Why does a pituitary tumor lead to dizziness and vision problems?

Tumor, if large enough, can expand up into the brain and against optic nerves

What hormones are secreted by the anterior pituitary? What connects the hypothalamus to the anterior pituitary? (both anatomically and vascularly?)

ACTH (Corticotrophs) TSH (Thyrotroph) FSH (Gonadotroph) LH (Gonadotroph) GH (Somatotroph) Prolactin (Lactotroph/Mammotroph) Connected anatomically via hypophysial stalk and connected vascularly via hypothalamic-hypophysial portal system

Hypothalamic hormones are delivered to the pituitary _ and in _ concentrations Hypothalamic hormones are _ in concentration in the systemic circulation

Directly, high concentration Lower

Primary endocrine disorder

Low or high levels of hormone D/t defect in peripheral endocrine gland

Secondary endocrine disorder

Low or high hormones D/t defect in pituitary gland

Tertiary endocrine disorder

Low or high levels of hormones D/t problems in the hypothalamus

How is acromegaly diagnosed?

IGF-1 levels are elevated!! (Do not just rely on GH, because secretion of GH varies depending on the time of day) Glucose load test (oral glucose tolerance test)-will show increase in GH release (normally should be lowered with increased BGL) Pituitary mass seen on MRI

Treatment for Acromegaly

Somatostatin analog/agonist Octreotide Lanreotide Gh receptor antagonist Pegvisomant Dopamine receptor agonist (\<25% effective) Bromocriptine Cabergoline

Hypothalamic Pituitary Relationships Flashcards by Madison Hahn

Why does a pituitary tumor lead to dizziness and vision problems?

Tumor, if large enough, can expand up into the brain and against optic nerves

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Supraoptic Nuclei (SO) from hypothalamus extending into posterior pituitary secrete _
Paraventricular Nuclei (PVN) from hypothalamus extending into posterior pituitary secrete _

ADH
Oxytocin

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What hormones are secreted by the anterior pituitary?
What connects the hypothalamus to the anterior pituitary? (both anatomically and vascularly?)

ACTH (Corticotrophs)
TSH (Thyrotroph)
FSH (Gonadotroph)
LH (Gonadotroph)
GH (Somatotroph)
Prolactin (Lactotroph/Mammotroph)
Connected anatomically via hypophysial stalk and connected vascularly via hypothalamic-hypophysial portal system

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Hypothalamic hormones are delivered to the pituitary _ and in _ concentrations
Hypothalamic hormones are _ in concentration in the systemic circulation

Directly, high concentration
Lower

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Primary endocrine disorder

Low or high levels of hormone
D/t defect in peripheral endocrine gland

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Secondary endocrine disorder

Low or high hormones
D/t defect in pituitary gland

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Tertiary endocrine disorder

Low or high levels of hormones
D/t problems in the hypothalamus

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Different cell types in the hypothalamus are organized into families based on _ and _ morphology
- ACTH family
- TSH, FSH, and LH family
- GH and Prolactin family

Structural and functional

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_ stimulates thyrotrophs in the anterior pituitary to secrete TSH

_ stimulates corticotrophs in the anterior pituitary to secrete ACTH

_ stimulates gonadotrophs in the anterior pituitary to secrete LH,FSH

_ stimulates somatotrophs in the anterior pituitary to secrete GH

_ inhibits somatotrophs in the anterior pituitary from secreting GH

_ stimulates lactotrophs in the anterior pituitary to secrete Prolactin

TRH
CRH
GnRH
GHRH
Somatostain
PIF (dopamine) AND TRH (elevated)

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Acromegaly
Pathophysiology

Excessive prolonged secretion of GH
Also have elevated levels of IGF-1 as a consequence of elevated GH
Increase in BGL
Excessive growth of soft tissue (chondrocytes)
Organomegaly and HTN can result
Gradually develops
Pathophysiology
- Pituitary GH excess
- Extrapituitary GH excess
- GHRH excess

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GH stimulates _ gene transcription and secretion by the liver

IGF-1 (somatomedin C)

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What inhibits GH release from the anterior pituitary?
What inhibits secretion of GHRH from the hypothalamus?
What stimulates GH release from the anterior pituitary?
What stimulates the hypothalamus to secrete somatostatin (SRIF)?

Somatomedins and Somatostatin
GHRH
GHRH
GH and somatomedins

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How is acromegaly diagnosed?

IGF-1 levels are elevated!! (Do not just rely on GH, because secretion of GH varies depending on the time of day)
Glucose load test (oral glucose tolerance test)-will show increase in GH release (normally should be lowered with increased BGL)
Pituitary mass seen on MRI

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Treatment for Acromegaly

Somatostatin analog/agonist
- Octreotide
- Lanreotide
Gh receptor antagonist
- Pegvisomant
Dopamine receptor agonist (<25% effective)
- Bromocriptine
- Cabergoline

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GH is secreted from somatotrophs in a _ manner
Amount secretted each day is higher during _ than in younger children/adults

Pulsatile

Puberty

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Pathophysiology of GH deficiency

Decreased secretion of GHRH (hypothalamic issue)
Decreased GH secretion by anterior pituitary
Failure to generate somatomedins (effects of GH that are mediated by somatomedins would be impaired)
GH or somatomedin resistance

Pathophysiology of GH excess

Usually d/t pituitary adenoma secreting excess GH
Before puberty: Gigantism
After puberty: Acromegaly increase in periosteral bone growth, organomegally, increase in extremity size, insulin resistance and glucose intolerance

Metabolic functions of GH

Diabetogenic effect (increases BGL)
- Causes insulin resistance
- Decreases glucose uptake and utilization
- Increases lipolysis in adipose tissue
- Results in increase in Insulin levels (d/t increase in BGL)
Increase protein synthesis and organ growth (mediated by somatomedins)
- Increase uptake of AAs
- Stimulates synthesis of DNA, RNA, and proteins
Increased linear growth (mediated by somatomedins)
- Stimulates synthesis of DNA, RNA, and protein
- Increased metabolism in cartilage forming cells
- Chondrocyte proliferation

_ is an important determinant of GH, IGF-1 and insulin levels

Nutritional status

Hyperprolactinemia suppresses _ and _ secretion
How does this cause amenorrhea?

LH and FSH suppressed

Amenorrhea results b/c excess prolactin inhibits GnRH release from the hypothalamus, and inhibiting secretion of LH and FSH to ovaries

How are pituitary adenomas classified?

Size
- Micro < 1 cm, Macro > 1cm
Agressiveness
- Most benign and slow growing
Hormone secretion
- Functional: release active hormone in excess (usually)
  - Ex: Prolactinoma-hypogonadism and galactorrhea .
  - Cushings
  - Acromegaly, Gigantism
- Clinically non functioning: do not release an active hormone
  - Ex: FSH or LH

Causes of hypopituitarism

Brain damage
Pituitary tumors (if large, compresses pituitary and affects release of hormones-adenomas for ex)
Non-pituitary tumors
- Ex: Craniopharyngioma-affects HP axis in kids
Infections
Infarction
- Sheehan syndrome
AID
Pituitary hypoplasia/aplasia
Genetic causes

Sheehan syndrome

Postpartum hypopituitarism d/t necrosis of pituitary gland
Agalactorrhea-can’t make breast milk
Amenorrhea
Some present with hypothyroidism

Regulation of oxytocin secretion

* ADH secretion diagram summary

* **What are the triggers of ADH secretion?** * **What cells sense these triggers?** * **Where do they send their information?**

* **Low blood pressure-sensed by cardiac and aortic baroreceptors**, sends signals via **sensory neuron** to hypothalamus * **Decreased arterial stretch d/t low blood volume**-sensed by **atrial stretch receptors** and sent via **sensory neuron** to hypothalamus * **Increased plasma osmolarity** sensed by **hypothalamic receptors** that communicate with rest of hypothalamus via **interneurons** * Also stimulated by **angiotensin II, sympathetics, dehydration**

Secretion of ADH is most sensitive to changes in \_ Overall actions of ADH? How does it perform these actions?

* Plasma osmolarity (as low as 1%) * Increase blood pressure * Increase blood volume * **Acts on v1 receptors of blood vessels for vasoconstriction** * **Acts on v2 receptors (GPCR, cAMP, PKA) of kidneys and increases insertion of AQP 2s on apical surface of cortical collecting duct to increase H2O reabsorption**

* Hypoosmolarity and hypervolemia _ release of ADH * Hyperosmolarity and hypovolemia _ release of ADH

* Inhibit * Stimulate

* Control of ADH secretion by osmolarity and extracellular fluid volume

* ***Diabetes insipidus***

* Lack of ADH in collecting duct * Frequent urination * Large volumes of dilute urine

* ***Central versus neprhogenic diabetes insipidus***

* **Central** * ****Lack of ADH (decreased plasma ADH) * Damage to pituitary or hypothalamus * **TREATABLE WITH DESMOPRESSIN** * **Nephrogenic** * ****Kidneys unable to respond to ADH * Chronic disorders (PKD, sickle cell anemia) * Lithium use * **NOT TREATABLE WITH DESMOPRESSIN**

* ***How does the water deprivation test for DI work?***

* Patient is allowed fluids overnight * No fluids with breakfast * Weigh patient * Allow no fluid for 8 hr (evert 1-2 hr: weigh patient, measure pt urine osmolarity/volume; measure plasma osmolarity) * Administer Desmopressin * Measure urine plasma osmolarity, urine volume

***SIADH***

* Syndrome of inappropriate ADH secretion * Excessive secretion of ADH * Excessive water retention * Hypoosmolarity fails to inhibit ADH release