demyelinating disease (multiple sclerosis, ADEM), progressive dementia, encephalopathy, and movement disorders. If a finding on CT scan is suspi- cious for a focal lesion, order an MRI for con firmation. Also, if a CT scan is not helpful to confirm a strong clinical suspicion, MRI is necessary. When to Refer The many reasons for consultation include one or more of the following: patient comfort, diagnosis, and management. Consistent with the scope of this book, this section discusses referrals for diagnosis. Case manage- m ent is a separate consideration, and the neurologist and pediatrician should be partners in care, with one or the other taking the primary role. After taking a careful history and completing a physical examination , the primary care physician should obtain neurologic consultation when ques- tions remain unanswered. Often a conversation between the pediatrician and the neurologist before referral saves time and expense. A single diag- nostic test suggested by the neurologist and ordered by the pediatrician may obviate the need for further consultation. As a rule, only order diag- nostic tests if t hey will influence patient management. Too often an unneces- sary imaging study done at the parent’s request identifies an unrelated normal variant that leads to further anguish and expense. A thoughtful consulta nt orders tests sequentially, and one who orders panels of tests at the onset has no idea what is wrong and is fishing for an answer. The urgency for consultation should be a clinical decision based on rapidit y of onset and progression of symptoms. In practice, parental concern and tolerance for delay often dictate urgency. Congenital. CT scan detects most major malformations. MRI is required to observe many migrational defects and to further clarify the extent of many congenital anomalies. Inborn errors of metabolism may cause structural abnormalities of the brain, and genetic consultation is helpful even in the absence of dysmorphic features (see Chapter 6). Genetic/metabolic. Every pediatrician should be aware of the specific dis- eases that comprise the newborn screen in the state of birth. Most inborn errors of metabolism have charact eristic clinical features that lead to specific evaluation. Computer-based resources such as On- line Mendelian Inheritance in Man (OMIM) and Geneclinics provide guidelines for evaluation and diagnosis. See Chapter 5 fo r state screening. After initial screening, separate organic acidemias from urea cycle defects and aminoacidopathies. Acidosis owing to inborn errors of metab- olism and some aminoacidopathies will have an incre ased anion gap. Some aminoacidopathies have normal pH and ammonia levels. Aci- dosis is characteristic of organic acidemias, some aminoacidopathies, and carboxylase deficiencies. Urea cycle diso rders typically have elevated ammonia levels with normal pH. See TABLE 12–10 and consult a neurology text for more details about each of these metabolic dis- orders, as well as mitochondrial, gray matter, white matter, myop athic, When to Refer 397 TABLE 12–10 Rarer Congenital/Metabolic/Genetic Diagnoses Diagnosis Clinical Points I. Inborn errors of metabolism a. Aminoacidopathies Phenylketonuria (PKU) Seizures, vomiting, DD, musty odor, fair skin, ↑ phenylketones Tyrosinemia (type I) Boiled cabbage odor, hepatorenal disease, PN, ↑ fumaryloacetoacetate Branched-chain ketoaciduria Maple syrup urine (skin, cerumen); MR Sz, spasticity ↑Leu, Iso, Val. b. Urea cycle defects ↑NH 3 , normal pH, AC, MR, ↑ornithine, citrulline, argininosuccinate c. Organic acidemias Acidosis, nl or ↑NH 3 level, Sz, DD, vomiting Isovaleric acidemia “Sweaty sock” odor, AC Sz, coma, occ ↑NH 3 , and hypoglycemia MCAD Sz, lethargy, coma,” tomcat urine” odor, FTT, eczematoid rash, ↑ infection Biotin deficiency Skin rash, Sz, hyp., MR, ↑ infection, biotin or biotinidase deficiency Methylmalonic acidemia (MMA) Sz, lethargy vomiting, acidosis, ↑NH 3 . May have nl dev.; occurs in attacks Propionic acidemia Similar to MMA +MR, and MD II. Mitochondrial disorders a. MELAS syndrome Myoclonic epilepsy, lactic acidosis, and stroke b. MERRF syndrome Myoclonic epilepsy with red ragged fibers c. Kearns-Sayre syndrome Retinal degen, ophthalmoplegia, at., heart block, ↑CSF protein d. Leigh disease Hyp, spasticity DR, MD, lactic acidosis, cardiomyopathy e. Alper Sz, DR, blindness, lactic acidosis, grey matter degen., cirrhosis of liver III. Gray matter degeneration a. Lesch-Nyhan Hyp., MD, MR, aggressiveness, self-mutilation, ↑uric acid level b. Rett Females, hand-wringing, Sz, DR, at., autism, microcephaly c. Menkes Kinky hair, lethargy, myoclonic Sz, ↓ serum Cu, and ceruloplasmin d. Ceroid lipofuscinosis. Sz, DR, blindness, pigmented CNS and eyes; infantile and juvenile forms. 398 IV. White matter degeneration a. Alexander disease (dis) DR, Sz, ↑ head size, MRI criteria for dx, Rosenthal fibers on biopsy b. Pelizaeus-Merzbacher dis. Head nod, at., MD, DR, optic atrophy, demyelination on MRI c. Canavan disease DR, hyp. at first, then spastic, ↑ head, optic atrophy d. Adrenoleukodystrophy DR, at., behavioral change, blindness/deafness, adrenal insuff, ↑ long chain FA V. Storage diseases a. Gaucher type II, infa ntile Hyp. → spasticity, head retraction, sucking prob., pursed lips, DR, ↑ spleen, ↓glucocerebroside activity b. Tay-Sachs GM 2 gangliosidosis ↑ Startle, DR (motor and mental), cherry red macula, ↑ in AJP, hex. A defic. c. Sandhoff GM 2 gangliosidosisLike Tay-Sachs + hepatosplenomegaly (HSM); hex. A and hex. B deficiency d. Niemann-Pick (sphingomyelin) DR, FTT, blindness, opisthotonus, emaciation, HSM, cherry red macula e. Metachromatic leukodyst At. , DR quadriplegia; infantile and juvenile; arylsulfatase A deficiency f. Mucopolysaccharidoses Coarse facies, gibbus deform., corneal clouding, deafness, DR; see individual types for degree of variation VI. Spinal musc. atrophy a. Werdnig-Hoffman (SMA I) Infantile form, hyp. (in ureters), facial weakness, swallowing problem, fasciculations b. Kugelberg-Welander (SMA III) Juvenile form, gait instability, proximal weakness, tremor, ↓ refl exes VII. Neuropathy a. Charcot-Marie-Tooth disease Childhood, slow onset, pes cavus, foot drop, distal weakness (peroneal → gastrocnemius), ↓ reflexes and position sense VIII. Myopathy A. Musc. dystrophy (limb-griddl e) a. Duchenne (DMD) Onset < 5 y, ↓ motor dev., prox. weakness, +Gower sign, toe-walking, pseudohypertrophy, prog. weakness, ↓ reflexes, contractures, cardiac, LD b. Becker (mild form of DMD) Onset >10 y, shoulder girdl e → humerus → facial muscles, occ. blind and deaf c. Facioscapulohumeral Emery-Dreifuss (onset age 5, slow progression, contractures, cardiomyopathy), d. OthersBetlem (onset age 2, slow prog., contractures) 399 (Continued) 400 TABLE 12–10 Rarer Congenital/Metabolic/Genetic Diagnoses (Continued) Diagnosis Clinical Points B. Cong. myopathy a. Nemaline myopathy Variable clinical forms, face, neck proximal weakness, rods on biopsy b. Central core disease Mild hypotonia at birth, slow prog., weakness prox. > distal, upper ext. > lower, contractures, scoli osis, hip dislocation, malignant hypothermia, bx diagnosis c. OthersMyotubular myopathy, multiminicore disease IX. Neurocutaneous a. Incontinentia pigmenti Sz, MR, bullae → pigment whorls → depigmented whorls ; spasticity, Sz, MR, other ectodermal defects (hair, eyes) b. Linear nevus sebaceous Unilateral linear nevus, hemihypertrophy, ocular abn., Sz, MR, FW, ↑ head size Ataxia, dev regression, ↓ reflexes, ↓ propri oception c. Hypomelanosis of Ito Sz, MR, eye abnorm., whorls of hypopigmentation, ↑ head size X. Progressive ataxias. Spinocerebellar degen. b. AbetalipoproteinemiaRetinitis pigmentosa, low cholesterol, acanthocytosis c. Refsum disease Retinitis pigmentosa, polyneuropathy, ataxia, ↑ phytanic acid d. Friedreich ataxiaChildren and adults, progressive, ataxia, pes cavus, ↓ position and vibration, cardiac failure Abbreviations: Sz = seizures; DD = developmental delay; PN = peripheral nerves; AC = altered consciousness; MR = mental retardataion; FTT = failue to thrive; hyp. = hypotonia; MD = movement disorder; at. = ataxia; DR = developmental regression; AJP = Ashkenazi Jewish Population; at = ataxia; cong = congenital; degen = degeneration; def = deformity; dev = development; ext = extremity; HSM = hepatosplenomegaly; insuff = insufficiency; nl = normal; occ = occasional; Cu = copper; le u = leucine; iso = isoleucine; val = valine; Hex A = hexosaminidase A; leukodyst = leukodystrophy; MELAS = mitochondrial encephalopathy lactic acidosis, strokelike episodes; MSUD = Maple Syrup Urine Disease; SMA: spinal muscular atrophy. lysosomal storage, spinocerebellar degenerative diseases, and spinomuscu- lar atrophies. Note the recent advances in molecular genetics, and always include a geneticist in consultation with patients with these co nditions. Neurocutaneous syndromes such as neurofibromatosis I and II and tuberous sclerosis are usually clinical diagnoses with some help from imaging. However, molecular genetics studies are available for tuber - ous sclerosis and are employed to differentiate genotypes. Infectious/inflammatory. Specific bacterial, viral, fungal, or rickettsial cul- tures or other serologic or immunologic evidence of infection, e.g., fluo rescent antibodies, obtained by antibody titers is most helpful to determine an etiology of an acute infectious or postinfectious pro- cess, e.g., rubella, measles, EBV, or campylobacter in Guillain-Barré disease . It still may be necessary for the neurologist to order nerve conduc- tion velocities or electromyography to differentiate neuropathy from myopathy. Imaging studies may be helpful, examples of which are localizati on in the temporal lobe of herpes encephalitis and demyeli- nating lesions in ADEM. Traumatic. Most acute trauma is diagnosed immediately during the acute event. History, physical exam ination, and imaging studies are usu- ally sufficient to elucidate the diagnosis. Neoplastic. The primary care physician may identify tumors, but the neu- rologist and/or neurosurgeon is necessa ry to delineate the specific histologic type. If neuroimaging studies are normal and there is still clinical suspicion of a space-occupying lesion, a neurologist is help- ful to review findings and to consider additional stud ies. Vascular. The primary care physician always should be mindful of clot- ting disorders, vasculitides, and congenital malformations that may cause thrombotic or hemorrhagic strokes. If CT scan and MRI are nor- mal and the clinicia n still suspects vascular disease, arteriography may be necessary. When to Refer 401 This page intentionally left blank 403 The Endocrine System 13 Chapter The goals of this chapter are 1.To summarize developmental, anatomic, and functional aspects of the endocrine system(s) 2.To review symptoms that suggest an endocrine disorder as pre- sented by infants, children, and adolescents and to suggest di fferent endocrine diagnoses that may explain these symptoms 3.To present details of physical findings that are due to endocrine dis- orders and discuss how they support consideration of endocrine diagnoses 4.To provide a systemati c approach to laboratory evaluation based on the history and physical examination 5.To assist with the decision about when a consultation with an endocrinologist is helpful Anatomy and Developmental Physiology There is truly a plethora of substances that can act as hormones. Hor- mones are produced in one cell, transmitted to another cell by means other than direct cell-to-cell contact (as in neuronal transmission of signals), in- teract with specific receptors of the target cell, and have an effect on a spe- cific function or functions of that cell. There is often a negative-feedback loop operating between the hormone-secreting cell a nd the hormone target cell to maintain homeostasis and avoid oscillation of the effects of the hor- mone. One typically thinks of the hypothalamic-pituitary-endocrine gland axes as being of major importance; however, the gastro intestinal tract can be considered to interact in a pseudoendocrine manner with the pancreas by providing changing concentrations of nutrients as a signal. Gut- derived peptides not only signal satiety but influence rele ase of insulin and growth hormone. The central nervous system (CNS) is also involved in meal-related activation of the pancreas. The immune system and en- docrine system have numerous interactions as well. For purposes of diagnosis, we will limit this chapter to the more classically defined en- docrine subsystems, their development and function, and disorders that manife st when they malfunction. FIGURE 13–1 shows the anatomic locatio n of the endocrine glands. Martin B. Draznin and Manmohan Kamboj Copyright © 2008 by The McGraw-Hill Companies, Inc. Click here for terms of use. The role of hormones begins in utero. One critical function is sexual differentiation. This process requires chromosomal components to cause the gonad to differentiate either to ovary or testis. The gonad th en mi- grates caudally to a location appropriate for the se x of the embryo under the influence of human chorionic gonadotropin (hCG) and, later, pituitary luteinizing hormone (LH). The testes release testoster one to virilize the external genitalia and mullerian inhibiting hormone to sup- press the persistence of the uterus and fallopian tubes to complete male differentiation. Female structures seem to develop without requiring any furth er stimulus at this stage. There is evidence that male and female brains contain subtle structural differences owing in part to androgen exposure during the gestation, but there also may be genetic differences. The thyroid g land coalesces from branchial clefts and migrates to the front of the lower neck by 40 days of gestational age. Its secretion of thy- roid hormone gradually increases throughout gestation, more during the third trimester, a nd then with the postdelivery surge of thyroid- stimulating hormone (TSH), it increases dramatically. The peripheral deiodination of T 4 during gestation is preferentially to the inactive reverse 404 Chapter 13: The Endocrine System Pineal gland Hypothalamus Pituitary gland Thyroid gland Thymus Adrenal gland Pancreas Ovary Testis Parathyroid gland FIGURE 13–1 Endocrine Organs. (From Van de Graaff KM: Human Anatomy. New York: McGraw-Hill, 1998.) T 3 form. On delivery, the newborn preferentially produces T 3 ; thus the gland works in concert with the peripheral tissues, as well as the hy- pothalamus and pituitary, to control thyroid economy. Deficiency of both fetal and maternal thyroid hormone leads to profound hypothy- roidism at birth with attenda nt high risk of severe developmental delay if not rapidly treated. Calcitonin from the thyroid C cells is involved in calcium accretion by bones in utero. Parathyroid hormone is relatively inacti ve, but a parathyroid hormone– like peptide is of vital importance in tissue differentiation and develop- ment in many organ systems. The vitamin D receptor is very important in emb ryogenesis. Adrenal hormones generated in the fetal zone of the adrenal pass through the placenta. They are vital in maintaining the pregnancy to term. The fetal pancreas is capable of secreting insulin to allow nutrients ent ry to cells. Insulin acts as a growth peptide in utero. Following delivery, the endocrine syste ms mediate growth and development, energy metabolism, balance of fluids and e lectrolytes, control of circulating calcium within a na rrow range of concentration, and sexual maturation and function. Symptoms owing to endocrine dysfunction may be very subtle or quite dramati c. Signs also may not be readily apparent early in the course of an endocrine di sorder. Numerous other conditions may suggest an endocrine problem when none is present. History Infants Infants have a limited repertoire of symptoms, exhibit a few more signs than symptoms, and do not speak for themselves. Thus the ability to in- terpret parents’ understanding of their problems is the key to progress in making a diagnosis. There are few symptoms that by themselves declare an endocrine diagnosis. As with any subspecialty area, a thorough general history is the foundation on which to base endocrine-specific questio ns. Present- ing problems that are due to endocrine dysfunction include changes in general well-being, disordered growth, disordered energy metabolism, disordered sexual development or function, alterations of skin and its ap- penda ges, and altered gastrointestinal motility, thirst, and urine output. The review of systems from the general history touches on endocrine function at many levels. We address growth di sorders by focusing on the complaint—too little or too much growth—in a comprehensive manner; i.e., when was the problem first noted, how has the growth changed, does it cause dif- ficulties for the patient, and did other family members have problems or concerns with their growth? Other helpful questions in clude whether the parent replaces clothes and shoes because they are worn out or be- cause they are outgrown, whether the patient can keep up with age peers History 405 [...]... at them from behind A helpful technique to bring the thyroid into relief from behind the strap muscles is to allow the patient’s head to hang over the end of the examination table in the supine position Again, do this in such a way as to avoid frightening the patient Measure the length of each lobe, measure the distance between the upper poles of the thyroid across the neck, measure the diameter of the. .. with the Prader orchidometer standards Stretch the penis and measure the length from the base of the shaft at the pubic symphysis to the tip of the glans This may require pressing the end of the ruler down into a significant fat pad for an accurate measurement Likewise, measure clitoral length from the suspensory ligament to the tip of the glans Do not include the preputial skin Also measure the diameter... bottom of the heels on another right-angle surface that slides to adjust to the length of the infant Measuring in any other fashion introduces significant errors Measure heights with feet flat on a stationary surface instead of the movable doctor’s office scale The back of the heels, the sacrum, the thoracic spine, and the occiput should all touch this plane with the knees fully locked Pull the head... head gently upward with pressure on the mastoid processes while the Frankfort plane (outer canthus of the eye to the top of the auditory canal) is parallel to the floor Measurement at the vertex of the skull is then possible While a wall-mounted stadiometer-like device is preferable, a metal tape and right-angle triangle used for mechanical drawing can work as well The most recent growth norms are listed... If the fingertips slide on the skin, that tactile impression may interfere with feeling the gland Depending on the age of the child and the skill of the examiner, palpation from behind, from the side, or from directly in front of the 4 16 Chapter 13: The Endocrine System TABLE 13–1 Average Growth Velocity per Year Age First year Second year 3–4 years 5–7 years 7 years–puberty Puberty Cm/yr 25 10 7 6. .. manifest early in life Questions that are useful in a family history are whether there are any other affected family members, whether there were any early infant deaths, whether there were any exposures of the mother to androgenic agents during the pregnancy or if she experienced virilization, or for undervirilized males, if there was any exposure to putative endocrine disruptors or estrogenic compounds... development of the patient Proper plotting of values, at the precise age and on the correct chart, will maximize ability to interpret these values Measure length in infants supine on a flat, firm surface with a fixed surface at right angles to the horizontal backboard at one end, against which an assistant gently holds the vertex of the skull The examiner gently but fully stretches the legs and places the bottom... upper poles of the thyroid across the neck, measure the diameter of the neck at the level of the isthmus, and measure the cephalad-to-caudal distance across the isthmus Feel for, and measure, if possible, a “Delphian” lymph node just above the isthmus or for a pyramidal thyroid lobe arising from the cephalad edge of the isthmus These measurements make it much easier to compare thyroid size at subsequent... phosphaturia and even a Fanconi syndrome-like effect with glycosuria and aminoaciduria KEY PROBLEM Constitutional Infants may show little energy, poor feeding, weak cry, poor muscle tone, and other nonspecific variations of activity The older they are, the more specific the parents can make their characterizations The endocrine and endocrine-related conditions that may present with these complaints include hypoglycemia,... only, ignoring preputial size The distance from the anus to the posterior edge of the vaginal opening or fourchette should be less than 50 percent of the distance from the anus to the pubis (anogenital ratio normally less than 50 percent) There should not be fusion or rugation of the labia majora in a female newborn KEY FINDING External Male Genitalia Testes should be in the scrotum by 32 weeks of gestational . history are whether there are any other affected family members, whether there were any early infant deaths, whe ther there were any exposures of the mother to androgenic agents during the pregnancy. muscle tone, and other nonspecific variations of activ- ity. The older they a re, the more specific the parents can make their char- acterizations. The endocrine and endocrine-related conditions. did other family members have problems or concerns with their growth? Other helpful questions in clude whether the parent replaces clothes and shoes because they are worn out or be- cause they