1. Endocrine disorders1 Endocrine Disorders Dr. Manal Kloub

2. Endocrine disorders2 Phenylketonuria PKU

3. Endocrine disorders3 What is PKU?  it is an Autosomal recessive inborn error of metabolism found on the 12th chromosome  Causing an inherited metabolic disease that passes through families  It is rare condition characterized by the deficiency in the enzyme (Phenylalanine Hydroxylase).  Normally: phenylalanine  tyrosine by liver enzyme phenylalanine hydroxylase (PAH)

4. Endocrine disorders4 PKU Genogram

5. Endocrine disorders5 How PKU is Inherited?  In order for a child to inherit PKU, both parents must be PKU carriers.  Boys and girls are equally at risk of inheriting this disorder.  In this condition, an amino acid called phenylalanine builds up in the bloodstream, causing brain damage.

6. Endocrine disorders6 Incidence of PKU  1 out of 50 people are carriers of this defective gene; causing incidence of 1 in 10,000 to 1in 15,000 births.  Mostly those of northern European background.  Asians, and Africans are less commonly affected.

7. Endocrine disorders7 Etiology of PKU  Phenylalanine is one of the essential amino acids found in many foods.  The baby is born lacking the ability to break down phenylalanine into tyrosine.  It is characterized by higher than normal levels of phenylalanine in the blood  The brain suffers and damaged due to a tremendous buildup of phenylalanine which causes mental retardation  In which mental retardation can be prevented by a specific diet low in Phenylalanine and higher in Tyrosine

8. Endocrine disorders8 Diagnosis of PKU  Nearly all cases of PKU in the United States are found in newborns screening tests after birth  A small sample of blood to test if the trait is present on the 12th chromosome.  A “heel stick” is done and then collected on special blotter paper

9. Endocrine disorders9 Diagnostic findings  Normal: 120 – 360 umol/L or 1.6mg/dl  PAH Deficient: Mild: 600 – 1200 umol/L Classical: > 1200 umol/L

10. Endocrine disorders10 Physical Findings  Because Phenylalanine is involved in the body’s production of melanin which is the pigment for skin and hair color – children with PKU generally have lighter skin, hair and eyes (Albinism).  Defficience inTyrosine, affect the formation of Hormones like Epinephrine and Thyroxine Accumulation of Phynylalanine leads to decreasd neurotransmitters; Dopamine and Tryptophan which affect the normal development of the brain and CNS leading to disturbance in the cortical lamination that leads to mental retardation

11. Endocrine disorders11 Symptoms of PKU  Vomiting  Skin Rashes  Hyperactivity  Small head size  Mental Retardation  Behavioral and social problems  Seizures tremors or jerking movements  A musty odor in the skin, breath or urine caused by too much Phenylketonuria The inability to change Phenylalanine Hydroxylase to Phenylalanine causes all of these symptoms.

12. Endocrine disorders12 Treatment of PKU  A life long restricted diet of a reduced protein diet is recommended to reduce build up of phenylalanine  Association with attention-deficit hyperactivity disorder (ADHD) most common problem in those who don’t follow a strict diet  If diet is properly followed especially in first few years of life where it is most crucial an outcome of better physical and mental health will follow

13. Endocrine disorders13 Treatment of PKU  Frequent monitoring of phenylalanine levels  Once weekly during 1 st year  Twice monthly from 1 – 12 years  Monthly after 12 years  Possible supplementation of tyrosine to promote normal growth and development  Foods high in phenylalanine, such as breast milk, meat, chicken, fish, nuts, cheese.breast milkmeatchickenfishnutscheese  Kuvan is the first FDA approved drug for treating PKU.

14. Endocrine disorders14 Medical Nutrition Therapy  Initial Treatment implemented 7 – 10 days old Phenylalanine-free formula  Infants and Toddlers  90% protein requirements  80% energy requirements  Reliable source of vitamins and minerals  Supplemented with evaporated milk, regular infant formula, or breast milk during infancy and early childhood

15. Endocrine disorders15 Medical Nutrition Therapy  Later Low-phe content foods introduced at the appropriate age and used as a supplement to the formula mixture  Vegetables  Fruits  Breads/cereals  Fats  Free foods 5-6 months: Pureed foods 7-8 months: Finger foods 8 – 9 months: Use of cup

16. Endocrine disorders16 Daily Phenylalanine Requirement  0 – 3 months = 40- 70 mg/kg  4 - 6 months = 30 - 50 mg/kg  7 – 12 months = 30 - 40 mg/kg  1 – 3 years = 20 – 40 mg/kg  4 – 6 years = 15 – 35 mg/kg  7 – 15 years = 10 – 25 mg/kg  15 – 18 years = 5 – 15 mg/kg  Adult = 5 – 10 mg/kg Daily Tyrosine Requirements  0 – 5 months  60 – 80 mg/kg  6 – 12 months  40 – 60 mg/kg  1 – 10 years  25 – 85 mg/kg

17. Endocrine disorders17 Prevention of PKU  Patients are highly recommend to have strong relationship with physician  An Enzyme Assay can determine if parents carry defective gene  Chorionic villus Sampling - screen unborn baby for possibility of PKU  It is very important that women with PKU closely follow a strict low- phenylalanine diet both before becoming pregnant and throughout the pregnancy, since build-up of this substance will damage the developing baby even if the child has not inherited the defective gene.

18. Endocrine disorders18 Nursing considerations  Although PKU is a life-long disease, people who have PKU have the same average life expectancy as those who do not have the disease.  Genetic counseling is important especially to newly married and diagnosed couples  Provide parental and professional support to promote normal growth and development

19. Endocrine disorders19 Research findings  Several studies indicated that the discontinuation of the restricted diet might lead to deficits in: Neuropsychological functions Cognitive ability  Also it showed: Severe mental and psychiatric disorders such as anxiety, depression, phobias, social withdrawal and tremors  It is recommended to continue the restricted diet to life-long, or at least till age 20 – with some modifications.

20. Endocrine disorders20 Hypothyroidism and Hyperthyroidism

21. Endocrine disorders21 Congenital Hypothyroidism- CH  Clinical condition associated with decreased function of the thyroid gland and a decrease in the circulating level of thyroid hormones  1:3500 to 1:4000 newborns  One of most common preventable causes of mental retardation

22. Endocrine disorders22 Causes of CH  The most common cause of congenital hypothyroidism is iodine deficiency.iodine  Most commonly due to defect of development of the thyroid gland itself, resulting in an absent (athyreosis) or underdeveloped (hypoplastic) gland. A hypoplastic gland may develop higher in the neck or even in the back of the tongue. A gland in the wrong place is referred to as ectopic, and an ectopic gland at the base or back of the tongue is a lingual thyroid.

23. Endocrine disorders23 Causes of CH  Some of these cases of developmentally abnormal glands result from genetic defects, and some has no identifiable cause.genetic defects  Genetic defects of thyroxine or triiodothyronine synthesis within a structurally normal gland.triiodothyronine  Among specific defects are: 1. thyrotropin (TSH) resistanceTSH 2. organification defect 3. iodine trapping defect  The defect sometimes might be due to a deficiency of thyroid stimulating hormone, either isolated or as part of congenital hypopituitarism.hypopituitarism

24. Endocrine disorders24 Iodine Deficiency Disorders (IDD)  Endemic goiter  Endemic cretinism  Intellectual disability  Growth retardation  Neonatal hypothyroidism  Increased early and late pregnancy loss  Increased perinatal and infant mortality

25. Endocrine disorders25 Iodine Deficiency Disorders (IDD)  Most common preventable cause of mental deficits in the world  The WHO estimated that 20 million people in the world had varying degrees of preventable brain damage due to effects of iodine deficiency on fetal brain development  Population at risk for IDD caused by low levels of iodine in the soil was estimated to be 1 billion, approximately 20% of whom have goiter  Estimates of prevalence of neonatal hypothyroidism in various regions where goiter is endemic range from 1 to 10%, as compared with only 0.025% in iodine-sufficent regions

26. Endocrine disorders26 Iodine Deficiency Disorder  IDD severe to cause goiter in 30% or more of population  Correction of iodine deficiency before pregnancy  Severe hypothyroidism in infancy termed cretinism  Maternal hypothyroidism is a factor contributing to cretinism

27. Endocrine disorders27 CH – Signs and Symptoms  Anemia is due to decreased oxygen carrying requirement  Retardation of mental development and growth manifest in later infancy and largely irreversible  Feeding problems, failure to thrive, constipation, a hoarse cry  Protuberance of abdomen, dry skin, poor growth of hair and nails, delayed eruption of deciduous teeth, umbilical hernia  Delay in holding up the head, sitting, walking and talking  Limb disproportionately short in relation to the trunk  Severe mental deficiency, and low IQ

28. Endocrine disorders28 CH – Signs and Symptoms  Delayed closure of fontanelles, head to be large in relation to the body  Naso-orbital configuration remains infantile  Maldevelopment of femoral epiphyses  waddling gait  The teeth are malformed and susceptible to caries  A broad, flat nose, wide set eyes, periorbital puffiness, large protruding tongue, sparse hair, rough skin, short neck, and protuberant abdomen with umbilical hernia  A small but significant number (3-7%) of infants with congenital hypothyroidism have other birth defects, mainly atrial and ventricular septal defects in their heart

29. Endocrine disorders29 CH Screening  Highly sensitive immunoassay methods  Direct measurement of serum thyroxine and TSH  Filter paper blood spots  Gurantee detection and treatment from the first weeks of life  Majority of children who were treated early experienced normal growth and neurologic development and normal-range IQ values

30. Endocrine disorders30 Diagnosis of CH  Diagnosis of primary hypothyroidism is confirmed by decreased levels of serum thyroid hormone (total or free T4) and elevated levels of TSH.  Thyroxin-binding globulin (TBG) levels can be measured in infants with suspected TBG deficiency.

31. Endocrine disorders31 Treatment of CH  The rule in the treatment of congenital hypothyroidism is early diagnosis and thyroid hormone replacement.  Most important treatment variables are the dose and timing of thyroxine therapy (Levothyroxine).  Initial thyroxine dose 10-15 ug/kg/day, Can be given as a single weekly dose  Endemic cretinism can be prevented by appropriate iodine supplementation. Iodization of salt is the usual method.  Calcium supplements may be useful, Vitamin D therapy is necessary, and IV calcium gluconate is recommended.

32. Endocrine disorders32 Nursing care  Patients who have been treated for hyperthyroidism need to be followed closely because they may develop Hypothyroidism, signs of seizures, or tetany.  Follow up care includes: Check thyroid function test every 4-6 weeks Follow up on medications and dose adjustment

33. Endocrine disorders33 Thank you for listening Have a blessed day