(42) Dysregulated Puberty in Panhypopituitarism

Background: Panhypopituitarism among patients with optic nerve hypoplasia ranges from 6% to 82% (Oatman, McClellan, Olson, et al., 2015). In keeping with hypothalamic-pituitary dysfunction, pubertal disturbances like hypogonadotropic hypogonadism are logically anticipated. Current limited estimates indicate that among patients with optic nerve hypoplasia and panhypopituitarism, 40% of females have normal pubertal development (menarche from age 10.5 to 13 years) (Oatman, McClellan, Olson, et al., 2015). In a case series of 101 children with optic nerve hypoplasia and panhypopituitarism, 50% of subjects had gonadotropin deficiency while 2% had precocious puberty (Oatman, McClellan, Olson, et al., 2015).

Case: Our patient is a female with past medical history of panhypopituitarism secondary to optic nerve hypoplasia, blindness, developmental delay, obesity, and limited mobility. Her pituitary deficiencies include secondary hypothyroidism requiring levothyroxine, secondary adrenal insufficiency requiring hydrocortisone, diabetes insipidus requiring DDAVP, and growth hormone deficiency requiring growth hormone. Her parents first noticed breast development as early as age 5 years and 7 months. Breast exam at this time was most consistent with lipomastia. Labs at this age were prepubertal with LH of < 0.03, FSH of 3.06, and estradiol < 2. At age 7 years 4 months her parents noted further breast development, but no pubic hair. Labs at this age were pubertal with an LH of 0.71, FSH of 4.44, and estradiol of 14. At age 8 years and 6 months her parents again reported further breast development and new pubic hair. Exam at this time showed tanner stage III breasts (though exam was limited by habitus) and tanner stage II pubic hair. Labs at age 8 years 8 months were again pre-pubertal with LH < 0.03, FSH of 0.8, and estradiol of < 2.0. A MRI at age 8 years and 7 months demonstrated slight enlargement of her anterior pituitary, absent posterior pituitary tissue, and no pituitary masses consistent with her known diagnosis of panhypopituitarism and excluding a pituitary mass.

Comments: Normal puberty and gonadotrophin deficiency seem to be the most common pubertal outcomes among children with optic nerve hypoplasia. At this point, our patient’s puberty is best characterized by dysregulation given her fluctuations in LH. Her case as well the 11 other cases of precocious puberty since 1978 highlight that though logically unexpected, precocious puberty is still possible in the setting of panhypopituitarism (Oatman, McClellan, Olson, et al., 2015; Huseman, Kelch, Hopwood, Zipf, 1978). Together they lend importance to pubertal assessment in children with optic nerve hypoplasia and panhypopituitarism.