Cost-effectiveness of somatrogon in the Spanish pediatric population with growth hormone deficiency.

OBJECTIVE: To analyze the cost-effectiveness of weekly somatrogon compared to daily growth hormones (GH-d) in the pediatric population of Spain with growth hormone deficiency (GHD). METHODS: Markov model with two states (patients with or without GH-d or somatrogon treatment) in prepubertal children (3 to 11 years and 3 to 12 years in girls and boys, respectively) with GHD in isolation or as part of multiple pituitary hormone deficiency and without previous treatment, from the perspective of the National Health System. The simulation of the economic model ends at the age of 18. The costs of hormones and monitoring were obtained from Spanish sources. The utilities were obtained from the literature. Spanish clinical experts validated the assumptions of the model. RESULTS: In the deterministic analysis, somatrogon would be cost-effective, compared to GH-d, with a cost per QALY (quality-adjusted life year) gained of €19,259 and a clinically relevant QALY gain (0.336). This result was confirmed in deterministic sensitivity analyses. According to the probabilistic analysis, somatrogon would be the dominant treatment, with a 61% probability of a willingness to pay of €25,000 per QALY gained. CONCLUSION: Compared to GH-d, somatrogon is cost-effective in the Spanish pediatric population with GHD.

Papillary thyroid carcinoma after recombinant GH therapy for Turner syndrome.

Turner syndrome (TS) has been included for several years among the indications for GH treatment, generally with satisfactory outcomes. Nevertheless, the long-term effects of this treatment in non-GH deficient patients are not fully known. The incidence of thyroid carcinoma is rare in patients during childhood, it is unusual to find this neoplasia in children under sixteen years old. This article reports the cases of two Spanish patients with papillary thyroid carcinoma after GH treatment for TS. Recent studies have indicated a possible relationship between the GH-IGF axis and the pathogenesis of neoplasias, questioning the chance association of these two pathologies. In line with this, we detected GH receptor expression in the papillary carcinoma cells. Long-term prospective studies are required to clarify the possible effects of GH treatment on the risk of neoplasia.

Endocrine disruptors.

Man does not come into the world pre-determined. The lifetime set of environmental conditions impinging on a given individual has been termed the ambiome, which together with the genome and the proteome determines each individual's development and construction. Among the most important elements making up the ambiome are endocrine disruptors. An endocrine disruptor is a chemical substance that has adverse effects on an organism or its progeny, through the endocrine system. The number of known endocrine disruptors is large and continuously increasing, and includes both naturally occurring and synthetic substances. We are convinced that they entail genuine problems; although it is difficult to assess their magnitude and real significance, and we will certainly need some time, probably several decades, to obtain conclusive results; but even so, we consider that the existing body of evidence about effects of endocrine disruptors on human health is sufficiently worrying to justify precautionary measures.

Therapeutic optimization of growth hormone deficiency in children and adolescents.

More than 40 years after the introduction of growth hormone (GH) treatment, many questions remain unanswered. Clearly, with the availability of rhGH and with current treatment protocols, treatment efficacy has improved. However, it still remains unclear whether current treatment protocols are the best possible. Before GH deficiency was recognized as a chronic disease, children only received treatment until normal adult height had been reached. However, it has recently been shown that not all GH-dependent body structures and functions normalize in parallel with height. Furthermore, in adolescents with GH deficiency, the interruption of GH substitution leads to severe hormone deficiency symptoms in adulthood. In the case of an adolescent who meets the biochemical criteria for GH deficiency in adulthood, but does not show alterations of metabolism, body structure, or emotional state, should GH treatment be started in adolescence, or only if and when the clinical syndrome becomes apparent? This is a difficult question to which there is not yet any clear answer, and we suggest that there is a need for further studies in this area. Furthermore, it will be necessary to re-evaluate the situation of patients who have completed their growth, and definitive conclusions will require controlled studies.

Genetic basis of short stature.

Growth in humans is a complex process controlled by many genetic and non-genetic factors. It is influenced by endogenous factors like genetics, hormones and metabolism as well as exogenous ones like nutrition, physical activity and psychosocial status. Growth is one of the most sensitive markers of children's health, their nutritional status and genetic background. Besides, deviation from normality may be the first manifestation of an underlying congenital or acquired pathology. Thus, it is important to know the growth process and the disorder that can disturb it. Short stature is defined as a condition in which the height of an individual is more than 2 SD below the corresponding mean height for a given age, sex and population group. This disorder is a major concern for patients and their parents, and represents a diagnostic challenge to the clinician. A correct diagnosis is particularly important in view of the availability of effective, but costly, therapy in a small subset of cases. Cytogenetic and molecular analysis can be of great value in this diagnostic process. Emphasis can be made on the advances of molecular genetics, which have characterized human genes involved in the hypothalamus-pituitary-GH axis such as GH, POU1F1, PROP1, GHRHR, GHR, IGF, IGFR, HESX1, LHX3, LHX4, among others. Our current line of investigation is related to the study of some of these genes and the genotype-phenotype relation with the aim of identifying features that add some more light on the genetic origins of short stature.