The cortisol biosynthesis pathway affected by 21OH deficiency in CAH
The most common enzyme deficiency found in children with CAH is 21-hydroxylase deficiency (21OHD), accounting for approximately 95% of cases (Speiser et al., 2010). These patients have varying levels of deficiency in mineralocorticoids (aldosterone) and glucocorticoids (cortisol) and an excess of androgens. Cortisol deficiency leads to stimulation of adrenocorticotropic hormone (ACTH) and results in hyperplasia of the adrenal gland (Sharma and Seth, 2013). Since 21OHD is the most common cause of CAH, the remainder of this discussion will focus on this enzyme deficiency.
Clinical Manifestations of CAH
The clinical manifestations of CAH are the result of adrenal insufficiency, accumulated precursors proximal to the enzymatic block, and androgen excess. CAH can be divided into classic and non-classic forms based on symptoms and the degree of enzyme activity. Classic CAH can then be subdivided into salt-wasting (SW) and non-salt-wasting (NSW) types.
Salt-wasting CAH comprises 75% of classic CAH cases and is characterized by the complete absence of 21OH, which results in a deficiency of cortisol and aldosterone production and excess testosterone production. Lack of aldosterone leads to renal sodium loss, hypovolemia, and hyperkalemia. Clinically, patients usually present in the second week of life with nonspecific and insidious symptoms such as poor feeding, poor weight gain, emesis, and irritability (Fleisher and Ludwig, 2010). Symptoms may progress to adrenal crisis and potentially fatal hypovolemic shock, as with the infant in the vignette. Girls with SW-CAH may be diagnosed at an earlier age, due to ambiguous genitalia. These girls are virilized in utero resulting in phenotypes ranging from clitoral hypertrophy and partial labioscrotal fusion to completely phenotypically male genitalia. An apparently male neonate with no palpable testes warrants careful scrutiny. Ambiguous genitalia should prompt urgent genetic and gonadal sex determination. Boys with SW-CAH may have more subtle effects of androgen and ACTH excess, such as mild phallic enlargement or hyperpigmentation (due to stimulation of melanocyte-stimulating hormone along with ACTH) (Sharma and Seth, 2013). The subtle changes in male genitalia can lead to delayed diagnosis until the infant presents in shock.
The remaining 25% of classic cases are non-salt-wasting CAH. In these patients, 1% to 2% of enzyme activity remains, resulting in mild virilization, sparing of aldosterone, and no salt wasting. Girls may have ambiguous genitalia; however, diagnosis is often delayed until puberty. Boys may present with precocious puberty (Sharma and Seth, 2013).
In non-classic CAH, remaining 21OH activity is 20% to 50%. Most patients are asymptomatic or exhibit mild symptoms such as precocious pubarche or signs of androgen excess in female adolescence, such as acne, hirsutism, and menstrual irregularities (Sharma and Seth, 2013). The following discussion focuses on classic congenital adrenal hyperplasia.
Diagnosis of CAH
Although CAH screening is included in the newborn screening program in all 50 states in the United States and at least 40 other countries, the ED clinician should note that these results might not be available for three to four weeks (Antal and Zhou, 2009; Fleisher and Ludwig, 2010; Merke, 2014a). The diagnosis of CAH in the ED is based on clinical suspicion, physical examination including vital signs and a genitourinary exam, and laboratory abnormalities.
The most urgent blood tests to obtain are serum electrolytes and blood glucose. The first clue to an underlying diagnosis of CAH in a boy with normal appearing genitalia is often the combination of hyperkalemia and hyponatremia. It is important to note that expected elevation in serum potassium seen in CAH may be obscured by ongoing GI losses caused by the acute salt-wasting crisis leading to an initial normal serum potassium level. Blood glucose levels may be low due to decreased oral intake and decreased cortisol levels, or they may be normal. Metabolic acidosis, evidenced by low pH and bicarbonate level, is present in patients in moderate to severe hypovolemic shock (Fleisher and Ludwig, 2010).
Ideally, prior to administering hydrocortisone, blood should be drawn for the following laboratory tests: cortisol, 17-hydroxyprogesterone (17OHP), dehydroepiandrosterone (DHEA), androstenedione, and testosterone; however, treatment should not be delayed in a critically ill infant (Fleisher and Ludwig, 2010). The serum level of 17-hydroxyprogesterone (17OHP) is elevated in CAH (usually greater than 100 ng/mL in the classic form) (Sharma and Seth, 2013).
Management of CAH
The infant in hypovolemic shock from a salt-wasting crisis requires aggressive intravenous (IV) fluid resuscitation. A time-sensitive and goal-directed algorithm for pediatric shock includes 60 mL/kg normal saline bolus in the first 15 minutes, followed by catecholamines if there is no response to fluids. In neonates of both sexes, with fluid and catecholamine-refractory shock, the clinician should administer hydrocortisone, as there is a high risk of adrenal insufficiency caused by CAH.
Maintenance fluids for CAH patients should include 5% dextrose at 1.5 to 2 times maintenance rates for adrenal crisis (Sharma and Seth, 2013). Hydrocortisone should be administered as 50–100 mg/m2 IV bolus (typically 25 mg for a neonate) followed by 50–100 mg/m2 of hydrocortisone per day divided every 6 hours. Mineralocorticoid replacement is unnecessary in the acute setting due to the mineralocorticoid effects of hydrocortisone at high doses. CAH-induced hyperkalemia usually requires only fluid resuscitation. In the setting of a hyperkalemia-induced arrhythmia, 10% calcium gluconate should be administered to stabilize the cardiac membranes. Hypoglycemia can be treated with glucose 0.25 g/kg and subsequent inclusion of 10% dextrose in IV fluids.
Once the patient is stabilized in the ED, the patient should be admitted to a pediatric intensive care unit (PICU) for further management and non-urgent aspects of the evaluation for CAH, including karyotype and pelvic ultrasound to identify gonadal structures. The female infant (46XX) who is diagnosed in the neonatal period after in utero androgen exposure is given a Prader score, which grades the degree of genital virilization (Fleisher and Ludwig, 2010; Merke, 2014b).
Post-ED Care
Once the diagnosis of CAH is made, a conference with the parents, the endocrinologist, the urologist (and the patient if the child is old enough to understand and participate) may include the following topics: growth and hormone replacement, gender assignment, sexual orientation, feminizing surgery, and fertility.
Both girls and boys with CAH display rapid growth during the neonatal period, due to androgen excess. Boys with undetected CAH may have brisk increase in height with precocious puberty; however, they may also have early fusion of physes leading to short stature as adults. Preservation of full adult height requires close follow-up by an endocrinologist (Sharma and Seth, 2013).
Development of gender identity depends on the degree of in utero androgen exposure and a host of other factors during childhood, including gender assignment (Jordan-Young, 2012). Gender assignment in the female child (46XX) with highly virilized genitalia is an issue that requires sensitivity and the expertise of a multidisciplinary team. A study of 12 46XX people who were assigned male gender at birth (based on high Prader scores) and diagnosed with CAH after age 3 found that most subjects maintained male gender identity with sexual attraction to females. Two of these subjects were reassigned to female gender in childhood but subsequently reassigned themselves to male. Those patients with ambiguous gender who did the poorest with regard to self-esteem, body image, masculinity, and social adjustment had less familial and social support (Lee et al., 2010). Consultation with a mental health specialist may be helpful for patients with CAH (Speiser et al., 2010). These reports underscore the significance of psychosocial support for children with CAH.
In utero androgen exposure affects sexual orientation. Females (46XX) with CAH recalled more “male-typical” play during childhood, had reduced satisfaction with identifying as female gender, reduced heterosexual interest, and increased rates of bisexual and homosexual orientation when compared to controls. Males with CAH did not differ from unaffected males in these respects (Hines et al., 2004). Moreover, homosexual and bisexual identity among a cohort of females (46XX) with CAH was correlated with the degree of prenatal androgenization as well as global measures of masculinization of nonsexual behavior (Meyer-Bahlburg et al., 2008). These findings are explained by the brain organization theory, which suggests that in utero androgen exposure affects brain development and consequently sexual orientation, gender identity, and nonsexual behavior (such as aggression or play activity levels in children) (Meyer-Bahlburg, 2011; Jordan-Young, 2012; Pasterski et al., 2007).
Females (46XX) with virilized genitalia may require feminizing surgery. Current literature suggests that the effects of feminizing surgery on sexual function are not satisfactory. Clitoral sensitivity after clitoroplasty has been shown to be impaired and is associated with anorgasmia (Crouch et al., 2008; Nordenstrom, 2011). Vaginal reconstruction carries the risk of stricture formation, vaginal penetration difficulties, dyspareunia, stenosis, and lower urinary tract problems (Gastaud et al., 2007; Crouch et al., 2008; Lee et al., 2012; van der Zwan et al., 2013). Current trends and guidelines favor postponing feminizing surgery unless patients have moderate or severe signs of virilization (Nordenstrom, 2011).
Subfertility is common in both female and male CAH patients. In females, the subfertility depends on the severity of virilization, combined with psychosocial and psychosexual issues related to gender identity (Gastaud et al., 2007; van der Zwan et al., 2013). Subfertility in males is related to aberrant adrenal tissue that can cause testicular adrenal rest tumors and abnormal sperm quality (Falhammar et al., 2012).
Although growth, gender identity, sexual orientation, and fertility are not strictly pediatric or acute care issues, these problems can be predicted at the onset of illness and highlight the importance of early pediatric endocrinology and urology consultation (Otten et al., 2005).
Conclusion
Clinicians treating infants in fluid and catecholamine-refractory shock should consider congenital adrenal hyperplasia in the differential diagnosis and administer corticosteroids early. Because of the variations in the severity of CAH, girls may present with ambiguous genitalia, while boys may have hyperpigmented genitalia or phallic enlargement, although most affected male infants have normal appearing genitalia.
Case Conclusion
The boy received IV hydrocortisone, which immediately improved his vital signs and perfusion. His response strongly suggested that he was in adrenal crisis, likely secondary to CAH. Pediatric endocrinology, urology, and the PICU were notified, and the patient was admitted for ongoing management of adrenal crisis and a workup for CAH.
Gaps in Knowledge
There are too few prospective long-term studies on the psychological and functional effects of early feminizing surgery compared to delayed (postpubertal) feminizing surgery (Braga and Pippi Salle, 2009). Additionally, more neuroanatomic research studies are needed to clarify the effects of in utero androgen exposure on brain development and gender identity (Meyer-Bahlburg, 2011). More complete evidence would provide families with the knowledge necessary to make life-altering decisions for their female children with CAH. Furthermore, as surgical expertise increases, more effective feminizing surgery techniques that yield more satisfactory results for sexual function will improve quality of life for female patients with CAH.
Case 3: Lower abdominal pain in an adolescent
A 14-year-old female presented with two days of severe right lower quadrant abdominal pain. Review of systems was positive for two episodes of non-bilious, non-bloody emesis and was otherwise negative. Vital Signs: heart rate 110 beats per minute, respiratory rate 20 breaths per minute, blood pressure 110/80, O2 saturation 99%, and oral temperature 36.7°C Exam: She was in moderate discomfort from pain, her abdomen was soft with moderate tenderness in the right lower quadrant, and involuntary guarding without rebound tenderness.
Introduction
The differential diagnosis of lower abdominal pain in adolescents is broad and varies depending on the sex of the patient. Illnesses that cause lower abdominal pain in both sexes range in severity from mild conditions to surgical emergencies, including appendicitis, nephrolithiasis, and constipation.
In girls, lower abdominal pain can be gynecologic in origin and encompass entities such as pelvic inflammatory disease (PID), ovarian pathology, and ectopic pregnancy. A surgical emergency that can cause similar, nonspecific symptoms in boys is testicular torsion. Significant components of the adolescent history that the clinician must obtain are the date of the most recent menses in girls, sexual history, and high-risk behaviors. When interviewing the adolescent, the clinician should consider local consent laws and confidentiality issues (Kruszka and Kruszka, 2010). Work-up always includes a pregnancy test in all menstruating females, even if the history and exam seem conclusive (Balachandran et al., 2013). The following discussion reviews sex differences in each of these conditions.
Appendicitis
Clinical Presentation of Appendicitis
While appendicitis is more common in boys (and men), the clinical presentation of appendicitis is similar in children and adults and there is no difference in boys’ and girls’ presentation. Symptoms and diagnostic findings may include periumbilical pain that migrates to the right lower quadrant, anorexia, nausea, vomiting, leukocytosis with left shift, and fever. The incidence of appendicitis in children peaks in the second decade of life, with median age of 10–11. The male to female ratio is approximately 1.4:1 (Pepper et al., 2012; Shah, 2013).
Diagnosis of Appendicitis
The most well-studied clinical prediction rules for appendicitis in children include the modified Alvarado score and the Pediatric Appendicitis Score (PAS) (Kulik et al., 2013). Both scores were more accurate in boys than in girls, which was consistent with studies of the Alvarado score in adults of both sexes (Mandeville et al., 2011).
Efforts to reduce ionizing radiation exposure in children have led to the use of ultrasound (US) as the preferred first-line imaging modality for appendicitis in children and young women (Shademan and Tappouni, 2013). The approach of US followed by computed tomography (CT) or magnetic resonance imaging (MRI) when US is non-diagnostic has shown increased cost effectiveness and high accuracy when compared to CT alone for both sexes (Wan et al., 2009; Aspelund et al., 2014). US was more successful for diagnosis of appendicitis in children than adults and in boys as compared to girls (Yu et al., 2005b). In a multi-institutional study comparing US to CT for diagnosis of appendicitis, all children younger than age 5 and girls older than age 10 had a higher negative appendectomy rate (NAR) when using US alone for diagnosis. NAR is defined as a normal appendix on histopathology. US is more challenging in younger children and in pubescent females (Bachur et al., 2012). This is consistent with other reports that NAR was independently associated with younger age and female sex (Oyetunji et al., 2012). The larger number of abdominal conditions that mimic appendicitis may have contributed to US’s decreased accuracy diagnosing appendicitis in girls. Pelvic MRI may be an alternative to CT scan for difficult cases (Shademan and Tappouni, 2013).
Pubertal females are diagnostically challenging because they are more likely to present with non-classical symptoms of appendicitis, and they may have gynecologic conditions that mimic appendicitis. Pelvic examination was not found to delay the diagnosis of appendicitis in women; therefore, this examination should be performed if clinically indicated and feasible (McGann Donlan and Mycyk, 2009). Obesity in children can obscure physical examination findings. Obese girls with appendectomies have significantly higher NAR than obese boys (24.6% vs. 17.4%, p<0.05) (Kutasy and Puri, 2013).
The clinician may consider observation rather than immediate CT in adolescent girls with mild lower abdominal pain. A study of adolescents and adults in whom US found normal pelvic structures but did not visualize the appendix determined that these patients were at significantly lower risk for appendicitis. These results suggest that if the appendix is not visualized on US, the clinician may follow a staged approach, with clinical observation rather than immediate CT; the CT can then be obtained for persistent or worsening abdominal pain (Stewart et al., 2012).
Management of Appendicitis
The primary management of uncomplicated appendicitis is appendectomy, either laparoscopic appendectomy (LA) or open appendectomy (OA). LA has additional benefits in girls and women of reproductive age because it allows direct visualization of the abdominal and pelvic contents, an improved cosmetic outcome, and less risk of postoperative adhesions that can increase the risk of infertility (Markar et al., 2012; Sauerland et al., 2010; Tzovaras et al., 2007). The benefit of LA is reduced in prepubescent females who are less likely to have abdominal pain caused by gynecologic pathology (Markar et al., 2012). LA is as safe as OA in boys but has not proved to provide any clear benefit (Tzovaras et al., 2007). Retrospective reviews note that boys were more likely to have open appendectomy, whereas girls had higher rates of laparoscopic appendectomy (Markar et al., 2012; Oyetunji et al., 2011).
Complications of Appendicitis
Perforation of the appendix is a potential complication of appendicitis. In studies combining children and adults, men had an earlier and greater rate of perforation than women; this complication was more common in elderly patients than in children (Augustin et al., 2011; Barreto et al., 2010; Sulu et al., 2010).
Nephrolithiasis
Clinical Presentation of Nephrolithiasis
Children with nephrolithiasis present to Emergency Departments with abdominal or flank pain, hematuria, fever, or dysuria (Alpay et al., 2013). In contrast to stones formed by adults, pediatric kidney stones are more often caused by genetic or metabolic conditions. In recent decades, the overall prevalence of pediatric kidney stones has been increasing in both sexes (Matlaga et al., 2010; Novak et al., 2009). Boys have a predilection for kidney stones in the first decade of life due to genetic and metabolic conditions diagnosed in infancy, and girls in the second decade of life (Sas, 2011; Sas et al., 2010; Wood et al., 2013; Matlaga et al., 2010; Novak et al., 2009; Habbig et al., 2011).
One theory explaining young boys’ increased risk of stone formation is that boys are more likely to have anatomical malformations resulting in urinary obstruction and stasis. Another theory associates puberty in girls with kidney stone formation, suggesting that estrogen has a lithogenic effect; this theory has its basis in studies of postmenopausal women on hormone replacement therapy (Matlaga et al., 2010; Novak et al., 2009). Estrogen may also affect stone formation in pubertal girls by stimulating adiposity and enhanced bone mineralization. These theories are not well studied and remain an area of exploration for future research.
Diagnosis of Nephrolithiasis
Pediatric kidney stones are often found incidentally, presenting only with nonspecific symptoms (Habbig et al., 2011). Initial assessment of a child with symptoms of renal colic may include urinalysis for microscopic hematuria and urine calcium/creatinine ratio. Imaging may include abdominal ultrasound, X-ray, or CT scan, based on clinical presentation (Kalorin et al., 2009). Efforts to limit radiation in children are encouraged.
Management of Nephrolithiasis
Management of pediatric kidney stones is the same for either sex. Prevention is the primary approach to management of pediatric kidney stones. Hydration, which decreases solute concentration in the urine, dietary modifications, and certain medications are important aspects of prevention (Habbig et al., 2011). Pain control is accomplished with oral therapy or parenteral analgesia if oral medication is not tolerated. Overall stone passage rate has been reported at 34% for children younger than age 10 and 29% for children older than age 10, with no apparent differences by sex (Kalorin et al., 2009).
Invasive management of kidney stones may be pursued for obstruction, infection, or depressed renal function. These interventions include ureteroscopy, shock wave lithotripsy, and percutaneous nephrolithotomy, with similar approaches in both sexes (Kalorin et al., 2009).
Complications of Nephrolithiasis
Complications of kidney stones include upper urinary tract infection; ureteral obstruction; hydronephrosis; and, if chronic and untreated obstruction is present, renal failure (Alexander et al., 2012; Alpay et al., 2013; Habbig et al., 2011). One study noted that kidney stones were a common cause of acute renal failure in older children and that acute renal failure was more common in boys than girls, for unclear reasons (Jamal and Ramzan, 2004).
Constipation
Clinical Presentation of Constipation
Constipation presents with abdominal pain and infrequent stooling. The passage of infrequent, large-caliber stools is highly suggestive of functional constipation (Biggs and Dery, 2006). During the toilet training period, straining at defecation and infrequent stooling were reported significantly more often for girls, whereas fecal soiling of underclothes and passage of large bowel movements were reported more often in boys (Wald et al., 2009; de Lorijn et al., 2004). Encopresis in children with constipation is more common in boys (Biggs and Dery, 2006; Nurko and Scott, 2011; de Lorijn et al., 2004).
Clinicians have identified an association between bowel and bladder dysfunction, which is termed “dysfunctional elimination syndrome.” Different types of dysfunctional elimination were described in each sex. Constipation and dysfunctional voiding were more common in girls, whereas boys had more encopresis and idiopathic detrusor overactivity disorder (Combs et al., 2013).
Diagnosis of Constipation
The diagnosis of constipation does not differ by sex. Diagnosis of functional constipation is usually based on bowel hygiene history and physical examination. The clinician should perform a digital rectal exam and visual inspection of the anus. The presence of impacted stool or anal fissures suggests functional constipation (Biggs and Dery, 2006). A thorough history and review of systems is important to rule out organic causes of constipation such as Hirschsprung’s disease, spinal cord abnormality, hypothyroidism, cystic fibrosis, gluten enteropathy, congenital anorectal malformations, or sexual abuse (Biggs and Dery, 2006). The clinician may use radiography when the diagnosis of constipation is uncertain, but there is insufficient evidence to support routine imaging (Berger et al., 2012; Reuchlin-Vroklage et al., 2005). Treatment and complications of functional constipation are similar for both boys and girls and are beyond the scope of this discussion.
Pelvic Inflammatory Disease
Clinical Presentation of PID
Pelvic inflammatory disease (PID) is an ascending infection that spreads from the lower to the upper genital tract. The mechanism of infection begins with attachment of infectious agents to columnar epithelium of the cervix (Banikarim and Chacko, 2005). PID is common among sexually active women, with an increased prevalence in adolescents in part due to high-risk behaviors (Abu Raya et al., 2013; Datta et al., 2012).
Microbiology of PID includes Neisseria gonorrhea, Chlamydia trachomatis, and other aerobic and anaerobic microorganisms (Banikarim and Chacko, 2005; Abu Raya et al., 2013). In the United States, Chlamydia infections are more common in women than in men ages 14 to 39 (2.2% vs. 1.1%, respectively). There was a declining prevalence of Chlamydia infections in both sexes from 1999 to 2008, with a more notable decline in men and adolescents of both sexes (Datta et al., 2012).
PID presents with nonspecific symptoms including lower abdominal or pelvic pain, cramping, vaginal bleeding or discharge, urinary symptoms, fever, or dyspareunia (Abu Raya et al., 2013).
Gonorrhea and Chlamydia infections in men often present as urethritis but may also cause epididymitis or prostatitis. Urethritis from either organism may present with urethral discharge or dysuria, or may be asymptomatic. Asymptomatic urethritis occurs more commonly with Chlamydia than with Gonorrhea and is more common in women than in men (Cecil et al., 2001; Detels et al., 2011; Sherrard and Barlow, 1996).
Diagnosis of PID
PID is a clinical diagnosis based on either uterine/adnexal tenderness or cervical motion tenderness. Additional diagnostic criteria may include fever >38.3°C, abnormal cervical discharge, white blood cells on wet mount of cervical discharge, elevated erythrocyte sedimentation rate or C-reactive protein, or identification of N. gonorrhea or C. trachomatis in cervical discharge (Banikarim and Chacko, 2005).
N. gonorrhea or C. trachomatis can be diagnosed with the gold standard test of cervical culture, but the test most frequently utilized is the highly sensitive and specific nucleic acid amplification test (NAAT) (Abu Raya et al., 2013). NAAT can be performed on urine or on material obtained from vaginal swabs that the patient can self-administer.
Management of PID
The CDC recommends parenteral and oral regimens for PID (Table 13B.3) (Banikarim and Chacko, 2005; Abu Raya et al., 2013). Hospitalization for parenteral treatment is indicated for failed outpatient therapy, inability to tolerate oral intake, or clinical signs of peritoneal inflammation and should be considered in patients who are at high risk for noncompliance (Banikarim and Chacko, 2005).
| Parenteral Regimens |
|---|
| Option A |
|
| PLUS |
|
| Option B |
|
| PLUS |
|
| Oral Regimens |
| Option A |
|
| PLUS |
|
| WITH OR WITHOUT |
|
| Option B |
|
| PLUS |
|
| WITH OR WITHOUT |
|
| Option C |
|
| PLUS |
|
| WITH OR WITHOUT |
|
The US Preventative Services Task Force (USPSTF) recommends screening all sexually active women age 25 and younger, and screening all high-risk women older than age 25 (Abu Raya et al., 2013). Outpatient screening of women at risk, coupled with appropriate treatment, has been shown to reduce hospitalized PID, ectopic pregnancies, and ED-diagnosed Gonorrhea and Chlamydia (Anschuetz et al., 2012; Gray-Swain and Peipert, 2006).
Complications of PID
PID can lead to significant morbidity, including infertility, ectopic pregnancy, chronic pelvic pain, recurrent infections, tubo-ovarian abscess, and possibly ovarian cancer (Abu Raya et al., 2013; Banikarim and Chacko, 2005).
Tubo-ovarian abscess occurs when bacteria and inflammatory material collect in the fallopian tubes, forming an abscess. Pathogens include aerobes and anaerobes, including those causing PID. The clinician should suspect this diagnosis in patients with moderate to severe pain who are ill appearing. Often, however, these patients’ presentations are similar to those of women who have PID. Pelvic ultrasound can identify the abscess. Treatment includes hospitalization for parenteral triple antibiotic therapy, with broad spectrum agents including clindamycin, ampicillin, and gentamicin, and serial ultrasounds to monitor response to therapy (Banikarim and Chacko, 2005). Surgical drainage must be considered if medical therapies fail.
Ovarian Cysts
Clinical Presentation of Ovarian Cysts
Follicular cysts result when follicles fail to regress after completion of the menstrual cycle. Large ovarian cysts may rupture, causing an abrupt onset of pain, or may become the lead point for ovarian torsion (Ackerman et al., 2013). Hemorrhagic cysts are uncommon in early adolescence but have the potential to cause massive hemoperitoneum or hypotension (Ackerman et al., 2013; Kayaba et al., 1996).
Ovarian cysts may occur in prepubertal girls, but their diameter is usually less than 2 cm. These are usually asymptomatic, are found incidentally, and regress spontaneously. Occasionally, recurrent bleeding is due to hormonally active cysts and may suggest a genetic disorder, such as McCune-Albright syndrome. McCune-Albright syndrome has a variable presentation, including precocious puberty, café-au-lait spots, and polyostotic fibrous dysplasia. Ovarian cysts are one of several manifestations of this condition (Pienkowski et al., 2012).
Diagnosis of Ovarian Cysts
Ultrasound is the imaging modality of choice to visualize the adnexa and uterus. Pelvic US that is performed in the ED requires advanced imaging skills and experience and should be performed by experienced sonographers rather than the bedside clinician (Leeson and Leeson, 2013). Follicular cysts appear as simple, unilocular, or minimally complicated cysts with thin walls, sharply marginated borders, internal fluid, and no internal vascularity. Hemorrhagic cysts have variable appearance depending on the age of the blood products, including a complex cystic appearance with internal echoes, thickened walls, or fluid levels (Ackerman et al., 2013).
Management of Ovarian Cysts
Simple cysts <3 cm in diameter are considered physiologic. Cysts 3–5 cm are usually benign and do not require follow up. Cysts 5–7 cm should be reimaged annually and cysts that are >7 cm should be further evaluated by MRI or a surgical consultant (Ackerman et al., 2013). Cystectomy is indicated for cysts that are growing, persistent, symptomatic, or appear suspicious for malignancy (Tofteland et al., 2010). Non-ruptured hemorrhagic cysts generally resolve in 8 weeks, but if they are >5 cm, they should be reimaged to ensure resolution (Ackerman et al., 2013). Cystectomy and oophorectomy can be done laparascopically in children (Akkoyun and Gulen, 2012; Savasi et al., 2009).
Ovarian Torsion
Clinical Presentation of Ovarian Torsion
Adnexal torsion (AT) is the cause of approximately 3% of episodes of acute abdominal pain in girls (Appelbaum et al., 2013). AT involves the rotation of the ovary, fallopian tube, or both, on its vascular pedicle. In children, intermittent or non-radiating abdominal or pelvic pain has been significantly associated with AT (Appelbaum et al., 2013). Pain from AT has a predilection for the right ovary and thus is more often right sided (Spinelli et al., 2013). Additional findings may include nausea and vomiting; occasionally a mass can be palpated on physical examination (Breech and Hillard, 2005; Ackerman et al., 2013).
Diagnosis
Torsion is often associated with increased adnexal size, an ovarian cyst, or mass (Appelbaum et al., 2013; Spinelli et al., 2013; Ackerman et al., 2013). The most common lesions found in torsed ovaries of adolescents are follicular or corpus luteal cysts, often >5 cm (Ackerman et al., 2013). Ultrasound with Doppler is the test of choice to evaluate the pelvic organs in females. In AT, US may identify adnexal masses or enlargement, and Doppler may identify absence of venous or arterial flow. The most frequent finding is a decrease or absence of venous flow (Ackerman et al., 2013). However, presence of blood flow seen with Doppler does not always exclude torsion, because the patient may be having intermittent torsion or have developed collateral blood flow (Breech and Hillard, 2005; Cass, 2005). At times, CT scan may be necessary to rule out alternative causes of nonspecific abdominal pain (Ackerman et al., 2013).
Clinicians must maintain a high index of suspicion for AT in girls with atypical abdominal pain (Breech and Hillard, 2005). Delayed diagnosis is more common in ovarian torsion than in testicular torsion. This disparity is in part the result of the anatomy of male genitalia; the testes and scrotum are more easily palpated and examined by the clinician. Furthermore, abdominal pain in girls generates a broader differential than abdominal or scrotal pain in boys. Girls with gonadal torsion present later after the onset of pain, wait 2.5 times longer for diagnostic imaging, wait 2.7 times longer to go to the operating room for definitive treatment, and have a gonadal salvage rate that is less than half that of boys (Piper et al., 2012). More liberal use of diagnostic laparoscopy in girls, when imaging is non-diagnostic, would improve ovary salvage rate (Piper et al., 2012).
Management of Ovarian Torsion
Laparoscopic detorsion has become the preferred approach in children with AT, with consideration of oophoropexy at the time of surgery (Ackerman et al., 2013; Cass, 2005; Breech and Hillard, 2005). Cystectomy is performed if needed and efforts to limit oophorectomy are encouraged to preserve reproductive function as well as sexual development in prepubertal children (Breech and Hillard, 2005). A number of studies report viability of the ovary despite a necrotic appearance; most experts recommend leaving the ovary in situ regardless of duration of symptoms or gross appearance (Spinelli et al., 2013; Piper et al., 2012).
Ectopic Pregnancy
Clinical Presentation of Ectopic Pregnancy
Ectopic pregnancies may present with crampy abdominal or pelvic pain that is often unilateral; sometimes vaginal bleeding occurs. Cervical motion tenderness, adnexal mass, and adnexal tenderness increase the likelihood of ectopic pregnancy (Crochet et al., 2013). A ruptured ectopic pregnancy is a surgical emergency and can present with hypotension, tachycardia, or shock (Barnhart, 2009).
Diagnosis of Ectopic Pregnancy
Unruptured ectopic pregnancy is diagnosed by pelvic ultrasound in conjunction with βhCG (Barnhart, 2009). A study of ED physicians performing ultrasound for possible ectopic pregnancy demonstrated a sensitivity of 99.3% and a negative predictive value of 99.96%, suggesting that visualization of intrauterine pregnancy by emergency physicians was sufficient to rule out ectopic pregnancy (Stein et al., 2010). A single βhCG value does not identify the location of a pregnancy, but trending values may be used to estimate gestational age and determine viability of a pregnancy (Barnhart, 2009).
Management of Ectopic Pregnancy
Medical or surgical management of an ectopic pregnancy must be determined by an obstetrician. Medical management includes administration of systemic methotrexate if there are no signs of rupture, the βhCG is <5,000 IU/L, routine lab tests are normal, and the patient is reliable to follow-up. Surgical management includes saplingetcomy or salpingostomy. Surgery is indicated for patients with signs of rupture, βhCG >5,000 IU/L, need for laparoscopic diagnosis, or suspicion for a concurrent viable intrauterine pregnancy (known as a heterotopic pregnancy). Expectant management may be considered when a reliable patient has no evidence of rupture and has a βhCG <1,500 IU/L that decreases within 48 hours (Farquhar, 2005; Lozeau and Potter, 2005).
Testicular Torsion
Clinical Presentation of Testicular Torsion
Testicular torsion typically presents with testicular or abdominal pain, often unilateral, with nausea and vomiting (Gunther and Rubben, 2012). Physical examination may show the testis in a horizontal lie, scrotal induration, swelling or discoloration, and an absent cremasteric reflex. Intermittent torsion may present with repeated, severely painful episodes with spontaneous resolution (Eaton et al., 2005).
Diagnosis of Testicular Torsion
Significant ischemic damage is estimated to occur after four to eight hours (Gunther and Rubben, 2012). Urinalysis with evidence of pyuria may suggest an alternative diagnosis of epididymitis or orchitis, although this may be present in torsion as well. The diagnostic study of choice is US with color Doppler, which identifies a torsed testis with absent blood flow (Gunther and Rubben, 2012). Presence of blood flow, however, does not definitively rule out torsion, and a high clinical suspicion warrants surgical consultation regardless of Doppler results (Mellick, 2012). Studies of emergency physicians performing ultrasound of the testes are ongoing (Leeson and Leeson, 2013).
Management of Testicular Torsion
Surgical detorsion should be performed without delay when torsion is identified or highly suspected. Bilateral orchiopexy is performed at the time of surgery to reduce the likelihood of torsion of the contralateral testis. Orchiectomy may be indicated for a nonviable testis (Gunther and Rubben, 2012).
Conclusion
The differential diagnosis of lower abdominal pain in the adolescent includes several life-threatening or fertility-threatening diagnoses that the clinician must not miss. It is essential to consider the anatomical differences between sexes, as well as high-risk behaviors common in adolescents when evaluating teenagers with abdominal pain. Building rapport with a young patient to obtain a thorough history and a complete examination of reproductive organs is important.
Case Conclusion
This patient had persistent pain despite the administration of morphine and had a normal white blood cell count. The pelvic US with Doppler identified an enlarged right ovary with absent venous or arterial flow, consistent with ovarian torsion. She was transferred to the operating room for laparoscopic detorsion.
Gaps in Knowledge/Research Questions
Boys with gonadal torsion are diagnosed earlier and have a higher gonad salvage rate than girls (Piper et al., 2012). The reproductive consequences of a nonviable gonad after torsion are substantial. Future research should explore ways to reduce delay in diagnosis of ovarian torsion. Early laparoscopic intervention to evaluate nonspecific abdominal pain in girls needs study.
Case 4: Knee pain
A 13-year-old boy presented with right-sided knee pain for one week. There was no preceding trauma, although the patient played soccer daily before the pain began. Pain was worse with ambulation, mildly improved with rest or ibuprofen. Review of systems was notable for a cold the previous week and was negative for fever or other complaints. Vital Signs: heart rate 110 beats per minute, respiratory rate 20 breaths per minute, blood pressure 110/80, O2 saturation 99%, and oral temperature 36.7°C Exam: Antalgic gait involving the right leg, no point tenderness at the knee, decreased range of motion of the right hip and knee due to pain; the right lower extremity was neurovascularly intact. There was no tenderness with varus or valgus stress at the knee joint, and no excess laxity on anterior and posterior drawer testing; the Lachman test was negative.
Related posts:
Sex and Gender; Pharmacology, Efficacy, Toxicity, and Toxicology
Overcoming Resistance: Importance of Sex and Gender in Acute Infectious Illnesses
A Sex and Gender Based Perspective on Traumatic Injury
Digesting Sex and Gender: Gastroenterology
Sex and Gender in Medical Education: The Next Chapter
Special Populations
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
