eMedicine Specialties > Pediatrics: General Medicine > Endocrinology

Persistent Hyperinsulinemic Hypoglycemia of Infancy: Treatment & Medication

Author: Robert S Gillespie, MD, MPH, Consulting Staff, Department of Nephrology, Cook Children's Medical Center
Coauthor(s): Stephen Ponder, MD, CDE, Director, Division of Pediatric Endocrinology, Department of Pediatrics, Driscoll Children's Hospital; Professor, Texas A&M College of Medicine
Contributor Information and Disclosures

Updated: Nov 7, 2008

Treatment

Medical Care

  • The only major expert consensus document on persistent hyperinsulinemic hypoglycemia of infancy (PHHI) was developed by The European Network for Research into Hyperinsulinism (ENRHI).7
  • Immediate treatment of hypoglycemia is essential. Patients may require continuous IV glucose infusion. Glucagon may also be administered emergently to maintain adequate blood glucose levels.
  • Diazoxide (Hyperstat [IV], Proglycem [PO]) is an antihypertensive agent that relaxes smooth muscle in the peripheral arterioles.
    • Diazoxide is related to the thiazide class of drugs but has no diuretic action. It promotes opening of the potassium adenosine triphosphate (ATP) channel, which inhibits pancreatic secretion of insulin, stimulates glucose release from the liver, and stimulates catecholamine release. (This effect is opposite that of the sulfonylurea drugs used in diabetes mellitus, which close the ATP channel.)
    • Diazoxide causes sodium and water retention and should be used cautiously in patients with congestive heart failure or poor cardiac reserve. Hypertrichosis, coarsening of the facies, decreased serum immunoglobulin G levels, and hyperosmolar nonketotic comas have been reported with diazoxide, especially with long-term use.
    • Patients should be monitored for hypotension while using diazoxide, especially during intravenous (IV) administration, because blood pressure may drop rapidly. Usually, oral diazoxide is used for the treatment of hypoglycemia.
    • Some authors recommend using chlorothiazide in conjunction with diazoxide for a synergistic effect. Chlorothiazide activates a different potassium channel, and its diuretic action helps counteract the salt and water retention associated with diazoxide therapy.
  • Octreotide (Sandostatin, SMS 201-995) is a long-acting analogue of somatostatin. Octreotide has a wide array of endocrinologic functions, including inhibition of insulin release. Octreotide therapy may avert or postpone the need for surgery. Most patients develop tolerance to octreotide over time, requiring increased doses. Experience with long-term use of octreotide in patients with PHHI is limited. Suppression of growth hormone and decreased linear growth may be important adverse effects of octreotide, and the patient's growth parameters should be monitored carefully during octreotide therapy. Gallbladder sludging and gallstones have been reported as a late complication in patients who are taking octreotide. Octreotide suppresses thyroid-stimulating hormone (TSH), but clinical hypothyroidism is very rare. Mild diarrhea and abdominal bloating are common and, usually, transient adverse effects.
  • Nifedipine is a calcium channel blocker that helps reduce the influx of calcium into beta cells, which is a necessary step for insulin secretion. This effect occurs with doses much lower than those traditionally used for other indications, such as angina pectoris. The adverse effects observed at these low doses have been minimal.
  • Patients should use a home glucose meter to monitor glucose levels. A physician should review the results periodically to assist in adjusting medications. More frequent glucose monitoring may be necessary during illness, when changing medications, or after dose adjustments. During illness, when oral intake is lower, patients may be at higher risk for hypoglycemia. Patients with persistent vomiting or diarrhea may require hospital admission for IV glucose administration until they are able to tolerate oral intake. Continuous feeding by a nasogastric or gastrostomy tube may be helpful in some patients to maintain adequate blood glucose levels. Continuous feeding is particularly useful during sleep.

Surgical Care

  • Despite many years of experience and extensive reports in the literature, surgical therapy remains frustrating. Rates of initial failure to control hypoglycemia are high, followed by, paradoxically, high rates of subsequent development of diabetes mellitus. Surgical treatment is indicated if medical therapy does not maintain normoglycemia, if a discrete lesion can be identified, or if the patient or patient's family is unable or unwilling to comply with medical therapy. In one study, 50% of patients with congenital hyperinsulinism required pancreatectomy to obtain adequate glucose control. Although most centers routinely perform extensive pancreatectomy, one center in Israel has reported success with a consistently nonsurgical approach.8
  • The distinction between focal and diffuse lesions is critical in planning surgical intervention. Every effort should be made, both before and during surgery, to identify or rule out a focal lesion. Because of the difficulty in detecting many small lesions, multiple techniques should be employed. Finding a focal lesion can potentially prevent unnecessary pancreatic resection, which can help prevent future development of diabetes mellitus, with its well-known and devastating morbidity and mortality. If a focal lesion can be identified and excised, the prognosis is excellent. Most patients maintain reference-range serum glucose levels without the need for medication or dietary intervention. However, most focal lesions are too small to identify by CT scanning, MRI, ultrasonography, or even intraoperative palpation. Pancreatic venous sampling or intra-arterial calcium stimulation may help identify a focal lesion (see Procedures).
  • If a focal lesion is found before or during surgery, the lesion may be excised locally without further pancreatic resection. However, multiple focal lesions may be present. Intraoperative glucose monitoring during a trial of glucose-free IV fluids may guide the surgeon in determining the need to search for additional lesions. The patient's ability to maintain normoglycemia without IV glucose suggests that no hypersecretory foci remain.
    • The recommended surgical approach involves taking multiple biopsy samples from different parts of the pancreas (head, body, isthmus, and tail). These samples are sent for frozen-section evaluation to help determine intraoperatively whether the pathology is diffuse or focal.
    • The finding of abnormal beta-cell nuclei in all specimens suggests a diffuse lesion, for which extensive pancreatectomy is indicated. In contrast, if only one specimen contains abnormal beta-cell nuclei, a focal lesion may be present. This approach is recommended.
    • Nuclear abnormalities include greatly increased size or abnormal (crescent or ovoid) shapes of beta cells. Since these histologic findings also occur in some persons without hyperinsulinemic hypoglycemia, clinical confirmation of hyperinsulinism and hypoglycemia before surgery is essential.
  • Some investigators have reported success in distinguishing focal pathology from diffuse pathology using mean nuclear radius and nuclear crowding indices of beta cells in pancreatic specimens. Studies suggest that this procedure, which is currently investigational, could be performed intraoperatively to determine the extent of pancreatic resection required.
  • If no focal lesion is found, the surgeon performs a partial pancreatectomy. Extensive experience with varying degrees of pancreatic resection in infants and children has been reported. Although some controversy remains, the 95% or subtotal pancreatectomy is the most widely accepted procedure for infants and children. In this procedure, the tail, body, uncinate process, and most of the head of the pancreas are removed, leaving a portion of pancreas to the right of the common bile duct and a thin rim along the second portion of the duodenum and the pancreaticoduodenal arteries. Resection of less than 95% of the pancreas is associated with a higher rate of treatment failure and need for reoperation.
  • The more aggressive 98% pancreatectomy removes all but a few small islands of pancreatic tissue along the pancreaticoduodenal arteries. This procedure is associated with a higher rate of diabetes mellitus postoperatively; however, patients with lesser degrees of pancreatic resection also remain at substantial risk for future development of diabetes mellitus. Some authors advocate a more conservative initial procedure, with reoperation later if hypoglycemia persists. Future advances in medical therapy may provide better glycemic control with fewer side effects, permitting less radical pancreatic resection.
  • Regardless of the procedure used, hypoglycemia may recur, and the patient may require continued medical therapy. Reoperation with additional pancreatic resection may be indicated if optimal medical management cannot provide adequate glycemic control. In refractory cases, which are rare, total resection of the pancreas has been performed.
  • In infants, surgery is usually performed within the first 2 months of life. Laparoscopic procedures can be done in all age groups.
  • Published material on the surgical management of adult PHHI is limited. The extent of pancreatic resection necessary for optimal outcomes in adults is not known. Pancreatic resections ranging from 30-95% have been reported with widely variable results. Until more data are available, some authors have suggested a more conservative resection of the pancreas as the initial procedure in adults, with possible reoperation if adequate glycemic control is not achieved.
  • Some authors advocate cryopreservation of islet cells from the resected portion of the pancreas for possible future autotransplantation if the patient develops diabetes mellitus. In theory, this process would cure diabetes without the need for immunosuppression or risk of rejection, as is observed in pancreatic or islet cell allotransplants. Since 1977, several centers have reported success using this approach in adults undergoing total pancreatectomy for severe pancreatitis or pancreatic tumors. Success in eliminating insulin requirements varies from 50-100%; in small series, this approach has been reported to prevent the development of diabetes for at least 13 years.
    • No cases of islet cell autotransplantation in patients with PHHI have been published to date. However, some patients (or their families, in the case of infants) have elected to have islet cell cryopreservation performed, in anticipation of future developments in this area.
    • Ethical, technical, and safety considerations related to this therapy have not been fully developed, but the concept appears promising, especially given the rapid progress being made in islet cell allotransplantation. Patients or their families should consider islet cell preservation for possible future autotransplantation, as the knowledge base continues to develop.

Consultations

  • Pediatric endocrinologist
  • Pediatric surgeon
  • Dietician (ideally experienced in the care of diabetes because dietary management of PHHI is related to that of diabetes)
  • Medical geneticist

Diet

  • A diet of 3 meals and 3 snacks daily helps maintain adequate serum glucose levels. Patients should avoid fasting (eg, skipping meals and scheduled snacks) because hypoglycemia may develop quickly.
  • A high-protein, high-carbohydrate diet is preferred. The carbohydrates provide the most long-acting source of glucose to counter the continuous release of insulin, and concurrent protein helps prolong this effect.
  • Patients should always have access to a rapid-acting carbohydrate, such as glucose tablets, glucose gel, fruit juice, hard candy, or sugar cubes. Uncooked cornstarch may be used to provide additional carbohydrates, and it may be helpful in preventing fasting hypoglycemia during sleep if administered at bedtime.

Activity

Regular activity should be encouraged, with appropriate precautions.

  • Patients or parents should always carry a supply of rapid-acting carbohydrate (eg, glucose tablets or gel, sugar cubes, fruit juice, hard candy) to use in case of hypoglycemia.
  • Patients should increase their carbohydrate intake when increased exertion is anticipated, such as before strenuous exercise.

Medication

Diazoxide, octreotide,9 and nifedipine are the primary medications used in long-term treatment of persistent hyperinsulinemic hypoglycemia of infancy (PHHI). Some authors also recommend using chlorothiazide in conjunction with diazoxide for a synergistic effect. All these drugs are used widely for other indications, and diazoxide and octreotide are associated with increased serum glucose levels as a well-known adverse effect. Their hyperglycemic action is beneficial in the treatment of PHHI, but their other therapeutic actions may become a burden in patients with PHHI, who lack the conditions the drugs were originally intended to treat. For example, diazoxide, primarily used as an antihypertensive, may cause hypotension in the normotensive child with PHHI. In addition, most agents have significant adverse effects, especially with long-term use. Nifedipine is a relatively new addition to the therapeutic armamentarium, and it appears to have considerably fewer adverse effects than the otheragents.10

Different doses for each drug have been used in different centers. The exact medication regimen, including doses and selection of drugs, must be highly individualized on the basis of therapeutic response, adverse-effect tolerance, and individual factors (eg, patient acceptance of subcutaneous injections). Many patients require years of drug therapy, and regular reassessment and dose adjustments are required. Because of the potential for significant adverse effects with long-term administration of these agents, patient adherence to the medication regimen may be suboptimal. The best way to ensure good adherence is by having open discussions with patients about the risks and benefits of the drugs, by scheduling regular follow-up appointments, and by tailoring drug regimens for each patient.

Insulin secretion inhibiting agents

Insulin secretion may be altered by various mechanisms. Diazoxide inhibits pancreatic secretion of insulin, stimulates glucose release from the liver, and stimulates catecholamine release, which elevates blood glucose levels. Octreotide is a peptide with pharmacologic action similar to that of somatostatin, which inhibits insulin secretion. In persistent hyperinsulinemic hypoglycemia of infancy (PHHI), functional abnormalities are believed to exist in the ATP-sensitive potassium channels (composed of the sulfonylurea receptor [SUR gene abnormality] and the potassium channel pore protein [Kir6.2 gene abnormality]).

These channels initiate depolarization of the beta-cell membrane and opening of calcium channels. The resultant increase in intracellular calcium triggers insulin secretion. Calcium channel blockers block the action of these calcium channels, decreasing insulin secretion. Nifedipine is the only calcium channel blocker for which clinical trials have been performed in patients with PHHI. The use of other calcium channel blockers given in liquid formulations or by alternative drug-delivery systems remains a promising area for future research. Thiazide diuretics also inhibit insulin secretion. In PHHI, chlorothiazide should be used in conjunction with diazoxide. It exerts a synergistic effect on inhibiting insulin secretion by activating a different potassium channel.


Diazoxide (Hyperstat [IV], Proglycem [PO])

An antihypertensive agent that relaxes smooth muscle in the peripheral arterioles. Related to the thiazide class of drugs but has no diuretic action. Inhibits pancreatic secretion of insulin, stimulates glucose release from the liver, and stimulates catecholamine release.

Adult

1 mg/kg PO q8h initially; titrate to effect

Pediatric

Neonates and infants: 8-10 mg/kg/d PO divided q8h initially; titrate to effect
Children: Administer as in adults

Highly bound to serum protein and displaces other protein-bound substances such as bilirubin or coumarin, increasing their serum levels; may cause excessive hypotension, especially when administered with other antihypertensive drugs; may decrease serum hydantoins, possibly resulting in decreased anticonvulsant effects; thiazide diuretics may potentiate hyperuricemic and antihypertensive effects of diazoxide

Documented hypersensitivity; treatment of compensatory hypertension, such as that associated with aortic coarctation or arteriovenous shunt

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in patients hypersensitive to other thiazides or sulfonamide-derived drugs because cross-reactivity may occur; injectable form should be administered by peripheral IV only; SC injection may cause inflammation and pain; blood glucose levels should be monitored closely during use because severe hyperglycemia may occur; half-life may be prolonged in patients with renal impairment; causes sodium and water retention (caution in CHF or poor cardiac reserve); monitor for hypotension, especially during IV administration, because blood pressure may be reduced rapidly


Chlorothiazide (Diuril)

When combined with diazoxide, elicits synergistic effect on inhibiting insulin secretion by activating a different potassium channel. Also counteracts the salt and water retention induced by diazoxide.

Adult

Not well defined for PHHI; the usual diuretic dose is 250-1000 mg PO/IV qd/qid; the dose for PHHI may be much smaller.

Pediatric

7-10 mg/kg/d PO/IV divided bid

May decrease effectiveness of anticoagulants, antigout agents, and sulfonylureas; effectiveness may be decreased by bile acid sequestrants, methenamine, and NSAIDs; may increase toxicity of allopurinol, anesthetics, antineoplastics, calcium salts, diazoxide, digitalis, lithium, loop diuretics, methyldopa, muscle relaxants, and vitamin D; potentiates diuresis when coadministered with loop diuretics

Documented hypersensitivity; anuria; hypokalemia

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

May cause hypercalcemia, hypomagnesemia, and increased plasma cholesterol levels; avoid IM or SC administration


Octreotide (Sandostatin)

A peptide with pharmacologic action similar to somatostatin. More potent inhibitor of insulin, glucagon, and growth hormone secretion than somatostatin. Elicits diverse endocrine effects, including suppression of LH response to GnRH, decreased splanchnic blood flow, inhibition of release of serotonin, gastrin, vasoactive intestinal peptide (VIP), secretin, motilin, pancreatic polypeptide, and thyroid-stimulating hormone (TSH). Decreases gallbladder contractility and bile secretion. Used in PHHI primarily for its ability to inhibit insulin secretion.

Adult

50 mcg SC tid initially; may increase dose to 500 mcg SC tid; doses of 300-600 mcg/d or higher seldom result in additional biochemical benefit

Pediatric

1-10 mcg/kg/d SC divided q6-8h

May decrease absorption of PO administered drugs; may decrease blood levels of cyclosporine; patients may require dose adjustments of insulin, PO hypoglycemic agents, beta blockers, calcium channel blockers, or agents to control fluid and electrolyte balances while on this drug

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Associated with gallbladder sludging or gallstones, pancreatitis, hypothyroidism, and altered fat absorption; bradycardia, conduction abnormalities, arrhythmias, and ECG changes have been reported in patients taking octreotide for acromegaly; patients may experience hypoglycemia or hyperglycemia due to the alteration of multiple interrelated glucose regulatory pathways; diarrhea, nausea, and abdominal discomfort are common adverse effects


Nifedipine (Adalat, Procardia)

Use of this drug in nesidioblastosis is relatively new, but initial reports suggest that it is effective and extremely well tolerated. Most information on adverse effects of, and interactions with, nifedipine has been obtained from studies of adults using the drug for angina pectoris at proportionately higher doses than those used in children for PHHI. A liquid formulation is not available commercially. The drug is supplied as a 10-mg liquid-in-gelcap. The contents may be aspirated with a syringe and needle to measure smaller doses, but it is very difficult to do so accurately, due to the extremely small volume of fluid in the gelcap. ER formulations have also been employed in PHHI.

Adult

10-30 mg PO tid/qid

Pediatric

0.25-2.5 mg/kg/d PO divided q6-8h

Caution with coadministration of any agent that can lower BP, including beta blockers and opioids; H2 blockers (eg, cimetidine) may increase toxicity; may increase serum levels of digoxin or quinidine; nifedipine levels may be affected by CYP3A4 inhibitors (eg, erythromycin, itraconazole) or inducers (eg, carbamazepine, rifampin)

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

No adverse effects have been reported with use for PHHI in children; however, the number of reported cases is small and no data on long-term use are available; overdosage may result in hypotension; the most common adverse effects reported in adults during clinical trials at proportionately higher doses for angina pectoris were peripheral edema, dizziness, light-headedness, nausea, headache, flushing, and weakness; allergic hepatitis has occurred rarely; risk of measurement errors when removing drug from capsule for doses <10 mg; drug degrades upon removal from capsule and should not be withdrawn until ready for administration

Dextrose and glucose stimulators

Prompt-acting glycogenolysis is achieved with glucagon. Emergent blood glucose level elevation requires IV dextrose. Corticosteroids are rarely used for gluconeogenesis long term because of their risk of toxicity.


Dextrose (D-glucose)

Used to promptly elevate serum glucose. Monosaccharide absorbed from the intestine and then distributed, stored, and used by the tissues. Parenterally injected dextrose is used in patients unable to sustain adequate PO intake. Direct PO absorption results in a rapid increase in blood glucose concentrations. Dextrose is effective in small doses, and no evidence indicates that it may cause toxicity. Concentrated dextrose infusions provide higher amounts of glucose and increased caloric intake in a small volume of fluid.

Adult

10-25 g IV bolus; may follow with continuous IV infusion according to patient requirements

Pediatric

250-500 mg/kg IV (5-10 mL of 25% dextrose); may follow with continuous IV infusion of 10% dextrose according to patient requirements

Caution with coadministration with drugs that may increase blood glucose

Anuria; diabetic coma if blood glucose levels are extremely high; severely dehydrated patients (avoid dextrose); administration of a concentrated solution if intraspinal or intracranial hemorrhage is present; dehydration with delirium tremens, hepatic coma, or glucose-galactose malabsorption syndrome (avoid dextrose)

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

May cause nausea, which may also occur with hypoglycemia; IV dextrose solutions may result in dilution of serum electrolyte concentrations or overhydration when fluid overload occurs; caution in patients with congested states or pulmonary edema; hypertonic dextrose administered peripherally may cause phlebitis or thrombosis (prolonged administration of >10% dextrose solution requires a central venous catheter); caution in subclinical diabetes mellitus or carbohydrate intolerance; risk of inducing significant hyperglycemia or hyperosmolar syndrome exists if solution is administered rapidly, especially in patients with chronic uremia or carbohydrate intolerance; concentrated solutions should not be administered SC or IM; rates of dextrose infusion >0.5 g/kg/h may produce glycosuria; at infusion rates of 0.8 g/kg/h, the incidence of glycosuria is 5%; monitor fluid balance, electrolyte concentrations, and acid-base balance closely; dextrose administration may produce vitamin B complex deficiency


Glucagon

Pancreatic alpha cells of the islets of Langerhans produce glucagon, a polypeptide hormone. Exerts opposite effects of insulin on blood glucose. Glucagon elevates blood glucose levels by inhibiting glycogen synthesis and enhancing formation of glucose from noncarbohydrate sources such as proteins and fats (gluconeogenesis). Increases hydrolysis of glycogen to glucose (glycogenolysis) in liver in addition to accelerating hepatic glycogenolysis and lipolysis in adipose tissue. Glucagon also increases force of contraction in heart and has a relaxant effect on GI tract.

Adult

1 mg (1 U) IV/IM/SC

Pediatric

<20 kilograms: 0.5 mg (0.5 U) IV/IM/SC or 20-30 mcg/kg; not to exceed 1 mg/dose
>20 kilograms: Administer as in adults

Effects of anticoagulants may be enhanced by glucagon (although onset may be delayed); monitor prothrombin activity and monitor for signs of bleeding in patients receiving anticoagulants; adjust dose accordingly

Documented hypersensitivity; pheochromocytoma

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Monitor blood glucose levels in hypoglycemic patients until they are asymptomatic; glucagon is effective in treating hypoglycemia only if sufficient liver glycogen is present; because liver glycogen availability is necessary to treat hypoglycemic patients, glucagon has virtually no effect on patients in states of starvation, adrenal insufficiency, or chronic hypoglycemia

More on Persistent Hyperinsulinemic Hypoglycemia of Infancy

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Differential Diagnoses & Workup: Persistent Hyperinsulinemic Hypoglycemia of Infancy
Treatment & Medication: Persistent Hyperinsulinemic Hypoglycemia of Infancy
Follow-up: Persistent Hyperinsulinemic Hypoglycemia of Infancy
Multimedia: Persistent Hyperinsulinemic Hypoglycemia of Infancy
References
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Further Reading

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Keywords

persistent hyperinsulinemic hypoglycemia of infancy, PHHI, nesidioblastosis, congenital hyperinsulinism, CHI, islet cell dysmaturation syndrome, islet cell adenomatosis, nesidioblastoma, familial hyperinsulinism with pancreatic nesidioblastosis, focal adenomatous hyperplasia, diffuse discrete beta cell abnormality, beta cell, beta-cell, B cell, B-cell, focal adenomatous hyperplasia, seizures, developmental delay, focal neurologic deficits, hepatomegaly, glycogen-storage disorder, galactosemia, fructosemia

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Contributor Information and Disclosures

Author

Robert S Gillespie, MD, MPH, Consulting Staff, Department of Nephrology, Cook Children's Medical Center
Robert S Gillespie, MD, MPH is a member of the following medical societies: American Society of Nephrology, American Society of Pediatric Nephrology, and Texas Medical Association
Disclosure: Nothing to disclose.

Coauthor(s)

Stephen Ponder, MD, CDE, Director, Division of Pediatric Endocrinology, Department of Pediatrics, Driscoll Children's Hospital; Professor, Texas A&M College of Medicine
Stephen Ponder, MD, CDE is a member of the following medical societies: American Academy of Pediatrics, American Diabetes Association, Endocrine Society, Lawson-Wilkins Pediatric Endocrine Society, and Southern Society for Pediatric Research
Disclosure: Nothing to disclose.

Medical Editor

Thomas A Wilson, MD, Professor of Clinical Pediatrics, Department of Pediatrics; Director of Pediatric Endocrinology, Division of Pediatric Endocrinology, Department of Pediatrics, State University of New York at Stony Brook
Thomas A Wilson, MD is a member of the following medical societies: Endocrine Society, Lawson-Wilkins Pediatric Endocrine Society, and Phi Beta Kappa
Disclosure: Nothing to disclose.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from broker recommendation; Avanir Pharma Stock Investment from broker recommendation

Managing Editor

George P Chrousos, MD, FAAP, MACP, MACE, FRCP(London), Professor and Chair, First Department of Pediatrics, Athens University Medical School, Aghia Sophia Children's Hospital, Greece
George P Chrousos, MD, FAAP, MACP, MACE, FRCP(London) is a member of the following medical societies: American Academy of Pediatrics, American College of Endocrinology, American College of Physicians, American Pediatric Society, American Society for Clinical Investigation, Association of American Physicians, Endocrine Society, Lawson-Wilkins Pediatric Endocrine Society, and Society for Pediatric Research
Disclosure: Nothing to disclose.

CME Editor

Merrily P M Poth, MD, Professor, Department of Pediatrics and Neuroscience, Uniformed Services University of the Health Sciences
Merrily P M Poth, MD is a member of the following medical societies: American Academy of Pediatrics, Endocrine Society, and Lawson-Wilkins Pediatric Endocrine Society
Disclosure: Nothing to disclose.

Chief Editor

Stephen Kemp, MD, PhD, Professor, Department of Pediatrics, Section of Pediatric Endocrinology, University of Arkansas and Arkansas Children's Hospital
Stephen Kemp, MD, PhD is a member of the following medical societies: American Academy of Pediatrics, American Association of Clinical Endocrinologists, American Pediatric Society, Endocrine Society, Phi Beta Kappa, Southern Medical Association, and Southern Society for Pediatric Research
Disclosure: Genentech, Inc. Honoraria Speaking and teaching; Pfiser, Inc. Honoraria Consulting

 
 
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