3.1. Treatment Goals
The clinical management of the patient with CAH is inherently age and gender specific [8–11]. In devising regimens for individuals with CAH, the endocrinologist should first review the treatment goals. Confirmation of the diagnosis of CAH (and also of the clinical form) may be necessary using hormonal and/or genetic testing depending on the pediatric medical information available. The CCC should develop a structured process for age-appropriate discussions to educate a patient about his or her disorder, its treatment, and how to handle emergencies away from home. Eventually, the patient should be able to describe CAH and its potential complications, understand the need for stress glucocorticoid dosing and the need to wear medical alert identification jewelry, and know his/her own medications, dose and schedule. Therapy should be individualized based on age, gender, prior history, body composition, other illnesses, and immediate goals .
Parents often worry about giving 3-4 doses of medication per day to their children within school and activity schedules. Many adults perceive that they cannot take divided doses of hydrocortisone due to work schedules; however, chronic therapy with longer-acting and more potent synthetic glucocorticoids may increase risks for side effects, including obesity, glucose intolerance, bone loss, skin fragility, poor sleep, and immunosuppression. The endocrinologist should emphasize that individual responses to specific medications are only somewhat predictable, and trial periods are necessary to assess the benefits and complications of each regimen. It is recommended that CCCs develop pamphlets to discuss treatment options. The CCC should be able to elicit the input of secondary providers, including dietitians, physical therapists, and personal trainers, to help the patient manage weight gain and deconditioning that might arise when therapies are intensified. Although these specialists need not be a part of the CCC, specific individuals in the region should be identified and also educated about CAH to provide better care.
3.2. Timing of Changes
Significant regimen changes should be avoided during times of major life changes, such as starting school, moving, going away to college, getting married, or starting a new job. These changes should begin several weeks prior to or started several weeks after the event transpires. For adolescents and adults, many of these events are associated with weight gain, fatigue, poor sleep, and emotional changes; consequently, these symptoms might be erroneously attributed to the new treatments if not separated in time. While laboratory monitoring is important, clinical responses are paramount, and overtreatment simply to have laboratory values in the normal range is strongly discouraged.
3.3. The Newborn
As discussed above, infants should be referred to the CCC by PCPs or by newborn screening programs. Goals include confirmation of the diagnosis of CAH, initiation of hormone replacement therapy, and family education. In addition to pediatric endocrinologists, pediatric urologists/surgeons, endocrine nurse educators, and behavioral health specialists may be involved. The initial visits should form the basis for long-term relationships between the family and the CCC.
3.4. The Child
Every clinic visit for a child or adolescent with CAH should include a comprehensive endocrine evaluation and an assessment/screening of behavioral health status. Involvement of the child in this conversation, as appropriate for his/her level of maturity, is important to educate the child about why he/she takes daily medications and may occasionally need to miss school for doctors' appointments. Medical issues addressed should include adequacy of hormone replacement therapies, adherence to treatment recommendations, evaluation of growth and pubertal status, evaluation for excessive androgen secretion, reinforcement of appropriate stress glucocorticoid coverage, and use of medical alert identification. Hormone determinations and radiographic testing should be performed as necessary to assess adequacy of hormone replacement therapy. From the time of diagnosis, sharing of information with the child with CAH should be planned with the parents through an ongoing dialogue regarding what is developmentally appropriate for the child . Medical education and counseling for children is a continuous process, gradually increasing in sophistication, in which teaching occurs at a level that is commensurate with the progressing cognitive and psychological development of the child, with specific emphasis on fostering open parent-child communication . Thus, open and honest communication with the patient and the family is essential. Behavioral health assessment ideally consists of a brief interview conducted separately with both patient and parents by a qualified behavioral health provider.
3.5. The Adolescent
Although the pediatric endocrinologist will continue to be the dominant care provider during adolescence, the adolescent must develop an understanding of his or her condition. The pediatric endocrinology team has the responsibility for educating the child and the parents about the child's impending independence. Discussions about puberty should be initiated at the appropriate age for each child as they develop, with discussion of privacy and appropriate boundaries. Transitioning the adolescent patient into adult care should be gradual process that begins years prior to the change in health care providers . This process should include provision of medical records which include information on the type of CAH, genetic reports (if mutation(s) is/are known), age of diagnosis, current and significant past treatment regimens (including rationales for deviation from typical therapies), genital and gonadal surgeries, other medical problems and surgeries, family and social history, allergies, psychological issues (if any), and recent laboratory data. A summary paragraph capturing the patient's essential characteristics, treatment, and particular needs should conclude the transfer form or referral letter. Joint meetings between the adult and pediatric health care providers are ideal, but some centers may be structured such that the patient will see the endocrinologist in a different physical location and/or at a different hospital.
During the middle school and high school years, age-appropriate education should occur with and without the parent present, and should foster independent knowledge and eventual self-management. Patients should be encouraged to ask questions during each office visit. Independent health care behaviors should begin to develop in the pediatric setting. Parents must be educated about how to give the child increasing responsibility for his/her healthcare. Adolescents should be provided with time alone with the physician(s) without the parent(s) in the exam room. The adolescent needs to be offered the opportunity to discuss personal issues such as menstruation, contraception, fertility, gender identity concerns, and use of tobacco, alcohol, and recreational drugs in the absence of their parents.
Subjects covered during the transition from pediatric to adult care providers should include planning for health care insurance coverage/governmental health plan for the child after age 18 years or after college. Additional topics include sexual, urological, and reproductive health including contraceptive counseling, genetic counseling, mental health issues, body weight concerns, and understanding the genetics of CAH. Pertinent discussions should include how to stay healthy in college or other after high school situations, potential alcohol/recreational drug abuse, healthy eating, and weight-gain avoidance. Discussions about how to handle illnesses and emergencies should be held. Specific plans should include telling a roommate about CAH and the potential need for glucocorticoid injections, knowing locations of college health center facilities and the local emergency department, and knowledge of insurance information. Additional topics for the college-bound adolescent include how to handle homesickness, stress, anxiety, and depression, and how to care for mental health. Emphasizing the profound cosmetic and reproductive side effects of nonadherence with medications and monitoring can often have a bigger impact for teens than merely emphasizing the health aspects of noncompliance. Young adults should be prepared with more knowledge about CAH than their new healthcare providers in college health/armed forces health services . Thus, they need to learn to advocate for themselves in the healthcare setting and learn how to explain CAH and their health needs to new healthcare providers.
Adolescent girls need to understand their history, if any, regarding ambiguous genitalia at birth and the extent of surgery. Issues related to sexuality, sexual function, and genital anatomy including the use of vaginal dilators versus surgical options may warrant discussion. When appropriate, this discussion should include how to responsibly approach sexual activity, talking to a sexual partner about genital reconstruction, and preparing for the first sexual experience. Family discussions should be encouraged and some education should occur prior to gynecology referrals. Caregivers should be sensitive to cultural differences in relating information. They must educate parents about adverse long-term psychological consequences of withholding medical information if parents are resistant to such discussions. CAH nurse educators should reinforce educational content, review anatomy, teach the use of vaginal dilators, and answer questions related to and in conjunction with the first gynecologic visit. They should help the patient determine questions and goals related to such visits. Some women with CAH may have the false impression that pregnancy will not be possible. Since many women with CAH have trouble conceiving, they should be aware that pregnancy may take longer to achieve and should have this information available for family planning. They should also know that CAH is not an effective form of birth control and be informed about the types of contraception available. Counseling women about prevention of sexually transmitted infections and HPV vaccination should be included in their gynecological care.
3.6. The Adult Female
Adult females also require periodic assessments of the adequacy of glucocorticoid replacement, the possible development of myelolipomas, bone health, and reproductive function. There is also a need to address genetic counseling concerns, update health education, and assess health maintenance activities . Women with nonclassical CAH (NCAH) often come to medical attention for infertility, oligoanovulation, and hirsutism; treatment should be directed to these needs . The degree of androgen excess in NCAH varies, and CCC physicians should not underestimate the need for, or complexity of, treatment. The same goal-directed principles guiding therapies apply as for women with classical CAH. The care of the adult female is further complicated by additional needs for gynecological care and, in some instances, obstetrical care. Specialized behavioral health care may be required to assist the patient in discussing issues that might be unique to CAH, especially sexuality and gender identity. The adult female should be assured that although her care may be complex, the CCC has sufficient expertise in all relevant areas. Adult females should also receive routine screening and health maintenance testing (Pap smears and mammograms).
Each CCC should have an available gynecologist (or another caregiver trained in gynecological exams and issues) who is knowledgeable about CAH to both examine and discuss issues with CAH females. Pap smears are recommended by the American College of Obstetricians and Gynecologists by age 21 or within 3 years of sexual intercourse . Having a health care provider who is comfortable discussing sexuality and has a relationship with the patient is extremely important. A comfortable patient-physician relationship will facilitate discussion of feelings about genital appearance and/or sexual and/or reproductive functioning. A solid relationship will also foster involvement of additional health providers, including psychosexual specialists and sex therapists, gynecological and/or urological specialists, and/or reproductive endocrinologists. Many females may begin seeing a gynecologist prior to or along with seeing an internal medicine endocrinologist, depending on the individual patient's needs.
For women with classical CAH, treatment regimens will vary with their reproductive needs and sensitivity to androgens and progesterone. For women who do not want to become pregnant, nonglucocorticoid therapies should be discussed and offered to minimize exposure to supraphysiological doses of glucocorticoids. These adjunctive measures include antiandrogens, oral and transdermal contraceptives, intrauterine devices, and topical or mechanical depilation methods. The CCC should provide mechanisms or forums to review and to optimize individual patient treatment plans with the endocrinologist, gynecologist, and other relevant providers in a case-review format . Most importantly, the endocrinologist should emphasize that a woman is not locked into a single regimen for life, and alterations are often desirable as the needs and goals change.
3.7. Pregnancy Considerations
Women with both classical and NCAH desiring pregnancy should be offered preconception counseling prior to pregnancy. This counseling may include genetic counseling and testing the partner (when appropriate), discussing the likelihood of dose titration during pregnancy, the increased need for Caesarian section in classical patients, and the use of stress-dose glucocorticoids during labor and delivery. A reproductive endocrinologist should assess the need for fertility treatment. A team approach to pregnancy, including an endocrinologist, a reproductive endocrinologist (as needed), and an obstetrician (maternal-fetal medicine specialist when indicated), is highly recommended. Discussion regarding the risk-benefit ratio of prenatal dexamethasone therapy may be considered, but only in the context of a research setting, per current Endocrine Society guidelines . The CCC team plays a key role during pregnancy, during which time close communication is important between the endocrinologist and the obstetrician. After becoming pregnant, women with CAH should be aware that their glucocorticoid and mineralocorticoid doses may change during gestation.
3.8. The Adolescent and Adult Male
Adult males with CAH require periodic evaluation to assure adequate glucocorticoid replacement, monitor for the development of testicular rests and adrenal myelolipomas, monitor bone health, and address fertility issues (if desired), and for general health maintenance. Males with CAH may have concerns about fertility if they have known adrenal rest tissue. Some may be under the false assumption that they are unable to father children and may need to be reminded that CAH is not a form of birth control. Males who have a history of precocious puberty may have concerns about the normalcy of their development. Open discussion and ongoing developmentally appropriate education is warranted throughout adolescence and adulthood .
For men with classical CAH, moderate doses of hydrocortisone or a longer-acting glucocorticoid, along with fludrocortisone, are generally sufficient to prevent adrenal insufficiency, maintain fluid and electrolyte balance, avoid suppression of gonadotropins, and prevent development of tumors, such as adrenal rests in the testes and myelolipomas in the adrenals. Higher doses or more potent glucocorticoids, as well as the reinforcement of good compliance may be necessary to induce regression of these tumors and promote fertility. The CCC should coordinate urological evaluation (testis size, need for sperm retrieval, etc.) and screening for complications with treatment changes and monitoring schemes instituted by the endocrinologist. Men with NCAH rarely require treatment.
The internal medicine endocrinologist should manage hormonal therapies and related endocrine issues, and the PCP should generally handle unrelated and acute problems, and routine health maintenance. Access to genetic counseling and DNA testing should be readily available for affected individuals, partners, and other interested family members. Education of the patient, who may have relied on his parents to manage his CAH, is an important goal. Patients should receive age-appropriate routine screening examinations as coordinated with their PCP (blood pressure, fasting lipids, and colon and prostate cancer screening). Attention to conditions exacerbated by chronic glucocorticoid use, for example, metabolic syndrome, obesity, and osteoporosis, should be considered.
3.9. Bone Health
Treatment of CAH demands life-long glucocorticoid replacement. However, finding the "exact" or "best" dose remains elusive. Undertreatment has been associated with adrenal insufficiency (adrenal crisis) and androgen excess (virilization and short stature), whereas overtreatment causes iatrogenic Cushing syndrome with numerous physical and metabolic consequences. Although treatment requires supraphysiological dosing compared to adrenal insufficiency of other etiologies (such as Addison's disease), excessive dosing beyond that required for good control of CAH, especially after the newborn period, may be deleterious to bone health over the lifespan. Furthermore, addition of medications to maximize a child's height potential may affect bone mineral density [24–26]. Although such treatments have positive outcomes (height, self-esteem, etc.), the risk/benefit with regard to bone health demands that the CCC be attentive to skeletal integrity and consider screening during the course of these regimens. Because the potential risk for osteoporosis remains to be quantified, the CCC should have the capacity to monitor and treat bone disease, even in young patients .