Patient: Sarah, a 25-year-old woman from Karachi, Pakistan, presented with a two-year history of progressive weight gain, excessive daytime sleepiness, and difficulty staying awake during the day. Sarah reported uncontrolled hunger cravings leading to overeating, poor quality sleep with frequent early morning awakenings, and a constant feeling of fatigue despite getting 8-10 hours of sleep. She denied any history of medical conditions, medication use, or substance abuse.
Physical Examination: Sarah was obese with a BMI of 34 kg/m2. Her blood pressure and heart rate were within normal limits. Neurological examination revealed no focal deficits.
Laboratory Investigations: Thyroid function tests, complete blood count, and electrolyte levels were normal. Fasting blood glucose, HbA1c, and lipid profile were also within the normal range. Sleep study was inconclusive due to technical difficulties.
Diagnostic Challenges: Sarah’s presentation suggested a rare endocrine disorder, but the limited diagnostic resources and awareness of uncommon conditions in Pakistan posed a challenge. The combination of obesity, excessive sleepiness, and normal hormonal profiles pointed towards a central etiology, possibly involving the hypothalamus.
Differential Diagnosis: Initially, the differential diagnosis included Prader-Willi syndrome, narcolepsy, hypothyroidism, depression, and obstructive sleep apnea. However, genetic testing ruled out Prader-Willi syndrome, and the absence of cataplexy and REM sleep without atonia made narcolepsy less likely. The normal thyroid function tests refuted hypothyroidism, and depression with atypical features wasn’t consistent with Sarah’s presentation. Due to inconclusive sleep study results, obstructive sleep apnea remained a possibility.
Unveiling the Orexin Connection: Given the central nature of Sarah’s symptoms and the limited diagnostic options, a specialist suggested exploring the potential role of orexin deficiency. A specialized test revealed significantly low levels of orexin in Sarah’s cerebrospinal fluid. This finding provided a crucial clue, suggesting hypothalamic orexin deficiency as the likely underlying cause of her obesity and excessive sleepiness.
Management and Prognosis: With the orexin connection established, Sarah received specialist referral for comprehensive metabolic and sleep management. Dietary counseling and behavioral therapy were initiated to address her overeating behavior and promote weight loss. Additionally, stimulant medications and sodium oxybate, both known to stimulate orexin receptors, were considered to improve her daytime alertness and sleep quality. The long-term prognosis for Sarah will depend on adherence to treatment and lifestyle modifications. Continued monitoring of her weight, sleep patterns, and orexin levels will be crucial to optimize her management plan.
Significance: This case study highlights the importance of considering orexin deficiency as a potential cause of unexplained obesity and excessive sleepiness, especially in patients with normal biochemical profiles. Early recognition and diagnosis can lead to targeted treatment strategies, potentially improving quality of life for individuals like Sarah. Additionally, it emphasizes the need for increased awareness and accessibility to advanced diagnostic tools in Pakistan, which are essential for accurate diagnosis and effective management of rare endocrine disorders.