TY  - JOUR
AU  - Doknić, Mirjana
AU  - Gašić, Vladimir
AU  - Stojanović, Marko
AU  - Pavlović, Sonja
AU  - Marinković, Snežana
AU  - Miljić, Dragana
AU  - Pekić, Sandra
AU  - Manojlović-Gacić, Emilija
AU  - Damjanović, Dusan
AU  - Soldatović, Ivan
AU  - Petakov, Milan
PY  - 2020
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1404
AB  - Twenty years after the first description of combined hypopituitarism (CPHD) caused by PROP1 mutations, the phenotype of affected subjects is still challenging for clinicians. These patients suffer from pituitary hormone deficits ranging from IGHD to panhypopituitarism. ACTH deficiency usually develops later in life. Pituitary size is variable. PROP1 mutation is the most frequent in familial congenital hypopituitarism (CH). Reports on initiation of hormonal replacement including growth hormone (GH) in adults with CH are scarce. We identified 5 adult siblings with CPHD due to PROP1 mutation (301-302delAG), aged 36-51 years (4 females), never treated for hormone deficiencies. They presented with short stature (SD from - 3.7 to - 4.7), infantile sexual characteristic, moderate abdominal obesity and low bone mineral density in 3 of them. Complete hypopituituitarism was confirmed in three siblings, while two remaining demonstrated GH, TSH, FSH and LH deficiencies. Required hormonal replacement including rhGH was initiated in all patients. After several months necessity for hydrocortisone replacement developed in all patients. After 2 years of continual replacement therapy, BMD and body composition (measured by DXA-dual X-ray absorptiometry) improved in all subjects, most prominently in two younger females and the male sibling. Besides rhGH therapy, these three patients have received sex hormones contributing to the favorable effect. The male sibling was diagnosed with brain glioblastoma two years following complete hormonal replacement. This report provides important experience regarding hormonal replacement, particularly rhGH treatment, in adults with long-term untreated CH. Beneficial effect of such therapy are widely acknowledged, yet these subjects could be susceptible to certain risks of hormonal treatment initiated in adulthood. Careful and continual clinical follow-up is thus strongly advised.
PB  - Springer, New York
T2  - Pituitary
T1  - Hypopituitarism in five PROP1 mutation siblings: long-lasting natural course and the effects of growth hormone replacement introduction in middle adulthood
EP  - 408
IS  - 4
SP  - 400
VL  - 23
DO  - 10.1007/s11102-020-01049-9
ER  - 

@article{
author = "Doknić, Mirjana and Gašić, Vladimir and Stojanović, Marko and Pavlović, Sonja and Marinković, Snežana and Miljić, Dragana and Pekić, Sandra and Manojlović-Gacić, Emilija and Damjanović, Dusan and Soldatović, Ivan and Petakov, Milan",
year = "2020",
abstract = "Twenty years after the first description of combined hypopituitarism (CPHD) caused by PROP1 mutations, the phenotype of affected subjects is still challenging for clinicians. These patients suffer from pituitary hormone deficits ranging from IGHD to panhypopituitarism. ACTH deficiency usually develops later in life. Pituitary size is variable. PROP1 mutation is the most frequent in familial congenital hypopituitarism (CH). Reports on initiation of hormonal replacement including growth hormone (GH) in adults with CH are scarce. We identified 5 adult siblings with CPHD due to PROP1 mutation (301-302delAG), aged 36-51 years (4 females), never treated for hormone deficiencies. They presented with short stature (SD from - 3.7 to - 4.7), infantile sexual characteristic, moderate abdominal obesity and low bone mineral density in 3 of them. Complete hypopituituitarism was confirmed in three siblings, while two remaining demonstrated GH, TSH, FSH and LH deficiencies. Required hormonal replacement including rhGH was initiated in all patients. After several months necessity for hydrocortisone replacement developed in all patients. After 2 years of continual replacement therapy, BMD and body composition (measured by DXA-dual X-ray absorptiometry) improved in all subjects, most prominently in two younger females and the male sibling. Besides rhGH therapy, these three patients have received sex hormones contributing to the favorable effect. The male sibling was diagnosed with brain glioblastoma two years following complete hormonal replacement. This report provides important experience regarding hormonal replacement, particularly rhGH treatment, in adults with long-term untreated CH. Beneficial effect of such therapy are widely acknowledged, yet these subjects could be susceptible to certain risks of hormonal treatment initiated in adulthood. Careful and continual clinical follow-up is thus strongly advised.",
publisher = "Springer, New York",
journal = "Pituitary",
title = "Hypopituitarism in five PROP1 mutation siblings: long-lasting natural course and the effects of growth hormone replacement introduction in middle adulthood",
pages = "408-400",
number = "4",
volume = "23",
doi = "10.1007/s11102-020-01049-9"
}

Doknić, M., Gašić, V., Stojanović, M., Pavlović, S., Marinković, S., Miljić, D., Pekić, S., Manojlović-Gacić, E., Damjanović, D., Soldatović, I.,& Petakov, M.. (2020). Hypopituitarism in five PROP1 mutation siblings: long-lasting natural course and the effects of growth hormone replacement introduction in middle adulthood. in Pituitary
Springer, New York., 23(4), 400-408.
https://doi.org/10.1007/s11102-020-01049-9

Doknić M, Gašić V, Stojanović M, Pavlović S, Marinković S, Miljić D, Pekić S, Manojlović-Gacić E, Damjanović D, Soldatović I, Petakov M. Hypopituitarism in five PROP1 mutation siblings: long-lasting natural course and the effects of growth hormone replacement introduction in middle adulthood. in Pituitary. 2020;23(4):400-408.
doi:10.1007/s11102-020-01049-9 .

Doknić, Mirjana, Gašić, Vladimir, Stojanović, Marko, Pavlović, Sonja, Marinković, Snežana, Miljić, Dragana, Pekić, Sandra, Manojlović-Gacić, Emilija, Damjanović, Dusan, Soldatović, Ivan, Petakov, Milan, "Hypopituitarism in five PROP1 mutation siblings: long-lasting natural course and the effects of growth hormone replacement introduction in middle adulthood" in Pituitary, 23, no. 4 (2020):400-408,
https://doi.org/10.1007/s11102-020-01049-9 . .

TY  - JOUR
AU  - Doknić, Mirjana
AU  - Savić, Dragan
AU  - Manojlović-Gacić, Emilija
AU  - Raicević, Savo
AU  - Bokun, Jelena
AU  - Milenković, Tatjana
AU  - Pavlović, Sonja
AU  - Vreca, Misa
AU  - Anđelković, Marina
AU  - Stojanović, Marko
AU  - Miljić, Dragana
AU  - Pekić, Sandra
AU  - Petakov, Milan
AU  - Grujicić, Danica
PY  - 2018
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1095
AB  - Background: Intracranial germinomas (ICG) are uncommon brain neoplasms with extremely rare familial occurrence. Because ICG invades the hypothalamus and/or pituitary, endocrine dysfunction is one of the common determinants of these tumours. We present two brothers with a history of ICG. Patient 1 is a 25-year-old male who suffered from weakness of the right half of his body at the age of 18 years. Cranial MRI revealed a mass lesion in the left thalamus. He underwent neurosurgery, and the tumour was removed completely. Histopathological (HP) and immunohistochemical analyses verified the diagnosis of pure germinoma. He experienced complete remission of the tumour after radiation therapy. At the age of 22 years a diagnosis of isolated growth hormone deficiency (IGHD) was established and GH replacement was initiated. Molecular genetic analysis of the tumour tissue detected the mutation within exon 2 in KRAS gene. Patient 2 is a 20-year-old man who presented with diabetes insipidus at the age of 12 years. MRI detected tumour in the third ventricle and pineal region. After endoscopic tumour biopsy the HP diagnosis was pure germinoma. He received chemotherapy followed by radiotherapy and was treated with GH during childhood. At the age of 18 years GH replacement was reintroduced. A six-month follow-up during the subsequent two years in both brothers demonstrated the IGF1 normalisation with no MRI signs of tumour recurrence. Conclusion: To the best of our knowledge, so far only six reports have been published related to familial ICG. The presented two brothers are the first report of familial ICG case outside Japan. They have been treated successfully with GH therapy in adulthood.
PB  - Via Medica, Gdansk
T2  - Endokrynologia Polska
T1  - Clinical case seminar - familial intracranial germinoma
EP  - 618
IS  - 5
SP  - 612
VL  - 69
DO  - 10.5603/EP.2018.0060
ER  - 

@article{
author = "Doknić, Mirjana and Savić, Dragan and Manojlović-Gacić, Emilija and Raicević, Savo and Bokun, Jelena and Milenković, Tatjana and Pavlović, Sonja and Vreca, Misa and Anđelković, Marina and Stojanović, Marko and Miljić, Dragana and Pekić, Sandra and Petakov, Milan and Grujicić, Danica",
year = "2018",
abstract = "Background: Intracranial germinomas (ICG) are uncommon brain neoplasms with extremely rare familial occurrence. Because ICG invades the hypothalamus and/or pituitary, endocrine dysfunction is one of the common determinants of these tumours. We present two brothers with a history of ICG. Patient 1 is a 25-year-old male who suffered from weakness of the right half of his body at the age of 18 years. Cranial MRI revealed a mass lesion in the left thalamus. He underwent neurosurgery, and the tumour was removed completely. Histopathological (HP) and immunohistochemical analyses verified the diagnosis of pure germinoma. He experienced complete remission of the tumour after radiation therapy. At the age of 22 years a diagnosis of isolated growth hormone deficiency (IGHD) was established and GH replacement was initiated. Molecular genetic analysis of the tumour tissue detected the mutation within exon 2 in KRAS gene. Patient 2 is a 20-year-old man who presented with diabetes insipidus at the age of 12 years. MRI detected tumour in the third ventricle and pineal region. After endoscopic tumour biopsy the HP diagnosis was pure germinoma. He received chemotherapy followed by radiotherapy and was treated with GH during childhood. At the age of 18 years GH replacement was reintroduced. A six-month follow-up during the subsequent two years in both brothers demonstrated the IGF1 normalisation with no MRI signs of tumour recurrence. Conclusion: To the best of our knowledge, so far only six reports have been published related to familial ICG. The presented two brothers are the first report of familial ICG case outside Japan. They have been treated successfully with GH therapy in adulthood.",
publisher = "Via Medica, Gdansk",
journal = "Endokrynologia Polska",
title = "Clinical case seminar - familial intracranial germinoma",
pages = "618-612",
number = "5",
volume = "69",
doi = "10.5603/EP.2018.0060"
}

Doknić, M., Savić, D., Manojlović-Gacić, E., Raicević, S., Bokun, J., Milenković, T., Pavlović, S., Vreca, M., Anđelković, M., Stojanović, M., Miljić, D., Pekić, S., Petakov, M.,& Grujicić, D.. (2018). Clinical case seminar - familial intracranial germinoma. in Endokrynologia Polska
Via Medica, Gdansk., 69(5), 612-618.
https://doi.org/10.5603/EP.2018.0060

Doknić M, Savić D, Manojlović-Gacić E, Raicević S, Bokun J, Milenković T, Pavlović S, Vreca M, Anđelković M, Stojanović M, Miljić D, Pekić S, Petakov M, Grujicić D. Clinical case seminar - familial intracranial germinoma. in Endokrynologia Polska. 2018;69(5):612-618.
doi:10.5603/EP.2018.0060 .

Doknić, Mirjana, Savić, Dragan, Manojlović-Gacić, Emilija, Raicević, Savo, Bokun, Jelena, Milenković, Tatjana, Pavlović, Sonja, Vreca, Misa, Anđelković, Marina, Stojanović, Marko, Miljić, Dragana, Pekić, Sandra, Petakov, Milan, Grujicić, Danica, "Clinical case seminar - familial intracranial germinoma" in Endokrynologia Polska, 69, no. 5 (2018):612-618,
https://doi.org/10.5603/EP.2018.0060 . .