Endocrine Disorders - Introduction PDF

NMHS33250 Introduction to Endocrine Disorders Dr Suja Somanadhan Associate Professor in Children’s Nursing Module Co-ordinator NMHS33250 01/10/2024  After studying this subject, you will be able to:...

NMHS33250 Introduction to Endocrine Disorders Dr Suja Somanadhan Associate Professor in Children’s Nursing Module Co-ordinator NMHS33250 01/10/2024  After studying this subject, you will be able to: Define endocrine system Identify the function of important hormone of the endocrine system Learning objectives Discuss clinical manifestations that indicate an endocrine conditions in childhood Understand diagnosis and management of common endocrine conditions in childhood Discuss the care of a child with altered endocrine functions NMHS33250  Can you describe a situation where you or someone you know experienced an adrenaline rush? NMHS33250  What is a Hormone? ▪ Leave gland and enters A hormone is a chemical bloodstream messenger produced by glands in the endocrine system that ▪ Reach “target tissues” regulates various physiological processes in the body Hormones are released ▪ Binds to “receptor sites” directly into the bloodstream and travel to target organs or tissues, influencing growth, ▪ A specific response occurs metabolism, reproduction, in the cell mood, and overall homeostasis (balance within the body). NMHS33250 The Endocrine System is made up of glands that produce and secrete hormones What does the endocrine system do and how does it work? Positive &Negative Feedback If levels of a particular hormone are low, the hypothalamus tells the pituitary gland to send out releasing factors which in turn signal the gland to make more of that particular hormone NMHS33250 Endocrine Functions Maintain homeostasis through the regulation of nutrient Maintain metabolism, and water and electrolyte balance. Regulate Regulate growth and production of cells. Control the responses of the body to external stimuli, Control especially stress. Control Control reproduction. Control and Control and integrate circulatory and digestive activities in integrate collaboration with the autonomic nervous system. NMHS33250  Hypothalamus Hypothalamus: This gland is located in your brain and controls your endocrine system. It uses information from your nervous system to determine when to tell other glands, including the pituitary gland, to produce hormones. The hypothalamus controls many processes in your body, including your mood, hunger and thirst, sleep patterns and sexual function. NMHS33250 Hypothalamus The hypothalamus secretes various hormones that are then transported to the anterior pituitary Corticotropin releasing hormone (CRH) Growth hormone-releasing hormone (GHRH) Thyrotropin releasing hormone (TRH) Gonadotropin releasing hormone (GnRH) Somatostatin (inhibits growth hormone secretion) Prolactin releasing and prolactin inhibitor hormones Hypothalamus The pituitary gland also secretes hormones in response to hypothalamic release hormones: Thyroid stimulating hormone (TSH) Adrenocortical stimulating hormone (ACTH) Follicle stimulating hormone (FSH) Luteinizing hormone (LH) Prolactin Melanocyte-stimulating hormone (important for protecting the skin from UV rays) Endorphins Supraoptic and paraventricular nuclei of the hypothalamus also secrete hormones that are transported to the posterior pituitary to be released into the circulation. These are: Anti-diuretic hormone (ADH): regulates plasma osmolality Oxytocin: regulates ejection of milk and uterine contractions. Hypothalamus Disorders of the hypothalamus can result in appetite, temperature and sleep disorders. Disorders of the hypothalamus and/or anterior pituitary can also result in hypopituitarism, including adrenal insufficiency hypothyroidism hypogonadism growth hormone deficiency prolactin deficiency (inability to lactate). Disorders of the posterior pituitary can result in diabetes insipidus and disorders pertaining to oxytocin deficiency Pituitary NMHS33250  Functions of the pituitary gland Anterior lobe Growth hormone Prolactin (to stimulate milk production in the female breast) ACTH (adrenocorticotropic hormone which regulates the adrenal glands ) TSH (thyroid-stimulating hormone which regulates the thyroid gland ) FSH (follicle-stimulating hormone which regulates the ovaries and testes) LH (luteinizing hormone which regulates the ovaries or testes) Posterior lobe ADH (antidiuretic hormone is actually produced in the hypothalamus and stored in the pituitary gland; it increases absorption of water by the kidneys. It also increases blood pressure) Oxytocin (to contract the uterus during childbirth and stimulate the release of milk during breastfeeding) NMHS33250 Thyroid gland Located at the lower front of the neck 2 connected lobes Involved in the regulation of metabolism →Thyroid hormones essential for normal growth and development NMHS33250 Thyroid Hormone Production ▪ Hypothalamus secretes TRH ▪ Stimulates Pituitary Gland to produce TSH ▪ TSH signals the Thyroid Gland to capture iodine to synthesize, store and release Thyroxine (T4) ▪ When T4 reaches the target cells, it is converted to Triiodothyronine (T3) ▪ Reduced output of TRH and TSH once T4 reaches adequate circulating levels and resume again when T4 level drops NMHS33250 Types of thyroid disease Hypothyroidism (underactive thyroid) Hypothyroidism refers to an underactive thyroid gland that does not produce enough of the active thyroid hormones triiodothyronine (T3) and levothyroxine (T4). This condition can be present at birth or acquired anytime during childhood or adulthood (PES, 2018) Hyperthyroidism (overactive thyroid) A disorder in which thyroid hormones levels are increased resulting excessive levels of circulating thyroid hormones NMHS33250 Acquired Hypothyroidism (PES, 2018) ▪ The causes of hypothyroidism can arise from the gland itself or from the pituitary. ▪ The thyroid can be damaged by direct antibody attack (autoimmunity), radiation, or surgery. The pituitary gland can be damaged following a severe brain injury or secondary to radiation treatment. ▪ Certain medications and substances can interfere with thyroid hormone production. ▪ For example, too much or too little iodine in the diet can lead to hypothyroidism. ▪ Overall, the most common cause of hypothyroidism in children and teens is direct attack of the thyroid gland from the immune system. ▪ This disease is known as autoimmune thyroiditis or Hashimoto disease. NMHS33250  Modest weight Signs and Tiredness gain (no more Symptoms of than 5–10 lb) Hypothyroidism Feeling cold Dry skin Hair loss Constipation Goiter Poor growth (enlarged thyroid gland) Sensitivity to cold temperatures NMHS33250 Treatment Thyroxine medication for life, essential for brain development Safe medication, minimal side effects Absorption can be affected by iron and soya products Small % of babies can have transient hypothyroidism Regular F/Up and Audiology referral NMHS33250  Sometimes thyroid releases too much T4. Graves' disease. Graves' disease is an autoimmune disorder in which antibodies produced by immune system stimulate thyroid to produce too much T4. It's the most common cause of hyperthyroidism. Hyperfunctioning thyroid nodules (toxic adenoma, toxic multinodular goiter or Hyperthyroidism Plummer's disease). This form of (overactive hyperthyroidism occurs when one or more adenomas of your thyroid produce too thyroid) much T4. Thyroiditis. Sometimes your thyroid gland can become inflamed after pregnancy, due to an autoimmune condition or for unknown reasons. The inflammation can cause excess thyroid hormone stored in the gland to leak into your bloodstream. Some types of thyroiditis may cause pain, while others are painless. NMHS33250 Risk factors A family history, particularly of Female sex A personal history of certain Graves' disease chronic illnesses, such as type 1 diabetes, pernicious anemia and primary adrenal insufficiency NMHS33250 Diagnostic Test Diagnostic Study Hypothyroidism Hyperthyroidism Serum T4 (tests level of thyroxine) Decreased Markedly elevated Serum T3 (tests level of Normal Markedly elevated triiodothyronine) Serum TSH tests level of TSH) Elevated Decreased The test, called a thyroid function test, looks at levels of thyroid-stimulating hormone (TSH) and thyroxine (T4) in the blood. NMHS33250  Unintentional weight loss Rapid heartbeat (tachycardia) — commonly more than 100 beats a minute Irregular heartbeat (arrhythmia) Pounding of your heart (palpitations) Increased appetite Nervousness, anxiety and irritability Signs and Tremor — usually a fine trembling in your hands and fingers Excessive Sweating Symptoms Changes in menstrual patterns Increased sensitivity to heat Changes in bowel patterns, especially more frequent bowel movements An enlarged thyroid gland (goiter), which may appear as a swelling at the base of your neck Fatigue, muscle weakness Difficulty sleeping Skin thinning Fine, brittle hair NMHS33250 Typical reference ranges for healthy adults are: Test From To Units TSH mU/l (milliunits 0.4 4.0 per litre) pmol/l FT4 9.0 25.0 (picomoles per litre) pmol/l FT3 3.5 7.8 (picomoles per litre) NMHS33250 Graves' ophthalmopathy Signs and symptoms of Graves' ophthalmopathy include: ▪ Dry eyes ▪ Red or swollen eyes ▪ Excessive tearing or discomfort in one or both eyes ▪ Light sensitivity, blurry or double vision, inflammation, or reduced eye movement ▪ Protruding eyeballs NMHS33250 Management There are 3 main ways to treat hyperthyroidism: antithyroid medications, radioactive iodine ablation, and surgery. Sometimes, medications called beta (β)-blockers are used initially to help relieve the symptoms of hyperthyroidism, but they do not reduce thyroid hormone levels. Antithyroid medications. Thionamides/Methimazole is the first-line medical therapy in children. Potential side effects include hives, and rarely joint aches, high liver enzymes, and low white blood cell counts. (Propylthiouracil, a drug related to methimazole, is used less often in children because of a higher risk of serious liver side effects.) NMHS33250 Management (PES, 2018) Radioactive iodine ablation. Radioactive iodine is swallowed as a capsule or drink. It painlessly destroys the thyroid gland slowly over several months, so that the thyroid gland no longer makes thyroid hormone. The individual eventually has hypothyroidism (too little thyroid hormone) and must take a pill containing thyroid hormone every day. This treatment is very well tolerated and safe in children. It should not be given to women of childbearing age without first ensuring that they are not pregnant. Surgery. Surgical removal of the thyroid gland causes a rapid decrease in thyroid hormone levels. Subsequently, the individual has hypothyroidism and must replace thyroid hormone by taking a pill each day. Thyroid surgery is more risky than radioiodine and should be performed by an experienced surgeon. Possible risks include damage to the nearby parathyroid glands (which control blood calcium levels) and recurrent laryngeal nerve (which controls the voice). NMHS33250 The Pancreas Islets of Langerhans Alpha cells → Glucagon ß cells → Insulin NMHS33250 Hormones which influence Blood Glucose Levels Insulin: Changes cell permeability, allowing glucose into the cells thereby ↓ BGL’s Glucagon: Converts glycogen to glucose, opposite effect to insulin Promotes formation of glucose from non-CHO substances Promotes FFA release Glucagon, growth hormone and cortisol ↑BGL’s NMHS33250 What is diabetes insipidus (DI)? Diabetes insipidus is a rare disorder in which a person urinates an excessive amount, is more thirsty than usual, and drinks an excessive amount of fluid. This can be caused by a hormone deficiency (anti-diuretic hormone or ADH) or a decreased ability of the kidney to resp It is important to differentiate diabetes insipidus from diabetes mellitus. The term “diabetes” was first used to describe a condition with frequent urination. NMHS33250  Diabetes Insipidus Characterised by A large volume of urine (diabetes) That is hypotonic, dilute and tasteless (insipid) Versus the sweet urine of diabetes mellitus (honey) Thirst → release of anti-diuretic hormone (ADH) ↓ Concentration of urine – re-absorption of water from distal tubule Inadequate ADH → Tubules do not reabsorb water ↓ Polyuria NMHS33250 Etiology Four fundamentally distinct defects Central DI, a primary deficiency of ADH Nephrogenic DI, caused by an inappropriate renal response to ADH Transient DI of pregnancy, caused by vasopressinase produced by placenta Primary Polydipsia, in which pathology is secondary to ingestion, rather than elimination of, fluid How common is diabetes insipidus? It’s very rare, occurring in approximately 1 in 30,000 children. ▪ Among those children who have diabetes insipidus, nearly 98 percent have the central variety, while 2 percent have the harder-to-treat nephrogenic type of the condition. NMHS33250 Signs and Symptoms Increased thirst (polydipsia) Increased urination (polyuria) – urine is often clear or a very faint yellow in color Getting up to go the bathroom several times at night (nocturia) Signs of dehydration such as elevated heart rate, dry mouth, sunken eyes or dizziness going from sitting to standing Problems gaining weight and growing because they are drinking such an excessive amount of fluid, they feel too full to eat food NMHS33250  Diagnosis Water deprivation test Vasopressin test NMHS33250  Diagnosis: urine osmolality, serum sodium, MRI, Plasma arginine vasopressin (AVP) level Treatment Treatment depends on cause: Central ADH deficiency – Oral desmopressin acetate (DDAVP) - ↓urine output It is available as a pill, a nasal spray or subcutaneous (under the skin) injection that can be given at home. Sometimes child will be asked to drink more or less water depending on their sodium level and level of dehydration. Nephrogenic diabetes insipidus – thiazide diuretics NMHS33250 Congenital Hyperinsulinism (CHI, 2021)  Congenital Hyperinsulinism is a condition where there is an inappropriate secretion of high levels of insulin from the pancreas, which in turn causes persistently low/unstable blood glucose levels (hypoglycemia) in the body.  Hypoglycemia due to CHI is relatively rare but potentially a serious condition occurring after birth.  Can be transient or prolonged (focal or diffuse), can be due to a genetic mutation  The most common cause of persistent hypoglycemia in infants and children  CHI has an estimated global prevalence of 1/50,000 live births but the incidence can be as high as 1 in 2,500 in populations with high consanguinity rates.  Remember the neonatal brain is at high risk of injury NMHS33250 What is Insulin and how does it work? When blood glucose levels drop When food is eaten, blood glucose (e.g., during fasting or sleep), insulin levels rise, prompting the pancreas secretion slows or stops, allowing to release insulin to maintain a glycogen from the liver to maintain normal range of 3.5 to 6 mmol/L. glucose levels. During this time, the Glucose from food fuels the body by body can also use protein and fat moving through the bloodstream stores as an alternative energy source NMHS33250 Diagnostic Criteria: Glucose requirements > 6-8 mg/kg/min to maintain BG > 2.6-3 mmol/L Detectable insulin levels at time of hypoglycaemia Absence of ketones at the time of hypoglycaemia BG rise of > 1.7mmol/L following glucagon stimulation test NMHS33250 Signs and Symptoms Floppiness Shakiness Poor feeding Sleepiness Irritability. These symptoms occur because of persistent hypoglycemia, and if not corrected, this may result in seizures, prolonged unconsciousness and the possibility of permanent brain impairments, hence the importance of maintaining the blood glucose between 3.5mmol/l to 6mmol/l. NMHS33250 Transient CHI ▪ Transient CHI means that the increased insulin production is only present for a short duration of time (weeks to months), and it is found in conditions such as: ▪ Babies with a low birth weight/born small for gestational age ▪ Infants of mothers with Type 1 / Type2 / gestational diabetes (not all on insulin) ▪ Babies stressed at the time of birth, a difficult or traumatic births ▪ Transient CHI can also occur in infants with no predisposing factors such as those listed above, the reason for this is unclear. Some of the transient forms of CHI will need treatment with medication for a period NMHS33250 Persistent CHI (Histology) (GOSH, 2020) The two main histological forms of persistent CHI are focal and diffuse. ▪ In focal CHI, a specific area of the pancreas is affected. Focal lesions are usually small, measuring 2mm to 10mm across. Beta-cells in the focal lesion have enlarged nuclei (centre of the cell) surrounded by normal tissue. Around 40 to 50 per cent of infants with persistent CHI will have the focal form. ▪ Diffuse CHI affects the entire pancreas. It can be inherited in a recessive or dominant manner or occur sporadically. ▪ The management of diffuse and focal disease is different. Focal disease can now be cured if the lesions are located accurately and removed completely. However, if it does not respond to medical management, diffuse disease will require the removal of almost the entire pancreas. NMHS33250 How is CHI diagnosed? Medical history. Family history. Physical exam. Signs and symptoms Hypoglycemic work-up (this is usually done through detailed blood and urine tests taken while a child’s blood glucose level is low) The results of the genetic analysis helps in determining whether your child will need an 18-F-DOPA scan. NMHS33250 18-F-DOPA Positron Emission Tomography (PET) A PET scan gives very detailed, three- dimensional images of the body. It works by injecting an isotope. The isotope used is called 18-F-DOPA so you may hear the scan referred to by this name. PET scanning is a relatively new technology. The focal lesion is very tiny and cannot be seen by other X-ray techniques. With this scan, the doctors are trying to identify the area of the pancreas from which excessive insulin is being produced. The treatment recommended by the doctors depends on the results of the scan. NMHS33250  Acute Management: 2mls/kg IV Dextrose 10% bolus +/- continuous infusion. If remains hypoglycaemic , increase glucose concentration or consider a glucagon infusion Medical Management 1. Diazoxide (5-15mgs/kg/day in 2-3 divided doses) Action: Insulin Inhibitor SE: Fluid retention, hypertrichosis and appetite Management suppression of CHI Chlorthiazide (3-5mgs/kg/day in 2 divided doses) Action: Potassium sparing diuretic SE: Hyponatraemia, hypokalaemia 2. Octreotide (5-20mcgs/kg/day IV/SC) Action: Insulin inhibitor, but very short half life SE: Suppression of GH,TSH and ACTH, Steatorrhoea, ↑ LFT’s, Gall Stones, Abdominal distension,↓GV and NEC NMHS33250 Management of CHI Glucagon Infusion: (1mg /day IV divided over 24 hours) A bolus dose IM can be used for Tx of hypoglycaemia if IV access is lost (transient hyperglycaemic response only) Action: ↑ gluconeogenesis Side effects: Nausea and Vomiting NMHS33250 Nursing Management of Hyperinsulinism (Moloney, 2022) Frequent BG monitoring Maintenance of IV access, central line insertion is usually indicated Frequent U+E monitoring to determine electrolyte balance IV Fluid Management Administration of prescribed medications Strict Intake and Output Monitoring Daily Weights, BD weights in neonates Continuous enteral feeding via NG tube. Avoid bolus feeding until the condition stabilised Apnoea Monitor ( ↑ Risk associated with hypoglycaemia) NMHS33250 Nursing Management Prolonged hospital admission Risk of infections Feeding difficulties/ oral aversion Parental stress and financial difficulties Parental education pre-discharge NMHS33250  Parathyroid Glands 4 Glands Release PTH Role in regulation of serum calcium levels and bone metabolism https://www.youtube.com/watch?time_continue=231&v=sD9st1ZPFrQ NMHS33250  Pineal Body Located in middle of brain ▪ Produces melatonin ▪ Melatonin influences the circadian rhythms of the body→ influencing the day-night cycle NMHS33250  The Thymus Produces hormones involved in the development of a normal immune system NMHS33250 Adrenal Glands 2 triangular glands Consist of 2 parts Cortisol involved in blood glucose metabolism, maintenance of blood pressure and the body’s response to ‘stress’ Aldosterone regulates salt concentrations in the body NMHS33250 An adrenal gland is made of two main parts: The adrenal cortex is the outer region and also the largest part of an adrenal gland. It is divided into three separate zones: zona glomerulosa, zona fasciculata and zona reticularis. Each zone is responsible for producing specific hormones. The adrenal medulla is located inside the adrenal cortex in the center of an adrenal gland. It produces “stress hormones,” including adrenaline. NMHS33250 Adrenal Glands (NORD, 2019) 1. corticosteroids, which gauge the body's response to illness or injury; 2. mineralocorticoids, which regulate salt and water levels 3. androgens, which are male sex hormones NMHS33250 Congenital adrenal hyperplasia (CAH) (GOSH, 2018) Congenital adrenal hyperplasia is group of inherited conditions that are present at birth (congenital) where the adrenal gland is larger than usual (hyperplasia). In CAH, the body is missing an enzyme (chemical substance) that stimulates the adrenal glands to release the cortisol hormone. Lacking this hormone means that the body is less able to cope with physiological stress, which can be life threatening. It also makes the level of androgen (male hormone) increase, which causes male characteristics to appear early in boys or inappropriately in girls. NMHS33250  Congenital adrenal hyperplasia (CAH) ▪ Approximate incidence of 1:1,000 live births ▪ It is an autosomal recessively inherited condition causing inadequate production of cortisol and aldosterone and excess adrenal androgens. ▪ Specific enzymes are involved in synthesis of adrenal steroid hormones. ▪ CAH is categorised as salt wasting, simple virilising and non-classical (Knowles et al 2014). ▪ A deficiency in the enzyme 21-hydroxylase is the most common category of CAH(90-95%) NMHS33250 Congenital Adrenal Hyperplasia CAH is disorder of adrenal cortex 11-Beta hydroxylase deficiency 17a-hydroxylase deficiency 21-hydroxylase deficiency 3-Beta-hydroxysteroid dehydrogenase deficiency congenital lipoid adrenal hyperplasia p450 oxidoreductase deficiency NMHS33250 Types (1) 21-hydroxylase deficiency: An enzyme deficiency in the synthesis of cortisol and aldosterone (2) Salt wasting: Insufficient production of aldosterone and cortisol leading to loss of sodium (3) Virilising: Masculinisation of external genitalia due to excessive androgen production in fetal development, about tenth week of gestation or can present later in childhood NMHS33250 Signs and Symptoms Nausea, Vomiting, Fatigue/lethargyDizziness Hypotension Weight loss Salt craving (primary adrenal insufficiency) Hyperpigmentation (seen in chronic Addison’s disease). This may be generalised (child may be sallow in appearance) or localised to areas such as knuckles, elbows and knees Abdominal pain and pyrexia (seen in acute onset) Ambiguous genitalia NMHS33250 Diagnosis (GOSH, 2018) Most cases of CAH are diagnosed soon after birth or in early childhood CAH can be diagnosed before birth now that the affected gene has been identified. If a baby is born with ambiguous genitalia, blood tests are usually used to determine genetic gender. Blood and urine tests are also used to work out the levels of minerals and hormones in the body, so that they can be replaced. X-rays to look at a child’s bone age Genetic testing may be used to identify the specific type of CAH and the associated gene deficiency or mutation. NMHS33250 Management (GOSH, 2018) Children with Congenital Adrenal Hyperplasia (CAH) are usually managed by a multidisciplinary team, including endocrinologists and urologists (genitourinary system specialists). Initial treatment involves stabilising the child with intravenous fluids to restore electrolyte balance. Once stabilised, cortisol and/or aldosterone replacement therapy begins, with regular blood tests to monitor hormone levels for optimal dosing. Treatment aims to suppress excess adrenal hormone production using oral glucocorticoids (cortisol) or, in some cases, reconstructive surgery. In cases of cortisol deficiency, the inability to produce additional cortisol during illness can be life-threatening. NMHS33250 Cortisol Function Regulating your body’s stress response. Helping control your metabolism. Suppressing inflammation. Regulating blood pressure. Regulating blood sugar. Helping control your sleep-wake cycle. NMHS33250 Adrenal Insufficiency (Addison) Deficiency of Rare glucocorticoids (cortisol) Autoimmune process Weakness, fatigue, (may be acquired post anorexia, skin changes, bacterial or fungal bronzing of skin, , infection) abdominal pain, Adrenal crisis – fluid Treatment – oral resuscitation, IV hydrocortisone glucose, IV hydrocortisone NMHS33250 Adrenal crisis An adrenal crisis is a life-threatening condition in which your adrenal glands don’t make enough cortisol. Causes include damage to your adrenal glands and other stressors. Symptoms include abdominal pain, fatigue and weakness. Healthcare providers can diagnose an adrenal crisis with different blood tests. Treatment includes hydrocortisone injections. An adrenal crisis may cause a lack of blood flow (shock). Shock progresses quickly and may damage your organs. Without treatment, up to 20% of people in shock may die from an adrenal crisis. An adrenal crisis can affect anyone. However, it most commonly affects people between the ages of 30 and 50. NMHS33250 Reproductive Glands 2 ovaries in the female 2 testes in the male Both necessary for puberty and fertility NMHS33250 Hormones Affecting Puberty GnRH (Hypothalamus) Stimulates pituitary gland to produce gonadotropins LH and FSH (Pituitary) LH controls production of testosterone in boys and triggers ovulation and controls menstruation in girls FSH controls sperm production in boys and starts the ova ripening and helps control the menstrual cycle in girls. Oestrogen and Progesterone Testosterone (Testes) (Ovaries) Controls male sexual Act with LH and FSH to control development the menstrual cycle Oestrogen also controls female sexual development NMHS33250 Pubertal hormones Gland Hormone Action Hypothalamus Gonadotrophin-releasing hormone Stimulates the anterior pituitary (GnRH) gland to produce gonadotrophins Anterior pituitary Luteinising hormone (LH) Controls production of testosterone Triggers ovulation Follicle-stimulating hormone (FSH) Controls sperm production Helps control menstrual cycle Ovaries Oestrogen Initiates and advances female sexual development Progesterone and oestrogen Acts with FSH and LH to control menstrual cycle Testes Testosterone Initiates and advances male sexual development NMHS33250 Precocious Puberty The parents of a 6-year-old girl bring her to a pediatrician because of breast development. Her medical history is unremarkable. The parents are of average height, and the mother reports first menstruating when she was 11 years old. On physical examination, the girl is 125 cm tall (in the 97th percentile for her age), weighs 28 kg, and has a body-mass index of 17.9 (90th percentile for her age). Her breast development is classified as Tanner stage 3, and she has Tanner stage 2 pubic hair. Review of her previous growth data indicates that she has grown 8 cm during the past year. How should her condition be evaluated and managed? Carel, J., M.D., & Léger, J., MD. (2008). Precocious puberty. The New England Journal of Medicine, 358(22), 2366- 2377. doi:https://doi.org/10.1056/NEJMcp0800459 NMHS33250 Precocious puberty When puberty begins before age 8 in girls and before age 9 in boys, it is considered precocious puberty The cause of precocious puberty often can't be found. Rarely, certain conditions, such as infections, hormone disorders, tumors, brain abnormalities or injuries, may cause precocious puberty. Treatment for precocious puberty typically includes medication to delay further development. NMHS33250 Symptoms Enlarged testicles Breast growth and and penis, facial Pubic or underarm first period in girls hair and deepening hair voice in boys Rapid growth Acne Adult body odor NMHS33250 Causes of early puberty (HSE, 2022) It's not always clear what causes early puberty. It may be something that runs in your family. Sometimes the cause can be: a problem in the brain, such as a tumor damage to the brain as a result of an infection, surgery, or radiotherapy a problem with the ovaries or thyroid gland a genetic disorder, such as McCune-Albright syndrome Early puberty mostly affects girls and often has no obvious cause. It's less common in boys. NMHS33250  Central precocious puberty ▪ Central precocious puberty (CPP) is characteriSed by the same biochemical and physical features as normally timed puberty but occurs at an abnormally early age ▪ Most cases of CPP are seen in girls, in whom it is usually idiopathic ▪ In rare cases, central precocious puberty may be caused by: ▪ A tumor in the brain or spinal cord (central nervous system) ▪ A defect in the brain present at birth, such as excess fluid buildup (hydrocephalus) or a noncancerous tumor (hamartoma) ▪ Radiation to the brain or spinal cord ▪ Injury to the brain or spinal cord ▪ McCune-Albright syndrome — a rare genetic disease that affects bones and skin color and causes hormonal problems ▪ Congenital adrenal hyperplasia — a group of genetic disorders involving abnormal hormone production by NMHS33250 the adrenal glands ▪ Hypothyroidism — a condition in which the thyroid gland doesn't produce enough hormones NMHS33250 Estrogen or testosterone in your child's body causes this type of precocious puberty. In both girls and boys, the following may lead to peripheral precocious puberty: ▪ A tumor in the adrenal glands or in the pituitary Peripheral gland that releases estrogen or testosterone ▪ McCune-Albright syndrome, a rare genetic precocious disorder that affects the skin color and bones and causes hormonal problems puberty ▪ Exposure to external sources of estrogen or testosterone, such as creams or ointments In girls, peripheral precocious puberty may also be associated with: ▪ Ovarian cysts ▪ Ovarian tumors NMHS33250 Keeping your child away from external sources of estrogen and testosterone — such as prescription medications for adults in the house or dietary supplements containing estrogen or testosterone. Precautions Encouraging your child to maintain a healthy weight NMHS33250 a blood test to check hormone levels a hand x-ray to help determine likely Tests and adult height an ultrasound scan or MRI scan to treatments check for problems such as tumors for early puberty Treatment for early puberty (HSE, 2022) includes: treating any underlying cause using medication to reduce hormone levels and pause sexual development NMHS33250 Tanner staging, also known as Sexual Maturity Rating (SMR) is an objective classification system that providers use to document and track the development and sequence of secondary sex Diagnostic characteristics of children during puberty. investigations Tanner Stage 1 corresponds to the pre-pubertal form for all three development sites, with progression to Tanner Stage 5, the final adult form.  Pubic Hair Scale (both males and NMHS33250 females) 1 2 3 4 5 Stage 1: No hair Stage 2: Downy hair Stage 3: Scant Stage 4: Terminal Stage 5: Terminal terminal hair hair that fills the hair that extends entire triangle beyond the inguinal overlying the pubic crease onto the region thigh  Female Breast Development Scale NMHS33250 1 2 3 4 5 Stage 1: No Stage 2: Breast bud Stage 3: Breast Stage 4: Areola Stage 5: The areolar glandular breast palpable under the tissue palpable elevated above the mound recedes into tissue palpable areola (1st pubertal outside areola; no contour of the a single breast sign in females) areolar breast, forming a contour with areolar development “double scoop” hyperpigmentation, appearance papillaedevelopmen t, and nipple protrusion  Male External Genitalia Scale NMHS33250 1 2 3 4 5 Stage 1: Testicular Stage 2: 4 ml-8 ml (or Stage 3: 9 ml-12 ml Stage 4: 15-20 ml (or Stage 5: > 20 ml (or > volume < 4 ml or long 2.5 to 3.3 cm long), (or 3.4 to 4.0 cm 4.1 to 4.5 cm long) 4.5 cm long) axis < 2.5 cm 1st pubertal sign in long) males NMHS33250 Prader orchidometer The measurement of testicular volume (TV) by Prader orchidometer is a practical and inexpensive method of pubertal staging, with testicular size correlating to pubertal stage NMHS33250 Central precocious puberty (CPP) evaluation ± treatment of the underlying cause Plus – gonadotrophin-releasing hormone (GnRH) agonist Consider – growth hormone (GH) NMHS33250  Delayed puberty NMHS33250 Boys have no signs of testicular development by 14 years of age girls have not started to develop breasts by 13 years of age girls have developed breasts but their periods have not started by 15  Causes of delayed puberty NMHS33250 ▪ It's not always clear what causes delayed puberty ▪ a long-term illness, such as cystic fibrosis, diabetes or kidney disease ▪ malnutrition, from an eating disorder or a condition such as cystic fibrosis or coeliac disease ▪ a problem with the ovaries, testes, thyroid gland or pituitary gland ▪ a disorder of sexual development, such as androgen insensitivity syndrome ▪ a genetic condition, such as Kallman syndrome and Klinefelter syndrome NMHS33250 ▪ a blood test to check hormone levels ▪ a hand x-ray to help determine likely adult height Tests and ▪ an ultrasound scan or MRI scan to treatments for check for problems with glands or organs delayed puberty ▪ Treatment for delayed puberty (HSE, 2022) includes: ▪ treating any underlying cause ▪ using medication for a few months to increase hormone levels and trigger the start of puberty  Disorders of sex development NMHS33250 There are some congenital conditions in which children who have the outward appearance of one sex, may genetically be of the opposite sex. There are also conditions where children have extra chromosomes in different combinations such as XXY, XXXY, or XXYY or missing chromosomes (45X). Most people are born with 46 chromosomes, 44 of which are in 22 pairs. The remaining two are what determines sex at birth. Most males have one X chromosome and one Y chromosome, while most females have two X chromosomes.  Disorders of sex development NMHS33250 5 alpha reductace deficiency Androgen Insensitivity Syndrome Cryptorchidism/ Undescended testes Hypospadias Klinefelter’s syndrome Micropenis Mixed Gonadal Dysgenesis 5 alpha reductace  Klinefelter’s syndrome NMHS33250 Klinefelter’s syndrome results from an extra X chromosome in a male giving a karyotype of 47XXY. It is one of the more common chromosomal anomalies. There may also be undescended testes at birth. Often the diagnosis is not made until puberty as the symptoms are subtle. Symptoms may include muscle weakness, sparse body hair, small genitalia and breast growth and the child may also have developmental delay. In later life infertility is a primary feature. Pediatric Disorders of Sexual Development (DSD) A pediatric disorder of sexual development (DSD) happens when a child is born with sex organs that did not develop properly due to a chromosomal abnormality or the production of hormones. The disorder can range from mild to serious, affecting the development of genitalia and reproductive organs at different ages. It may be hard to tell if the child is male or female at birth, or the disorder can become apparent during puberty when sex hormones trigger growth and secondary sex changes. NMHS33250 Growth in Childhood NMHS33250 NMHS33250 Normal Growth: 3 Phases Infancy: Rapid Growth (approx. 24 cms in the first year) Childhood: extends through school until the child reaches adolescence Pubertal Growth Spurt (Rapid Growth) Age Range: Onset of puberty to adulthood (typically 10-14 for girls, 12-16 for boys) The GH-RH/GH/IGF-1* axis: the hormonal stimulation and suppression pathways that bring about linear growth NMHS33250 Causes of Short Stature Genetic short stature Pubertal and Growth SGA/IUGR Delay Dysmorphic Endocrine Disorders Chronic Paediatric Syndromes i.e.: Turner eg: GHD, Cushing’s diseases i.e.: Asthma, Syndrome, Prader-Willi syndrome and UnTx JIA, and renal failure syndrome hypothyroidism Psychosocial deprivation NMHS33250  Puberty and Growth NMHS33250 Adolescent growth spurt (AGS) is the most rapid phase of growth after the neonatal/postnatal period. There is a well-recognised phenomenon of men being taller than women – with an average 13-14cm height difference (Raine et al 2011) On average, puberty for girls starts two years before boys and it stops two years earlier, which means that boys have two further years of prepubertal growth. The peak height velocity for girls during puberty is about 8cm a year, compared with about 10cm a year for boys.  Puberty NMHS33250 ▪ Most complex growth phase ▪ Pattern of growth changes between sexes ▪ Starts with breast enlargement in girls and testicular enlargement in boys ▪ AGS starts 2 years earlier in girls than boys ▪ Average differences in adult final height is approx. ▪ 13 -14 cms ▪ Auxology is the scientific term that describes the study of human growth and development using repeated measurements of the same individual over a period of time (Raine et al 2011).  Head circumference (Martin and Collin, 2015) Newborn head circumference is on average 33-35cm. Average head growth is 1-1.5cm per month in the first year, and increase reflects brain growth. A tape measure should be positioned midway between the eyebrows and hairline, and over the occipital prominence at the back. NMHS33250 Using a stadiometer to measure height (Martin and Collin, 2015) NMHS33250 NMHS33250 Length For babies and toddlers, a neonatometer or infantometer is used. These are horizontal, flat-surfaced pieces of equipment with a fixed headboard and movable footplate. Two people are required to carry out this procedure, and whenever possible the parent or carer should be involved. To comfort the infant, the parent or carer should stand at the head of the infantometer  Other factors used in the assessment of growth NMHS33250 Decimal age Age is expressed as a decimal rather than in years and months, for example, five years and three months = 5.25 years Height velocity Calculated by dividing the change in height by the period of time that has passed Body mass index (BMI) Expressed as weight in kilograms divided by the square of the height in metres, that is, weight in kilograms/(height in metres x height in metres) https://bmicalculatorireland.com/ Skeletal assessment of Often referred to as ‘bone age’ bone maturation Radiological means of assessing a growing child’s skeletal maturity  Diagnosis Growth measurement and plotting. Check that the height velocity is normal over a reasonable period of time (usually at least a year) Bone age Bone age is a measure of the space left before growth ceases. Bone age is of little value in children under 3. Calculate parental target height People can be very inaccurate in estimating height so measure parents if required. This is definitely not a “height prediction” (so don’t tell the parents that) but a rough assessment of genetic contribution to height. karyotype* The features of Turner syndrome FBC ESR Coeliac set B12, folate Serum iron, ferritin The pick up of coeliac disease and other gastrointestinal problems in short children is extremely low- excluding this as a cause may be of value. NMHS33250 Testing ▪ Thyroid function ▪ IGF 1, IGFBP3, LFTs ▪ A marker of GH action- may be helpful if GH deficiency seems likely ▪ Skeletal survey: Consider a skeletal dysplasia if the child is disproportionate. ▪ Glucagon stimulation test NMHS33250  Diagnosis NMHS33250 Growth measurement and plotting. Check that the height velocity is normal over a reasonable period of time (usually at least a year) Bone age Bone age is a measure of the space left before growth ceases. Bone age is of little value in children under 3. Calculate parental target height People can be very inaccurate in estimating height so measure parents if required. This is definitely not a “height prediction” (so don’t tell the parents that) but a rough assessment of genetic contribution to height. karyotype* The features of Turner syndrome FBC ESR Coeliac set B12, folate Serum iron, ferritin The pick up of coeliac disease and other gastrointestinal problems in short children is extremely low- excluding this as a cause may be of value.  Testing ▪ Thyroid function ▪ IGF 1, IGFBP3, LFTs ▪ A marker of GH action- may be helpful if GH deficiency seems likely ▪ Skeletal survey: Consider a skeletal dysplasia if the child is disproportionate. ▪ Glucagon stimulation test ▪ Insulin-like Growth Factor-1 (IGF-1) ▪ Insulin-like growth factor-binding protein 3, also known as IGFBP- NMHS33250 3  Treatment Growth Hormone Replacement: A single daily injection of recombinant growth hormone can provide physiologic replacement. In order for growth hormone replacement to be effective, other pituitary deficiencies should be treated. Response to growth hormone therapy is measured (every 3-6 mo) by sequential height determinations and by occasional bone age determinations. Growth hormone replacement – Somatotropin ( NICE guidelines 2002) Growth hormone resistant – Mecasermin (Increlex) NMHS33250 Daily subcutaneous injection NMHS33250 Deodati & Cianfarani S. (2017) Indications approved by Food and Drug Administration and European Medicines Agency for growth hormone therapy Assessment Management of symptoms To maintain adequate growth of height and weight To educate parents on the importance Nursing of proper medication administration Management To monitor thyroid hormone levels frequently. Providing support NMHS33250  Learning outcomes ❖Defined endocrine system ❖Identified the function of important hormone of the endocrine system ❖Discussed clinical manifestations that indicate a endocrine conditions in childhood ❖Understood diagnosis and management of common endocrine conditions in childhood ❖Discussed the care of a child with altered endocrine functions NMHS33250  Reference NMHS33250 Hendry, C., Farley, A., McLafferty, E. and Johnstone, C. (2013) 'Endocrine system: part 2', Nursing Standard, 28(39), pp. 43-48. doi: 10.7748/ns.28.39.43.e7778. Scott, W.N. (2011) Anatomy & Physiology Made Incredibly Easy. Philadelphia, PA: Lippincott Williams & Wilkins. Johnstone, C., Hendry, C., Farley, A. and McLafferty, E. (2013) 'Endocrine system: part 1', Nursing Standard, 28(38), pp. 42-49. doi: 10.7748/ns.28.38.42.e7471. Gelder, C. (2014) 'Best practice injection technique for children and young people with diabetes', Nursing Children and Young People, 26(7), pp. 32-36. doi: 10.7748/ncyp.26.7.32.e458. Martin, L. and Collin, J. (2015) 'An introduction to growth and atypical growth in childhood and adolescence', Nursing Children and Young People, 27(6), pp. 29-37. doi: 10.7748/ncyp.27.6.29.e591.  Reference NMHS33250 Patti, G., Ibba, A., Morana, G., Napoli, F., Fava, D., di Iorgi, N. and Maghnie, M. (2020) 'Central diabetes insipidus in children: Diagnosis and management', Best Practice & Research Clinical Endocrinology & Metabolism, 34(5), pp. 101440. doi: 10.1016/j.beem.2020.101440. Epub 2020 Jun 29. PMID: 32646670. Thornton, P.S., Stanley, C.A., De Leon, D.D., Harris, D., Haymond, M.W., Hussain, K. and others (2015) 'Recommendations from the Pediatric Endocrine Society for Evaluation and Management of Persistent Hypoglycemia in Neonates, Infants, and Children', The Journal of Pediatrics, 167(2), pp. 238–245. Marshall, W.A. and Tanner, J.M. (1969) 'Variations in pattern of pubertal changes in girls', Archives of Disease in Childhood, 44(235), pp. 291-303.Kang, E., Cho, J.H., Choi, J.H. and Yoo, H.W. (2016) 'Etiology and therapeutic outcomes of children with gonadotropin-independent precocious puberty', Annals of Pediatric Endocrinology & Metabolism, 21(3), pp. 136-142. doi: 10.6065/apem.2016.21.3.136. Epub 2016 Sep 30. PMID: 27777905; PMCID: PMC5073159. Deodati, A. and Cianfarani, S. (2017) 'The Rationale for Growth Hormone Therapy in Children with Short Stature', Journal of Clinical Research in Pediatric Endocrinology, 9(Suppl 2), pp. 23-32. doi: 10.4274/jcrpe.2017.S003. Epub 2017 Dec 27. PMID: 29280742; PMCID: PMC5790327. NMHS33250