Endocrinology

Question 1

What is the common cause of congenital hypothyroidism?

Answer 1

Thyroid Dysgenesis

Thyroid dysgenesis (including dysgenesis, agenesis, and ectopic thyroid) is the most common cause of congenital hypothyroidism, resulting in > 90% of the diagnoses. Congenital hypothyroidism occurs in 1/2,000–4,000 newborns.

Question 2

A “short” child presents with the following:

• Normal growth velocity
• Normal bone age
• Family history of short stature

What is the most likely diagnosis?

Answer 2

Genetic Short Stature

The 3 etiologies of short stature are constitutional growth delay, genetic short stature, and growth hormone deficiency. Use growth velocity, bone age, and family history to differentiate among these. Of the 3, only genetic short stature presents with normal bone age.

Question 3

A 5-year-old girl has a solitary maxillary central incisor.

Which endocrine deficiency is likely?

Answer 3

Growth Hormone Deficiency

Midfacial anomalies, such as a solitary maxillary central incisor, indicate a high likelihood of growth hormone deficiency.

Question 4

What is treatment of a newly diagnosed Type 2 diabetic aimed at first?

Answer 4

Weight Loss and Increased Physical Activity

Unfortunately, this approach is frequently unsuccessful. Metformin and sulfonylureas are usually used next.

Question 5

An adolescent girl on no medication, except for oral contraceptive pills, presents because of abnormal laboratory tests. She had been “tired,” and someone had ordered a total T4; it surprisingly came back elevated. Repeat testing shows a normal free T4 and a normal TSH.

What is causing the total T4 to be elevated?

Answer 5

Oral Contraceptive Pills

OCPs are increasing her estrogen levels, which increases her thyroxine-binding globulin (TBG), resulting in an elevated total T4 but still a normal FT4. Because she is euthyroid, her TSH is normal as well.

Question 6

A 17-year-old girl presents with:

• Obesity
• Acanthosis nigricans
• Type 2 diabetes
• Hirsutism
• Secondary amenorrhea
• LH:FSH ratio is elevated at 4:1
• Testosterone is also elevated

What is the most likely diagnosis?

Answer 6

Polycystic Ovary Syndrome (PCOS)

(Steven-Leventhal Syndrome)

PCOS is classically described as irregular menses with symptoms or biochemical evidence of hyperandrogenism (such as hirsutism and acne) ± bilaterally enlarged polycystic ovaries (confirmed by ultrasound). High testosterone with an elevated LH:FSH ratio helps diagnosis. Associated obesity and insulin resistance with resulting hyperinsulinemia, and a predisposition to Type 2 DM and cardiovascular disease are common.

Question 7

• Intrauterine growth retardation
• Fasting hypoglycemia
• Postprandial hyperglycemia with profound insulin resistance
• Serum insulin levels are 100× normal.
• Acanthosis nigricans
• Death is common before 1 year of age.

What is the syndrome with these characteristics?

Answer 7

Leprechaunism (Donohue Syndrome)

Donahue syndrome is a rare syndrome with the listed characteristics. The profound insulin resistance is usually caused by mutation or deletion of both insulin receptor genes.

Question 8

What hypothalamic hormone is responsible for onset and progression of puberty?

Answer 8

Gonadotropin-releasing Hormone (GnRH)

Hypothalamic pulsatile GnRH secretion regulates the production of LH and FSH, and thus is responsible for the onset and progression of puberty.

Question 9

Which type of diabetes insipidus (DI), central or nephrogenic, responds to desmopressin therapy?

Answer 9

Central DI

Remember that central DI is an ADH deficiency, so giving desmopressin corrects this by increasing urine osmolality and decreasing serum osmolality. Nephrogenic DI is not a deficiency in ADH but is a receptor problem, so giving desmopressin has no effect.

Question 10

A girl presents with the following:

• Short stature
• Webbing of the neck
• Pectus carinatum
• Cubitus valgus
• Hypertelorism
• Downward-slanting palpebral fissures
• High-frequency hearing loss
• Pulmonary valve stenosis

What is the most likely diagnosis?

Answer 10

Noonan Syndrome

Be careful with associations. Many see “webbing of the neck” and go for Turner syndrome because this is a girl. However, Noonan syndrome can have many of the features of Turner syndrome—a key difference here is the pulmonary stenosis. (Turner has aortic valve problems.) Intellectual disability also occurs in Noonan’s (about 25% of patients) and not Turner’s. (Although patients with Turner syndrome can have difficulty in math and problem solving.) Noonan syndrome has normal karyotype.

Question 11

A 6-year-old boy who was abused and kept locked up in a basement for 6 months presents with:

• Irritability
• Weakness
• Growth retardation
• Flared wrists
• Genu valgum
• Nodules on the ribs
• Elevated alkaline phosphatase
• Low phosphorus
• Very low 25-hydroxylase vitamin D

What is the likely diagnosis?

Answer 11

Vitamin D-Deficient Rickets

Vitamin D−deficient rickets is mainly seen in those with limited sun exposure or in babies who are being breastfed by vitamin D–deficient mothers. This differs from familial hypophosphatemic rickets (FHR), the most common form in the U.S. FHR is a kidney disease where the PTH is normal. It is a phosphorus-wasting disease, due to decreased renal tubular resorption of phosphorus.

Question 12

A tumor has destroyed the pituitary stalk, and the patient has developed pituitary hormone deficiency.

What tumor is most likely to do this?

Answer 12

Craniopharyngioma

Due to its precarious location in the intrasellar space, craniopharyngioma is the most common tumor to destroy the hypothalamus, pituitary, or its stalk and cause pituitary hormone deficiency. Radiation or previous surgery can also cause problems.

Question 13

What gene on the Y chromosome is necessary for male phenotype to occur?

Answer 13

SRY gene

Ordinarily, “maleness” requires a Y chromosome and specifically, an intact SRY gene and other genes to direct the undifferentiated gonad into a testis. Conditions exist wherein an X chromosome atypically has an intact SRY gene, resulting in an XX male, or a Y chromosome loses its SRY gene, resulting in an XY female.

Question 14

A boy with Klinefelter’s is at risk for what type of cancer?

Answer 14

Breast Cancer

Boys with Klinefelter syndrome can get breast cancer (same incidence as women). Follow the 2015 American Cancer Society breast cancer screening guidelines for women.

Question 15

A child presents with:

• Retinitis pigmentosa
• Obesity
• Mental retardation
• Polydactyly
• Genital hypoplasia with hypogonadism

What is this syndrome called?

Answer 15

Laurence-Moon-Biedl/Bardet-Biedl Syndrome

This syndrome is very rare, but presents with these findings. If you can remember the retinitis pigmentosa with hypogonadism, that is probably enough to stick in your mind.

Question 16

A tall 16-year-old boy with mild intellectual disability presents with gynecomastia. He has normal pubic hair development, but his penis and testes are small for his age.

What is the most likely diagnosis?

Answer 16

Klinefelter Syndrome

Klinefelter syndrome is generally not diagnosed until puberty, when penis and testes size do not develop normally. Intellectual disability and psychiatric problems occur early. The adrenal gland is fine, so you see normal pubic hair development; however, the testes do not fully develop due to seminiferous tubule dysgenesis. The classic karyotype is 47,XXY.

Question 17

All children with Type I diabetes should be screened regularly for what endocrine disorder?

Answer 17

Autoimmune Thyroid Disease

Chronic autoimmune thyroiditis (a.k.a. Hashimoto disease or chronic lymphocytic thyroiditis) is the most common cause of goiter and hypothyroidism in children > 6 years of age. Hashimoto thyroiditis occurs in 10–15% of those with Type 1 diabetes and usually presents about 5 years after the onset of the diabetes.

Question 18

A 12-year-old girl has the following:

• Type I diabetes
• Autoimmune thyroiditis
• Adrenal cortical insufficiency

What is the syndrome called?

Answer 18

Schmidt Syndrome

(a.k.a. Autoimmune Polyglandular Syndromes [APS] Type 2)

APS2 is primarily Type 1 DM, thyroid disease, and Addison’s. It is associated with HLA-DR3 and HLA-DR4 and is more common in females. Most cases that occur after the first few years of life are due to autoimmune disease. Remember that APS2 is not a multiple endocrine neoplasia syndrome!

Question 19

A 13-year-old presents with the following:

• Muscle weakness
• Anxiety
• Palpitations
• Increased appetite
• Declining school performance
• A thyroid bruit is heard
• TSH is undetectable
• FT4 is very high

What is the most likely diagnosis?

Answer 19

Juvenile Graves Disease

Juvenile Graves disease is the most common cause of thyrotoxicosis in children and adolescents. Children do not have the eye manifestations seen in adults.

Question 20

What is the most common brain lesion to cause true central precocious puberty?

Answer 20

Hypothalamic Hamartoma

Hypothalamic hamartoma consists of ectopic neural tissue that contains GnRH-secretory neurons and functions as an accessory GnRH pulse generator. On MRI, it appears as a small, pedunculated mass attached to the tuber cinereum or on the floor of the 3rd ventricle. Other lesions causing CPP include postencephalitic scars, tuberculous brain involvement, hydrocephalus, tuberous sclerosis, head trauma, and neoplasms (about 50% are germinomas or astrocytomas).

Question 21

Which drug is most commonly known to induce nephrogenic diabetes insipidus (DI)?

Answer 21

Lithium

Disorders associated with nephrogenic DI include polycystic kidney disorder, sickle cell disease, chronic pyelonephritis, sarcoidosis, amyloidosis, and urinary tract obstruction.

Question 22

What is the management of a child newly diagnosed with Type 2 diabetes who presents with ketosis or diabetic ketoacidosis (DKA)?

Answer 22

Insulin, Diet, and Exercise

Start children with Type 2 diabetes who are metabolically decompensated at the time of presentation (i.e., ketotic or with blood glucose > 300 mg/dL) on insulin therapy as the 1st line treatment. Diet and exercise are included in daily therapy. This can be continued until the child is metabolically stable, then they can be weaned off insulin if possible.

Question 23

A child with Type 1 DM presents with emesis.

What should you always rule out as a possibility when presented with this?

Answer 23

Diabetic Ketoacidosis (DKA)

DKA should always be considered in any child with Type 1 DM who presents with emesis. Ketoacidosis is the presenting finding in about 25% of children with diabetes.

Question 24

A 12-year-old girl presents with:

• Constipation
• Weight for age is much greater than height for age
• Bone age is delayed
• Deep tendon reflexes are slow, with a delayed relaxation phase
• TSH returns HIGH
• Free T4 is Low

What is the most likely diagnosis?

Answer 24

Primary Hypothyroidism

Acquired hypothyroidism is more common than congenital and is more frequently seen in girls than in boys. Its onset is typically insidious, and the most common cause is autoimmune thyroiditis. You know this is the primary disease because FT4 is low and the pituitary is trying to stimulate it to no avail with TSH, which is high.

Question 25

A neonate presents with severe dehydration after a preterm complication of polyhydramnios. You find the infant has Hyperaldosteronism with increased renin secretion without hypertension. There is also increased calcium excretion in the urine.

What is the most likely diagnosis?

Answer 25

Bartter Syndrome

Bartter syndrome is a form of hyperaldosteronism with increased renin secretion but without hypertension. These patients are also at risk for kidney stones due to hypercalciuria.

Question 26

A newborn girl presents with virilization and salt-wasting.

What is the most likely diagnosis?

Answer 26

21-hydroxylase Deficiency

21-hydroxylase deficiency is the most common cause of congenital adrenal hyperplasia (95% of cases), and most infants have the salt-wasting + virilizing form. About 25% have only the simple virilizing form (non–salt-wasting). The classic presentation is of an XY infant presenting in adrenal crisis at 2 weeks of age.

Question 27

An 18-year-old girl presents with:

• Headache
• Amenorrhea
• Galactorrhea
• Serum pregnancy test is negative

What is the most likely diagnosis?

Answer 27

Prolactinoma

In adolescents, prolactin-secreting tumors are the most common anterior pituitary tumor. MRI is the best diagnostic tool to find small adenomas. Prolactinomas are generally larger in children, and visual-field defects are common.

Question 28

What is the fasting plasma glucose number that defines the diagnosis of diabetes mellitus (DM)?

Answer 28

≥ 126 mg/dL​

The diagnosis can also be made with one of the following:

1. Classic symptoms of hyperglycemia and a random plasma glucose ≥ 200 mg/dL
2. A 2-hour plasma glucose ≥ 200 mg/dL during a standard oral glucose tolerance test (OGTT)
3. A hemoglobin A1c ≥ 6.5%

Any abnormal value must be repeated on a ­subsequent day before the diagnosis is confirmed.

Question 29

A solitary thyroid nodule is found in a 10-year-old girl.

What is the best management here, reassurance or getting tissue?

Answer 29

Get Tissue

A solitary nodule of the thyroid is much more likely to be cancerous in children than adults; therefore, it must be evaluated. Reassurance in this case is insufficient! According to the 2015 American Thyroid Association evaluation guidelines:

1. Obtain a thyroid ultrasound to evaluate nodule size and features.
2. Check TSH; if TSH is suppressed, do an uptake scan to evaluate for hot nodules.
3. If nodule is hyperfunctioning, do FNA.
4. If FNA is benign, repeat ultrasound in 6–12 months; if FNA is inadequate/nondiagnostic, repeat ultrasound in 3–6 months; if FNA is indeterminate/suspicious, perform surgery.

Question 30

A 9-year-old boy presents with:

• Obesity
• Hyperphagia
• Light brown to blond hair
• Blue eyes with fair skin
• Mental retardation (IQ 50)
• Small hands and feet
• Small penis with history of cryptorchidism

What is the chromosomal deletion, and from which parent did the deletion come from?

Answer 30

Deletion of q11-13 of Chromosome 15 from the Father

This is Prader-Willi syndrome, which is due to deletion of q11-13 of chromosome 15 from the father. This same deletion, if it comes from the mother, is Angelman syndrome.

Question 31

A newborn fails his newborn screen with a low T4. On repeat testing he has a normal free T4 and a normal TSH.

What is the most likely diagnosis?

Answer 31

Thyroid-binding Globulin Deficiency

TBG deficiency causes a falsely low total T4 but has a normal FT4 and a normal TSH. These children are euthyroid, and therefore do not require levothyroxine replacement or further follow-up.

Question 32

A 15-month-old girl presents with isolated breast development. There is no involvement of the adrenal glands, with no evidence of body odor, pubic hair, axillary hair, or acne. Height and weight, bone age, and genitals are normal. She has normal estradiol, FSH, and LH levels for her age. There is no known exposure to exogenous estrogen.

What is the most likely diagnosis?

Answer 32

Premature Thelarche

Premature thelarche is a diagnosis of exclusion but is a normal variant of normal growth. This is commonly a benign condition but could be the first sign of true precocious puberty. So after the normal laboratory and evaluation returns, monitor the child closely. The breast tissue may persist for 3–5 years but can regress during this time.

Question 33

Patients with cleft lip or cleft palate have a 4% chance of having what endocrine deficiency?

Answer 33

Growth Hormone Deficiency

Also, don’t forget the solitary maxillary central incisor and bilateral or unilateral optic nerve hypoplasia is associated with growth hormone deficiency as well.

Question 34

A child presents with hypertension and hypokalemia. Renin is low, but aldosterone is also low. There are several family members with this syndrome.

What is the likely syndrome?

Answer 34

Liddle Syndrome

Liddle syndrome is an autosomal dominant disorder that presents as described. The problem is dysregulation of the epithelial sodium channel (ENaC), leading to a high number of the channels being in the collecting duct, which causes a hyperaldosterone effect.

Question 35

What is the most frequent X chromosome abnormality in girls?

Answer 35

Triple X Syndrome (47,XXX)

Triple X syndrome (a.k.a. trisomy X or 47,XXX) occurs in 1/1,000 live-born females and is due to maternal meiotic nondisjunction. Phenotypically, girls with this disorder are normal females and not recognized routinely in infancy. By 2 years of age, however, speech and language delays manifest, along with poor coordination, poor academic performance, and immature behavior. These girls tend to be tall and gangly, commonly with behavior disorders.

Question 36

A 4-year-old girl presents with vaginal bleeding. You note that she has very large cafe-au-lait spots, and bone radiographs show fibrous dysplasia of the skeletal system.

What is the most likely diagnosis?

Answer 36

McCune-Albright Syndrome (MAS)

In girls, MAS presents with vaginal bleeding (the classic endocrine presentation for this syndrome). These girls have markedly enlarged ovaries and cysts. There is evidence of autonomous endocrine hyperfunction due to a missense mutation in the alpha subunit of the stimulatory G protein. The glands work independently, and there is no feedback loop. Clinically, you can see activation of TSH, FSH, LH, GHRH, and ACTH receptors.

Question 37

A child was born at the 95^th percentile, then grew rapidly in the 1st year of life to the 99^th percentile. This has continued for his first 5 years. Now in his 6^th year, it appears he has slowed to a normal growth rate. He is “clumsy” and has big feet and hands for his age. His bone age is advanced, compatible with his height.

What is the most likely diagnosis?

Answer 37

Sotos Syndrome (Cerebral Gigantism)

Sotos syndrome (cerebral gigantism) is due to a mutation in one of the NSD1 genes located on 5q35 and is not an endocrine disorder, per se. GH levels are always normal, and these children typically grow to normal adult heights. Puberty occurs at the normal time or slightly early.

Question 38

An 8-year-old boy presents with the following:

• Cushing syndrome
• Blue nevi
• Cardiac and skin myxomas
• Sexual precocity

What is this complex called?

Answer 38

Carney Complex

Carney complex is an autosomal dominant disease that presents as described (with the sexual precocity seen in boys). Frequently, thyroid tumors, pituitary tumors, and melatonin schwannomas are part of the syndrome. Primary pigmented nodular adrenocortical disease, which is part of the Carney complex, is an ACTH-independent cause of Cushing syndrome.

Question 39

A pregnant woman is exposed to androgens after the 13th week of gestation.

What is the likely effect on her developing daughter?

Answer 39

Clitoral Enlargement

Congenital adrenal hyperplasia (CAH) in the mom or the baby is the most common cause of 46,XX DSD. If the adrenal exposure was during weeks 8−13, the baby can have labial fusion. Continual androgen exposure from 8 weeks of gestation to birth causes clitoral enlargement and labial fusion.

Question 40

A child with Type 1 DM presents with high morning blood glucose levels. You draw a 3 a.m. glucose and it is 95 mg/dL, but the 7 a.m. glucose is 210 mg/dL.

What is the likely diagnosis?

Answer 40

Dawn Phenomenon

The dawn phenomenon is due to the waning effects of available insulin due to increased clearance of insulin and to nocturnal increases in GH, which antagonizes insulin’s metabolic effects.

Question 41

What is the best screening test for Cushing syndrome?

Answer 41

24-hour Urinary Free Cortisol

24-hour urinary free cortisol is elevated in Cushing syndrome. If the diagnosis is unclear, do a low-dose dexamethasone suppression test. Give dexamethasone at 11:00 p.m. and the following morning at 8:00 a.m. Patients with a cortisol level of < 5 µg/dL do not have Cushing syndrome.

Question 42

A newborn girl presents with the following:

• Marked edema of the dorsa of her hands and feet
• Loose skin folds at the nape of her neck
• She is at the 5th percentile for height and weight.

What is the most likely diagnosis?

Answer 42

Turner Syndrome

This is a tough one because there isn’t much to go on. Newborns with Turner’s commonly do not have many of the typical characteristics except for the puffy hands and feet (sometimes the only clue). But the neck finding is included here! Later, the other findings appear.

Question 43

A 16-year-old boy presents with:

• History of adrenal cortex deficiency
• New-onset clumsiness

You suspect adrenoleukodystrophy.

What levels of what type of fatty acids do you expect to be elevated?

Answer 43

Levels of Very Long-Chain Fatty Acids

Adrenoleukodystrophy is adrenal cortex deficiency with demyelination of the CNS. It is associated with very high levels of very long-chain fatty acids in tissues and body fluids due to their lack of breakdown in peroxisomes.

Question 44

A 10-year-old boy presents with severe hypertension. He has headaches, palpitations, abdominal pain, and dizziness. Sweating also occurs. Sometimes his blood pressure is normal, but for the most part, it is sustained elevated.

What is the most likely diagnosis?

Answer 44

Pheochromocytoma

Pheochromocytoma is a catecholamine-secreting tumor that originates from the chromaffin cells (usually in the adrenal medulla). Children make up about 10% of cases, with most occurring between 6 and 14 years of age. These patients can have sustained or paroxysmal HTN. (In fact, anytime paroxysmal HTN occurs [adult or child], pheochromocytoma is the most likely etiology.) Headache, palpitations, dizziness, sweating, emesis, and seizures are also symptoms. They have a good appetite but will have growth failure.

Question 45

What syndrome is associated with anosmia and hypogonadism?

Answer 45

Kallmann Syndrome

It is isolated deficiency of gonadotropin and affects the hypothalamus (deficiency of GnRH) instead of the pituitary. It is X-linked and is due mutation of the KAL gene on Xp22.3.

Question 46

A child is born and has normal stature and complete female phenotype at birth with vagina, uterus, and Fallopian tubes. However at puberty, she does not develop breasts or menstruate. The gonads are undifferentiated streaks. Chromosome analysis is done and “she” is XY.

What is the name of this syndrome?

Answer 46

Swyer Syndrome (XY Pure Gonadal Dysgenesis)

An individual with Swyer syndrome has karyotype 46,XY and is phenotypically female at birth due to pure gonadal dysgenesis. Dysgenesis results in an absence of Leydig cells, so there is no testosterone to support the Wolffian structures. Also, the Sertoli cells do not form, so the Müllerian structures develop. Most cases are due to a mutation in the SRY gene, but the Y chromosome is cytogenetically normal.

Question 47

Which has a stronger genetic component: Type 1 or Type 2 DM?

Answer 47

Type 2 DM

Concordance rates for identical twins are near 100% for Type 2 but only 30–50% for Type 1. But there is no HLA-type association with Type 2.

Question 48

A 1-week-old boy comes in for a health supervision checkup. He had normal length and weight at birth. You notice that his penis is small, and it measures 1.7 cm in length.

What is the most likely diagnosis?

Answer 48

Growth Hormone Deficiency

Microphallus (micropenis) is a clue in males to growth hormone deficiency. Other clues include hypoglycemia and a direct hyperbilirubinemia. These infants have normal birth weight and height. Those with severe defects in GH production fall lower than 4 standard deviations below the mean by 1 year of age.

Question 49

A 6-year-old boy had a severe motor vehicle accident with resulting fractures that require him to be immobilized in bed for 6 months. At about 4 months into his immobilization, he presents with:

• Nausea
• Emesis
• Increased bed wetting

What electrolyte abnormality is most likely?

Answer 49

Hypercalcemia

Immobilization results in stimulation of bone resorption, increasing the risk of hypercalcemia. Because immobilization hypercalcemia is an uncommon cause of hypercalcemia, testing must be done to rule out other more common causes, such as hyperparathyroidism (the most common cause). Laboratory testing for this condition shows elevated serum calcium of > 12 mg/dL, reduced phosphorus levels of < 3 mg/dL, and elevated PTH levels.

Question 50

A child presents with hypertension. Baseline laboratory tests show that he has hypokalemia and suppressed plasma renin levels.

What is the most likely diagnosis?

Answer 50

Primary Hyperaldosteronism

Primary hyperaldosteronism is rare in children and includes all disorders in which overproduction of aldosterone occurs that is independent of the renin-angiotensin system. Suspect primary hyperaldosteronism if you see hypertension, hypokalemia, and low plasma renin levels, as in this case.

Question 51

A newborn girl presents with virilization, no salt-wasting, and hypertension.

What is the most likely diagnosis?

Answer 51

11β-hydroxylase deficiency​

11β-hydroxylase deficiency can be differentiated from 21-hydroxylase deficiency by the absence of salt-wasting and presence of hypertension. The hypertension is due to elevation of 11-deoxycorticosterone (DOC), a potent mineralocorticoid.

Question 52

An 8-year-old boy presents with the following:

• Normal growth through the 1st year of life
• Then growth rate slowed, so that his height and weight became less than the 3rd percentile around 2 years of age
• After age 3, he has been growing at > 5 cm/year
• Bone age is delayed by 2 years
• His father is of normal height, but was also a “slow grower” early on and “caught up” during puberty–but he had delayed puberty by several years compared to his peers

What is the most likely diagnosis?

Answer 52

Constitutional Growth Delay

Constitutional growth delay is a variant of normal growth. Children grow at around the 3rd percentile. When puberty kicks in, they accelerate and reach normal adult heights. Bone age is delayed and mirrors height age in these children. This separates constitutional growth delay from “genetic” short stature, where bone age is consistent with chronological age—kids who are just genetically short. So, for constitutional growth delay: normal growth velocity, delayed bone age, and family history of delayed puberty.

Question 53

A child with Type 1 DM presents with complaints of nocturnal sweating and bad nightmares. However, in the morning the blood glucose level is elevated, so the family has been increasing the bedtime insulin, but the nocturnal events are getting worse.

What is the most likely diagnosis?

Answer 53

Somogyi Phenomenon

It is due to excess insulin being given at bedtime resulting in hypoglycemia in the middle of the night, with counterregulatory measures kicking in and resulting in hyperglycemia by morning. The key is to reduce the bedtime insulin, not increase it.

Question 54

A 17-year-old girl presents with:

• Increased pigmentation of her hands and face, particularly in the creases of her palms
• Increased pigmentation is also especially prominent around her umbilicus, axilla, and nipples.
• Anorexia
• Fatigue
• Nausea and vomiting without diarrhea
• Salt craving
• Weakness

What is the most likely diagnosis?

Answer 54

Addison Disease (Adrenocortical deficiency)

Addison disease is the most common etiology of adrenal insufficiency and is predominantly caused by autoimmune destruction of the adrenal cortex, with antiadrenal antibodies detected in the plasma. The diagnostic key here is the increased pigmentation, which is due to excess proopiomelanocortin (POMC), a precursor polypeptide for ACTH and melanocyte-stimulating hormone (MSH). In adrenal insufficiency, the low cortisol causes an increase in POMC, and having increased ACTH and MSH results in hyperpigmentation. Salt craving is also a classic finding.

Question 55

Name the syndrome:

• Autosomal recessive
• Growth retardation
• Microcephaly
• Ptosis
• Anteverted nares
• Broad alveolar ridges
• Syndactyly of the 2^nd and 3^rd toes
• Severe mental retardation
• Pyloric stenosis

Answer 55

Smith-Lemli-Opitz Syndrome

Smith-Lemli-Opitz syndrome is a mutation in one of the enzymes necessary for cholesterol synthesis. Patients with this syndrome have the listed characteristic findings. In addition, genotypic males commonly have genital ambiguity. Müllerian ducts are absent.

Question 56

An infant is born with fetal overgrowth and hypertrophy. He has macroglossia, hepatosplenomegaly, nephromegaly, and pancreatic B-cell hyperplasia.

What is the most likely diagnosis?

Answer 56

Beckwith-Wiedemann Syndrome (BWS)

BWS is very rare, occurring in 1/14,000 births. These children are at risk for Wilms tumor, adrenocortical carcinoma, and hepatoblastoma. Hence, they need an abdominal and renal U/S every 3 months until 8 years of age, and alpha-fetoprotein every 6 weeks until 6 years of age. BWS has been mapped to chromosome 11p15.

Question 57

Name the syndrome:

• 46, XY
• Nephropathy, with renal failure common by 3 years of age
• Ambiguous genitalia
• Total deficiency of testicular function

Answer 57

Denys-Drash Syndrome

Denys-Drash syndrome is a disorder of sexual differentiation (DSD) that occurs in 46,XY individuals and presents as described. Wilms tumor can occur as well. The total deficiency of testicular function is so complete that Müllerian ducts are found.

Question 58

A newborn presents with the following findings:

• Absence of the optic chasm
• Optic nerve hypoplasia
• Agenesis of the corpus callosum
• Hypothalamic insufficiency

What is the likely syndrome?

Answer 58

Septo-optic dysplasia (SOD) or de Morsier Syndrome

SOD commonly involves the hypothalamic-pituitary axis and can affect the anterior, posterior, or both axes. It is associated with an abnormality in the transcription factor, HESX1.

Question 59

A child is born to a woman at home. The mother is distrustful of modern health care and does not seek medical attention for herself or her baby after delivery. The baby is brought in by the child’s grandmother who has temporary custody of the child because her daughter has schizophrenia and has been admitted to a psychiatric hospital. The child is listless and somnolent. Her temperature is 94.5° F (34.7° C), and she has an enlarged posterior fontanelle.

What is the most likely diagnosis?

Answer 59

Congenital Hypothyroidism

An enlarged posterior fontanelle is the most classic finding for congenital hypothyroidism in the newborn. Another common finding is a lack of the distal femoral epiphysis. This is normally present at birth but is absent in hypothyroid infants. Without therapy, affected infants progress to global developmental delay with significantly poor linear growth. Early detection is clinically difficult, leading to universal newborn screening of all infants. Prognosis is good for those who begin treatment in the first few weeks of life.

Question 60

What urine test should be done to detect signs of kidney disease in diabetic patients?

Answer 60

Urine Albumin Excretion

Nephropathy affects nearly 40% of those who have had Type 1 diabetes mellitus (DM) for 25 years or more. It is the single leading cause of end-stage renal disease and accounts for nearly 50% of the deaths attributable to Type 1 DM. The 2017 American Diabetes Association (ADA) screening guidelines recommend annual urine albumin excretion testing, starting at 5 years after diagnosis. Per the ADA guidelines, treat patients who have ­persistent micro- or macroalbuminuria (albuminuria 30–300 mg/24 hr) with ACE inhibitors or angiotensin II receptor blockers (ARBs).

Question 61

A 15-year-old girl presents with the following:

• Low posterior hairline
• Small mandible
• Prominent ears
• Epicanthal folds
• Broad chest with widely spaced nipples
• Cubitus valgus
• “Spooning” of her fingernails
• Short stature
• Sensorineural hearing loss
• Sexual maturity rating (SMR; [Tanner]) 1–2 breast development; pubic hair, axillary hair are SMR 4
• Primary amenorrhea

What is the likely cardiac abnormality in this patient?

Answer 61

Nonstenoic Bicuspid Aortic Valve

The girl has Turner syndrome. Be aware that the only 100%, always-present finding for Turner’s is the short stature. The rest of the listed symptoms may or may not be there. (We even left out the classic webbed neck.) Bicuspid aortic valve occurs in nearly 50% of girls with Turner’s, and 20% have aortic coarctation. Due to their risk of aortic dissection, follow up with cardiology and get an echo every 5–10 years for life.