Feb 25, 1993 - We present an 8½-year-old girl who had a hypoglycaemic convulsion .... but circadian rhythmicity was absent with midnight. (sleeping) values ...
Journal of the Royal Society of Medicine Volume 87 February 1994 immunosuppression. Meshing the dermis allows a larger surface area to be grafted and allows simultaneous grafting with cultured keratinocytes. Unfortunately, the demand for cadaver skin greatly outstrips supply and there is a need for a connective tissue component (dermal substitute) that can be produced in the laboratory. Various techniques have been tried leading to the formation of a number of composite skin grafts or 'artificial skin substitutes'. Collagen gels contracted by incorporation of fibroblasts have had keratinocytes cultured on the surface to form a composite culture graft4 and a combination of bovine collagen and shark chondroitin-6sulphate has been overlaid with sheets of Silastic in an attempt to produce a stable skin substitute5. In fact, a number of complex culture systems exist, containing substrates of human, rat or bovine collagen some cross linked with glycoproteins and others containing fibroblasts. Unfortunately, many groups have reported poor handling with these systems6 and dermo-epidermal separation remains a problem. Certainly, at present, intact whole dermis appears to be the best substrate available.
References 1 Rheinwald JG, Green H. Serial cultivation of strains of human keratinocytes: the formation in keratinising colonies from single cells. Cell 1975;6:331-44 2 Leigh IM, Navsaria H, Purkis PE, McKay I. Clinical Practice and Biological Effects of Keratinocyte Grafting. Ann Acad Med Singapore 1991;20(4):549-55 3 Leigh IM, Purkis PE, Navsaria H, Phillips TA. Treatment of chronic venous ulcers with sheets of cultured allogenic keratinocytes. Br J Dermatol 1987;117:591-7 4 Bell E, Sher S, Hull B, Merrill C, Rosen S, Chamsen A, et al. The reconstruction of living skin. J Invest Dermatol 1983;81:2s-lOs 5 Burke JF, Yannas IV, Quinby WC, Bondoc CC, Jung WK. Successful use of a physiologically acceptable artificial skin in the treatment of extensive burn injury. Ann Surg 1981; 194:413-28 6 Nanchahal J, Davies D. Cultured composite skin grafts for burns. BMJ 1990;301:1342-3
Hypoglycaemia and Golytely in distal intestinal obstruction syndrome
suggested cirrhosis. In view of her poor nutrition and weight which was below the 3rd centile, she was commenced on overnight nasogastric feeds with 800 ml of medium chain triglyceride (MCT) peptides which she tolerated very well. During this period, she had recurrent episodes of DIOS characterized by nausea, vomiting and abdominal pain mainly in the right iliac fossa. This was treated initially with lactulose, oral acetylcysteine and cisapride. Her intestinal obstruction recurred and she was therefore treated with Golytely. Between these episodes, her main source of calories was through the overnight feeds. Golytely solution is prepared by adding lukewarm drinking water to the powder in the ready made bottles. The chemical composition of the solution is sodium 125 mmolIl, potassium 10 mmol/l, sulphate 40 mmol/l, bicarbonate 20 mmolIl, chloride 35 mmol/l, polyethylene glycol (4000) 17.6 mmol/l. Following a period of 1 to 3 h fasting the solution is administered orally or through a nasogastric tube at a rate of 500 to 1000 ml/h. The total volume of infusate required ranges from 1 to 5 1, but the infusion is continued until the discharge per rectum becomes clear of faecal material. In this case the patient became drowsy and had a convulsion when she had received approximately 1.2 1 of Golytely over a period of 1 h. She had then been fasted for a total of 2 h. Blood sugar was low (0.8 mmolIl) and she responded to 10% dextrose intravenously becoming fully conscious and with no further seizures. A subsequent 24 h blood glucose profile showed intermittently high insulin levels (range 5 to 65.3 Iu/l, normal 0 to 10 iu/l). The insulin/glucose ratio during fasting was, however, normal. Fasting levels of ,B-3-hydroxy buterate, free fatty acids, growth hormone and lactate were normal. On fasting over 8 h, she had low levels of plasma cortisol, though the synacthen test was normal.
Arvind Shah MRCP Su Madge SRN RSCN Robert Dinwiddie FRCP Parviz Habibi MRCP Hospital for Sick Children, Great Ormond Street, London, UK
Keywords: distal intestinal obstruction syndrome; cystic fibrosis; Golytely; hypoglycaemia
Distal intestinal obstruction syndrome (DIOS) is a well recognized complication of cystic fibrosis (CF). Osmotic agents such as gastrografin or a balanced intestinal lavage solution, Golytely (Seward Medical, London, UK) are often used in treating this condition with few side effects'-4. Cleghorn et al.V have shown that Golytely produces clinical and radiological improvement in DIOS and that it is well accepted, safe and effective3. These reports refer to patients in the adolescent age group or older. There are no reports of its use in younger children. We present an 8½-year-old girl who had a hypoglycaemic convulsion following treatment with Golytely.
Case report SJ was an 8½/2-year-old girl with CF who had presented with meconium ileus. She required a partial ileal resection in the neonatal period and by the age of 7 years had developed chronic liver disease. The main clinical problems were weight loss and peripheral oedema with hepatomegaly of 5 cm and her spleen was not enlarged. Investigations showed an elevated AST 125 u/l, a prolonged KPTT (57 s, control 36 s), abnormal prothrombin time (20 s, control 13 s) and low albumin 20 g/l. Liver ultrasound showed changes suggestive of fatty infiltration and an imino diacetic (HIDA) scan showed evidence of chronic gall bladder involvement. Her liver disease progressed, she developed portal hypertension with grade II-III oesophageal varices and ultrasonography Correspondence to: Dr A Shah, Consultant Paediatrician, The North Middlesex Hospital Trust, Sterling Way, Edmonton, London N18 1QX, UK
109
(Accepted 7 June 1993)
Discussion
Golytely (recently renamed 'Klean-Prep') is a non-absorbable osmolar agent with minimal transmucosal flux of fluid and electrolytes which has become popular in the treatment of DIOS1'3. At the Hospital for Sick Children in London, Golytely has been used since 1986 for 22 episodes of DIOS in a total of 12 CF children. Their ages ranged from 8 to 15.5 years and the volume of Golytely infused ranged from 1 to 51. Side effects were minimal. Nausea, abdominal discomfort, bloating and occasional vomiting have been reported previously1'3'4. A hypoglycaemic convulsion following Golytely has not previously been reported. The
Case presented to Section of Paediatrics, 25 February 1993
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Journal of the Royal Society of Medicine Volume 87 February 1994
manufacturers and the Committee on Safety of Medicines are not aware of this particular side effect. It is interesting to speculate as to the aetiology. DIOS is more common in CF complicated by chronic liver disease5. This patient had liver disease with cirrhosis and portal hypertension, her nutritional state was poor and Golytely may have caused hypoglycaemia by inducing intestinal hurry so depleting her residual energy intake during that period. Limited glycogen stores and impaired gluconeogenesis may have been contributed to the problem. This patient developed profound hypoglycaemia despite a fast for only 2 h. No other metabolic problems were found and she had two subsequent periods of fast which she tolerated very well. It is suggested that Golytely or other colonic cleaning agents should be used cautiously in young CF patients, especially those on special feeding regimes in whom there is also evidence of associated liver disease. A continuous energy supply should be given intravenously throughout this treatment period.
References 1 Cleghorn GJ, Stringer DA, Forstner GG, Durie PR. Treatment of distal intestinal obstruction syndrome in cystic fibrosis with balanced intestinal lavage solution. Lancet 1986;i:8-11 2 Batten JC, Matthew DJ. The respiratory system. In: Hodson ME, Norman AP, Batten JC, eds. Cystic fibrosis. London: BailliereTindall, 1983:209-18 3 Koletzko S, Stringer DA, Cleghorn GO, Durie P. Lavage treatment of distal intestinal obstruction syndrome in children with cystic fibrosis. Paediatrics 1989;83:727-33 4 Tolia V, Fleming S, Dubois RS. Use of Golytely in children and adolescents. J Paediatr Gastroenterol Nutr 1984;3:468-70 5 Maurage C, Lenaerts C, Weber A, Brochu P, Yousef I, Roy CR. Meconium ileus and its equivalent as a risk factor for the development of cirrhosis: An autopsy study in cystic fibrosis. J Paediatr Gastroenterol Nutr 1989;9:17-20
Primary pigmented nodular adrenocortical dysplasia: a rare form of a rare disorder
Imaging Chest X-ray PA - normal. Computerized tomography (CT) and magnetic resonance imaging (MRI) scan pituitary and hypothalamus - normal sized pituitary gland, no lesion identified. CT adrenals - normal sized adrenal glands. Seleno-cholesterol scans of adrenals - slight bilateral adrenal uptake. CT thorax - normal. A diagnosis of PPNAD was made on clinical and biochemical grounds; an echocardiogram was obtained and was reported normal with no evidence of myxoma or intra-cardiac lesion. The patient was therefore pre-treated with metyrapone for 6 weeks in order to normalize his serum cortisol in preparation for surgery, and then underwent bilateral adrenalectomy. On gross pathology, both adrenal glands appeared normal-sized weighing 5.6 and 5.8 g and had a grey mottled multinodular appearance, the nodules being 1-2 mm in diameter. On histology, they showed well-circumscribed cortical nodules; some of the nodules had a brown pigment deposition. The intervening cortical tissue showed crowded fasciculata with shrinkage of cells. These appearances were consistent with PPNAD.
A Jabbar MRCP1 D Grant FRCP' M Savage FRCP1 A Grossman FRCP1 'Department of Endocrinology, St Bartholomew's Hospital, London and 2The Hospital for Sick Children, Great Ormond Street, London, UK
Keywords: Cushing's syndrome; primary pigmented nodular adrenocortical disease; Carney complex
Primary pigmented nodular adrenocortical disease (PPNAD) is a rare cause of Cushing's syndrome which may be familial and usually presents in childhood or young adults.
Case report Our patient was a 17-year-old boy who at the age of 12 years was noted to be markedly obese and short, with a low growth velocity. He gained about 12 kg of weight over 6 to 8 months. On examination, he was short with plethoric face, truncal obesity, buffalo hump, purple striae, gynaecomastia, some proximal muscle wasting and bruise marks. Numerous brown lentigines were noted on the trunk. At the age of 14 years, he had stage IV pubic hair but his testes were only 4 ml in volume. Laboratory investigations. His plasma electrolytes were in normal range. Plasma glucose 4.9 mmol/l, serum T4 95 nmol/l, TSH 1.6 MU/ml, and prolactin 133 iu/l. Serum cortisol was 309 nmol/l at 0900 h (normal 200-600 nmol/l), but circadian rhythmicity was absent with midnight (sleeping) values at 109-326 nmol/l (normal < 50 nmol/l). Serum cortisol at 0900 h failed to suppress with either low-dose or high-dose dexamethasone suppression tests according to standard criteria (Trainer and Grossman, 1991). Following human corticotrophin-releasing hormone 100 yg iv, plasmic adrenocorticotrophic hormone (ACTH) was undetectable (< 10 yg/l) in all samples and serum cortisol remained unchanged.
Correspondence to: Dr Abdul Jabbar, Department of Medicine, The Aga Khan University, Stadium Road, PO Box 3500, Karachi 74800, Pakistan
(Accepted 21 July 1993)
Follou-up. Post-operatively the patient is currently well on hydrocortisone and fludro cortisone replacement therapy, and has restarted his college course. Disscussion PPNAD is a rare cause of Cushing's syndrome, and was initially reported in 1984 by Carney et al. 1. In the initial review of 24 cases of PPNAD, three were familial; as Carney had noted the coincidence of two PPNAD with cardiac myxomas in one family, he explored the Mayo clinic records and literature for reports of patients with the combination of Cushing's syndrome, cardiac myxomas and other myxoid tumours and spotty skin pigmentation. This review revealed that these diverse lesions are possibly pathogenetically related and constitute a specific clinical syndrome now referred to as the 'Carney complex'. The complex includes: (1) myxomas; (2) spotty skin pigmentation; (3) endocrine overactivity; and (4) peripheral nerve tumours (Schwannomas)14. Our patient did not have a family history of either of these lesions, but did have spotty skin pigmentation with Cushing's syndrome due to PPNAD. Cushing's syndrome due to PPNAD differs from other causes in its early presentation (mean age 19 years), and being ACTH - independent in the absence of any gross adrenal lesion. The disease involves both adrenal glands as opposed to functional adrenal adenoma or carcinoma which may show similar laboratory findings. Macronodular adrenocortical hyperplasia is yet another cause of bilateral adrenal involvement presenting as Cushing's syndrome, but this usually presents in adults and on imaging shows enlarged adrenal glands; in PPNAD the adrenal glands are
Case presented to Section of Endocrinology, 28 October 1992
