Therapy-Induced Growth and Sexual Maturation in a Developmentally Infantile Adult Patient with a PROP1 Mutation.

BACKGROUND: Hypopituitarism as a result of PROP1 (prophet of PIT1) mutation represents the most common genetic cause of combined deficiency of pituitary hormones and due to growth retardation it is typically diagnosed in childhood. CASE DESCRIPTION: We present a unique case report of a prepubertal woman with growth retardation in whom combined pituitary hormone deficiency [central hypopituitarism, hypogonadism, and growth hormone (GH) deficiency] caused by homozygous mutation c.150delA in the PROP1 gene was diagnosed late in young adulthood due to unfavorable life circumstances. Through cautiously combined GH therapy and sex hormone therapy, she has achieved better than expected height (exceeding predictions based on family height) and sexual maturation, including regular menstrual cycles. CONCLUSION: Early diagnosis of panhypopituitarism due to PROP1 mutation is essential for successful treatment; however, our case report shows that carefully titrated GH treatment and sex hormone substitution, although initiated in adulthood, enable restoration of physiological growth and sexual development in a hormonally infantile adult woman with a PROP1 mutation.

[The transrectal ultrasonography of prostate in men with congenital hypogonadism treated by long term testosterone replacement therapy]. / Transrektální sonografie prostaty u muzu s vrozeným hypogonadismem léceným dlouhodobou substitucní terapií testosteronem.

BACKGROUND: The aim of the study was to evaluate prostate transrectal ultrasonography findings in men with congenital hypogonadism treated by long term testosterone replacement therapy. METHODS: We have gradually included 31 men with congenital hypogonadism in period of 2001-2011. The average follow-up was 7.3 years (2 months - 10.8 years). We have used Sustanon® 250 i.m. every 3 weeks or Nebido® i.m. every 3 months for continual testosterone replacement therapy. We performed to all patients the transrectal ultrasonography of prostate and seminal vesicles by biplanar rectal probe every 6 months. RESULTS: During the transrectal ultrasonography we observed in 22 (71.0 %) patients changes in prostatic tissue. In case of 12 patients were diagnosed asymptomatic prostatic cysts, in 9 patients prostatolithiasis and in 5 patients changes in echogenity of prostatic tissue. In 2 patients was found simultaneous occurrence of prostatic cyst and prostolithiasis, in further 2 patients simultaneous occurrence of hyperechogenic prostatic lesion and prostatolithiasis. The above described findings were diagnosed in 5 patients in the treatment lasting from 3 to 5 years, for the other 17 men with hormone replacement therapy longer than 5 years. CONCLUSIONS: The study presents long term results of complex treatment in patients with disorders of sexual development, onset and progress of puberty. The long term treatment of these patients in interdisciplinary cooperation of endocrinologist and andrologist may significantly contribute to clarify an impact of testosterone replacement therapy on prostate development.

[Calcitriol endocrine microsystems - developmental aspects and prerequisites for their lifelong functionality]. / Endokrinní mikrosystémy kalcitriolu - vývojové aspekty a predpoklady jejich celozivotní funkcnosti.

New findings regarding the local synthesis of calcitriol, its binding on nuclear receptors and its regional tissue effects have led to discovery of its endocrine microsystems. Their application in growing organisms and their lifelong functionality provide possible preventive and treatment modalities in multiple ailments, mostly by natural and minimally expensive means.

Auxological and endocrine phenotype in a population-based cohort of patients with PROP1 gene defects.

OBJECTIVE: Multiple pituitary hormone deficiency (MPHD) may result from defects of transcription factors that govern early pituitary development. We aimed to establish the prevalence of HESX1, PROP1, and POU1F1 gene defects in a population-based cohort of patients with MPHD and to analyse the phenotype of affected individuals. DESIGN AND METHODS: Genomic analysis was carried out on 74 children and adults with MPHD from the Czech Republic (including four sibling pairs). Phenotypic data were collected from medical records and referring physicians. RESULTS: One patient carried a heterozygous mutation of POU1F1 (71C > T), and 18 patients (including three sibling pairs) had a PROP1 mutation (genotypes 150delA/301delGA/9/, 301delGA/301-delGA/8/, or 301delGA/349T > A/1/). A detailed longitudinal phenotypic analysis was performed for patients with PROP1 mutations (n = 17). The mean ( +/-s.d.) birth length SDS of these patients (0.12 +/- 0.76) was lower than expected based on their mean ( +/-s.d.) birth weight SDS (0.63 +/- 1.27; P = 0.01). Parental heights were normal. The patients' mean ( +/-s.d.) height SDS declined to -1.5 +/- 0.9, -3.6 +/- 1.3 and -4.1 +/- 1.2 at 1.5, 3 and 5 years of age, respectively. GH therapy, initiated at 6.8 +/- 3.2 years of age (mean dose: 0.022 mg/kg per day), led to substantial growth acceleration in all patients. Mean adult height (n = 7) was normal when adjusted for mid-parental height. ACTH deficiency developed in two out of seven young adult patients. CONCLUSIONS: PROP1 defects are a prevalent cause of MPHD. We suggest that testing for PROP1 mutations in patients with MPHD might become standard practice in order to predict risk of additional pituitary hormone deficiencies.