Hypothalamus and Pituitary Flashcards
What is the long loop of feedback regulation within the H-P-end organ axis?
systemic hormones that act on the hypothalamus or pituitary
What is the short loop of feedback regulation within the H-P-end organ axis?
pituitary hormones that act on the hypothalamus
Describe the GH axis.
- GHRH and somatostatin from the hypothalamus stimulate and inhibit GH release from the pituitary, respectively
- GH targets the liver to produce IGF-1
- together, GH and IGF-1 act on end-organs to promote lean growth and hyperglycemia
Describe the TSH axis.
- TRH induces release of TSH from the pituitary
- TSH acts on the thyroid to promote release of T3/T4
What are thyroxine and triiodothyronine?
T4 and T3, respectively
Describe the ACTH axis.
- CRH stimulates the release of ACTH from the anterior pituitary
- ACTH then acts on the adrenal cortex
- the adrenal cortex releases mineralocorticoids, glucocorticoids, and androgens in response
Describe the FSH/LH axis.
- GnRH stimulates the release of both from the anterior pituitary
- FSH and LH then act on the gonads to stimulate a rise in sex steroids and other reproductive functions
Describe the prolactin axis.
- release of prolactin form the anterior pituitary is stimulated by CRH and inhibited by dopamine
- it acts on the breast to stimulate milk production and in the hypothalamus to inhibit GnRH production, suppressing the FSH/LH axis
Growth Hormone Deficiency
- presents, most often, in childhood as growth failure
- can arise due to hypopituitarism, IGF-1 deficiency, receptor mutations, etc.
- diagnosis requires careful documentation of growth rate
- the deficiency impairs appropriate growth, lean body mass, and adequate bone density
- treatment involves recombinant GH, which promotes longitudinal bone growth until epiphyseal closure, and allows most children to reach normal adult height
What are the normal effects of growth hormone?
it stimulates linear growth and lean muscle mass (lipolysis and AA uptake) in addition to suppressing the effects of insulin to promote a hyperglycemic state
Describe GH treatment. What is used? How does it differ from endogenous GH? When should cessation occur?
- we use recombinant GH
- it has a much longer half-life than endogenous GH, which is more pulsatile in nature
- cessation occurs when epiphyseal closure occurs
Laron Dwarfism
- a primary growth hormone insufficiency caused by homozygous or compound heterozygous mutations in the GH receptor gene
- characterized by severe postnatal growth failure
- more common in those from the Mediterranean, Middle East, Ecuador, or South Asia
- labs show elevated GH but low IGF-1 and IGFBP-3
- treatment involves Mecasermin, a recombinant IGF-1
What is Mecasermin? What is it used to treat? What is it’s major side effect?
- a recombinant IGF-1 used in the treatment of Laron Dwarfism
- major side effect is hypoglycemia (contrary to normal action), so it is given with a meal
Prader-Willi Syndrome
- a classic syndrome resulting from deletion of genes on the paternal copy of chromosome 15, which results in little GH activity
- presents with growth failure, obesity, and carbohydrate intolerance as well as mild-to-moderate retardation
- GH replacement decreases body fat and increases lean body mass
Turner Syndrome
- females with an XO karyotype (subject to mosaicism)
- present with absent or rudimentary ovaries and a GH deficiency
- often treated, in part, with GH
What are several indications for GH therapy?
- Laron Dwarfism
- Prader-Willi syndrome
- Turner syndrome
- AIDS disease
- short bowel syndrome who are dependent on total parenteral nutrition
What are the toxicities and contraindications of GH therapy?
- pseudotumor cerebri
- slipped capital femoral epiphysis
- hyperglycemia
- increased risk of sleep apnea in those with Prader-Willi
- arthralgia and myalgia
- carpal tunnel syndrome (rarely)
- contraindicated in those with an active malignancy
Acromegaly
- an adult disorder characterized by excess GH
- has an insidious onset with slow growth of course facial features, enlargement of hands and feet, frontal posing
- may manifest with carbohydrate intolerance, left ventricular hypertrophy, hypertension
- they are at increased risk for colon polyps and GI malignancy
- the best screening test is a finding of elevated somatostatin C (known as IGF-1)
- can confirm diagnose because GH level doesn’t decrease in response to a 100g glucose load (post-prandial growth hormone suppression test)
- suggests looking for a pituitary adenoma and, if present, surgical removal
- can also treat with octreotide, a somatostatin analogue, which can reduce GH levels and shrink pituitary adenomas in 50% of cases
- do not use a GH receptor antagonist, this will cause an increase in GH levels because of the feedback mechanisms in place
What is octreotide used for? What are it’s effects? How is it administered? What are it’s adverse effects?
- it is a somatostatin analogue used to suppress the GH axis, particularly in those with a pituitary adenoma presenting with gigantism or acromegaly
- lowers GH levels and shrinks the tumor in 50% of patients
- requires parenteral administration
- possible side effects include nausea, cramps, steatorrhea, and gall stones
Pituitary Apoplexy
- ischemic necrosis of an enlarging adenoma due to compression of the superior hypophyseal artery against the sellar diaphragm followed by hemorrhage into the necrotic area resulting in rapid enlargment
- ## presents with acute pain, cranial nerve palsies, and pituitary insufficiency (secondary hypothyroidism, secondary adrenal insufficiency, etc. so for example, T3 will be low and TSH will also be inappropriately low)
What are the effects of TSH?
- stimulate growth of the thyroid gland
- stimulate synthesis and release of T3/T4
Levothyroxine
- a form of T4 used in the treatment of hypothyroidism
- begin with 1.5 mcg/kg for severe cases
- needs to be taken on an empty stomach one hour removed from food
- absorption decreased by calcium and iron supplements
How should acute adrenal insufficiency (adrenal crisis) be treated? What patient education should follow?
- stabilize with IV dexamethasone or hydrocortisone
- prescribe continued steroids and tell patient to take double or triple dose during times of acute stress (flu, heart attack, bleeding etc.)
- prescribe an injectable form for when adrenal crisis causes severe nausea
What is inhibin?
a hormone secreted by the testes or ovaries which serves to inhibit FSH and LH synthesis and release
What contraindications are there for testosterone therapy?
- young men who wish to bear children should not be placed on exogenous testosterone (lowers sperm count and decreases testicular size)
- those with known prostate or breast cancer
- cases of untreated sleep apnea, erythrocytosis, or urinary obstruction
What is the most common side effect of testosterone therapy in men?
an increase in hemoglobin content
What is the number one kind of hormone-producing pituitary adenoma?
prolactinoma
Why is the prolactin axis unique compared to the other anterior pituitary hormones?
- because it has a direct effect on it’s target tissue and does not require production of a hormone by the target tissue
- as such there is no feedback inhibition for this axis
Prolactinoma
- the number one kind of hormone-producing pituitary adenoma
- highly amenable to pharmacologic treatment compared to other adenomas
- often presents with elevated prolactin levels and decreased levels of the other anterior pituitary hormones due to a mass effect of the tumor
- in premenopausal women, hyperprolactinemia causes hypogonadism with symptoms including galactorrhea, infertility, oligomenorrhea, or amenorrhea
- postmenopausal women are already hypogonadal, so hyperprolactinemia does not change that; however, headaches and impaired vision are common due to mass effect
- men experience hypogonadotropic hypogonadism with decreased libido, impotence, infertility, gynecomastia, and galactorrhea
- Rx: D2 agonist (cabergoline or bromocriptine) is first line
Cabergoline
- a well-tolerated selective D2 agonist used to treat prolactinomas
- effective at shrinking tumors, lowering prolactin levels, and restoring ovulation
- initiated at 0.25 mg twice weekly and increased gradually according to prolactin levels (max 1 mg twice weekly)
Bromocriptine
- a semi-synthetic ergot alkaloid with moderate D2 agonist activity
- secondary to cabergoline for treatment of prolactinomas because it has greater incidence of adverse effects
- these include nausea, vomiting, headache, and postural hypotension
- taken daily after evening meal, beginning with 1.25 mg
How do you expect someone with central diabetes insipidous to fair on a water deprivation test?
- in a normal individual, as fasting state continues, plasma osmolality should remain stable as urine osmolality increases
- in a patient with central diabetes insipidous, plasma osmolality will rise without a significant change in urine osmolality (they can’t concentrate urine)
- after administering desmopressin (a synthetic ADH), they gain the ability to concentrate urine
- as such, plasma osmolality will begin to fall/return to normal and urine osmolality will increase
- if he or she had nephrogenic diabetes insipidous, no change would be seen after administering desmopressin
What are the symptoms of vasopressin deficiency?
- thirst
- polydipsia
- polyuria
