The Child with Endocrine Dysfunction

http://evolve.elsevier.com/wong/essentials

Animations—Adrenal Function; Insulin Injection

Case Studies—Diabetes Mellitus; Diabetes Insipidus

Nursing Care Plans—The Child with Diabetes Mellitus; The Child with Diabetic Ketoacidosis (DKA)

The Endocrine System

The endocrine system consists of three components: (1) the cells, which send chemical messages by means of hormones; (2) the target cells, or end organs, which receive the chemical messages; and (3) the environment through which the chemicals are transported (blood, lymph, extracellular fluids) from the sites of synthesis to the sites of cellular action. The endocrine system controls or regulates metabolic processes governing energy production, growth, fluid and electrolyte balance, response to stress, and sexual reproduction (Baxter and Ribeiro, 2004). The endocrine glands, which are distributed throughout the body, are listed in Table 29-1; also listed are several additional structures sometimes considered endocrine glands, although they are not usually included. The pathophysiology review in Figure 29-1 provides a summary of the principle pituitary hormones and their target organs.

TABLE 29-1

Hormones and Their Function

HORMONE	EFFECT	HYPOFUNCTION	HYPERFUNCTION
Adenohypophysis (Anterior Pituitary)*
STH or GH (somatotropin) Target tissue—Bones	Promotes growth of bone and soft tissues Has main effect on linear growth Maintains a normal rate of protein synthesis Conserves carbohydrate utilization and promotes fat mobilization Is essential for proliferation of cartilage cells at epiphyseal plate Is ineffective for linear growth after epiphyseal closure Has hyperglycemic effect (anti-insulin action)	Epiphyseal fusion with cessation of growth Prepubertal dwarfism Pituitary cachexia (Simmonds disease) Generalized growth retardation Hypoglycemia	Prepubertal gigantism Acromegaly (after full growth is attained) Diabetes mellitus Postpubertal hypoproteinemia
Thyrotropin (TSH) Target tissue—Thyroid gland	Promotes and maintains growth and development of thyroid gland Stimulates TH secretion	Hypothyroidism Marked delay of puberty Juvenile myxedema	Hyperthyroidism Thyrotoxicosis Graves disease
ACTH Target tissue—Adrenal cortex	Promotes and maintains growth and development of adrenal cortex Stimulates adrenal cortex to secrete glucocorticoids and androgens	Acute adrenocortical insufficiency (Addison disease) Hypoglycemia Increased skin pigmentation	Cushing syndrome
Gonadotropins Target tissue—Gonads	Stimulate gonads to mature and produce sex hormones and germ cells	Absent or incomplete spontaneous puberty	Precocious puberty Early epiphyseal closure
FSH Target tissue—Ovaries, testes	Male—Stimulates development of seminiferous tubules; initiates spermatogenesis Female—Stimulates graafian follicles to mature and secrete estrogen	Hypogonadism Sterility Absence or loss of secondary sex characteristics Amenorrhea	Precocious puberty Primary gonadal failure Hirsutism Polycystic ovary Early epiphyseal closure
Luteinizing hormone (LH)^† Target tissue—Ovaries, testes	Male—Stimulates differentiation of Leydig cells, which secrete androgens, principally testosterone Female—Produces rupture of follicle with discharge of mature ovum; stimulates secretion of progesterone by corpus luteum	Hypogonadism Sterility Impotence Absence or loss of secondary sex characteristics Ovarian failure Eunuchism	Precocious puberty Primary gonadal failure Hirsutism Polycystic ovary Early epiphyseal closure
Prolactin (luteotropic hormone) Target tissue—Ovaries, breasts	Stimulates milk secretion Maintains corpus luteum and progesterone secretion during pregnancy	Inability to lactate Amenorrhea	Galactorrhea Functional hypogonadism
MSH Target tissue —Skin	Promotes pigmentation of skin	Diminished or absent skin pigmentation	Increased skin pigmentation
Neurohypophysis (Posterior Pituitary)
ADH (vasopressin) Target tissue—Renal tubules	Acts on distal and collecting tubules, making them more permeable to water, thus increasing reabsorption and decreasing excretion of urine	Diabetes insipidus	SIADH Fluid retention Hyponatremia
Oxytocin Target tissue—Uterus, breasts	Stimulates powerful contractions of uterus Causes ejection of milk from alveoli into breast ducts (letdown reflex)
Thyroid
THs—T₄ and T₃	Regulate metabolic rate; control rate of growth of body cells Especially important for growth of bones, teeth, and brain Promote mobilization of fats and gluconeogenesis	Hypothyroidism Myxedema Hashimoto thyroiditis General growth greatly reduced; extent dependent on age at which deficiency occurs Intellectual disability in infant	Exophthalmic goiter (Graves disease) Accelerated linear growth Early epiphyseal closure
Thyrocalcitonin	Regulates calcium and phosphorus metabolism Influences ossification and development of bone
Parathyroid Glands
PTH	Promotes calcium reabsorption from blood, bone, and intestines Promotes excretion of phosphorus in kidney tubules	Hypocalcemia (tetany)	Hypercalcemia (bone demineralization) Hypophosphatemia
Adrenal Cortex
Mineralocorticoids Aldosterone	Stimulate renal tubules to reabsorb sodium, thus promoting water retention but potassium loss	Adrenocortical insufficiency	Electrolyte imbalance Hyperaldosteronism
Sex hormones—Androgens, estrogens, progesterone	Influence development of bone, reproductive organs, and secondary sex characteristics	Male feminization	Adrenogenital syndrome
Glucocorticoids Cortisol (hydrocortisone and compound F) Corticosterone (compound B)	Promote normal fat, protein, and carbohydrate metabolism Mobilize body defenses during periods of stress Suppress inflammatory reaction	Addison disease Acute adrenocortical insufficiency Impaired growth and sexual function	Cushing syndrome Severe impairment of growth with slowing in skeletal maturation In excess, tend to accelerate gluconeogenesis and protein and fat catabolism
Adrenal Medulla
Epinephrine (adrenaline), norepinephrine (noradrenaline)	Produce vasoconstriction of heart and smooth muscles (raise blood pressure) Increase blood glucose via glycolysis Inhibit GI activity Activate sweat glands		Hyperfunction caused by: Pheochromocytoma Neuroblastoma Ganglioneuroma
Islets of Langerhans of Pancreas
Insulin (β cells)	Promotes glucose transport into the cells Increases glucose utilization, glycogenesis, and glycolysis Promotes fatty acid transport into cells and lipogenesis Promotes amino acid transport into cells and protein synthesis	Diabetes mellitus	Hyperinsulinism
Glucagon (α cells)	Acts as antagonist to insulin, thereby increasing blood glucose concentration by accelerating glycogenolysis Able to inhibit secretion of both insulin and glycogen		Hyperglycemia May be instrumental in genesis of DKA in DM
Somatostatin (δ cells)	Able to inhibit secretion of both insulin and glycogen
Ovaries
Estrogen	Accelerates growth of epithelial cells, especially in uterus after menses Promotes protein anabolism Promotes epiphyseal closure of bones Promotes breast development during puberty and pregnancy Plays role in sexual function Stimulates water and sodium reabsorption in renal tubules Stimulates ripening of ova	Lack of or repression of sexual development	Precocious puberty, early epiphyseal closure
Progesterone	Prepares uterus for nidation of fertilized ovum and aids in maintenance of pregnancy Aids in development of alveolar system of breasts during pregnancy Inhibits myometrial contractions Has effect on protein catabolism Promotes salt and water retention, especially in endometrium
Testes
Testosterone	Accelerates protein anabolism for growth Promotes epiphyseal closure Promotes development of secondary sex characteristics Plays role in sexual function Stimulates testes to produce spermatozoa	Delayed sexual development or eunuchoidism	Precocious puberty, early epiphyseal closure

ACTH, Adrenocorticotropic hormone; ADH, antidiuretic hormone; DKA, diabetic ketoacidosis; DM, diabetes mellitus; FSH, follicle-stimulating hormone; GH, growth hormone; GI, gastrointestinal; MSH, melanocyte-stimulating hormone; PTH, parathyroid hormone; SIADH, syndrome of inappropriate antidiuretic hormone secretion; STH, somatotropin hormone; T₃, triiodothyronine; T₄, thyroxine; TH, thyroid hormone; TSH, thyroid-stimulating hormone.

^*For each anterior pituitary hormone there is a corresponding hypothalamic-releasing factor. A deficiency in these factors caused by inhibiting anterior pituitary hormone synthesis produces the same effects. (See text for more detailed information.)

^†In males, LH is sometimes known as interstitial cell–stimulating hormone (ICSH).

A hormone is a complex chemical substance produced and secreted into body fluids by a cell or group of cells that exerts a physiologic controlling effect on other cells (Kliegman, Stanton, St. Geme, and others, 2011). These effects may be local or distant and may affect either most cells of the body or specific “target” tissues. Hormones are released by the endocrine glands into the bloodstream, and production is regulated by a feedback mechanism (see Table 29-1). The master gland of the endocrine system is the anterior pituitary, which is in turn controlled by the hypothalamus. Some hormones, such as insulin, are regulated by other mechanisms.

Disorders of Pituitary Function

The pituitary gland is divided into two lobes, the anterior and the posterior lobes. Each lobe is responsible for different hormones. Disorders of the anterior pituitary hormones may be attributable to organic defects or have an idiopathic etiology and may occur as a single hormonal problem or in combination with other hormonal disorders. The clinical manifestations depend on the hormones involved and the age of onset. Panhypopituitarism is often defined clinically as the loss of all anterior pituitary hormones, leaving only posterior function intact (Toogood and Stewart, 2008).

Nursing Alert

Children with panhypopituitarism should wear medical identification, such as a bracelet.

Hypopituitarism

Hypopituitarism is diminished or deficient secretion of pituitary hormones. The consequences of the condition depend on the degree of dysfunction and can lead to gonadotropin deficiency with absence or regression of secondary sex characteristics; growth hormone (GH) deficiency, in which children display retarded somatic growth; thyroid-stimulating hormone (TSH) deficiency, which produces hypothyroidism; and corticotropin deficiency, which results in manifestations of adrenal hypofunction. Hypopituitarism can result from any of the conditions listed in Box 29-1. The most common organic cause of pituitary undersecretion is tumors in the pituitary or hypothalamic region, especially the craniopharyngiomas. Congenital hypopituitarism can be seen in newborn infants, often as a result of birth trauma. Symptoms of hypoglycemia and seizure activity often manifest within the first 24 hours after birth (Toogood and Stewart, 2008).

Box 29-1 Clinical Manifestations of Panhypopituitarism

Growth Hormone

Short stature but proportional height and weight

Delayed epiphyseal closure

Retarded bone age proportional to height

Premature aging common in later life

Increased insulin sensitivity

Thyroid-Stimulating Hormone

Short stature with infantile proportions

Dry, coarse skin; yellow discoloration, pallor

Delayed dentition, loss of teeth

Gonadotropins

Absence of sexual maturation or loss of secondary sexual characteristics

Atrophy of genitalia, prostate gland, breasts

Amenorrhea without menopausal symptoms

Decreased spermatogenesis

Adrenocorticotropic Hormone

Severe anorexia, weight loss

Hypoglycemia

Hypotension

Hyponatremia, hyperkalemia

Adrenal apoplexy, especially in response to stress

Melanocyte-Stimulating Hormone

Decreased pigmentation

Idiopathic hypopituitarism, or idiopathic pituitary growth failure, is usually related to GH deficiency, which inhibits somatic growth in all cells of the body (Miller and Zimmerman, 2004). Growth failure is defined as an absolute height of less than −2 standard deviation (SD) for age or a linear growth velocity consistently less than −1 SD for age. When this occurs without the presence of hypothyroidism, systemic disease, or malnutrition, then an abnormality of the GH–insulin-like growth factor (IGF-I) axis should be considered (Richmond and Rogol, 2008). Not all children with short stature have GH deficiency. In most instances, the cause is either familial short stature or constitutional growth delay. Familial short stature refers to otherwise healthy children who have ancestors with adult height in the lower percentiles. Constitutional growth delay refers to individuals (usually boys) with delayed linear growth, generally beginning as a toddler, and skeletal and sexual maturation that is behind that of age mates (Halac and Zimmerman, 2004; Miller and Zimmerman, 2004). Typically, these children will reach normal adult height. Often there is a history of a similar pattern of growth in one of the child’s parents or other family members. The untreated child will proceed through normal changes as expected on the basis of bone age. Although treatment with GH is not usually indicated, its use has become controversial, especially in relation to parental and child requests for treatment to accelerate growth.

Clinical Manifestations

Children with hypopituitarism generally grow normally during the first year and then follow a slowed growth curve that is below the third percentile. Skeletal proportions and weight are normal for the age, but these children may appear younger than their chronologic age. Dentition is delayed, and teeth may be overcrowded and malpositioned because of the undeveloped jaw. Sexual development is usually delayed but is otherwise normal unless the gonadotropin hormones are deficient. Growth may extend into the third or fourth decade of life, but permanent height is usually diminished if the disorder is left untreated. Symptoms such as headache and vision changes may indicate the presence of a tumor. Clinical manifestations of panhypopituitarism are listed in Box 29-1.

Diagnostic Evaluation

Only a small number of children with delayed growth or short stature have hypopituitary dwarfism. In the majority of instances, the cause is constitutional delay. Diagnostic evaluation is aimed at isolating organic causes, which, in addition to GH deficiency, may include hypothyroidism, oversecretion of cortisol, gonadal aplasia, chronic illness, nutritional inadequacy, Russell-Silver dwarfism, or hypochondroplasia.

A complete diagnostic evaluation should include a family history, a history of the child’s growth patterns and previous health status, physical examination, psychosocial evaluation, radiographic surveys, and endocrine studies. Accurate measurement of height (using a calibrated stadiometer) and weight and comparison with standard growth charts are essential. Multiple height measures reflect a more accurate assessment of abnormal growth patterns (Box 29-2) (Hall, 2000). Parental height and familial patterns of growth are important clues to diagnosis.

Box 29-2

Evaluating the Growth Curve

Ensure reliability of measurements. Accurately obtain and plot height and weight measurements.

Determine absolute height. The child’s absolute height bears some relationship to the likelihood of a pathologic condition. However, the majority of children who have a height below the lowest percentile (either the third or fifth percentile on the height curve) do not have a pathologic growth problem.

Assess height velocity. The most important aspect of a growth evaluation is the observation of a child’s height over time, or height velocity. Accurate determination of height velocity requires at least 4 and preferably 6 months of observation. A substantial deceleration in height velocity (crossing several percentiles) between 3 and 12 or 13 years of age indicates a pathologic condition until proven otherwise.

Determine weight-to-height relationship. Determination of the weight-to-height ratio has some diagnostic value in ascertaining the cause of growth retardation in a short child.

Project target height. The height of a child can be judged inappropriately short only in the context of his or her genetic potential. Determine the target height of the child with the formula:

[Father’s height (cm) + Mother’s height (cm) + 13]/2 for boys

[Father’s height (cm) + Mother’s height (cm) − 13]/2 for girls

Most children achieve an adult stature within approximately 10 cm (4 inches) of the target height.

Modified from Vogiatzi MG, Copeland KC: The short child, Pediatr Rev 19(3):92–99, 1998.

A skeletal survey in children younger than 3 years of age and radiographic examination of the hand–wrist for centers of ossification (bone age) (Box 29-3) in older children are important in evaluating growth.

Box 29-3

Bone Age for Evaluating Growth Disorders

Bone age refers to a method of assessing skeletal maturity by comparing the appearance of representative epiphyseal centers obtained on x-ray examination with age-appropriate published standards.

Most conditions that cause poor linear growth also cause a delay in skeletal maturation and a retarded bone age. Observation of even a profoundly delayed bone age is never diagnostic or even indicative of a specific diagnosis. A delayed bone age merely indicates that the associated short stature is to some extent “partially reversible” because linear growth will continue until epiphyseal fusion is complete. In comparison, a bone age that is not delayed in a short child is of much greater concern and may, in fact, be of some diagnostic value under certain circumstances.

Modified from Vogiatzi MG, Copeland KC: The short child, Pediatr Rev 19(3):92–99, 1998.

Definitive diagnosis is based on absent or subnormal reserves of pituitary GH. Because GH levels are variable in children, GH stimulation testing is usually required for diagnosis. Initial assessment of the serum IGF-I and IGF binding protein 3 (IGFBP3) indicates a need for further evaluation of GH dysfunction if levels are less than −1 SD below the mean for age. It is recommended that GH stimulation tests be reserved for children with low serum IGF-I and IGFBP3 levels and poor growth who do not have other causes for short stature (Richmond and Rogol, 2008). GH stimulation testing involves the use of pharmacologic agents such as levodopa, clonidine, arginine, insulin, propranolol, or glucagon to provoke the release of GH (Kliegman, Stanton, St. Geme, and others, 2011). Children with poor linear growth, delayed bone age, and abnormal GH stimulation tests are considered GH deficient.

Nursing Tip

Optimum dosing is often achieved when GH is administered at bedtime. Physiologic release is more normally stimulated as a result of pituitary release of GH during the first 45 to 90 minutes after the onset of sleep.

Even when hormone replacement is successful, these children attain their eventual adult height at a slower rate than their peers; therefore, they need assistance in setting realistic expectations regarding improvement. Because these children appear younger than their chronologic age, others frequently relate to them in infantile or childish ways. Parents and teachers benefit from guidance directed toward setting realistic expectations for the child based on age and abilities. For example, in the home, such children should have the same age-appropriate responsibilities as their siblings. As they approach adolescence, they should be encouraged to participate in group activities with peers. If abilities and strengths are emphasized rather than physical size, such children are more likely to develop a positive self-image.

Professionals and families can find resources for research, education, support, and advocacy from the Human Growth Foundation.* The treatment is expensive, but the cost is often partially covered by insurance if the child has a documented deficiency. Children with panhypopituitarism should be advised to wear medical identification at all times.

Pituitary Hyperfunction

Excess GH before closure of the epiphyseal shafts results in proportional overgrowth of the long bones until the individual reaches a height of 2.4 m (8 ft) or more. Vertical growth is accompanied by rapid and increased development of muscles and viscera. Weight is increased but is usually in proportion to height. Proportional enlargement of head circumference also occurs and may result in delayed closure of the fontanels in young children. Children with a pituitary-secreting tumor may also demonstrate signs of increasing intracranial pressure, especially headache.

If oversecretion of GH occurs after epiphyseal closure, growth is in the transverse direction, producing a condition known as acromegaly. Typical facial features include overgrowth of the head, lips, nose, tongue, jaw, and paranasal and mastoid sinuses; separation and malocclusion of the teeth in the enlarged jaw; disproportion of the face to the cerebral division of the skull; increased facial hair; thickened, deeply creased skin; and an increased tendency toward hyperglycemia and diabetes mellitus (DM). Acromegaly can develop slowly, leading to delays in diagnosis and treatment.

Diagnostic Evaluation

Diagnosis is based on a history of excessive growth during childhood and evidence of increased levels of GH. Radiographic studies may reveal a tumor in an enlarged sella turcica, normal bone age, enlargement of bones (e.g., the paranasal sinuses), and evidence of joint changes. Endocrine studies to confirm excess of other hormones, specifically thyroid, cortisol, and sex hormones, should also be included in the differential diagnosis.

Therapeutic Management

If a lesion is present, surgery is performed to remove the tumor when feasible. Other therapies aimed at destroying pituitary tissue include external irradiation and radioactive implants. New pharmacologic agents have evolved and may be use in combination with other therapies (Natchtigall, Delgado, Swearingen, and others, 2008). Depending on the extent of surgical extirpation and degree of pituitary insufficiency, hormone replacement with thyroid extract, cortisone, and sex hormones may be necessary.

Nursing Care Management

The primary nursing consideration is early identification of children with excessive growth rates. Although medical management is unable to reduce growth already attained, further growth can be retarded. The earlier the treatment, the more control there is in predetermining a normal adult height. Nurses should also observe for signs of a tumor, especially headache, and evidence of concurrent hormonal excesses, particularly the gonadotropins, which cause sexual precocity. Children with excessive growth rates require as much emotional support as those with short stature.

Precocious Puberty

Manifestations of sexual development before age 9 years in boys or age 8 years in girls have traditionally been considered precocious development, and these children were recommended for further evaluation (Kempers and Otten, 2002; Midyett, Moore, and Jacobson, 2003). Recent examination of the age limit for defining when puberty is precocious reveals that the onset of puberty in girls is occurring earlier than previous studies have documented (Biro, Huang, Crawford, and others, 2006; Slyper, 2006). The mean onset of puberty was 10.2 years in white girls and 9.6 years in African-American girls. Based on these findings, precocious puberty evaluation for a pathologic cause should be performed for white girls younger than 7 years of age or for African-American girls younger than 6 years of age. No change in the guidelines for evaluation of precocious puberty in boys is recommended. However, recent data suggest that boys may be beginning maturation earlier as well (Herman-Giddens, 2006; Slyper, 2006).

Normally, the hypothalamic-releasing factors stimulate secretion of the gonadotropic hormones from the anterior pituitary at the time of puberty. In boys, interstitial cell–stimulating hormone stimulates Leydig cells of the testes to secrete testosterone; in girls, follicle-stimulating hormone (FSH) and luteinizing hormone stimulate the ovarian follicles to secrete estrogens (Nebesio and Eugster, 2007). This sequence of events is known as the hypothalamic–pituitary–gonadal axis. If for some reason the cycle undergoes premature activation, the child will display evidence of advanced or precocious puberty. Causes of precocious puberty are found in Box 29-4.

Box 29-4

Causes of Precocious Puberty

Central Precocious Puberty