Hypothalamus and Anterior Pituitary Hormones Flashcards
What are the major functions of hormones?
- Regulation of energy storage, production, and utilization
- Adaptation to new environments or conditions of stress
- Facilitation of growth and development
- Maturation and function of the reproductive system
Posterior Pituitary Gland
Releases hormones synthesized in the hypothalamus
* Oxytocin
* Vasopressin
Oxytocin
- Causes contraction of the smooth muscles in the breast during lactation
- It also plays a role in uterine contraction during childbirth
Vasopressin
Essential for proper fluid balance and acts on the renal collecting ducts to conserve water
* can also stimulate ACTH
Anterior Pituitary
6 major peptide hormones of the anterior pituitary regulate peripheral endocrine glands (the thyroid, adrenals, and gonads) as well as growth and lactation
What are the five endocrine axes?
- Growth Hormone-releasing hormone (GHRH) & Somatostatin (SST)
- Corticotropin-releasing hormone (CRH)
- Thyrotropin-releasing hormone (TRH)
- Gonadotropin-releasing hormone (GnRH)
- Dopamine (DA)
Name what anterior pituitary trophic (signal) factors, target organ, and target organ hormones comes from Growth hormone-releasing hormone (GHRH)?
- (+) Growth hormone (GH-somatotropin)
- Liver
- Insulin-like growth factor-1 (IGF-1) (somatomedin)
Name what anterior pituitary trophic (signal) factors, target organ, and target organ hormones comes from Somatostatin (SST)?
- (-) Growth hormone (also called somatotropin)
- Liver
- Insulin-like growth factor-1 (IGF-1) (somatomedin)
Name what anterior pituitary trophic (signal) factors, target organ, and target organ hormones comes from Corticotropin-releasing hormone (CRH)?
- (+) Adrenocorticotropic hormone (ACTH) also called corticotropin
- Adrenal cortex
- Corticosteroids
Name what anterior pituitary trophic (signal) factors, target organ, and target organ hormones comes from Thyrotropin-releasing hormone (TRH)?
- (+) Thyroid-stimulating hormone (TSH) also called thyrotropin
- Thyroid
- Thyroid hormones
Name what anterior pituitary trophic (signal) factors, target organ, and target organ hormones comes from Gonadotropin-releasing hormone (GnRH)?
- (+) Follicle-stimulating hormone (FSH) and Luteinizing hormone (LH) also called gonadotropins
- Gonads
- Estradiol, Progesterone, Testosterone
Name what anterior pituitary trophic (signal) factors, target organ, and target organ hormones comes from Dopamine (DA)?
- (-) Prolactin
- Mammary glands
- No target organ
T/F: ALL hypothalamic releasing hormones, except dopamine, are peptides
T
What are some considerations for exogenous hormone administration?
- Peptides and proteins are NOT absorbed intact from the GI tract (NOT by mouth-oral)
- Chemical instability, photo instability, physical instability
- Reconstitution increases instability
- Shorter shelf-life 12-18 months
- Many are stored refrigerated or protected from light
Thyrotropin releasing hormone (TRH, protirelin)
- Very simple—only 3 amino acids
- Used for diagnostic purpose (differentiate between primary and secondary problems with the axis)
- Interpretation relies on concept that TRH should increase TSH levels (but leave the interpretation to the endocrinologist)
Thyroid stimulating hormone (Thyrotropin alpha, rhTSH, Thyrogen)
- Recombinant (mimics human TSH) product generated from hamster cells
- Contains natural amino acid sequence—identical to native hormone
What is the indication for Thyroid stimulating hormone (Thyrotropin alpha, rhTSH, Thyrogen)?
- Diagnostic: Used to monitor for recurrence of thyroid carcinoma—give prior to radioactive iodine to “prime” active tissue—better detect “hot spots”
- Treatment: Used prior to high dose of radioactive iodine for more effective ablation of the thyroid cells
What are the pharmaceutical products of CRH for the adrenal axis?
- Human CRH, Corticoreline
- Sheep CRH, Corticoreline ovine, Acthrel
Sheep CRH, Corticoreline ovine, Acthrel
- Slightly different from human amino acid sequence
- Has a longer half-life (18 min), more potent, preferred
What are the indications of Sheep CRH, Corticoreline ovine, Acthrel?
Diagnostic to determine if ACTH release is normal
* Differentiate between a tertiary and secondary problem
What is ACTH1-24, Cortrosyn indication?
- Diagnostic
- Inflammatory disorders, infantile spasms
Tesamorelin (Egrifta)
- Growth hormone releasing hormone (GHRH) analog given SC
- FDA approved HIV-induced lipodystrophy
What are the GH secretagogues?
- Ghrelin
- Arginine, leucine
- Clonidine
- L-dopa
- Insulin-induced hypoglycemia
- Sleep, fasting, exercise, and stress
What are GH secretagogues used for?
- For diagnostic use
- Should induce Growth hormones
- FDA recommends 2 independent test
What are effects of growth hormone on lipid and carbohydrate metabolism?
- Anti-insulin effect
- Decreases utilization of glucose by peripheral tissues, increases lipolysis, and increases muscle mass
- Stimulates gluconeogenesis in hepatocytes, impairs post-receptor insulin action
Growth Hormone Axis
- Stimulate the formation of IGF-1 (mainly in the liver) which acts as direct stimulator of cell proliferation and growth
- Secreted in pulsatile fashion, wtih several short bursts that occur most at night
When is the secretion GH at its peak?
- At night
- At adolescence
What are the disorders of GH excess?
- Acromegaly
- Giantism/gigantism (very rare)
Acromegaly
a. Excess production of GH
b. Occurs after puberty (adults), AFTER growth plates close
c. Most often due to pituitary adenoma
Gigantism/gigantism
a. Excess GH
b. Occurs BEFORE epiphysial closure in children
What are the symptoms of acromegaly?
- Soft tissue overgrowth
- Growth of skeletal tree in THICKNESS (not length)
- Bones in adults CANNOT elongate, but they can get thicker—diagnosis by measuring circumference of middle finger
- Disfiguring appearance (jaw and fingers especially)
- Glucose intolerance or overt diabetes
Symptoms are gradual in onset
How do you diagnosis acromegaly?
- If high levels of insulin-like growth factor-1 (IGF-1), then get a glucose tolerance test
- Postprandial hyperglycemia should inhibit the secretion of GH for at least 1 to 2 hours. Therefore, an oral glucose load would be expected to suppress GH concentrations. However, patients with acromegaly continue to secrete GH during the OGTT
What are the drug therapy options for patients diagnosed with acromegaly?
- Somatostatic analogs
- Dopamine agonists
- GH receptor antagonist that acts on the liver
What are the mechanisms of the GH release inhibitory hormone agent (somastatin analog)?
a. Inhibits release GH
b. Inhibits release of intestinal and pancreatic peptides: gastrin, cholecystokinin, pepsin, renin, insulin, glucagon, etc.
c. Inhibits GI motility and bile flow
Octreotide (Sandostatin)
i. Longer acting 8 amino acid analog of somatostatin
ii. Given SC or IV, half life 1.5 hours (vs. 1.5 minutes for native hormone)
iii. Sandostatin LAR depot: IM, monthly (microspheres)
iv. Used as an alternative to radiation and surgery for acromegaly (adults)
v. Pharmaceutical product of GH release inhibitory hormone (GHRIH) Agents
What is Octreotide (Sandostatin) used for?
- carcinoid tumors
- vasoactive intestinal peptide-secreting tumors (VIPomas)
- GI fistulas
- variceal bleeding
- diarrheal states
- irritable bowel syndrome
What are the side effects of Octreotide (Sandostatin)?
- Nausea/vomiting
- Flatulence
- Gallstones
- Increases or decreases in blood glucose
Lanreotide
- (Somatuline depot) deep SC, monthly
- Octapeptide structure similar to octreotide
- For acromegaly
Pasireotide
- Pasireotide (Signifor LAR) monthly IM for acromegaly
- (another formulation—SC BID for Cushing disease)
- Broader affinity for SST receptor subtypes
Bromocriptine and Cabergoline
a. Paradoxical decrease in GH in patients with acromegaly
b. Only completely effective in about 10% of patients
c. Dopamine agonist
d. For acromegaly
What are the side effects of Bromocriptine and Cabergoline?
- CNS symptoms such as headache, lightheadedness, dizziness, nervousness, and fatigue
- GI effects such as nausea, abdominal, or diarrhea
Pegvisomant (Somavert)
i. Given SC, daily
ii. Blocks ability of GH to stimulate production of IGF-1 (levels of GH remain high, but there is reduction in IGF-1 concentrations) in the liver
iii. GH receptor antagonist for acromegaly
What are the side effects of Pegvisomant (Somavert)?
- Nausea and diarrhea
- Flu-like symptoms
- Elevations in hepatic aminotransferase
Dwarfism (children)
- Short stature–commonly defined by a physical height that is more than two standard deviations below the population mean for a given age, sex, and population
- Increased body fat, decreased muscle mass
What are the recombinant GH (somatropin) for dwarfism?
- Genotropin
- Humatrope
- Norditropin
- Nutropin AQ
- Omnitrope
- Saizen
- Serostim
- Zomacitin
- Zorbtive