Hypopituitarism pathophysiology

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Hypopituitarism Microchapters


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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]


Hypopituitarism occurrs secondarly 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 of the hypophyseal vessels leading to interruption in the blood supply of the pituitary gland. Traumatic brain injury either primary or secondary also leads to pituitary gland dysfunction.


Background on pituitary gland blood supply

A pituitary gland anatomy By Henry Vandyke Carte - Via: Wikimedia.org[3]

Anterior pituitary (Adenohypophysis)

Posterior pituitary (Neurohypophysis)

Hypothalamic and pituitary hormones with their action on the target glands

Hypothalamic hormone Axis involved Mode of action Pituitary hormone

or target organ

Anterior pituitary hormones Thyrotropin-releasing hormone Hypothalmic-pituitary-thyroid (HPT) axis
HPT axis - By Mikael Häggström, Via: Wikimedia.org[5]
Stimulatory Thyrotropin Stimulates triiodothyronine and thyroxine production
Corticotropin-releasing hormone Hypothalmic-pituitary-adrenal (HPA) axis
HPA axis - By Brian M Sweis (Own work), Via: Wikimedia.org[6]
Stimulatory Corticotropin Stimulates production of cortisol and adrenal androgens
Stimulatory Prolactin Stimulates milk production from breasts in females
Gonadotropin-releasing hormone Hypothalamus pituitary testicles (HPG) axis
HPG axis - By Testosterona-ciclo, Via: Wikimedia.org[7]
Dopamine Inhibitory Prolactin _
Growth hormone-releasing hormone
Endocrine growth regulation - By Mikael Häggström. Via: Wikimedia.org[8]
Stimulatory Growth hormone Stimulates insulin-like growth factor 1 production
Somatostatin Inhibitory Growth hormone _
Posterior pituitary hormones Vasopressin Stimulatory Stimulates free water reabsorption in the collecting ducts
Oxytocin Stimulatory Breast, uterus Stimulates milk ejection and uterine contraction


Compression of the blood vessels

(a) Pituitary adenoma

(b) Sheehan's syndrome

(c) Carotid artery aneurysm

(d) Meningioma

(e) Craniopharyngioma

Traumatic brain injury (TBI)

Hypopituitarism may occur via any of the following mechanisms:

(a) Primary brain injury

(b) Trauma

(c) Brain injury due to other events like hypotension or hypoxia


Hypopituitarism is caused by a mutation in any one of the following genes.[16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35]


hormonal abnormalities

Gene Inheritance

[Autosomal Recessive (AR),

Autosomal Dominant (AD),

X-linked (XL)]

GH1 AD, AR Isolated GH deficiency
GHRHR AR Isolated GH deficiency
TSHB AR Isolated TSH deficiency
TRHR AR Isolated TSH deficiency
TPIT AR Isolated ACTH deficiency
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
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

Gross pathology

  • The predominant finding is hemorrhage with or without necrosis.
  • Pale, necrotic material is particularly found when there is a long interval between the acute clinical event and surgery.

Microscopic pathology

On microscopy, the following findings may be observed:

Histopathological image of nonfunctioning pituitary adenoma. Hematoxylin & eosin stain showing basophilic appearance of the cells - By Jensflorian (Own work), Via: Wikimedia.org[36]


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