ANSWERS of MCQS PUBLISHED ON 28/8/2019

ANSWERS of MCQS PUBLISHED ON 28/8/2019

MCQS#01

E. Half of the neonates born to mothers with Graves disease develop hyperthyroidism

Explanation:

Thyroid disease is a common entity in pregnancy. Graves disease occurs in 0.1% to 0.4% of all pregnancies, although only about 1% of neonates born to women with Graves will be clinically affected. The fetus/neonate is affected as a result of transplacental passage of thyroid-stimulating hormone (TSH) receptor-stimulating and receptor-blocking antibodies during the 2nd half of pregnancy. Because stimulating antibodies are more often produced, most affected neonates will develop hyperthyroidism. However, a small number of infants may develop hypothyroidism if the amount of blocking antibodies crossing the placenta is greater than the amount of stimulating antibodies. Evidence of fetal disease can be apparent even if the pregnant woman has inactive Graves disease (e.g., following removal or destruction of the thyroid gland) because the fetus is still exposed to maternal antibodies. Intrauterine signs of fetal disease include fetal tachycardia, growth restriction, and fetal hydrops. A fetal goiter may also be present. Post-birth, the symptoms of hyperthyroidism in a newborn are usually apparent within the first 10 days of life, although clinical symptoms can present up to 4 to 6 weeks of life. Thyrotoxicosis usually resolves by 2 months of age but may last as long as 5 months of life.

The signs and symptoms of neonatal hyperthyroidism is variable and include the following:

•Increased irritability and jitteriness

•Periorbital edema and exophthalmos

•Tachycardia

•Pulmonary hypertension

•Weight loss

•Diarrhea

•Sweating and flushing

•Advanced bone age

•Hepatosplenomegaly

•Bruising and petechiae

•Goiter

Infants with evidence of thyrotoxicosis should be managed immediately with anti-thyroid therapies and symptomatic relief can be provided by beta-blockade. Anti-thyroid options include propylthiouracil and carbimazole.

Reference:

Hernandez MI, Lee KW. Neonatal Graves disease caused by transplacental antibodies. NeoReviews. 2008; 9(7):e 305-e 208.

MCQS#02

C. There is a TSH surge after birth, with markedly elevated TSH concentrations compared to older infants

Explanation:

The timing of the newborn state screen is critical to interpret the results of thyroid function studies. Typically the newborn screen is performed 36 to 72 hours after birth in a healthy term infant. Because the state screen of the infant in this vignette was obtained shortly after birth, it may reflect normal physiologic changes that would be considered abnormal in a different situation. After birth, there is a dramatic increase in serum thyroid-stimulating hormone (TSH) concentrations with levels as high as 60 to 70 mU/L. While not completely understood, this process is thought to result from the infant’s initial exposure to the relatively cold atmosphere compared with the intrauterine environment. This TSH surge results in an increase in serum thyroxine (T4) and

triiodothyronine (T3) concentrations. The concentration of T4 in the first week of life is usually the highest than at any other time during life. The T3 levels tend to rise after the first week of life and continue to increase during the first month of life. In contrast, concentrations of reverse T3 (rT3) tend to decrease postnatally because of the increased action of deiodinase D, as well as loss of placental deiodinase D3. Free T4 and thyroid-binding globulin follow a similar path as T4, usually exhibiting a peak in the first week of life followed by a gradual decline. While an abnormally high TSH value would be concerning for congenital hypothyroidism, the infant in this vignette most likely has an elevated TSH because the screen was performed immediately after birth when the TSH is expected to be high because of normal physiologic adaptation.

Reference:

Feingold SB, Brown RS. Neonatal thyroid function. NeoReviews. 2010;11(11):e640-e645

MCQS#03

B. Hypercalcemia

Explanation:

Infants of a diabetic mother (IDM) are at increased risk for multiple problems after birth. Hypoglycemia typically occurs as a result of attenuation of the maternal supply of glucose once the umbilical cord is clamped. The fetal hyperinsulinemic state continues in the short-term and lack of maturity of the counter-regulatory hormones may result in persistent neonatal hypoglycemia. In

addition, the effect of insulin as a growth factor may result in intracardiac septal and ventricular wall thickening, which can lead to a transient cardiomyopathy. IDMs are at increased risk of having respiratory distress syndrome, although the risk has decreased over the years; this is probably because of more accurate fetal assessment of gestational age. The mechanism for surfactant deficiency may result from increased fetal insulin inhibitory action

on fibroblast-pneumocyte factor, which normally acts on type II alveolar cells to produce surfactant. IDMs are at increased risk of polycythemia, although the mechanism is not understood. In addition. IDMs are also at an increased risk for hypocalcemia (NOT HYPERcalcemia), possibly as a result of a delay in the neonatal parathyroid hormone surge due to urinary magnesium losses (which can decrease parathyroid hormone secretion, thus resulting in hypocalcemia)

References:

Dailey TL, Coustan DR. Diabetes in pregnancy. NeoReviews. 2010;11(11):e619-e625

Ogata, ES. Problems of the infant of the diabetic mother. NeoReviews. 2010;11(11):e627-e630

MCQS#04

B. Maternal thyroid-stimulating hormone (TSH)

Explanation:

Thyroid gland embryogenesis is completed by 10 to 12 weeks of gestation and the gland begins to secrete thyroid hormone at approximately 12 weeks’ gestation. The fetal thyroid-stimulating hormone (TSH) receptors, however, do not become responsive to TSH and TSH receptor antibodies (TRAbs) until ~20 weeks’ gestation. There is a progressive increase in thyroxine (T4) and thyroxine-binding globulin (TBG) in the fetus, as well as an increase in free T4 (fT4) between 18 and 36 weeks’ gestation. In the first half of pregnancy, small amounts of maternal T4 cross the placenta when fetal T4 remains low. Additionally, maternal thyroid-releasing hormone (TRH) can cross the placenta but only in small amounts because the maternal serum TRH concentration is low. However, maternal TSH does not cross the placenta. TRAb (both stimulating and blocking) are immunoglobulin G antibodies that readily cross the placenta. Additionally, anti-thyroid medications and iodide both can cross the placental barrier. Iodide placental passage can affect the fetus in the first half of pregnancy when the fetal thyroid hormone production is increasing.

Reference:

Hernandez MI, Lee KW. Neonatal Graves disease caused by transplacental antibodies. NeoReviews. 2008;9(7):e305-e208

MCQS#05

A. 5-alpha reductase deficiency

Explanation:

5-alpha reductase deficiency is an autosomal recessive disorder that limits the conversion of testosterone to dihydrotesterone. Males with 5-alpha reductase deficiency have ambiguous genitalia with appropriately differentiated Wolffian structures, absence of Müllerian-derived structures, small phallus, urogenital sinus with perineal hypospadias, and a blind vaginal pouch. Later in life, males have progressive virilization with decreased facial hair and small prostates. “Testicles at twelve” is sometimes used in reference to 5-alpha reductase deficiency because of virilization and descent of testes to the labial location at the time of puberty. Females have a normal phenotype. Thus, the infant in this vignette with a 46 XX chromosomal analysis is not likely to have 5-alpha reductase deficiency.

Aromatase deficiency prevents conversion of testosterone to estradiol, thus androstenedione is not ultimately converted to estrone (see Figure above). Affected females have Müllerian duct structures and absent Wolffian duct structures, evident by ambiguous genitalia or cliteromegaly. Affected females may also have multicystic ovaries, tall stature, virilization at puberty, and delayed bone age. If the fetus is exposed to maternal androgen and progesterone therapy between 8 to 13 weeks’ gestation, the female fetus is at risk for ambiguous genitalia, including posterior fusion of the vagina, scrotalization of the labia and some fusion of the urethral folds. If the female fetus is exposed to these maternal hormones after 13 weeks’ gestation, the fetus may develop cliteromegaly.

Congenital adrenal hyperplasia encompasses a group of enzymatic disorders that leads to ambiguous genitalia. 

Deficiencies in 21-hydroxylase, 11 beta-hydroxylase, and 3 beta-hydroxysteroid dehydrogenase lead to ambiguous external genitalia in females.

References:

Brodsky D, Martin C. Neonatology Review. 2nd edition. Lulu. 2010.

Fanaroff AA, Martin RJ, Walsh MC (eds). Neonatal-Perinatal Medicine: Diseases of the Fetus and Infant. 8th edition. Philadelphia: Mosby-Elsevier; 2006.

Sperling MA. Pediatric Endocrinology. 3rd edition. Philadelphia: WB Saunders; 2008.