Hypopituitarism pathophysiology

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Ahmed Elsaiey, MBBCH [2], Iqra Qamar M.D.[3]

Overview

Hypopituitarism is believed to be caused mainly due to ischemia of the pituitary gland. This ischemia can be due to hemorrhage, tumors, or brain injury. Compression of the blood vessels is one of the mechanisms that cause ischemia to the pituitary gland and leads to hypopituitarism. Pituitary adenomas cause compression to the hypophyseal vessels leading to interruption in the pituitary gland function. Traumatic brain injury either primary or secondary also leads to pituitary gland dysfunction.

Pathophysiology

Background on pituitary gland blood supply

Hypothalamic and pituitary hormones with their action on the target glands

Hypothalamic hormone Mode of action Pituitary hormone

or target organ

Action
Thyrotropin-releasing hormone Stimulatory Thyrotropin Stimulates triiodothyronine and thyroxine production
Corticotropin-releasing hormone Stimulatory Corticotropin Stimulates production of cortisol and adrenal androgens
Stimulatory Prolactin Stimulates milk production from breasts in females
Gonadotropin-releasing hormone Stimulatory
  • Follicle stimulating hormone
  • Leutinizing hormone
  • Males: stimulates testosterone production and spermatogenesis
  • Female: stimulates estradiol and progesterone production, ovulation and folliculogenesis
Dopamine Inhibitory Prolactin _
Growth hormone-releasing hormone Stimulatory Growth hormone Stimulates insulin like growth factor 1 production
Somatostatin Inhibitory Growth hormone _
Vasopressin Stimulatory Stimulates free water reabsorption in the collecting ducts
Oxytocin Stimulatory Breast, uterus Stimulates milk ejection and uterine contraction

Pathogenesis


Genetics

Hypopituitarism is caused by a mutation in any one of the following genes.[9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28]

Isolated

hormone abnormalities

Gene Inheritance Phenotype
GH1 AR, AD Isolated GH deficiency
GHRHR AR Isolated GH deficiency
TSHB AR Isolated TSH deficiency
TRHR AR Isolated TSH deficiency
TPIT AR Isolated ACTH deficiency
GnRHR AR HH
PC1 AR ACTH deficiency, hypoglycemia, HH, obesity
POMC AR ACTH deficiency, obesity, red hair
DAX1 XL Adrenal hypoplasia congenital and HH
CRH AR CRH deficiency
KAL1 XL Kallman syndrome, renal agenesis, synkinesia
FGFR1 AD, AR Kallman syndrome, cleft lip and palate, facial dysmorphism
Leptin AR HH, obesity
Leptin-R AR HH, obesity
GPR54 AR HH
Kisspeptin AR HH
FSHB AR Primary amenorrhea, defective spermatogenesis
LHB AR Delayed puberty
PROK2 AD Kallman syndrome, severe sleep disorder, obesity
PROKR2 AD, AR Kallman syndrome
AVP-NPII AR, AD Diabetes insipidus
Combined pituitary hormone deficiency POU1F1 AR, AD GH, TSH, and prolactin deficiencies
PROP1 AR GH, TSH, LH, FSH, prolactin, and evolving ACTH deficiencies
Specific syndromes HESX1 AR, AD Septo-optic dysplasia
LHX3 AR GH, TSH, LH, FSH, prolactin deficiencies, limited neck rotation
LHX4 AD GH, TSH, ACTH deficiencies with cerebellar abnormalities
SOX3 XL Hypopituitarism and mental retardation
GLI2 AD Holoprosencephaly and multiple midline defects
SOX2 AD Anophthalmia, hypopituitarism, oesophageal atresia
GLI3 AD Pallister-Hall syndrome
PITX2 AD Rieger syndrome

References

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