Block 9 Board Review Part 2 Endocrine 28Feb14 Chauncey D. Tarrant, M.D. Chief of Residents 13-14

Why are we STILL reviewing ENDOCRINE???

3.5% of Initial Certifying Exam!!!

Pediatrics In Review Articles Congenital Adrenal Hyperplasia Addison Disease Turner’s Syndrome

Congenital Adrenal Hyperplasia

What are the signs and symptoms of CAH (adrenal crisis)??

What are the signs and symptoms of CAH (adrenal crisis)?? Genital Ambiguity (severe form/females) Decreased activity/fatigue Altered sensorium/unresponsiveness Poor feeding/weak suck Dry mucus membranes Hyperpigmentation Abdominal pain Vomiting Hyponatremia Hyperkalemia Hypoglycemia Metabolic Acidosis Hypothermia Hypotension Dehydration Lack of Weight Gain

What is the lab evaluation for CAH?

What is the lab evaluation for CAH? CMP Dex ABG Cortisol ACTH 17OHP Pelvic Ultrasound Karyotype

Can CAH be diagnosed prenatally? How?

Can CAH be diagnosed prenatally? How? Yes Amniocentesis (14-18 wks) Chorionic Villous Sampling (10-12wks)

How do you treat adrenal crisis in a patient with CAH??

How do you treat adrenal crisis in a patient with CAH?? Fluid resuscitation (20ml/kg bolus 0.9% NaCl) Fluids at 1.5-2x maintenance Hydrocortisone (stress dose-100mg/m2) Central Access Pressors (with higher glucose concentrations) HyperK?? Consider C BIGK

What is the value in screening for salt losing CAH in male infants with normal genitalia?

What is the value in neonatal screening for salt losing CAH in male infants with normal genitalia? Prevent adrenal crisis in cases of male infant that might not have otherwise been suspected

Maternal exposure to what can lead to virilization in female infants?

Maternal exposure to what can lead to virilization in female infants? Androgens

Addison Disease

What are the signs and symptoms of Addison Disease?

What are the signs and symptoms of Addison Disease? Similar to adrenal crisis Abdominal pain, nausea, vomiting, fatigue, muscle weakness, poor weight gain, loss of pubic and axillary hair …BUT No elevated adrenal androgens Response of Cortisol and its precursors to ACTH is blunted or absent

How can you use lab tests to diagnose Addison disease?

How can you use lab tests to diagnose Addison disease? Electrolytes AM Cortisol Plasma Renin ACTH ACTH stim test

How do you treat adrenal crisis in a patient with Addison Disease?

How do you treat adrenal crisis in a patient with Addison Disease? Fluid resuscitation (20ml/kg bolus 0.9% NaCl) Fluids at 1.5-2x maintenance Hydrocortisone (stress dose-100mg/m2) Central Access Pressors (with higher glucose concentrations) HyperK?? Consider C BIGK

What are the complications of sudden withdrawal of steroids in patients with adrenal insufficiency?

What are the complications of sudden withdrawal of steroids in patients with adrenal insufficiency? Addisonian crisis sharp leg pain Lower back or abdominal pain nausea Vomiting hyponatremic dehydration hyperkalemia metabolic acidosis hypotension Hypoglycemia Shock sudden death

Turner’s Syndrome

What are the signs and symptoms of Gonadal Dysgenesis (Turner’s Syndrome)?

What are the signs and symptoms of Gonadal Dysgenesis (Turner’s Syndrome)? congenital lymphedema (swelling of the hands or feet) webbed neck Low hairline shield chest with inverted and widely spaced nipples Deformity of the ears nail dysplasia cubitus valgus short metacarpals micrognathia

What is the lab evaluation for gonadal dysgenesis?

What is the lab evaluation for gonadal dysgenesis? Karyotype Serum LH Serum FSH Serum Estradiol

What is the importance of evaluating for renal and cardiac disorders in gonadal dysgenesis (Turner Syndrome)

What is the importance of evaluating for renal and cardiac disorders in gonadal dysgenesis (Turner Syndrome)? High incidence of: Aortic valve defects (bicuspid Aortic valve) (20-30%) Coarctation of the Aorta (3-10%) Horshoe Kidney **Increased risk of aortic dissection, EKG abnormalities, and HTN Initial Cards workup with 4pt BP, EKG, Echo, or Echo and MRI

PREP

A 4-year-old girl in your practice was noted to have clitoromegaly at birth and was diagnosed with congenital adrenal hyperplasia (CAH). She was diagnosed as having classic CAH caused by 21-hydroxylase deficiency and has been doing well on glucocorticoids and mineralocorticoids prescribed by her pediatric endocrinologist. Her mother is considering another pregnancy and wishes to know what she needs to be aware of in a future pregnancy. Of the following, you are MOST likely to tell her that

A. at birth, an affected female would be expected to have a similar degree of virilization as her sister B. at birth, an affected male is likely to have ambiguous genitalia C. at birth, the majority of affected males will not require glucocorticoids and mineralocorticoids D. prenatal administration of dexamethasone is important for both male and female fetuses E. prenatal diagnosis for CAH can be accomplished using molecular technologies through amniocentesis

B. at birth, an affected male is likely to have ambiguous genitalia A. at birth, an affected female would be expected to have a similar degree of virilization as her sister B. at birth, an affected male is likely to have ambiguous genitalia C. at birth, the majority of affected males will not require glucocorticoids and mineralocorticoids D. prenatal administration of dexamethasone is important for both male and female fetuses E. prenatal diagnosis for CAH can be accomplished using molecular technologies through amniocentesis The young girl in this vignette has the most common form of congenital adrenal hyperplasia (CAH), which is caused by reduced activity of 21-hydroxylase. Classic CAH affects about 1 in 12,000 to 15,000 children and, undiagnosed, may lead to salt-wasting and shock in newborns. Prenatal diagnosis of CAH may enable treatment to prevent virilization of an affected female fetus and institute treatment promptly at birth to prevent salt-wasting. About three-quarters of individuals with classic 21-hydroxylase deficiency have an inability to synthesize both glucocorticoids and mineralocorticoids (salt wasting), whereas one-quarter have only the inability to synthesize glucocorticoids (simple virilization). Prenatal diagnosis is possible by determining amniotic fluid hormone levels, and, in recent years, more accurate diagnosis has become possible through use of molecular technologies to analyze fetal DNA obtained through chorionic villus sampling or amniocentesis. While female fetuses with classic CAH typically have some degree of virilization, the degree of virilization is quite variable even in affected daughters born to the same parents. Males with CAH due to 21-hydroxylase deficiency do not have ambiguous genitalia and may go undiagnosed until they develop clinical features of salt-wasting, which may present acutely in the newborn period with symptoms of shock. Affected males and females with the salt-wasting form of CAH require treatment with glucocorticoids and mineralocorticoids. While some controversy exists regarding the efficacy and safety of prenatal treatment of potentially affected fetuses with maternal administration of dexamethasone, the goal of this treatment is to prevent virilization of a female fetus. Ideally, this treatment should be instituted before the 6th week of pregnancy to completely suppress the fetal pituitary-adrenal axis. Early prenatal diagnosis can assist in treatment decisions, since dexamethasone therapy can be discontinued in the case of an unaffected female fetus or if the fetus is male. For affected female fetuses, maternal dexamethasone therapy would be continued throughout the pregnancy. Potential maternal complications of dexamethasone therapy include excessive weight gain, hypertension, glucose intolerance, chronic gastrointestinal problems, and features of Cushing syndrome.

A mother of a patient in your practice reports that she is currently 8 weeks pregnant and just discontinued use of danazol, which she was taking for treatment of severe endometriosis. She has been told that use of this medication in the first trimester of pregnancy can be associated with birth defects and wishes to know what possible birth defects can be seen with use of this medication in pregnancy. Of the following, you are MOST likely to tell her that use of danazol in pregnancy is associated with an increased risk for

A. anterior abdominal wall defects B. congenital heart defects C A. anterior abdominal wall defects B. congenital heart defects C. neural tube defects D. renal malformations E. virilization of a female fetus

A. anterior abdominal wall defects B. congenital heart defects C A. anterior abdominal wall defects B. congenital heart defects C. neural tube defects D. renal malformations E. virilization of a female fetus Danazol is a synthetic steroid derived from ethisterone and is a suppressor of the pituitary-ovarian axis. It is used to treat conditions such as endometriosis, fibrocystic breast disease, and hereditary angioneurotic edema. It is listed as a pregnancy category X drug and should not be used in pregnancy because of the risks for virilization of female fetuses. Under the best of circumstances, this medication should be discontinued well before attempting pregnancy since fetal genital development starts as early as the 6th week of gestation. Defects associated with in utero exposure of a female fetus to danazol include clitoral hypertrophy, labial fusion, urogenital sinus tract defects, vaginal atresia, and even genital ambiguity. Discontinuing this medication as soon as the pregnancy is known is certainly advisable, but this may not completely mitigate the effects of this potent hormone since she has been taking this throughout the first 2 months of pregnancy. This mother may benefit from genetic counseling about the potential fetal risks, and she may be offered additional prenatal screening, such as fetal sex determination (via chorionic villus sampling or amniocentesis) and level II ultrasonography to evaluate the fetal genitalia. Use of this medication in the first trimester of pregnancy is not associated with other problems, such as fetal anterior abdominal wall defects, cardiac defects, neural tube defects, or renal malformations. Use of this drug during breastfeeding is also not recommended, so prospective mothers who plan to restart danazol after delivery need to be told that use of this medication will preclude breastfeeding.

A 5-year-old girl with classic 21-hydroxylase deficiency (congenital adrenal hyperplasia) develops gastroenteritis with fever (up to 38.9°C), vomiting, and diarrhea. Her regular medications include hydrocortisone and fludrocortisone. Upon presentation to the emergency department, she is tired-appearing and remains febrile. Her pulse rate is 162 beats/min, blood pressure is 62/40 mm Hg, and capillary refill is poor. Laboratory tests drawn in the emergency department are still pending, but fingerstick glucose level is 42 mg/dL (2.3 mmol/L). The patient is treated with a bolus of normal saline to restore circulatory support. Of the following, the MOST important therapy to administer to this patient next is

A. cortisone acetate intramuscularly and aldosterone intravenously B A. cortisone acetate intramuscularly and aldosterone intravenously B. cortisone acetate intramuscularly and dextrose intravenously C. dopamine and dextrose intravenously D. hydrocortisone hemisuccinate and aldosterone intravenously E. hydrocortisone hemisuccinate and dextrose intravenously

A. cortisone acetate intramuscularly and aldosterone intravenously B A. cortisone acetate intramuscularly and aldosterone intravenously B. cortisone acetate intramuscularly and dextrose intravenously C. dopamine and dextrose intravenously D. hydrocortisone hemisuccinate and aldosterone intravenously E. hydrocortisone hemisuccinate and dextrose intravenously The girl described in this vignette has a known diagnosis of adrenal insufficiency due to 21-hydroxylase deficiency and is hemodynamically unstable during a febrile illness. Emergency treatment with high doses of steroids (stress dose steroids) is needed to mimic the high doses of steroids normally made under stress in patients with sufficient adrenal function. The treatment of choice for adrenal crisis (of any cause) is fluids, hydrocortisone, and dextrose intravenously. Hydrocortisone is quick acting and at an emergency stress dose (100 mg/m2) saturates all steroid receptors, causing a mineralocorticoid and glucocorticoid effect. In addition, hypoglycemia is common during adrenal crisis, so the patient’s glucose level should be checked and an intravenous bolus of dextrose given if hypoglycemia is present. Pediatricians should recognize that some steroids, such as methylprednisolone, commonly used in asthma, have no mineralocorticoid activity at any dose and would not be appropriate for this patient. Hydrocortisone stress dosing guidelines are shown (Item C184). Because there is no available intravenous form of aldosterone, choices A and D would be incorrect, and instead one should choose a quick-acting steroid with mineralocorticoid activity, in this case, hydrocortisone at high doses. Intramuscular hydrocortisone is commonly given to patients to take at home before coming to the hospital if they are severely ill, but once in the emergency department, intravenous hydrocortisone should be used due to its quick onset of action. Dopamine would not be used in the acute setting of adrenal crisis because intravenous hydrocortisone must be given first.

During a regularly scheduled visit, the mother of a 10-year-old boy who has had type 1 diabetes mellitus for 5 years expresses concern about her son’s increased frequency of hypoglycemic episodes over the past 3 months. She also notes that he is increasingly tired and that his skin is getting tanner even though he has not had any sun exposure. Of the following, the MOST appropriate next step in this boy’s management is to order a

A. cortisol level drawn at 7 am B. cortisol level drawnat 4 pm C. dexamethasone (1 mg) suppression test D. high-dose (250 μg) corticotropin stimulation test E. low-dose (1 μg) corticotropin stimulation test

A. cortisol level drawn at 7 am B. cortisol level drawnat 4 pm C. dexamethasone (1 mg) suppression test D. high-dose (250 μg) corticotropin stimulation test E. low-dose (1 μg) corticotropin stimulation test

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