Fig. 10.1
A 3 kg weight loss in the peripubertal period, when patients are naturally supposed to grow in height, weight, and BMI, can cause a steep decline in BMI percentile and profound nutritional deficiency. (a) Stature-for-age and weight-for-age percentiles. (b) Body mass index-for-age percentiles. Source: Developed by the National Center for Health Statistics in collaboration with the National Center for Chronic Disease Prevention and Health Promotion (2000). http://www.cdc.gov/growthcharts
When questioned about her decrease in weight, the patient notes that she became concerned that her diet was unhealthy after her health class talked about diabetes and obesity. Around the same time, her father was told by his doctor that he had prediabetes and should lose weight and decrease sugar intake. Her father has lost about 20 lb by decreasing his sugar intake, eating a more plant-based diet, and exercising regularly. Holly started to watch her sugar intake too and joined the gym with her father. She became a vegetarian and is now a vegan, because she is concerned about cruelty to animals. She now exercises at the gym with her father, goes for runs by herself around the school track, and does crunches in her bedroom. She used to think she would be happy at her current weight of 44 kg, but now that she is at this weight, she feels an urge to have a lower weight. She thinks she looks heavy when she looks in the mirror.
Her mother reports that Holly eats a full plate of food at every meal, but the food is very healthful. Holly’s diet recall is as follows: for breakfast, she had a bowl of oatmeal made with water and a spoonful of peanut butter. For lunch, she had an entire plate of greens with lentils, slices of avocado, and a bowl of watermelon. For dinner, she had two plain baked potatoes and salad; she did not eat the roast beef that the family had because she does not eat meat. She declined dessert last night as she does on most nights, although she will eat fruit for dessert.
Holly is questioned confidentially about her social history . She reports a good relationship with her mother, father, and two brothers at home. She feels safe and loved. She enjoys school and all of her activities. She is a competitive violinist and is involved in the student community service organization. She has friends and can name a best friend (Her mother later notes that Holly has been spending less time with her friends and avoids a lot of fun outings that she would have enjoyed when she was younger.). Holly denies all substance abuse. Her mood is “fine,” and she denies any depression or suicidality. There are no firearms in the home.
Holly’s vital sign s show bradycardia to 49 bpm supine and a blood pressure of 102/70. Standing vital signs are 88 bpm and 100/72. She has a normal temperature and oxygen saturation. Her weight is 44 kg, height is 163.5 cm, and BMI is 16.5. On physical exam, Holly is very thin and sallow appearing. She has a flat affect and speaks in a high, quiet voice. She has bitemporal wasting and no parotid enlargement. No dental decay is noted. She has shotty lymphadenopathy in her anterior cervical chain, without thyromegaly. She has no acne, hirsutism, or lanugo. Extremities are cool to palpation with good cap refill. Abdomen is scaphoid with hard stool palpated in the lower left quadrant. Spinous processes are prominent with an abrasion noted over the lumbar spine. Breasts are a small tanner 5, and pubic hair is tanner 4. Neurologic exam is within normal limits. Mental status exam is significant for a flattened affect, but Holly is otherwise lucid and communicative. You suspect that Holly has anorexia nervosa.
Questions from Patient and Family
How can a few pounds of weight loss lead to such malnutrition ?
Can we give her something to make her have a period?
What can we do to help Holly recover?
Discussion
Holly is a 15-year-old previously healthy young woman who presents with amenorrhea. Her history is significant for an increasingly restrictive diet and compulsive exercise. Holly has only lost 3 kg. However, she is at an age where the slopes of the normal growth curves for height, weight, and BMI all have an increased rate of rise. Therefore, to maintain her normal BMI percentile , she has to gain in height, weight, and BMI. In the peripubertal age range, even a small amount of weight loss or a failure to gain weight can cause a precipitous decline in BMI percentile and lead to profound nutritional deficiency as shown in Fig. 10.1.
Her physical exam shows several signs of nutritional deficiency: bradycardia, an orthostatic pulse, cool distal extremities, cachexia, a sallow appearance, and a flattened affect. The abrasion on her spinous processes results from compulsive stomach crunches in the setting of decreased protective fat over her spine. Her lab work supports a diagnosis of malnutrition: leukopenia with other cell lines being normal, a mild transaminitis, a low T3 with normal thyrotropin, and normal free thyroxine. Holly’s diagnosis is anorexia nervosa. The criteria for anorexia nervosa as delineated in the Diagnostic and Statistical Manual of Mental Disorders 5 (DSM 5) are listed in Table 10.1. It is important to note that although amenorrhea is a common sequela of anorexia, it is no longer required for the diagnosis.
Table 10.1
Diagnostic criteria for anorexia nervosa (patients must endorse all three)
Restriction of energy intake relative to requirements, leading to a significantly low body weight in the context of age, sex, developmental trajectory, and physical health |
Intense fear of gaining weight or of becoming fat, or persistent behavior that interferes with weight gain, even though at a significantly low weight |
Disturbance in the way in which one’s body weight or shape is experienced, undue influence of body weight or shape on self-evaluation, or persistent lack of recognition of the seriousness of the current low body weight |
Discussion
Holly has secondary amenorrhea, meaning that she has gone without menses for at least 3 months after the onset of menarche. The differential diagnosis for secondary amenorrhea can be grouped into estrogen-deficient and estrogen-replete conditions. Some common estrogen-replete conditions include pregnancy, polycystic ovary syndrome, and physiologic anovulation. These conditions are characterized by endometrial buildup without the regular shedding of the lining that is normally brought on by the proliferative phase of the menstrual cycle.
Estrogen-deficient conditions are characterized by a lack of endometrial buildup. Common estrogen-deficient conditions include hypothalamic amenorrhea from chronic illness, stress, or nutritional deficiency; primary ovarian insufficiency; or hyperprolactinemia. In anorexic patients, the pathophysiology starts with an energy (nutritional) deficit leading to suppression of GnRH secretion, mediated in part by low leptin levels [1]. Suppressed GnRH levels lead to suppressed LH and FSH levels, and thus ovarian estrogen and androgen production returns to prepubertal levels.
Other conditions that cause amenorrhea can usually be swiftly ruled out by history or basic blood work. Anorexic patients are usually bradycardic, and thus their clinical presentation of weight loss with concomitant bradycardia is not consistent with hyperthyroidism. A thyrotropin (TSH) level can rule out both hyper- and hypothyroidism, both of which can cause amenorrhea. A low FSH rules out primary ovarian insufficiency. A normal prolactin and a lack of galactorrhea or visual field deficits rule out hyperprolactinemia. A careful history and physical with judicious blood work can rule out insidious diseases such as celiac disease or lymphoma that can cause cachexia.
Patients with anorexia nervosa often present with a classic constellation of lab abnormalities, and documenting these objective measures of starvation can help crystallize the diagnosis for patients and parents. LH, FSH, and estradiol are suppressed to prepubertal levels. Commonly, a complete blood count shows leukopenia with other cell lines being normal (and in fact, patients have robust hemoglobins because of the cessation of menses). Electrolytes are usually normal while they are in the starved state, but hypophosphatemia can develop rapidly when patients are re-nourished. Thyroid studies show a low T3 with a normal TSH and free T4, as the thyroid gland preferentially creates reverse T3 in lieu of the more metabolically active T3 in the face of nutritional deficiency. Liver function tests can show a mild transaminitis; the etiology is unclear but may include hepatocyte injury due to glutathione depletion or autophagy [2]. Inflammatory markers are very low.