Background/Aims: Defects of the PROP1 gene are the most prevalent genetic cause of combined pituitary hormone deficiency. Previous observations in affected patients have shown pituitary size ranging from hypoplasia to overt pituitary mass and evolution of size over the lifespan. Methods: We evaluated pituitary size and morphology in PROP1-mutation carriers who originated from Central and Eastern Europe. We analyzed 112 pituitary magnetic resonance imaging (MRI) scans from 82 patients (42 males) aged 2.5–72.7 (median 16.6) years from 60 kindreds. Results: Among the 120 independent PROP1 alleles, the most prevalent mutations were delGA301/302 (99 alleles) and delA150 (13 alleles). Median pituitary height at first MRI was 4.7 mm (range 1.0–20.7) and median volume was 127.6 mm³ (range 7.5–3,087.0). Pituitary size did not differ between sexes and did not correlate with hormonal phenotype, but significantly decreased with increasing age. However, evaluation of individual values suggested a biphasic mode with increasing volume during childhood, peak in adolescence, and subsequent regression in adulthood. Conclusion: Although pituitary size was increased in a number of PROP1-deficient patients, none of them suffered permanent damage from pituitary mass; therefore, any proposed surgery should be postponed as long as possible and ultimately may not be necessary due to the self-limiting nature of the pituitary enlargement.

Patients with a PROP1 inactivating mutation present combined pituitary hormone deficiency (CPHD) and pituitary maldevelopment. A retrospective analysis of 31 CPHD patients with a PROP1 mutation revealed two individuals, aged 18 and 4.5 years, who had undergone subtotal surgery to remove pituitary tumors, 16.8 x 12 mm and 9 x 10 x 12 mm in size. Histological reassessment of tissue samples revealed epithelial cells, partially oxyphilic, forming gland-like microcystic structures, most of them filled with eosinophilic colloid. These structures were directly linked with fragments of the posterior lobe. Neither atypia nor any traces of proliferation activity (Ki-67 LI=0%) were noted. Immunohistochemistry showed the presence of all hormonal phenotypes of cells. These findings corresponded to the intermediate lobe of the pituitary gland. For this type of pathology we propose the term 'cystic hyperplasia of the intermediate pituitary lobe' and suggest PROP1 gene assessment in patients with CPHD in order to avoid unnecessary neurosurgical interventions.

Genotype–phenotype correlation in patients with Prader–Willi syndrome (PWS) has still not been fully described. We retrospectively analysed data of 147 patients and compared groups according to genetic diagnosis: paternal deletion of chromosome 15q11-q13 (DEL 15, n = 81), maternal uniparental disomy (UPD 15, n = 10), excluded DEL 15 (UPD 15 or imprinting centre defect, UPD/ID, n = 30). Group DEL 15 had an earlier genetic diagnosis and recombinant human growth hormone (rhGH) start (p = 0.00), with a higher insulin-like growth factor 1 (IGF1) level compared to group UPD/ID (p = 0.04). Among perinatal characteristics, there was only a tendency towards lower birth weight SDS in group UPD 15 (p = 0.06). We also compared data at rhGH start in relation to genetic diagnosis age—group 1: age ≤9 months, group 2: >9 months ≤ 2 years, group 3: > 2 years. Group 1 had the earliest rhGH start (p = 0.00), with lower body mass index (BMI) SDS (p = 0.00) and a tendency towards a higher IGF1 level compared to group 3 (p = 0.05). Genetic background in children with PWS is related to time of diagnosis and rhGH start, with a difference in IGF1 level before the therapy, but it seems to have little impact on perinatal data. Early genetic diagnosis leads to early rhGH treatment with favourable lower BMI SDS.

Pituitary stalk lesions (PSL) are a very rare pathology. The majority of conditions affecting the infundibulum do not present with clinically apparent symptoms, what makes the diagnosis difficult. The recognition might be also complicated by the non-specific and transient characteristics of hormonal insufficiencies. In our study, we retrospectively analysed demographic, biochemical, and clinical long-term data of 60 consecutive, unselected adult patients (34 women and 26 men) with PSL diagnosed in the Department of Endocrinology, Jagiellonian University in Krakow. The diagnosis of PSL were categorized as confirmed, probable, or undetermined in 26, 26 and 8 patients, accordingly. Given the possible aetiology congenital, inflammatory, and neoplastic stalk lesions were diagnosed in 17, 15 and 20 patients, accordingly. In eight cases the underlying pathology remained undetermined. The most common pituitary abnormality was gonadal insufficiency diagnosed in 50.8% of cases. Diabetes insipidus was detected in 23.3% of cases. In 5% of patients the pituitary function recovered partially over time. Stalk lesions were extensively discussed in the context of the current literature. Based on the published data and our own experience a diagnostic algorithm has been proposed to help physicians with the management of patients with this challenging condition.

Lack of polydipsia and polyuria, the key symptoms of diabetes insipidus (DI), may delay the diagnosis of aDI and may lead to severe complications of chronic hyperosmolar status. The fluid intake in patients diagnosed with aDI need to be supervised daily based on calculated constant volume of oral fluids, daily measurements of fluid balance, body weight and sodium levels, especially in patients whose vision is compromised or who are physically unable to take care of themselves.