eMedicine Specialties > Pediatrics: General Medicine > Endocrinology

Persistent Hyperinsulinemic Hypoglycemia of Infancy: Follow-up

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

Follow-up

Further Inpatient Care

  • Admit patients with persistent hyperinsulinemic hypoglycemia of infancy (PHHI) to a neonatal intensive care unit (NICU) or ICU until blood glucose levels are stabilized. Arrange for family and patient education to begin immediately.

Further Outpatient Care

  • Patients should have regular follow-up visits with a pediatric endocrinologist to review blood glucose levels, diet, growth, and medication side effects.
  • Patients should record blood glucose levels and bring these records to follow-up visits or use a home glucose meter with a memory that can be downloaded.

Inpatient & Outpatient Medications

  • Home therapy must be individualized, usually involving one or more of the following:
    • Oral diazoxide, possibly in conjunction with oral chlorothiazide
    • Oral nifedipine
    • Subcutaneous octreotide
    • Subcutaneous glucagon (for emergency use)

Transfer

  • Newborns with persistent hypoglycemia should be transferred to the NICU for stabilization, monitoring, and further diagnostic evaluation.
  • Other patients should be transferred to a specialized center if appropriate monitoring, therapy, and consultation cannot be provided at the facility to which the patient initially presents.

Complications

  • The most dangerous complication is hypoglycemia with resultant brain damage or death if not treated promptly. Hypoglycemia may occur even with optimal medical and surgical treatment; therefore, glucose monitoring and patient/family education are essential.
  • Early complications of surgery include bleeding and wound infection. Late complications of surgical treatment include pancreatic exocrine insufficiency and glucose intolerance or frank diabetes mellitus.
  • Complications of medical therapy primarily are related to adverse effects of medications (see Medication).

Prognosis

  • Cure
    • If a solitary focal lesion can be identified and excised, the patient usually maintains blood glucose levels within the reference range without the need for medication or continuous feedings.
    • Hypoglycemia often persists even after a 95-98% pancreatectomy. Hypoglycemia may be easier to control after partial pancreatectomy and may resolve months or years later or persist throughout life.
    • In one study of 101 patients, 50% of patients who underwent a 95% or greater pancreatectomy were cured (ie, they did not require medical or dietary treatment to maintain normoglycemia within the follow-up period of the study). The mean time from surgery to cure was 4.7 years. However, in some series, 40-63% of patients managed with medical therapy alone had late remission of hypoglycemia. Later onset of disease is correlated with a higher likelihood of being able to discontinue medical therapy.
  • Future development of diabetes mellitus
    • Patients who undergo partial pancreatectomy are at high risk for developing diabetes mellitus later in life. The risk of diabetes mellitus appears to increase with the extent of pancreatic resection; however, the risk is significant even with conservative surgical procedures.
    • In one series, 14% of children with diffuse lesions developed diabetes mellitus, regardless of the surgical procedure performed. The mean time from surgery to development of diabetes mellitus was 9.6 years. Most series are limited by relatively short follow-up times, so the lifetime incidence of diabetes mellitus is not well understood. Islet cell preservation and autotransplantation remain promising but untested therapies for patients who develop diabetes mellitus.
    • Diabetes mellitus is extremely rare following resection of focal lesions.
    • In a series of 3 patients treated without pancreatic resection, 2 developed impaired glucose tolerance, and one developed diabetes mellitus.11  All 3 patients had mutations of the ABCC8 (also known as SUR1) gene. The significance of this small series is uncertain but suggests that development of impaired glucose tolerance may be part of the underlying disease process and not solely due to surgical reduction in islet cell mass.
    • Patient/family education and long-term follow-up are essential to prevent delays in the diagnosis of disease recurrence, glucose intolerance, or diabetes mellitus.
  • Neurodevelopmental outcome: In some series, a high frequency of mental retardation, developmental delay, and nonhypoglycemic seizures has been observed. These findings are generally attributed to minimal brain damage from early hypoglycemic events, although the existence of these disorders as inherent comorbid conditions with PHHI has not been fully excluded. Other series, usually in conjunction with medication studies, have shown normal developmental progress in patients with PHHI. Some data suggest that patients with early, severe disease treated with early, aggressive surgery have a better neurodevelopmental outcome. No comprehensive long-term studies of neurodevelopmental outcomes in patients with PHHI are available, and the heterogeneity of the disease likely confounds many neurodevelopmental studies.

Patient Education

  • Patients (if old enough) and family members should be taught how to use a home blood glucose monitor.
  • Patients and family members should understand the signs and symptoms of hypoglycemia and how to treat this condition with rapid-acting oral carbohydrates and subcutaneous glucagon.
  • Family members must understand the importance of prompt treatment of hypoglycemia to prevent severe complications or death. Family members should be instructed to call the local emergency medical service (EMS) if they are unable to treat a hypoglycemic episode or if the patient does not respond to treatment promptly. Many areas of the United States still do not have 911 services. Family members should know the local emergency phone number if 911 service is not available in their area.
  • Patients should wear a medical ID bracelet.
  • A nutritionist should provide dietary education and meal-planning assistance.
  • Patients and family members should be reminded to carry medications, a glucose meter, a rapid-acting carbohydrate source, and glucagon when traveling. Families should carry sufficient supplies for several extra days in case of unexpected travel delays.
  • Patients who have undergone surgery, as well as their family members, should be reminded of the risk of future development of diabetes mellitus and the importance of long-term follow-up. Failure to educate families about this potential late complication could result in a delay of diagnosis of diabetes mellitus if it occurs.
  • Genetic counseling with regard to risk of recurrence may be appropriate. Techniques for prenatal diagnosis are currently limited to investigational use but may be available at some medical centers.

Miscellaneous

Medicolegal Pitfalls

  • Failure to recognize and treat hypoglycemia
  • Misdiagnosis of hypoglycemic seizure as epileptic seizure, resulting in inappropriate treatment with anticonvulsants and failure to treat with glucose
  • Failure to diagnose PHHI, with resulting morbidity or mortality
  • Failure to identify associated endocrine abnormalities, such as multiple endocrine neoplasia type I

Special Concerns

  • Little is known about PHHI in pregnancy. One report describes a 36-year-old woman with PHHI treated successfully with octreotide during pregnancy.
    • The use of medications should be reviewed. Diazoxide is known to decrease fetal survival in animals, although this effect has not been documented in humans. Studies of octreotide and glucagon in pregnant animals have not shown harm to the fetus, even at doses far greater than those used in humans. These medications are classified as pregnancy category B. No adequate and well-controlled studies of these agents in pregnant women exist; therefore, these drugs should be used with caution and only if clearly needed. The safety of nifedipine in pregnancy has not been established.
    • Pregnancy frequently causes disturbances of glucose metabolism. Because both hypoglycemia and hyperglycemia pose considerable risks to the fetus, patients should practice diligent glucose monitoring with regular medical follow-up. Therapeutic modalities should be individualized and adjusted as indicated.
    • Early prenatal care and close follow-up are essential. Referral to a maternal-fetal medicine specialist or high-risk pregnancy clinic should be considered.
    • Prenatal diagnosis by measurement of amniotic fluid insulin, C-peptide, and glucose levels has been described, but very limited data are available.
    • Infants of mothers with PHHI should be closely monitored for hypoglycemia by physical examination and blood sampling. If possible, arranging delivery at a facility with a NICU may be prudent to facilitate prompt treatment in the event the infant has persistent hypoglycemia.
 


More on Persistent Hyperinsulinemic Hypoglycemia of Infancy

Overview: Persistent Hyperinsulinemic Hypoglycemia of Infancy
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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