Hypothalamic and Pituitary Hormones Flashcards
_____________: integrates information received from various parts of the brain, humoral factors and physiochemical parameters from the circulation
Hypothalamus
What part of the pituitary is composed of axons of hypothalamic neurons and, thus, is an extension of the hypothalamus?
Posterior pituitary
What part of the pituitary is known as the master gland and why?
Anterior pituitary because it regulates the activities of all major organs of the body.
What part of the pituitary receives hypothalamic hormonal inputs through the hypothalamic hypophyseal portal vein system, which collects venous blood from the hypothalamus and drains it to the pituitary?
Anterior pituitary
What are the pharmacological applications for pituitary hormones?
1) Replacement therapy for hormone deficiency
2) Antagonists for diseases of hormone production
3) Diagnostic tool for identifying endocrine disorders
What type of capillaries are seen in the pituitary portal vein circulation?
Fenestrated capillaries which results in easy access of releasing hormones from the hypothalamus to the anterior pituitary
What are the different hormones released from the hypothalamus?
- Growth Hormone Releasing Hormone (GHRH)
- Gonadotropin-Releasing Hormone (GnRH)
- Thyrotropin-Releasing Hormone (TRH)
- Corticotropin-Releasing Hormone (CRH)
- Dopamine (DA)
What is another name for Corticotropin-Releasing hormone?
Corticorelin
What are the different hormones released from the Anterior pituitary?
- Growth Hormone (GH)
- Luteinizing Hormone (LH)
- Follicle Stimulating Hormone (FSH)
- Prolactin
- Thyroid-Stimulating Hormone
- Adrenocorticotropin (ACTH)
What are the different hormones released from the posterior pituitary?
- Oxytocin
- Vasopressin (Antidiuretic hormone, ADH)
Which pituitary hormone is used to distinguish Cushing’s syndrome from ectopic ACTH secretion?
Corticorelin/CRH
An increase in TRH leads to an increase in TSH which leads to an increase in what?
Thyroxine (in thyroid)
An increase in CRH leads to an increase in ACTH which leads to an increase in what?
Glucocorticoids and mineralocorticoids (adrenal cortex)
An increase in GnRH leads to an increase in FSH and LH. When these hormones increase what occurs and where?
Increase in sex steroids in gonads due to LH
Increase in inhibit in gonads due to FSH
An increase in GNRH leads to an increase in GH, which leads to an increase in what?
Insulin-like growth factor-1 (IGF-1) which is in the liver, muscles, bone, and kidney
What are the pituitary inhibiting hormones and what do they do?
- Somatostatin: Decrease in GH and TSH
- Dopamine: Decrease in prolactin and in high doses, decrease in GH as well.
What hormones are secreted by the hypothalamus and act directly on the periphery? What do they do?
- Arginine Vasopressin: regulation of renal water conservation
- Oxytocin: Milk-let down and partuition (child birthing)
Growth promotion in humans is mediated by regulating the production of which factors?
IGF-1 and IGF-2 (insulin-growth factor)
These factors are insulin-like and can cause hypoglycemia
What hormone is involved in lipid and carbohydrate metabolism, and promotes lean body mass and bone density?
Growth Hormone
Anabolic effects in muscle and catabolic effects in lipid cels
What does a deficiency of GH in childhood result in?
Failure to reach adult height and increased body fat and decreased muscle mass.
What does a deficiency of GH in adulthood result in?
Decreased lead body mass, obesity, asthenia (weakness), and reduced cardiac output
What are the pharmacokinetics of GH?
Plasma half-life: 20-25 minutes, undergoes hepatic clearance
Administration: Subcutaneous injections 6-7 times per week; peak plasma concentration is 2-4 hours
GH promotes ____________ growth indirectly until the closure of the epiphyses at the end of puberty.
LONGITUDINAL
GH promotes LONGITUDINAL growth indirectly until the closure of the epiphyses at the end of puberty.
GH effects are mediated through which cytokine receptor superfamily?
JAK/STAT
GH (increases/decreases) insulin sensitivity.
Decreases
GH DECREASES insulin sensitivity -> Mild hyperinsulinemia
-Increases blood glucose and free fatty acids
What is the recombinant form of growth hormone used to treat growth hormone deficiency (can be genetic or the result of trauma to the pituitary or hypothalamus)?
Somatropin (rGH)
Patients with short bowel syndrome who are dependent on total parenteral nutrition (TPN) should be given what? why?
GH in combination with glutamine
This has trophic effects on the intestinal mucosa, increasing growth and function.
T/F - GH is used for anti-aging remedy.
False - There are unsubstantial claims as an “anti-aging” remedy - it has actually been shown to decrease life-span in animal models.
What are some reasons that GH is used to treat non-GH deficiencies?
- Prader-Willi syndrome
- Turner’s syndrome
- Renal insufficiency pre-transplant
- Idiopathic short stature (ISS)
What is Prader-Willi syndrome and how will treating a patient with GH help?
It is an autosomal dominant genetic disease that is associated with growth failure, obesity, and carbohydrate intolerance
Treatment increase lean body mass, linear growth, and energy expenditure.
What is Turner’s syndrome (45 X) and how will treating a patient with GH help?
This is a genetic disease where there is a congenitally missing X chromosome. Patients have a short stature, webbed neck and underdeveloped gonads.
High-dose treatment effective in increasing height 4-6 inches. It is combined treatment with sex steroids.
What is definition of Idiopathic short stature?
> 2.25 standard deviations below the norm.
Many years of treatment result in an average increase of adult height from 1.57-2.67 inches
Cost is $5-40K annually - Cost risk benefit
T/F - GH is well tolerated in children and side effects are rare.
True
What are some of the adverse effects for children when taking GH?
- Pseudotumor cerebri, slipped capital femoral epiphysis, progression of scoliosis, peripheral edema, muscle pain, hyperglycemia
- Prader-Willi or patients with sleep apnea: increased risk of asphyxiation in severely obese patients
- Treatment with GH requires periodic evaluation of anterior pituitary hormones to monitor deficiency in hydrocortisone, levothyroxine, or gonadal hormones and diabetes
- Contraindications: Diabetic retinopathy, epiphyseal closure, trauma, obesity, neoplastic disease (tumors).
What is used for treatment in children with growth failure that have severe IGF-1 deficiency and that are unresponsive to GH?
- Mecasmerin (Increlex)
- Mecasermin rinfibrate (IPLEX)
Wy are Mecasmerin and Mecasermin used instead of just GH?
GH has a short half life (20-25 mins). These drugs are combinations of rhIGF-1 and rhIGF-3, which significantly increases the circulating half life of rhIGF-1.
What are the adverse effects of Mecasmerin and Mecasermin?
Hypoglycemia, intracranial hypertension and elevation of liver enzymes.
Patients are told to consume carbohydrate-containing meals 20 minutes prior to drug administration
What is Somatostatin and where is it released?
Somatostatin is a 14-amino acid peptide that is the most widely distributed hypothalamic hormone. It is also produced in pancreatic D cells
What is the action of somatostatin?
It inhibits the release of growth hormone, insulin, glucagon, and gastrin.
What is somatostatin’s half life and is it used greatly in the treatment of patients with GH excess?
Half life: 1-3 minutes (Very short)
Somatostatin has limited clinical usefulness due to its short duration.
It is metabolized and excreted via renal system (kidneys).
Somatostatin inhibits which two factors?
Inhibits GH and TH
This causes there to be a decrease in GH and TH.
What is Octeotide (Sandostatin)?
Somatostatin analog with a much longer half life of 80 minutes.
40 Xs more potent than somatostatin in inhibiting GH
2 Xs more potent than somatostatin in inhibiting Insulin
Can be given as long acting medicine (IM injections)
What are the clinical indications for Octeotide (Sandostatin)?
Acromegaly, Thyrotropin pituitary adenoma and carcinomas, Gastrinoma, acute bleeding control from esophageal varicose, glucagonoma
What are the adverse effects of Octeotide (Sandostatin)?
- Significant gastrointestinal disturbances
- Biliary sludge/gallstones (frequency 20-30% (>6 mos treatment))
- Sinus bradycardia (25% frequency)
- Conduction disturbances (10%)
What four drugs are used to treat acromegaly?
1) Octreotide (Sandostatin)
2) Lanreotide (Somatuline)
3) Pegvisomant (Somavert)
4) Bromocriptine (Parlodel)
All have soma- except my Bro
What is Lanreotide (Somatuline)?
- Long acting drug used to treat acromegaly
- Equally as efficacious to octreotide in reducing GH levels and normalizing IGF-1 concentrations
What is Pegvisomant (Somavert)? Use, MOA, Adverse Effects
- GH receptor antagonist
- Allows for GH receptor dimerization, but blocks the conformational changes needed for signal transduction.
- Used for acromegaly - reduction and subsequent normalization of IGF-1
- Adverse effects: Pain at injection sight, swelling of limbs, chest pain, hypoglycemia, and nausea
What is Bromocriptine (Parlodel)?
- Dopamine D2 receptor agonist (More effective at inhibiting prolactin secretion)
- In high doses will inhibit GH
- Used in treatment of small GH-secreting tumors (Acromegaly)
Where is gonadotropin-releasing hormone produced?
Arcuate nucleus of the hypothalamus
Pulsatile secretion of GnRH is necessary for the production of which two hormones?
FSH & LH
_______________ is the acetate salt of synthetic human GnRH.
Gonadorelin
What are some synthetic forms of GnRH that are more potent and longer lasting?
- Leuprolide (Lupron)
- Nafarelin (Synarel)
- Goserelin (Zoladex)
- Histerlin (Supprelin)
- Triptorelin (Trelstar)
*Leuprolide and the -relins
When theres a pulsatile IV of GnRH analogs, how frequent is it given?
Every 1-4 hours
Can GnRH synthetic drugs be used over a long period of time?
No, long term use is avoided because of toxicity.
How is delayed puberty tested to see if its due to constitutional delay or hypogonadotropic hypogonadism?
LH response is tested following subcutaneous GnRH bolus.
- Peak LH > 15.6 mlU/mL = Normal (indicating puberty will occur soon)
- Peak LH response impaired suggests hypogonadotropic hypogonadism (probably indicative of pituitary/hypothalamic dysfunction but it does not rule out constitutional delay).
T/F - GnRH analogs can be used for both stimulation as well as inhibition of different things.
TRUE
How are GnRH analogs used in stimulation?
- Infertility due to hypothalamic hypogonadotropic hypogonadism (both sexes), used to stimulate pituitary function
- Programmable pump technology allows pulsatile GnRH treatment (frequency: every 90 minutes) - patient has to take into account inconvenience/cost issues
What are some different things that GnRH analogs are used for inhibition?
- Prostate cancer
- Endometriosis
- Uterine Leiomyomata (fibroids)
- Precocious puberty
GnRH analog agonists along with androgen receptor antagonists are used to help in the treatment of _________________________.
Prostate cancer
These drugs reduce circulating testosterone levels. During the “flare period” patients can experience pain in patients with bone metastases, tumor growth, and can worsen urinary obstruction.
Why are GnRH analog agonists used in endometriosis?
Diminishes pain by elimination of cyclic changes to estrogen and progesterone.
Treatment is max 6 months due to a decrease in bone density as a result of ovarian suppression.
Why is treatment of endometriosis with GnRH analog agonists limited to 6 months only?
Decrease in bone density due to ovarian suppression
What drugs are used to reduce fibroid size in uterine leiomyomata (fibroids)?
Leuprolide
Goserlin
Nafarelin
How long are the drugs used to reduce fibroid size in uterine leiomyomata (fibroids)?
Used for 3-6 months plus supplemental iron to reduce anemia
What type of drugs are used to treat precocious puberty and when do children start taking it?
GnRH analog agonists used to slow puberty. Given to children who start to show secondary sex characteristics early (females- 7&8 and males 9).
1 month IM injection of Leuprolide, or yearly implant of Histrelin acetate
Treatment until 11 in females and 12 in males.
