Index of Suspicion

A 10-month-old girl is referred to a tertiary care hospital because of growth failure and tachypnea over the preceding 7 months. She is formula-fed, and her weight gain and development are appropriate for a 3-month-old. Her perinatal history was normal, her birth measurements were at the 50th percentile, and no dysmorphism was noted. Both parents are healthy and are not related biologically; the family history is noncontributory. The patient lives in a remote and medically underserviced community.Since age 3 months, her weight gain velocity has slowed considerably, despite a normal diet and no problems with swallowing, reflux, or stooling. “Comfortable” resting tachypnea (75 breaths/min) was recorded initially at her 3-month assessment. Marked diaphoresis has been noted occasionally during feedings or sleep. No other abnormalities are documented.Multiple investigations at a regional general hospital at 6 months of age included a radiograph of the chest that showed right middle lobe opacity. Her ECG was interpreted as normal. Echocardiography suggested no anatomic abnormality of the heart. CT scan of the chest was reported to show left upper lobe hyperlucency presumed to be due to emphysematous changes. Central pulmonary arteries of “generous” size were described. CBC, venous blood gases, and sweat test yielded normal results. Fortified formula was given.On physical examination today, the infant's weight is below the 3rd percentile. She exhibits tachypnea, moderate distress, and subcostal retractions. Her heart rate is 120 beats/min, blood pressure is 90/50 mm Hg, and peripheral oxygen saturation is 98%. With crying, there is no visible cyanosis, but the oxygen saturation declines transiently to 90%. Her chest appears mildly hyperinflated and the precordium mildly hyperdynamic. There is a palpable left parasternal impulse, but no thrill. Her lung fields are clear with prominent breath sounds; no heart murmur is noted. The second heart sound is split narrowly, with increased intensity of the pulmonic component.Repeat radiography shows a normal heart size, with prominent pulmonary vascular markings in the right lung and hyperlucency of the left upper lobe. Venous blood gases are normal. Additional testing reveals the underlying diagnosis.A 5–7/12-year-old boy presents for a second opinion because of a 12.7-kg weight gain in 7 months and recurrent fevers. Other than the new onset of a voracious appetite, the boy has been asymptomatic and has no findings of note on his past medical history. He has had normal development, including verbal and motor skills. The family history includes thyroid disease, celiac disease, and obesity.On physical examination, the boy looks well, with a weight of 32.2 kg (>95th percentile), height of 116.8 cm (75th to 90th percentile), and body mass index of 23.6 (>95th percentile). All findings are normal except for obesity.Laboratory results include: thyroid-stimulating hormone of 1.72 international units/mL (normal, 0.35 to 5.50 micro-international units/mL), free thyroxine of 0.87 ng/dL (11.2 nmol/L) (normal, 0.9 to 1.4 ng/dL [11.6 to 18.0 nmol/L]), serum prolactin of 91.5 ng/dL (normal, 2.0 to 20.0 ng/dL), serum morning cortisol of 9.6 mcg/dL (264.8 nmol/L) (normal, 4.3 to 22.4 mcg/dL [118.6 to 618.0 nmol/L]), fasting serum glucose of 85 mg/dL (4.7 mmol/L), sodium of 150 mEq/L (150 mmol/L), potassium of 3.3 mEq/L (3.3 mmol/L), chloride of 114 mEq/L (114 mmol/L), and carbon dioxide of 27 mEq/L (27 mmol/L). A CBC reveals normal results.Suspicion of a CNS tumor such as a craniopharyngioma leads to obtaining an MRI of the head, but no tumor is found. During the MRI, the sedated boy experiences hypoxic episodes, and a subsequent sleep study reveals sleep apnea. Expert consultation determines the boy's diagnosis.A 16-year-old Hispanic girl is seen because of temperatures to 102.0°F (38.9°C), vomiting, facial pain, and congestion. Her pediatrician had diagnosed sinusitis and prescribed amoxicillin. At first, she showed improvement, but 1 week later, she developed a painful rash on her thighs and lower legs with bilateral foot swelling. She denies upper respiratory and GI tract symptoms. She is admitted to the hospital for persistent pain and swelling of her legs, with concern for cellulitis.She has mild asthma, has a cat at home, and traveled to Mexico 3 months ago. No findings of note are reported in her family history.On physical examination, the girl has normal vital signs, a mildly injected throat, and extensive dark, nodular, 1- to 2-cm lesions covering the anterior aspects of both thighs and pretibial regions. The lesions are erythematous, warm, and painful to palpation. Both feet are markedly swollen but have normal pulses and sensation. All other findings are normal.Laboratory results are: WBC count of 10.4×103/mcL (10.4× 109/L) with 67% neutrophils and 26% lymphocytes, Hgb of 13.4 g/dL (134.0 g/L), platelet count of 442.0×103/mcL (442.0×109/L), C-reactive protein of 15.3 mg/dL (153 mg/L) (normal, 0 to 0.5 mg/dL [0 to 50 mg/L]), ESR of 85 mm/h (normal, 4 to 25 mm/h), creatine kinase of 31 units/L (normal, 10 to 80 units/L), AST of 56 units/L, ALT of 93 units/L, antistreptolysin of 30 international units/mL (normal, <200 international units/mL), coccidioidomycosis titer of less than 1:2, negative antinuclear antibody titer, and normal findings on urinalysis. Blood culture and tuberculin test results are negative. Radiographs of the lower extremities show soft-tissue swelling.Cefazolin and subsequently clindamycin are prescribed because of concern for cellulitis but are discontinued when the diagnosis is made. An additional test reveals the likely cause of her condition.Repeat ECG documented sinus tachycardia with rightward QRS axis deviation, right ventricular and possibly biventricular hypertrophy, and an ST configuration in the right precordial leads consistent with right ventricular strain (Fig. 1). Repeat echocardiography, performed because of clinical and ECG findings suggestive of right ventricular pressure loading, showed a large, unrestrictive patent ductus arteriosus (PDA) measuring 0.84 cm, with low-velocity (1.8 msec−1) left-to-right shunting. The main pulmonary artery was mildly enlarged, as were the right and left pulmonary arteries. No other abnormality was noted. Repeat CT angiography confirmed the diagnosis and ruled out any other occult pathologic process involving the mediastinal airway. Bronchoscopy showed significant external compression of the left upper lobe main bronchus.This patient presented with an unusual degree of subtlety in that no murmur was detected to indicate the presence of a PDA. It can be speculated that the murmur and other symptoms of heart failure were overlooked previously, accounting for her sustained failure to thrive. The inaudible nature of her large arterial duct resulted from the lack of turbulence due to low-velocity flow through her large PDA. This case demonstrates the importance of making a timely diagnosis when the ductus arteriosus remains patent but is inaudible to auscultation.Although a PDA usually is associated with a heart murmur (as first published by Bernutz in 1847), the absence of a murmur does not ensure the absence of a hemodynamically important duct. The first reports of clinically significant PDA not manifesting an audible cardiac murmur on repeated examinations but discovered on postmortem examination date back to the 1940s, and the association of acquired pulmonary vascular disease with an undiagnosed PDA is well known to cardiologists, although encountered infrequently in the current era.In clinical practice, an asymptomatic and hemodynamically insignificant “silent PDA” may be diagnosed incidentally during echocardiographic testing for other reasons. However, more than 95% of symptomatic patients exhibit the characteristic murmur. In rare instances, a hemodynamically significant PDA may produce no murmur or a subtle murmur. Persistence of a hemodynamically significant PDA is not a benign condition because it may result in the progressive development of heart failure or pulmonary vascular disease and also constitutes an ongoing but small risk for infective endocarditis.Following birth, if a PDA remains large, the effective pressure differential at each end is relatively small, and net flow is determined by the differential of the pulmonary/systemic circuit resistances. (1) Because systemic vascular resistance remains largely constant after birth, the degree of flow through a large PDA is determined primarily by the level of pulmonary vascular resistance in an inverse relationship.The characteristic continuous PDA murmur first described by Gibson (2) reflects turbulent flow through a patent duct. This dissipation of kinetic energy to vibratory sound waves varies in auscultatory intensity and is determined by the interaction of: 1) the pressure difference between pulmonary and systemic circuits (which differs during the phases of the cardiac cycle); 2) the degree of flow turbulence (due to ductal shape and size); 3) the volume of blood passing through the duct; and 4) physical factors, including the distance of sound origin to the stethoscope and the amount and character of intervening tissues between source and stethoscope. A tiny PDA (or “silent ductus” in the current vernacular) that has minimal flow or a very large PDA that has a low pressure differential may not evidence any murmur. In this case, the lack of an audible murmur at the time of referral for tertiary care evaluation was attributed to the presence of a large-diameter duct that had minimal turbulence as well as moderate elevation of pulmonary arterial pressure.A large PDA generally results in excessive pulmonary blood flow and symptomatic failure to thrive. This sequence depends on a decrease in pulmonary vascular resistance (PVR) in early infancy. If PVR remains moderately elevated, shunt flow may be partially limited and the degree of failure to thrive become more gradual. This effect frequently is noted if a PDA is tolerated beyond 7 or 8 months of age. Unfortunately, perfusion of the pulmonary vascular bed at elevated pressures eventually results in reactive changes in the pulmonary arterioles, progressing to established pulmonary vascular disease, with such changes becoming evident by 15 to 18 months of age in most patients.Although the ultimate disorder in this case was the PDA, the presenting examination and ECG findings were indicative of the pulmonary hypertension, which could have several causes.This patient's findings were atypical in that an unusual degree of elevation in pulmonary resistance resulted in physical findings and ECG characteristics of pulmonary hypertension and right ventricular hypertrophy. The more typical findings of a large PDA are early development of congestive symptoms, physical findings of a large left-to-right shunt (tachypnea, prominent apical impulse, continuous murmur), and an ECG reading suggestive of left ventricular dilatation with prominent left-sided forces.The decision to close such a chronic defect surgically should be made carefully because right-sided heart failure could develop after PDA ligation, owing to the persistence of elevated pulmonary vascular resistance. Preoperative hemodynamic assessment in some, but not all, cases requires cardiac catheterization as well as assessment of pulmonary vascular reactivity to oxygen and nitric oxide in some cases. Such a procedure may be risky in the setting of established pulmonary vascular disease or in primary pulmonary hypertension. Moderately elevated PVR was considered likely in this patient, but in the presence of continued left-to-right shunting at younger than 1 year of age, documentation of pulmonary vascular reactivity was considered unnecessary and unlikely to modify the management plan.This patient's PDA was ligated 3 months later, and she experienced an uneventful postoperative course. Her respiratory rate normalized over the next 2 months, and catch-up weight gain ensued over 5 months. Repeat echocardiography and chest CT scan 7 months after PDA ligation revealed no evidence of pulmonary parenchymal or vascular disease.It is important for clinicians to be aware that an undiagnosed and inaudible PDA may occur beyond the newborn period and may pose a diagnostic challenge. Nevertheless, this disorder is corrected easily if detected early enough. The finding of two clinically significant signs, such as failure to thrive and tachypnea in this case, should prompt additional evaluation, especially if they are persistent and unexplained. This evaluation should focus on both pulmonary and cardiac causes.That the PDA was not diagnosed during the first echocardiographic study emphasizes that the reliability of many imaging modalities is highly operator-dependent. Results obtained from centers unaccustomed to imaging children should be interpreted with caution and either reviewed or repeated. This case emphasizes the importance of the need to re-evaluate a child who is not doing well by avoiding the tendency to think, “We have looked at and settled that issue and no longer have to consider it.” Clinicians evaluating children who have tachypnea of unexplained origin should realize that a PDA might be present, even when the characteristic murmur is not. (Mathieu Lemaire, MSc, MD, Paul Kantor, MBBCh, DCH, David Manson, MD, Hartmut Grasemann, MD, PhD, The Hospital for Sick Children, Toronto, Ontario, Canada)The two most likely diagnoses in a child who exhibits the rapid onset of obesity and hypothalamic dysfunction are CNS tumor and Prader-Willi syndrome (PWS). No tumor was found on MRI, and several features of PWS were absent. An example of genetic imprinting, PWS is a disorder resulting from a deletion of a paternally derived allele within chromosome 15q11–13. PWS is associated with hyperphagia, obesity, and sleep disorders, as were present in this patient. However, other features of PWS, such as short stature, hypotonia, mild intellectual disability, and hypogonadism, were not present.This patient exhibited rapid-onset obesity, fevers, hyperprolactinemia, hypernatremia, and a borderline low thyroxine concentration. The expert consultant, a pediatric endocrinologist, diagnosed rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation (ROHHAD). (1) This recently described disorder of unknown cause presents in the first decade of life with rapid weight gain as the initial feature. Hypothalamic dysfunction follows, but can occur simultaneously and may manifest as hypernatremia, growth hormone deficiency, hyperprolactinemia, hypothyroidism, adrenal insufficiency, or pubertal irregularity.Other features of autonomic dysregulation that may manifest are ophthalmologic dysfunction, GI dysmotility, thermal dysregulation, and neural crest tumor formation. Hypoventilation is the last feature of the disorder to appear and may lead to death.The underlying pathophysiology involved in ROHHAD is unclear. The wide spectrum of involved organ systems suggests a genetic defect in the development of the autonomic nervous system. However, a has to be and imaging have been in a the determined the presence of this relatively described disorder for this each of his features a of most likely is due to such as and energy and is by a increased or and who have obesity also have growth in a short child of an disorder such as thyroid disease, growth hormone deficiency, or cortisol The short child who has age and rapid weight gain should evaluation of thyroid An of or should be when hypertension, glucose and are associated with the weight A test and growth hormone can to out syndrome and growth hormone deficiency, with PWS, other genetic such as and syndrome also are associated with Other features of the disorder and intellectual is associated with both and large and an increased risk of and genetic of obesity are genetic consultation is to the appropriate finding of a prolactin be interpreted carefully because of prolactin is and can occur with sleep and can be by a hypothyroidism, chest and to in with for a of prolactin also may occur in the first a thyroid and testing are is as a sodium than mEq/L and may be by or a of the of the underlying cause is by obtaining the and the of and serum and glucose concentration. results in a of sodium of less than of can occur with or to a A serum glucose due to leads to an and may be if a patient's is or sodium can be through formula or by of or sodium sodium from an increased effect can occur in cause of is or to and and are serum is of vascular and MRI of the can if is by a CNS with an and a carefully study also should be of the evaluation for beyond the period most is due to during sleep. and to can cause and or and abnormalities also can cause who have and of can sleep due to to a patent is the to evaluation of sleep should prompt initial evaluation for are the most likely cause of recurrent including disease, and other are on a CNS lesions also can the and cause care is in the of ROHHAD because of the many abnormalities associated with the The requires evaluation, and referral to a respiratory for performed during and sleep should be The patient may early and close with and of carbon dioxide If the can lead to may be for sleep to a for the underlying axis and and and are for both patient and and imaging with CT or MRI should be performed to 18 months as for neural crest the past 6 months, this boy has been for with and his serum sodium have in the of to mEq/L to mmol/L). The sleep The development and of abnormalities have the challenge. to and the boy has with and He has been at medical by a and no underlying cause of his syndrome has been syndrome be considered when a patient presents with abnormalities involving the features can be Expert consultation is when a patient experiences an unusual of and symptoms, as in the disorder MD, MD, of additional test was a which The clinical findings suggested in this case presenting as an of At the time of this evaluation, no GI symptoms were Because was from the were not is and in the of a healthy may a an extensive and evaluation was performed for this patient, was appears to be the likely for the in this has been associated with GI with has been reported as a of but in was the primary from in patients who had more than cases have been reported in the a clinical can other manifesting as of can be by and less and such as by can and should be pretibial by and can that have and can deficiency, and should be considered if the be diagnosed on history and physical or if symptoms beyond is symptoms and In consultation and may be is a associated with several and a resulting in of The has been to be 1 to 5 with the seen between and 30 of age and a of not cases in children and with both erythematous, palpable over the of the lower upper and (Fig. is the they changes to of a over a period of 2 to 8 in with new lesions as as 6 after The of may be in children because the underlying usually is not In or of weight and is 1 to 3 to the of In to are less likely in The ESR frequently is elevated, but may be normal in to of cases. In an elevated ESR with the of finding of on examination of an child should prompt an underlying systemic no cause is found to in In for which a cause is remains the most of and and associated with of disease is the most but celiac disease, disease, and also are and are the most in evaluation should a CBC with differential titer, and of a tuberculin radiography should be obtained to out and which may indicate or of develop chronic or of may is a that in 1 to 2 months or This pain and over 2 months. primarily is and includes bed is the most significant in most can be with pain management may be for recurrent or cases. potassium has been in small to of some has been this has not been in is In or cases of and have been have been also should focus on of any underlying that the underlying condition may of the is a of systemic disease, on physical examination should a for a Results of physical examination, and testing can the cases of are but disease, and may be and should be ruled GI of should be even in who have no GI symptoms, as was the case in this patient.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.