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Diabetes Mellitus, Obesity, Lipoprotein Disorders and other Metabolic Diseases
Published in John S. Axford, Chris A. O'Callaghan, 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.
Cardiovascular Drugs during Pregnancy
Published in “Bert” Bertis Britt Little, 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).
Hypertensive Disorders
Published in Vincenzo Berghella, Maternal-Fetal Evidence Based Guidelines, 2022
There are two indications of antihypertensive medications for women with CHTN: (1) acute lowering of severe HTN in the hospital (Table 1.4), or (2) chronic treatment in outpatient setting (Table 1.5). Based on finding of the Cochrane systematic review [30], there is no clear evidence that one antihypertensive is preferable to the others for improving outcome for women with very high blood pressure during pregnancy. Therefore, the choice of antihypertensive should depend on the experience and familiarity of an individual clinician with a particular drug and on what is known about adverse maternal and fetal side effects. Three drugs (high-dose diazoxide [31], ketanserin, and nimodipine) have serious disadvantages and so should probably be avoided for women with very high blood pressure during pregnancy.
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].
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].
Surgical management of pancreatic neuroendocrine tumors: an introduction
Published in Expert Review of Anticancer Therapy, 2019
Elisabeth Hain, Rémy Sindayigaya, Jade Fawaz, Joseph Gharios, Gaspard Bouteloup, Philippe Soyer, Jérôme Bertherat, Frédéric Prat, Benoit Terris, Romain Coriat, Sébastien Gaujoux
Insulinomas are the most frequent functional pNETs with an incidence of 4 cases per million inhabitants per year [33]. Patients with this condition suffer from severe postprandial hypoglycemia, during fasting or exercise, confusion, behavioral changes, and visual troubles. Because of highly variable and nonspecific symptoms, the diagnostic of insulinoma is frequently only done several years after initial symptoms [9,34]. The diagnosis is confirmed with low serum glucose, inappropriately elevated serum insulin and C-peptide in exclusion of other causes of hypoglycemia [17,26]. Fasting test should only be performed under strict medical surveillance. As for gastrinoma, it is important to remember that initial treatment of insulinoma must be in controlling the consequences of hormonal hypersecretion. This is done with appropriate diet (frequent small meals), patient education and when needed diazoxide. In additional to diazoxide, long-acting somatostatin analogs (SSAs) can be used as 30–50% of patients with hyperinsulinism related to insulinoma can respond, but patients have to be monitored carefully because this can sometimes worsen cases [35–41]. In patients with malignant insulinoma, the mTOR inhibitor everolimus is effective in controlling glycemia and is now frequently used [42,43].