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1.
Clin Endocrinol (Oxf) ; 60(4): 457-60, 2004 Apr.
Article in English | MEDLINE | ID: mdl-15049960

ABSTRACT

OBJECTIVE: To compare the outcome of different treatment options used in several cases of non-islet cell tumour hypoglycaemia (NICTH). PATIENTS: Eight cases of NICTH were referred for diagnosis and monitoring following either surgical or medical treatment. METHODS: Serum samples collected throughout the time-course of each case were analysed for glucose, insulin, C-peptide, IGF-I, total IGF-II, total IGF-II to IGF-I ratio and, in most of the cases, big IGF-II. RESULTS: Surgical excision was successful in the relief of symptoms and normalization of the biochemical parameters. Therapeutic treatment with glucocorticoids confirmed previous studies showing the suppressive effect on tumour (big) IGF-II production. The present data show that the effect was dose-dependent and reversible if doses were below a critical level. CONCLUSIONS: Within the limits of the cases studied, and the time-scales involved, moderate- to high-dose glucocorticoid therapy had immediate beneficial influence on symptomatic hypoglycaemia and, if tolerated in the long term, was effective in correcting the underlying biochemical dysfunction, unlike other therapeutic regimens. This effectiveness was only achieved when the dose exceeded a threshold level specific to the patient. In addition, reduction of the dose or withdrawal of the drug caused a return of the abnormal biochemical profile. Surgical removal of the malignancy, where this was an option, was successful within the periods studied.


Subject(s)
Glucocorticoids/administration & dosage , Hypoglycemia/drug therapy , Hypoglycemia/etiology , Neoplasms/complications , Prednisolone/administration & dosage , Adult , Aged , Aged, 80 and over , Blood Glucose/analysis , C-Peptide/blood , Female , Glucocorticoids/therapeutic use , Human Growth Hormone/therapeutic use , Humans , Hypoglycemia/blood , Insulin/blood , Insulin-Like Growth Factor I/analysis , Insulin-Like Growth Factor II/analysis , Male , Middle Aged , Neoplasms/drug therapy , Neoplasms/surgery , Prednisolone/therapeutic use , Protein Precursors/analysis
2.
Ann Clin Biochem ; 40(Pt 6): 689-93, 2003 Nov.
Article in English | MEDLINE | ID: mdl-14629810

ABSTRACT

BACKGROUND AND METHODS: We report a case of insulinoma in which the diagnosis was very challenging as some of the biochemical data were consistently equivocal. In order to assess the relative reliability of the analytical tests, retrospective biochemical data on 45 other cases of histologically confirmed insulinoma were evaluated, enabling the most secure diagnostic process to be identified. RESULTS: The data showed that insulin concentrations alone, although measurable, were equivocal in 17% of cases. The addition of C-peptide values clarified the diagnosis in about 50% of the borderline cases, whilst ketone (beta-hydroxybutyrate) concentrations were low during the prevailing hypoglycaemia in all cases. CONCLUSION: The combination of these three tests is suggested as the most effective method for the biochemical diagnosis of hypoglycaemia due to insulinoma.


Subject(s)
Insulinoma/diagnosis , 3-Hydroxybutyric Acid/blood , Adult , Aged , Aged, 80 and over , Blood Glucose/analysis , C-Peptide/blood , Female , Humans , Hypoglycemia/blood , Hypoglycemia/complications , Hypoglycemia/diagnosis , Insulin/blood , Insulinoma/blood , Insulinoma/complications , Insulinoma/physiopathology , Male , Middle Aged , Predictive Value of Tests , Reference Values , Reproducibility of Results , Retrospective Studies
3.
J Clin Pathol ; 56(9): 641-6, 2003 Sep.
Article in English | MEDLINE | ID: mdl-12944543

ABSTRACT

Adult spontaneous hypoglycaemia is not a diagnosis per se but a manifestation of a disease. Although rare, it is important to identify spontaneous hypoglycaemia and its causes because treatment may be preventative or curative. Hypoglycaemia can occur as an epiphenomenon in many serious diseases. It is sufficient to recognise the disease's association with hypoglycaemia and then take appropriate action to prevent the recurrence of hypoglycaemia. In investigating apparently healthy individuals, common pitfalls to avoid are: failure to recognise subacute neuroglycopenia clinically; failure to document hypoglycaemia adequately during symptoms; failure to measure pancreatic hormones, counter-regulatory hormones, and ketones in hypoglycaemic samples; failure to recognise pre-analytical and analytical limitations of laboratory assays; and failure to abandon obsolete and inappropriate investigations. Providing these caveats are met, appropriate laboratory and radiological investigations will almost always uncover the cause of spontaneous hypoglycaemia.


Subject(s)
Clinical Laboratory Techniques , Hypoglycemia/diagnosis , Acute Disease , Adult , Autoantibodies/blood , Blood Glucose/analysis , C-Peptide/blood , Diagnosis, Differential , Exercise Test , Fasting , Homeostasis , Humans , Insulin/blood , Insulin/immunology , Insulinoma/diagnosis , Pancreatic Neoplasms/diagnosis , Postprandial Period , Proinsulin/blood , Receptor, Insulin/immunology
4.
J R Soc Med ; 95(8): 381-5, 2002 Aug.
Article in English | MEDLINE | ID: mdl-12151486

ABSTRACT

The most important cause of hypoglycaemia in the presence of high insulin and C-peptide concentrations is insulinoma. However, a similar picture arises from use of sulphonylureas, which is sometimes covert. All specimens received in two years by a supraregional assay service laboratory from adults with low glucose and inappropriately high insulin and C-peptide concentrations were tested for sulphonylureas by a radioimmunoassay that employed antibodies to glibenclamide. In sulphonylurea-positive cases a questionnaire was sent to the consultant responsible for the patient, to elicit further information. Samples from 93 adult patients met the criteria, and 34 (37%) of these gave a positive result on screening for sulphonylureas. The consultants provided further information on 31 of the 34, and in 20 the presence of a sulphonylurea was unexpected. In 10 the features were such as to raise the possibility of factitious drug ingestion. A simple screening technique applied to specimens from patients with hyperinsulinaemic hypoglycaemia indicated that, in a substantial proportion of cases, the patient was taking a sulphonylurea.


Subject(s)
Hypoglycemia/diagnosis , Sulfonylurea Compounds/blood , Adolescent , Adult , Aged , Aged, 80 and over , Biomarkers/blood , C-Peptide/blood , Child , Female , Humans , Hypoglycemia/etiology , Insulin/blood , Male , Mass Screening/methods , Middle Aged , Radioimmunoassay/methods , Sensitivity and Specificity
5.
J Clin Pathol ; 55(7): 503-7, 2002 Jul.
Article in English | MEDLINE | ID: mdl-12101194

ABSTRACT

AIM: To assess the extent to which biochemical analytical services contribute to the diagnosis and management of clinical cases of hypoglycaemia. METHODS: All cases of confirmed hypoglycaemia, referred during a six month period, were included in the survey. Questionnaires were sent to each referring laboratory requesting information on the clinical progress and current status of the patient. RESULTS: The level of influence exerted by analytical data was assigned in each case and those with similar outcomes combined. Identifiable case groups were: (1) Results not recorded in the patients' notes (15.7%). (2) Inappropriate requesting of insulin and C peptide measurements in cases of diabetes (11.4%). (3) Patient died soon after investigation (20.0%). (4) Patient recovered spontaneously (17.1%). (5) Patient received effective medical or surgical treatment (12.9%). (6) Patient awaiting or not requiring pathology based treatment (31.4%). (7) Inconclusive outcome prompting further investigation (5.7%). CONCLUSIONS: Within the timescale of the survey (approximately 12 months), positive progress had been made towards diagnosis and subsequent treatment in only 10% of cases. Another 30% were either awaiting some form of treatment or further diagnostic tests. The remaining 60% did not appear to benefit in any way from the biochemical investigations.


Subject(s)
C-Peptide/blood , Diagnostic Services/standards , Hypoglycemia/diagnosis , Insulin/blood , Treatment Outcome , Adolescent , Adult , Age Factors , Aged , Aged, 80 and over , Autopsy , Child , Child, Preschool , England , Enzyme-Linked Immunosorbent Assay , Health Care Surveys , Health Services Research , Humans , Infant , Infant, Newborn , Laboratories, Hospital/standards , Middle Aged
6.
Clin Lab Med ; 21(1): 79-97, 2001 Mar.
Article in English | MEDLINE | ID: mdl-11321938

ABSTRACT

Hypoglycemia occurs as an epiphenomenon in many serious diseases and further investigation may be unnecessary. In other, often seemingly healthy individuals, it is responsible for their presenting symptoms. In them preliminary diagnosis depends on demonstrating a low blood glucose concentration during spontaneous symptoms by ambulatory self-collection of capillary blood and its analysis for glucose in the laboratory. Subsequent investigation requires appropriate plasma hormone analysis on blood collected while the patient is hypoglycemic.


Subject(s)
Blood Glucose/metabolism , Hypoglycemia , Insulin/metabolism , Humans , Hypoglycemia/diagnosis , Hypoglycemia/metabolism , Hypoglycemia/physiopathology
8.
Endocrinol Metab Clin North Am ; 28(3): 555-77, 1999 Sep.
Article in English | MEDLINE | ID: mdl-10500931

ABSTRACT

Therapeutically administered antidiabetic drugs, notably insulin and the sulfonylureas, are undoubtedly the most common cause of hypoglycemia encountered in clinical practice. Nevertheless, an impressive list of other drugs can produce hypoglycemia unpredictably in seemingly healthy individuals in whom it may masquerade as spontaneous hypoglycemia. Unless the true cause is identified when the patient is first seen, fruitless and expensive overinvestigation may ensue. The most important drugs are discussed herein and brief mention made of those for which coincidence has not been eliminated.


Subject(s)
Hypoglycemia/chemically induced , Central Nervous System Depressants/adverse effects , Ethanol/adverse effects , Humans , Hypoglycemic Agents/adverse effects
9.
Endocrinol Metab Clin North Am ; 28(3): 579-601, 1999 Sep.
Article in English | MEDLINE | ID: mdl-10500932

ABSTRACT

Factitious diseases are characterized by physical or psychologic symptoms that are voluntarily self-induced. These diseases are as old as mankind. Once called "malingerers," these patients must be distinguished from hysterics in whom symptoms are produced unconsciously. In factitious diseases, illness is produced by deliberate acts by the patient who when seeking medical help omits to mention them and may continue strenuously to deny them even when confronted with the evidence. Factitious diseases occur in patients who simulate or exaggerate symptoms or disability to obtain some kind of discernible personal gain or avoid an unpleasant situation; however, such actions may only produce disadvantages by exposing the patient to the risk of death or permanent injury. This has been described as Munchausen syndrome, which is probably a manifestation of severe psychiatric disease. The use of medicines or poisons to induce illness in others also produces a type of factitial disease and presents similar or greater difficulties in diagnosis. In both situations, the clinical history, ordinarily the most important clue to the correct diagnosis, is not only incomplete but often misleading. Sometimes referred to as Munchausen by proxy, this form of factitial disease may be impossible to distinguish from attempted murder or grievous bodily harm. The subtle differences between these disorders, if any, have not been discussed herein.


Subject(s)
Factitious Disorders , Forensic Medicine , Homicide , Hypoglycemia , Hypoglycemic Agents/administration & dosage , Suicide , Factitious Disorders/chemically induced , Factitious Disorders/diagnosis , Factitious Disorders/therapy , Humans , Hypoglycemia/chemically induced , Hypoglycemia/diagnosis , Hypoglycemia/therapy , Insulin/administration & dosage , Suicide, Attempted , Sulfonylurea Compounds/administration & dosage
11.
Clin Endocrinol (Oxf) ; 49(4): 491-8, 1998 Oct.
Article in English | MEDLINE | ID: mdl-9876347

ABSTRACT

OBJECTIVE: To assess the relative efficacy of hGH and glucocorticoids in the treatment of non-islet cell tumour hypoglycaemia (NICTH) by examination of their influence on the composition of the various molecular species involving tumour and mature forms of IGF-II in association with IGFBP-3. DESIGN: Two groups each of 4 patients, all diagnosed as cases of NICTH, were treated with either hGH or glucocorticoids. Through the use of acidic size exclusion chromatography serum levels of tumour (big) and mature IGF-II were evaluated. Neutral size exclusion chromatography was used in the separation of molecular species before assay for immunoreactive IGF-II and IGFBP-3 content. RESULTS: High-dose hGH treatment produced increases in serum levels of big and mature IGF-II and IGFBP-3 but without generation of high molecular weight complexes. Glucocorticoid treatment suppressed big IGF-II permitting re-establishment of normal IGF/IGFBP association patterns. CONCLUSION: Glucocorticoid therapy has been demonstrated to consistently reverse the biochemical abnormalities caused by tumour-derived big IGF-II compared with the potentially adverse stimulatory effects of hGH treatment in causing increases in serum levels of big IGF-II.


Subject(s)
Glucocorticoids/therapeutic use , Human Growth Hormone/therapeutic use , Hypoglycemia/etiology , Insulin-Like Growth Factor II/metabolism , Neoplasms/complications , Protein Precursors/metabolism , Adult , Aged , Aged, 80 and over , Depression, Chemical , Drug Therapy, Combination , Female , Humans , Hypoglycemia/drug therapy , Hypoglycemia/metabolism , Insulin-Like Growth Factor Binding Protein 3/analysis , Insulin-Like Growth Factor II/analysis , Male , Middle Aged , Neoplasms/metabolism , Protein Precursors/analysis , Syndrome
12.
Growth Horm IGF Res ; 8(6): 447-54, 1998 Dec.
Article in English | MEDLINE | ID: mdl-10985756

ABSTRACT

We describe a case of non-islet cell tumour hypoglycaemia (NICTH) associated with a renal cell carcinoma. Serum insulin-like growth factors (IGFs) (including IGF-II E peptide), IGF-binding proteins (IGFBPs), insulin and C-peptide were measured before and after surgical removal of the tumour. IGFBPs were visualized by Western ligand blotting. Preoperatively 'big' IGF-II and IGFBP-2 levels were raised. IGF-I, IGFBP-1 and IGFBP-3 were low, while insulin, C-peptide and GH were undetectable. These changes were reversed by 2 days postoperatively. Protease assays showed little IGFBP-3 protease activity preoperatively. Preoperatively, neutral chromatography demonstrated most of the immunoassayable IGFBP-3 in a high molecular weight form with a small amount of IGF-II. Most of the IGF-II and big IGF-II eluted in lower molecular weight forms. Postoperative samples showed a shift in IGF-II which became increasingly associated with IGFBP-3 in both low and high molecular weight complexes. By Northern blotting, expression of all species of IGF-II mRNA in the tumour was 10-fold greater than in normal human liver. The tumour did not express IGFBP-1 or IGFBP-2. IGFBP-3 was expressed in small amounts, while the expression of IGFBP-4 was two-fold higher than in liver. In conclusion, we have confirmed high levels of big IGF-II and IGFBP-2 in NICTH, changes which are reversed postoperatively. The IGF-II is derived from the tumour which overexpresses these genes but IGFBP-2 probably arises from extratumour upregulation.


Subject(s)
C-Peptide/blood , Carcinoma, Renal Cell/blood , Hypoglycemia/etiology , Insulin-Like Growth Factor Binding Proteins/blood , Insulin-Like Growth Factor II/metabolism , Insulin-Like Growth Factor I/metabolism , Insulin/blood , Kidney Neoplasms/blood , Aged , Blotting, Northern , Carcinoma, Renal Cell/genetics , Carcinoma, Renal Cell/surgery , Female , Follow-Up Studies , Humans , Insulin-Like Growth Factor Binding Protein 1/blood , Insulin-Like Growth Factor Binding Protein 1/genetics , Insulin-Like Growth Factor Binding Protein 2/blood , Insulin-Like Growth Factor Binding Protein 2/genetics , Insulin-Like Growth Factor Binding Protein 3/blood , Insulin-Like Growth Factor Binding Protein 3/genetics , Insulin-Like Growth Factor Binding Proteins/genetics , Insulin-Like Growth Factor I/analysis , Insulin-Like Growth Factor I/genetics , Insulin-Like Growth Factor II/analysis , Insulin-Like Growth Factor II/genetics , Kidney Neoplasms/genetics , Kidney Neoplasms/surgery , RNA, Messenger/genetics
13.
Ann Clin Biochem ; 34 ( Pt 6): 627-31, 1997 Nov.
Article in English | MEDLINE | ID: mdl-9366999

ABSTRACT

We investigated whether pancreatic beta-cell dysfunction has a role in the pathogenesis of glucose intolerance in acromegaly by comparing plasma intact proinsulin, immunoreactive insulin, C-peptide and glucose concentrations during a 75 g oral glucose load in six patients with active acromegaly and eight healthy volunteers. Only acromegalic patients with normal glucose tolerance were studied. Glucose concentrations were similar in acromegalic patients and controls. Acromegalic patients had higher fasting insulin (P < 0.005) and fasting C-peptide (P < 0.005) concentrations than controls. Although fasting proinsulin levels were higher in acromegalic patients than controls, this did not achieve statistical significance. Integrated insulin (P < 0.05), C-peptide (P < 0.05) and proinsulin (P < 0.005) concentrations were greater in acromegalic patients than control subjects. Integrated (P < 0.05) proinsulin:insulin molar ratios were higher in acromegalic patients than controls. Fasting and integrated insulin:C-peptide molar ratios were similar in acromegalic patients and controls. These results indicate that hyperproinsulinaemia contributes to the hyperinsulinaemia which characterizes active acromegaly. The disproportionate hyperproinsulinaemia in acromegaly suggests that prolonged and excessive growth hormone secretion may result in pancreatic beta-cell dysfunction which may predispose acromegalic subjects to glucose intolerance.


Subject(s)
Acromegaly/physiopathology , Islets of Langerhans/metabolism , Proinsulin/blood , Acromegaly/blood , Adult , Blood Glucose/analysis , C-Peptide/blood , Female , Glucose Tolerance Test , Humans , Insulin/blood , Male , Middle Aged
14.
Clin Endocrinol (Oxf) ; 47(1): 43-50, 1997 Jul.
Article in English | MEDLINE | ID: mdl-9302371

ABSTRACT

OBJECTIVE: IGF-I and IGF binding protein (IGFBP)-3 levels in man are positively regulated by GH status; in contrast, evidence suggests an inverse relationship between GH status and IGFBP-2. We investigated the effects of somatropin administration on the serum concentrations of these analytes, together with serum and urinary concentrations of GH, to evaluate their potential as markers in the development of a test for detecting doping with GH in sports competitors. DESIGN: Somatropin was administered subcutaneously at a dose of 0.15 U/kg bodyweight/day at 1000 h for 3 days to eight healthy men (20-32 years old). MEASUREMENTS: Serum concentrations of GH, IGF-I, IGFBP-2 and -3 were determined in blood samples collected at 1600 h on the days prior to (day -1), during (days 0, 1 and 2), and following administration (days 3 and 7). Urine was collected continuously from days -2 to 3 and then on day 7. RESULTS: Serum and urinary concentrations of GH were only raised on the days of administration whereas, following cessation of somatropin, the increases in the serum concentrations of IGF-I and IGFBP-3 were sustained for at least 1 day (30 h). Serum IGFBP-2 decreased during the period of administration and was still suppressed on day 3. The concentration ratios of IGFBP-3 to IGFBP-2 and IGF-I to IGFBP-2 increased markedly with administration and both ratios were still significantly augmented compared with basal values 30 h after the last administration. CONCLUSION: With acute administration of somatropin to healthy men the serum concentration of IGFBP-2 decreases and the ratios of serum IGF-I/ IGFBP-2 and IGFBP-3/IGFBP-2 increase. These ratios should be considered in the development of a test for detecting somatropin administration in sport.


Subject(s)
Doping in Sports , Growth Hormone , Insulin-Like Growth Factor Binding Protein 2/blood , Insulin-Like Growth Factor Binding Protein 3/blood , Insulin-Like Growth Factor I/analysis , Substance Abuse Detection/methods , Adult , Biomarkers/blood , Growth Hormone/blood , Growth Hormone/urine , Humans , Male , Predictive Value of Tests , Time Factors
15.
Clin Endocrinol (Oxf) ; 45(3): 327-31, 1996 Sep.
Article in English | MEDLINE | ID: mdl-8949571

ABSTRACT

OBJECTIVE: While the effects of age on the growth hormone/insulin-like growth factor (IGF) axis are well documented, the influence of ethnic background is unknown. The differences in IGF and IGF binding proteins (IGFBPs) were investigated in two ethnic groups. DESIGN: A cross-sectional study of an age-selected cohort of healthy, normoglycaemic, non-obese Caucasian (C) and Asian (A) subjects. PATIENTS: Fifty-three (27 C, 26 A) subjects with a mean age (+/- SD) of 20.6 +/- 0.8 years were studied. MEASUREMENTS: Fasting measurements of glucose, insulin, IGF-I, IGF-II, IGFBP-1 and IGFBP-3. Western ligand blotting and immunoblotting with IGFBP-2 and IGFBP-3 of serum samples. RESULTS: There were no significant differences in IGF-I levels between Caucasian and Asian subjects (C 218 +/- 55 vs A 229 +/- 40 micrograms/l; P = 0.44). IGF-II (C 707 +/- 110 vs A 583 +/- 75 micrograms/l; P < 0.0001) and IGFBP-3 (C 5.9 +/- 1.2 vs A 5.12 +/- 1.17 mg/l; P = 0.01) levels were significantly higher in Caucasian subjects. Immunoblotting of ligand blots revealed no protease activity on either IGFBP-3 or IGFBP-2 to account for these ethnic differences. CONCLUSIONS: Ethnic differences in IGFBP-3 and associated IGF-II levels may affect the inter-relationships of IGFs and their binding proteins and need to be considered when interpreting IGF data on growth and metabolism.


Subject(s)
Asian People , Insulin-Like Growth Factor Binding Protein 3/blood , Insulin-Like Growth Factor II/analysis , White People , Adult , Cross-Sectional Studies , Female , Humans , Immunoblotting , Insulin-Like Growth Factor Binding Protein 2/blood , Insulin-Like Growth Factor I/analysis , Male
17.
Clin Endocrinol (Oxf) ; 44(6): 727-31, 1996 Jun.
Article in English | MEDLINE | ID: mdl-8759187

ABSTRACT

A patient presented with frequent episodes of spontaneous hypoglycaemia due to a solitary fibrous tumour of pleural origin, secreting incompletely processed pro-insulin-like growth factor II (big IGF-II). Somatostatin receptors were demonstrated in the tumour by 111 inlabelled octreotide scintigraphy, but despite maximal doses of octreotide, there was no suppression of big IGF-II secretion and the hypoglycaemia persisted. The combination of GH and glucocorticoid therapy abolished the hypoglycaemia.


Subject(s)
Hypoglycemia/etiology , Pancreatic Neoplasms/complications , Aged , Bendroflumethiazide/therapeutic use , Drug Therapy, Combination , Female , Glucocorticoids/therapeutic use , Humans , Hypoglycemia/diagnostic imaging , Hypoglycemia/drug therapy , Insulin-Like Growth Factor II/metabolism , Octreotide/therapeutic use , Pancreatic Neoplasms/diagnostic imaging , Pancreatic Neoplasms/drug therapy , Prednisolone/therapeutic use , Protein Precursors/metabolism , Radionuclide Imaging , Receptors, Somatostatin/analysis , Somatostatin/therapeutic use
19.
J Int Fed Clin Chem ; 6(5): 164-8, 1995 Nov.
Article in English | MEDLINE | ID: mdl-10155148

ABSTRACT

Selected combinations of tests for growth hormone and the growth mediating peptides, insulin-like growth factors, and their binding proteins have improved the diagnostic reliability of the procedures used in the investigation of growth abnormalities (GH deficiency, GH and IGF receptor deficiencies, GH excess, diabetes, or undernutrition) and in malignancies associated with hypoglycemia.


Subject(s)
Growth Disorders/diagnosis , Growth Hormone/blood , Insulin-Like Growth Factor Binding Proteins/blood , Somatomedins/metabolism , Abdominal Neoplasms/blood , Abdominal Neoplasms/complications , Abdominal Neoplasms/diagnosis , Body Height , Child , Diabetes Complications , Diabetes Mellitus/blood , Diabetes Mellitus/diagnosis , Growth Disorders/blood , Growth Disorders/etiology , Humans , Hypoglycemia/blood , Hypoglycemia/complications , Hypoglycemia/diagnosis , Protein-Energy Malnutrition/blood , Protein-Energy Malnutrition/complications , Protein-Energy Malnutrition/diagnosis
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