A 42-Year-Old Woman with Untreated Growth Hormone Insensitivity, Diabetic Retinopathy, and Gene Sequencing Identifies a Variant of Laron Syndrome

Abstract

Patient: Female, 42 Final Diagnosis: Never-treated growth hormone insensitivity due to IGF-1 deprivation Symptoms: Cataracts • mammary underdevelopment • severe hearing loss Medication: — Clinical Procedure: Early detection of IGF-1 deprivation and urgent consensus for current diagnosi Specialty: Endocrinology and Metabolic Objective: Rare co-existance of disease or pathology Background: Growth hormone insensitivity and reduced levels of insulin-like growth factor-1 (IGF-1) are associated with metabolic syndrome that includes obesity, hyperglycemia, type 2 diabetes mellitus, and dyslipidemia. Laron syndrome is a rare autosomal recessive condition associated with insensitivity to growth hormone that results in short stature and metabolic syndrome and is usually diagnosed in childhood. This report is of a 42-year-old Mexican woman with untreated growth hormone insensitivity and diabetic retinopathy, in whom gene sequencing supported the identification of a variant of Laron syndrome. Case Report: A 42-year-old Mexican woman with untreated growth hormone insensitivity, metabolic syndrome, and type 2 diabetes mellitus was diagnosed with cataracts, severe retinopathy and hearing loss. She was investigated for genetic causes of reduction in IGF-1. Next-generation sequencing (NGS) showed genetic changes in the growth hormone and IGF-1 axis. The patient’s phenotype and genetic changes were consistent with Laron syndrome. Conclusions: The early detection of reduced IGF-1 and identification of the cause of growth hormone insensitivity require international consensus on the approach to diagnosis and treatment methods, including effective IGF-1 replacement therapy. Early diagnosis may reduce the clinical consequences of complications that include short stature the development of metabolic syndrome, type 2 diabetes mellitus, and retinopathy.

Effect of Ethanol Consumption on the Placenta and Liver of Partially IGF-1-Deficient Mice: The Role of Metabolism via CYP2E1 and the Antioxidant Enzyme System

“…During development, the establishment of a proper intrauterine environment for fetal development is mandatory, a situation where IGF-1 plays a key role. To date, several case reports in women have shown that partial IGF-1 deficiency might be involved in alterations in the reproductive system and the attainment and maintenance of pregnancy [ 38 , 39 , 40 ], and also its implications in metabolism, which could alter the metabolism of xenobiotic substances such as ethanol. For this reason, the development of an animal model that resembles the physiological alterations due to partial IGF-1 deficiency is crucial for studying the mechanisms and molecular targets involved in its development, especially in critical periods such as pregnancy.…”

Cycle day 2 serum levels of insulin-like growth factor-1 as a prognostic indicator for poor responders to controlled ovarian hyperstimulation

“…8 Decreased GH/IGF-1 signaling is associated with reproductive issues, as seen in conditions like Laron syndrome and certain genetic variations in the African Pygmy tribe, where fertility is affected. 9,10 The aim of study is to study whether patients exhibiting poor ovarian response have abnormal levels of serum insulin-like growth factor (IGF)-1 on cycle day 2 when compared with age-matched normal and high responders. As shown in Table 2; there is significant positive correlation between Age of females and FSH, IGF-1, and significant negative correlation between Age of females and AMH.…”