinal mo- is linked to elevated blood motilin levels, which in turn tilin levels are linked to elevated risks of IC.
  • The Effect of Gastrin on Basal- and Glucose-Stimulated Insulin Secretionin

    The Effect of Gastrin on Basal- and Glucose-Stimulated Insulin Secretionin

    The Effect of Gastrin on Basal- and Glucose-Stimulated Insulin Secretion in Man JENS F. REHFEU and FLEMMING STADIL From the Department of Clinical Chemistry, Bispebjerg Hospital, and Department of Gastroenterology C, Rigshospitalet, Copenhagen, Denmark A B S T R A C T The effect of gastrin on basal- and glu- INTRODUCTION cose-stimulated insulin secretion was studied in 32 nor- Gastrointestinal hormones probably contribute signifi- mal, young subjects. The concentration of gastrin and in- cantly to the stimulation of insulin secretion during in- sulin in serum was measured radioimmunochemically. gestion of glucose or protein (1-4). It has been sug- Maximal physiologic limit for the concentration of gested that more than half the insulin response to oral gastrin in serum was of the order of 160 pmol per liter intake of glucose is caused by enteric hormones (5). At as observed during a protein-rich meal. Oral ingestion the present time there is a considerable debate as to of 50 g glucose produced a small gastrin response from which hormone or hormones mediate the insulin response. 28±3 to 39+5 pmol per liter (mean +SEM, P < 0.01). Concerning the action of gastrin on insulin secretion, Intravenous injection or prolonged infusion of gastrin stimulation (6-11), no effect (12-16), as well as inhibi- increased the concentration of insulin in peripheral ve- tion (17) have been reported. The conflicting results nous blood to a maximum within 2 min followed by a may in part be due to the use of pharmacological doses decline to basal levels after a further 10 min.