The pituitary gland produces hormones that play important roles in both the development and homeostasis of the body. Ontogeny of the anterior and posterior pituitary is orchestrated by inputs from neighboring tissues, cellular signaling molecules and transcription factors. Disruption of expression or function of these factors has been implicated in the etiology of combined pituitary hormone deficiency (CPHD). These include the transcription factors HESX1, PROP1, POU1F1, LHX3, LHX4, OTX2, SOX2, SOX3 and GLI2. This review focuses on summarizing most recent mutations in LHX4 and OTX2 responsible for pituitary hormone deficiency. In both genetic defects of LHX4 and OTX2, there is high variability in clinical manifestations even in the same family. In addition, there is no clear phenotype-genotype correlation. These findings indicate that the other genetic and/or environmental factors influence the phenotype. In addition, the variability might reflect a plasticity during pituitary development and maintenance. Over the past two decades, a genetic basis for pituitary hormone deficiency and the mechanism of pituitary development have been clarified. It should be kept in mind that this review is not comprehensive, and defects of other transcriptional factors have been described in patients with CPHD. Furthermore, the causes in many patients with CPHD have not yet been determined. Therefore, continuing efforts for the clarification of the etiology are necessary.

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To evaluate the psychosocial status of short children with and without growth hormone therapy (GHT) and that of their parents, self-administered questionnaires were collected from patients and parents who regularly visit the outpatient clinics participating in the Child Health and Development Network. Completed questionnaires were received for one hundred and thirteen patients with GHT and 67 patients without GHT. According to the parents, both children with GHT and without GHT have no difficulty in their daily lives (89% vs. 95%) and are positive (56% vs. 65%), respectively. Ninety-eight percent of parents of children with GHT and 83% of parents of children without GHT had expected the current treatment strategy to be effective. Parents of children with GHT are more satisfied with the current therapy than those without GHT (79% vs. 50%), and feel less anxiety about the on-going therapy than (31% vs. 58%, respectively). Children treated with or without equally reported having no difficulty in their daily lives (90% vs. 93%), and being positive in their lives (81% vs. 75%, respectively) despite their short stature. Although less than one third of the patients have been bullied in their classroom (26% with GHT vs. 29% without GHT), younger and shorter children tend to be bullied more often. Short children undergoing GHT and their parents have anxiety regarding their height and expectations of the effect of GHT. It is important for doctors to inform their patients regarding realistic height expectations before starting GHT. Additionally, medical consultation is recommended for patients who remain below -2 SD in height despite GHT.

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Leprechaunism is a rare autosomal recessive disease that is characterized by severe insulin resistance. This disease is caused by a defective insulin receptor and features abnormal glucose metabolism and retarded intrauterine and postnatal growth. However, there are few reports on the long-term course of leprechaunism. We reported the long-term clinical course and rh-IGF-1 treatment in a patient with leprechaunism. During follow-up her diabetes gradually deteriorated despite of treatment of rh-IGF-1. Furthermore, she developed endometrioid adenocarcinoma at the age of 24 yr. The development of endometrial disease must be carefully followed up in this disease.

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