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 . .