The patient was a 17-year-old boy on rhGH therapy for 14 years because of a GH deficiency that was diagnosed at the age of 2 years and 3 months. Therapy was stopped 9 months before the beginning of symptoms—fatigue, decreased muscle strength and severe headache. However, the patient had not come for retesting one month after discontinuation of rhGH treatment.\nThe propositus was the first child of non-consanguineous Italian parents. The mother was in treatment for post-partum depression. The maternal grandfather was in treatment for autoimmune hyperthyroidism.\nThe mother’s height was 152 cm and she had menarche at the age of 13; the father’s height was 168 cm and he had a normal development. The target height was 166.0 ± 6.0 cm (−1.70 SDS). All auxological data were normalized for chronological age by conversion to standard deviation scores (SDS) that were calculated according to the following formula: patient value - mean of age-related reference value/standard deviation of the age-related reference value [].\nThe child was born at 40 weeks of gestation with an uncomplicated delivery. The birth weight was 2970 g (−1.15 SDS), length at birth was 50 cm (−0.30 SDS), and his occipito-frontal head circumference (OFC) was 34 cm (−0.61 SDS). He had neonatal jaundice requiring phototherapy. The child’s neuromotor development was normal: he sat at 6 months, walked independently at 12 months, and began to use language at 14 months.\nAt 6 months, the patient exhibited very deficient growth (Fig. ). At 2 years and 3 months, he was admitted to our Paediatric Endocrine Unit for an endocrinological evaluation. His height, evaluated according the growth charts compiled by Cacciari et al. [], was 78.6 cm (−2.79 SDS). His weight was 9.830 kg (−2.78 SDS), and his BMI was 15.91 (−0.28 SDS) (Fig. ). Extensive biochemical, endocrinological and metabolic examinations did not reveal any abnormalities with the exception of plasma concentrations of IGF-I and IGFBP-3 that were low for his age and sex: 27 ng/mL and 1.38 μg/mL, respectively. Thus, GH stimulation tests were performed and showed a reduced response after the clonidine (GH peak of 5.2 ng/mL) and insulin (glucose nadir 2.0 mmol/L at 30 min; GH peak of 3.9 ng/mL) tests. This revealed a GH deficiency (GHD). Bone age was assessed according to the Greulich and Pyle method [], and it was delayed (1 year and 2 months versus a chronological age of 2 years and 3 months). Brain MRI of the hypophyseal region showed the presence of a pituitary hypoplasia (height 1.8 mm and width 2.7 mm). Consequently, hGH therapy (0.22 mg/kg/wk) was started.\nThe child responded very well to rhGH treatment (Fig. ) and at 3 years and 4 months old, his height was 94.5 cm (−1.14 SDS), weight 12.450 kg (−2.10 SDS), height velocity 15.06 cm/yr (5.05 SDS), and BMI 13.94 (−1.75 SDS). At 4 years and 3 months old, his height was 101.9 cm (−0.82 SDS), his weight was 15.300 kg (−1.24 SDS), his height velocity was 8.05 cm/yr (1.12 SDS), and his BMI was 14.73 (−0.82 SDS).\nThe onset of puberty occurred at 12 years old with normal onset, timing, tempo, and magnitude of pubertal changes []. He stopped rhGH treatment at 16 years and 3 months old when he reached the definitive stature []: his height was 170.8 cm (−0.64 SDS) and his weight was 51.800 kg (−1.56 SDS) with a BMI of 17.76 (−1.63 SDS) (Fig. ).\nAt 17 years old, his GH secretion was re-tested by the growth-hormone-releasing hormone (GHRH) + arginine test, which is a reliable test of ITT in retesting patients who had undergone GH treatment in childhood []. The test confirmed a severe GH deficiency (basal GH value of 0.18 ng/mL; GH peak of 2.42 ng/mL).\nMRI angiography was performed because of the severe growth hormone deficiency (GHD) and headache; it confirmed the presence of adenohypophyseal hypoplasia (height 2.5 mm and width 3.5 mm) with a lack of posterior pituitary hyperintensity. The MRI angiography also showed the absence of a normal flow void in the left ICA (Fig. ).\nNo abnormal findings were noted in the electrocardiogram. Chromosomal studies of the peripheral lymphocyte cultures revealed a 46,XY normal male karyotype. An array of CGH analyses on the patient’s DNA was performed with an Agilent 60 K array platform with a resolution of approximately 100 kb. No genomic imbalances were detected. A complete examination was performed with particular attention to neurology, metabolism, and endocrinology (Table ). The only abnormal result was a very low IGF-I value (31 ng/mL). In light of these results, the patient restarted rhGH therapy, and his symptoms at the time of referral disappeared.
The patient was a 63-year-old female with hypertension and diabetes. She had no history of smoking or heart disease. She had undergone surgery to clip a cerebral aneurysm 3 years previously and the treating neurosurgeon responsible at the time had reported difficulty with catheterization of cervical arteries. She was examined with Doppler ultrasonography of carotid and vertebral arteries, which showed that the left common carotid artery had a smaller caliber than the right ( ), the left carotid bifurcation could not be observed, and the left common carotid artery only led to the left external carotid artery ( ). Angiotomography was ordered, showing agenesis of the left internal carotid artery ( ). The patient remains asymptomatic and attends regular follow-up consultations.