Insulinoma
Demetrius Pertsemlidis, William B. Inabnet III, Michel Gagner in Endocrine Surgery, 2017
The ultimate goal for the medical treatment is to avoid hypoglycemic episodes, and any patient scheduled for surgery needs to be preoperatively controlled to avoid these. Therefore, the patient should be told to have frequent meals and snacks, and to avoid prolonged intervals without intake of carbohydrates. This means that the patient has to wake up at night for a meal. Diazoxide is an antihypertensive and hyperglycemic drug that suppresses insulin secretion and enhances glycogenolysis, in doses between 50 and 300 (occasionally 600) mg/day [71]. However, diazoxide has a number of side effects, such as edema, renal impairment, and hirsutism. Usually, in a patient with a benign insulinoma, it is possible to avoid this drug. It is also important to await introduction of diazoxide until after the diagnosis of organic hyperinsulinism is clear, to avoid difficult workup. However, in malignant disease one often has to introduce the drug early.
Cardiovascular Drugs during Pregnancy
“Bert” Bertis Britt Little in Drugs and Pregnancy, 2022
Diazoxide is a thiazide (Hyperstat) that is used parenterally as an antihypertensive. An oral form of this drug (Proglycem) is also used to treat hypoglycemia secondary to hyperinsulinism. No epidemiologic studies of diazoxide have been published. An anecdotal case report of abnormalities of body and scalp hair, including alopecia, in four neonates of women who received oral diazoxide during the last trimester of pregnancy has been published (Milner and Chonskey, 1972). Maternal diazoxide therapy was also reportedly associated with hyperglycemia in the neonate (Milsap and Auld, 1980). No animal teratology studies are available. Pancreatic islet cell damage was found in the offspring of sheep and goats treated with intravenous diazoxide (Boulos et al., 1971). Diazoxide may inhibit uterine contractions (Landesman et al., 1969) and has been used in the past by some clinicians as a tocolytic agent. Only two infants were exposed to diazoxide in the first trimester in the Swedish Birth Defects Registry (Kallen, 2019).
Diabetes Mellitus, Obesity, Lipoprotein Disorders and other Metabolic Diseases
John S. Axford, Chris A. O'Callaghan in Medicine for Finals and Beyond, 2023
The diagnosis requires demonstration of inappropriately high or non-suppressed insulin levels during hypoglycaemia. This can be done by fasting the patient for a prolonged period (48–72 hours) and monitoring blood glucose concentrations. An important differential diagnosis is factitious hypoglycaemia secondary to insulin injection or use of sulphonylureas. Insulin for injection does not contain C-peptide so elevated C-peptide in the presence of hypoglycaemia suggests either insulinoma or sulphonylurea use. Sulphonylureas may be detected in blood or urine samples. Most insulinomas are benign tumours and surgical excision is usually curative. Preoperatively, the tumour may be localized by a number of techniques including CT/MRI scanning, PET scans and pancreatic angiography. Diazoxide, which inhibits insulin release by pancreatic β cells, may be used to prevent hypoglycaemia in preoperative patients or in those unfit or unwilling to undergo surgery.
Diazoxide during pregnancy and lactation: drug levels in maternal serum, cord blood, breast milk, and infant serum: a case report
Published in Gynecological Endocrinology, 2022
Jumpei Saito, Hiroyo Kawasaki, Natsuho Adachi, Aiko Sasaki, Naho Yakuwa, Tomo Suzuki, Haruhiko Sago, Akimasa Yamatani, Reiko Horikawa, Atsuko Murashima
Diazoxide inhibits insulin secretion by opening ATP-dependent potassium channels in pancreatic β cells. Medical therapy with diazoxide is effective for hypoglycemia in patients with hyperinsulinemic hypoglycemia [6–8]. However, only one case of a pregnant woman with hyperinsulinemia treated with diazoxide has been previously reported [9]. In addition, data on humans exposed to diazoxide in utero are sparse. When diazoxide is used for the treatment of hypertensive emergencies in pregnancy during the second and third trimesters, it reportedly causes reversible alopecia or hypertrichosis in the newborn [10]. In animal embryos with in vitro or in vivo exposure to diazoxide during early stages of development, variable defects including fetal resorption and heart and skeletal malformations have been reported [11]. With this context, caution should be taken in women with hyperinsulinism, with consideration of discontinuing diazoxide before and during pregnancy. For lactating women, breastfeeding is discouraged due to the lack of information on the use of diazoxide during lactation and the need to further increase carbohydrate intake [12].
Insulin acts as a repressive factor to inhibit the ability of PAR2 to induce islet cell transdifferentiation
Published in Islets, 2018
Seung-Hee Lee, Ergeng Hao, David Scharp, Fred Levine
To determine whether insulin was the factor responsible for repressing the ability of 2fLI to induce islet cell transdifferentiation, we studied isolated human islets in vitro. In those primary human islets, there were very few cells coexpressing insulin and glucagon (Figure 2a, quantified in e). Primary human islets contain a normal complement of β−cells, and so there is a great deal of insulin present. To inhibit insulin secretion and action, we used the drugs diazoxide and S961. Diazoxide is an inhibitor of insulin secretion through effects on the potassium channel expressed in β-cells.18 Once secreted, insulin acts by binding to the insulin receptor, a tyrosine kinase growth factor expressed on the cell surface. S961 is a peptide that acts as an antagonist of the insulin receptor.19,20
Perspectives on the current pharmacotherapeutic strategies for management of functional neuroendocrine tumor syndromes
Published in Expert Opinion on Pharmacotherapy, 2021
Tetsuhide Ito, Robert T Jensen
In patients with insulinomas, many can have their symptoms initially, adequately controlled with frequent, small feedings and if not, then by the addition of diazoxide, which inhibits insulin release by inhibiting ATP-sensitive potassium channels on the insulinoma cells [5,36,67,68]. This is effective in 47–50%, however, its use can be associated with prominent side-effects which can limit its continued use [67–70]. Side-effects include edema due to fluid/electrolyte retention (thus, generally diazoxide is used with a diuretic), as well as hirsutism, thrombocytopenia, and renal failure [36,67–71]. In most patients this treatment is short-term, allowing time to perform tumor localization studies(see paragraph below for more detail). This is the case because >90% of insulinoma patients can be surgically cured [5,35,72].
Related Knowledge Centers
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- Sulfonylurea
- Thiazide
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- Heart Failure
- Hypoglycemia
- Thrombocytopenia
- Pancreatic Neuroendocrine Tumor
- Leucine-Sensitive Hypoglycemia of Infancy
- Generic Drug