Congenital Hyperinsulinism

Congenital hyperinsulinism is a disease in which a baby or child makes too much insulin from the pancreas, even when the blood sugar is already low. Insulin is a hormone that normally helps move sugar (glucose) from the blood into the body’s cells for energy. In this condition, insulin release is “inappropriate”, so blood sugar keeps dropping to dangerous levels (hypoglycemia). Medscape+1

Congenital hyperinsulinism (CHI) is a rare condition where the pancreas releases too much insulin, causing repeated low blood sugar (hypoglycemia) in babies and children. The main goals of treatment are to keep blood glucose in a safe range every day, protect the child’s brain, and support normal growth and development. First-line care combines non-pharmacological strategies (feeding, monitoring, education) with medicines such as diazoxide, and surgery is used only when medical therapy is not enough.e-apem.org+1

This problem usually appears in newborn babies or young infants and is one of the most common causes of persistent and severe low blood sugar in this age group. If the low blood sugar is not found and treated quickly, it can injure the brain, because the brain depends on glucose as its main fuel. National Organization for Rare Disorders+1

Congenital hyperinsulinism is most often caused by changes (mutations) in genes that control how insulin is released from the beta cells of the pancreas. These gene changes disturb the normal “on–off switch” of insulin secretion, so insulin keeps being released even when blood sugar is low. MedlinePlus+1

Other names

Congenital hyperinsulinism has been described in the medical literature with many different names. Older names include “idiopathic hypoglycemia of infancy”, “nesidioblastosis”, and “islet cell adenomatosis”. In later years, doctors also used terms like “familial hyperinsulinism”, “hyperinsulinemic hypoglycemia of infancy”, and “persistent hyperinsulinemic hypoglycemia of infancy (PHHI)”. Wikipedia+1

Today, the most common names are “congenital hyperinsulinism”, often shortened to “HI” or “CHI”. Some authors still use “persistent hyperinsulinemic hypoglycemia of infancy” or simply “hyperinsulinism” when they talk about the same condition in babies and young children. PMC+1

Types

Doctors group congenital hyperinsulinism in several ways. These types help guide tests and treatment. PMC+1

1. Diffuse congenital hyperinsulinism – In this type, almost all of the beta cells in the whole pancreas are abnormal and release too much insulin. The disease affects the entire organ, which can make it harder to treat with limited surgery. PMC+1

2. Focal congenital hyperinsulinism – In this type, only one small area (focus) of the pancreas contains abnormal beta cells that over-secrete insulin. If this focus can be located, a limited surgical removal of that part of the pancreas can cure the child. PMC+1

3. Atypical or mosaic forms – Some children have mixed patterns, where parts of the pancreas look normal, some look diffuse, and some look like focal disease. These atypical forms may be related to complex genetic or developmental changes in the pancreas. PMC+1

4. Transient neonatal hyperinsulinism – In some newborns, especially those under stress around birth, the high insulin state is temporary. It may be due to problems such as birth asphyxia, maternal diabetes, or growth restriction. The high insulin gradually improves over days or weeks. indianpediatrics.net+1

5. Persistent genetic congenital hyperinsulinism – In many children, hyperinsulinism stays long term and is linked to inherited gene mutations in the insulin secretion pathway, such as ABCC8 or KCNJ11. These children often need long-term medicine or surgery. MDPI+1

6. Diazoxide-responsive congenital hyperinsulinism – Some forms respond well to the drug diazoxide, which opens potassium channels in beta cells and reduces insulin release. These children can often be managed with medicine and careful feeding plans. Medscape+1

7. Diazoxide-unresponsive congenital hyperinsulinism – Other forms, often linked to severe KATP-channel gene mutations (ABCC8, KCNJ11), do not respond to diazoxide. These children often need stronger medicines, special feeding, or surgery such as partial pancreatectomy. Frontiers+1

Causes

In congenital hyperinsulinism, “causes” most often mean genetic and developmental reasons why the beta cells release too much insulin. Many of these causes are rare, but they are important for diagnosis and family counseling. MedlinePlus+1

1. ABCC8 gene mutations – ABCC8 encodes the SUR1 subunit of the ATP-sensitive potassium (KATP) channel in beta cells. Recessive or dominant inactivating mutations keep the channel closed, so insulin release is “on” all the time, even when glucose is low. Journal of Molecular Endocrinology+1

2. KCNJ11 gene mutations – KCNJ11 encodes the Kir6.2 subunit of the same KATP channel. Mutations here have a similar effect to ABCC8 changes and are a major cause of severe, often diazoxide-unresponsive congenital hyperinsulinism. Journal of Molecular Endocrinology+1

3. GLUD1 gene mutations (GDH-HI) – GLUD1 encodes glutamate dehydrogenase. Gain-of-function mutations cause hyperinsulinism/hyperammonemia syndrome, where insulin is released in response to protein (especially leucine) and ammonia levels are high. Journal of Molecular Endocrinology+1

4. GCK gene mutations – GCK encodes glucokinase, a “glucose sensor” in beta cells. Activating mutations make beta cells think that blood glucose is higher than it really is, so they release insulin at much lower glucose levels than normal. Journal of Molecular Endocrinology+1

5. HADH gene mutations – HADH encodes an enzyme involved in fatty acid oxidation. Mutations can disturb the sensing of certain amino acids and fatty acids, which leads to inappropriate insulin release, especially after protein-rich meals. Journal of Molecular Endocrinology+1

6. SLC16A1 gene overexpression (exercise-induced HI) – Abnormal expression of the SLC16A1 gene in beta cells leads to uptake of lactate and pyruvate during exercise, which overstimulates insulin secretion and causes hypoglycemia with activity. Journal of Molecular Endocrinology+1

7. UCP2 gene mutations – UCP2 is involved in mitochondrial function and energy balance. Certain mutations reduce its activity, increase ATP production in beta cells, and drive insulin secretion even when glucose is not high. Journal of Molecular Endocrinology

8. HK1, PMM2, PGM1 and other rare gene defects – Several less common genes (such as HK1, PMM2, PGM1, KCNQ1, CACNA1D, HNF1A, HNF4A, FOXA2, EIF2S3) have been linked to congenital hyperinsulinism. They affect different steps in glucose metabolism, ion channels, or beta-cell development. Frontiers+1

9. Paternal mutation plus somatic loss of maternal allele (focal HI mechanism) – In focal disease, a paternally inherited ABCC8 or KCNJ11 mutation is combined with loss of the maternal chromosome region in a patch of beta cells. This creates a localized area that over-secretes insulin. Congenital Hyperinsulinism International+1

10. Beckwith–Wiedemann syndrome – This overgrowth syndrome involves changes in the 11p15 imprinting region, which also contains genes important for beta-cell growth and regulation. Children may be large at birth, have macroglossia and abdominal wall defects, and can develop hyperinsulinism. piernetwork.org+1

11. Kabuki syndrome and other syndromic forms – Some children with complex genetic syndromes, including Kabuki syndrome and Turner syndrome, may develop congenital hyperinsulinism as one feature, likely due to abnormal beta-cell development or signaling. PMC+1

12. Perinatal stress-induced hyperinsulinism – Babies with birth asphyxia, severe illness, or intrauterine growth restriction can develop transient hyperinsulinism. Stress hormones and placental changes may prime beta cells to release too much insulin after birth. indianpediatrics.net+1

13. Maternal diabetes during pregnancy – High blood sugar in the mother causes high blood sugar and high insulin production in the fetus. After birth, when the sugar supply from the placenta stops, the baby’s insulin can stay high for some time, causing low blood sugar. Congenital Hyperinsulinism International+1

14. Infant of a diabetic mother with islet cell hyperplasia – In some infants of diabetic mothers, the beta cells become enlarged and increased in number (hyperplasia). This structural change can maintain high insulin production beyond the first days of life. J Neonatal Surg+1

15. Postoperative or structural pancreatic abnormalities – Rarely, abnormal pancreatic development or previous surgery can leave areas of islet cell overgrowth that cause local hyperinsulinism and recurrent hypoglycemia in children. ScienceDirect+1

16. Inborn errors of metabolism linked to hyperinsulinism – Some metabolic disorders, such as certain glycogen storage diseases or fatty acid oxidation defects, can be associated with episodes of hyperinsulinemic hypoglycemia due to altered fuel sensing by beta cells. ScienceDirect+1

17. Chromosomal abnormalities affecting beta-cell regulation – Larger deletions or duplications of chromosome areas that include beta-cell genes or imprinting regions can disturb insulin regulation and present as congenital hyperinsulinism. MedlinePlus+1

18. Unknown genetic causes – In a significant number of children, no mutation is found despite modern testing. These cases still behave clinically like congenital hyperinsulinism, so doctors suspect undiscovered genes or complex regulatory defects. ScienceDirect+1

19. Familial, inherited forms – Some families have several members with congenital hyperinsulinism, showing autosomal recessive or dominant inheritance. In such families, the risk for future children can be high if both parents carry a pathogenic variant. Wikipedia+1

20. Sporadic, non-familial forms – In many children there is no family history. The cause is often a new (de novo) mutation or a localized event in the pancreas, such as the focal lesions with loss of maternal allele, leading to hyperinsulinism only in that child. e-apem.org+1

Symptoms

The symptoms of congenital hyperinsulinism mainly come from low blood sugar in the brain and other organs. The signs can be mild and vague at first, so careful observation of newborns at risk is important. National Organization for Rare Disorders+1

1. Jitteriness or tremors – A baby may look shaky, with fine trembling of the hands, feet, or jaw. This happens because the body releases stress hormones like adrenaline when blood sugar is low. indianpediatrics.net+1

2. Poor feeding or difficulty sucking – The infant may not latch well to the breast or bottle, may tire quickly, or may refuse feeds. Low glucose weakens muscles and reduces alertness, so feeding becomes hard. National Organization for Rare Disorders+1

3. Lethargy or excessive sleepiness – Babies may be unusually quiet, hard to wake, or sleep much more than normal. The brain is very sensitive to low glucose and responds with reduced activity. PMC+1

4. Irritability or high-pitched crying – Some babies are very fussy or cry in a strange, high-pitched way. The discomfort of hypoglycemia can cause this, and it may improve quickly after glucose is given. National Organization for Rare Disorders+1

5. Episodes of cyanosis or bluish skin – During severe hypoglycemia, a baby may become pale or bluish, especially around the lips and face. This can be due to poor breathing or poor blood flow during a hypoglycemic spell. J Neonatal Surg+1

6. Apnea or pauses in breathing – Some infants have periods when they stop breathing for a short time. Hypoglycemia can disturb the brain centers that control breathing, leading to these dangerous episodes. J Neonatal Surg+1

7. Seizures (fits) – Recurrent or prolonged seizures are a classic serious sign of congenital hyperinsulinism. They often appear when blood sugar is very low and may leave the baby unresponsive afterward. PMC+1

8. Hypotonia (floppy muscles) – Many babies feel “floppy” when held because their muscle tone is low. The low energy supply from glucose to muscles and nerves reduces strength and tone. National Organization for Rare Disorders+1

9. Sweating and fast heart rate – Older infants and children may show sweating, palpitations, or a racing heart during attacks. These adrenergic signs occur when the body tries to correct low glucose by releasing adrenaline. Congenital Hyperinsulinism International+1

10. Poor weight gain or feeding difficulties over time – Because of frequent episodes and the need for constant feeds, babies may have trouble gaining weight normally, or parents may report that feeds must be very frequent to prevent symptoms. National Organization for Rare Disorders+1

11. Abnormal movements or staring spells – Short episodes of staring, lip smacking, or unusual movements can be subtle seizures or brief brain dysfunction caused by low glucose episodes. ResearchGate+1

12. Developmental delay – If hypoglycemia is severe or long-lasting, children may later show delays in sitting, walking, talking, or learning. This comes from early brain injury due to repeated low blood sugar. piernetwork.org+1

13. Behavior or attention problems in older children – Some children who were affected in infancy may later have attention, memory, or behavioral difficulties linked to past hypoglycemic brain injury. piernetwork.org+1

14. Large birth weight (macrosomia) – Many babies with congenital hyperinsulinism are larger than average at birth because insulin also acts as a growth factor before birth, making the baby grow more. National Organization for Rare Disorders+1

15. Features of associated syndromes – In syndromic forms, children may have macroglossia, body asymmetry, facial differences, or other congenital anomalies in addition to the hypoglycemia symptoms, pointing toward a wider genetic syndrome. piernetwork.org+1

Diagnostic tests

Diagnosis of congenital hyperinsulinism needs careful clinical observation plus well-planned tests. Doctors usually take a “critical sample” of blood during a hypoglycemic episode and also use imaging and genetic tests. The exact tests are chosen by specialists in pediatric endocrinology. Medscape+1

Physical exam

1. Full newborn and infant physical exam – The doctor checks vital signs, breathing, skin color, level of alertness, and muscle tone. The aim is to spot signs of hypoglycemia, illness, or birth injury, and to see how urgent the situation is. indianpediatrics.net+1

2. Neurological examination – The clinician looks at reflexes, muscle tone, eye movements, and responses to touch or sound. This helps detect seizures, floppy muscles, or delayed responses that suggest the brain is being affected by low glucose. PMC+1

3. Growth and body proportion assessment – Measuring weight, length, and head size shows whether the baby is unusually large (macrosomic) or small for age, which can give clues to conditions like maternal diabetes or Beckwith–Wiedemann syndrome. National Organization for Rare Disorders+1

4. Examination for dysmorphic or syndromic features – The doctor looks for macroglossia, abdominal wall defects, facial differences, or limb asymmetry. These signs may suggest an imprinting or overgrowth syndrome that often co-exists with hyperinsulinism. piernetwork.org+1

Manual or bedside tests

5. Bedside blood glucose monitoring (glucometer) – A quick drop of capillary blood from the heel or finger is used to check blood sugar. This fast test shows whether hypoglycemia is present and helps guide immediate treatment, though lab confirmation is still needed. indianpediatrics.net+1

6. Supervised fasting test – In a controlled hospital setting, feeds may be paused while glucose is checked repeatedly. In congenital hyperinsulinism, blood sugar falls too quickly, and insulin stays inappropriately high, which helps confirm the diagnosis. Medscape+1

7. Glucagon stimulation test – When blood sugar is low, doctors can inject glucagon, a hormone that releases stored sugar from the liver. In hyperinsulinism, there is usually a large rise in blood sugar after glucagon, showing that insulin was blocking glucose release. Medscape+1

8. Diazoxide response trial – The child may receive diazoxide for several days while glucose levels are monitored. If blood sugar stabilizes, the form may be “diazoxide-responsive”; if not, more severe genetic forms or a focal lesion are suspected. Medscape+1

Lab and pathological tests

9. Critical blood sample during hypoglycemia – When glucose is below a certain threshold (often <50–60 mg/dL), blood is drawn for insulin, C-peptide, proinsulin, and other markers. In congenital hyperinsulinism, insulin and C-peptide are inappropriately high despite low glucose. Medscape+1

10. Ketone bodies and free fatty acid levels – During normal fasting hypoglycemia, ketones and free fatty acids rise as the body burns fat. In hyperinsulinism, insulin blocks this, so ketones and free fatty acids stay low, which is a key biochemical clue. Medscape+1

11. Cortisol and growth hormone levels – These “counter-regulatory” hormones should increase when blood sugar is low. Measuring them helps distinguish hyperinsulinism from deficiencies of cortisol or growth hormone, which are other causes of hypoglycemia. indianpediatrics.net+1

12. Basic metabolic panel and liver/kidney tests – Blood tests for electrolytes, liver enzymes, and kidney function help rule out other serious illnesses such as sepsis or organ failure that can also cause hypoglycemia in newborns. indianpediatrics.net+1

13. Ammonia, lactate, and acylcarnitine profile – These tests screen for inborn errors of metabolism. In GLUD1-related hyperinsulinism, ammonia is often chronically elevated, while other patterns may suggest fatty acid oxidation disorders or mitochondrial disease. Journal of Molecular Endocrinology+1

14. Genetic testing panel for CHI genes – Modern panels sequence genes known to cause congenital hyperinsulinism, including ABCC8, KCNJ11, GLUD1, GCK, HADH and others. Finding a mutation can confirm the diagnosis, suggest prognosis, and guide decisions about surgery or medical therapy. Frontiers+1

15. Pancreatic histopathology (after surgery) – If surgery is done, the removed pancreatic tissue is examined under the microscope. Diffuse disease shows abnormal beta cells throughout the gland, while focal disease shows a localized cluster of enlarged, abnormal islets. PMC+1

Electrodiagnostic tests

16. Electroencephalogram (EEG) – EEG records the brain’s electrical activity. In babies with seizures due to hypoglycemia, EEG helps confirm seizure patterns and can show changes related to repeated low glucose episodes or early brain injury. ResearchGate+1

17. Electrocardiogram (ECG) – An ECG checks heart rhythm and electrical conduction. Severe hypoglycemia and stress hormones can sometimes affect heart rate and rhythm; ECG helps rule out cardiac causes of collapse or cyanotic episodes. indianpediatrics.net+1

Imaging tests

18. Abdominal ultrasound of the pancreas – Ultrasound uses sound waves to image the abdomen. It can detect large pancreatic masses or structural abnormalities, and helps exclude other causes of hypoglycemia such as tumors or major organ malformations. ScienceDirect+1

19. 18F-DOPA PET-CT scan of the pancreas – This specialized scan uses a radiolabeled form of DOPA taken up by beta cells. Focal lesions show a bright spot of uptake, while diffuse disease shows uniform uptake across the pancreas. It is now a key test to locate focal CHI before surgery. PMC+1

20. MRI (and sometimes CT) of brain and pancreas – MRI of the brain helps look for signs of hypoglycemic injury in children with seizures or developmental delay. MRI or CT of the abdomen can also help define pancreatic anatomy or plan surgery when focal lesions are suspected from PET-CT results. PMC+1

Non-pharmacological treatments

1. Avoiding prolonged fasting
   One of the most powerful “treatments” in congenital hyperinsulinism is simply avoiding long gaps without food. Babies and children with CHI can drop their blood sugar very quickly if they go many hours without eating. Doctors and dietitians set a maximum safe fasting time based on age and disease severity. Parents are taught to wake the child for feeds if necessary, especially overnight, to keep blood sugar stable and to prevent seizures and brain injury.e-apem.org+1

2. Frequent, small daytime feeds
   Children with CHI often need small, frequent meals rather than three large meals per day. Each meal combines complex carbohydrates, some protein, and healthy fats to release glucose slowly over time. This pattern helps “smooth out” peaks and dips in blood sugar and reduces the risk of sudden hypoglycemia between feeds. A dietitian personalizes the schedule so it fits family life while still providing enough energy, protein, vitamins, and minerals for growth.Congenital Hyperinsulinism International

3. Continuous overnight feeding via tube
   In more severe CHI, doctors may recommend continuous feeding overnight through a nasogastric or gastrostomy tube. A pump delivers a steady flow of formula or expressed breast milk, giving slow, constant carbohydrate input while the child sleeps. This reduces the need for repeated night-time waking and lowers the risk of dangerous, unnoticed low blood sugar episodes during long sleep periods. The rate and feed composition are carefully calculated by the medical team.e-apem.org+1

4. High-carbohydrate or fortified feeds
   Some children benefit from feeds that are slightly higher in carbohydrates or fortified with glucose polymers to give more calories and longer-lasting energy per milliliter. Dietitians may use special formulas or add carbohydrate powders to breast milk or standard formula. The purpose is to provide enough energy without overly large feed volumes that the child cannot tolerate. This strategy helps maintain blood sugar and support weight gain and brain growth.PMC+1

5. Emergency fast-acting oral carbohydrate
   Families are taught to keep fast-acting carbohydrate on hand, such as glucose gel, sugary drink, or juice, to use if the child is awake, cooperative, and has mildly low blood sugar. The purpose is to raise glucose quickly while arranging urgent medical review if needed. The mechanism is simple: rapidly absorbed glucose from the gut enters the bloodstream within minutes. Doctors give clear instructions about when to use this step and when to go straight to hospital or call emergency services.Congenital Hyperinsulinism International+1

6. Home blood glucose monitoring
   Parents and older children learn to check blood sugar with a finger-stick glucose meter. Regular checks are done before feeds, during illness, after long car rides, or any time the child looks unwell. This allows early detection of low readings before symptoms appear. The aim is to treat hypoglycemia early, review patterns with the endocrine team, and adjust feeds or medicines safely. Training includes meter use, hygiene, and how to record results clearly.Congenital Hyperinsulinism International+1

7. Continuous glucose monitoring (CGM)
   In some centers, continuous glucose monitoring sensors are used off-label in CHI. A small device under the skin tracks glucose trends every few minutes and sends data to a receiver or smartphone. Parents can receive alarms for falling glucose, especially at night. While accuracy can vary in very low ranges, CGM trends help doctors fine-tune feeding schedules and medicine doses, and give families more confidence in day-to-day life.Karger Publishers+1

8. Individualized “sick-day” plan
   During illness, poor appetite, vomiting, or diarrhea, the risk of hypoglycemia rises because the child eats less while insulin over-secretion continues. The endocrine team provides a sick-day plan explaining when to check glucose more often, when to give extra carbohydrate, when to hold or adjust medicines, and when to go to the emergency department. This written plan reduces panic and helps families respond quickly and safely.Congenital Hyperinsulinism International+1

9. Hospital admission and IV glucose support
   For unstable CHI, severe illness, or very low sugar that cannot be controlled at home, the child is admitted to hospital. Intravenous glucose is given at a carefully calculated glucose infusion rate to keep blood sugar in the safe range while doctors adjust medicines or prepare for surgery. The purpose is to protect the brain during crisis periods and allow full monitoring of heart rate, breathing, electrolytes, and feeding tolerance.ResearchGate+1

10. Neurodevelopmental monitoring and early intervention
    Because repeated hypoglycemia can affect brain development, children with CHI need regular developmental checks (movement, speech, learning, behavior). If any delay is found, early-intervention therapies such as physiotherapy, occupational therapy, and speech therapy are started. The goal is to support the child’s abilities as much as possible and to catch and treat problems early. This is a non-drug but essential part of long-term management.SciELO+1

11. Dietitian-led nutrition planning
    A pediatric dietitian experienced in CHI designs an individualized meal plan. This includes total calories, feed timing, macro-nutrient balance, and any needed supplements. The purpose is to prevent hypoglycemia while also preventing overweight or feeding aversion. The dietitian also helps families transition from tube feeds to oral feeds, plan school lunches, and adapt meals during travel or religious fasts (often by providing alternatives instead of fasting).Congenital Hyperinsulinism International+1

12. School and daycare care plans
    Children with CHI often attend daycare or school. Staff must know how to recognize low blood sugar, when to give snacks, and when to call parents or emergency services. Written care plans explain symptoms, target glucose ranges, and emergency steps. This non-pharmacological measure keeps the child safe outside the home and reduces anxiety for both family and teachers.Congenital Hyperinsulinism International+1

13. Genetic counseling for families
    CHI is frequently caused by mutations in genes such as ABCC8 or KCNJ11. Genetic counseling explains inheritance patterns, recurrence risk in future pregnancies, and options such as prenatal diagnosis. The purpose is to help parents make informed reproductive choices and to identify other at-risk relatives. Understanding the gene defect can also guide decisions about surgery versus long-term medical therapy.Karger Publishers+1

14. Vaccination and infection prevention
    Infections can trigger hypoglycemia by reducing appetite and increasing metabolic demands. Routine childhood vaccinations and good hygiene (hand-washing, avoiding contact with sick people when possible) help reduce infection risk. Fewer infections mean fewer sick-days, less hospital admission, and more stable glucose control. Doctors also encourage rapid medical review if a child with CHI has fever, vomiting, or breathing difficulty.Congenital Hyperinsulinism International+1

15. Temperature and stress management
    Extreme cold, overheating, or intense physical or emotional stress can change how quickly a child uses glucose. Parents are advised to dress the child appropriately, avoid very hot environments, and plan rest during tiring activities. The idea is to keep energy use more predictable so feeding and medicines can match the child’s needs and avoid unexpected hypoglycemia.e-apem.org

16. Planned, supervised physical activity
    Physical activity is healthy, but in CHI it can lower blood sugar more quickly. Families and doctors plan safe activities, ensure the child eats before exercise, and sometimes check glucose before and after sports. The purpose is to allow normal play while reducing risk. Older children learn to listen to their body and stop activity if they feel shaky, dizzy, or unwell.Congenital Hyperinsulinism International+1

17. Psychological support for child and family
    Living with a serious rare disorder can cause anxiety, guilt, or burnout in parents and stress in children, especially after hospitalizations or seizures. Access to psychologists, social workers, or counselors helps families process these experiences, improve coping skills, and maintain adherence to complex treatment plans. Good mental health supports better day-to-day care and overall quality of life.SciELO+1

18. Family and peer support groups
    Support groups, including online communities and patient organizations dedicated to hyperinsulinism, connect families who share similar experiences. Parents can learn practical tips about feeding, school, and hospital stays, and feel less isolated. These groups also share updates about new treatments and clinical trials. While not a medical treatment, this peer support can significantly improve resilience and long-term outcomes.Congenital Hyperinsulinism International+1

19. Telemedicine and remote data review
    Remote consultations and sharing of glucose logs or CGM data allow specialists to adjust management without frequent travel. This is especially helpful for families living far from expert centers. The purpose is to maintain close follow-up, spot trends early, and reduce emergency visits. Telemedicine became more common during and after the COVID-19 era and remains a useful tool for rare diseases like CHI.Karger Publishers

20. Structured transition to adult care
    As children with CHI grow, some remain at risk of hypoglycemia or develop diabetes after pancreatectomy. A planned transition to adult endocrinology services ensures continued monitoring and support. This includes teaching the young person about their condition, medications, contraception and pregnancy planning, driving safety, and work or university life. The goal is safe, independent self-management in adulthood.Karger Publishers+1

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Key drug treatments

Safety note: Exact doses, timing, and combinations must be set by a pediatric endocrinologist. For a website, describe these as examples of therapies used under specialist supervision, not as DIY protocols.

Because CHI is rare, only diazoxide is currently FDA-approved specifically for hyperinsulinemic hypoglycemia; most other medicines are used off-label or in research.PMC+1 Below are some of the most important agents with FDA prescribing information plus evidence in CHI.

1. Diazoxide oral suspension (PROGLYCEM)
   Diazoxide is the first-line drug for most forms of CHI. It is a potassium-ATP (K_ATP) channel opener that keeps pancreatic beta-cell channels open, helping cells stay “hyperpolarized” and reducing insulin release. The FDA label for PROGLYCEM indicates its use for hypoglycemia due to hyperinsulinism in infants, children, and adults.FDA Access Data+1 Dose is weight-based and divided through the day, then adjusted according to glucose profiles and side-effects such as fluid retention and excessive hair growth. Side-effects are monitored with blood pressure checks, fluid balance, and sometimes echocardiography.

2. Hydrochlorothiazide (supportive with diazoxide)
   Hydrochlorothiazide is a thiazide diuretic. In CHI, it is often used together with diazoxide to counter fluid retention, cardiac overload, and risk of pulmonary hypertension caused by diazoxide.PMC The medicine acts in the kidney to increase sodium and water excretion. Dose and timing are individualized, and doctors monitor electrolytes and kidney function. Side-effects can include low potassium, dehydration, and low blood pressure, so children must be watched carefully.

3. Short-acting octreotide injection (SANDOSTATIN)
   Octreotide is a synthetic somatostatin analogue. It is licensed by the FDA for conditions like acromegaly and certain neuroendocrine tumors, but is widely used off-label as second-line therapy in CHI that does not respond to diazoxide or where diazoxide is not tolerated.FDA Access Data+1 It binds somatostatin receptors on beta cells and reduces insulin secretion. In CHI, it is given by subcutaneous injections or continuous pump infusion, always under specialist supervision. Potential side-effects include gastrointestinal upset, gallstones, and, in infants, serious intestinal complications, so close monitoring is mandatory.FDA Access Data+1

4. Long-acting octreotide LAR depot
   Long-acting octreotide (e.g., Sandostatin LAR Depot) is an intramuscular, once-monthly formulation approved for acromegaly and certain tumors.FDA Access Data Some expert centers use it off-label in selected older children with CHI to reduce the burden of multiple daily injections. The mechanism is the same as short-acting octreotide, but the drug is slowly released from a depot. Long-acting forms require careful dose titration and are generally avoided in very young infants because of safety concerns described for octreotide in pediatrics.FDA Access Data+1

5. Lanreotide depot (SOMATULINE DEPOT)
   Lanreotide is another long-acting somatostatin analogue approved for acromegaly and gastroenteropancreatic neuroendocrine tumors.FDA Access Data+1 It binds somatostatin receptors and reduces hormone secretion, including insulin. Off-label, some centers have tried lanreotide in difficult CHI cases to decrease injection frequency compared with short-acting octreotide. Injections are given every four weeks by trained staff. Side-effects overlap with octreotide (diarrhea, abdominal pain, gallstones), and pediatric safety data in CHI are limited, so it is usually reserved for highly selected patients.

6. Glucagon emergency injection (GLUCAGON for injection / GVOKE / GlucaGen)
   Glucagon is an antihypoglycemic hormone that works by stimulating the liver to release stored glycogen as glucose. FDA-approved glucagon products are indicated for severe hypoglycemia in people with diabetes.FDA Access Data+1 In CHI, glucagon is used off-label as emergency rescue at home or as continuous infusion in hospital to raise glucose while other treatments are adjusted. Dose is weight-based, and families are trained in injection technique and when to call emergency services. Common side-effects are nausea, vomiting, and temporary blood pressure changes.

7. Concentrated intravenous dextrose solutions
   High-concentration dextrose solutions (for example D10W, D20W, or higher in central lines) are essential in acute management of CHI. They are not “drugs” in the classic sense, but are prescribed and infused as medicines in hospital to keep blood sugar within a safe range while diagnosis is made and long-term therapy is planned. The mechanism is straightforward: they directly provide glucose into the bloodstream. Doctors adjust the glucose infusion rate (GIR) frequently, based on repeated glucose measurements, to prevent both low and excessively high levels.ResearchGate+1

8. Nifedipine (off-label calcium channel blocker)
   Nifedipine is a calcium-channel blocker approved for hypertension and angina. In CHI, small studies and case reports have explored nifedipine as a third-line option, especially combined with octreotide, by reducing calcium entry into beta cells and thereby decreasing insulin secretion.PMC+1 Evidence is limited and mixed, and international guidelines advise that nifedipine should not be routine therapy and, if used, should ideally be within clinical research or under strict expert oversight because benefit may be modest and side-effects (low blood pressure, flushing, edema) can occur.Congenital Hyperinsulinism International

9. Sirolimus (mTOR inhibitor – experimental)
   Sirolimus is an mTOR inhibitor licensed for prevention of transplant rejection and certain tumors. It has been tried experimentally in severe diffuse CHI where diazoxide and octreotide fail, aiming to reduce insulin production through mTOR pathway blockade.New England Journal of Medicine+1 Some case series show improved glucose control, but other data highlight limited efficacy and significant potential toxicity (immune suppression, infections, lipid changes), so major CHI organizations now recommend extreme caution and use only in rigorously monitored research settings.SpringerLink+1

10. Alpelisib (PI3K inhibitor – very early research)
    Alpelisib is a PI3K-alpha inhibitor approved for certain cancers. Recently, small reports have described its experimental use in children with severe CHI due to KATP-channel mutations, with some success in avoiding pancreatectomy.endocrine-abstracts.org The idea is to interfere with insulin signaling pathways and reduce unregulated insulin release. This treatment is highly experimental, with unknown long-term safety in infants, and should only be given within closely monitored research protocols and ethics approval.

11. Hydrocortisone (supportive in selected cases)
    Hydrocortisone is a glucocorticoid sometimes used in intensive care settings if a child with CHI also has relative adrenal insufficiency or low stress hormone response. It increases gluconeogenesis and can help stabilize blood sugar in specific situations. However, long-term steroid use has many side-effects (weight gain, high blood pressure, weakened bones, suppressed immunity), so it is not a standard chronic treatment for CHI but rather a short-term supportive therapy when indicated.ResearchGate+1

12. Other somatostatin receptor drugs in development
    Newer somatostatin receptor agonists, including oral formulations such as those approved for acromegaly (for example, the oral agent in the PALSONIFY label), are under study as more convenient ways to suppress hormone secretion.FDA Access Data+1 In the future, some of these may be adapted for CHI, but at present they are not standard care in infants and children and should be considered experimental.

(For SEO clarity on your site, you can add a general sentence after this section such as: “Always talk to a pediatric endocrinologist before using any medicine for congenital hyperinsulinism; doses, times, and combinations must be tailored to your child’s exact condition.”)

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Dietary molecular supplements

Important: Supplements should never replace diazoxide, octreotide, or other prescribed therapy. They are only supportive and must be approved by the treating team.

1. Uncooked cornstarch (glucose polymer)
   Uncooked cornstarch is sometimes used in older children to provide a very slow, steady release of glucose between meals and overnight. The powder is mixed in cold liquids or soft foods. Enzymes in the gut break it down gradually, giving a drip-feed of glucose. Dose is based on weight, tolerance, and blood sugar patterns, and is set by a dietitian. Overuse can cause stomach discomfort, gas, or excess weight gain.

2. Medium-chain triglyceride (MCT) oil
   MCT oil is a fat that is absorbed quickly and used as an energy source. In CHI, it may be added in small amounts to feeds to increase calories without large volumes. The functional role is to support growth and provide an alternative fuel when glucose is borderline. The mechanism is mainly through rapid oxidation of MCTs in the liver. Excess intake can cause diarrhea or stomach cramps, so dose is increased slowly under dietitian guidance.

3. Complete pediatric multivitamin
   Many children with CHI have feeding difficulties, tube dependence, or restricted diets. A complete age-appropriate multivitamin ensures they receive enough vitamins and trace minerals for immune function, bone health, and brain development. The dose usually follows the manufacturer’s age guideline and may be adjusted if blood tests show deficiency. Over-the-counter doses are generally low, but mega-doses should be avoided without medical supervision.

4. Vitamin D supplement
   Vitamin D is vital for bone health, immune regulation, and muscle function. Children with chronic illness, tube feeding, or limited sun exposure are at high risk of deficiency. Vitamin D supplements help maintain normal blood levels and prevent rickets or low bone density. Dose is based on age, baseline blood levels, and local guidelines. Too much vitamin D can cause high calcium and kidney problems, so monitoring is important.

5. Calcium supplement (if needed)
   Calcium supports bones, teeth, and nerve and muscle function. If blood tests show low calcium, or if the child has limited dairy intake, doctors may recommend a calcium supplement. The mechanism is simple replacement of what is missing. Dose depends on age and diet; excessive calcium can cause constipation or kidney stones. Supplementation should be coordinated with vitamin D and overall nutrition planning.

6. Iron supplement (for anemia)
   Repeated blood tests, chronic illness, and poor intake can lead to iron deficiency anemia. Iron tablets or liquid improve red blood cell production, oxygen delivery, and energy levels. The mechanism is providing iron needed for hemoglobin synthesis. Doses are weight- and age-based and can cause dark stools or stomach upset. Because iron overdose is dangerous, supplements must be stored safely away from children.

7. Omega-3 fatty acids (fish oil)
   Omega-3 fatty acids support brain development, eye health, and may help reduce inflammation. In children with CHI, they do not treat hypoglycemia directly but may support long-term neurodevelopment alongside good glucose control. Typical doses are calculated from the amount of DHA and EPA per capsule or syrup, with pediatric guidance. Side-effects can include a fishy taste or mild stomach discomfort.

8. Probiotics
   Probiotic supplements aim to support a healthy gut microbiome, especially in children who have had repeated hospitalizations, antibiotics, or tube feeding. A balanced microbiome may improve digestion and nutrient absorption. Probiotic strains and doses vary widely; pediatricians choose products with evidence for safety in infants and children. Side-effects are usually mild (gas, bloating), but in very immunocompromised children, probiotics must be used cautiously.

9. Carnitine supplement (selected cases)
   Carnitine is involved in fat metabolism in the mitochondria. Some children with metabolic stress or long-term illness may develop low carnitine levels, which can reduce energy use from fats. In such cases, doctors may prescribe carnitine supplementation to support energy production. Dose is weight-based and tailored to blood carnitine levels. Excess doses can cause body odor or gastrointestinal upset.

10. Zinc supplement (if deficient)
    Zinc is important for immune function, skin health, and appetite regulation. Chronic illness and poor intake can lead to deficiency. A zinc supplement, at age-appropriate doses, can help support normal growth and resistance to infections. High doses, however, may interfere with copper absorption, so supplementation is given only when needed and sometimes monitored with blood tests.

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Regenerative and stem-cell-related approaches

Currently no stem cell or “regenerative” drugs are approved for congenital hyperinsulinism. The items below describe areas of research, not standard care. Families should avoid any clinic offering unregulated stem-cell “cures” for CHI.

1. Pancreatic islet cell transplantation research
   Researchers are exploring ways to transplant healthy insulin-producing cells or gene-corrected cells. For CHI, the goal would be to replace or repair overactive beta cells so insulin release becomes normal. At present, this work is experimental in the lab or small trials, with no standard dosing or approved product for children with CHI. Risks include rejection, infection, and long-term immunosuppression.

2. Induced pluripotent stem cell (iPSC)–derived beta cells
   Scientists can create beta-like cells from a patient’s own reprogrammed cells. In the future, corrected iPSC-derived cells might be transplanted to restore balanced insulin secretion. Dosing would relate to the number of cells infused and the target insulin output, but this remains theoretical. These therapies are only in preclinical or very early research and are not available as routine treatment.

3. Gene therapy targeting KATP-channel mutations
   Many CHI cases are caused by mutations in ABCC8 or KCNJ11. Gene-therapy strategies aim to deliver correct gene copies or edit faulty genes in pancreatic cells. This could normalize K_ATP channel function and restore proper insulin control. Delivery systems (viral vectors, gene-editing tools) and doses are still under study. Any future use in children will require rigorous, long-term safety data.

4. mTOR-pathway modulation as regenerative strategy
   Sirolimus shows that manipulating the mTOR pathway can affect beta-cell function, but current use has safety concerns.New England Journal of Medicine+1 Future regenerative approaches may use more selective or safer mTOR or related pathway modulators to “reset” beta-cell growth and insulin secretion. Any such drugs would have complex dosing based on blood levels and organ function and must be tested in controlled trials.

5. Immune-modulating biologics in syndromic CHI
   Some rare CHI forms are part of broader genetic or immune syndromes. In theory, biologic drugs that modulate immune pathways might help specific subgroups. For now, there is no high-quality evidence supporting their routine use in CHI. Dosing and regimens, where tried, follow protocols for the underlying syndrome rather than CHI itself, always under specialist teams and ethics approval.

6. Organ-preserving surgical-plus-regenerative strategies
   Future care may combine less extensive pancreatic surgery with local regenerative treatments, such as growth-factor-loaded scaffolds or engineered tissues, to preserve function and reduce later diabetes risk. These approaches are still conceptual and belong in research settings only. Parents should be counseled that, outside clinical trials, the safest path remains established medical and surgical management in expert centers.

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Surgeries

1. Focal lesionectomy
   When imaging and genetic tests show a focal area of abnormal beta cells, surgeons can remove only that part of the pancreas.Karger Publishers+1 The aim is to cure CHI while preserving most normal pancreas tissue, greatly lowering the risk of later diabetes or exocrine insufficiency. Lesionectomy is usually done through open or minimally invasive surgery in specialized centers.

2. Partial distal pancreatectomy
   If abnormal cells are mainly in the body or tail of the pancreas, surgeons may remove that segment (distal pancreatectomy). The goal is to reduce insulin secretion enough to stop dangerous hypoglycemia while keeping as much normal tissue as possible. This operation carries risks of bleeding, infection, and later glucose intolerance, so it is reserved for clear cases where medicines have failed.

3. Near-total pancreatectomy (≈95% resection)
   In diffuse CHI affecting the whole pancreas and unresponsive to maximal medical therapy, surgeons may remove about 95% of the pancreas.ScienceDirect+1 This often improves hypoglycemia but can lead to diabetes and pancreatic enzyme insufficiency later in life. Families must be counseled about the balance between protecting the brain from ongoing severe hypoglycemia and long-term metabolic risks.

4. Redo or completion pancreatectomy
   Sometimes children continue to have severe hypoglycemia after an initial surgery. If imaging and clinical data show persistent disease, a redo or completion pancreatectomy may be considered. The reason is to control life-threatening hypoglycemia that remains despite prior surgery and intensive medical therapy. This decision is complex and taken by a multidisciplinary team with detailed discussion of long-term consequences.

5. Laparoscopic approaches to pancreatic surgery
   In selected cases and experienced hands, parts of the pancreas can be removed laparoscopically (keyhole surgery). The purpose is to provide the same disease control with smaller incisions, less pain, and faster recovery. However, in tiny babies or very complex CHI, open surgery is often preferred for safety and precision.

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Prevention strategies

1. Start treatment quickly when CHI is suspected in a newborn.

2. Avoid long fasting periods; follow the maximum fasting time set by the specialist.

3. Keep regular feeding schedules and do not skip meals.

4. Use sick-day plans during illness, with extra glucose checks and earlier feeds.Congenital Hyperinsulinism International

5. Attend all follow-up visits with endocrinology, dietetics, and neurology.

6. Monitor development and start early therapies if delays are noticed.SciELO

7. Ensure age-appropriate vaccinations and infection prevention.

8. Educate all caregivers (family, babysitters, teachers) about CHI and emergency steps.

9. Store all medicines and supplements safely and give them exactly as prescribed.

10. Seek support from CHI foundations and support groups to stay informed about new evidence.Congenital Hyperinsulinism International+1

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When to see doctors

Parents should contact their child’s doctor or emergency services immediately if the child with congenital hyperinsulinism has symptoms of low blood sugar such as shakiness, sweating, sudden sleepiness, irritability, confusion, unusual crying, seizures, or loss of consciousness. They should also seek urgent care if home glucose readings are repeatedly below the target range despite extra feeds, if vomiting or diarrhea prevent normal feeding, or if the child looks very unwell in any way. Regular, non-urgent visits are also important to adjust medicines, review growth and development, plan surgery if needed, and discuss school, sports, and future life stages.e-apem.org+1

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What to eat and what to avoid

1. Eat: frequent meals with complex carbohydrates (whole grains, potatoes, rice, pasta) to give steady glucose.

2. Eat: good-quality protein at each meal (milk, yogurt, cheese, eggs, beans, lentils, lean meat) to slow digestion and provide building blocks.

3. Eat: healthy fats (olive oil, nut butters if age-appropriate, avocado) to increase calories when needed.

4. Eat: fruits and vegetables spread through the day for vitamins, minerals, and fiber.

5. Eat: bedtime snacks rich in complex carbohydrate and some protein when recommended by the endocrinology/dietitian team.Congenital Hyperinsulinism International

6. Avoid: long gaps without food, especially skipping breakfast or bedtime snacks.

7. Avoid: large amounts of simple sugar alone (like only juice or sweets) without follow-up complex carbohydrate, as this can cause a rapid rise and then fall in glucose.

8. Avoid: unplanned fasting for religious or cultural practices in children with CHI; doctors can help families find safe alternatives.

9. Avoid: high-caffeine drinks or energy drinks in older children and teens, as they may mask low-sugar warning signs like palpitations or shakiness.

10. Avoid: extreme restrictive diets or weight-loss plans without medical supervision; CHI management must always balance safety and nutrition.

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Frequently asked questions

1. Is congenital hyperinsulinism curable?
   Some children with focal CHI can be cured by surgery that removes only the abnormal part of the pancreas. In diffuse CHI, long-term medical therapy or near-total pancreatectomy may be needed. Even when CHI cannot be fully cured, good treatment can prevent severe hypoglycemia and protect the brain, allowing many children to grow and develop well.e-apem.org+1

2. Will my child definitely need surgery?
   No. Many children respond well to diazoxide and feeding strategies and never need an operation. Surgery is usually considered when CHI is severe, poorly controlled despite maximal medical therapy, or proven to be focal and surgically curable. The decision is made by a specialist team after detailed imaging and genetic testing.e-apem.org+1

3. Can congenital hyperinsulinism go away with age?
   Some genetic forms become milder over time, and feeding can become easier as children grow and can tolerate longer fasting periods. Other forms remain active for years or require surgery. Regular follow-up is needed to reassess how active the disease is at each stage of life.

4. What are the main risks if CHI is not controlled?
   The biggest risk is repeated or prolonged hypoglycemia causing seizures and permanent brain injury, which can lead to learning difficulties, movement disorders, or epilepsy. There are also risks from emergency hospitalizations and, after pancreatectomy, later diabetes and digestive problems. This is why tight glucose control from early life is so important.SciELO+1

5. Is diazoxide safe for my baby?
   Diazoxide is the only FDA-approved long-term medicine for hyperinsulinemic hypoglycemia and has been used for many years.FDA Access Data+1 Like all medicines, it can have side-effects, including fluid retention, excessive hair growth, and rarely heart or pulmonary problems. Careful dosing, regular check-ups, and sometimes adding a diuretic help manage these risks. Parents should never change the dose without medical advice.

6. Why would my doctor suggest octreotide if it is off-label?
   Octreotide is not officially approved for CHI, but long experience and studies show it can help many diazoxide-unresponsive children by reducing insulin secretion.Congenital Hyperinsulinism International+1 Because there are risks, especially in very small babies, its use is limited to centers with CHI expertise, with close monitoring of gut and gallbladder health.

7. Can supplements replace medicines for CHI?
   No. Supplements like vitamins, omega-3, or probiotics can support general health but do not stop abnormal insulin secretion. Stopping diazoxide or other prescribed medicines and relying only on “natural” products is dangerous and can lead to severe hypoglycemia and brain injury. Supplements should be used only as part of a full plan designed by the medical team.

8. Will my child develop diabetes in the future?
   Children who have had near-total pancreatectomy have a significant risk of developing diabetes later, often in childhood or adolescence, because much of the insulin-producing tissue has been removed.ScienceDirect+1 Even without surgery, some genetic forms of CHI can evolve toward diabetes. Lifelong follow-up is needed to monitor glucose and manage any changes early.

9. Can my child go to normal school and play sports?
   With good control and a clear care plan, most children with CHI can attend regular school and participate in many activities. Schools must be informed about the condition, trained to recognize symptoms, and know when to give snacks or call parents. For sports, snacks before activity and extra monitoring may be needed.

10. Is CHI inherited?
    Many forms of CHI are inherited, often in an autosomal recessive or dominant pattern, depending on the gene. Genetic testing can clarify the cause and help estimate recurrence risk in future pregnancies. Genetic counseling is recommended for families to understand this in simple language and plan accordingly.Karger Publishers+1

11. Are experimental drugs like sirolimus or alpelisib right for my child?
    These medicines are still under study, usually for very severe cases that do not respond to standard therapy. They may help some children but also carry important risks and unknown long-term effects.New England Journal of Medicine+1 Decisions about such drugs should only be made within recognized clinical trials or specialist centers, after detailed discussion of benefits and risks.

12. Can we ever fast for religious or cultural reasons?
    Fasting is dangerous for most children with active CHI. Families should discuss their religious needs with their medical team and religious leaders. Often alternatives (such as charitable acts or adjusted practices) are suggested. For older adolescents with milder disease or after surgery, supervised test fasts may be done in hospital to see what is safely possible, but this must never be done at home without monitoring.

13. What happens during a hypoglycemia emergency at home?
    If the child is awake but showing symptoms and the glucose meter confirms low blood sugar, parents usually give fast-acting carbohydrate, then a complex-carbohydrate snack, following the plan from their doctor. If the child is drowsy, unconscious, or cannot swallow safely, emergency glucagon injection may be given if prescribed, and ambulance services must be called immediately.FDA Access Data+1

14. How often will my child need blood tests and scans?
    At diagnosis and in early management, blood tests may be frequent to check glucose, insulin, electrolytes, liver and kidney function, and drug levels if needed. Imaging (such as ^18F-DOPA PET or specialized MRI) may be done to distinguish focal from diffuse disease. After stabilization, visits and tests usually become less frequent but continue throughout childhood to monitor growth, development, and treatment side-effects.e-apem.org+1

15. Where can we find reliable information and support?
    Families should rely on information from recognized medical centers, peer-reviewed articles, and reputable patient organizations dedicated to congenital hyperinsulinism. Websites from CHI foundations, endocrine societies, and government drug agencies (such as FDA labels on accessdata.fda.gov) provide evidence-based guidance.Congenital Hyperinsulinism International+1

Disclaimer: Each person’s journey is unique, treatment plan, life style, food habit, hormonal condition, immune system, chronic disease condition, geological location, weather and previous medical  history is also unique. So always seek the best advice from a qualified medical professional or health care provider before trying any treatments to ensure to find out the best plan for you. This guide is for general information and educational purposes only. Regular check-ups and awareness can help to manage and prevent complications associated with these diseases conditions. If you or someone are suffering from this disease condition bookmark this website or share with someone who might find it useful! Boost your knowledge and stay ahead in your health journey. We always try to ensure that the content is regularly updated to reflect the latest medical research and treatment options. Thank you for giving your valuable time to read the article.

The article is written by Team RxHarun and reviewed by the Rx Editorial Board Members

Last Updated: December o2 , 2025.