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Diagnosing and treating anterior pituitary hormone deficiency in pediatric patients

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Abstract

Hypopituitarism, or the failure to secrete hormones produced by the anterior pituitary (adenohypophysis) and/or to release hormones from the posterior pituitary (neurohypophysis), can be congenital or acquired. When more than one pituitary hormone axis is impaired, the condition is known as combined pituitary hormone deficiency (CPHD). The deficiency may be primarily due to a hypothalamic or to a pituitary disorder, or concomitantly both, and has a negative impact on target organ function. This review focuses on the pathophysiology, diagnosis and management of anterior pituitary hormone deficiency in the pediatric age. Congenital hypopituitarism is generally due to genetic disorders and requires early medical attention. Exposure to toxicants or intrauterine infections should also be considered as potential etiologies. The molecular mechanisms underlying the fetal development of the hypothalamus and the pituitary are well characterized, and variants in the genes involved therein may explain the pathophysiology of congenital hypopituitarism: mutations in the genes expressed in the earliest stages are usually associated with syndromic forms whereas variants in genes involved in later stages of pituitary development result in non-syndromic forms with more specific hormone deficiencies. Tumors or lesions of the (peri)sellar region, cranial radiation therapy, traumatic brain injury and, more rarely, other inflammatory or infectious lesions represent the etiologies of acquired hypopituitarism. Hormone replacement is the general strategy, with critical periods of postnatal life requiring specific attention.

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Fig. 1

Reprinted from Shields et al. [2]

Fig. 2
Fig. 3

Reprinted, with permission, from Sykiotis et al. [8]

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Abbreviations

ACTH:

adrenocorticotropic hormone

ADH:

antidiuretic hormone

a-GSU:

α-subunit of glycoprotein hormones

AMH:

anti-Müllerian hormone

AVP:

arginine-vasopressin

CHARGE:

coloboma of the eye, heart defects, atresia of the nasal choanae, restricted growth and/or development, genital

CPHD:

combined pituitary hormone deficiency

CRH:

corticotropin-releasing hormone

DAVID:

deficient anterior pituitary with variable immune deficiency

DAX1:

DSS-AHC critical region on the X chromosome gene 1

DHEA:

dehydroepiandrosterone

DHEA-S:

dehydroepiandrosterone-sulfate

FSH:

follicle-stimulating hormone

GH:

growth hormone

GH:

somatotropin or growth hormone

GHRH:

GH-releasing hormone

GHRHR:

GH releasing hormone receptor

GnRH:

gonadotropin-releasing hormone

GNRHR:

GnRH receptor

GSHR:

growth hormone secretagogue receptor

hCG:

human chorionic gonadotropin

hCS:

chorionic somatotropin

hGH-V:

placenta growth hormone

IGF1:

insulin-like growth factor 1

IGF2:

insulin-like growth factor 2

IGFBP3:

insulin-like growth factor binding protein 3

IGSF1:

immunoglobulin superfamily member 1

IRS4:

insulin receptor substrate 4

LH:

luteinizing hormone

NCoR-SMRT:

nuclear receptor corepressor-silencing mediator for retinoid and thyroid hormone receptors

OBAIRH:

obesity, adrenal insufficiency, and red hair

PC1:

proprotein convertase-1

PIT1:

Pituitary-specific transcription factor 1

POMC:

proopiomelanocortin

POU1F1:

POU domain class 1 transcription factor 1

PRL:

prolactin

rhGH:

recombinant human GH

TBL1X:

Transducin beta-like X-linked

TBX19:

T-box transcription factor 19

TRH:

TSH-releasing hormone

TRHR:

TRH receptor

TSH:

thyroid-stimulating hormone

TSHB:

TSH beta subunit

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  1. Centro de Investigaciones Endocrinológicas “Dr. César Bergadá” (CEDIE), CONICET – FEI – División de Endocrinología, Hospital de Niños Ricardo Gutiérrez, Buenos Aires, C1425EFD, Argentina

    Rodolfo A. Rey, Ignacio Bergadá, María Gabriela Ballerini, Débora Braslavsky, Ana Chiesa, Analía Freire, Romina P. Grinspon, Ana Keselman & Andrea Arcari

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Rey, R.A., Bergadá, I., Ballerini, M.G. et al. Diagnosing and treating anterior pituitary hormone deficiency in pediatric patients. Rev Endocr Metab Disord (2023). https://doi.org/10.1007/s11154-023-09868-4

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