what factor is least likely to lead to hypoglycemia
J Cancer. 2019; 10(26): 6475–6480.
Hypoglycemia as a Symptom of Neoplastic Disease, with a focus on Insulin-like Growth Factors Producing Tumors
Jan Schovanek
1Department of Internal Medicine III - Nephrology, Rheumatology and Endocrinology, Kinesthesia of Medicine and Dentistry, Palacky University Olomouc and University Hospital Olomouc, Czech republic.
Lubica Cibickova
aneSection of Internal Medicine Three - Nephrology, Rheumatology and Endocrinology, Faculty of Medicine and Dentistry, Palacky University Olomouc and Academy Hospital Olomouc, Czechia.
Filip Ctvrtlik
2Department of Radiology, Faculty of Medicine and Dentistry, Palacky University Olomouc and Academy Infirmary Olomouc, Czech republic.
Zbynek Tudos
2Department of Radiology, Faculty of Medicine and Dentistry, Palacky University Olomouc and University Hospital Olomouc, Czechia.
David Karasek
1Department of Internal Medicine Three - Nephrology, Rheumatology and Endocrinology, Faculty of Medicine and Dentistry, Palacky University Olomouc and University Infirmary Olomouc, Czech republic.
Maurizio Iacobone
threeEndocrine Surgery Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, Italy, Via Giustiniani 2, 35128 Padova, Italy.
Zdenek Frysak
1Department of Internal Medicine Iii - Nephrology, Rheumatology and Endocrinology, Kinesthesia of Medicine and Dentistry, Palacky University Olomouc and University Hospital Olomouc, Czech Commonwealth.
Received 2019 Jan 11; Accustomed 2019 Jun 23.
Abstruse
This article reviews the current knowledge of uncommon causes of hypoglycemia, with a focus on neoplastic affliction. However, these situations are rare. They normally accompany severely ill patients and therefore a proper diagnosis is the basis for relevant treatment. Here we discuss the pathophysiological foundation of hypoglycemia - situations caused by increased insulin production or sensitivity - but nosotros also focus on different cytokines which could cause hypoglycemia, especially IGF-II production in what are called nonislet cell tumors. From the clinical perspective we can divide the patients who are affected into "seemingly sick" or "good for you patients" and lead the diagnostic process appropriately.
Keywords: Nonislet jail cell tumor (NICT), Nonislet jail cell tumor hypoglycemia (NICTH), insulin-like growth cistron two (IGF-Ii), Adrenal Glands
Introduction
A driblet in glucose serum levels leading to hypoglycemia becomes fully manifested by neuroglycopenic symptoms with changes in level of consciousness. Attending physicians face difficult situations resulting from a plethora of potential causes, clinically presenting equally the classic Whipple's triad of a low blood glucose level, clinical symptoms of hypoglycemia at the time of the low glucose level, and the relief of those symptoms later on the restoration of glucose levels. The symptoms of hypoglycemia depend on the drib in the glucose level and tin be categorized equally neurogenic or neuroglycopenic 1. Neurogenic symptoms are connected to sympathoadrenal activation and include sweating, shakiness, tachycardia, anxiety, and a sensation of hunger. Neuroglycopenic symptoms are acquired by the affection of neuronal functions and include weakness, tiredness, and, in extreme cases, coma or somewhen death.
In an outpatient setting, apart from the inadequate dosing of glucose-lowering drugs (whether intentional or unintentional), nosotros must call back of diet mistake and alcohol abuse. In a hospital setting, in addition to the in a higher place-mentioned causes, nosotros too have to think of errors in the administration of medication. Hospitalized patients likewise tend to be more ill than patients in outpatient clinics. The patients at higher chance of hypoglycemia are those suffering from malnutrition, severe sepsis, or liver, kidney, or centre failure. On the endocrine ward nosotros can confront hypoglycemia as a sign of endocrine disruption caused past hypopituitarism, hypocorticism, or low glucagon levels. On the surgical ward, hypoglycemia could develop equally a result of gastric featherbed surgery, dumping syndrome, and other mail service-surgical conditions.
Hypoglycemia accompanying neoplastic diseases, known as tumor-related hypoglycemia, is a split up topic and tin can, on the basis of its pathogenesis, be divided into four groups; encounter Table 1. Hypoglycemia with high insulin levels presenting a symptom of a neuroendocrine tumor - insulinoma (islet cell tumor) or functional disorder of pancreatic β-cells - nesidioblastosis. However, in many of the cases of what is called tumor-induced hypoglycemia the etiological agent of hypoglycemia is non an insulin only its structurally like polypeptide, somatomedin A also called insulin-like growth factor Ii (IGF-II), and the hypoglycemia is referred to as nonislet cell tumor hypoglycemia (NICTH) 2. Other substances produced past the tumor could also interfere with glucose metabolism, including insulin receptor antibodies and various cytokines (tumor necrosis factor-α, interleukin-one and -vi) and catecholamines (in pheochromocytomas). Finally, hypoglycemia could be direct related to the growth of the tumor - destruction of the liver or adrenal gland by infiltration of the tumor 3. In all cases we should think about the patient in a complex way and the potential causes of hypoglycemia, not omitting the rare causes, as they are the focus of this review.
Table 1
Pathophysiological classification of tumor-related hypoglycemia. Modified from 3.
| Islet Prison cell Tumors | Eutopic insulin production |
|---|---|
| Insulinoma | |
| Nonislet Jail cell Tumors | Neuroendocrine tumors |
| Mesenchymal tumors | |
| Adrenal, Hepatocellular, Gastrointestinal, Ovarian carcinomas | |
| Ectopic insulin production (Pheochromocytoma, Small-cell carcinomas) | |
| Massive tumor burden/liver infiltration | |
| Tumor production of autoantibodies confronting insulin or the insulin receptor |
Pathophysiology
Humans accept very effective systems for the prevention of hypoglycemia 4 and the value of the plasma glucose level itself is not sufficient to prove the full image of this clinical condition. Even salubrious people exhibit clinical symptoms of hypoglycemia if their glucose level drops below 3 mmol/l 5.
Insulin-like Growth Factors I and II (IGF-I, IGF-Two) have well-described structural similarities to insulin and together form a group of what are chosen somatomedins half-dozen. Hormones fulfill their functions by acting on several types of signaling tyrosine kinase receptors, mainly the insulin receptor (IR) and insulin-like growth cistron I receptor (IGF-IR). IGF-2 too binds to the non-signaling IGF type 2 receptor (IGF-IIR), which regulates the amount of circulating and tissue IGF-Ii past transporting the ligand into the cell and degrading it 7. The glucose-lowering effect of IGFs is 10 times lower than that of insulin, but in healthy subjects the serum concentration of IGFs is near thousand times higher than that of insulin 8. However, in contrast to insulin, in circulation most of the IGFs (90%) are tightly bound to IGF-binding proteins (IGFBPs) two. IGF-I suppresses liver glucose product, stimulates peripheral glucose utilization, and has an inhibitory outcome on insulin secretion. Its role is of import for childhood growth and during adulthood it has an anabolic outcome. The synthesis of IGF-I largely depends on its stimulation by growth hormone (GH) through the GH receptor, whereas the synthesis of IGF-Two is relatively contained of GH action 2. IGF-II is usually produced by the liver and plays an important role in fetal and postnatal evolution; during this menstruation an A-isoform of an insulin receptor is the main receptor for IGF-2. This isoform of IR is predominantly expressed during prenatal life and enhances the effects of IGF-Two during embryogenesis and fetal development 9. Non much is known virtually the physiological functions of IGF-2 in adulthood. Nearly of the IGF-II produced by the liver forms stabilizing tertiary complexes with a molecular weight of 150-kD with IGF-bounden protein three (IGFBP3). These big complexes do non interact with the insulin receptor and therefore do not crusade hypoglycemia x. On the contrary, in a patient suffering from what are called nonislet prison cell tumors the IGF-II can exist produced equally a upshot of abnormal post-translational processing in the form of a "big" molecule with a molecular weight of xi-18kD. It seems likely that in many neoplastic cells the levels of the various enzymes involved in post-translational processing are non sufficient to handle the relatively high amounts of "big" IGF-Two that are produced adequately 2. This later binds to the IGF-binding poly peptide 2 (IGFBP2), forming smaller binary complexes with a molecular weight of l-kD (in contrast to physiological 3rd complexes with IGFBP3) and likewise a fraction of the IGF-II stays in the free unbound class, every bit reported by Frystyk et al., and the complimentary form of IGF-II was found to be increased 20-fold (not discriminating between complimentary mature and free "big" IGF-II) in comparison to control subjects; however, the levels of total IGF-2 were normal 11 or could even be decreased 12. Birthday, in the serums of patients suffering from NICTH increased levels of complimentary IGF-II were found, and also of "big" IGF-II with greater capillary permeability, and thus increased IGF bioavailability to the tissues; these combinations can lead to hypoglycemia as a issue of increased glucose utilization in the skeletal muscles and as well suppressed gluconeogenesis and glycogenolysis in the liver 10 , 11. Moreover, considering of increased negative feedback on growth hormone (GH) production by the anterior pituitary gland, the synthesis of GH and GH-dependent IGFBP-3 is reduced - closing the hypoglycemic loop.
Even though the information are not always consistent, information technology is nowadays believed that IGFs in general and IGF-II in particular tin promote tumor growth in situ in an autocrine or paracrine fashion once the tumor has been established. Increased expression of IGF-I, IGF-Two, and IGF-IR has been determined in a variety of neoplasia, including brain tumors, mammary carcinoma, gastrointestinal cancer, including pancreatic carcinoma, and ovarian carcinoma xiii , 14.
Clinical perspective
The sensation of hypoglycemia can differ broadly betwixt people, equally clinicians experienced in performing insulin tolerance tests are aware. The latest Endocrine Society Clinical Practice Guideline recommends as an initial pace in the diagnostic approach to a patient presenting with hypoglycemia without evidence of diabetes mellitus handling to review the patient's history, concrete findings, and all available laboratory information in order to seek clues pointing to specific disorders - drugs, disquisitional illness, hormone deficiencies, and also NICTH, or, in patients with no obvious cause of hypoglycemia, "seemingly well people", to measure plasma glucose, insulin, C-peptide, proinsulin, and β-hydroxybutyrate (representative of ketones) and to screen for oral hypoglycemic agents (ideally all available sulfonylureas and glinides) and then correct the hypoglycemia with the injection of 1.0 mg glucagon iv with measurement of the plasma glucose response. These information volition distinguish endogenous (and exogenous) hyperinsulinemia from other causes of hypoglycemia four. Additionally, the measurement of insulin antibodies is recommended, withal, not necessarily during the hypoglycemia. Their presence indicates rare insulin autoimmune hypoglycemia xv.
In "seemingly well people" endogenous hyperinsulinemia must be evaluated past the above-mentioned laboratory tests and then confirmed by imaging studies and in indicated cases by biopsy. Insulinoma as a solid source of insulin overproduction can be imaged with low sensitivity and specificity by intestinal ultrasound; amend clinical usability is obtained with computed tomography, nuclear magnetic resonance, and scintigraphy imaging. The gilded standard to confirm insulinoma is to perform endoscopic ultrasonography of the pancreas, which also allows for a biopsy; however, although this procedure is highly valued past clinicians, its performance is highly good-dependent and thus bachelor but in specialized centers 16.
If insulinoma is excluded, another possible cause of endogenous insulin overproduction is nesidioblastosis - hypertrophy/hyperplasia of pancreatic β-cells 17. Its confirmation is extremely complicated and demanding. Thompson et al. used with high specificity and sensitivity selective arterial calcium stimulation with hepatic venous sampling in 116 patients 18. The correct interpretation of the results that are obtained is conditioned by good knowledge of the pancreatic arteries. Surgery could be a curative selection for these patients 18 - 20.
Pheochromocytoma (PHEO) as a tumor of the adrenal gland has a circuitous effect on glucose homeostasis. Xx-five to seventy-five percent of patients with PHEO accept altered glucose tolerance 21 , 22. Catecholamines (especially norepinephrine) stimulate α2 adreno-receptors and thus inhibit insulin secretion and too increment insulin resistance 22. On the other hand, hypoglycemia was also reported in patients with PHEO, most commonly in the postoperative stage, probably as a issue of the sudden loss of catecholamines 23. In this case hypoglycemia manifests with classic symptoms, which could, nonetheless, be masked by the effect of residue anesthesia and the presence of β-blockage 24. Severely sick patients with PHEO can present with hypoglycemia as a result of liver metastasis (low glycogen stores) or secondarily equally a result of directly consumption of glucose past the tumor (case report of a big tumor of the adrenal gland) 25. In some patients the domination of β2 adreno-receptors effect of catecholamines (esp. epinephrine) results in insulin release and consequent hypoglycemia, usually in conditions where glycogen stores were depleted 26.
Nonislet cell tumor hypoglycemia, also called Doege-Potter syndrome, is a rare disease with an estimated incidence of one case per million 27 , 28. NICTH, as excellently reviewed past de Groot et al., is idea to exist rather a fasting hypoglycemia characterized by diminished hepatic glucose production resulting from the inhibition of glycogenolysis and gluconeogenesis; macerated lipolysis in adipose tissue resulting in depression levels of serum-free fatty acids and increased peripheral glucose consumption 2. These symptoms instigating towards insulin-similar activity are, however, acquired past tumor production of insulin-like growth factor. Those clinical signs and symptoms were described in patients with mesenchymal tumors, fibromas, carcinoid, myelomas, lymphomas and hepatocellular, and colorectal carcinomas 28.
A diagnosis of NICTH is based upon clinical and the above-mentioned laboratory evaluation; in seemingly sick patients the diagnosis might exist more straightforward than in healthy-looking people in whom hypoglycemia would be the first symptom of the underlying cancer 29. The measurement of total, free, or "large" IGF-II is not routinely available and is also unnecessary for establishing the diagnosis. Chromatography is considered equally a aureate standard for IGF-Ii measurement; however, the total levels of IGF-II might not be significantly changed, equally explained above; rather, the ratio of produced "large" IGF-2/IGF-Ii might exist of clinical importance, as might the ratio of IGF-I/IGF-Ii 29 , 30. There is no unifying statement equally to whether the existence of NICTH is of prognostic value with respect to predicting the degree of malignancy of a tumor or the (disease-free) survival of the patient two , 31.
The diagnostic approach could exist guided by Effigy i.
Clinical guidance on potential causes of hypoglycemia with some corresponding laboratory findings in cases of tumor-related hypoglycemia. Modified from 3 , 4 , 32 , 37 , 38. Shortcuts: OHA - oral hypoglycemic agents, I - insulin, C-P - C-peptide, DS - drug screen, IGF * - increased pro-IGF-II, free IGF-II, IGF-Ii/IGF-I ratio, IAS - Insulin Autoimmune Syndrome ("Hirata disease"), TAS - Tumor Autoimmune Syndrome, A - insulin antibody (presence of either anti-insulin antibodies [insulin autoimmune syndrome, Hirata affliction] or anti-insulin receptor antibodies [blazon B insulin resistance]. If TAN antibodies are produced past the tumor, ↑ - increased, ↓ - decreased, + - nowadays, - - absent-minded, North - normal
Treatment
Like any hypoglycemic country, NICTH requires proper treatment by glucose or glucagon. The mainstay of the NICTH is treatment of the primary tumor; complete removal of the tumor mass is curative and leads to the restitution of normoglycemia, but for many patients information technology is often delayed or unfeasible. There is no articulate "standard of intendance" for managing those tumors 32. In selected cases systemic or local chemotherapy, tumor embolization, or radiations therapy might be effective; yet, the overall experience with these methods tends rather not to back up their use 32. A mutual offset-line mensurate is to increase the oral intake of diet, sometimes accompanied by parenteral nutrition; notwithstanding, while this could assistance to stabilize glucose levels, it cannot serve as a permanent solution. The most effective treatment, and also the one with the nearly consistent results, seems to exist glucocorticoid therapy. Information technology has an immediate upshot on the hypoglycemia and likewise corrects the metabolism in the long term or before curative surgery can be performed.
Glucocorticoids stimulate gluconeogenesis, and at to the lowest degree partially suppress "big" IGF-Two and correct biochemical abnormalities involving the GH-IGF axis 2 , 5 , 33. The utilise of recombinant homo growth hormone (rhGH) has been successful in many cases, every bit information technology suppresses peripheral glucose intake and increases levels of IGF-I and IGF-Ii bounden proteins. Combination therapy with glucocorticoids and rhGH might potentiate the benefits of those medications and at the same fourth dimension prevent some side-effects 34; however, some practise non recommend its use except in cases of palliative treatment 31.
The offset-line and just curative option for insulinoma is surgical excision by enucleation or partial pancreatectomy 3. In cases of irresectable or malignant tumors (about 5-10% of cases) medical therapy with diazoxide or somatostatin analogs could be used to control hypoglycemic symptoms. However, the data on the use of somatostatin analogs are very inconsistent; their use in extremely resistant cases might exist advocated. Experience with systemic chemotherapy in malignant insulinoma is limited. The traditional regimen of option has been streptozocin and doxorubicin, only dubiousness as to its efficacy, besides as the toxicity of this regimen (nausea, prolonged myelosuppression, renal failure), has prevented its widespread acceptance. Molecularly targeted therapy options with pocket-sized molecule tyrosine kinase inhibitors and inhibitors of the mammalian (mechanistic) target of rapamycin (mTOR), equally well equally peptide receptor radioligand therapy, are expected 35.
In pheochromocytoma, hypoglycemia is mainly acquired by the outcome of insulin; therefore the standard hypoglycemia treatment options should exist effective 36. The same is valid for the nigh common case of postoperative hypoglycemia, which needs to be correctly diagnosed in order to be promptly managed with glucose intravenous therapy 24.
Conclusions
Hypoglycemia is a common clinical condition. Hypoglycemia in severely ill or oncology patients is not rare; however, the establishment of a right diagnosis of NICTH requires a expert level of cognition and especially the courage to recollect about a rare diagnosis. When we are thinking about NICTH, the diagnosis itself is not then difficult to establish.
Acknowledgments
The present study was supported by the Ministry of Health of the Czech Republic (grant no. 17-31847A) and the Ministry building of Health of the Czech Democracy - Conceptual evolution of research organisation (FNOL, 00098892).
References
1. Cryer PE. Hypoglycemia, functional encephalon failure, and encephalon death. The Journal of Clinical investigation. 2007;117:868–70. [PMC gratuitous commodity] [PubMed] [Google Scholar]
2. de Groot JW, Rikhof B, van Doorn J, Bilo HJ, Alleman MA, Honkoop AH. et al. Not-islet prison cell neoplasm-induced hypoglycaemia: a review of the literature including two new cases. Endocrine-related cancer. 2007;fourteen:979–93. [PubMed] [Google Scholar]
3. Iglesias P, Diez JJ. Direction of endocrine disease: a clinical update on tumor-induced hypoglycemia. European journal of endocrinology. 2014;170:R147–57. [PubMed] [Google Scholar]
4. Cryer PE, Axelrod 50, Grossman AB, Heller SR, Montori VM, Seaquist ER. et al. Evaluation and management of adult hypoglycemic disorders: an Endocrine Social club Clinical Practice Guideline. The Periodical of clinical endocrinology and metabolism. 2009;94:709–28. [PubMed] [Google Scholar]
5. Boyle PJ, Schwartz NS, Shah SD, Clutter WE, Cryer PE. Plasma glucose concentrations at the onset of hypoglycemic symptoms in patients with poorly controlled diabetes and in nondiabetics. The New England journal of medicine. 1988;318:1487–92. [PubMed] [Google Scholar]
6. Frysak Z, Schovanek J, Iacobone Thou, Karasek D. Insulin-like Growth Factors in a clinical setting: Review of IGF-I. Biomedical papers of the Medical Faculty of the University Palacky, Olomouc, Czechoslovakia. 2015;159:347–51. [PubMed] [Google Scholar]
7. Hassan AB. Keys to the hidden treasures of the mannose 6-phosphate/insulin-like growth factor 2 receptor. The American journal of pathology. 2003;162:3–half dozen. [PMC gratis article] [PubMed] [Google Scholar]
8. Rinderknecht E, Humbel RE. The amino acid sequence of human insulin-like growth factor I and its structural homology with proinsulin. The Journal of biological chemistry. 1978;253:2769–76. [PubMed] [Google Scholar]
ix. Belfiore A, Frasca F, Pandini G, Sciacca Fifty, Vigneri R. Insulin receptor isoforms and insulin receptor/insulin-like growth gene receptor hybrids in physiology and illness. Endocrine reviews. 2009;thirty:586–623. [PubMed] [Google Scholar]
10. Hizuka N, Fukuda I, Takano 1000, Asakawa-Yasumoto K, Okubo Y, Demura H. Serum high molecular weight form of insulin-like growth factor Ii from patients with non-islet jail cell tumor hypoglycemia is O-glycosylated. The Journal of clinical endocrinology and metabolism. 1998;83:2875–7. [PubMed] [Google Scholar]
xi. Frystyk J, Skjaerbaek C, Zapf J, Orskov H. Increased levels of circulating free insulin-like growth factors in patients with non-islet cell tumour hypoglycaemia. Diabetologia. 1998;41:589–94. [PubMed] [Google Scholar]
12. Hoekman K, van Doorn J, Gloudemans T, Maassen JA, Schuller AG, Pinedo HM. Hypoglycaemia associated with the production of insulin-like growth factor II and insulin-like growth cistron binding protein 6 by a haemangiopericytoma. Clinical endocrinology. 1999;51:247–53. [PubMed] [Google Scholar]
xiii. Bergman D, Halje M, Nordin M, Engstrom Due west. Insulin-like growth factor 2 in evolution and disease: a mini-review. Gerontology. 2013;59:240–9. [PubMed] [Google Scholar]
fourteen. Cerrato F, Sparago A, Verde G, De Crescenzo A, Citro Five, Cubellis MV. et al. Unlike mechanisms cause imprinting defects at the IGF2/H19 locus in Beckwith-Wiedemann syndrome and Wilms' neoplasm. Human molecular genetics. 2008;17:1427–35. [PubMed] [Google Scholar]
15. Service FJ. Nomenclature of hypoglycemic disorders. Endocrinology and metabolism clinics of Northward America. 1999;28(six):501–17. [PubMed] [Google Scholar]
16. Kann PH. Endoscopic Ultrasound in Endocrinology: Imaging of the Adrenals and the Endocrine Pancreas. Frontiers of hormone research. 2016;45:46–54. [PubMed] [Google Scholar]
17. Anlauf Thou, Wieben D, Perren A, Sipos B, Komminoth P, Raffel A. et al. Persistent hyperinsulinemic hypoglycemia in 15 adults with diffuse nesidioblastosis: diagnostic criteria, incidence, and characterization of beta-prison cell changes. The American journal of surgical pathology. 2005;29:524–33. [PubMed] [Google Scholar]
xviii. Thompson SM, Vella A, Thompson GB, Rumilla KM, Service FJ, Grant CS. et al. Selective Arterial Calcium Stimulation With Hepatic Venous Sampling Differentiates Insulinoma From Nesidioblastosis. The Journal of clinical endocrinology and metabolism. 2015;100:4189–97. [PMC free article] [PubMed] [Google Scholar]
19. Thompson GB, Service FJ, Andrews JC, Lloyd RV, Natt North, van Heerden JA. et al. Noninsulinoma pancreatogenous hypoglycemia syndrome: an update in ten surgically treated patients. Surgery. 2000;128:937–44. discussion 44-5. [PubMed] [Google Scholar]
20. Thompson SM, Vella A, Service FJ, Grant CS, Thompson GB, Andrews JC. Affect of variant pancreatic arterial anatomy and overlap in regional perfusion on the estimation of selective arterial calcium stimulation with hepatic venous sampling for preoperative localization of occult insulinoma. Surgery. 2015;158:162–72. [PMC gratuitous article] [PubMed] [Google Scholar]
21. Turnbull DM, Johnston DG, Alberti KG, Hall R. Hormonal and metabolic studies in a patient with a pheochromocytoma. The Journal of clinical endocrinology and metabolism. 1980;51:930–3. [PubMed] [Google Scholar]
22. Wiesner TD, Bluher One thousand, Windgassen M, Paschke R. Improvement of insulin sensitivity later on adrenalectomy in patients with pheochromocytoma. The Periodical of clinical endocrinology and metabolism. 2003;88:3632–half-dozen. [PubMed] [Google Scholar]
23. Thonangi RP, Bhardwaj Yard, Kulshreshtha B. A case report of reactive hypoglycemia in a patient with pheochromocytoma and it'southward review of literature. Indian periodical of endocrinology and metabolism. 2014;18:234–seven. [PMC costless article] [PubMed] [Google Scholar]
24. Chen Y, Hodin RA, Pandolfi C, Ruan DT, McKenzie TJ. Hypoglycemia afterward resection of pheochromocytoma. Surgery. 2014;156:1404–eight. discussion 8-ix. [PubMed] [Google Scholar]
25. Habra MA, Nunez R, Chuang H, Ayala-Ramirez G, Rich T, Kyle K. et al. Fatal hypoglycemia in malignant pheochromocytoma: direct glucose consumption as suggested by (18)F-two-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography imaging. Endocrine. 2010;37:209–12. [PubMed] [Google Scholar]
26. Cerasi E, Effendic S, Luft R. Role of adrenergic receptors in glucose-induced insulin secretion in man. Lancet. 1969;2:301–2. [PubMed] [Google Scholar]
27. Ahluwalia N, Attia R, Green A, Cane P, Routledge T. Doege-Potter Syndrome. Annals of the Purple College of Surgeons of England. 2015;97:e105–7. [PMC gratis article] [PubMed] [Google Scholar]
28. Marks 5, Teale JD. Tumours producing hypoglycaemia. Diabetes/metabolism reviews. 1991;7:79–91. [PubMed] [Google Scholar]
29. Fukuda I, Hizuka Northward, Ishikawa Y, Yasumoto Chiliad, Murakami Y, Sata A. et al. Clinical features of insulin-like growth factor-II producing non-islet-prison cell tumor hypoglycemia. Growth hormone & IGF research: official journal of the Growth Hormone Enquiry Society and the International IGF Inquiry Society. 2006;sixteen:211–6. [PubMed] [Google Scholar]
30. Miraki-Moud F, Grossman AB, Besser K, Monson JP, Camacho-Hubner C. A rapid method for analyzing serum pro-insulin-like growth factor-II in patients with non-islet jail cell tumor hypoglycemia. The Journal of clinical endocrinology and metabolism. 2005;90:3819–23. [PubMed] [Google Scholar]
31. Service FJ, Vella A, Hirsch IB, Mulder JE. Nonislet cell tumor hypoglycemia. In: Post T, editor. UpToDate. UpToDate, Waltham, MA. (Accessed on July 19, 2018); 2018. [Google Scholar]
32. Bodnar TW, Acevedo MJ, Pietropaolo One thousand. Management of non-islet-cell tumor hypoglycemia: a clinical review. The Journal of clinical endocrinology and metabolism. 2014;99:713–22. [PMC free commodity] [PubMed] [Google Scholar]
33. Teale JD, Marks V. Glucocorticoid therapy suppresses abnormal secretion of large IGF-II past non-islet cell tumours inducing hypoglycaemia (NICTH) Clinical endocrinology. 1998;49:491–viii. [PubMed] [Google Scholar]
34. Bourcigaux N, Arnault-Ouary Thou, Christol R, Perin L, Charbonnel B, Le Bouc Y. Treatment of hypoglycemia using combined glucocorticoid and recombinant human growth hormone in a patient with a metastatic not-islet cell tumor hypoglycemia. Clinical therapeutics. 2005;27:246–51. [PubMed] [Google Scholar]
35. Service FJ, Vella A. Insulinoma. In: Postal service T, editor. UpToDate. UpToDate, Waltham, MA. (Accessed on July 19, 2018); 2018. [Google Scholar]
36. Araki Due south, Kijima T, Waseda Y, Komai Y, Nakanishi Y, Uehara S. et al. Incidence and predictive factors of hypoglycemia afterward pheochromocytoma resection. International journal of urology: official journal of the Japanese Urological Association. 2019;26:273–7. [PubMed] [Google Scholar]
37. Skrha J. Hypoglykemie: od patofyziologie ke klinické praxi. Praha: Maxdorf; 2013. [Google Scholar]
38. Kantarova D, Sagova I, Stancik M, Sadlonova J. Hypoglycemia associated with not-islet cell tumors. Neoplasma. 2015;62:841–v. [PubMed] [Google Scholar]
Articles from Journal of Cancer are provided here courtesy of Ivyspring International Publisher
rogersninespere1969.blogspot.com
Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6856902/
0 Response to "what factor is least likely to lead to hypoglycemia"
Post a Comment