A 19-year-old young woman presents with rapid onset weight loss. What's the diagnosis?
A 19-year-old woman presents to a pediatric emergency department (ED), accompanied by her parents, with a chief complaint of weight loss.
The patient reports that she used to be “chubby.” Her highest weight was 75 kg with a height of 4’10” when she was 16 years old (body mass index [BMI] > 95th percentile). Two years ago, she began avoiding junk food because she was worried that she was overweight. She gradually dropped to 54 kg (BMI at 56th percentile) over 18 months. However, 6 months ago, she began restricting more aggressively and lost weight more rapidly. Her current weight is 34 kg (BMI < 0.01 percentile), representing 20 kg of additional weight loss over 6 months. She denies using other methods to lose weight such as excessive exercise, self-induced vomiting, or abuse of diuretics, laxatives, or diet pills. At the time of admission, the patient felt that she was underweight.
She experiences lightheadedness daily, but denies syncope. She has cold extremities, constipation, and says that her last menstrual period was 2 years ago. The patient reports no abdominal pain, blood in her stool, diarrhea, difficulty swallowing, fever, headache, jaundice, joint pain or swelling, nausea, night sweats, polyuria or polydipsia, rash, or vomiting.
Over the last 3 months, her mother has observed decreased energy and altered cognition, which are worsening. The patient struggles with word finding, is slow to respond to questions, and is less alert. She rarely sleeps more than 3 hours a night. The patient endorses feeling “slow.”
Her mother reports that she does not eat unless someone supervises her. She eats very slowly and will only take a few bites if not frequently redirected. She does not even want to drink water. When her mother offers her food, the patient cries, shakes, appears anxious, and asks her mother to take it away.
The patient admits that she previously worried about being overweight, but now her weight loss is unintentional because she “keeps a strict schedule” and does not know how to “fit eating into her day.” Specifically, she needs to pray a certain number of times per day, making it hard to find time to eat. Her mother says that her daughter spends the majority of the day in prayer; her praying increased dramatically when her eating got worse 6 months ago.
The patient lives with her parents and older sister, attending community college. Her family is very religious. She reports that her favorite activities are reading the Bible and praying. She reports no use of alcohol, tobacco, or other drugs. She has never had sex and has never been in a romantic relationship, but identifies as heterosexual. She has no history of depressed mood, self-harm, or suicidal ideation.
She has no other significant past medical or psychiatric history, takes no medications, has no allergies, and is fully immunized. There is no pertinent family history, including no known anxiety, eating, or depressive disorders, or substance abuse. She has no known travel history.
Her initial vital signs include blood pressure 102/64; pulse 52 beats/minute; temperature 36.6°C; respiratory rate 14/minute; height 147.4 cm; weight 34.8 kg; and BMI 14.06 kg/m.
Physical exam is significant for an extremely thin female patient who is alert but slow to respond to questions and pauses to find words, which occasionally causes her frustration. She has staring spells and appears to be responding to internal stimuli. She is calm with restricted affect, occasionally smiling inappropriately. She has cool extremities, dry skin, and lanugo on her trunk and arms. She has a 2- x 3-cm mass on the right side of her neck, mobile and nontender without overlying erythema, which elevates when she swallows. The patient reports that she has had the mass for years, but has been too self-conscious to show it to a doctor. There is no lymphadenopathy. Abdominal, cardiovascular, and respiratory exams are unremarkable. There are no hand callouses, palatal abrasions, or poor dentition to suggest purging.
Initial labs include a complete blood count (CBC) significant for a mildly decreased white blood cell count of 3.4 (reference 4.0-10.5 TH/uL) with an absolute neutrophil count of 1.88 (reference 2.00-6.50 TH/uL) and an absolute lymphocyte count of 1.2 (reference 1.5-3.5 TH/uL). Hemoglobin is slightly decreased at 12.3 (reference 12.5-16 g/dL) but the anemia is normocytic. Sodium, potassium, chloride, bicarbonate, magnesium, phosphorus, renal function tests, liver enzymes, prealbumin, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), thyroid stimulating hormone (TSH), free thyroxine (T4), urinalysis, pregnancy test, and urine drug screen are all unremarkable. Estradiol is < 2 pg/mL. Electrocardiogram (EKG) shows a rate of 73 beats/min and normal sinus rhythm, but with right axis deviation, counterclockwise QRS axis, and no Q wave in the left chest.
The patient is admitted to the hospital for severe malnutrition of unknown etiology. She is initially placed on bed rest and 24-hour cardiorespiratory monitoring with vital signs checked every 6 hours, including daily orthostatic vitals. She is started on a 1600 kcal/day refeeding diet with close supervision and daily bloodwork monitoring for refeeding syndrome.
What is the differential diagnosis of an adolescent girl with significant weight loss?
The differential diagnosis of weight loss in an adolescent is broad and includes both organic and inorganic causes (Table 1).
Gastrointestinal (GI) causes include inflammatory bowel disease, celiac disease, malabsorption syndromes, pancreatic insufficiency, and hepatic disease including infectious or autoimmune hepatitis. Suggestive symptoms include abdominal discomfort, diarrhea, fever, hematochezia, jaundice, melena, nausea, and/or vomiting. Given the patient’s lack of these signs/symptoms and a normal ESR/CRP, it is unlikely that her weight loss is because of a GI cause.
Endocrine causes include adrenal insufficiency, diabetes mellitus, and hyperthyroidism. The patient has normal electrolytes and blood pressure making adrenal insufficiency unlikely, and has no polyuria, polydipsia, or glucose abnormalities suggestive of diabetes mellitus. Hyperthyroidism could have a variety of causes including autoimmune thyroiditis or a productive thyroid nodule, and may present with psychiatric symptoms. Other symptoms of hyperthyroidism might include diarrhea, heat intolerance, increased appetite, increased perspiration, palpitations, tremor, and/or weakness, which are absent. The patient has a normal TSH and T4, but even in the absence of hyperthyroidism, the presence of thyroid antibodies alone could cause neuropsychiatric changes.1
Given the patient’s neck mass, malignancy is a concerning possibility, particularly a thyroid malignancy as it elevates with swallowing. Further questioning about risk factors for malignancy and biopsy of the mass would be important next steps. Malignancy of any kind could cause weight loss and may be associated with fatigue, fevers, and night sweats. The most common malignancies in adolescents are leukemias/lymphomas and central nervous system tumors. The patient has cytopenias on her CBC but this is often seen in malnourished states and reverses with renourishment2; usually more severe cell line suppression is seen with hematologic malignancy. Her neurological examination is unremarkable, but her neuropsychiatric symptoms in association with weight loss warrant intracranial imaging.
Cardiorespiratory failure is frequently associated with weight loss. The patient has an abnormal EKG, which should be followed up with an echocardiogram. Of note, weight loss itself causes cardiac muscle wasting, which could create the EKG abnormalities observed.
Inflammatory disorders such as systemic lupus erythematosus, juvenile idiopathic arthritis, or other vasculitis can cause weight loss and neuropsychiatric symptoms. However, a normal ESR/CRP makes this unlikely in our patient. She also has no hematuria, joint swelling, rash, or other typical associated symptoms.
Infectious etiologies include chronic GI infections such as amoebiasis, giardiasis, or cryptosporidium, which would present with chronic diarrhea and/or vomiting; tuberculosis, which might present with fever, adenopathy and/or hemoptysis; or HIV/AIDS with recurrent infections and other manifestations of immunodeficiency. However, given the patient’s past medical history, lack of known travel history, lack of substance abuse or sexual exposure, and absence of typical presenting symptoms or physical examination findings, an infectious cause is unlikely.
Inorganic causes of weight loss include eating disorders, primary psychiatric disorders, and psychosocial causes. Restrictive eating disorders include anorexia nervosa, avoidant restrictive food intake disorder, and other unspecified eating disorders with features of restriction, overexercise, and/or purging. The patient previously struggled with body image and was intentionally trying to lose weight. Although she states that her current weight loss is unintentional and that she recognizes she is underweight, she still has fear around eating, making a restrictive eating disorder a possibility.
Primary psychiatric disorders such as major depressive disorder (MDD), generalized anxiety disorder (GAD), obsessive compulsive disorder (OCD), primary psychotic disorders, and bipolar disorder may all cause weight loss through changes in appetite and/or behavioral changes that interfere with eating. Our patient exhibits decreased concentration and energy, difficulties with sleep, low mood, and weight loss, all of which could suggest MDD. Her rigid daily routines and hyper-religiosity suggest OCD or psychosis. Although she has had decreased need for sleep and appears distractible, she does not meet criteria for mania as her family does not describe grandiosity, pressured speech, racing thoughts, or increased goal-directed behavior. In adolescents, one should always consider Wilson’s disease as a medical cause of psychosis.
Psychosocial contributors to weight loss include abuse, food insecurity, neglect, or substance abuse. History about this should be obtained.
Importantly, malnutrition itself may be causing many of this patient’s physical symptoms including amenorrhea, cold intolerance, constipation, cytopenias, EKG abnormalities, fatigue, impaired cognition, and neuropsychiatric changes, all of which would be reversible with renourishment.3 Deficiency of micronutrients such as vitamin B12, folate, iron, or zinc can contribute to neuropsychiatric changes and fatigue.
The patient is admitted to a pediatric inpatient ward. She begins a standard refeeding diet with gradual increases in caloric intake. A dietitian is consulted to guide safe weight gain. Electrolytes are checked daily to monitor for refeeding syndrome.
Micronutrient labs reveal no deficiencies in B12, folate, iron, vitamin D, or zinc. Ceruloplasmin is normal. An echocardiogram demonstrates there is normal structure and function of the heart.
Further history determines that she has never had radiation exposure to her neck and has no family history of thyroid disorders. Endocrinology is consulted. Antithyroglobulin and antithyroid peroxidase antibodies are undetectable. Ultrasound reveals a 1.8-cm diameter complex mass in the right lobe of the thyroid gland. Fine needle aspiration of the nodule reveals that it is benign. Endocrinology recommends nonurgent removal of the mass after the patient’s nutritional status improves.
Neurology is consulted regarding the patient’s neuropsychiatric changes. Brain magnetic resonance imaging is normal. Neurology reports a normal neurological exam and recommends an electroencephalograph (EEG) to rule out absence seizures, which would not cause weight loss but could explain the patient’s impaired cognition. EEG reveals no epileptiform discharges.
The patient is confidentially asked about a history of abuse, food insecurity, neglect, and/or trauma, but she denies these. The patient states that she is close to her parents and all of her siblings. There have been no recent tensions or conflict at home. She has never been in a romantic relationship. She has friends from school but states she has not been seeing them outside of school lately.
Psychiatry and psychology are consulted as the patient struggles to eat in the hospital and continues to have staring spells, inappropriate smiling, and delayed responses to questions. She is frequently distressed and crying. She endorses moderate depressive symptoms, scoring 19 on the Patient Health Questionnaire-9, a 9 item screening questionnaire for depression.4 However, it is unclear whether her depression is the primary problem or secondary to another psychiatric disorder.
While hospitalized, she spends the majority of her time praying and will not stop praying to eat. When she does eat, she states that she must take 3 bites at a time and then raise her hands to give thanks to God. Consequently, the patient takes hours to finish meals and snacks. She does not avoid any particular foods; she says that she likes foods like quesadillas and ice cream, and feels sad that she cannot enjoy them because eating has become so difficult. Multiple interviews by psychologists reveal no body dysmorphia or fear of fatness. The patient recognizes that she is too thin and wants to gain weight.
The Yale-Brown Obsessive Compulsive Scale (Y-BOCS) is administered and confirms a diagnosis of severe OCD.5 The diagnosis is discussed with the patient and her family and her team recommends initiation of a selective serotonin reuptake inhibitor (SSRI). However, it is acknowledged that the severity of the patient’s malnutrition may also be contributing to the patient’s cognitive changes, and that nutritional rehabilitation itself could improve her mental status. The patient opts to start with nutritional restoration alone while under close observation in the hospital.
The patient receives nutritional rehabilitation for several weeks and her weight improves. Her energy level and concentration appear better, but praying and other rituals continue to interfere with her eating. She continues to exhibit significant psychological distress. She meets daily with a psychologist but is too distressed and distracted to meaningfully engage in the therapy.
She is offered SSRI medication again and this time she agrees. She begins taking escitalopram 2.5 mg daily, with a gradual dose increase to 10 mg daily. Within 1 week, she experiences significant improvement in her concentration, energy, and ability to engage in interactive conversation. She can engage in cognitive behavioral therapy (CBT). She spends much less time praying, can stop praying to eat, and can finish her food quickly without interruptions. Her mood improves significantly. The patient expresses joy that she is able to eat and enjoy food again.
Despite having an underlying psychiatric etiology, this patient’s rapid weight loss and severe malnutrition put her at high medical risk necessitating inpatient stabilization. Comprehensive assessment required a detailed personal and family history, physical exam, and a thorough medical workup to rule out organic contributors to weight loss and to assess for sequelae of malnutrition. Involvement of a multidisciplinary team including mental health providers was invaluable to assess psychosocial and psychiatric contributors to eating behaviors, facilitating accurate diagnosis, and initiation of effective treatment.
Although OCD was once considered rare in youth, several studies estimate that the prevalence is 0.25% to 3% among children and adolescents.6-8 Compared with adults, children and adolescents are less likely to have insight into the irrationality of their obsessions and compulsions. To an observer, their symptoms may be difficult to differentiate from psychosis.
OCD alone may be severe enough to interfere with eating and other activities of daily living. However, OCD is also frequently comorbid with eating disorders such as anorexia nervosa and bulimia nervosa.9 It was possible for this patient to have had anorexia nervosa in addition to OCD, but this was ruled out with extensive psychological evaluation.
The diagnosis of OCD in children and adolescents can only be made after a detailed evaluation of the adolescent’s medical, developmental, and family history with corroborative history from caregivers.10 The Y-BOCS is a commonly used assessment scale for the diagnosis of OCD.5 To treat OCD, a combination of CBT and SSRI are superior to pharmacological treatment alone.11
Malnutrition itself has deleterious effects on cognition and results in a variety of neuropsychiatric symptoms.12,13 Serotonin is a nutritionally dependent neurotransmitter; malnutrition results in reduced brain serotonin leading to lower mood and increased anxiety.14 Additionally, starvation results in increased dopaminergic brain activity, generating dopamine-mediated psychiatric manifestations including psychosis and abnormal behaviors.13 Increased dopamine signaling plays a significant role in adolescent brain development.15 Consequently, adolescents are more likely than adults to experience neuropsychiatric manifestations from starvation.16 Although the patient had OCD, weight restoration was as critical as therapy and medication for her psychiatric recovery.
The patient continued CBT and escitalopram and gained almost 9 kg over a 6-week hospital stay, with complete normalization of her mental status. She was discharged on 10 mg of escitalopram and referred for outpatient follow-up with psychology and psychiatry. One year after discharge, the patient is close to her ideal body weight and remains on medication with no recurrence of her psychiatric symptoms.