Role of the GH-IGF1 axis on the hypothalamus–pituitary–testicular axis function: lessons from Laron syndrome

Abstract

BACKGROUND. Animal studies suggest that insulin-like growth factor 1 (IGF1) may influence the function of the hypothalamus-pituitary-testicular axis, especially in childhood, but the evidence in humans is scanty. Laron syndrome, a human model of IGF1 deficiency, may help to solve this issue. PURPOSE. This systematic review aims to analyze puberty onset and progression, testicular volume, gonadotropin, and total testosterone serum levels, sperm parameters and fertility, and penile length in patients with Laron syndrome. METHODS. Specific key-words were used. All data on male patients with Laron syndrome were included. RESULTS. Seventeen articles matched the inclusion criteria and entered in the analysis, for a total of 125 male patients. Puberty was absent in 8.9% and delayed in 35.6% of untreated patients of pubertal age. After onset, the duration of the pubertal process was prolonged in 76.9% of untreated patients. The growth spurt was absent in 52.6% and delayed in 31.6% of untreated patients. The testicular volume was small in the two patients who did not receive any treatment. Treatment with IGF1 increased gonadotropin and testosterone serum levels in 5 out of 5 patients of pubertal age. No effect was found in 4 out of 4 patients younger than 5 years. No study reported data on sperm parameters and fertility. Micropenis occurred in 67.2% of patients. CONCLUSION AND FUTURE PERSPECTIVES. Delayed puberty is common in patients with Laron syndrome. The growth hormone-IGF1 axis may influence the time of puberty onset. Serum levels of IGF1 should be investigated in children with delayed puberty, scarce progression of testicular growth, and/or micropenis.IGF1 levels might be measured in children with delayed puberty, poor testicular growth, and/or micropenis.

Establishment of Novel Non-stretched Penile Length (Flaccid) Cut-off Point and Normative Data in Iranian Prepubertal Children and its Significance: Observational Analytical Study

“…It is important to evaluate penis size in routine examinations because external genitalia abnormality may indicate underlying endocrine dysfunction, genetic disease, or structural malformations (10)(11)(12)(13). Misdiagnosis causes anxiety and stress for the child and parents and imposes addi-tional and unnecessary diagnostic and treatment costs on the patient and his family.…”

Are androstenedione, dihydrotestosterone, thyroid‐stimulating hormone, insulin‐like growth factor I, and insulin‐like growth factor binding protein 3 necessary for isolated micropenis healthy boys' evaluation without any phenotypic abnormalities? A cross‐sectional study

“…Cannarella et al (2021) reported the clinical features of IGF‐I deficiency in 125 children. Their most common findings were no puberty (8.9%), delayed puberty (35.6%), absent (52.6%) or delayed growth spurt (31.6%), and micropenis (67.2%).…”

“…Hypotonia (55.7%), feeding problem (36.5%), obesity (30.7%), cryptorchidism (69.2%), and small penis (15.3%) were the most clinical presentations. They suggested that IFG‐I should be measured in children with specific phenotypes such as midline anomalies, growth retardation, delayed puberty, small testis, and micropenis (Cannarella et al, 2021; Dağdeviren Çakır et al, 2021; Juul & Skakkebæk, 2019). However, our study demonstrated that IGF‐I levels were normal in most isolated micropenis healthy children without other genitalia and physical abnormalities, and no significant relationship was observed with penis size.…”

Síndrome de Laron: aspectos clínicos y pronóstico en pacientes tratados con mecasermina

“…Ya en el desarrollo después del nacimiento encontramos la manifestación clínica principal que es la talla por debajo del rango normal, que se encuentran establecidos, y es inmediatamente después de los tres meses de edad donde se empieza a notar, además conlleva que el crecimiento normal de los huesos se vea ralentizado (10,25).…”

“…Existen características típicas presentada a nivel facial y en el cráneo, como lo es que el cabello antes escaso se vuelve normal después de los 14 años, la voz suele tener un tinte agudo debido a un defecto en la formación de la laringe y las cavidades orbitarias suelen ser limitadas (10,25).…”