Case 3: Psychiatric Distress, Hypertension, and Weight Gain in an Adolescent Male

Presented here are three patients who have a common chief complaint. All three cases have discussions on presentation, the differential diagnosis, and management that collectively serve as a Review article. Following the three cases, an expert weighs in in a short commentary with 5 questions for CME credit.A 14-year-old boy presents to the emergency department after developing an acute headache and abdominal pain while at school. He revealed to school staff that he had ingested a large amount of pills, including 30 tablets of dextroamphetamine, an unknown amount of ibuprofen, 15 to 20 tablets of aspirin, and 2 tablets of meloxicam. His intent was to “die a peaceful death” because of discomfort due to recurrent abdominal pain and reported anxiety about the current COVID-19 surge and stress associated with school. He started having episodes of abdominal pain 2 months before this presentation. His parents also noted that during the COVID-19 pandemic he had become progressively more depressed and anxious and expressed fear regarding the return to in-person school. His parents did not believe that he was suffering from depression and anxiety but were concerned about his ongoing symptoms related to abdominal pain. His pediatrician evaluated the pain via abdominal ultrasonography, which was notable for an umbilical hernia. The pediatrician also noted hypertension and advised lifestyle changes through limitation of intake of salt and sugar-sweetened beverages. His parents encouraged these lifestyle changes and were pleased with his progressive weight loss during the preceding months. However, the intermittent abdominal pain continued and was treated with ibuprofen by the parents. Dosing and frequency of ibuprofen administration is not available in the patient’s history. At baseline, the parents report him to be academically successful and high achieving before this sentinel event.He is admitted to the PICU. Initial vital signs include blood pressure of 196/119 mm Hg, heart rate of 120 to 130 beats/min, respiratory rate of 15 breaths/min, and normal temperature and oxygen saturation. He weighs 223 lb (101.5 kg) (99%), with a BMI of 30.3 (98%), and measures 70.5 in (179 cm) tall (95%). On examination, he is initially alert, oriented, and anxious; however, with continued observation, he becomes confused with tangential speech and exhibits facial tics. His overall body habitus is remarkable for increased adipose tissue in the supraclavicular and dorsocervical regions and the abdomen. His eyes are clear and without conjunctival injection. A complete funduscopic examination is not performed. His face is round, with flushed cheeks. Findings on examination of the oropharynx and thyroid are normal. He has a regular tachycardia, and respiratory effort and lung auscultation are normal. He has generalized abdominal tenderness with guarding. It is difficult to palpate the liver and spleen because of the patient’s abdominal tenderness and his large body habitus. Cranial nerves are intact and deep tendon reflexes are present, but the patient is unable to stand without support or bend without losing his balance. He exhibits proximal muscle weakness primarily in his upper thighs, with motor strength 3/5 bilaterally. A Romberg test is not performed. Wide, red to purple striae are noted in the region of the axilla, chest, and lateral abdomen, and he does not have acanthosis nigricans. Initial laboratory values (Table 1) are remarkable for hypokalemia, metabolic alkalosis, elevated salicylate levels, and positive urine screening for amphetamine. Thyroid function study results are abnormal and are attributed to nonthyroidal illness syndrome in the setting of critical illness.The patient is initially administered a benzodiazepine as recommended by poison control to both treat his anxiety and improve his blood pressure, but this treatment fails, and his anxiety and hypertension continue unabated. A nicardipine drip is instituted for blood pressure control. Given the nonsteroidal anti-inflammatory drug and salicylate ingestions, serial chemistry analyses are obtained and are negative for renal abnormalities or acid-base derangements. Mental health support is provided to the patient and inpatient psychiatric consultation is recommended, but parents decline inpatient psychiatric assistance. The patient’s previous growth charts are obtained from his pediatrician and demonstrate that weight was 123 lb (55.8 kg) (>99%) at age 9 years, with a rate of weight gain of approximately 10 to 18 lb (4.54–8.16 kg) per year. This accelerated to 64 lb (29.03 kg) gained in the first year of the COVID pandemic, with a weight of 256 lb (116.12 kg) (>99%) and a BMI of 35 (>99%) at 14 years of age (Fig 1). After he undertook lifestyle modifications, he lost 30 lb (13.61 kg) in 3 months and was 223 lb (101.15 kg) (>99%) when he presented for treatment after purposeful polypharmacy ingestion. There has been no growth deceleration (Fig 1A). For his abdominal pain, repeated abdominal ultrasonography is performed, with no abnormalities except the known umbilical hernia. An abdominal radiograph is normal, and a computed tomographic scan is not performed. Due to the history of abdominal pain, upper and lower endoscopies are performed on day 4 of admission, with no significant findings outside of small ulcerations in the stomach and terminal ileum believed to be associated with his recent ingestion. His mood symptoms of depression and anxiety as well as his hypertension do not abate beyond the 24-hour window that may be attributable to his initial ingestion. Poison control advised that the elimination window for dextroamphetamines is 10 to 14 hours in therapeutic dosing, but symptoms of ongoing agitation and hypertension require treatment if not resolving past 14 hours as the elimination window is unpredictable in the setting of an overdose. After the negative gastrointestinal evaluation, due to persistent symptoms and based on his history and clinical presentation, a 24-hour urine collection for free cortisol level is obtained.As the clinical history unfolded, the medical diagnosis expanded from polypharmacy ingestion with suicidality to consideration of an underlying disease that contributed to the patient’s mental health crisis. His clinical features included persistent hypertension in the setting of obesity, wide striae of the skin due to rapid weight gain, acute on chronic abdominal pain, hypokalemia, proximal myopathy, and mood symptoms culminating in suicidal behavior. The differential diagnosis included metabolic syndrome in association with essential hypertension in combination with a separate mood disorder, inflammatory bowel disease causing abdominal pain and leading to mental health distress, gastroesophageal reflux disease and exogenous obesity, hyperaldosteronism, and hypercortisolism (Cushing syndrome).Screening tests for Cushing syndrome (Table 2) were abnormal and established the diagnosis of hypercortisolism, which was shown to be corticotropin-dependent because of the corticotropin level in the upper normal range. Subsequently, a high-dose dexamethasone suppression test was performed to distinguish pituitary from ectopic corticotropin secretion, and the results were concordant with pituitary disease (Table 2). Based on these test results, a preliminary diagnosis of corticotropin-dependent Cushing disease (CD) was made, and a pituitary magnetic resonance image was obtained. Although pituitary imaging was initially interpreted as negative, the high index of suspicion led to a secondary imaging review that identified evidence of a pituitary adenoma (Fig 2). The patient ultimately had a transsphenoidal resection of a tumor in the right anterior pituitary gland. Pathology confirmed a corticotroph adenoma with immunohistochemical analysis positive only for corticotropin.CD, the most common cause of endogenous Cushing syndrome in pediatric patients, specifically refers to hypercortisolism due to the increased production of corticotropin from neoplastic corticotroph cells of the anterior pituitary gland, which in turn increases cortisol production from the adrenal gland cortex. (1)(2) Besides CD, other etiologies of Cushing syndrome include exogenous glucocorticoid use, corticotropin-independent Cushing syndrome secondary to overproduction of cortisol from an adrenocortical tumor, and ectopic corticotropin secretion, which is a subtype of corticotropin-dependent hypercortisolism due to corticotropin secretion by a neuroendocrine tumor outside of the pituitary gland, most commonly in the lungs.Hypercortisolism causes a characteristic appearance of central obesity with relative sparing of the extremities, although this may not be the case in all patients. This centralized adiposity includes excessive fat in the supraclavicular fossae, as seen in our patient. Although the appearance of a dorsocervical fat pad (“buffalo hump”) is classically associated with hypercortisolism, it is also commonly identified in children with exogenous obesity and, therefore, is not as helpful as the finding of abnormal supraclavicular fat in suggesting the diagnosis of Cushing syndrome. The dermatologic manifestation of wide, dark red or violet striae in the axilla, abdomen, or inner thighs as well as a peculiar appearance of the face (“moon facies”) with ruddy cheeks are often apparent and highly suggestive of the diagnosis. (1)(3) Most pediatric patients with CD experience growth failure with weight gain, (1) but not all have growth failure, as demonstrated in our patient and as noted in previous publications. (2) Fatigue and a sense of generalized weakness due to proximal myopathy from cortisol excess can be significant. Hypertension, diabetes mellitus, and gastroesophageal reflux can also occur. Depression and anxiety are common, and similar to our patient, a large percentage of patients with hypercortisolism express suicidal ideation in the course of their disease. (3) The possibility of pseudo-Cushing syndrome due to activation of the hypothalamic-pituitary-adrenal axis in the context of severe anxiety/depression was considered but ruled out due to the patient’s classic phenotype on examination, clinical course while hospitalized, and ultimate confirmation of a corticotroph pituitary adenoma.Screening tests for hypercortisolism include a 24-hour urinary cortisol collection, a low-dose dexamethasone suppression test, and measurement of late-night salivary cortisol level. (4)(5) Once corticotropin-dependent hypercortisolism is confirmed, high-dose dexamethasone suppression testing helps to further clarify the etiology of corticotropin excess. Inferior petrosal sinus sampling can also be used to distinguish pituitary from ectopic cases and may be required in cases in which imaging of the pituitary is negative or equivocal.CD is a challenging disease to diagnose and treat, and it requires a high index of suspicion. The diagnosis requires a multidisciplinary evaluation and documentation of biochemical evidence of hypercortisolism. When suspected clinically, the diagnosis of Cushing syndrome can be confirmed in consultation with a pediatric endocrinologist using serial testing of cortisol secretion and dexamethasone suppression testing. (4)(5) Once hypercortisolism and a nonsuppressed corticotropin level (typically >20 pg/mL [>4.40 pmol/L]) is confirmed, pituitary-based CD would be the likely diagnosis and pituitary imaging would be recommended.Postoperatively, the patient developed central adrenal insufficiency, an expected outcome after successful surgery for CD, and he was treated with physiologic corticosteroids for 5 months. No other pituitary hormone deficits developed postoperatively, and thyroid function studies normalized. A year and a half later, his abdominal pain remains resolved and his mood symptoms improved. BMI has improved after surgery (Fig 1B). He is treated for essential hypertension and continues to have normal 24-hour urinary free cortisol and salivary cortisol levels.During the COVID pandemic, there was an increase in mental health distress, particularly among adolescent patients. Although the pandemic did worsen our patient’s mental health, he ultimately had an underlying medical diagnosis that contributed to his psychiatric symptoms.The diagnosis of Cushing syndrome is challenging. Although physical examination findings can suggest hypercortisolism, only confirmed abnormal cortisol dynamics can make the formal diagnosis.