Primary Amenorrhea and Hyperandrogenism: Presenting Features of a Growth Hormone Producing Pituitary Adenoma in a Female Adolescent

Abstract

Background: The combination of obesity, metabolic syndrome, hyperandrogenism and amenorrhea can be a common presentation of conditions such as polycystic ovarian syndrome. Growth hormone (GH) secreting pituitary adenomas are rare in children, but can present with a similar picture. Clinical Case: A 15-year 4-month old female was evaluated for primary amenorrhea and metabolic syndrome. Her weight was +2.96 SD, height +3.0 SD (mid-parental height 44th percentile, -0.1 SD) and BMI +2.53 SD, all >99th percentile. Weight and BMI were >99th percentile (weight +3.0 SD, BMI +2.4 SD) since 11 years of age and height was >99th percentile (+ 2.7 SD) since 8 years of age. Physical exam was remarkable for acanthosis, deepened voice, no hirsutism, Tanner III breasts and Tanner IV pubic hair. Laboratory evaluation was notable for prolactin (PRL) 147.8 ng/dL (2.6-18.0), LH <0.02 mIU/mL, FSH <0.09 mIU/mL, estradiol 23 pg/mL, total testosterone 81 ng/dL (<41), androstenedione 673 ng/mL (43-180), DHEA-S 627 mcg/dL (42-162), dyslipidemia and normal 17 hydroxy-progesterone and thyroid function tests. Bone age was 16 years. Brain MRI showed a 15x7mm pituitary macroadenoma without suprasellar invasion. Pituitary evaluation revealed IGF-1 619 ng/mL (192-568), IGF-BP3 5.15 mg/L (2.64-6.43) and adrenal insufficiency. Treatment with cabergoline 0.5 mg/week and maintenance hydrocortisone were initiated. An OGTT demonstrated baseline GH 4.9 ng/mL (0-6) and nadir 3.62 ng/mL (normal <1) consistent with GH excess. Surgery for the pituitary adenoma was recommended but unfortunately postponed. Four months later, her BP was elevated, she had clinical signs of diabetes insipidus (DI), PRL was 43.2 ng/dL and she failed a repeat GH suppression test. Follow-up MRI showed pituitary mass enlargement (17x9mm). Patient underwent total trans-sphenoidal tumor resection. Pathology confirmed a sparsely granulated (SG) GH adenoma immunoreactive for GH, PRL and estrogen receptor. Post-operative OGTT showed adequate GH suppression, normal prolactin levels, persistent testosterone elevation and DI. Conclusions: Hyperprolactinemia, hyperandrogenism and metabolic syndrome could be the presenting features of pituitary GH adenomas even in the absence of acromegalic features. Specifically, SG pituitary adenomas are frequently seen in young adults, are larger, more invasive and less likely to respond to medical treatment. Timely diagnosis and surgical treatment of GH adenomas is essential to prevent the high morbidity and mortality.