Pituitary tumors causing acromegaly are usually macroadenomas at the time of diagnosis, and they can grow aggressively, infiltrating surrounding tissues. Difficulty in achieving complete tumor removal at surgery can lead toward a strong tendency for recurrence, making it necessary to consider a means of treatment other than those currently used such as somatostatin analogs (SSAs), growth hormone (GH) receptor antagonist, surgical removal, and radiotherapy. The purpose of this paper is to describe a patient diagnosed with an aggressive, giant GH-secreting tumor refractory to medical therapy but ultimately treated with the radiolabeled somatostatin analog 90Y-DOTATATE. A 26-year-old male with an invasive macroadenoma of the pituitary gland (5.6 × 2.5 × 3.6 cm) and biochemically confirmed acromegaly underwent 2 partial tumor resections: the first used the transsphenoidal approach and the second used the transcranial method. The patient received SSAs pre- and postoperatively. Because of the progression in pituitary tumor size, he underwent classic irradiation of the tumor (50 Gy). One and a half years later, the patient presented with clinically and biochemically active disease, and the tumor size was still 52 mm in diameter (height). Two neurosurgeons disqualified him from further surgical procedures. After confirming the presence of somatostatin receptors in the pituitary tumor by using 68Ga-DOTATATE PET/CT, we treated the patient 4 times with an SSA bound with 90Y-DOTATATE. After this treatment, the patient attained partial biochemical remission and a reduction in the tumor mass for the first time. Treatment with an SSA bound with 90Y-DOTATATE may be a promising option for some aggressive GH-secreting pituitary adenomas when other methods have failed.

The role of genetic background in childhood-onset combined pituitary hormone deficiency (CPHD) has been extensively studied. The major contributors are the PROP1, POU1F1, LHX3, LHX4 and HESX1 genes coding transcription factors implicated in pituitary organogenesis. The clinical consequences of mutations encompass impaired synthesis of a growth hormone (GH) and one or more concurrent pituitary hormones (i.e. LH, FSH, TSH, PRL). Manifestation of the disorder may vary due to various mutation impacts on the final gene products or an influence of environmental factors during pituitary organogenesis. We describe the clinical and molecular characteristics of two brothers aged 47 and 39 years presenting an uncommon manifestation of congenital hypopituitarism. Sequencing of the PROP1, POU1F1, LHX3, LHX4 and HESX1 genes was performed to confirm the genetic origin of the disorder. A compound heterozygosity in the PROP1 gene has been identified for both probands. The first change represents a mutational hot spot (c.150delA, p.R53fsX164), whereas the second is a novel alteration (p.R112X) that leads to protein disruption. Based on precise genetic diagnosis, an in silico prediction of a p.R112X mutation on protein architecture was performed. The resulting clinical phenotype was surprisingly distinct compared to most patients with genetic alterations in PROP1 reported in the current literature. This may be caused by a residual activity of a newly identified p.R112X protein that preserves over 70 % of the homeodomain structure. This examination may confirm a key role of a DNA-binding homeodomain in maintaining PROP1 functionality and suggests a conceivable explanation of an unusual phenotype.

Primary hyperparathyroidism (HPTo) nowadays is most often recognized incidentally in the asymptomatic period as a result of biochemical screening or evaluation of low bone mass. Classical manifestations of the disease are present in about 15-20% of patients. We present the case of a 28-year-old male patient who had been treated for two years for osteoclastoma of the proximal tibia, first by intralesional curettage with cement filling followed by bone grafting, and finally with a reconstructive arthroplasty of the knee joint. The patient had been consulted in different medical centers by at least 14 doctors representing 9 different specialties, but the correct diagnosis of HPTo had not been made, although classic manifestations of the disease had been present for 5-6 years. This suggests that a diagnosis of HPTo is difficult nowadays. Therefore, determination of serum calcium concentration and other markers of calcium and phosphate metabolism should be obligatory in patients with bone lesions.

IntroductionPituitary autoantibodies can be determined both in patients with pituitary disease as well as patients with autoimmune endocrine diseases. The purpose of the study was to isolate and purify pituitary autoantigen using sera of patients and the microsomal fraction of the pituitary.Material and methodsTo isolate a pituitary autoantigen, patient sera were used, which showed a strong immune response to pituitary antigens. Pituitary microsomal fractions were prepared from pituitary tissue homogenates. In the study, sera of patients with pituitary disease, Addison and Graves’ disease were used. The initial stages were carried out by affinity chromatography on CN -Br sepharose column whereas purification was continued by column liquid chromatography on AcA54 Ultrogel. Chromatofocusing was performed by Polybuffer exchanger PBE 94.Results 125I-labeled pituitary antigens after isolation appeared in column chromatography in three peaks. The first peak contained 50-70 kDa proteins, the second peak – 17 to 22 kDa proteins and the third peak contains 125-iodides. Three fractions obtained from filtration on Ultrogel were separated in a polyacrylamide gel. In the first peak two bands 67 and 55 kDa appeared. The second peak contained low molecular weight substances, and the third peak contained 125I. The first peak from Ultrogel was isolated by chromatofocusing – the first peak with pH 5.9 and the second one with pH 4.9.ConclusionsIsolation and purification of pituitary autoantigen with the use of column liquid chromatography and chromatofocusing resulted in obtainment of two antigenic proteins of specific gravity of 67 and 55 kDa.

W Ws st tę ęp p: : Guzy neuroendokrynne grasicy to bardzo rzadkie nowotwory, stanowiące 2-4% guzów śródpiersia. Opisywane są przypadki ektopowego wydzielania hormonów w przebiegu tej patologii, z czego zespół ektopowego wydzielania ACTH jest najczęstszą endokrynopatią. W pracy zaprezentowano przypadek zespołu nieadekwatnego wydzielania wazopresyny w przebiegu tego nowotworu. O Op pi is s p pr rz zy yp pa ad dk ku u: : U 55-letniego mężczyzny na rutynowo wykonanym zdjęciu rentgenowskim klatki piersiowej wykryto guz śródpiersia. Po badaniu tomograficznym klatki piersiowej i badaniu PET-CT pacjenta skierowano na leczenie operacyjne, wycięto guz ze śródpiersia o wymiarach 11 × 8 × 4 cm, który naciekał płuco lewe i osierdzie. Badanie histopatologiczne wykazało raka neuroendokrynnego grasicy. Z uwagi na wznowę chorego poddano chemioterapii, a następnie leczono analogami somatostatyny z uwagi na pozytywny wynik scyntygrafii receptorowej i aktywność hormonalną nowotworu dającą zespół rakowiaka. W trakcie terapii hormonalnej wykryto zespół nieadekwatnego wydzielania wazopresyny. D Dy ys sk ku us sj ja a: : Przeprowadzono krótką charakterystykę zespołu nieadekwatnego wydzielania wazopresyny oraz raków neuroendokrynnych grasicy, uwzględniając sposoby leczenia tych jednostek chorobowych. W przypadku guzów o zachowanej ekspresji receptorów somatostatynowych należy brać pod uwagę możliwość zastosowania analogów somatostatyny w formie terapii przewlekłej. S Sł ło ow wa a k kl lu uc cz zo ow we e: : guzy neuroendokrynne, grasica, zespół nieadekwatnego wydzielania wazopresyny.