Pediatric Endocrine Disorders

A $7$-year-old boy is brought to the clinic by his parents due to a $2$-month history of bedwetting. He had been completely toilet trained during the day and night since the age of $4$. His parents note that he now frequently asks to use the bathroom during school and constantly craves cold water. The patient has no history of head trauma or recent illnesses. His temperature is $37.0^\circ\text{C}$ ($98.6^\circ\text{F}$), blood pressure is $95/60 \text{ mm Hg}$, and pulse is $98\text{/min}$. Physical examination is unremarkable, and his growth is tracking along the $50^{\text{th}}$ percentile for both height and weight.

Initial laboratory results are as follows:

A formal water deprivation test is performed. After $6$ hours, his urine osmolality remains low at $120 \text{ mOsm/kg H}_2\text{O}$, and his serum sodium rises to $152 \text{ mEq/L}$. Subcutaneous desmopressin is then administered. Two hours later, his urine osmolality increases to $580 \text{ mOsm/kg H}_2\text{O}$.

Which of the following is the most appropriate next step in the management of this patient?

An 18-month-old boy is evaluated in the pediatric clinic for progressive bowing of his legs and a waddling gait. The parents note that he began walking independently at 14 months of age, but his leg bowing has worsened since then. He was exclusively breastfed until 6 months, after which appropriate solid foods were introduced. He receives daily multivitamin drops containing 400 IU of cholecalciferol. His height is at the 3rd percentile, and his weight is at the 25th percentile. Physical examination reveals frontal bossing, widening of the wrists, and pronounced genu varum. Laboratory studies show:

Which of the following is the most likely underlying pathophysiology of this patient's condition?

Match each pediatric clinical presentation to its most likely underlying enzymatic deficiency.

A $5$-year-old boy is brought to the clinic by his parents due to rapid growth, facial acne, and the development of pubic hair over the past $6$ months. The parents also report that he has recently developed adult-type body odor. His height is at the $99$ th percentile for his age, whereas it was at the $50$ th percentile one year ago. His weight is at the $90$ th percentile. Vital signs are within normal limits. Physical examination reveals coarse, dark pubic hair (Tanner stage III) and facial acne. Genitourinary examination shows a stretched penile length of $6$ cm and bilaterally enlarged, symmetric testes with a volume of $8$ mL each. Neurologic examination is unremarkable.

Laboratory studies show:
Testosterone: $180$ ng/dL (Normal prepubertal: $<30$ ng/dL)
Basal luteinizing hormone (LH): $0.1$ mIU/mL (Normal prepubertal: $<0.3$ mIU/mL)
Thyroid-stimulating hormone (TSH): $1.8$ $\mu$ U/mL

A radiograph of the left hand and wrist reveals a bone age of $8$ years.

Which of the following is the most appropriate next step in the evaluation of this patient?

A 16-year-old girl, who recently immigrated from a region with limited access to pediatric healthcare, is brought to the clinic for evaluation of primary amenorrhea and severe, progressive facial hair growth. Her mother notes that she has had a deep voice and experienced a rapid growth spurt during early childhood. Her blood pressure is 162/100 mm Hg, and her pulse is 78/min. Physical examination reveals severe nodulocystic acne, temporal hair thinning, and Tanner stage 5 pubic hair development, but Tanner stage 1 breast development. Pelvic examination demonstrates significant clitoromegaly and partial fusion of the labioscrotal folds. A transabdominal pelvic ultrasound confirms the presence of a uterus and bilateral ovaries. Laboratory testing shows a serum sodium of 146 mEq/L and a serum potassium of 2.8 mEq/L. Which of the following serum laboratory profiles (17-hydroxyprogesterone, 11-deoxycorticosterone, and plasma renin activity) is most likely present in this patient?

A $9$-year-old boy is brought to the emergency department by his parents due to lethargy and recurrent vomiting for the past $24\text{ hours}$. Over the preceding two weeks, he has had increased thirst, frequent urination, and a $3\text{ kg}$ ($6.6\text{ lbs}$) weight loss. He has no significant past medical history.

On initial presentation, he is lethargic but arousable to verbal commands. Temperature is $37.0^\circ\text{C}$ ($98.6^\circ\text{F}$), blood pressure is $90/55\text{ mmHg}$, pulse is $135/\text{min}$, and respiratory rate is $32/\text{min}$ with deep, rapid respirations. Mucous membranes are dry, and capillary refill is $4\text{ seconds}$.

Initial laboratory studies:
- Serum sodium: $132\text{ mEq/L}$
- Serum potassium: $4.8\text{ mEq/L}$
- Serum chloride: $98\text{ mEq/L}$
- Serum bicarbonate: $8\text{ mEq/L}$
- Serum glucose: $580\text{ mg/dL}$
- Arterial pH: $7.15$
- Arterial $pCO_2$: $22\text{ mmHg}$
- TSH: $0.4\text{ mIU/L}$ (Normal: $0.5-5.0\text{ mIU/L}$)
- Free T4: $0.8\text{ ng/dL}$ (Normal: $0.9-1.7\text{ ng/dL}$)

The patient receives a $20\text{ mL/kg}$ bolus of $0.9\%$ normal saline over $1\text{ hour}$. Subsequently, a continuous intravenous infusion of regular insulin is started at $0.1\text{ units/kg/hr}$ along with appropriate maintenance fluids containing potassium.

Four hours later, the nurse urgently calls the physician because the patient has become increasingly obtunded and is complaining of a severe, diffuse headache.

Current vital signs:
- Blood pressure: $140/90\text{ mmHg}$
- Pulse: $58/\text{min}$
- Respiratory rate: $16/\text{min}$

Which of the following is the most appropriate next step in the management of this patient?

During a routine health maintenance visit, a $16$-year-old adolescent female and her mother express concern regarding the patient's worsening facial acne and irregular menstrual periods. Menarche occurred at age $12$, but over the past $2$ years, her menses have become increasingly unpredictable, occurring every $3$ to $5$ months. Recently, she has also noticed the development of coarse, dark hair on her upper lip and chin. The patient takes no medications and has no other medical conditions. Her blood pressure is $112/72\text{ mmHg}$, and her body mass index is $24\text{ kg/m}^2$. Physical examination reveals moderate cystic acne on the face and back, as well as significant hirsutism. A transabdominal pelvic ultrasound demonstrates bilaterally enlarged ovaries with multiple small peripheral cysts.

Laboratory studies obtained the previous week show the following:

Based on the clinical presentation and laboratory findings, which of the following is the most appropriate next step in the management of this patient?

A $6$-year-old girl is evaluated in the pediatric endocrinology clinic for recent episodes of vaginal spotting and bilateral breast enlargement. Her parents report an unusually rapid growth spurt over the last $8$ months. Her medical history is notable for a recent nondisplaced right femur fracture after a minor trip and fall, which was attributed to a localized lytic bone lesion on radiographs.

Physical examination shows Tanner stage $3$ breast development and Tanner stage $1$ pubic hair. A large, flat, hyperpigmented skin macule with irregular, jagged margins is present on her left lateral trunk. Bone age radiography reveals a skeletal age of $10$ years.

Laboratory evaluation:

Pelvic ultrasound reveals a $3.5\text{-cm}$ unilateral ovarian cyst.

Which of the following pharmacologic mechanisms is most appropriate to halt the progression of this patient's pubertal development?

A 6-year-old girl is brought to the clinic by her parents due to breast development and the appearance of pubic hair over the past 6 months. Her parents also report that she has outgrown her clothes rapidly during this period. She has no significant past medical history and takes no medications. Her height is at the 98th percentile, and her weight is at the 90th percentile. Vital signs are within normal limits for her age. Physical examination reveals Tanner stage 3 breast development and Tanner stage 2 pubic hair. There is no axillary hair, acne, or clitoromegaly.

Initial workup reveals the following:
- Radiograph of the left wrist: Bone age of 9 years
- Basal luteinizing hormone (LH): 0.1 mIU/mL (normal prepubertal: < 0.3 mIU/mL)
- Follicle-stimulating hormone (FSH): 0.2 mIU/mL
- Estradiol: 45 pg/mL (elevated for age)

A gonadotropin-releasing hormone (GnRH) stimulation test is performed, and the peak LH level is measured at 0.2 mIU/mL.

Which of the following is the most appropriate next step in management?

A 4-week-old female infant is brought to the clinic by her parents due to increased sleepiness and poor feeding over the past week. The parents report that she has to be awakened for feeds and has had only one hard, pellet-like bowel movement in the last four days. She was delivered at home at 39 weeks gestation to a 28-year-old primigravid woman and did not undergo state-mandated newborn screening. Vital signs include a heart rate of 92/min and a temperature of 36.0°C (96.8°F). Physical examination reveals a lethargic infant with mild scleral icterus, a large anterior fontanelle, a protuberant abdomen with an umbilical hernia, and hypotonia. Which of the following serum laboratory patterns is most likely to be found in this patient?

A female adolescent seeks evaluation at the outpatient endocrinology clinic due to distressing changes in her physical appearance. Over the preceding year, she has developed coarse, dark hair on her chin and upper lip, along with persistent nodulocystic acne that has not responded to topical therapies. She achieved menarche at $12$ years of age, but her menstrual cycles have become increasingly erratic, currently occurring at intervals of $3$ to $5$ months. Blood pressure is $112/72 \text{ mmHg}$ and body mass index is $23 \text{ kg/m}^2$. Physical examination reveals a Ferriman-Gallwey score of $11$, with normal breast and female external genital development. There is no clitoromegaly.

Early morning serum analyses yield the following results:
Total testosterone: $92 \text{ ng/dL}$ (Normal: $15-70 \text{ ng/dL}$)
Dehydroepiandrosterone sulfate (DHEA-S): $580 \text{ } \mu\text{g/dL}$ (Normal: $65-380 \text{ } \mu\text{g/dL}$)
$17$-hydroxyprogesterone: $3,800 \text{ ng/dL}$ (Normal: $< 200 \text{ ng/dL}$)
Thyroid-stimulating hormone (TSH): $1.6 \text{ mU/L}$ (Normal: $0.5-5.0 \text{ mU/L}$)
Free thyroxine (T4): $1.1 \text{ ng/dL}$ (Normal: $0.8-2.0 \text{ ng/dL}$)

Transabdominal ultrasonography reveals normal-appearing ovaries with no evidence of cysts.

Which of the following best describes the fundamental pathophysiologic mechanism responsible for this patient's condition?

A $5$-month-old male infant is brought to the pediatric clinic by his parents for a well-child visit. The parents report that he is a "very quiet baby" who sleeps most of the day, but they are concerned because he frequently strains to pass hard, pellet-like stools. He is not yet rolling over and rarely coos. He was born at $39$ weeks gestation via uncomplicated vaginal delivery. The state's newborn screening program primarily measures thyroid-stimulating hormone (TSH) levels, which were reported as normal. On physical examination, his length is at the $5$ th percentile and weight is at the $25$ th percentile. His heart rate is $90$/min and temperature is $36.4^\circ\text{C}$ ($97.5^\circ\text{F}$). He exhibits generalized hypotonia and a stretched penile length of $1.5 \text{ cm}$ (normal $> 2.5 \text{ cm}$). Laboratory evaluation reveals:

Serum thyroid-stimulating hormone (TSH): $2.1 \mu\text{U/mL}$ (normal: $0.5$–$5.0 \mu\text{U/mL}$)
Serum free thyroxine (T4): $0.4 \text{ ng/dL}$ (normal: $0.9$–$2.2 \text{ ng/dL}$)
Serum glucose: $52 \text{ mg/dL}$

Which of the following is the most likely cause of this infant's condition?

A 12-year-old girl is brought to the clinic by her parents due to fatigue, poor school performance, and constipation over the past 6 months. Her parents also note that she frequently complains of feeling cold, even in warm weather. Growth chart review shows her height has dropped from the 50th percentile two years ago to the 15th percentile currently, while her weight has increased from the 50th to the 75th percentile. Physical examination reveals dry skin, a diffusely enlarged and non-tender thyroid gland (goiter), and delayed relaxation of the deep tendon reflexes. Laboratory studies show a low serum free T4 level and a markedly elevated TSH level. Which of the following is the most likely underlying mechanism of this patient's condition?

Match the following pediatric endocrine conditions to their most characteristic clinical or laboratory presentation.

A 12-year-old boy is brought to the pediatric endocrinology clinic by his parents due to poor growth and increasing fatigue over the past 12 months. He used to be energetic but now frequently falls asleep in class. He also complains of feeling cold, even during the summer, and reports new-onset frequent morning headaches. Over the past year, his height has plateaued, falling from the 50th percentile to below the 10th percentile. Physical examination reveals a pale, prepubertal boy with dry skin and delayed relaxation phase of deep tendon reflexes. Visual field testing by confrontation reveals diminished peripheral vision bilaterally. Which of the following serum laboratory patterns is most likely present in this patient?

A 9-year-old boy is brought to the pediatrician by his parents for evaluation of fatigue, constipation, and poor growth. The parents report that he has been feeling cold even in warm weather and has not outgrown any of his clothes over the past year. Review of his growth chart shows a decline in height from the 50th percentile to the 10th percentile. Physical examination reveals dry skin and delayed relaxation of the ankle reflexes. Laboratory evaluation shows a free T4 level of $0.5 \text{ ng/dL}$ (normal: $0.9-1.7 \text{ ng/dL}$) and a thyroid-stimulating hormone (TSH) level of $2.1 \text{ }\mu\text{U/mL}$ (normal: $0.5-4.5 \text{ }\mu\text{U/mL}$). Which of the following is the most likely diagnosis?

Correlate each distinct clinical and laboratory vignette with its most accurate diagnosis.

A 10-year-old boy with a known history of type 1 diabetes mellitus is brought to the emergency department with altered mental status, deep and rapid breathing, and a fruity odor to his breath. Laboratory evaluation confirms the diagnosis of severe diabetic ketoacidosis (DKA). Arrange the following initial management steps in the correct chronological order according to standard pediatric DKA treatment protocols.

Match the following rare congenital adrenal hyperplasia variants and related steroidogenesis defects with their most characteristic clinical and laboratory presentations in neonates.

A previously healthy $9$-year-old boy is evaluated in the emergency department for a $24$-hour history of severe abdominal pain, intractable vomiting, and progressive somnolence. His parents report that he has been drinking an unusual amount of water and waking up multiple times at night to urinate over the past month. He has lost $3 \text{ kg}$ during this time. On presentation, he is lethargic but arousable. Respirations are deep and rapid at $32\text{/min}$, heart rate is $135\text{/min}$, and blood pressure is $95/60 \text{ mmHg}$. His mucous membranes are markedly dry. Capillary refill is $3 \text{ seconds}$.

He receives a $10 \text{ mL/kg}$ intravenous bolus of $0.9\%$ normal saline. A continuous intravenous insulin infusion and $0.45\%$ normal saline at maintenance rates are initiated.

Which of the following is the most appropriate next step in management?