Hypothalamic Pituitary Relationships Flashcards
The communications between the hypothalamus and ________ _____ are neural and hormonal
Anterior pituitary
Hormones of anterior pituitary
ACTH TSH FSH LH GH Prolactin
What is a hallmark symptom of pituitary tumors?
Vision changes d/t impingement of optic chiasm and optic n
What is the direct route of delivery of hormones from the hypothalamus to the anterior pituitary?
Hypothalamic hypophysial portal system
T/F: Hormones from the anterior pituitary appear in high concentrations in systemic circulation
False; they have high concentration within the gland itself
The anterior pituitary has neural and hormonal signals with the hypothalamus. The posterior pituitary has ____ signals only
Neural
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
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
Compare/contrast primary vs. secondary vs. tertiary endocrine disorders
Primary = at the level of peripheral gland
Secondary = problem with pituitary
Tertiary = problem with hypothalamus
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)
Match the releasing hormone with its target in anterior pituitary and hormone secreted:
TRH
Thyrotrophs —> TSH
Match the releasing hormone with its target in anterior pituitary and hormone secreted:
CRF
Corticotrophs —> ACTH
Match the releasing hormone with its target in anterior pituitary and hormone secreted:
GnRH
Gonadotrophs —> LH, FSH
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
PIF (dopamine) from hypothalamus acts on ______ in anterior pituitary to inhibit secretion of _____
Lactotrophs; PRL
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
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
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
Growth hormone is produced by somatotropes
It targets _____ and ______ (organs)
The GH receptor is linked to _______ signaling
Liver; bone
Jak-stat
Growth hormone is inhibited by ____ and _____ as part of a negative feedback mechanism
Somatostatin (GHIH)
IGF-1
What are the 2 primary stimulators of GH secretion?
Fasting/hunger/starvation
Hypoglycemia
[also puberty hormones, exercise, sleep, and stress]
GH binds directly to target cells in ____ and ____
Bones; muscle
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)
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)
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:
- Increased serum IGF-1
- Failure to suppress serum GH
- 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