Endocrine Abstracts

Introduction: Activating and inactivating mutations of the GNAS gene (encoding the Gsα protein) cause McCune–Albright Syndrome and Albright’s Hereditary Osteodystrophy, respectively. In both, the bone and the endocrine system are often affected. In McCune–Albright Syndrome the most common endocrine manifestation is precocious puberty, but thyroid lesions and hormonal overproduction are also described. In Albright’s Hereditary Osteodystrophy there may be obesity, pseudohypoparathyroidism and other hormonal resistance.

Results (cases presentation)

Case 1: 20-year-old female patient, with McCune–Albright Syndrome. Followed in endocrinology appointments with subclinical hyperthyroidism, increased prolactin and GH/IGF-1. Currently 1.51 m, 59.2 kg, body mass index (BMI) 25.9 kg/m²; prolactin 8.7 ng/ml (5.2–26.5) under bromocriptine; GH 7.3 µg/l (<1) and IGF-1 568 ng/ml (116–358) without therapy, having recently started lanreotide. Past medical history (PMH): Diagnosis at 2 years of age in the context of café au lait spots, stature acceleration, early peripheral puberty and bone dysplasia. During follow-up, she presented: elevation of GH/IGF-1 and growth >97 percentil (under sandostatin from age 10–15); hyperprolactinemia/galactorrhea (under bromocriptine from the age of 14); menstrual irregularities under combined oral contraceptive pills from age 11–19.

Case 2: 19 year-old, male patient, carrier of a GNAS mutation with suspected Albright’s Hereditary Osteodystrophy. Followed in endocrinology appointments with TSH resistance hypothyroidism, currently with normal thyroid function under levothyroxine; short stature (1.43 m); normal/slightly elevated parathormone with calcium, phosphate and magnesium in the normal reference range; without other hormonal abnormalities.

PMH: primary hypothyroidism since the first year of life; genetic diagnosis performed at age 14 in the context of short stature, round face, brachydactyly and delayed psychomotor development.

Case 3: Female sex, 24 years-old with Albright’s Hereditary Osteodystrophy. Followed in endocrinology appointments, currently presenting: overweight (body mass index of 28 kg/m²), dyslipidemia and pre-diabetes (A1C 5.7%); slight elevation in parathormone 79 pg/ml (9–72) with calcium, phosphate and magnesium within the reference range and slight vitamin D deficiency; goiter with normal thyroid function; magnetic resonance with pineal cyst. Current medication: vitamin complex.

PMH: Genetic diagnosis of AHO at 12 years of age due to global developmental retardation, obesity and shortening of the 4th and 5th metatarsals and 4th metacarpals; self-injurious behaviours.

Discussion: Mutations with opposite effect on the same gene give rise to McCune–Albright Syndrome and Albright’s Hereditary Osteodystrophy. Both affect the endocrine and skeletal systems differently. Due to the rarity and diversity of manifestations, they require multidisciplinary monitoring throughout life.