Endocrinology Past Paper PDF

140 Introduction  Endocrine system is like an orchestra  Hypothalamus is the maestro  Pituitary is the conductor  Glands are musicians Causes of hormonal disorders:  Hypothalamus affected by severe CNS insult affects it.  Like encephalitis, trauma, t...

140 Introduction  Endocrine system is like an orchestra  Hypothalamus is the maestro  Pituitary is the conductor  Glands are musicians Causes of hormonal disorders:  Hypothalamus affected by severe CNS insult affects it.  Like encephalitis, trauma, tumor, toxins  Pituitary gland affected mainly by tumor  such as craniopharyngeoma  or trauma to the nose roof  Causes: CITTTAN Hormones of hypothalamus: Releasing factors of hormones:  ACTH –RF  TSH-RF  FSH-RF  LH-RF  GH-RF Every hormone disorder could be:  Congenital  Increase secretion  Central: deficiency  Acquired  Decrease secretion  Peripheral: unresponsive receptors Hormones of pituitary gland: Hormones of pituitary gland: Anterior pituitary: Posterior pituitary:  ACTH  Vasopressin  TSH  Oxytocin  FSH  GH  FSH  LH  PL  141 A. Hormones of posterior pituitary 1. Antidiuretic hormone=vasopressin: It is responsible for reabsorption of water by kidney tubules Diabetes insipidus Its deficiency leads to diabetes insipidus Its increase release leads to SIADH Types:  Central  Peripheral Clinical picture:  Vomiting  Dehydration  Failure to thrive  Unexplained fever  Electrolytes disorder& seizures  Older children: Polyuria& polydipsia > 2 L/m2/day Investigations:  Urine sp. Gravity: low : 1002-1005 mos/L  Plasma osmolality: high:> 295 mos/L  Water deprivation test for 6 hours  Vasopressin stimulation test Management: Supportive& Specific: Central DI:  Correct dehydration  Correct failure to thrive  Correct electrolyte disturbance  Desmopressin intranasal spray BD or IV or PO Peripheral DI:  Correct dehydration  Correct electrolyte disturbance  Indomethacin oral tablets daily  Potassium sparing diuretics e.g. hydrochlorothiazide Give desmopressin as diagnostic therapy: Concentrated urine ……… Central cause No or Partial response …….. Nephrogenic or Peripheral cause  142 Syndrome of inappropriate antiduretic hormone secretion SIADH  Over secretion of ADH leads to water retention  It occurs in meningitis, encephalitis, head trauma, head surgery…etc Clinical picture:  Patient in PICU post RTA or encephalitis   level of consciousness  Oliguria +/-  Na  No signs of shock Investigations:  Normal HCO3  Hyponatremia 95th centile. Acromegaly: if it increase after puberty. Prominence of chin, fingers& nose Decrease production: Short stature < 3rd centile Growth hormone deficiency: Clinical picture: Growth hormone  Normal at birth.  With time gets short& chubby.  He has normal mental& motor development. Diagnosis of GH deficiency:  Exclude familial cause  Exclude constitutional cause Primordial dwarfism  Exclude pathological causes e.g. chronic illness, nutritional, intrauterine insult, psychological causes, other endocrine disorder, disproportionate short stature or genetic diseases e.g. down $. Evaluation of short stature: A SHORT  Age: Chronological age/ Height age/ Bone age  Segments: upper/lower (proportionate)  Height of parents: Mid-parental height Ruussel-silver syndrome  Obesity/Other dysmorphism  Rapidity of growth  Tanner staging Investigations:  Wrist X-ray  Exclude FTT causes  IGF-1 for screening first  IGF-BP 3 insulin lie growth factor binding protein 3  GH provocation test, ATT, thyroid profile, urine analysis Management:  Growth hormone S.C. or IM  0.15-0.3 mg/kg/week in 6 days/week at bedtime  Follow pt& titrate dose accordingly.  height 4-6 cm.  Stimulate its excretion by early bedtime, playing& avoid sweets.  144 Indications of growth hormone:  GH deficiency  Chronic renal failure  Idiopathic short stature  Small for gestational age  Turner syndrome& noonan syndrome  Russel silver syndrome& prader willi syndrome Growth hormone resistance: Infant delivered smaller than usual. They persists like a doll. The disorder is defective receptor response to growth hormone. Follow up of growth must be done routine for every child in every visit. If the patient doesn’t respond to growth hormone or it is severe short stature, consider IUGR or intrauterine insult, nutritional cause or other endocrine or syndrome is hidden. Growth hormone resistance syndromes Primordial dwarfism  Seckel $  Laroon $  Temple $  Russel-silver $  Prader-willi $  Bradet Biedl Moon $ Management:  A trial of growth hormone in infancy  Avoid hypoglycemia in some cases Seckel syndrome  145 Other hormones of anterior pituitary gland Other hormones of anterior pituitary gland:  Endorphin  Prolactin hormone  Luteinizing hormone  Follicular stimulating hormone  Thyroid stimulating hormone  Adreno-cortico-trophic hormone Endorphine: It is responsible for pain control Its action is similar to morphine. Now it is believed that it is hormone of happiness. In addition to other hormones like dopamine, serotonin& oxytocin. Prolactin hormone: It is important for milk synthesis. Overproduction leads to milk over production. Luteinizing hormone: Important for ova release from ovary. Follicular stimulating hormone: It is important in menstrual cycle And for ova production Thyroid stimulating hormone: It is responsible to stimulate thyroid to release thyroxin Adrenocorticotropic hormone: it is the coordinator of steroids& androgen release from suprarenal gland.  146 Thyroid disorders The thyroid is like butterfly in the neck It is responsible for anabolism, mental& motor growth Thyroid profile:  TSH-RF  TSH  T3  T4 Thyroid disorders:  Hypothyroidism  Hyperthyroidism Hypothyroidism:  Congenital hypothyroidism  Acquired& late hypothyroidism Hypothyroidism: Congenital Neonatal screening for all deliveries to discover the S&S early and treat before squeals Clinical picture: Infant S&S: Neonatal S&S:  Wrinkled forehead  Sleepy  Sparse eyebrows  Anemia  Low hairlines  Lethargy  Puffy eyelids  Hoarse cry  Large tongue  Constipation  Thick lips  Feeding difficulties  Cold  Abdominal distension  Cold dry rough thick skin Child S&S:  Prolonged physiological jaundice  Widely open anterior fontanel  Scanty rough dry scalp hair Late S&S:  Rough dry thick cold skin  Fatigue  Dentition is delayed  Hair loss  Short neck with fat  Depression  Short broad hands  Puffy face& lids  Distended abdomen  Loss of eyebrows  Umbilical hernia  Rough, deep voice  Hoarse voice  Goiter& low heart rate  Constipation  Weight gain& constipation  Hypotonia  Dry rough pale cold bold skin  Anemia  Amenorrhea, infertility& decreased desire  147 Investigations:  T3, T4, TSH  Wrist X-ray Management:  L-troxin tab on empty stomach  Neonate: 15 mcg/kg/day  Infant: 10 mcg/kg/day  Child: 5 mcg/kg/day  TSH F/up monthly Hyperthyroidism: Congenital Transient: It happen in infant of hyperthyroid mother or receiving thyroxin Neonatal S&S: Child S&S:  Irritable  Goiter  Cachexic  Tremor  Tachycardia  Fatigue  Exophthalmous  Sweating  Hyperdefecation  Nervous  Shiny, smooth skin  Hair loss  lid lag, ophthalmopathy  Sweating  Tachycardia Management:  Muscle pain  Propylthiouracil tab. 5-7 mg/kg/day or  Weight loss  Methimazole tab. 0.5-0.7 mg/kg/day  Exophthalmous  Propranolol tab. 2-3 mg/kg/day  Menorrhagia& infertility  Is started if symptoms are severe& tachycardia  Surgical treatment consists of partial or complete thyroidectomy Goiter: Congenital: It is due to high TSH due to low thyroxin (maternal ingestion of antithyroid drugs) Acquired:  Hashimoto thyroiditis: in females (Autoimmune disorder leads to hypothyroidism)  Endemic goiter: due to low iodine intake Common in mountainous areas. Investigations:  T3, T4, TSH Management:  L-troxin tab  Monthly F/up of T3,T4,TSH  148 Parathyroid hormone  It is responsible for calcium& phosphate metabolism  It mobilized calcium& phosphorus from the bone to blood  Increase calcium reabsorption from the kidney  Increase phosphate excretion to urine  Increase calcium uptake by intestine Hypoparathyridism: Congenital: Transient neonatal hypocalcemia in:  Preterm  Artificial milk  Low birth weight  Infant of diabetic mother  Infant of hyperparathormone mother Clinical picture:  Convulsions  Carpo-pedal spasm  Latent or overt tetany Acquired:  Autoimmune in:  Addison disease  Pernicious anemia  Hashimoto thyroiditis  Pseudohypoparathyoidism:  Unresponsive receptors in organs Management:  Calcium infusion 2 ml/kg/dose QID  Vitamin D Hyperparathyroidism: Clinical picture:  Hypercalcemia  Hypercalciuria  Hypophosphatemia  Extensive bone demineralization Management:  Calcitonin inj.  149 Diabetes mellitus Important definitions:  Normal blood glucose level: FBS 80 mg /dl RBS 120 mg / dl  Impaired glucose tolerance: Fasting glucose 125 mg/d OGTT: RBS >140 mg/dL (2 hours PP)  Diabetes mellitus: FBS > 125 mg/dl RBS > 200 mg / dl Pathogenesis of DM: Types of DM: A. Genetic predisposition: HLA-DR3&DR4  MEN B. Autoimmune antibodies against islet cells  MODY  Iatrogenic C. Progressive loss of beta cells function  IDDM type I D. Onset of clinical disease  NIDM type II E. Transient remission  Neonatal diabetes F. Established disease  Gestational diabetes G. Complications MEN: multiple endocrine neoplasia Clinical insulin deficiency stages: MODY: maturity onset diabetes of 1. Postprandial hyperglycemia. youth 2. Then fasting hyperglycemia. 3. Hyperglycemia exceeds the renal threshold for glucose reabsorption (approximately 180 mg/dL), glycosuria occurs. 4. Glycosuria causes an osmotic diuresis (including obligate loss of sodium, potassium, and other electrolytes), leading to dehydration. 5. Polydipsia occurs as the patient attempts to compensate for the excess fluid losses. 6. Weight loss results from the persistent catabolic state and the loss of calories through glycosuria& ketonuria. 7. Ketogenesis is a sign of more complete insulin deficiency 8. The classic presentation of DM1 in adults is polyuria, polydipsia, polyphagia, and weight loss, but it differs in pediatrics.  150 Predisposing factors:  Seasons: after autumn  Stressful event as fear or anger  Viruses: mumps, CMV& rubella  Cow milk feeding before 2 years age  Early introduction of gluten to infant’s food  Due to similar antigen to immature gut protein  Bovine serum albumin similar to human glycodelin PP4 IDDM co-morbidities:  Hashimoto thyroiditis  Celiac disease  Vitiligo Classification of diabetes mellitus Type I Type II Etiology Autoimmune Insulin resistance Peak age 12 years 60 years Prevalence 0.3% 6% Presentation Osmotic S& S Weight loss Osmotic symptoms DKA Patients usually obese Diabetic complications Management Diet& insulin Diet& exercise Oral hypoglycemic insulin later Classic clinical picture: 4 P  Polyuria  Polydepsia  Polyphagia  Body weight loss Investigations:  FBS, RBS, HbA1c  GUE, CBC, CRP  Others Management:  Insulin  Diet& lifestyle changes but not like adults. IDDM treatment goals:  Insulin daily for life.  Normal activity, growth& development.  Proper action with the disease & the treatment.  151 Types of insulin:  Very short acting: Lispro, aspart,  Short acting Regular  Intermediate acting: NPH, lente  Long acting: Glargine, ultralente Usually the patient take combination of 2 types of insulin: The best regimen is: aspart& glargin Other regimen is: lispro& ultralent Other regimen is: lispro& NPH Start RBS correction by the following table Sub-cutaneous insulin dosing in pediatrics Age Target Target insulin Basal insulin Bolus insulin Bolus Years glucose IU/Kg/day % of total Per 100 insulin mmg/dl insulin dose mg/dl above Per 15 g of target meal 0-5 100-200 0.6-0.7 25-30 0.5 0.5 5-12 80-150 0.7-1.0 40-50 0.75 0.75 12-18 80-130 1.0-1.2 40-50 1.0-2.0 1.0-2.0 Education:  How store insulin  How to measure RBS  How to calculate insulin units  How to draw insulin in its syringe  How & where to do the injection for himself  Insulin by SC administration or pump or inhaler  Regular F/up to control RBS, search for complications  152 Follow up: Short term F/up:  UOP& BW  FBS, RBS& PPBS Long term F/up:  HA1c: 6-8 every 3 mo  Annual ophthalmic F/up  Annual GUE for albuminuria  Annual BP F/up & lipid profile Long-term complications of DM type 1 include:  Retinopathy  Nephropathy  Neuropathy  Angiopathy Side effects of insulin: Acute: Hypoglycemia: S&S are He is TIRED:  Headache  Sweating Glucometer  Tachycardia  Irritability  Restlessness  Excessive hunger Insulin syringe  Diaphoresis/ Drowsiness Chronic: Insulin antibodies Atrophy or hypertrophy of S.C. fat. Management of hypoglycemia: If the patient is alert: oral sugar water Insulin pen If unconscious: IV bolus of DW 10% 4 ml/kg then maintenance. Atrophy& hypertrophy  153 Usual problems during treatment: Honeymoon period: Stable RBS Reason: The remaining functional beta cells seem to recover Action: decrease insulin dose but not stop Down phenomenon: Glucometer patch High morning FBS Reason: increase counter regulatory hormones Action: Increase intermediate insulin Somogi phenomenon: High morning FBS Reason: high insulin then high counter hormones Action: decrease intermediate insulin Insulin S.C. pump Brittle diabetes: Adolescent female, with fluctuating RBS Reason: hormonal changes during menstruation Evidence of organ damage caused by hyperglycemia is rare in patients with duration of diabetes of less than 5 to 10 years. So, complication usually occurs in late adolescent Diabetic ketoacidosis DKA: It will be discussed in emergency chapter. NIDDM type II: Very rare disorder in children. It comes in obese children with family history of NIDDM Management: Oral hypoglycemic drugs  154 Adrenal gland It is located above the kidney& secretes different types of hormones Adrenal gland parts:  Cortex  Medulla Adrenal gland cortex hormones:  It is responsible for 3 S hormones  Salt, Sugar & Sex hormones  Zona glomerulosa: Salt hormones: Mineralocorticoids: Aldosterone& Corticosterone  Zona fasciculate: Sugar hormones: Glucocorticoids: Cortisol& Cortisone  Zona reticularis: Sex hormones: Androgens: Estrogen& Testosterone Adrenal gland medulla hormones:  It is responsible for 2 S hormones Stress hormones: Catecholamines:  Adrenaline  Noradrenaline Disorders of adrenal gland: Hypoactivity:  Acute insufficiency: adrenal crisis or addisonian crisis  Chronic insufficiency: Addison disease  Congenital adrenal hyperplasia Hyperactivity  Cushing syndrome  Hyperaldosteronism  Adrenogenital syndrome  155 Adrenal insufficiency: Primary, secondary& tertiary. Acute adrenal insufficiency=Addisonian crisis:  Abdominal pain, vomiting, diarrhea& dehydration  Delirium or confusion, hypoglycemia& general weakness  In addition to hypotension, hyperkalemia, hyponatremia& shock Chronic adrenal insufficiency: Addison disease:  It grows very slowly over months  Suppression of gland by prolonged steroid use  When the patient developed any stress as illness it becomes clear  Weakness, skin pigmentation& striae, hypotension, hypoglycemia, anorexia  Salt craving, abdominal pain, muscle pain, depression, hair loss, sexual dysfunction Causes: ADDISON  Autoimmune  Drugs: ketoconazole, DIC  Degenerative: amyloidosis  Infectious agents: TB& HIV& Iatrogenic  Secondary causes: hypopituitarism  Other causes: adrenal hemorrhage  Neoplasia& Nelson syndrome Clinical picture: FATIGUED  Fatigue  Antibodies anti-adrenal- antithyroid, antiparietal cells  Triad of: hyponatremia. Hyperkalemia& azotemia  Increased pigmentation of skin& tongue  Gastrintestinal: anorexia& BW  Nausea& vomiting  Electrolytes disturbance  Dehydration Investigations:  Cortisol at 8 AM  ACTH stimulation test Management:  Rapid volume expansion to correct hypotension  Sufficient dextrose infusion to correct hypoglycemia  Hydrocortisone 50 mg/m2 IV bolus followed by 50 mg/m2/day infusion  156 Congenital adrenal insufficiency= Congenital adrenal hyperplasia  Autosomal recessive disease  It is characterized by deficiency of the enzyme required for cortisol  Cortisol deficiency leads to high ACTH adrenal hyperplasia  The most common form is ambiguous genitalia in girls  21-hydroxylase deficiency accounts for 90% of cases Types:  Classic: complete enzyme deficiency o Salt wasting: severe due to loss of both hormones o Non salt wasting: less severe due to preserved mineralocorticoid o Occurs at 1-2 weeks with S&S of adrenal insuffucincy o Diagnosis: 17-hydroxyprogesterone, testosterone in ♀ &androstenedione in ♂  Non classic: partial enzyme deficiency o Simple virilizing form, the adrenal insufficiency occurs under stress. o Manifested as androgen excess after infancy; precocious pubarche, irregular menses, hirsutism, acne& advanced bone age. o Diagnosis: 17-hydroxyprogesterone, but it require ACTH stimulation test Gene mutation  21 hydroxylase deficiency Cortisol & Aldosterone  stimulate pituitary to release ACTH Adrenal hyperplasia   Androgen  size of clitoris Investigations:  Electrolytes  17- ketosteroids  Karyotyping  Buccal smear for bar bodies  Abdominal ultrasound to look for: uterus& vagina for ♀ or undescended testis in ♂  Biopsy& histopathology to determine the real sex* Management:  Identify sex early& give the name clearly  Glucocorticoid maintenance:  Adrenal insufficiency: Hydrocortisone 6-9 mg/m2/day PO  Congenital adrenal hyperplasia: 10-20 mg/m2/day  Titrate the dose according to skeletal development  Mineralocorticoid maintenance:  Salt losing form: Fludrocortisone 0.1-0.2 mg/day PO  Infants need 1-2 g of sodium daily requirement  Stress dose glucocorticoid: the dose should increase during illness  Stress dose: Hydrocortisone 25-50 mg/m2/day infusion or IV divided  Surgery or severe illness: 50-125 mg/m2/day IV  157 Cortisone excess:  Adrenogenital syndrome  Precocious puberty  Cushing syndrome True hermaphroditism: o Both male& female genitalia are present Pseudohermaphroditism: o Only one sex genitalia present but it is abnormal; o Large clitosis& labia majora fusion in females o Small penis& undescended testis in males Precocious puberty: Development of secondary sex characters before the expected age Usually before 10 years in boys& before 8 years in girls. Secondary sexual characters:  Breast   Acne vulgaris  Change in voice  Dark coarse pubic hair True precocious puberty: Occurrence of spermatogenesis or ovulation (mensis) due to activation of: Hypothalmic-pituitary axis LH& FSH Causes: Causes of gynecomastia:  Infection MAKE BREAST  Trauma  Marjuana  Tumor  Alcohol Pseudoprecocious puberty:  Klinefelter syndrome Appearance of secondary sexual characters only due to:  Estrogen excess  Baby ( maternal estrogen) Increase androgen-estrogen pathway  Receptor blocker Investigations: (ketoconaole, calcium blocker,  Radiology: H2 blocker)  Bone age  Elderly  Brain tumor  Antineoplastic agents  Endocrinology:  Spironolactone  17-ketosteroid  Tumors ( adrenal or testicular)  Pregnandiol, FSH&LH Management: Teamwork Search for the cause of abnormal hormonal release. Give counter hormonal therapy& surgical ttt. Precocious puberty is dangerous in boys. It is mostly malignant tumor.  158 Delayed puberty: Boys: no testicular enlargement after 14 years old. Girls: no pubertal development after 14 years old No menarche & no secondary sexual characters at 14 years old or No menarche but there is secondary sexual characters at 16 years old. lutenizing hormone& follicle-stimulating hormone is the corner stone Types:  Hypergonadotrophic hypogonadism: High LH& FSH means primary gonadal failure due to turner $, Klinefelter $, tumor, androgen insensitivity& chemotherapy.  Hypogonadotrophic hypogonadism: Low or normal LH& FSH due to isolated gonadotropin deficiency, pituitary tumor or other CNS tumor Evaluation of delayed puberty:  Hypopituitarism.  Constitutional delay  Chromosomal abnormality. Cushing syndrome: Causes: Exogenous: o Iatrogenic   CRH& ACTH Endogenous: o Pituitary adenoma:  ACTH o Para-neoplastic tumor o Adrenal carcinoma or nodular adrenal hyperplassia Clinical picture: Lemon on sticks  Generalized weakness  Bone osteoporosis Clinical picture:  Mood disorder MOON FACE  Moon face  Menstrual changes  Glaucoma  Osteoporosis  Cataract  Obesity  Obesity  Striae  Neurosis  HTN  Facial plethora  CMP  Altered muscle Management:  Calor (hot skin)  Stop the exogenous source of sateroid gradually  Elevated blood pressure  Search for the source of endogenous steroid  159 Medulla hormones: Adrenaline& noradrenaline They are fight or flight hormones They help the body to respond to stress by Adrenaline rush Pheochromocytoma: It is a tumor of adrenal medulla Neuroblastoma is a tumor of nerve ganglia or medulla Clinical picture (Main):  Abdominal bloating  Watery diarrhea  Hypertension  Anemia  Fever Symptoms of pheochromocytoma: 6P  Pallor  Palpitation  Perspiration  Panic attacks  Pain of the head  Postural dizziness Signs of pheochromocytoma:  Hypertension  Hyperglycemia  Tachycardia  Numbness  Sweating  Tremor  Pallor Investigations:  Urine VMA Management:  Supportive& specific  Control hypertension by labetalol  Surgery, radiation or ablation therapy of the tumor  160 Cortisol sequence Addison disease Cushing-adrenal tumor Cushing disease