Chapter 51 - Endocrine Conditions PDF

UNIT 12 Health Conditions of Children 51 Endocrine Conditions Cheryl Sams and Nancy Caprara Originating US chapter by Cheryl C. Rodgers http://evolve.elsevier.com/Canada/Perry/maternal OBJECTIVES On completion of this chapter the reader will be able to: 1. Differentiate between the disorders cause...

UNIT 12 Health Conditions of Children 51 Endocrine Conditions Cheryl Sams and Nancy Caprara Originating US chapter by Cheryl C. Rodgers http://evolve.elsevier.com/Canada/Perry/maternal OBJECTIVES On completion of this chapter the reader will be able to: 1. Differentiate between the disorders caused by hypopituitary and hyperpituitary dysfunction. 2. Describe the manifestations of thyroid hypofunction and hyperfunction and the care of children with the disorders. 3. Distinguish between the manifestations of adrenal hypofunction and hyperfunction. 4. Differentiate among the various categories of diabetes mellitus. 5. Discuss care of the child with diabetes mellitus in the acute care setting. 6. Distinguish between a hypoglycemic and a hyperglycemic reaction. 7. Design a teaching plan for a child with diabetes mellitus along with their family. THE ENDOCRINE SYSTEM DISORDERS OF PITUITARY FUNCTION The endocrine system controls or regulates metabolic processes governing energy production, growth, fluid and electrolyte balance, response to stress, and sexual reproduction. 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 pathophysiology review in Figure 51.1 provides a summary of the principal pituitary hormones and their target organs. The pituitary gland is divided into two lobes—the anterior (adenohypophysis) and the posterior (neurohypophysis) lobe. Each lobe is responsible for secreting 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 disorder or in combination with other hormonal disorders. The clinical manifestations of pituitary dysfunction depend on the hormones involved and the age of the patient. Panhypopituitarism is defined clinically as the loss of all anterior pituitary hormones, leaving only posterior function intact (Lang et al., 2015). Clinical manifestations of panhypopituitarism are listed in Box 51.1. Hormones A hormone is a complex chemical substance produced and secreted into body fluids by a cell or group of cells that exerts a physiological controlling effect on other cells. 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. The master gland of the endocrine system is the anterior pituitary gland, which is responsible for stimulation and inhibition of tropic hormones. However, some hormones, such as insulin, are regulated by other mechanisms. NURSING ALERT Children with panhypopituitarism should wear a medical alert bracelet or necklace. Hypopituitarism Hypopituitarism is diminished or deficient secretion of one or more pituitary hormones. The consequences of the condition depend on the degree of dysfunction. It often leads to gonadotropin deficiency 1377 1378 UNIT 12 Health Conditions of Children Hypothalamic nerve cell Bone Growth hormone (GH) Anterior pituitary Posterior pituitary Antidiuretic hormone (ADH) Adrenocorticotropic hormone (ACTH) Adrenal cortex Kidney tubules Thyroidstimulating hormone (TSH) Thyroid gland Gonadotropic hormones (FSH and LH) Oxytocin (OT) Melanocytestimulating hormone (MSH) Uterus smooth muscle Prolactin (PRL) Testis Mammary glands Ovary Skin Mammary glands Fig. 51.1 Principal anterior and posterior pituitary hormones and their target organs. FSH, Follicle-stimulating hormone; LH, luteinizing hormone. (From Patton, K. T., & Thibodeau, G. A. [2016]. Anatomy and physiology [9th ed.]. Elsevier.) BOX 51.1 Clinical Manifestations of Panhypopituitarism Growth Hormone • Short stature but proportional height and weight • Delayed epiphyseal closure • Delayed 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 • Cold intolerance • Constipation • Somnolence • Bradycardia • Dyspnea on exertion • 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 • Circulatory collapse Antidiuretic Hormone • Polyuria • Polydipsia • Dehydration Melanocyte-Stimulating Hormone • Decreased pigmentation CHAPTER 51 Endocrine Conditions with absence or regression of secondary sex characteristics; growth hormone (GH) deficiency, in which children display stunted somatic growth; thyroid-stimulating hormone (TSH) deficiency, which produces hypothyroidism; and adrenocorticotropic hormone (ACTH) deficiency, which results in adrenal hypofunction. Hormones associated with this condition and the respective clinical manifestations are listed in Box 51.1. The most common organic cause of pituitary undersecretion is a tumour in the pituitary or hypothalamic region, especially the craniopharyngiomas. Congenital hypopituitarism can be seen in newborns and can run in families, suggesting a genetic cause (Alatzoglou & Dattani, 2010). Symptoms of apnea, cyanosis, severe hypoglycemia, prolonged newborn cholestatic jaundice, and seizure activity often manifest in infants with congenital hypopituitarism (Patterson & Felner, 2020). Idiopathic hypopituitarism, or idiopathic pituitary growth failure, is usually related to GH deficiency, which inhibits somatic growth in all cells of the body (Patterson & Felner, 2020). Growth failure is defined as an absolute height of less than
2 standard deviations (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, an abnormality of the GH–insulin-like growth factor (IGF-I) axis should be considered (Patterson & Felner, 2020). 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 (Patterson & Felner, 2020). 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. BOX 51.2 1379 Clinical Manifestations. Children with GH deficiency generally grow normally during the first year and then follow a slowed growth curve that is below the third percentile. These children may appear overweight or obese due to stunted height in combination with good nutrition. A nourished appearance is an important diagnostic clue that may differentiate patients with GH deficiency from patients with failure to thrive. 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. Because of an underdeveloped jaw, teeth may be crowded or malpositioned. Diagnostic Evaluation. Only a small number of children with delayed growth or short stature have hypopituitary-related growth failure. In most 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, and psychosocial evaluation. Specific radiographic imaging, including magnetic resonance imaging (MRI), endocrine studies, and genetic testing, may be warranted. Accurate measurement of height and weight and comparison with standard growth charts are essential. Multiple height measures reflect a more accurate assessment of abnormal growth patterns (Box 51.2). Parental height and familial patterns of growth are important clues to the diagnosis. A skeletal survey in children less than 3 years of age and radiographic examination of the hand-wrist for centres of ossification (bone age) in older children are important in evaluating growth (Box 51.3). 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 pathological condition. However, most children who have a height below the lowest percentile (either third or fifth percentile on the height curve) do not have a pathological growth condition. Assess height velocity—The most important aspect of a growth evaluation is 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 pathological condition until proven otherwise. Determine weight-to-height relationship—Determination of the weight-toheight ratio has some diagnostic value in ascertaining the cause of growth restriction in a short child. Project target height—The height of a child can be judged inappropriately short only in the context of their genetic potential. The target height of the child can be determined with the formula: [Father’s height (cm) + Mother’s height (cm) + 13] /2 for boys or [Father’s height (cm) + Mother’s height (cm)
13] /2 for girls Most children achieve an adult stature within approximately 10 cm of the target height. Modified from Vogiatzi, M. G., & Copeland, K. C. (1998). The short child. Pediatrics in Review, 19(3), 92–99. BOX 51.3 Bone Age for Evaluating Growth Disorders Bone age refers to a method of assessing skeletal maturity by comparing the appearance of representative epiphyseal centres 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 restricted 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,” since 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, M. G., & Copeland, K. C. (1998). The short child. Pediatrics in Review, 19(3), 92–99. 1380 UNIT 12 Health Conditions of Children Definitive diagnosis of GH deficiency 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. 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 (Patterson & Felner, 2020). GH stimulation testing involves the use of pharmacological agents such as levodopa, clonidine, arginine, insulin, propranolol, or glucagon followed by the measurement of GH blood levels (Patterson & Felner, 2020). Children with poor linear growth, delayed bone age, and abnormal GH stimulation tests are considered GH deficient. Therapeutic Management. Treatment of GH deficiency caused by organic lesions is directed toward correction of the underlying disease process (e.g., surgical removal or irradiation of a tumour). The definitive treatment of GH deficiency is replacement of GH, which is successful in 80% of affected children. Biosynthetic GH is administered subcutaneously on a daily basis. Growth velocity increases in the first year and then declines in subsequent years. Final height is likely to remain less than normal and early diagnosis and intervention are essential (Patterson & Felner, 2020). Some patients develop hypothyroidism while under treatment with GH. Similarly, there is a risk of developing adrenal insufficiency as an associated component of hypopituitarism. If unrecognized, hypothyroidism and adrenal insufficiency can be fatal. Periodic evaluation of thyroid and adrenal function is indicated for all patients diagnosed with GH deficiency (Patterson & Felner, 2020). The decision to stop GH therapy is made jointly by the child, family, and health care team. Growth rates of less than 2.5 cm/year, a decision by the patient that they are tall enough, and a bone age of more than 14 years in girls and more than 16 years in boys are often used as criteria to stop GH therapy (Patterson & Felner, 2020). Children with other hormone deficiencies require replacement therapy to correct the specific disorders. This may involve administration of thyroid extract, cortisone, testosterone, or estrogens and progesterone. Treatment with the sex hormones is usually begun during adolescence to promote normal sexual maturation. Nursing Care. The principal nursing consideration is identifying children with growth deficiencies. Even though the majority of growth issues are not a result of organic causes, any delay in normal growth and sexual development can pose emotional adjustments for these children. The nurse may be a key person in helping to establish a diagnosis. For example, if serial height and weight records are not available, the nurse can question parents about the child’s growth compared with that of siblings, peers, or relatives. Preparation of the child and family is especially important if a number of tests are being performed, and the child requires particular attention during provocative testing. Blood samples are usually taken every 30 minutes over a 3-hour period. Children also have difficulty overcoming hypoglycemia generated by tests, surgeries, and procedures, so they must be observed carefully for signs of hypoglycemia. Children receiving glucagon are at risk for nausea and vomiting. Clonidine may cause hypotension, requiring administration of intravenous (IV) fluids. Child and family support. Children undergoing hormone replacement require additional support. The nurse should provide education for patient self-management during the school-age years. Nursing functions include family education concerning medication preparation and storage, injection sites, injection technique, and syringe disposal (see Chapter 44). Administration of GH is facilitated by family routines that include a specific time of day for the injection. Younger children may enjoy using a calendar and colourful stickers to designate received injections. NURSING ALERT Optimum dosing is frequently achieved when growth hormone (GH) is administered at bedtime. Physiological release is more normally stimulated due to 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 that of their peers; therefore, they need assistance in setting realistic expectations regarding improvement. Because these children appear younger than their chronological 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, these children should have the same ageappropriate 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, these children are more likely to develop a positive self-image. 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 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 tumour 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 increased tendency toward hyperglycemia and diabetes mellitus (DM). Acromegaly can develop slowly, which may delay diagnosis and treatment. Diagnostic Evaluation. Excessive secretion of GH by a pituitary adenoma causes most cases of acromegaly. Diagnosis is based on a history of excessive growth during childhood and evidence of increased levels of GH. MRI may reveal a tumour or an enlarged sella turcica, normal bone age, enlargement of bones (e.g., the paranasal sinuses), and evidence of joint changes. Endocrine studies to confirm an 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, surgical treatment by cryosurgery or hypophysectomy is performed to remove the tumour, when feasible. Other therapies aimed at destroying pituitary tissue include external irradiation and radioactive implants. Several pharmacological agents have been developed that may be used in combination with other therapies (Ali, 2020). Depending on the extent of surgical excision and degree of pituitary insufficiency, hormone replacement with thyroid extract, cortisone, and sex hormones may be necessary. CHAPTER 51 Endocrine Conditions Nursing Care. 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 restricted. The earlier the treatment, the more control there is in predetermining adult height. Nurses in ambulatory settings who are frequently involved in growth screening should refer children who demonstrate excessive linear growth for a medical evaluation. They should also observe for signs of a tumour, 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. Children and their parents need an opportunity to express their thoughts. A compassionate nurse can be supportive to these children, especially before adolescence, when they are larger than their peers. 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. The onset of puberty varies among children and may be influenced by ethnicity, making this a subjective definition. 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 had documented (Garibaldi & Chemaitilly, 2020). Mean onset of puberty is presently 10.2 and 9.6 years in White and Black girls, respectively (Latronico et al., 2016). Based on this pattern, it is recommended that precocious puberty evaluation for a pathological cause be performed for White girls younger than 7 years of age and for Black girls younger than 6 years of age. There is a concern that early menarche will increase the risk of future breast cancer (Canadian Cancer Society, 2021). No change in the guidelines for evaluation of precocious puberty in boys is recommended. 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’s cells of the testes to secrete testosterone; in girls, folliclestimulating hormone (FSH) and luteinizing hormone (LH) stimulate the ovarian follicles to secrete estrogens. 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 listed in Box 51.4. BOX 51.4 1381 Isosexual precocious puberty is more common among girls than boys. Approximately 80% of children with precocious puberty have central precocious puberty (CPP), in which pubertal development is activated by the hypothalamic gonadotropin-releasing hormone (GnRH) (Garibaldi & Chemaitilly, 2020). This produces early maturation and development of the gonads with secretion of sex hormones, development of secondary sex characteristics, and sometimes production of mature sperm and ova. CPP may be the result of congenital anomalies; infectious, neoplastic, or traumatic insults to the central nervous system (CNS); or treatment of long-standing sex hormone exposure (Latronico et al., 2016). CPP occurs more frequently in girls and is usually idiopathic, with 90% of cases demonstrating no causative factor (Garibaldi & Chemaitilly, 2020). A CNS insult or structural abnormality is found in more than 75% of boys with CPP (Garibaldi & Chemaitilly, 2020). Peripheral precocious puberty includes early puberty resulting from hormone stimulation other than the hypothalamic GnRH–stimulated pituitary gonadotropin release. Isolated manifestations that are usually associated with puberty may be seen as variations in normal sexual development (Garibaldi & Chemaitilly, 2020). They appear without other signs of pubescence and are probably caused by unusual endorgan sensitivity to prepubertal levels of estrogen or androgen. Included are premature thelarche (development of breasts in prepubertal girls), premature pubarche (premature adrenarche, early development of sexual hair), and premature menarche (isolated menses without other evidence of sexual development). Therapeutic Management. Treatment of precocious puberty is directed toward the specific cause, when known. In 50% of cases, precocious pubertal development regresses or stops advancing without any treatment. If needed, precocious puberty of central (hypothalamic– pituitary) origin is managed with monthly injections of a synthetic analogue of luteinizing hormone–releasing hormone, which regulates pituitary secretions (Garibaldi & Chemaitilly, 2020). The available preparation, leuprolide acetate (Lupron Depot), is given intramuscularly once every 4 to 12 weeks depending on the preparation. The GnRH analogue (GnRHa) histrelin has been formulated to implant in the subdermal tissue and may be useful for patients who want to avoid injections (Garibaldi & Chemaitilly, 2020). Once treatment is initiated, breast development regresses or does not advance, and growth returns to normal rates, enhancing predicted height. Studies suggest that not all patients attain adult targeted heights Causes of Precocious Puberty Central Precocious Puberty Idiopathic, with or without hypothalamic hamartoma Secondary • Congenital anomalies • Postinflammatory—Encephalitis, meningitis, abscess, granulomatous disease • Radiotherapy • Trauma • Neoplasms After effective treatment of long-standing pseudosexual precocity Peripheral Precocious Puberty Familial male-limited precocious puberty Albright syndrome Gonadal or extragonadal tumours Adrenal • Congenital adrenal hyperplasia • Adenoma, carcinoma • Glucocorticoid resistance Exogenous sex hormones Primary hypothyroidism Incomplete Precocious Puberty Premature thelarche Premature menarche Premature pubarche or adrenarche Modified from Garibaldi, L. R., & Chemaitilly, W. (2020). Disorders of pubertal development. In R. M. Kliegman, J. St. Geme, N. J. Blum, et al. (Eds.), Nelson textbook of pediatrics (21st ed.). Elsevier. 1382 UNIT 12 Health Conditions of Children and the addition of GH therapy may be warranted (Garibaldi & Chemaitilly, 2020). Treatment is discontinued at a chronologically appropriate time, allowing pubertal changes to resume. Nursing Care. Psychological support and guidance of the child and family are the most important aspects of nursing care. Both parents and the affected child should be taught the injection procedure. Parents need anticipatory guidance, support and information resources, and reassurance of the benign nature of the condition. Dress and activities for the physically precocious child should be appropriate to the chronological age. Sexual interest is not usually advanced beyond the child’s chronological age, and parents need to understand that the child’s mental age is congruent with the chronological age. Diabetes Insipidus The principal disorder of posterior pituitary hypofunction is diabetes insipidus (DI), also known as neurogenic DI, resulting from undersecretion of antidiuretic hormone (ADH), also known as vasopressin, and producing a state of uncontrolled diuresis (Breault & Majzoub, 2020). This disorder is not to be confused with nephrogenic DI, a rare hereditary disorder affecting primarily males and caused by unresponsiveness of the renal tubules to the hormone. Neurogenic DI may result from a number of different causes. Primary causes are familial or idiopathic; in about 10% of children the etiology is idiopathic. Other pituitary hormone deficiencies may be present. Over time, up to 35% of those with idiopathic DI will develop other hormone deficiencies or have an underlying etiology identified (Breault & Majzoub, 2020). Secondary causes include trauma (accidental or surgical), tumours, granulomatous disease, infections (meningitis or encephalitis), and vascular anomalies (aneurysm). Certain drugs, such as alcohol or phenytoin (diphenylhydantoin), can cause a transient polyuria. DI may be an early sign of an evolving cerebral process (Breault & Majzoub, 2020). The cardinal signs of DI are polyuria and polydipsia. In the older child, signs such as excessive urination accompanied by a compensatory insatiable thirst may be so intense that the child does little more than go to the toilet and drink fluids. Frequently the first sign is enuresis. In infants, the initial symptom is irritability that is relieved with feedings of water but not milk. These infants are also prone to dehydration, electrolyte imbalance, hyperthermia, azotemia, and potential circulatory collapse. Dehydration is usually not a serious issue in older children, who are able to drink larger quantities of water. However, any period of unconsciousness, such as after trauma or anaesthesia, may be life-threatening because the voluntary demand for fluid is absent. During such instances careful monitoring of urine volumes, blood concentration, and IV fluid replacement is essential to prevent dehydration. NURSING ALERT The child with DI complicated by congenital absence of the thirst centre must be encouraged to drink sufficient quantities of liquid to prevent electrolyte imbalance. urine concentration (specific gravity or osmolality), and frequent weight checks. A weight loss between 3 and 5% indicates significant dehydration and requires termination of the fluid restriction. NURSING ALERT Small children require close observation during fluid deprivation to prevent them from drinking from toilet bowls, flower vases, or other unlikely sources of fluid. If this test is positive, the child should be given a test dose of injected aqueous vasopressin, which should alleviate the polyuria and polydipsia. Unresponsiveness to exogenous vasopressin usually indicates nephrogenic DI. An important diagnostic consideration is to differentiate DI from other causes of polyuria and polydipsia, especially DM. Therapeutic Management. The usual treatment is intranasal, oral, or parenteral desmopressin (DDAVP), a synthetic hormone replacement of aqueous lysine vasopressin. The injectable form of DDAVP has the advantage of lasting 48 to 72 hours; however, it has the disadvantage of requiring frequent injections and proper preparation of the medication (Breault & Majzoub, 2020). Nursing Care. The initial objective is identification of the disorder. Because an early sign may be sudden enuresis in a child who has achieved toilet independence, excessive thirst with bed-wetting is an indication for further investigation. Another clue is persistent irritability and crying in an infant that is relieved only by bottle-feedings of water. After head trauma or certain neurosurgical procedures, the development of DI can be anticipated; these patients must be closely monitored. Assessment includes measurement of body weight, serum electrolytes, blood urea nitrogen (BUN), hematocrit, and urine specific gravity taken before surgery and every other day after the procedure. Fluid intake and output should be carefully measured and recorded. Alert patients are able to adjust intake to urine losses, but unconscious or very young patients require closer fluid observation. In children who have not achieved toilet independence, collection of urine specimens may require application of a urine-collecting device. After confirmation of the diagnosis, parents need a thorough explanation regarding the condition with specific clarification that DI is a different condition from DM. They must realize that treatment is lifelong. If children are to receive the injectable vasopressin, ideally two caregivers should be taught the correct procedure for preparation and administration of the medication. Once children are old enough, they should be encouraged to assume full responsibility for their care. For emergency purposes, these children should wear a medical alert identifier. Older children should carry the nasal spray with them for temporary relief of symptoms. School personnel need to be aware of the child’s condition so they can grant children unrestricted use of the lavatory. Failure to permit this may result in embarrassing accidents that often lead to a child’s unwillingness to attend school. Diagnostic Evaluation. The simplest test used to diagnose this con- Syndrome of Inappropriate Antidiuretic Hormone dition is restriction of oral fluids and observation of consequent changes in urine volume and concentration. Normally, reducing fluids results in concentrated urine and diminished volume. In DI, fluid restriction has little or no effect on urine formation but causes weight loss from dehydration. Accurate results from this procedure require strict monitoring of fluid intake and urine output, measurement of The disorder that results from hypersecretion of ADH from the posterior pituitary hormone is known as syndrome of inappropriate antidiuretic hormone (SIADH). It is observed with increased frequency in a variety of conditions, especially those involving infections, tumours, or other CNS disease or trauma, and is a common cause of hyponatremia in the pediatric population (Greenbaum, 2020). CHAPTER 51 Endocrine Conditions The manifestations are directly related to fluid retention and hypotonicity. Excess ADH causes most of the filtered water to be reabsorbed from the kidneys back into central circulation. Serum osmolality is low, and urine osmolality is inappropriately elevated. When serum sodium levels are diminished to 120 mmol/L, affected children display anorexia, nausea (and sometimes vomiting), stomach cramps, irritability, and personality changes. With progressive reduction in sodium, other neurological signs, stupor, and convulsions may be evident (Greenbaum, 2020). The symptoms usually disappear when the underlying disorder is corrected. The immediate management consists of restricting fluids. Subsequent management depends on the cause and severity. Fluids continue to be restricted to one-fourth to one-half maintenance. When there are no fluid abnormalities but SIADH can be anticipated, fluids are often restricted expectantly at two-thirds to three-fourths maintenance. Nursing Care. The first goal of nursing care is recognizing the presence of SIADH from symptoms described in patients at risk, especially those in the pediatric critical care unit. NURSING ALERT Nausea, vomiting, and malaise may precede the onset of more severe stages, such as disorientation, confusion, coma, and seizures (Greenbaum, 2020). Accurately measuring intake and output, noting daily weight, and observing for signs of fluid overload are primary nursing functions, especially in children receiving IV fluids. Seizure precautions should be implemented, and the child and family need education regarding the rationale for fluid restrictions. Rarely, children with chronic SIADH will be placed on long-term ADH-antagonizing medication, and the child and family will require instructions for its administration. DISORDERS OF THYROID FUNCTION The thyroid gland secretes two types of hormones: thyroid hormone (TH), which consists of the hormones thyroxine (T4) and triiodothyronine (T3), and calcitonin. The secretion of thyroid hormones is controlled by TSH from the anterior pituitary, which in turn is regulated by thyrotropin-releasing factor (TRF) from the hypothalamus as a negative feedback response. Consequently, hypothyroidism or hyperthyroidism may result from a defect in the target gland or from a disturbance in the secretion of TSH or TRF. Because the functions of T3 and T4 are qualitatively the same, the term TH is used throughout this discussion. The synthesis of TH depends on available sources of dietary iodine and tyrosine. The thyroid is the only endocrine gland capable of storing excess amounts of hormones for release as needed. During circulation in the bloodstream, T4 and T3 are bound to carrier proteins (thyroxinebinding globulin). They must be unbound before they are able to exert their metabolic effect. The main physiological action of TH is to regulate the basal metabolic rate and thereby control the processes of growth and tissue differentiation. Unlike GH, TH is involved in many more diverse activities that influence the growth and development of body tissues. Therefore, a deficiency of TH exerts a more profound effect on growth than that seen in GH deficiency. Calcitonin helps maintain blood calcium levels by decreasing the calcium concentration. Its effect is the opposite of parathyroid hormone (PTH) in that it inhibits skeletal demineralization and promotes calcium deposition in the bone. 1383 Juvenile Hypothyroidism Hypothyroidism is one of the most common endocrine conditions of childhood. In Canada, hypothyroidism affects 1in 4 000 children (Thyroid Foundation of Canada, 2018). It may be either congenital or acquired and represents a deficiency in secretion of TH. Beyond infancy, primary hypothyroidism may be caused by a number of defects. For example, a congenital hypoplastic thyroid gland may provide sufficient amounts of TH during the first year or two but be inadequate when rapid body growth increases demands on the gland. A partial or complete thyroidectomy for cancer or thyrotoxicosis can leave insufficient thyroid tissue to furnish hormones for body requirements. Radiotherapy for Hodgkin disease or other malignancies may lead to hypothyroidism (Wassner & Smith, 2020). Infectious processes may cause hypothyroidism. It can also occur when dietary iodine is deficient, which is rare in Canada, due to iodized salt availability. Rare cases of hypothyroidism have been reported following use of iodinated contrast media (ICM), particularly in term and preterm newborns (Government of Canada, 2018). Clinical manifestations depend on the extent of dysfunction and the child’s age at onset. Primary congenital hypothyroidism is characterized by low levels of circulating thyroid hormones and raised levels of TSH at birth. If left untreated, congenital hypothyroidism causes intellectual disability. In Canada, all newborns are screened for hypothyroidism at birth, and this has led to earlier detection and prevention of complications. This screening may not detect rarer disorders such as central hypothyroidism or congenital primary hypothyroidism with delayed TSH elevation. The presenting symptoms are decelerated growth from chronic deprivation of TH or thyromegaly. Impaired growth and development are less severe when hypothyroidism is acquired at a later age, and, because brain growth is nearly complete by 2 to 3 years of age, intellectual disability and neurological sequelae are not associated with juvenile hypothyroidism. Other manifestations are myxedematous skin changes (dry skin, puffiness around the eyes, sparse hair), constipation, sleepiness, and cognitive decline. Therapy is TH replacement, the same as for hypothyroidism in the infant, although the prompt treatment needed in the infant is not required in the child. In children with severe symptoms, the restoration of euthyroidism is achieved more gradually with administration of increasing amounts of L-thyroxine daily over a period of 4 to 8 weeks to avoid symptoms of hyperthyroidism, which can occur with treatment of chronic hypothyroidism. Children who are treated early continue to have mild delays in skills in reading, comprehension, and math but catch up by grade 6. However, adolescents may demonstrate difficulties with memory, attention, and visuospatial processing. Nursing Care. Growth cessation or restriction in a child whose growth has previously been normal should alert the nurse to the possibility of hypothyroidism. After diagnosis and implementation of thyroxine therapy, the importance of adhering to the treatment and periodic monitoring of response to therapy should be stressed to parents. Children should learn to take responsibility for their own health as soon as they are old enough. Goitre A goitre is an enlargement or hypertrophy of the thyroid gland. It may occur with deficient (hypothyroid), excessive (hyperthyroid), or normal ( euthyroid) TH secretion. It can be congenital or acquired. Congenital disease usually occurs as a result of maternal administration of antithyroid medications or iodides during pregnancy. Acquired disease can result from increased secretion of pituitary TSH in response to decreased circulating levels of TH or from infiltrative neoplastic or inflammatory processes. In most children, goitre is caused by chronic 1384 UNIT 12 Health Conditions of Children autoimmune thyroiditis (Latronico et al., 2016). In areas where dietary iodine (essential for TH production) is deficient, goitre can be endemic. Enlargement of the thyroid gland may be mild and noticeable only when there is an increased demand for TH (e.g., during periods of rapid growth). Enlargement of the thyroid at birth can be sufficient to cause severe respiratory distress. Colloid goitres are diffuse and benign and occur more frequently in adolescent girls. Thyroid function is normal, and the gland will gradually decrease over several years without treatment. TH replacement is necessary to treat the hypothyroidism and reverse the TSH effect on the gland. Therapeutic Management. Large goitres are identified by their obvious appearance. In older children, each lobe of the thyroid should be approximately the same as the terminal phalanx of the child’s thumb (Wassner & Smith, 2020). Smaller nodules may be evident only on palpation. Benign enlargement of the thyroid gland may occur during adolescence and should not be confused with pathological states. Nodules rarely are caused by a cancerous tumour but always require evaluation. Questions regarding exposure to radiation should be included in the assessment (see Chapter 33 for thyroid examination technique). NURSING ALERT If an infant is born with a goitre, immediate precautions need to be instituted for emergency ventilation, such as giving supplemental oxygen and having a tracheostomy set nearby. Hyperextension of the neck often facilitates breathing. Immediate surgery to remove part of the gland may be lifesaving in newborns with a goitre. Lymphocytic Thyroiditis Lymphocytic thyroiditis (Hashimoto disease, juvenile autoimmune thyroiditis) is the most common cause of thyroid disease in children and adolescents and is associated with the largest percentage of juvenile hypothyroidism. It accounts for many of the enlarged thyroid glands formerly designated thyroid hyperplasia of adolescence or adolescent goitre. Although it can develop during the first 3 years of life, it occurs more frequently after age 6. It reaches a peak incidence during adolescence, and there is evidence that the disease is self-limiting. The presence of a goitre and elevated thyroglobulin antibody with progressive increase in both thyroid peroxidase antibody and TSH may be predictive factors for future development of hypothyroidism (Wassner & Smith, 2020). The presence of an enlarged thyroid gland is usually detected by the health care provider during a routine examination, although it may be noted by parents when the youngster swallows. In most children the entire gland is enlarged symmetrically (though it may be asymmetrical) and is firm, freely movable, and nontender. There may be manifestations of moderate tracheal compression (sense of fullness, hoarseness, and dysphagia), but it is extremely rare for a nontoxic diffuse goitre to enlarge to the extent that it causes airway obstruction. Most children are euthyroid, but some display symptoms of hypothyroidism, including delayed growth and puberty and declining school performance. Other signs suggestive of lymphocytic thyroiditis are listed in Box 51.5. Diagnostic Evaluation. Thyroid function tests are usually normal, though TSH levels may be slightly or moderately elevated. With progressive disease the T4 decreases, followed by a decrease in T3 levels and an increase in TSH. Most affected children have antithyroid antibody titres. However, levels in children are lower than in adults; BOX 51.5 Clinical Manifestations of Lymphocytic Thyroiditis Enlarged thyroid gland • Usually symmetrical • Firm • Freely movable • Nontender Tracheal compression • Sense of fullness • Hoarseness • Dysphagia Hyperthyroidism (possible) • Nervousness • Irritability • Increased sweating • Hyperactivity repeated measurements may be needed in doubtful cases, since titres may increase later in the disease. Therapeutic Management. In many cases the goitre is transient and asymptomatic and regresses spontaneously within a year or two. Therapy of a nontoxic diffuse goitre is usually simple, uncomplicated, and effective. Oral administration of TH decreases the size of the gland significantly and provides the feedback needed to suppress TSH stimulation, and the hyperplastic thyroid gland gradually regresses in size. TSH levels should be monitored with the goal of restoring normal growth and development. Surgery is contraindicated in this disorder. Untreated patients should be evaluated periodically. Nursing Care. Nursing care consists of identifying the child with thyroid enlargement, reassuring the child and parents that the condition is probably only temporary, and reinforcing instructions for thyroid therapy. Hyperthyroidism The largest percentage of hyperthyroidism in childhood is caused by Graves’ disease, which is usually associated with an enlarged thyroid gland and exophthalmos. Graves’ disease occurs in approximately 1 in 5 000 children. Graves’ disease has a peak incidence in the 11- to 15-year-old age group, and there is a 5 to 1 female-to-male ratio. Many children with Graves’ disease have a family history of autoimmune thyroid disease. Although rare, Graves’ disease has been reported in children between 6 weeks and 2 years of age born to mothers without a history of hyperthyroidism (Wassner & Smith, 2020). The hyperthyroidism of Graves’ disease is apparently caused by an autoimmune response to TSH receptors, but no specific etiology has been identified. There is definitive evidence for familial association, with a high concordance incidence in twins. There may be an association with other autoimmune diseases such as rheumatoid arthritis and lupus. The development of manifestations is highly variable. Signs and symptoms develop gradually, with an interval between onset and diagnosis of approximately 6 to 12 months. The principal clinical features are excessive motion, irritability, hyperactivity, short attention span, tremors, insomnia, and emotional lability. Clinical manifestations are presented in Box 51.6. CHAPTER 51 Endocrine Conditions BOX 51.6 1385 Clinical Manifestations of Hyperthyroidism (Graves’ Disease) Cardinal Signs Emotional lability Physical restlessness, characteristically at rest Decelerated school performance Voracious appetite with weight loss in 50% of cases Fatigue Physical Signs Tachycardia Widened pulse pressure Dyspnea on exertion Exophthalmos (protruding eyeballs) Wide-eyed, staring expression with lid lag Tremor Goitre (hypertrophy and hyperplasia) Warm, moist skin Accelerated linear growth Heat intolerance (may be severe) Hair fine and unable to hold a curl Systolic murmurs Thyroid Storm Acute onset: • Severe irritability and restlessness • Vomiting • Diarrhea • Hyperthermia • Hypertension • Severe tachycardia • Prostration May progress rapidly to: • Delirium • Coma • Death Exophthalmos (protruding eyeballs), observed in many children, is accompanied by a wide-eyed staring expression, increased blinking, eyelid lag, lack of convergence, and absence of wrinkling of the forehead when looking upward. As protrusion of the eyeball increases, the child may not be able to completely cover the cornea with the lid. Visual disturbances may include blurred vision and loss of visual acuity. Eye disease associated with hyperthyroidism can develop long before or after the onset of hyperthyroidism. addition to antithyroid medications, is administration of beta-adrenergic blocking agents (propranolol), which provide relief from the adrenergic hyperresponsiveness that produces the disturbing adverse effects of the reaction. Therapy is usually required for 2 to 3 weeks. The Thyroid Foundation of Canada has extensive information related to the prevention, treatment, and cure of thyroid disease (see Additional Resources at the end of this chapter). Diagnostic Evaluation. The diagnosis is established on the basis of dren with hyperthyroidism. Because the clinical manifestations often appear gradually, the goitre and ophthalmic changes may not be noticed, and the excessive activity may be attributed to behavioural issues. Nurses in ambulatory settings need to be alert to signs that suggest this disorder, especially weight loss despite an excellent appetite, academic difficulties resulting from a short attention span and inability to sit still, unexplained fatigue and sleeplessness, and difficulty with fine motor skills such as writing. Exophthalmos may develop long before the onset of signs and symptoms of hyperthyroidism and may be the only presenting sign. Much of the care of these children is related to treating physical symptoms before a response to medication therapy is achieved. Children with hyperthyroidism need a quiet, unstimulating environment that is conducive to rest. Increased metabolic rate may cause heat intolerance and increased food intake in these patients. Mood swings and irritability can disrupt relationships, creating difficulties within and outside the home. A school consultation is important to provide education and suggest ways to assist a child after diagnosis. The child and parents should be encouraged to express their feelings about the behaviour and its effect on others. Heat intolerance may be minimized by the use of light cotton clothing, good ventilation, air conditioning or fans, frequent baths, and adequate hydration. Dietary requirements should be adjusted to meet the child’s increased metabolic rate. Rather than three large meals, the child’s appetite may be better satisfied by five or six moderate meals throughout the day. increased levels of T4 and T3. TSH is suppressed to unmeasurable levels. Graves’ disease is confirmed by measurement of the thyroidstimulating immunoglobulins. Other tests are rarely indicated. Therapeutic Management. Therapy for hyperthyroidism has not been firmly established, but all methods are directed toward slowing the rate of hormone secretion. The three acceptable modes available are the antithyroid medications, including propylthiouracil (PTU) and methimazole (MTZ, Tapazole), which interfere with the biosynthesis of TH; subtotal thyroidectomy when other treatments are not effective; and ablation with radioiodine (131I iodide) (Wassner & Smith, 2020). Each treatment is effective, but each has its own advantages and disadvantages. Pharmacological therapy may induce a remission, and treatment may be discontinued. However, relapse may occur. Radioactive iodine ablation is usually effective but response may be slower, and there have been concerns about a possible link to thyroid cancer in younger children. Surgery is often used when other treatments are not effective. These children require lifelong monitoring. When affected children exhibit signs and symptoms of hyperthyroidism (e.g., weight loss, tachycardia, increased pulse pressure, and hypertension), their activity should be limited to quiet and lowimpact play and to classwork. Vigorous exercise is restricted until thyroid levels are decreased to normal or near-normal values. Thyrotoxicosis (thyroid crisis or thyroid storm) may occur from the sudden release of the hormone. Although thyrotoxicosis is unusual in children, a crisis can be life-threatening. These “storms” are evidenced by the acute onset of severe irritability and restlessness, vomiting, diarrhea, hyperthermia, hypertension, severe tachycardia, and prostration (see Box 51.6). There may be rapid progression to delirium, coma, and even death. A crisis may be precipitated by acute infection, surgical emergencies, or discontinuation of antithyroid therapy. Treatment, in Nursing Care. The initial nursing objective is identification of chil- NURSING ALERT Children being treated with propylthiouracil or methimazole must be carefully monitored for adverse effects of the medication. Because sore throat and fever accompany the grave complication of leukopenia, these children should be seen by a health care provider if such symptoms occur. Parents and children should be taught to recognize and report symptoms immediately. 1386 UNIT 12 Health Conditions of Children DISORDERS OF PARATHYROID FUNCTION The parathyroid glands secrete parathyroid hormone (PTH), the main function of which, along with vitamin D and calcitonin, is homeostasis of serum calcium concentration. The effect of PTH on calcium is opposite that of calcitonin. The net result of the integrated action of PTH and vitamin D is maintenance of serum calcium levels within a narrow normal range and the mineralization of bone. Secretion of PTH is controlled by a negative feedback system involving the serum calcium ion concentration. Low ionized calcium levels stimulate PTH secretion, causing absorption of calcium by the target tissues; high ionized calcium concentrations suppress PTH. Hypoparathyroidism Hypoparathyroidism entails a spectrum of disorders that result in deficient PTH. Congenital hypoparathyroidism may be caused by a specific defect in the synthesis or cellular processing of PTH or by aplasia or hypoplasia of the gland (Doyle, 2020b). Hypoparathyroidism can also occur secondary to other causes, including infection and autoimmune syndromes. Postoperative hypoparathyroidism may follow thyroidectomy with acute or gradual onset and be transient or permanent. Two forms of transient hypoparathyroidism may be present in the newborn, both of which are the result of a relative PTH deficiency. One type is caused by maternal hyperparathyroidism or maternal DM. A more common, later form appears almost exclusively in infants fed a milk formula with a high phosphate-to-calcium ratio. Pseudohypoparathyroidism occurs when there is a genetic defect in the cellular receptors to PTH. The result is normal parathyroid gland and elevated PTH levels. Abnormal calcium and phosphorus levels are not affected by administration of PTH. Affected children typically have a short, stocky build; a round face; and abnormally shaped hands and fingers. Other endocrine dysfunction may be found concurrently. These children have an increased risk for neuropsychiatric disorders, cataracts, and seizures (Doyle, 2020b). Clinical signs of hypoparathyroidism are presented in Box 51.7. Muscle cramps are an early symptom, progressing to numbness, stiffness, and tingling in the hands and feet. A positive Chvostek or Trousseau sign BOX 51.7 or laryngeal spasms may be present. Convulsions with loss of consciousness may occur. These episodes may be preceded by abdominal discomfort, tonic rigidity, head retraction, and cyanosis. Headaches and vomiting with increased intracranial pressure and papilledema may occur and may suggest a brain tumour (Doyle, 2020b). Diagnostic Evaluation. The diagnosis of hypoparathyroidism is made on the basis of clinical manifestations associated with decreased serum calcium and increased serum phosphorus. Magnesium levels also need to be checked. Levels of plasma PTH are low in idiopathic hypoparathyroidism but high in pseudohypoparathyroidism. Endorgan responsiveness is tested by the administration of PTH with measurement of urinary cyclic adenosine monophosphate (cAMP). Kidney function tests are included in the differential diagnosis to rule out renal insufficiency. Although bone radiographs are usually normal, they may demonstrate increased bone density and suppressed growth. NURSING ALERT The earliest indication of hypoparathyroidism may be anxiety and mental depression, followed by paresthesia and evidence of heightened neuromuscular excitability: Chvostek sign—Facial muscle spasm elicited by tapping the facial nerve in the region of the parotid gland Trousseau sign—Carpal spasm elicited by pressure applied to nerves of the upper arm Tetany—Carpopedal spasm (sharp flexion of wrist and ankle joints), muscle twitching, cramps, seizures, and stridor Therapeutic Management. The objective of treatment is to maintain normal serum calcium and phosphate levels with minimum complications. Acute or severe tetany is corrected immediately by IV and oral administration of calcium gluconate and follow-up daily doses to achieve normal levels. Twice-daily serum calcium measurements are taken to monitor the efficacy of therapy and prevent hypercalcemia. When diagnosis is confirmed, vitamin D therapy is begun. Vitamin D therapy is somewhat difficult to regulate because the medication has a prolonged onset and a long half-life (Doyle, 2020b). Clinical Manifestations of Hypoparathyroidism Pseudohypoparathyroidism Short stature Round face Short, thick neck Short, stubby fingers and toes Dimpling of skin over knuckles Subcutaneous soft tissue calcifications Intellectual disability a prominent feature Idiopathic Hypoparathyroidism None of the above physical characteristics observed May include papilledema May have intellectual disability Both Types Dry, scaly, coarse skin with eruptions Hair often brittle Nails thin and brittle with characteristic transverse grooves Dental and enamel hypoplasia Muscle contractions: • Tetany • Carpopedal spasm • Laryngospasm (laryngeal stridor) • Muscle cramps and twitching • Positive Chvostek sign or Trousseau’s sign Neurological: • Headache • Seizures (generalized, absence, or focal) • Swings of emotion • Loss of memory • Depression • Confusion possible • Paresthesias, tingling Gastrointestinal: • Muscle cramps • Diarrhea • Vomiting Delayed skeletal growth CHAPTER 51 Endocrine Conditions Long-term management usually consists of vitamin D and oral calcium supplementation. Serum calcium and phosphorus are monitored frequently until the levels have stabilized, then routinely thereafter. Renal function, blood pressure, and serum vitamin D levels are measured every 6 months. Serum magnesium levels are measured to detect hypomagnesemia, which may raise the requirement for vitamin D. Nursing Care. The initial objective is recognition of hypocalcemia. Unexplained convulsions, irritability (especially to external stimuli), gastrointestinal symptoms (diarrhea, vomiting, cramping), and positive signs of tetany are signs of hypocalcemia related to hypoparathyroidism. Much of the initial nursing care is related to the physical manifestations and includes institution of seizure and safety precautions; reduction of aggravating environmental stimuli, such as avoiding sudden or loud noise, bright lights, and stimulating activities; and observation for signs of laryngospasm, such as stridor, hoarseness, and a feeling of tightness in the throat. A tracheostomy set and injectable calcium gluconate should be located near the bedside for emergency use. The administration of calcium gluconate requires precautions against extravasation of the medication and tissue destruction. After initiating treatment, the nurse should discuss with the parents the need for continuous daily administration of calcium salts and vitamin D. Because vitamin D toxicity can be a serious consequence of therapy, parents are advised to watch for its signs, which include weakness, fatigue, lassitude, headache, nausea, vomiting, and diarrhea. Early renal impairment is manifested by polyuria, polydipsia, and nocturia. Hyperparathyroidism Hyperparathyroidism is rare in childhood but can be primary or secondary. The most common cause of primary hyperparathyroidism is adenoma of the gland (Doyle, 2020a). The most common causes of secondary hyperparathyroidism are chronic renal disease, renal osteodystrophy, and congenital anomalies of the urinary tract. The common factor is hypercalcemia. The clinical signs of hyperparathyroidism are listed in Box 51.8. 1387 BOX 51.8 Clinical Manifestations of Hyperparathyroidism Gastrointestinal Nausea Vomiting Abdominal discomfort Constipation Central Nervous System Delusions Confusion Hallucinations Impaired memory Lack of interest and initiative Depression Varying levels of consciousness Neuromuscul