3
Section of Endocrinology
429
mmol/l) and' restricted oral fluids. Parenteral scanning. Hypothalamic dysfunction is a poshydrocortisone therapy was given, replaced after sibility, manifesting initially with primary amenorrhoea, yet permitting, or arising after, full 48 hours by oral prednisone. On Days 6-8 of her inpatient admission she skeletal development. received Synacthen Depot I mg i.m. daily. After The TRH test showed a continued rise in clinical improvement for seven days she became plasma TSH for 60 minutes, suggesting a possible psychotic and paranoid over the next two days. pituitary or hypothalamic disorder. In some such She then improved considerably but remained cases a high basal level of immunoreactive TSH apprehensive and uncooperative, limiting further has been reported (Patel & Burger 1973, Faglia investigations. She went home on the 18th day et al. 1973). It was considered that this might taking thyroxine 0.1 mg daily and prednisone reflect the secretion of biologically inactive TSH and so the samples from the TRH test were 2.5 mg three times a day. Further investigations: Pituitary tomography, re-assayed using the sensitive cytochemical bioEEG and ECG normal. Reiter protein comple- assay (CBA) (Mr V Petersen). The results disment fixation text and VDRL negative. Anti- played an atypical discrepancy from the radionuclear factor negative. Twenty-four-hour urinary immunoassay (RIA) results: LH 2 iu, FSH 1.5 iu. Karyotype: normal female. Adrenal function on Day 9 (soluble Synacthen Time (min) TSH (mu/i) by RIA TSH (mu/I) by CBA 7.0 0.3 0.25 mg i.m.): plasma cortisol at 0 min, 1.52 200 17.0 4.4 29.4 6.8 tkmol/l; at 30 min, 1.56 ,umol/l; at 60 min, 1.38 60 ,umol/l (all grossly elevated). On Day 11 (insulin 0.1 u/kg i.v.): no rise in plasma cortisol or serum Primary hypothyroidism was excluded by the subgrowth hormone (minimum blood sugar 0.5 normal basal level of bioassayable TSH (Petersen et al. 1975), by the absence of thyroid antibodies mmol/l). Thyroid status: Serum T4 56 nmol/l (normal 60- and positive thyroidal response to exogenous 150), Thyopac-4 126% (normal 95-119), free TSH. One previous case of biologically inactive thyroxine index 0.44 (normal 0.60-1.50), serum TSH secretion has been reported (Krieger 1974). T3 0.3 nmol/l (normal 1.2-2.8). Thyroid microREFERENCES somal and thyroglobulin antibodies negative. Blau N & Hinton J M (1960) Lancet i, 408 Serum cholesterol 5.1 mmol/l (normal 4.0-7.5). FagliaJ G, Beck-Peccoz P, Ferrari C, Ambrosi B, Spada A, TRH rest (200 ,tg i.v.): at 0 min 7.0 mu/I; at 10 Travaglini P & Paracchi S Journal (1973) min, 15.6; at 20 min, 17.0; at 40 min, 18.1; at 60 Krieger D T of Clinical Endocrinology and Metabolism 37, 595 (1974) Journal of Endocrinology and Metabolism 38, 964 min, 29.4 mu/I. Y C & Burger H G Follow up: A marked physical and mental im- Patel (1973) Journal ofClinical Endocrinology and Metabolism 37, 190 provement was made on thyroxine and prednisone Petersen V, Smith B R & Hall R replacement therapy. Six months later she per- (1975) Journal of Clinical Endocrinology and Metabolism 41, 199 mitted further investigations, previously refused, which disclosed: significant rise in neck uptake of 1311 following bovine TSH; a paradoxical fall in FSH and LH after LHRH (basal FSH 5.3 u/I; LH 3.6 u/I). At a later date an EMI scan of Glucagonoma Syndrome in a Young Man N G Soler MD MRCP, G D Oates FRCS her skull was normal. and J M Malins MD FRCP (General Hospital, Birmingham, B4 6NH) J Cassar MD MRCP and S R Bloom MD MRCP Comment A number of unusual features were present in this (Royal Postgraduate Medical School, London) case. The florid psychosis seemed to have a metabolic basis related to initial hypopituitarism Mr H B, aged 38 with adrenal and thyroid insufficiency and water History: Glycosuria was detected during life intoxication and then rapidly changing bio- insurance examination in 1972 and a glucose chemical status with correction of hypo-osmolality tolerance test confirmed mild diabetes. Treatment and rapid rise in plasma cortisol to elevated levels. with diet and tolbutamide was begun. A few Psychosis in hypopituitarism has been previously months later he presented with spider nwvi. In described (Blau & Hinton 1960). In addition it 1973 he attended the dermatology clinic with dryseemed likely that there was an underlying ness and splitting of the skin of his hands. In September 1974 he complained of feeling generally schizoid personality. The etiology of the pituitary failure also run down. Recurrent episodes of glossitis remains unclear. A pituitary tumour was effec- followed and more recently he developed a skin tively excluded radiologically and by EMI rash and excoriation around the scrotum and
430
Proc. roy. Soc. Med. Volume 69 June 1976
4
Discussion Glucagonomas are rare and although a few reports are found in the literature (Table 1) only 5 _ 100 1000 fully documented cases have been described (McGavran et al. 1966, Mallinson et al. 1974). _-gw Overproduction of glucagon is associated with a 800 symptom complex consisting of dermopathy, 600 60 C mild diabetes, anemia, glossitis and occasionally diarrhoea. This patient fulfils all the criteria for the diagnosis of a glucagonoma. (Croughs 1974): I 400 40 i he had the classical features, a high plasma level of glucagon, a tissue diagnosis supported by the Blood Glucose 20 200 identification of glucagon secreting granules on -- Plasma Glucagon electron microscopy and the tumour reacted only to pancreatic glucagon antibodies. Glucagonomas .0 0. are far commoner in females than in males, 40 60 20 0 -20 -40 although 3 cases have been reported in males Minutes (Grossner & Korting 1960, Unger et al. 1963, Fig 1 Plasma glucagon response following Mallinson et al. 1974). However, the patient intravenouis infusion of arginine O.Sglkg (_) described represents the first fully documented anus which then spread to involve the thighs. case of glucagonoma in a male. He is also the He also suffered from constipation with in- youngest patient reported apart from a woman who was diagnosed at 26 years of age (Yoshinga frequent episodes of diarrheea. etal. 1966). Family history: None of diabetes mellitus. This man was labelled as a diabetic when he On examination: Thin pale man with angular stomatitis and glossitis. There were spider navi first presented but his glucose tolerance tests were on the neck and shoulders and extensive excoria- always only marginally abnormal. The anmmia, tion of the skin around the scrotum and anus. glossitis and skin rash were intermittent, making Heart, lungs and abdomen were normal. Blood diagnosis more elusive. During a period of three weeks when he was under close observation in pressure 120/60 mmHg. His fundi were normal. Investigations: Hb 9.3 g/100 ml, ESR 115 mm in hospital these features appeared to improve 1 hour (Westergren), serum iron 100 ,ug/100 ml, spontaneously; in retrospect this improvement total iron-binding capacity 280 ,ug/100 ml, serum coincided with withdrawal of sulphonylurea B12 570 pg/ml, serum folate 6.6 ,ug/ml. Sternal therapy and may be related to the marked marrow smear showed mild dyserythropoiesis. release of glucagon provoked by these drugs Liver function tests and liver scan were normal. (Fig 2). Diarrhoea has been reported in some Barium meal and follow through and jejuhal patients with glucagonoma (Mallinson et al. biopsy normal. Fasting plasma glucagon was 1974) but constipation, which this patient 1268 pmol/l (normal 10), serum insulin 5 ,uu/ml. Plasma pancreatic peptide concentrations were Tolbutamide Test in the normal range. Further investigations IG i.v. showed a rise in glucagon levels following the 100 2000 . intravenous infusion of arginine (Fig 1) and G---QBlood Glucose tolbutamide (Fig 2). When a bolus of glucagon *--*Plasma Glucagon _80 w (1 mg) was injected intravenously the blood 1600glucose levels remained unaltered. Coeliac axis angiography demonstrated a large E C', I~~~~~ _60 co 1200. pancreatic tumour. cm Operation: Splenectomy and distal pancreatec- Ea ^ : 4 . tomy. A 5 x 4 cm firm irregular mobile tumour 0~ 800S. _40 liea A was found in the tail of the pancreas close to the ~~~~~~, 3 hilum of the spleen. There were multiple small to Arginine Infuslon 0. 5 gikg
-
o
.
*
*
.
*
I
*
I
..~
A
.
.
VA
metastases.
Histology: A well differentiated endocrine tumour showing positive immunofluorescence for glucagon.
Postoperative course: Uneventful recovery but still has fasting hyperglycemia. Plasma glucagon 140 pmol/l a week and 3 months after operation.
400
0_
*-.
_20
-A-' Ait
I
I
I
O0
-20 0 20 40 60 80 100 120 Minutes
Fig 2 Plasma glucagon response to Ig intravenous tolbutamide (arrow)
5
Section of Endocrinology
Table I
dietary carbohydrate restriction alone, he has normal postprandial blood sugars. This suggests that elevated glucagon levels are no more likely to be important in the etiology of diabetes than other known diabetogenic hormones such as cortisol or growth hormone. It is interesting to note that in spite of attempts to connect glucagon with developinent of ketoacidosis in diabetes mellitus (Gerich et al. 1975), neither this patient nor any of the other glucagonoma patients described developed ketoacidosis.
Reports of alpha pancreatic islet cell tumours
Becker et al. (1942) Grossner & Korting (1960) Unger et al. (1963) Yoshinga et al. (1966) McGavran et al. (1966) Church & Crane (1967) Wilkinson (1971) Mallinson
(1974)
Patients Sex Age F 45
Diagnosis made at
Tumour
Autopsy
Carcinoma
51
M
Autopsy
Carcinoma
62 ? 26
M Autopsy, F (3 cases) Autopsy F Laparotomy
Carcinoma-
42
F
Carcinoma-
Laparotomy
Adenoma,
Carcinoma*
Carcinoma*
61
F
55
F
Laparotomy
Carcinoma*
65
M
Autopsy (3),
Adenoma (2),
48-65
Fc(8
laparotomy (6) carcinoma (6)
Autopsy
The single patient described by McGavran et al. and 4 of the 9 in the series of Mallinson et al. were fully documented cases of glucagonoma * metastases present
suffered from, is more in keeping with the known physiological action of glucagon (Lefebvre & Unger 1972). Knowledge is limited about the prognosis for patients with glucagonoma. A history spanning 2-10 years before diagnosis was the rule in the series of Mallinson et al. (1974), suggesting that glucagonomas may be slow growing. In the original report of the glucagonoma syndrome McGavran et al. (1966) noted that their patient was alive two and a half years after the recognition of metastatic lesions and that no chemotherapy had been used. As regards response to chemotherapy, the only guidance is derived from reports of 4 patients with malignant islet cell tumours producing multiple hormones including glucagon (Murray-Lyon et al. 1968, Border & Carter 1973). Following treatment with streptozotocin, glucagon levels returned to normal in 2 of these patients whilst the rest did not respond. As streptozotocin does not affect the a-cells in animals given doses toxic to ,8-cells (Rakieten et al. 1963, Junod et al. 1967) it is an initially unpromising agent for the treatment of glucagonomas. Lightman & Bloom (1974) reported that, in a patient who had required insulin previously, resection of a malignant glucagonoma without metastases led to a return to normal glucose tolerance. In our case, although following resection of the primary lesion the plasma glucagon fell, the presence of metastases accounts for persistently high levels. In spite of the very high plasma glucagon in this patient, his diabetes has been mild throughout and at present, with
431
REFERENCES Becker S W, Kahn D & Rothman S
(1942)Archiyesof Dermatologyand Syphilology45, 1069 Border L D & Carter S K (1973) Annals of Internal Medicine 79, 101 Church R E & Crane WA (1967) British Journal of Dermatology 79, 284 Croughs R J M (1974) Clinics in Gastroenterology 3, 609 Gerich J E, Lorenzi M, Bier D M, Schneider V, Tsalikian E, Karam J H & Forsham P H (1975) New England Journal of Medicine 292, 985 Grossner W von & Korting G W (1960) Deutsche medizinische Wochenscrift 85, 434 Junod A, Lambert A E, Orci L, Pictet R, Gonet A E & Renold A E (1967) Proceedings of the Society for Experimental Biology and Medicine 126,201 Lefebvre P J & Unger R H (1972) Glucagon Molecular Physiology; Clinical and Therapeutic Implications. Pergamon, Oxford Lightman S L & Bloom S R (1974) British Medical Journal i, 367 McGavran M H, Unger R H, Recant L, Polk H, Kilo C & Levin M E (1966) New England Journal ofMedicine 274, 1408 Mallinson C N, Bloom S R, Warin A P, Salmon P R & Cox B (1974)Lancet ii, 1 Murray-Lyon I M, Eddleston A L W F, Williams R, Brown M et al. (1968) Lancet ii, 895
Rakieten N, Rakieten M L & Nadkarni M V (1963) Cancer Chemotherapy Reports 29, 91 Unger R H, Eisentrant A M & Lochner J D (1963) Journal of Clinical Investigation 42, 987 Wilkinson D S (1971) Proceedings of the Royal Society of Medicine 64, 1196 Yoshinga T, Okuno G, Shinji Y, Tsujii T & Nishikaiva M (1966) Diabetes 15, 709
The following cases were also presented:
Secondary Acromegaly Cured by Removal of Bronchial Carcinoid Adenoma Dr P H Sonksen, Dr C Lowy, Dr B Corrin, Dr G Jeremiah, Dr D Davies, Dr S Oaten and Dr T ET West (St Thomas's Hospital, London SE] 7EH) Untreatable Myxcedema Dr A Howell (for Professor R Hoffenberg)
(Queen Elizabeth Hospital, Birmingham, B15 2TH)
Virilizing Adrenal Carcinoma and Pituitary-dependent Cushing's Syndrome Dr D C Anderson, Dr D F Child, Dr C H Sutcliffe, Dr D Davies and Dr D Longson (Royal Infirmary, Manchester, M13 9 WL)
Section of Endocrinology
429
mmol/l) and' restricted oral fluids. Parenteral scanning. Hypothalamic dysfunction is a poshydrocortisone therapy was given, replaced after sibility, manifesting initially with primary amenorrhoea, yet permitting, or arising after, full 48 hours by oral prednisone. On Days 6-8 of her inpatient admission she skeletal development. received Synacthen Depot I mg i.m. daily. After The TRH test showed a continued rise in clinical improvement for seven days she became plasma TSH for 60 minutes, suggesting a possible psychotic and paranoid over the next two days. pituitary or hypothalamic disorder. In some such She then improved considerably but remained cases a high basal level of immunoreactive TSH apprehensive and uncooperative, limiting further has been reported (Patel & Burger 1973, Faglia investigations. She went home on the 18th day et al. 1973). It was considered that this might taking thyroxine 0.1 mg daily and prednisone reflect the secretion of biologically inactive TSH and so the samples from the TRH test were 2.5 mg three times a day. Further investigations: Pituitary tomography, re-assayed using the sensitive cytochemical bioEEG and ECG normal. Reiter protein comple- assay (CBA) (Mr V Petersen). The results disment fixation text and VDRL negative. Anti- played an atypical discrepancy from the radionuclear factor negative. Twenty-four-hour urinary immunoassay (RIA) results: LH 2 iu, FSH 1.5 iu. Karyotype: normal female. Adrenal function on Day 9 (soluble Synacthen Time (min) TSH (mu/i) by RIA TSH (mu/I) by CBA 7.0 0.3 0.25 mg i.m.): plasma cortisol at 0 min, 1.52 200 17.0 4.4 29.4 6.8 tkmol/l; at 30 min, 1.56 ,umol/l; at 60 min, 1.38 60 ,umol/l (all grossly elevated). On Day 11 (insulin 0.1 u/kg i.v.): no rise in plasma cortisol or serum Primary hypothyroidism was excluded by the subgrowth hormone (minimum blood sugar 0.5 normal basal level of bioassayable TSH (Petersen et al. 1975), by the absence of thyroid antibodies mmol/l). Thyroid status: Serum T4 56 nmol/l (normal 60- and positive thyroidal response to exogenous 150), Thyopac-4 126% (normal 95-119), free TSH. One previous case of biologically inactive thyroxine index 0.44 (normal 0.60-1.50), serum TSH secretion has been reported (Krieger 1974). T3 0.3 nmol/l (normal 1.2-2.8). Thyroid microREFERENCES somal and thyroglobulin antibodies negative. Blau N & Hinton J M (1960) Lancet i, 408 Serum cholesterol 5.1 mmol/l (normal 4.0-7.5). FagliaJ G, Beck-Peccoz P, Ferrari C, Ambrosi B, Spada A, TRH rest (200 ,tg i.v.): at 0 min 7.0 mu/I; at 10 Travaglini P & Paracchi S Journal (1973) min, 15.6; at 20 min, 17.0; at 40 min, 18.1; at 60 Krieger D T of Clinical Endocrinology and Metabolism 37, 595 (1974) Journal of Endocrinology and Metabolism 38, 964 min, 29.4 mu/I. Y C & Burger H G Follow up: A marked physical and mental im- Patel (1973) Journal ofClinical Endocrinology and Metabolism 37, 190 provement was made on thyroxine and prednisone Petersen V, Smith B R & Hall R replacement therapy. Six months later she per- (1975) Journal of Clinical Endocrinology and Metabolism 41, 199 mitted further investigations, previously refused, which disclosed: significant rise in neck uptake of 1311 following bovine TSH; a paradoxical fall in FSH and LH after LHRH (basal FSH 5.3 u/I; LH 3.6 u/I). At a later date an EMI scan of Glucagonoma Syndrome in a Young Man N G Soler MD MRCP, G D Oates FRCS her skull was normal. and J M Malins MD FRCP (General Hospital, Birmingham, B4 6NH) J Cassar MD MRCP and S R Bloom MD MRCP Comment A number of unusual features were present in this (Royal Postgraduate Medical School, London) case. The florid psychosis seemed to have a metabolic basis related to initial hypopituitarism Mr H B, aged 38 with adrenal and thyroid insufficiency and water History: Glycosuria was detected during life intoxication and then rapidly changing bio- insurance examination in 1972 and a glucose chemical status with correction of hypo-osmolality tolerance test confirmed mild diabetes. Treatment and rapid rise in plasma cortisol to elevated levels. with diet and tolbutamide was begun. A few Psychosis in hypopituitarism has been previously months later he presented with spider nwvi. In described (Blau & Hinton 1960). In addition it 1973 he attended the dermatology clinic with dryseemed likely that there was an underlying ness and splitting of the skin of his hands. In September 1974 he complained of feeling generally schizoid personality. The etiology of the pituitary failure also run down. Recurrent episodes of glossitis remains unclear. A pituitary tumour was effec- followed and more recently he developed a skin tively excluded radiologically and by EMI rash and excoriation around the scrotum and
430
Proc. roy. Soc. Med. Volume 69 June 1976
4
Discussion Glucagonomas are rare and although a few reports are found in the literature (Table 1) only 5 _ 100 1000 fully documented cases have been described (McGavran et al. 1966, Mallinson et al. 1974). _-gw Overproduction of glucagon is associated with a 800 symptom complex consisting of dermopathy, 600 60 C mild diabetes, anemia, glossitis and occasionally diarrhoea. This patient fulfils all the criteria for the diagnosis of a glucagonoma. (Croughs 1974): I 400 40 i he had the classical features, a high plasma level of glucagon, a tissue diagnosis supported by the Blood Glucose 20 200 identification of glucagon secreting granules on -- Plasma Glucagon electron microscopy and the tumour reacted only to pancreatic glucagon antibodies. Glucagonomas .0 0. are far commoner in females than in males, 40 60 20 0 -20 -40 although 3 cases have been reported in males Minutes (Grossner & Korting 1960, Unger et al. 1963, Fig 1 Plasma glucagon response following Mallinson et al. 1974). However, the patient intravenouis infusion of arginine O.Sglkg (_) described represents the first fully documented anus which then spread to involve the thighs. case of glucagonoma in a male. He is also the He also suffered from constipation with in- youngest patient reported apart from a woman who was diagnosed at 26 years of age (Yoshinga frequent episodes of diarrheea. etal. 1966). Family history: None of diabetes mellitus. This man was labelled as a diabetic when he On examination: Thin pale man with angular stomatitis and glossitis. There were spider navi first presented but his glucose tolerance tests were on the neck and shoulders and extensive excoria- always only marginally abnormal. The anmmia, tion of the skin around the scrotum and anus. glossitis and skin rash were intermittent, making Heart, lungs and abdomen were normal. Blood diagnosis more elusive. During a period of three weeks when he was under close observation in pressure 120/60 mmHg. His fundi were normal. Investigations: Hb 9.3 g/100 ml, ESR 115 mm in hospital these features appeared to improve 1 hour (Westergren), serum iron 100 ,ug/100 ml, spontaneously; in retrospect this improvement total iron-binding capacity 280 ,ug/100 ml, serum coincided with withdrawal of sulphonylurea B12 570 pg/ml, serum folate 6.6 ,ug/ml. Sternal therapy and may be related to the marked marrow smear showed mild dyserythropoiesis. release of glucagon provoked by these drugs Liver function tests and liver scan were normal. (Fig 2). Diarrhoea has been reported in some Barium meal and follow through and jejuhal patients with glucagonoma (Mallinson et al. biopsy normal. Fasting plasma glucagon was 1974) but constipation, which this patient 1268 pmol/l (normal 10), serum insulin 5 ,uu/ml. Plasma pancreatic peptide concentrations were Tolbutamide Test in the normal range. Further investigations IG i.v. showed a rise in glucagon levels following the 100 2000 . intravenous infusion of arginine (Fig 1) and G---QBlood Glucose tolbutamide (Fig 2). When a bolus of glucagon *--*Plasma Glucagon _80 w (1 mg) was injected intravenously the blood 1600glucose levels remained unaltered. Coeliac axis angiography demonstrated a large E C', I~~~~~ _60 co 1200. pancreatic tumour. cm Operation: Splenectomy and distal pancreatec- Ea ^ : 4 . tomy. A 5 x 4 cm firm irregular mobile tumour 0~ 800S. _40 liea A was found in the tail of the pancreas close to the ~~~~~~, 3 hilum of the spleen. There were multiple small to Arginine Infuslon 0. 5 gikg
-
o
.
*
*
.
*
I
*
I
..~
A
.
.
VA
metastases.
Histology: A well differentiated endocrine tumour showing positive immunofluorescence for glucagon.
Postoperative course: Uneventful recovery but still has fasting hyperglycemia. Plasma glucagon 140 pmol/l a week and 3 months after operation.
400
0_
*-.
_20
-A-' Ait
I
I
I
O0
-20 0 20 40 60 80 100 120 Minutes
Fig 2 Plasma glucagon response to Ig intravenous tolbutamide (arrow)
5
Section of Endocrinology
Table I
dietary carbohydrate restriction alone, he has normal postprandial blood sugars. This suggests that elevated glucagon levels are no more likely to be important in the etiology of diabetes than other known diabetogenic hormones such as cortisol or growth hormone. It is interesting to note that in spite of attempts to connect glucagon with developinent of ketoacidosis in diabetes mellitus (Gerich et al. 1975), neither this patient nor any of the other glucagonoma patients described developed ketoacidosis.
Reports of alpha pancreatic islet cell tumours
Becker et al. (1942) Grossner & Korting (1960) Unger et al. (1963) Yoshinga et al. (1966) McGavran et al. (1966) Church & Crane (1967) Wilkinson (1971) Mallinson
(1974)
Patients Sex Age F 45
Diagnosis made at
Tumour
Autopsy
Carcinoma
51
M
Autopsy
Carcinoma
62 ? 26
M Autopsy, F (3 cases) Autopsy F Laparotomy
Carcinoma-
42
F
Carcinoma-
Laparotomy
Adenoma,
Carcinoma*
Carcinoma*
61
F
55
F
Laparotomy
Carcinoma*
65
M
Autopsy (3),
Adenoma (2),
48-65
Fc(8
laparotomy (6) carcinoma (6)
Autopsy
The single patient described by McGavran et al. and 4 of the 9 in the series of Mallinson et al. were fully documented cases of glucagonoma * metastases present
suffered from, is more in keeping with the known physiological action of glucagon (Lefebvre & Unger 1972). Knowledge is limited about the prognosis for patients with glucagonoma. A history spanning 2-10 years before diagnosis was the rule in the series of Mallinson et al. (1974), suggesting that glucagonomas may be slow growing. In the original report of the glucagonoma syndrome McGavran et al. (1966) noted that their patient was alive two and a half years after the recognition of metastatic lesions and that no chemotherapy had been used. As regards response to chemotherapy, the only guidance is derived from reports of 4 patients with malignant islet cell tumours producing multiple hormones including glucagon (Murray-Lyon et al. 1968, Border & Carter 1973). Following treatment with streptozotocin, glucagon levels returned to normal in 2 of these patients whilst the rest did not respond. As streptozotocin does not affect the a-cells in animals given doses toxic to ,8-cells (Rakieten et al. 1963, Junod et al. 1967) it is an initially unpromising agent for the treatment of glucagonomas. Lightman & Bloom (1974) reported that, in a patient who had required insulin previously, resection of a malignant glucagonoma without metastases led to a return to normal glucose tolerance. In our case, although following resection of the primary lesion the plasma glucagon fell, the presence of metastases accounts for persistently high levels. In spite of the very high plasma glucagon in this patient, his diabetes has been mild throughout and at present, with
431
REFERENCES Becker S W, Kahn D & Rothman S
(1942)Archiyesof Dermatologyand Syphilology45, 1069 Border L D & Carter S K (1973) Annals of Internal Medicine 79, 101 Church R E & Crane WA (1967) British Journal of Dermatology 79, 284 Croughs R J M (1974) Clinics in Gastroenterology 3, 609 Gerich J E, Lorenzi M, Bier D M, Schneider V, Tsalikian E, Karam J H & Forsham P H (1975) New England Journal of Medicine 292, 985 Grossner W von & Korting G W (1960) Deutsche medizinische Wochenscrift 85, 434 Junod A, Lambert A E, Orci L, Pictet R, Gonet A E & Renold A E (1967) Proceedings of the Society for Experimental Biology and Medicine 126,201 Lefebvre P J & Unger R H (1972) Glucagon Molecular Physiology; Clinical and Therapeutic Implications. Pergamon, Oxford Lightman S L & Bloom S R (1974) British Medical Journal i, 367 McGavran M H, Unger R H, Recant L, Polk H, Kilo C & Levin M E (1966) New England Journal ofMedicine 274, 1408 Mallinson C N, Bloom S R, Warin A P, Salmon P R & Cox B (1974)Lancet ii, 1 Murray-Lyon I M, Eddleston A L W F, Williams R, Brown M et al. (1968) Lancet ii, 895
Rakieten N, Rakieten M L & Nadkarni M V (1963) Cancer Chemotherapy Reports 29, 91 Unger R H, Eisentrant A M & Lochner J D (1963) Journal of Clinical Investigation 42, 987 Wilkinson D S (1971) Proceedings of the Royal Society of Medicine 64, 1196 Yoshinga T, Okuno G, Shinji Y, Tsujii T & Nishikaiva M (1966) Diabetes 15, 709
The following cases were also presented:
Secondary Acromegaly Cured by Removal of Bronchial Carcinoid Adenoma Dr P H Sonksen, Dr C Lowy, Dr B Corrin, Dr G Jeremiah, Dr D Davies, Dr S Oaten and Dr T ET West (St Thomas's Hospital, London SE] 7EH) Untreatable Myxcedema Dr A Howell (for Professor R Hoffenberg)
(Queen Elizabeth Hospital, Birmingham, B15 2TH)
Virilizing Adrenal Carcinoma and Pituitary-dependent Cushing's Syndrome Dr D C Anderson, Dr D F Child, Dr C H Sutcliffe, Dr D Davies and Dr D Longson (Royal Infirmary, Manchester, M13 9 WL)
