Congenital Combined Pituitary Hormone Deficiency Research Articles

Clinical Characteristics of Children with Combined Pituitary Hormone Deficiency and the Effects of Growth Hormone Treatment.

We aimed to describe the clinical characteristics of patients with congenital combined pituitary hormone deficiency (CPHD) and evaluate the first-year growth responses of individuals with CPHD and isolated growth hormone deficiency (IGHD) in order to establish the influence of other hormone deficiencies on growth response. This retrospective study was conducted in four tertiary care centers in Turkey. The records of patients diagnosed with CPHD (n=39) and severe IGHD (n=50) were collected. Cases with acquired lesions or chronic diseases were not included in the study. Data are presented as median (interquartile range). Among 39 patients (13 females; 33%) with a diagnosis of CPHD, the majority of patients (64%) presented initially with combined deficits at baseline examination, whereas isolated deficiencies (36%) were less prevalent. Among all patients with GH deficiency, TSH, ACTH, FSH/LH, and ADH deficiencies were present in 94%, 74%, 44%, and 9% of patients, respectively. Patients with CPHD were diagnosed at a younger age (4.9 (8.4) vs. 11.6 (4.1), p<0.001, respectively) and had lower peak GH concentrations (0.4 (1.8) vs. 3.7 (2.9), p<0.001, respectively) than patients with IGHD. Patients with IGHD and CPHD had similar first-year growth responses (Δheight SD score of 0.55 (0.63) vs. 0.76 (0.71), respectively, p=0.45). We established the nature and timing of numerous hormonal deficits emerging over time. We also identified that the existence of CPHD did not hinder growth response.

Congenital combined pituitary hormone deficiency associated with primary ovarian insufficiency: a case report

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Growth Hormone Is Beneficial for Induction of Spermatogenesis in Adult Patients With Congenital Combined Pituitary Hormone Deficiency.

BackgroundGonadotropins are effective in inducing spermatogenesis in patients with congenital combined pituitary hormone deficiency (CCPHD). Data on recombinant human growth hormone(rhGH) adjuvant treatment to improve gonadotropin-induced spermatogenesis are limited.Design and SettingThis retrospective study included 60 male patients with CCPHD on a relatively large case series in a single center from mainland China. Twenty-nine patients who received gonadotropin therapy alone were defined as the Gn group, while 31 patients treated with a combination of rhGH and gonadotropins were defined as GH/Gn group.ResultsSpermatogenesis rate was 96.77% (30/31) and 62.07% (18/29) in the GH/Gn and Gn group, respectively (P < 0.001). The time for initial sperm appearance in the GH/Gn group was shorter than in the Gn group (14 versus 23 months, P < 0.001). A higher level of serum testosterone was achieved in the GH/Gn group than in the Gn group (4.79 versus 3.38 ng/mL, P = 0.026). After adjustment for potential confounders, rhGH supplementation was an independent beneficial factor on spermatogenesis (HR = 2.294, 95% CI: 1.143-4.604, P = 0.019).ConclusionsrhGH induces earlier spermatogenesis in patients with CCPHD, which encourages the co-treatment with rhGH and gonadotropins in CCPHD patients.

Relationship between growth hormone deficiency and nonalcoholic fatty liver disease in patients with pituitary stalk interruption syndrome.

Pituitary stalk interruption syndrome (PSIS), characterized by thinning or disappearance of the pituitary stalk, hypoplasia of the anterior pituitary, and an ectopic posterior pituitary, can lead to congenital combined pituitary hormone deficiency. There is a high prevalence of various metabolic disorders, including nonalcoholic fatty liver disease (NAFLD), in this population. To investigate the characteristics of NAFLD in Chinese adult patients with PSIS and its association with growth hormone deficiency. Retrospective cross-sectional study in a tertiary referral center of China. Adult patients with PSIS diagnosed, followed up between September 2019 and August 2021, were consecutively enrolled. Abdominal ultrasonography images were evaluated and noninvasive fibrosis scores were determined to assess the severity of NAFLD. Anthropometric, clinical, and biochemical parameters were compared between patients with and without NAFLD. Logistic regression was performed to assess the independent effects of insulin-like growth factor-1 (IGF-1) on NAFLD. A total of 93 patients (77 men, 16 women, mean age: 29.6 ± 7.1 years) were included. The prevalence of NAFLD and advanced fibrosis/cirrhosis was 50.5% and 4.3%, respectively. Insufficient hormone therapy and prominent metabolic disorders, including central obesity, dyslipidemia, insulin resistance, and metabolic syndrome, were more common in the NAFLD (+) group. After adjusting for multiple variables, IGF-1 &lt;-2 standard deviation score (SDS) was found to be associated with an increased prevalence of NAFLD (odds ratio [OR]: 4.92, 95% confidence interval [CI]: 1.21-24.55, p = .035). Per 1 SDS increase in IGF-1 was associated with a 27% lower risk of NAFLD (OR: 0.73, 95% CI: 0.52-0.97, p = .042). NAFLD is a frequent comorbidity among Chinese adult patients with PSIS and is strongly associated with lower IGF-1 levels. Timely and appropriate hormone replacement, particularly growth hormone may contribute to decreasing the risk of NAFLD in these patients.

Novel STAR gene variant in a patient with classic lipoid congenital adrenal hyperplasia and combined pituitary hormone deficiency

We report the first case of classic lipoid congenital adrenal hyperplasia and combined pituitary hormone deficiency. We identified pathogenic variants in the STAR gene: a novel variant of c.126_127delCCinsG, namely, p.Thr44Profs*2 and an already reported variant of c.634C>T, namely, p.Gln212*. The association with combined pituitary hormone deficiency might be just a coincidence.

Genetic analysis of adult Slovenian patients with combined pituitary hormone deficiency.

Among genetic causes of combined pituitary hormone deficiency (CPHD), mutations of genes coding for transcription factors involved in pituitary development have been implicated. Congenital CPHD is a rare disease; therefore, it is important to expand the knowledge about incidence and regional distribution of specific mutations. The aim of this paper is to report results of genetic analyses of adult Slovenian patients with CPHD. Twenty-three adult Slovenian patients with early childhood onset CPHD were included in the study. Blood samples were collected through the GENHYPOPIT network to assess possible mutations of six genes (PROP1/HESX1/LHX4/LHX3/POU1F1) involved in the pituitary development following an established algorithm. In seven out of 23 patients (30%) a specific mutation in genes encoding pituitary transcription factors was discovered. In five patients, two different mutations of the PROP1 gene (c.150delA and c.301-302delAG) were identified. One patient was heterozygous for a missense variant in the LHX4 gene. Additionally, one patient was positive for a mutation in the gene coding for prokineticin receptor-2. Our study confirms that the two most common mutations of the PROP1 gene globally are also the most frequent mutations in the cohort of adult Slovenian patients with CHPD. Other mutations of pituitary transcription factor genes are extremely rare.

Molecular analysis of brazilian patients with combined pituitary hormone deficiency and orthotopic posterior pituitary lobe reveals eight different PROP1 alterations with three novel mutations.

Mutations in PROP1, HESX1 and LHX3 are associated with combined pituitary hormone deficiency (CPHD) and orthotopic posterior pituitary lobe (OPP). To identify mutations in PROP1, HESX1 and LHX3 in a large cohort of patients with CPHD and OPP (35 Brazilian, two Argentinian). We studied 23 index patients with CPHD and OPP (six familial and 17 sporadic) as well as 14 relatives. PROP1 was sequenced by the Sanger method in all except one sporadic case studied using a candidate gene panel. Multiplex ligation-dependent probe amplification (MLPA) was applied to one familial case in whom PROP1 failed to amplify by PCR. In the 13 patients without PROP1 mutations, HESX1 and LHX3 were sequenced by the Sanger method. We identified PROP1 mutations in 10 index cases. Three mutations were novel: one affecting the initiation codon (c.1A>G) and two affecting splicing sites, c.109+1G>A and c.342+1G>C. The known mutations, c.150delA (p.Arg53Aspfs*112), c.218G>A (p.Arg73His), c.263T>C (p.Phe88Ser) and c.301_302delAG (p.Leu102Cysfs*8), were also detected. MLPA confirmed complete PROP1 deletion in one family. We did not identify HESX1 and LHX3 mutations by Sanger. PROP1 mutations are a prevalent cause of congenital CPHD with OPP, and therefore, PROP1 sequencing must be the first step of molecular investigation in patients with CPHD and OPP, especially in populations with a high frequency of PROP1 mutations. In the absence of mutations, massively parallel sequencing is a promising approach. The high prevalence and diversity of PROP1 mutations is associated with the ethnic background of this cohort.

A case of an infant with congenital combined pituitary hormone deficiency and normalized liver histology of infantile cholestasis after hormone replacement therapy.

.Congenital combined pituitary hormone deficiency (CPHD) may present with cholestasis in the neonate or during early infancy. However, its precise mechanism is unknown. A 3-mo-old boy presented with cryptorchidism and hypoplastic scrotum after birth. Neonatal jaundice was noted but temporarily improved with phototherapy. Jaundice recurred at 2 mo of age. Elevated direct bilirubin (D-Bil) and liver dysfunction were found but cholangiography showed no signs of biliary atresia (BA). Liver biopsy findings showed giant cell formation of hepatocytes with hypoplastic bile ducts. Subsequent magnetic resonance imaging (MRI) of the head revealed a hypoplastic pituitary gland with an ectopic posterior lobe, and the patient was diagnosed with congenital CPHD based on decreased secretion of cortisol and GH by the pituitary anterior lobe load test. D-Bil levels promptly improved after hydrocortisone (HDC) replacement. We subsequently began replacement with levothyroxine (L-T4) and GH, and liver histology showed normal interlobular bile ducts at 8 mo old. This is the first case report of proven histological improvement after hormone replacement therapy. This suggested that pituitary-mediated hormones, especially cortisol, might be involved in the development of the bile ducts.

Wielohormonalna niedoczynność przysadki - problemy diagnostyczne

Wielohormonalna niedoczynność przysadki - problemy diagnostyczne

Congenital combined pituitary hormone deficiency patients have better responses to gonadotrophin-induced spermatogenesis than idiopathic hypogonadotropic hypogonadism patients

Do patients with congenital combined pituitary hormone deficiency (CCPHD) have different responses to gonadotrophin-induced spermatogenesis compared with those with idiopathic hypogonadotropic hypogonadism (IHH)? CCPHD patients have a better response to gonadotrophin therapy than IHH patients. Gonadotrophins are effective in inducing spermatogenesis in patients with hypogonadotropic hypogonadism. This retrospective cohort study included 75 patients, 53 of whom had IHH and 22 CCPHD. They were diagnosed, treated and followed up between January 2008 and December 2013. Combined gonadotrophin therapy, consisting of human chorionic gonadotrophin and human menopausal gonadotrophin, was administered for 24 months. The success rate of spermatogenesis (≥1 sperm in ejaculate), serum total testosterone level, testicle size and sperm concentration during the treatment, as well as the first time sperm were detected in the ejaculate, were compared between the two diagnostic groups. All patients were treated in Peking Union Medical College Hospital. Spermatogenesis was successfully induced in 85% of IHH patients and 100% of CCPHD patients after 24-month combined gonadotrophin treatment (P = 0.03). In comparison with IHH, CCPHD patients had larger mean testicle sizes during the gonadotrophin treatment at 6, 12, 18 and 24 months (all P < 0.05). The initial time for sperm appearance in IHH group (n = 45) and CCPHD group (n = 22) was 13.2 ± 5.9 versus 10.4 ± 3.8 months (P = 0.045). Generally, CCPHD patients had higher sperm counts [median (quartiles)] than IHH patients during the treatment, but the difference was only statistically significant at 12 months of treatment, 3.3 (1.8, 12.0) versus 1.0 (0.0, 4.6) million/ml, P = 0.001. There was a higher level of serum total testosterone [mean (SD)] in the CCPHD group than the IHH group (676 ± 245 versus 555 ± 209 ng/dl, P = 0.035). First, the inherent nature of a retrospective designed study was a main shortcoming. Secondly, pathological gene mutations in IHH and CCPHD patients should be further investigated. Clarification of the underlying mechanisms between cryptorchidism and mutated genes may provide more information for the divergent therapeutic responses between two groups. Only a minority of patients were actively seeking to have children so information about fertility is limited. CCPHD patients had a lower incidence of cryptorchidism and a better response to gonadotrophin therapy than IHH patients, reflecting multiple defects on the different levels of reproduction axis in IHH. Furthermore, growth hormone is not indispensable for spermatogenesis in CCPHD patients. The study was supported by Natural Science Foundation of China (No: 81100416). None of the authors has any conflicts of interest to declare.

A case of congenital combined pituitary hormone deficiency who showed respiratory distress and hypoglycemia soon after birth

Congenital combined pituitary hormone deficiency (CCPHD) is a rare disease, presenting with respiratory distress, hypoglycemia and jaundice soon after birth. It is caused by .pituitary aplasia or hypoplasia or abnormality of transcription factor which related to pituitary development. We describe a Japanese patient with CCPHD, who presented with respiratory distress, hypoglycemia and jaundice soon after birth. The patient is now 13 months old Japanese girl. She was born by cesarean section because of fetal distress with 39 weeks and 4 days gestation after an uneventful pregnancy. Her parents were unrelated. Birth length and weight were 43.8cm (-2.2SD) and 2,100g and Apgar scores were 8 at both of 1 and 5 min. She had showed tachypnea and cyanosis since soon after birth and taken nasal-CPAP. However respiratory distress had not improved. She had also showed jaundice and hypoglycemia and was treated with phototherapy and infusion therapy. At 6 days old, we found her FT4 level was 0.4 pg/ml and TSH level was below 0.01 μIU/ml. She was suspected CPHD and anterior pituitary hormone levels were assessed. All of anterior pituitary hormones were undetectable. Anterior pituitary was not visible, posterior pituitary was detected at normal position and there were no other abnormality on brain magnetic resonance imaging. We diagnosed her as CCPHD and hydrocortisone was started since 6 days old and levothyroxine since 8 days old. After that respiratory distress and jaundice had improved rapidly. But hypoglycemia had appeared again after interrupting infusion therapy. GH level after arginine stimulation was also undetectable. She had also started growth hormone therapy since 25 days old and she has had no hypoglycemic episodes after that. Her length and weight were 70.3cm (-1.2SD) and 8,485g at 1 year old. GH replacement therapy that was started soon after diagnosis was able to prevent the severe growth retardation. She has no gene abnormalities of transcription factors, HESX1, LHX4 and OTX2, that involves pituitary development. Further studies are needed for investigating genetic basis of this patient. Careful and prompt clinical, endocrinological and neuroradiological assessment are needed for diagnosis of hypopituitarism in patients who show prolonged respiratory distress, hypoglycemia or jaundice soon after birth. Written informed consent was obtained from the patient's parent or guardian for publication of this abstract and any accompanying images. A copy of the written consent is available for review by the Editor of this journal.

PO-0592 Distinguishing Congenital Combined Pituitary Hormone Deficiency From Biliary Atresia As A Cause Of Cholestasis In Infants

<h3>Background and aims</h3> Neonatal cholestasis is caused by either biliary atresia or intrahepatic cholestasis. Congenital combined pituitary hormone deficiency (CPHD) is a rare disease and a recognised cause of intrahepatic cholestasis. It is important to differentiate cholestasis due to this entity from cholestasis due to biliary atresia, since both diseases can cause jaundice at about 1 month of age. However, doing so in a timely fashion remains a diagnostic dilemma. This retrospective study was performed to clarify differences between cholestasis due to congenital CPHD and cholestasis due to biliary atresia. <h3>Methods</h3> From 2004 to 2010, 4 infants (2 boys and 2 girls) with cholestasis due to congenital CPHD were admitted to Nagoya City University Hospital. Head magnetic resonance imaging of the 4 infants revealed an invisible pituitary stalk; 3 of these 4 infants had an ectopic posterior pituitary. Liver biopsy was performed in 3 of the 4 infants, and histological findings included giant cell hepatitis. Findings from these 4 infants were then compared with those from55 infants treated in our hospital for cholestasis due to biliary atresia. <h3>Results</h3> The results showed a significant difference in mean gamma-glutamyl transpeptidase levels between the two groups of infants (115.0 IU/l vs. 553.0 IU/l, respectively). <h3>Conclusions</h3> The gamma-glutamyl transpeptidase level was found to be useful for distinguishing congenital CPHD from biliary atresia as the cause of cholestasis. The diagnosis of hypopituitarism should always be considered in infants with unexplained neonatal hepatitis.

Genetic analyses of bone morphogenetic protein 2, 4 and 7 in congenital combined pituitary hormone deficiency

BackgroundThe complex process of development of the pituitary gland is regulated by a number of signalling molecules and transcription factors. Mutations in these factors have been identified in rare cases of congenital hypopituitarism but for most subjects with combined pituitary hormone deficiency (CPHD) genetic causes are unknown. Bone morphogenetic proteins (BMPs) affect induction and growth of the pituitary primordium and thus represent plausible candidates for mutational screening of patients with CPHD.MethodsWe sequenced BMP2, 4 and 7 in 19 subjects with CPHD. For validation purposes, novel genetic variants were genotyped in 1046 healthy subjects. Additionally, potential functional relevance for most promising variants has been assessed by phylogenetic analyses and prediction of effects on protein structure.ResultsSequencing revealed two novel variants and confirmed 30 previously known polymorphisms and mutations in BMP2, 4 and 7. Although phylogenetic analyses indicated that these variants map within strongly conserved gene regions, there was no direct support for their impact on protein structure when applying predictive bioinformatics tools.ConclusionsA mutation in the BMP4 coding region resulting in an amino acid exchange (p.Arg300Pro) appeared most interesting among the identified variants. Further functional analyses are required to ultimately map the relevance of these novel variants in CPHD.

Unilateral agenesis of internal carotid artery associated with congenital combined pituitary hormone deficiency and pituitary stalk interruption without HESX1, LHX4 or OTX2 mutation: a case report

Agenesis of internal carotid artery (ICA) is an unusual finding in subjects with congenital Combined Pituitary hormone deficiency (CPHD) with only nine cases being reported to date but to our best knowledge none of them was genetically investigated. A 10-years old girl presented with severe growth failure (height 103 cm) with substantial bone age delay (3 years). She had no history of perinatal insults or familial CPHD. There was no evidence of mental retardation or craniofacial dysmorphism or ophtalmological abnormalities. She was first diagnosed with GH and TSH deficiency. Cerebral magnetic resonance imaging (MRI) showed hypoplastic anterior pituitary, flat sella turcica, absent pituitary stalk with ectopic posterior pituitary as well as agenesis of the left ICA and the left carotid canal. Genomic analysis of pituitary transcription factor HESX1, LHX4 and OTX2 showed no mutations. Treatment with GH and thyroxine was started. The patient remained free of neurovascular symptoms for 5 years but she presented at the age of 15 years with delayed puberty related to an evolving gonadotropin deficiency. ICA agenesis associated with CPHD is unusual and is often asymptomatic in children. Since the CPHD with pituitary stalk interruption cannot be due to HESX1, LHX4 or OTX2 mutation in our case, other pathogenetic mechanisms may be responsible for CPHD associated with unilateral ICA agenesis.

The Course of Neonatal Cholestasis in Congenital Combined Pituitary Hormone Deficiency

Neonatal cholestatic hepatitis is frequently associated with congenital combined pituitary hormone deficiency (CCPHD). Data on the course of this hepatopathy are scarce. We retrospectively analyzed the data of all CCPHD infants with cholestasis who presented at the University Children's Hospital, Tuebingen. All infants (n = 9; 2 females) presented with early and prolonged jaundice, failure to thrive and recurrent hypoglycemia. All males had micropenis and 3/7 cryptorchidism. Median age at diagnosis was 1.4 months. Cholestasis began at a median age of 13 days (range 5-31) and resolved at 88 days (54-174). Maximum direct bilirubin level was 6.9 mg/dl (2.4-11.6). Peaks of ALP (median 721 U/l), ALT (148 U/l) and AST (195 U/l) occurred 2-4 weeks later, while GGT levels were elevated in only two infants (167 U/l). Functional liver parameters were always normal. Liver biopsies (n = 4) showed canalicular cholestasis and mild portal eosinophilic infiltration. TEBIDA radioisotope excretion into the intestinal tract was blocked. Substitution with Lthyroxine, hydrocortisone and growth hormone seemed to accelerate the cure from cholestasis. Liver function at follow-up (median 4 yr) stayed normal. Cholestasis in CCPHD follows the course described here, frequently with normal GGT levels.

Waxing and waning of a pituitary mass in a young woman with combined pituitary hormone deficiency (CPHD) due to a PROP-1 mutation

We describe a 23-yr old woman with congenital combined pituitary hormone deficiency (CPHD) diagnosed at 10 years of age and a large sellar mass discovered at the age of 19 years, when her first pituitary MRI was performed. The mass (height: 13 mm) extended to the suprasellar region, close to the optic chiasm, showed signal hyperintensity in T1- and hypointensity in T2-weighted images, with no enhancement after gadolinium injection. Although these MRI features were suggestive of Rathke's cleft cyst, cystic craniopharyngioma or previous hemorrhage, no visual symptoms, diabetes insipidus and/or hyperprolactinemia were present. In addition, similar MRI findings had been previously described in a few cases of CPHD due to PROP-1 mutations, which prompted us to carry out a molecular study before any therapeutic decision was made. A 301302delAG PROP-1 mutation was found in her DNA and the patient was closely followed through ophthalmologic evaluation and pituitary MRI scans. During a 3.6-year follow-up, we were able to document a marked initial growth followed by shrinkage and recurrent growth of the PROP-1 sellar mass. The patient remains free of compressive neuro-ophthalmological signs, suggesting that surgical intervention is unnecessary in these cases. However, they must be followed closely with sellar MRIs and campimetry until the mass completely regresses.

Ghrelin-stimulation test in the diagnosis of canine pituitary dwarfism

This study investigated whether ghrelin, a potent releaser of growth hormone (GH) secretion, is a valuable tool in the diagnosis of canine pituitary dwarfism. The effect of intravenous administration of ghrelin on the release of GH and other adenohypophyseal hormones was investigated in German shepherd dogs with congenital combined pituitary hormone deficiency and in healthy Beagles. Analysis of the maximal increment (i.e. difference between pre- and maximal post-ghrelin plasma hormone concentration) indicated that the GH response was significantly lower in the dwarf dogs compared with the healthy dogs. In none of the pituitary dwarfs, the ghrelin-induced plasma GH concentration exceeded 5 μg/l at any time. However, this was also true for 3 healthy dogs. In all dogs, ghrelin administration did not affect the plasma concentrations of ACTH, cortisol, TSH, LH and PRL . Thus, while a ghrelin-induced plasma GH concentration above 5 μg/l excludes GH deficiency, false-negative results may occur.

Cholestasis in neonates with congenital combined pituitary hormone deficiency: there is etiology besides endocrinology

Systematic studies on the neonatal hepatitis syndrome associated with congenital combined pituitary hormone deficiency (CCPHD) are missing. We analyzed in a retrospective and longitudinal study all children with CCPHD who presented with hypoglycemia and/or cholestasis at neonatal age and were referred to the Paediatric Endocrinology Section Tübingen between 1970 and 2004 (n=16; 9 females). Median follow-up was 5yrs (range, 0.5–25.7). All neonates were deficient for fT4, cortisol and GH. All males had a micropenis indicating gonadotropin deficiency. 2/16 were deficient for ADH.

Lack of aberrations of the BMP4, BMP2, and PTX1 genes in a patient with pituitary hypoplasia, os odontoideum, renal dysplasia, and right leg anomalies

We report on a 15-year-old girl who presented with pituitary hypoplasia, os odontoideum, renal dysplasia, an asymmetrically short right leg, and postaxial hypodactyly of the right foot. Her endocrinological data showed anterior pituitary hormone deficiency. The fact that she had healthy parents and an elder sister suggests that she had either a de novo mutation or autosomal recessive inheritance. We speculated that bone morphogenetic protein 4 (BMP4), BMP2, or pituitary homeobox 1 (PTX1) might be the responsible genes in this patient based on the similarity of her clinical symptoms and phenotypes to knock-out mice of these genes. We performed mutation analysis of these genes by direct sequencing of genomic DNA. In BMP2 gene, AGA right curved arrow AGT transversion in exon 3, converting arginine to serine was detected. In PTX1 gene, transversion of GCC right curved arrow GGC in exon 2, converting alanine to glycine at codon 184 was found in the patient and controls. We did not find any non-sense mutations although 5 polymorphisms of these genes were found. This constellation of findings may represent a new entity of congenital combined pituitary hormone deficiency.

MR imaging of the pituitary gland in children and young adults with congenital combined pituitary hormone deficiency associated with PROP1 mutations.

The aim of this study was to clarify the relationship between morphologic changes of the pituitary gland and the genotype of Prophet of Pit-1 (PROP1), a newly discovered gene responsible for congenital combined pituitary hormone deficiency, in a series of eight humans with this disorder. Congenital hypoplasia of the anterior pituitary gland is the most common MR imaging finding in patients with combined pituitary hormone deficiency. Our findings suggest a crucial role for PROP1 in pituitary organogenesis as well as anterior pituitary cell differentiation.