e.g. LH/FSH; TSH, fT4; prolactin; cortisol (9 a.m.); speci \201 c tests to assess secretory capacity of Treatment involves adequate and appropriate hormone replacement therapy and, where applicab le, management of underlying cause. 12_McClure_12.indd 449 11/14/2012 3:27:05 PM CHAPTER 12 Endocrinology and diabetes 450 Posterior pituitary: diabetes insipidus The posterior pituitary gland secretes two hormones , arginine vasopressin (AVP) and oxytocin. Diabetes insipidus (DI) is de \201 ned as the inappropriate passage of large volumes of di lute urine (<300mOsm/L). Due to either de \201 ciency in AVP production (cranial DI) or re sistance to its actions at the kidney (neph- rogenic DI). The most common cause of DI is pr imary de \201 ciency of AVP production (i.e. cranial DI). This may be acquired or inherite d in origin. Classi \201 cation of diabetes insipidus Cranial DI Inherited/familial \200 Autosomal dominant \200 Autosomal recessive \200 X -linked recessive (Xq28) \200 Wolfram syndrome (4p WFS1) Congenital \200 Midline cranio facial defects \200 Holoprosencephaly Acquired \200 Intracranial tumors \200 Cranioph aryngioma \200 Germinoma Primary polydipsia \200 Psychogenic \200 Dipsogenic (abnormal thirst) Nephrogenic DI Inherited/familial \200 Autosomal dominant: Aquaporin-2 gene \200 Autoso mal recessive: Aquaporin-2 gene \200 X-linked recessive: ADH receptor-2 gene Acquired \200 Idiopathic \200 Drugs (lithium; cisplatin) \200 Metabolic (hypercalcaemia) Traumatic brain injury \200 In \201 ltrative/in \202 ammation: Langerhan \200\231s cell histiocytosis \200 CNS infection Children present with polydipsia, polyuria, and nocturia, which must be distinguished from more common causes. Infants may exhibit failure to thrive, fever, and constipation. Other s ymptoms may be related to the underlying cause, e.g. headache, visual acuity/visual \201 eld impairment. Diagnosis When suspected, assessment of 24hr urinary volume and osmolality under conditions of ad libitum \202 uid intake should be undertaken. Serum osmolali- ty, U&E (Na+), and b lood glucose should also be measured. Blood hypertonicity (serum osmolality >300mOsm) with inappropriate urine hypotonicity (urin e osmolality <300mOsm) should be demonstrated. Diabetes mellitus and renal failure should b e excluded. A water deprivation test (see Box 12.6) and assessment of responses to exogenously administ ered ADH is required to diagnose the type of DI. Other tests to determine the underlying ca use of DI will also be needed (e.g. cranial MRI imaging). 12_McClure_12.indd 450 11/14/2012 3:27:05 PM POSTERIOR PITUITARY: DIABETES INSIPIDUS 451 Box 12.6 Water deprivation test Should be carried out in conditions of strict monitoring and in centers with experience wit h this test: \200 Allow \202 uids overnight. If primary polydipsia is suspected consider overnight \202 u id deprivation to avoid over hydration Commence \202 uid deprivation at 8 a.m. Serum osmo lality, serum Na sample voided Duration of water deprivation is seldom longer than 8 \200 \22312hr in children and 6 \200\2238hr in young infants. In any case, the water deprivation is terminated if there is either: \200 \200 \200 Serum osmolality: In those with ina dequate urinary concentration, desmopressin is administered: DDAVP 0.1mg/kg to maximum of 4 mg IM Interpretation of results: see table that follows \200 +, urine osmolalitiy. Each time urine \211 800mOsm/kg or urine osmolality concentrated: thirst becomes intolerable 5% dehydration (5% weight loss) or or \200 \211 300mOsm/L. Urine osmolality (mOsm/kg) After \202 uid deprivation After DDAVP Cranial DI (CDI) <300 >800 Nephrogenic <300 <300 Primary polydipsia >800 >800 Partial CDI/polydipsia >00 \200\223800 <800 Treatment Cranial DI Synthetic analog of ADH, DDAVP, which has a longer dura- tion of actio n, can be given intranasal or oral. Dose required varies con- siderably and must be titrate d for each patient. The dose and frequency of administration (1 \200\2233 times a day) is a djusted to maintain 24hr urine output volume within the normal range. Water retention shoul d be avoided. It is essential to educate all patients and families about the hazards of ex- cessive water intake. Patients with an intact thirst sensation mechanism should achieve th is. Nephrogenic DI Correction of underlying metabolic or iatrogenic causes, if possible. Mainte nance of an adequate \202 uid input is essential. Thiazide diuretics (e.g. hydrochlorthia zide), amiloride, and prostaglandin synthase inhibitors (e.g. indomethacin) can be effectiv e. Primary polydipsia Treatment is often dif \201 cult. Behavior modi \201 cation strategies usually required. 12_McClure_12.indd 451 11/14/2012 3:27:05 PM CHAPTER 12 Endocrinology and diabetes 452 Polycystic ovarian syndrome Polycystic ovarian syndrome (PCOS) is a common (5 to 10%) heter oge- neous condition, affecting females of reproductive age that is increasingly identi \201 ed in the adolescent population. It is a life-long condition charac- terised by chroni c anovulation, disordered gonadotrophin release, ovarian and adrenal hyperandrogenism, and insulin resistance. The pathogenesis of PCOS is uncertain, however, both genetic and envi- ronmental factors ar e thought to play a role. Risk factors include low birth weight for gestational age, premat ure adrenarche, atypical early pubertal development and obesity. A family history of PCOS i s often observed. The current diagnostic criteria for PCOS are de \201 ned as the presence of any two of the following three features: \200 \200 Oligo-and/or anovulation. Clinical or biochemical evidence of hyperandrogenism, provided ot her aetiologies of androgen excess (e.g. congenital adrenal hyperplasia, androgen-secreting tumors, Cushing \200\231s syndrome) have been excluded. Polycystic ovaries on US scan (i.e . the presence of 12 or more follicles in each ovary, measuring 2 \200\2239mm in diameter, and/or increased ovarian volume (>10mL)). The clinical and biochemical features of the syndrome are variable and the combination and degree of expression of these features vary between individuals. Typical signs and symptoms develop during or after puberty and may include any of the following: \200 \200 \200 \200 \200 oligo/amenorrhea; hirsuitism; acne; obesity; acanthosis nigricans. Laboratory \201 nding include: \200 Elevated androgen concentrations (e.g. testosterone; dehydroepiandrosterone sulfate (DHEAS) ). Elevated plasma LH:FSH ratio. Decreased sex hormone binding globulin (SHBG) concentratio ns. Hyperinsulinaemia (fasting, oral glucose tolerance test (OGTT), IVGT samples). Decrease d IGFBP-1 concentrations. \200 \200 PCOS is recognized to have important long-term health implications and is particularly asso ciated with a range of abnormalities that are characteris- tic of the metabolic syndrome. T hese include hyperinsulinaemia, impaired pancreatic -cell function, the development of ob esity, hyperlipidaemia, and an increased risk of T2DM and cardiovascular disease in later l ife. In addition, chronic anovulation is thought to carry an increased risk of endometrial cancer. 12_McClure_12.indd 452 11/14/2012 3:27:05 PM POLYCYSTIC OVARIAN SYNDROME 453 Treatment of PCOS is symptomatic and is directed at the presenting clinical problems. Lifes tyle modi \201 cations are an important \201 rst-line inter- vention particularly when o besity is evident. Other treatment approaches include the use of the following drugs: \200 \200 Metformin (insulin sensitizer). Combined oral contraceptive pill (suppress ovarian hyperand orgenism). Spironolactone (anti-androgen). Cyproterone acetate (synthetic progesterone \200 \224anti-androgen). Flutamide (anti-androgen). \200 \200 Cosmetic treatments such as electrolysis, laser hair removal, waxing, and bleaching, and us e of topical depilatory creams may be used when hirsuit- ism is a predominant clinical feat ure. 12_McClure_12.indd 453 11/14/2012 3:27:05 PM This page intentionally left blank 455 Chapter 13 Growth and puberty Normal growth 456 Normal puberty 458 Assessment of growth 460 Assessment of puberty 462 Sho rt stature 466 Constitutional delay in growth and puberty 468 Intrauterine growth retardati on 468 Turner \200\231s syndrome 469 Coeliac disease 469 Chronic in \202 ammatory disorder s 469 Skeletal dysplasias 469 Growth hormone de \201 ciency 470 Growth hormone de \201 ci ency: management 472 Tall stature 474 Delayed puberty: assessment 476 Delayed puberty: mana gement 478 Precocious puberty 480 Precocious puberty: management 482 Variants of normal pub erty 484 Disorders of sex development 486 Disorders of sex development: management 488 Andr ogen insensitivity syndrome 490 Micropenis 491 Gynaecomastia 492 13_McClure_13.indd 455 11/14/2012 11:29:31 PM CHAPTER 13 Growth and puberty 456 Normal growth Normal human growth can be divided into two distinct phases: prenatal (fetal) and postnatal. Prenatal/fetal growth This is the fastest period of growth, accounting for around 30% of ev entual height. Factors that determine growth during this period include maternal size, mate rnal nutrition, and intrauterine environment. Hormonal factors such as insulin, insulin-lik e growth factor (IGF) \200\223II, and human placental lactogen are important regulators of growth during this period. Postnatal growth This is classically divided into three overlapping periods. Infantile period From birth to 18 \200\22324mths of age. Rapid but decelerating growth rate (growth velocity range: 22 \200\2238cm/yr). Growth is largely under nutritional regulation during this period. Some infants (15 \200\22320%) may show signi \201 cant catch-up or ca tch-down in length and weight. By age 2yrs, height is more predictive of \201 nal adult h eight than at birth. Childhood period From age 2yrs until onset of puberty. Characterized by a slow, steady grow th velocity (range 8 \200\2235cm/yr). Growth is primarily dependent on growth hormone (GH), provided there is adequate nutrition and health. Puberty Growth during this period is dependent on growth hormone (GH) and the actions of se x steroid hormones (testosterone and estrogen). This combination induces the characteristic \200\230growth spurt \200\231 of puberty. In both males and females, estrogen induces the maturation of the epiphyseal growth centers of the bones, eventually resulting in fusion o f the growth plates, the cessation of linear growth, and the attainment of \201 nal heigh t. Sex differences in growth during puberty The onset of the pubertal growth spurt is earlier in females compared with males. Females are therefore, on average, taller than males betwee n the ages of 10 and 13yrs. In males, the pubertal growth spurt is later in onset and great er in magnitude. As a result males are, on average, 12 \200\22313cm taller than females at \201 nal height. 13_McClure_13.indd 456 11/14/2012 11:29:31 PM NORMAL GROWTH 457 13_McClure_13.indd 457 11/14/2012 11:29:32 PM CHAPTER 13 Growth and puberty 458 Normal puberty Puberty is a well-de \201 ned sequence of physical and physiological change s occurring during the adolescent years that culminates in attainment of full physical and sexual maturity. \200 Nocturnal, pulsatile, secretion of the hormone luteinizing hormone- releasing hormone (LHRH ) by the hypothalamus is the \201 rst step in the imitation of puberty. This results in t he pulsatile secretion of the gonadotrophin hormones LH and FSH by the anterior pituitary g land. LH stimulates sex hormone production from the gonads. The age of onset of puberty is earlier in females (mean (range) 10.5 (8.5 \200\22312.5)yrs) compared to males (12.0 (10 \200\22313.5)yrs). In each sex, puberty progresses in an orderly or \200\230consonant \200 \231 manner through distinct stages (see Table 13.1). In females, the \201 rst sign of pu berty is breast development, followed by pubic hair growth and growth acceleration. Menarch e (the onset of menstruation) occurs, on average, 2.5yrs after the start of puberty (averag e age 13.0yrs). In males, the \201 rst sign of puberty is an enlargement of testicular si ze to greater than 4mL in volume. Pubic hair development and growth acceleration follow. Pubertal growth spurt In females, peak growth (height) velocity occurs relatively earlier i n girls (Tanner stage 2 \200\2233) compared with boys (Tanner stage 3 \200\2234; testicular vol- umes 10 \200\22312mL). Note: The age of onset of puberty varies slightly between children of dif- ferent races. In Afro-Caribbean and African-American children, average age of onset of puberty may be earli er compared with that of White children. 13_McClure_13.indd 458 11/14/2012 11:29:32 PM NORMAL PUBERTY 459 Table 13.1 The normal stages of puberty ( \200\230Tanner stages \200\231) Boys Stage Genitalia Pubic hair Other events TV* <4mL I Prepubertal Vellus not thicker than on abdomen II Enlargement of testes and scrotum Sparse long pigmented strands at base of penis TV 4 \200\2238 mL Voice starts to change III Lengthening of penis Darker, curlier and spreads over pubes TV 8 \200\22310 mL Axillary hair IV Increase in penis length and breadth Adult type hair but covering a smaller area TV 10 \200\22315mL Upper lip hair Peak height velocity V Adult shape and size Spread to medial thighs (Stage 6: Spread up linea alba) TV 15 \200\22325 mL. Facial hair spreads to cheeks Adult voice Girls Stage Breast Pubic hair Other events I Elevation of papilla only Vellus not thicker than on abdomen II Breast bud stage: elevation of breast and papilla Sparse long pigmented strands along labia Peak height velocity III Further elevation of breast and areola together Darker, curlier and spreads over pubes IV Areola forms a second mound on top of breast Adult type hair but covering a smaller area Menarche V Mature stage: areola recedes and only papilla projects Spread to medial thighs (Stage 6: spread up linea alba) TV, testicular volume: measured by size-comparison with a Prader orchidometer. Source: Tann er JM (1962) Growth at adolescence, 2nd edn. Oxford: Blackwell Scienti \201 c Publications . 13_McClure_13.indd 459 11/14/2012 11:29:32 PM CHAPTER 13 Growth and puberty 460 Assessment of growth Growth must be measured accurately. Equipment used to measure weight a nd height must be regularly maintained, checked, and calibrated. Ideally, growth measuremen ts should be carried out by someone speci \201 cally training and experienced in measureme nt techniques (e.g. an auxologist). This will minimize measurement error. Assessment of height \200 From birth to age 2yrs, length is measured horizontally using a speci \201 cally designed measuring board (e.g. Harpenden Neonatometer). Two people need to ensure that child is lyin g straight with legs extended. In children, aged wall-mounted or free-standing stadiometer. A speci \201 c technique is required, with the person measuring applying moderate upward neck traction to the child \200\231s head with the child looking forward in the horizontal plane. Measurement of sitting height using a modi \201 ed stadiometer and calculation of t he leg length (standing height minus sitting height) allows an estimate of upper and lower body segments and body proportion. \211 2yrs, standing height is measured against a Growth data interpretation Weight and height measurement data should be plotted on a simple sex and age range appropriate standard growth centile chart (e.g. the UK 1990 Growth Refer ence charts). A UK-WHO growth chart for children from birth to 4yrs of age has been develop ed based on the WHO child growth standards. These describe optimal growth of healthy breast -fed children. Previous UK growth charts based on data from studies on breast- and formula- fed children, do not re \202 ect normal weight \202 uctuations of breast- fed infants in \201 rst few weeks (see Fig. 13.1). Height measurements should be plotted on speci \201 c population growth charts where necessary or applicable, e.g. Turner \200\231s syndrome; Down \200\231s syndrome. Single growth measurements should not be assessed in isolation from other previous measurem ents. Serial measurements are used to show a pattern of growth and to determine growth rate . To minimize error in the assessment of growth rate, calculation of height velocity (cm/ye ar) should be taken from measurements a minimum of 6mths apart, ideally using the same equi pment and by the same person. Final height and target height Final height is the height reached after the completion of p uberty and is estimated to be achieved when growth velocity has slowed to <2.0cm/ year. Thi s can be con \201 rmed by \201 nding epiphyseal fusion of the small bones of the hand an d wrist on assessing the bone age X-ray. Final height is largely genetically determined. A target height range can be estimated in e ach individual from their parent \200\231s heights, \201 rst calculating the mid-parental height (MPH). MPH (boys) = [(Mother \200\231s ht (cm) + Father \200\231s ht (cm))/2] + 6.5cm MPH (girls) = [(Mother \200\231s ht (cm) + Father \200\231s ht (cm))/2] \200\223 6.5cm Tar get height range = MPH 9 10cm 13_McClure_13.indd 460 11/14/2012 11:29:32 PM ASSESSMENT OF GROWTH 461 Bone age This is a measure of skeletal maturation, which can be assessed by the appearance of the epiphyseal centers of the long bones. Conventionally this is quanti \201 ed from X- rays of the left hand and wrist, with either com- pared with standard radiograph images (e. g. Gruelich and Pyle method) or assessed using an individual bone scoring system (Tanner \200\223Whitehouse methods). The difference between bone age (BA) score and chronological age at the time of assessment may be used as an estimation of the tempo of growth. The BA may also be used as an indicato r of the likely timing of puberty, which usually starts when BA is around 10.5yrs in female s and 11.5yrs in boys. The relationship between BA and age of onset of menarche is more rob ust. Girls usually reach skeletal maturity at a BA of 15.0yrs and boys when BA is 17.0yrs. The B A can therefore be used as an estimation of the remaining growth potential and can be used to predict \201 nal adult height. 13_McClure_13.indd 461 11/14/2012 11:29:32 PM CHAPTER 13 Growth and puberty 462 Assessment of puberty Puberty stage can be rated using the Tanner staging system. This invo lves identi \201 cation of pubertal stage particularly by assessment of stage of breast de velopment in girls and of testicular volume (by comparison with an orchidometer) in boys. 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44 46 48 50 52 BOYS 0 \200\2231 year 3 4 5 6 7 8 9 10 11 Preterm 50cm 50cm 9 9 . 6 t h Age in weeks/ months 49 49 9 8 t h Birth Head Circumference 48 48 9 1 s t 47 47 7 5 t h 40 d 46 46 5 0 t h 39 a 2 5 t h 45 45 e 38 9 t h h 44 44 37 2 n d 43 43 0 . 4 t h 36 42 42 99.6th 98th 91st 75th 50th 25th 35 99.6th 98th 91st 75th 50th 25th 9th 2 n d 0.4th 41 41 ) m c ( 34 40 40cm e c n e r e f m u c r i C d a e H 33 84cm 39 99.6th 32 82 38 9 9 . 6 t h h t 8 98th 31 80 37 9 9 1 s 91st t 30 78 36 75th t h 5 7 9th 2nd 0.4th 76 35 29 50th h h t 0 2 5 t h 9 t h 5 25th 74 34 t 28 g 9th 72 33 27 n 2nd 2 n d 0 . 4 t h 70 32 26 l e 0.4th Gestation in weeks 68 31cm 32 34 36 38 40 42 66 66cm Plotting preterm infants Use the low birthweight chart for infants less than 32 weeks gesta tion and any other requiring infants detailed assessment. Use this section for infants than 37 weeks of less gestation. As with term infants there may be some weight loss in the earl y days. From 42 weeks, plot on the 0 \200\2231 with chart year gestational correction. 64 64 62 62 99.6th 98th 91st 75th 50th 25th 9th 2nd 0.4th 60 60 58cm 58 99.6th 56 98th 91st 54 14kg 75th 52 13.5 50th 50 13 25th 9 9 . 6 t h 9th 48 12.5 Gestational age (7 weeks preterm) 2nd 46 12 9 8 t h Actual age 0.4th 44cm 11.5 Gestational correction Plot actual age then draw a line back the number of weeks the infant was preterm and mark the spot with an arrow; this is the gestationally corrected centile. 11 11kg 9 1 s t 10.5 10.5 Some degree of weight loss is common after birth. Calculating the percentage weight loss is a useful way to identify babies who need assessment. 7 5 t h 10 10 t h 5 0 t h 9.5 9.5 e i g 9 Birth Weight 9 2 5 t h 5.5 8.5 8.5 9 t h w 8 8 5 2 n d 7.5 7.5 0 . 4 t h 4.5 7 7 99.6th 98th 91st 75th 50th 25th 9th 2nd 0.4th 6.5 6.5 4 6 6 5.5 5.5 3.5 5 5 ) g k ( 99.6th 98th 91st 75th 50th 25th 9th 2nd 0.4th 99.6th 3 t h g i e 4.5 4.5 98th 91st W 4 4 75th 2.5 3.5 3.5 50th 25th 3 3 2 9th 2.5 2.5 2nd 0.4th 1.5 2 2 1.5 1.5 1 Age in weeks/ months 1 1 Gestation in weeks 1 2 3 4 5 6 7 8 9 10 11 0.5kg 0.5kg 32 34 36 38 40 42 0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44 46 48 50 52 Fig. 13.1 (a) Boys child growth charts 0 \200\2231. 13_McClure_13.indd 462 11/14/2012 11:29:32 PM ASSESSMENT OF PUBERTY 463 12 13 14 15 16 17 19 20 21 22 23 25 26 27 28 29 31 32 33 34 35 37 38 39 40 BOYS 1 \200\2234 years Adult Height Prediction 2 Data Recording 1 1/2 2 1/2 3 552cm 9 9 . 6 t h 9 8 t h 9 1 s t 7 5 t h 5 0 t h 2 5 t h 9 t h 2 n d 0 . 4 t h 124cm Birth Measurement Recording Date Age in months/ years 50 120 Weight ft/in 6.5 cm 195 h e a d Head Circumference 48 Measure length until age 2; measure height after age 2. A child \200\231s height is usually slightly less than their length. 116 6.4 Length/Height 99.6th h t 9 . 6 6.3 9 190 Location 46 112 98th 6.2 9 8 t h Health worker name 6.1 185 91st t s 1 Measurement 2 9 44 108 6.0 Recording Date 75th h 5.11 t 5 180 7 h t Weight 42 104 5.10 50th 5 0 t h Head Circumference g 5.9 175 25th i Length/Height 2 5 t h 40cm e 5.8 100 h 9th Location 5.7 170 9 t h Health worker name 5.6 96 96cm 2nd 2 n d 5.5 Measurement 3 165 0.4th Recording Date 5.4 0 . 4 t h 92 92 5.3 Weight 160 h t Head Circumference 88 88 g Plot child \200\231s height centile on the blue lines above; the black numbers show average male adult height for this centile; 80% of children will be within 6 cm of this value. n Length/Height 9 . 6 t h 8 t h s t 5 t h h t 0 h t h l e 9 9 84cm Location 84 Health worker name 1 9 30kg 80 Measurement 4 7 Recording Date 5 5 2 9 29 76 Weight t Head Circumference d n 2 0 . 4 28 72 h Length/Height t Location 27 68 Health worker name Measurement 5 26 64 Recording Date Weight 25 60cm Head Circumference Length/Height 24kg 24 Location Health worker name 23 23 h t 9 . 6 9 Measurement 6 Recording Date 22 22 Weight 21 h Head Circumference 21 t 8 9 Length/Height 20 20 Location Health worker name t s 1 9 19 19 Measurement 7 Recording Date 18 18 Weight 7 5 t h Head Circumference 17 17 Length/Height Location h t 0 5 16 t 16 Health worker name h Measurement 8 g 15 15 2 5 t h i Recording Date w e Weight 14 14 9 t h 9 . 6 t h Head Circumference 9 Length/Height 13 13 2 n d 8 t h Location 9 Health worker name 12 12 s t 1 0 . 4 t h 9 Measurement 9 11 11 Recording Date h t 5 7 Weight h t 0 5 10 10 Head Circumference h t 5 Length/Height 2 9 9 Location h t 9 Health worker name 2 n d 8 8 Measurement 10 h t 0 . 4 Recording Date 7 7 Weight Head Circumference 6 6 Age in months/ years Length/Height Location 5kg 5kg 1 1/2 2 1/2 3 1/2 2 3 Health worker name 12 13 14 15 16 17 19 20 21 22 23 25 26 27 28 29 31 32 33 34 35 37 38 39 40 41 43 44 45 46 47 48 Fig. 13.1 (b) Boys child growth charts 1 \200\2234. 13_McClure_13.indd 463 11/14/2012 11:29:33 PM CHAPTER 13 Growth and puberty 464 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44 46 48 50 52 GIRLS 0 \200\2231 year 3 4 5 6 7 8 9 10 11 Preterm 50cm 50cm Age in weeks/ months 49 49 9 9 . 6 t h Birth Head Circumference 48 48 9 8 t h 47 47 39 9 1 s t 46 46 7 5 t h 38 a d 45 45 5 0 t h 37 e 44 44 2 5 t h h 36 43 43 9 t h 35 2 n d 42 42 99.6th 98th 91st 75th 50th 25th 0 . 4 t h 41 41 34 ) m c ( 99.6th 98th 91st 75th 50th 25th 9th 2 n d 0.4th 40 40cm 33 e c n e r e f m u c r i C d a e H 39 32 38 82cm 31 9 9 . 6 t h h t 99.6th 37 80 30 98th 8 9 36 78 91st t s 1 9 29 9th 2nd 0.4th 35 76 75th h t 5 7 28 h 50th 34 74 h t 0 5 t 25th 27 33 72 t h 5 2 g 9th n 9 t h 32 70 26 2nd Gestation in weeks l e 2 n d 0 . 4 t h 0.4th 31cm 68 32 34 36 38 40 42 66cm 66 Plotting preterm infants low birthweight Use the chart for infants less than 32 weeks gesta tion and any other requiring infants detailed assessment. for infants Use this section than 37 weeks of less gestation. As with term infants there may be some weight loss in the earl y days. From 42 weeks, plot on the 0 \200\2231 with chart year gestational correction. 64 64 62 62 99.6th 98th 91st 75th 50th 25th 9th 2nd 0.4th 60 60 58 58cm 56 99.6th 98th 54 14kg 91st 52 13.5 75th 50th 50 13 25th 48 12.5 Gestational age (7 weeks preterm) t h 9 . 6 9th 9 2nd 46 12 Actual age 0.4th 44cm 11.5 t h 8 9 Gestational correction Plot actual age then draw a line back the number of weeks the infant was preterm and mark the spot with an arrow; this is the gestationally corrected centile. 11 11kg 10.5 10.5 Some degree of weight loss is common after birth. Calculating the percentage weight loss is a useful way to identify babies who need assessment. t 9 1 s 10 10 7 5 t h 9.5 9.5 t h 9 Birth Weight 9 5 0 t h 5.5 g 8.5 8.5 i e 2 5 t h 8 8 5 w 9 t h 7.5 7.5 4.5 7 7 2 n d 6.5 6.5 0 . 4 t h 99.6th 98th 91st 75th 50th 25th 9th 2 n d 0.4th 4 6 6 5.5 5.5 3.5 5 5 ) g k ( 99.6th 98th 91st 75th 50th 25th 9th 2nd 0.4th 99.6th 3 t h g i e 4.5 4.5 98th W 91st 4 4 2.5 75th 3.5 3.5 50th 25th 3 3 2 9th 2.5 2.5 2nd 0.4th 1.5 2 2 1.5 1.5 1 Age in weeks/ months 1 1 Gestation in weeks 1 2 3 4 5 6 7 8 9 10 11 0.5kg 0.5kg 32 34 36 38 40 42 0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44 46 48 50 52 Fig. 13.1 (c) Girls child growth charts 0 \200\2231. 13_McClure_13.indd 464 11/14/2012 11:29:33 PM ASSESSMENT OF PUBERTY 465 12 13 14 15 16 17 19 20 21 22 23 25 26 27 28 29 31 32 33 34 35 37 38 39 40 GIRLS 1 \200\2234 years Adult Height Prediction 2 Data Recording 1 1/2 2 1/2 3 124cm 52cm Birth Measurement Recording Date ft/in cm 9 9 . 6 t h 9 8 t h 9 1 s t 7 5 t h 5 0 t h 2 5 t h 9 t h 2 n d Age in months/ years 5.11 180 120 50 Weight 5.10 Head Circumference h e a d 116 48 5.9 175 Length/Height Measure length until age 2; measure height after age 2. A child \200\231s height is usually slightly less than their length. 99.6th h t 9 . 6 9 Location 5.8 112 46 98th h t 8 9 Health worker name 5.7 170 91st Measurement 2 t 108 9 1 s 44 0 . 4 t h 5.6 Recording Date 75th h t 5 7 Weight 5.5 104 165 42 t 50th t h h 0 Head Circumference 5 5.4 g Length/Height 100 25th 40cm 2 5 t h i 5.3 e 160 Location 9th 9 t h h Health worker name 96 5.2 96cm 2nd 2 n d Measurement 3 5.1 155 Recording Date 92 92 0 . 4 t h 0.4th 5.0 Weight h Head Circumference 88 88 150 4.11 t g Length/Height n Plot child \200\231s height centile on the pink lines above; the black numbers show average female adult height for this centile; 80% of children will be within 6 cm of this value. 9 .6 t h 8 t h s t 5 t h h t 0 h 5 84cm Location 84 l e 9 9 Health worker name 30kg 1 80 9 Measurement 4 7 Recording Date 5 2 29 76 Weight t Head Circumference h t 9 28 72 Length/Height d n 2 0 . 4 h t Location 27 68 Health worker name Measurement 5 26 64 Recording Date Weight 25 60cm Head Circumference Length/Height 24 24kg Location 9 . 6 t h 9 Health worker name 23 23 Measurement 6 Recording Date 22 22 Weight 8 t h 9 Head Circumference 21 21 Length/Height 20 20 Location Health worker name t s 1 9 19 19 Measurement 7 Recording Date 18 18 Weight h t 5 7 Head Circumference 17 17 Length/Height Location 16 h 16 t 0 5 Health worker name t h Measurement 8 15 15 Recording Date g 2 5 t h i Weight 14 14 w e Head Circumference 9 t h 9 . 6 t h 9 Length/Height 13 13 Location 2 n d h t 8 Health worker name 9 12 12 Measurement 9 0 . 4 t h s t 1 9 11 Recording Date 11 Weight h t 5 7 10 10 Head Circumference h t 0 Length/Height 5 9 9 Location h t 5 2 Health worker name t h 9 8 8 Measurement 10 n d 2 Recording Date 7 h 7 t 0 . 4 Weight Head Circumference 6 6 Age in months/ years Length/Height Location 5kg 1 1/2 2 1/2 3 1/2 5kg 2 3 Health worker name 12 13 14 15 16 17 19 20 21 22 23 25 26 27 28 29 31 32 33 34 35 37 38 39 40 41 43 44 45 46 47 48 Fig. 13.1 (d) Girls child growth charts 1 \200\2234. 13_McClure_13.indd 465 11/14/2012 11:29:33 PM CHAPTER 13 Growth and puberty 466 Short stature De \201 ned as a height 2 SDs or more below mean for the population. On a st andard growth chart this represents a height below the 2nd centile. Note: abnormalities of growth may be present long before height falls below this level and can be identi \201 ed much earlier by monitoring growth velocity and observing a child \200\231s height crossing centile lines plotted. Causes of short stature These are summarized in the Box 13.1. The most common cause is fami l- ial, where either one or both parents will also be short. Height correlates well with pa rental height and is probably of polygenic inheritance, but it should be noted that short p arents may have a dominantly inherited growth disorder. Assessment Antenatal history Pregnancy illness/drugs/complications Perinatal/infancy history \200 \200 \200 Gestational age and complications Birth weight (length and head circumference) Feeding and weight gain Past medical Chronic asthma Drug history Corticosteroids Systematic enquiry Headaches/visual disturbance Growth history Examine previous growth records if available Neurodevelopmental \200 \200 Developmental delay. School performance. Family history \200 \200 Short stature/pubertal delay. Endocrine disease. Examination \200 \200 \200 \200 \200 \200 Measure height; weight; head circumference. General systems examination. Puberty (Tanner) s taging. Observe for goiter; dysmorphic features; malnutrition. Assess growth velocity over (a minimum of) 6-monthly intervals. Measure parent \200\231s height and calculate MPH and f amily height target. 13_McClure_13.indd 466 11/14/2012 11:29:34 PM SHORT STATURE 467 Box 13.1 Causes of short stature \200 \200 \200 \200 \200 Familial (genetic) short stature Constitutional delay in growth & puberty ( Intrauterine gr owth retardation ( Growth hormone de \201 ciency ( Other endocrine disorders, e.g. hypothy roidism ( Cushing \200\231s syndrome (b p.434) Dysmorphic syndromes: \200 Turner syndrome ( \200 Noonan syndrome ( \200 Down syndrome ( Coeliac disease ( Chronic renal failure ( Chronic in \202 ammatory disorders ( disease (b p.332); rheumatic disease (b p.772) Skel etal dysplasia ( Metabolic bone disease: X-linked hypophosphataemic rickets (b p.445) Malnu trition b p.468) b pp.111, 468) b p.470) b p.424), b pp.469, 948) b p.941) b p.936) \200 \200 b p.336) b pp.366 \200\223369) b p.469): in \202 ammatory bowel \200 b p.766): achondroplasia/hypochrondroplasia Investigations The following baseline screening tests should be carried out: \200 \200 \200 \200 \200 \200 \200 \200 U&E (renal function). FBC and CRP (chronic disease/in \202 ammation). Calcium and phosphat e (bone disorder). Karyotype (chromosomal abnormalities, especially Turner \200\231s syndro me). Thyroid function tests. Serum IGF-I (and IGFBP-3) (GH de \201 ciency). Coeliac diseas e antibody screen. Urinalysis. Where clinically indicated: \200 \200 Bone age X-ray. GH provocation test. Management This will depend on the underlying cause (see later sections of this chap- ter). The diagnosis of a child with short stature is often a shock to the family, and they shoul d be offered detailed, reliable information about their child \200\231s condition and infor med where to get additional support and advice. In the UK the Restricted Growth Foundation (www.restricted- growth.co.uk) is a good resource. Familial short stature does not require any speci \201 c treatment. Note: Most short children are psychologically well adjusted. Where there are problems from being teased and bullied at school or poor self- esteem, psychological intervention measure s may be needed. 13_McClure_13.indd 467 11/14/2012 11:29:34 PM CHAPTER 13 Growth and puberty 468 Constitutional delay in growth and puberty Relative short stature occurs because of a delay in the timing of onset of puberty. It is a variation in the timing of normal puberty, rath er than an abnormal condition. It usually presents in early adolescence, although it may be recognized in earlier childhood. There is often a familial basis, of- ten having occurred in one of the parents. It is much commoner in males, although this may re \202 ect a bias in the level of concern. Characteristic features include short stature and delayed pubertal development by greater t han 2 SDs. Typically, there is a mild degree of skeletal disproportion with evidence of a s horter back (sitting height per- centile) relative to leg length. There is invariably delay in BA maturation, which usually remains consistent over time. Height velocity is appropria te for BA. Laboratory investigations are normal, including GH provocation tests. Management Usually no treatment is required as the onset of puberty and the accompa- nying growth spurt will occur spontaneously and an appropriate \201 nal adult target height is achieved. Treatment is sometimes indicated in those adolescents who have dif- \201 culty coping wit h their short stature or with the delayed physical devel- opment. Administration of sex ste roids for a period of 3 \200\2236mths can be used to induce pubertal changes and to acceler ate growth rate (boys: testosterone 50 \200\223100mg IM every 4wks). Intrauterine growth retardation See also b p.111. IUGR refers to reduction and restriction in expected fetal growth pattern. IUGR affects 3 \200\22310% of pregnancies and 20% of stil l- born infants are thought to have evidence of IUGR. Perinatal mortality rates are 4 \200 \2238 times higher for growth-retarded infants, and morbidity is present in 50% of survivin g infants. Growth outcome In placental causes of IUGR, \200\230catch-up growth \200\231 occurs after birth in the majority of infants during the \201 rst 1 \200\2232yrs of life, with infants regaining their genetically determined weight and height centiles. However, in approxi- ma tely 15 \200\22320% of infants with IUGR, catch-up growth does not occur and patients are a t risk of short stature. Recent studies also implicate IUGR in adult onset of hypertension and CHD, and in early onset obesity, polycys- tic ovarian disease, and type 2 diabetes. The se studies suggest that IUGR has long-term effects on insulin sensitivity and on endocrine function. 13_McClure_13.indd 468 11/14/2012 11:29:34 PM TURNER \200\231S SYNDROME 469 Turner \200\231s syndrome See also b p.948. This condition must always be considered in gir ls pre- senting with short stature, or height below parental target height range. Karyotype con \201 rms the diagnosis. The majority of girls with Turner \200\231s syndrome will not have the classi- cal phenotyp e of dysmorphic features and it may be dif \201 cult to identify, particularly where there is mosaicism in the karyotype. \200 Short stature is frequent. Typically growth rate begins to falter from age 3 \200\2235yrs a nd is due to an underlying skeletal dysplasia. Ovarian dygenesis and consequent gonadal fai lure result in loss of the pubertal growth spurt. Mean \201 nal height is consistently 20 cm below the norm. Treatment with daily SC injections of high dose recombinant human growth hormone (rhGH 10mg /m2/wk) increases \201 nal height, although individual responses are variable. Oral estro gen (ethinylestradiol) is required to induce puberty between ages 12 and 14yrs. Combination therapy, which also includes the anabolic steroid, oxandrolone, may fur- ther improve \201 nal height. Coeliac disease Also see b p.336. Coeliac disease may be asymptomatic or atypical in its pr esentation with few if any gastrointestinal symptoms or signs. Poor height velocity and evo lving short stature may be a presenting feature. Chronic in \202 ammatory disorders Poor growth and short stature is a common feature of lo ng-term in \202 am- matory conditions such as in \202 ammatory bowel disease and rheumati c dis- orders. It may be a presenting feature in Crohn \200\231s disease when GI symp- toms are initially minimal (see b p.332). Short stature is due to long-term use of immunosuppressive agents (e.g. corticosteroids) an d to the generation of in \202 ammatory factors (e.g. IL-6). Both lead to GH/IGF-I resista nce and suppression of bone growth. Management should be aimed at minimizing in \202 ammation, and reducing immunosuppressive therapy. rhGH may have a role in treatment. Skeletal dysplasias This heterogeneous group of disorders includes achondroplasia and hypoc hrondroplasia. Most disorders are characterized by severe short stature and often evidence of disproportion in body segment develop- ment. Skeletal survey may allow identi \201 cati on of speci \201 c condition (see b pp.766 \200\223767, 950). 13_McClure_13.indd 469 11/14/2012 11:29:34 PM CHAPTER 13 Growth and puberty 470 Growth hormone de \201 ciency Physiology: secretion GH is secreted from the somatomammotro pic cells of the anterior pitu- itary gland in a pulsatile pattern. Secretion is diurnal an d largely noctur- nal and is controlled by a rhythmically changing equilibrium between two hormones secreted by the hypothalamus: GH releasing hormone (GHRH) and GH-inhibiting hormon e (or somatostatin). GHRH induces GH syn- thesis and secretion whenever somatostatin is low . Different factors act at the level of the hypothalamus to regulate GH hormone secretion. GH secretion is regulated by negative feedback by circulating insulin-like growth factor-I (IGF-I) at the pituitary and hypothalamus, and by short loop-feedback by GH on the hypothal amus. Causes of growth hormone de \201 ciency These may be primary (or congenital) or secondary (acquired) in origin. In clinical practice the most frequent cause of GH de \201 ciency is s to cranial radiotherapy (Box 13.2). Box 13.2 Causes of GH de \201 ciency Primary or congenital causes \200 \200 \200 Idiopathic/isolated Congenital hypopituitarism (see Midline brain anomalies b p.449)