Introduction: Congenital hypopituitarism (CH) is characterized by a deficiency of one or more pituitary hormones. The pituitary gland is a central regulator of growth, metabolism, and reproduction. The anterior pituitary produces and secretes growth hormone (GH), adrenocorticotropic hormone, thyroid-stimulating hormone, follicle-stimulating hormone, luteinizing hormone, and prolactin. The posterior pituitary hormone secretes antidiuretic hormone and oxytocin.Epidemiology: The incidence is 1 in 4,000–1 in 10,000. The majority of CH cases are sporadic; however, a small number of familial cases have been identified. In the latter, a molecular basis has frequently been identified. Between 80–90% of CH cases remain unsolved in terms of molecular genetics.Pathogenesis: Several transcription factors and signaling molecules are involved in the development of the pituitary gland. Mutations in any of these genes may result in CH including HESX1, PROP1, POU1F1, LHX3, LHX4, SOX2, SOX3, OTX2, PAX6, FGFR1, GLI2, and FGF8. Over the last 5 years, several novel genes have been identified in association with CH, but it is likely that many genes remain to be identified, as the majority of patients with CH do not have an identified mutation.Clinical manifestations: Genotype-phenotype correlations are difficult to establish. There is a high phenotypic variability associated with different genetic mutations. The clinical spectrum includes severe midline developmental disorders, hypopituitarism (in isolation or combined with other congenital abnormalities), and isolated hormone deficiencies.Diagnosis and treatment: Key investigations include MRI and baseline and dynamic pituitary function tests. However, dynamic tests of GH secretion cannot be performed in the neonatal period, and a diagnosis of GH deficiency may be based on auxology, MRI findings, and low growth factor concentrations. Once a hormone deficit is confirmed, hormone replacement should be started. If onset is acute with hypoglycaemia, cortisol deficiency should be excluded, and if identified this should be rapidly treated, as should TSH deficiency. This review aims to give an overview of CH including management of this complex condition.

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Context:The human fetal adrenal (HFA) is an integral component of the fetoplacental unit and important for the maintenance of pregnancy. Low kisspeptin levels during pregnancy are associated with miscarriage, and kisspeptin and its receptor are expressed in the HFA. However, the role of kisspeptin in fetal adrenal function remains unknown.Objective:To determine the role of kisspeptin in the developing HFA.Design:Experiments using H295R and primary HFA cells as in vitro models of the fetal adrenal. Association of plasma kisspeptin levels with HFA size in a longitudinal clinical study.Setting:Academic research center and tertiary fetal medicine unit.Participants:Thirty-three healthy pregnant women were recruited at their 12-week routine antenatal ultrasound scan.Main Outcome Measures:The spatiotemporal expression of Kiss1R in the HFA. The production of dehydroepiandrosterone sulfate (DHEAS) from HFA cells after kisspeptin treatment, alone or in combination with adrenocorticotropic hormone or corticotropin-releasing hormone. Fetal adrenal volume (FAV) and kisspeptin levels at four antenatal visits (∼20, 28, 34, and 38 weeks’ gestation).Results:Expression of Kiss1R was present in the HFA from 8 weeks after conception to term and was shown in the inner fetal zone. Kisspeptin significantly increased DHEAS production in H295R and second-trimester HFA cells. Serial measurements of kisspeptin confirmed a correlation with FAV growth in the second trimester, independent of sex or estimated fetal weight.Conclusions:Kisspeptin plays a key role in the regulation of the HFA and thus the fetoplacental unit, particularly in the second trimester of pregnancy.

The expression of P2X and P2Y receptor subtypes in the smooth muscle of the rat ovary during the oestrus cycle and pregnancy was examined using immunohistochemistry. RT-PCR studies of P2X receptor mRNA were also carried out. In the non-pregnant rats, P2X₂ receptor protein was dominant in the smooth muscle of perifollicular rings and blood vessels. P2X₁ protein expression was seen on vascular smooth muscle too, but little, if any, was present on perifollicular smooth muscle. No changes in P2X₁ or P2X₂ receptor expression were seen during the oestrous cycle. During early and mid-late pregnancy, there was a switch from P2X₂ to P2X₁ receptor protein expression in the smooth muscle of the perifollicular ring; P2X₁ receptors were also more prominently expressed than P2X₂ receptors on ovarian vascular smooth muscle in non-pregnant animals, but during late pregnancy the expression of P2X₂ receptors was found to equal that of the P2X₁ receptors. There was a return to non-pregnant P2 receptor subtype distribution 2 days after birth. Ovarian vascular and perifollicular smooth muscle showed immunoreactivity for P2Y₁, but not for P2X_3–7, P2Y₂ or P2Y₄ receptors. P2Y₁ receptor expression in ovarian smooth muscle of both blood vessels and follicular rings did not show significant changes during the oestrus cycle or pregnancy. RT-PCR studies indicated that P2X₁ and P2X₂ receptor mRNA was present in the ovary during pregnant and non-pregnant conditions. P2X_4–6 receptor mRNA was also present in all stages studied, however no immunostaining showing receptor protein for these subtypes was seen on the ovarian sections examined. In summary, purinergic signalling to ovarian perifollicular smooth muscle changed from P2X₂ to P2X₁ receptors during pregnancy, while there was an increase in P2X₂ receptor expression on vascular smooth muscle.