Hypothalamic Pituitary Relationships Flashcards by Sarah Gillen

The communications between the hypothalamus and ________ _____ are neural and hormonal

Anterior pituitary

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Hormones of anterior pituitary

ACTH
TSH
FSH
LH
GH
Prolactin

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What is a hallmark symptom of pituitary tumors?

Vision changes d/t impingement of optic chiasm and optic n

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What is the direct route of delivery of hormones from the hypothalamus to the anterior pituitary?

Hypothalamic hypophysial portal system

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T/F: Hormones from the anterior pituitary appear in high concentrations in systemic circulation

False; they have high concentration within the gland itself

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The anterior pituitary has neural and hormonal signals with the hypothalamus. The posterior pituitary has ____ signals only

Neural

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The anterior pituitary is a collection of endocrine cells; the posterior pituitary is a collection of ______ whose cell bodies are located in the hypothalamus

Axons

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The cell bodies in the hypothalamus that communicate with the posterior pituitary are associated with what 2 nuclei? What neuropeptides do they secrete?

Supraoptic nucleus (SON) = secretes ADH

Paraventricular nucleus (PVN) = secretes oxytocin

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Compare/contrast primary vs. secondary vs. tertiary endocrine disorders

Primary = at the level of peripheral gland

Secondary = problem with pituitary

Tertiary = problem with hypothalamus

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Hormone families of the anterior pituitary are organized by structural and functional homology. What are the 3 families of the anterior pituitary?

ACTH family = corticotrophs; secrete ACTH

TSH, FSH, LH family = thyrotrophs (secrete TSH); gonadotrophs (secrete FSH and LH)

GH, Prolactin family = somatotrophs (secrete GH), lactotrophs (secrete prolactin)

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Match the releasing hormone with its target in anterior pituitary and hormone secreted:

TRH

Thyrotrophs —> TSH

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Match the releasing hormone with its target in anterior pituitary and hormone secreted:

CRF

Corticotrophs —> ACTH

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Match the releasing hormone with its target in anterior pituitary and hormone secreted:

GnRH

Gonadotrophs —> LH, FSH

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Match the releasing hormone with its target in anterior pituitary and hormone secreted:

GHRH vs. somatostatin

GHRH —> somatotrophs —> GH

Somatostatin inhibits somatotrophs secretion of GH

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PIF (dopamine) from hypothalamus acts on ______ in anterior pituitary to inhibit secretion of _____

Lactotrophs; PRL

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Activity of endocrine axes are maintained at a set point, often secreting hormones in pulsatile manner and entrained to circadian rhythms. What are the axes associated with the anterior pituitary gland?

Hypothalamic-Pituitary-Gonad (HPG)

Hypothalamic-Pituitary-Liver

Hypothalamic-Pituitary-Prolactin

Hypothalamic-Pituitary-testis/ovary

Hypothalamic-Pituitary-thyroid

Hypothalamic-Pituitary-Adrenal

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Rare disease characterized by excessive growth of soft tissue, cartilage, and bone in the face, hands, and feet; caused by prolonged and excessive secretion of growth hormone in adult life

Acromegaly

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Physical findings of acromegaly

Prominent supraorbital ridges
Lower teeth separation
Prominent lower jaw
Cardiomegaly
Organomegaly
Hyperglycemia
Enlarged head circumference
Hypertension
Large hands
Accelerated osteoarthrosis
Increased heel-pad thickness on x-ray
Large feet

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Growth hormone is produced by somatotropes

It targets _____ and ______ (organs)

The GH receptor is linked to _______ signaling

Liver; bone

Jak-stat

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Growth hormone is inhibited by ____ and _____ as part of a negative feedback mechanism

Somatostatin (GHIH)

IGF-1

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What are the 2 primary stimulators of GH secretion?

Fasting/hunger/starvation

Hypoglycemia

[also puberty hormones, exercise, sleep, and stress]

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GH binds directly to target cells in ____ and ____

Bones; muscle

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GH binds directly to bones and muscle. What effect does it have on growth?

Hypertrophy - increase in size/volume of cells (ex: increases bone thickness)

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GH binds directly to bones and muscle. What effect does it have on cell reproduction?

Hyperplasia = increase number of cells or proliferation rate via mitosis (ex: increase bone length)

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GH binds directly to bones and muscle. What effect does it have on metabolism?

Increase glycogen and fat breakdown for energy to increase protein synthesis

Another name for growth hormone

Somatotropin

Another name for insulin-like growth factor 1 (IGF-1)

Somatomedin C

In a normal hypothalamic-pituitary-growth hormone axis, the hypothalamus releases either ______ and ______, or ______, which act at the anterior pituitary which will either be stimulated or inhibited to release growth hormone. Two of the above will stimulate the release of growth hormone, which proceeds to the ______ which releases _______

Ghrelin; GHRH; somatostatin Liver; IGF-1

Describe a primary GH insensitivity in terms of the HPGh axis

The liver is insensitive to GH, so GH levels rise

Describe a secondary GH insensitivity in terms of the HPGh axis

Secondary = problem with pituitary Ghrelin and GHRH or somatostatin are released from hypothalamus, but GH cannot be released from anterior pituitary. IGF-1 does not get stimulated at all. GH levels are LOW

Describe a tertiary GH insensitivity in terms of the HPGh axis

Tertiary = problem with hypothalamus Ghrelin, GHRH, and somatostatin not getting secreted from hypothalamus, no GH being released from anterior pituitary, IGF-1 not stimulated at all. GH levels LOW

Excess growth hormone causes 2 different conditions depending on closure of bone epiphyses (growth plates); what are they?

Gigantism if GH excess occurs prior to growth plate closure — due to IGF-1 stimulated long bone growth Acromegaly if GH excess occurs after growth plate closure due to promotion of growth of deep organs and cartilaginous tissues

Growth promoting factors in the fed state are increased carb intake (leading to increased blood sugar and adequate insulin availability) and increased protein intake (leading to adequate amino acid availability) These two factors act on the liver to produce IGF-1 What are the 3 anabolic activites encouraged by IGF-1?

Mitogenesis Lipolysis Differentiation [increased activity of IGF-1 —> increased osteoblasts, collagen, and bone matrix]

What happens to GH if you have adequate insulin availability but inadequate amino acid availability?

GH is inhibited; liver will not produce IGF-1 Net result is weight gain d/t lipogenesis and carb storage

What happens to GH in conditions of adequate amino acid availability and inadequate insulin availability?

GH levels increase, liver will produce IGF-1, leading to increased lipolysis, ketogenic metabolism, and diabetogenesis (long term)

GH promotes lipolysis, but can also promote _____ insensitivity

Insulin [GH raises BG by decreasing peripheral glucose uptake and stimulating hepatic gluconeogenesis]

How are GH abnormalities diagnosed?

Elevated serum GH and IGF-1 levels AND Failure to suppress GH production in response to an oral load of glucose (very sensitive test for acromegaly)

Describe diabetogenic effects of GH

Increase in BG concentration causes insulin resistance Decreased glucose uptake and utilization by target tissues; increased lipolysis in adipose tissue Results in increased blood insulin levels

Increased protein synthesis and organ growth caused by GH leads to increased uptake of amino acids - this stimulates synthesis of DNA, RNA, and protein. It is mediated by ______

Somatomedins (IGF-1)

GH secretion fluctuates throughout the day but is primarily secreted during _________, so disturbances at this time perturb GH secretion GH secretion also peaks with ______

Sleep; exercise

What are different mechanisms of GH deficiency?

Decreased secretion of GHRH Decreased secretion of GH itself Failure to generate somatomedins GH or somatomedin resistance (deficiency of receptors)

Describe diagnosis of acromegaly using GH and the oral glucose tolerance test

Diagnosis of acromegaly requires: 1. Increased serum IGF-1 2. Failure to suppress serum GH 3. Pituitary enlargement on MRI

T/F: GH levels fluctuate throughout the day, whereas IGF-1 levels remain constant

True

Prolactin (PRL) is synthesized by _______, with an increase in secretion beginning around 5th week of pregnancy. Secretion is pulsatile. PRL is under tonic inhibition by hypothalamic _________ Its primary action is to stimulate and maintain _______

Lactotropes Dopamine Lactation

Prolactin suppresses _____ (thus inhibiting LH and FSH), decreasing reproductive function and suppressing sexual drive

GnRH

Major stimulatory factors affecting PRL secretion

``` Pregnancy (estrogen) Breastfeeding Sleep Stress TRH ```

Major inhibitory factors affecting PRL secretion

Dopamine Dopamine agonists Somatostatin Prolactin via negative feedback

A normal menstrual cycle in females depends on what 2 hormones?

LH; FSH

FSH and LH are secreted by _______ They promote _____ and ____ secretion in females and ______ production in males

Gonadotropes Estrogen; progesterone; testosterone

FSH and LH are regulated by hypothalamic GnRH What types of things can inhibit GnRH function?

Extreme energy deficits (anorexia nervosa or starvation), extreme exercise, and depression

What effect does hyperprolactinemia have on FSH and LH secretion?

Suppression

Why are the major symptoms of excess PRL galactorrhea (abnormal milk production) and infertility?

PRL suppresses GnRH

Pulsatile GnRH stimulates LH/FSH secretion from AP, while ______ GnRH secretion inhibits LH/FSH

Continuous

Ovaries may also secrete ___ and ____ that alter release of FSH in the feedback control mechanism

Inhibin; activin

Hyperpituitarism affecting corticotrophs leads to which of the following? ``` A. Cushing’s disease B. TSH-secreting Adenoma C. Acromegaly; gigantism D. Prolactinoma E. Non-functioning adenoma ```

A. Cushing’s disease

Hyperpituitarism affecting gonadotrophs leads to which of the following? ``` A. Cushing’s disease B. TSH-secreting Adenoma C. Acromegaly; gigantism D. Prolactinoma E. Non-functioning adenoma ```

E. Non-functioning adenoma

Hyperpituitarism affecting lactotrophs leads to which of the following? ``` A. Cushing’s disease B. TSH-secreting Adenoma C. Acromegaly; gigantism D. Prolactinoma E. Non-functioning adenoma ```

D. Prolactinoma

Hyperpituitarism affecting somatotrophs leads to which of the following? ``` A. Cushing’s disease B. TSH-secreting Adenoma C. Acromegaly; gigantism D. Prolactinoma E. Non-functioning adenoma ```

C. Acromegaly; gigantism

Hyperpituitarism affecting thyrotrophs leads to which of the following? ``` A. Cushing’s disease B. TSH-secreting Adenoma C. Acromegaly; gigantism D. Prolactinoma E. Non-functioning adenoma ```

B. TSH-secreting adenoma

How does hypopituitarism manifest in terms of GH?

Children have short stature Adults = no effect

How does hypopituitarism manifest in terms of FSH/LH?

Infertility, hypogonadism Males: reduced sperm count Females: menstrual irregularity

How does hypopituitarism manifest in terms of TSH?

Hypothyroidism

How does hypopituitarism manifest in terms of ACTH?

Loss of pigmentation | Hypoadrenalism

How does hypopituitarism manifest in terms of ADH

Diabetes insipidus

2 primary causes of hypopituitarism

Brain damage (TBI, subarachnoid hemorrhage, irradiation, stroke) Pituitary tumors (adenoma) [other causes include non-pituitary tumors, infections like meningitis/encephalitis/hypophysitis, infarction, autoimmune disorder, pituitary hypoplasia or aplasia, genetic disorder]

What is the most common non-pituitary tumor affecting the HP axis in children?

Craniopharyngioma

____ syndrome = pituitary in pregnancy is enlarged and more vulnerable to infarction

Sheehan syndrome

Diabetes insipidus is due to a lack of an effect of _____ on the renal collecting duct, resulting in polyuria, polydipsia, and polyphagia

ADH

What is the difference between central vs. nephrogenic diabetes insipidus?

Central = deficient secretion of ADH from hypothalamus or pituitary Nephrogenic = renal insensitivity to ADH

How does the ADH test distinguish between central and nephrogenic diabetes insipidus?

After exogenous ADH (desmopressin) administration: Central DI = kidneys respond by concentrating urine Nephrogenic DI = no change; kidneys cannot concentrate urine

In contrast to central DI, nephrogenic DI involves the kidneys unresponsiveness to ADH, resulting in ________ plasma [ADH] levels, chronic kidney disease, and _____ toxicity

Increased; lithium

What condition is characterized by excessive secretion of ADH leading to excessive water retention?

SIADH [hyposmolarity fails to inhibit ADH release]

What is the common electrolyte imbalance that occurs with acute SIADH? What occurs with chronic SIADH?

Acute = hyponatremia d/t water retention Ongoing volume expansion due to SIADH activates secondary natriuretic mechanisms, resulting in sodium and water loss. The net effet in chronic SIADH is sodium loss that is more prominent than water retention

What fluid/solute mechanisms are involved with euvolemic hyponatremia in terms of EC sodium and TBW?

EC sodium is normal TBW slightly increased [possible underlying causes = SIADH, COPD, malignancy]

What fluid/solute mechanisms are involved with hypervolemic hyponatremia in terms of EC sodium and TBW?

EC sodium increased TBW greatly increased [possible causes = CHF, renal impairment, cirrhosis]

Increased or decreased: SIADH ``` Urinary output ADH levels Plasma Na Hydration status Thirst TBW ```

``` Urinary output decreased ADH levels increased Plasma Na decreased Hydration status increased Thirst increased TBW normal or slightly increased ```

Increased or decreased: DI ``` Urinary output ADH levels Plasma Na Hydration status Thirst TBW ```

``` Urinary output increased ADH levels decreased (central) Plasma Na increased Hydration status decreased Thirst increased TBW decreased ```

2 primary actions of oxytocin

Milk ejection (stimulates contraction of myoepithelial cells lining milk ducts) Uterine contraction (stimulated by dilation of the cervix or orgasm)

Exogenous form of oxytocin used to induce labor

Pitocin

Hormone from hypothalamus: CRH Function on anterior pituitary?

Stimulates ACTH, MSH

Hormone from hypothalamus: dopamine Function on anterior pituitary?

Inhibits prolactin

Hormone from hypothalamus: GHRH Function on anterior pituitary?

Stimulates GH release

Hormone from hypothalamus: GnRH Function on anterior pituitary?

Stimulates FSH, LH release

Hormone from hypothalamus: somatostatin Function on anterior pituitary?

Inhibits GH, TSH

Hormone from hypothalamus: TRH Function on anterior pituitary?

Stimulates TSH, prolactin release