Childhood Cushing’s Syndrome

Abstract

A 16-year-old girl presented with weight gain, secondary amenorrhea, and increased facial hair for the past 2 years; however, her appetite was normal and there was no change in her lifestyle. She also complained of weakness and appearance of striae over the abdomen for the last 1 year. She had a history of poor gain in height during the last 4 years. Patient also had difficulty in climbing the stairs. However, there was no history of easy bruisibility, back pain, or pathological fracture. She had menarche at the age of 12 years and later oligomenorrhea, followed by secondary amenorrhea for the last 2 years. There was no history of any drug intake, or use of alternative medications, or steroid preparations, either inhalational or ointments. On examination, her height was 157 cm ( 75th percentile, weight age >20 years), BMI 24.1 Kg/m2, and blood pressure 112/74 mmHg. She had florid features of Cushing’s syndrome including moon facies, facial plethora, acne, dorso-cervical fat pad, and wide violaceous striae over lower abdomen and thighs. She also had cuticular atrophy, knuckle hyperpigmentation, and proximal muscle weakness. She had generalized obesity with waist circumference of 90 cm. However, she did not have bruise and pulp atrophy. Patient had hirsutism with Ferriman–Gallwey score of 15/36 and did not have features of virilization. There was no cafe-au-lait macule, lentigines, bony deformity, spine tenderness, or cutaneous fungal infection. Biochemical evaluation revealed serum potassium 4.2 mEq/L, liver, and renal function tests were normal. Fasting blood glucose was 92 mg/dl and 2 h plasma glucose after glucose load was 112 mg/dl with HbA1c of 5.0 %. Lipid profile showed serum cholesterol 159 mg/dl, LDL-C 99.6 mg/dl, triglyceride 198 mg/dl, and HDL-C 32.2 mg/dl. Cortisol dynamics showed 0800 h cortisol 567 nmol/L; awake 2300 h cortisol 520 nmol/L; 0800 h ACTH 16.8 pg/ml; awake 2300 h ACTH 63.7 pg/ml; late-night salivary cortisol 12.5 nmol/L and 28.7 nmol/L on two consecutive days, respectively; and 24 h urinary free cortisol on three consecutive days was 448 μg, 469 μg, and 532.8 μg, respectively. Serum cortisol after overnight dexamethasone suppression test (ONDST) was 464 nmol/L, low-dose dexamethasone suppression test (LDDST) 408 nmol/L, and after high-dose dexamethasone suppression test (HDDST) was 157 nmol/L. Serum prolactin was 8.63 ng/ml (N 4.7–23.3), T4 7.02 μg/dl (N 4.8–12.7), TSH 0.894 μIU/ml (N 0.27–4.2), testosterone 0.32 nmol/L (N 0.2–2.9), LH 0.24 mIU/ml (N 2.4–12.6), and FSH 0.32 mIU/ml (N 3.5–12.5). Ultrasound pelvis showed normal ovaries and uterus. Dynamic contrast-enhanced MRI sella revealed differentially enhancing 4.8 × 4.0 mm lesion which was hypointense on T1W and hyperintense on T2W images in the left half of the pituitary gland. She underwent bilateral inferior petrosal sinus sampling (IPSS) with 100 μg (IV bolus) human CRH. IPSS localized the source of ACTH excess to the pituitary and lateralized to right side of the pituitary gland. Serum ACTH and cortisol profile during IPSS are summarized in the table given below. She underwent transsphenoidal surgery, intraoperatively tumor was localized to the left side of the pituitary, and excision of the tumor was accomplished. Patient developed left lateral rectal palsy postoperatively, which recovered within 2 weeks. She was documented to have hypocortisolemia (83.5 nmol/l) on day 1 postoperatively and was started on hydrocortisone supplementation. Histopathology of the tumor tissue showed pituitary adenoma, while immunostaining for ACTH was negative. At 6 weeks, she had weight loss of 5 kg, resolution of plethora, disappearance of acne, and violaceous striae started fading. A 0800 h serum cortisol after the omission of hydrocortisone for 24 h was 4.6 nmol/L, and serum T4 was 10.5 μg/dl. She is continued with hydrocortisone supplementation and advised to follow up every three monthly (Fig. 4.1).