PROP1Mutations Cause Progressive Deterioration of Anterior Pituitary Function including Adrenal Insufficiency: A Longitudinal Analysis

Böttner, Antje; Keller, E; Kratzsch, Jürgen; Stobbe, H; Weigel, Johannes; Keller, Alexandra; Hirsch, Wolfgang; Kieß, Wieland; Blum, Werner; Pfäffle, Roland

doi:10.1210/jc.2004-0661

Cited by 128 publications

(87 citation statements)

References 38 publications

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“…In fact, the emergence of a second deficiency of anterior pituitary function was predicted by the finding of PPE (and a type 3 TSH response) in patient 16, who initially was considered TSH deficient only. This also draws attention to the fact that in patients diagnosed with isolated TSH deficiency, additional pituitary hormone deficiencies might emerge over time (47). These findings are of particular importance because MPHD is a condition with complex morbidity and high mortality (8,10).…”

Section: Discussionmentioning

confidence: 97%

Role of the Thyrotropin-Releasing Hormone Stimulation Test in Diagnosis of Congenital Central Hypothyroidism in Infants

Tijn

Vijlder

Vulsma

2008

The Journal of Clinical Endocrinology &Amp; Metabolism

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lp;&-8qContext:A shortage of thyroid hormone during prenatal life and the first years after birth results in a spectrum of neuropsychological disorders, depending on the duration and severity of the deficiency. In the case of congenital hypothyroidism of central origin (CH-C), the majority of patients have multiple pituitary hormone deficiencies (MPHD). This condition poses an additional threat to postnatal central nervous system development, primarily on account of neuroglycopenia due to ACTH/cortisol deficiency with or without additional GH deficiency. Therefore, in CH-C, rapid diagnosis is even more urgent than in congenital hypothyroidism of thyroidal origin. Objective:In the assessment of hypothalamic-pituitary-thyroid function, we considered the pituitary response to iv administration of TRH (TRH test) pivotal. We evaluated the usefulness of the TRH test in a cohort of infants with neonatal congenital hypothyroidism screening results indicative of CH-C by analyzing the results within the framework of investigations of the anatomical and functional integrity of the hypothalamo-hypophyseal system. Design and Setting:The study was a Dutch nationwide prospective study (1994 -1996). Patients were included if neonatal congenital hypothyroidism screening results were indicative of CH-C and patients could be tested within 3 months of birth. Patients:Ten male and five female infants with CH-C, detected by neonatal screening, and six infants with false-positive screening results, nonthyroidal illness, or transient hypothyroidism, were included in the study. Main Outcome Measures:Results of TRH tests, within the framework of extensive endocrinological examinations and cerebral magnetic resonance imaging, were measured.Results: All patients with type 3 TSH responses to TRH had MPHD, and the majority (67%) of patients with type 2 responses had isolated TSH deficiency. Conclusions:The TRH test has a pivotal role in the diagnosis of TSH deficiency in young infants. Abnormal TRH test results, especially a type 3 response, urge immediate assessment of integral hypothalamic-pituitary function because the majority of patients have MPHD. T hyroid hormone is extremely important for normal brain development. A shortage of thyroid hormone during prenatal life and the first years after birth results in a spectrum of neuropsychological disorders, depending on the duration and severity of the deficiency (1, 2). In the case of congenital hypothyroidism (CH), the damage appears to be especially related to postnatal T 4 deficiency (3). Apparently, central nervous system development can at least be partly preserved by

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Section: Discussionmentioning

confidence: 97%

Role of the Thyrotropin-Releasing Hormone Stimulation Test in Diagnosis of Congenital Central Hypothyroidism in Infants

Tijn

Vijlder

Vulsma

2008

The Journal of Clinical Endocrinology &Amp; Metabolism

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“…The cohort was extended by inviting collaboration from centers across Europe and the United States; 6 centers from Central and Eastern Europe contributed PROP1-deficient patients to join the study cohort. Thus, we included Czech patients from a population-based testing for genetic causes of pituitary insufficiency in childhood and adulthood [6], as well as pediatric and adult patients from Germany [16], Poland, Lithuania, and Russia. The study cohort was also complemented by several adult patients who originated from Austria [14].…”

Section: Methodsmentioning

confidence: 99%

“…The true nature, prevalence, and natural development of pituitary masses due to PROP1 mutations have so far been studied only in limited cohorts of patients [3,4,5,13,14,15,16,17,18,19]; therefore, we aimed to establish a representative group of affected patients allowing more detailed analysis over the lifespan.…”

Section: Introductionmentioning

confidence: 99%

Mutations and Pituitary Morphology in a Series of 82 Patients with PROP1 Gene Defects

Obermannová

Pfaeffle²,

Zygmunt-Górska³

et al. 2011

Horm Res Paediatr

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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.

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“…Therefore, the underlying mechanism of the cortisol deficiency appearing with advancing age in PROP1 -deficient patients remains unknown [18,19,20]. Conceivably, the gradual impairment of corticotroph function is the result of general pituitary dysfunction.…”

Section: Discussionmentioning

confidence: 99%

PROP1 Gene Mutations and Pituitary Size: A Unique Case of Two Consecutive Cycles of Enlargement and Regression

et al. 2007

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Background: Pituitary enlargement, which can regress with time, has been described in a number of PROP1-deficient patients. We report a PROP1-deficient patient with a unique variation in pituitary size. Case Description: A 4-year-old boy was first examined in 1989 for short stature (–2.3 standard deviation score). Growth hormone (GH) insufficiency was confirmed, and human GH (hGH) therapy was initiated and administered up to the age of 18.2 years. Levothyroxine was added 6 months after hGH initiation. Pituitary magnetic resonance imaging (MRI) obtained when the patient was 5 years old showed an enlarged pituitary gland, which grew larger by the age of 8.5 years and then regressed to normal size by the time the patient was 9.8 years old. MRI when the patient was 19 years old disclosed pituitary reenlargement, and another 3 years later indicated regression. On DNA analysis, the patient was found to be homozygous for the mutation 301–302ΔGA of the PROP1 gene. When the patient was 18.8 years old and asymptomatic, an impaired cortisol response to glucagon was detected. Conclusions: Regression of the pituitary enlargement in PROP1-deficient patients does not seem to constitute an end stage with respect to pituitary pathology. Further changes in pituitary morphology and size can be expected; therefore, long-term follow-up with pituitary MRI is advised.

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PROP1Mutations Cause Progressive Deterioration of Anterior Pituitary Function including Adrenal Insufficiency: A Longitudinal Analysis

Cited by 128 publications

References 38 publications

Role of the Thyrotropin-Releasing Hormone Stimulation Test in Diagnosis of Congenital Central Hypothyroidism in Infants

Role of the Thyrotropin-Releasing Hormone Stimulation Test in Diagnosis of Congenital Central Hypothyroidism in Infants

Mutations and Pituitary Morphology in a Series of 82 Patients with <i>PROP1</i> Gene Defects

<i>PROP1</i> Gene Mutations and Pituitary Size: A Unique Case of Two Consecutive Cycles of Enlargement and Regression

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