Hypothalamus and Pituitary

Question 1

What is the long loop of feedback regulation within the H-P-end organ axis?

Answer 1

systemic hormones that act on the hypothalamus or pituitary

Question 2

What is the short loop of feedback regulation within the H-P-end organ axis?

Answer 2

pituitary hormones that act on the hypothalamus

Question 3

Describe the GH axis.

Answer 3

• 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

Question 4

Describe the TSH axis.

Answer 4

• TRH induces release of TSH from the pituitary

- TSH acts on the thyroid to promote release of T3/T4

Question 5

What are thyroxine and triiodothyronine?

Answer 5

T4 and T3, respectively

Question 6

Describe the ACTH axis.

Answer 6

• 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

Question 7

Describe the FSH/LH axis.

Answer 7

• 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

Question 8

Describe the prolactin axis.

Answer 8

• 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

Question 9

Growth Hormone Deficiency

Answer 9

• 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

Question 10

What are the normal effects of growth hormone?

Answer 10

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

Question 11

Describe GH treatment. What is used? How does it differ from endogenous GH? When should cessation occur?

Answer 11

• 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

Question 12

Laron Dwarfism

Answer 12

• 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

Question 13

What is Mecasermin? What is it used to treat? What is it’s major side effect?

Answer 13

• 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

Question 14

Prader-Willi Syndrome

Answer 14

• 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

Question 15

Turner Syndrome

Answer 15

• females with an XO karyotype (subject to mosaicism)
• present with absent or rudimentary ovaries and a GH deficiency
• often treated, in part, with GH

Question 16

What are several indications for GH therapy?

Answer 16

• Laron Dwarfism
• Prader-Willi syndrome
• Turner syndrome
• AIDS disease
• short bowel syndrome who are dependent on total parenteral nutrition

Question 17

What are the toxicities and contraindications of GH therapy?

Answer 17

• 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

Question 18

Acromegaly

Answer 18

• 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

Question 19

What is octreotide used for? What are it’s effects? How is it administered? What are it’s adverse effects?

Answer 19

• 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

Question 20

Pituitary Apoplexy

Answer 20

• 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)

Question 21

What are the effects of TSH?

Answer 21

• stimulate growth of the thyroid gland

- stimulate synthesis and release of T3/T4

Question 22

Levothyroxine

Answer 22

• 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

Question 23

How should acute adrenal insufficiency (adrenal crisis) be treated? What patient education should follow?

Answer 23

• 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

Question 24

What is inhibin?

Answer 24

a hormone secreted by the testes or ovaries which serves to inhibit FSH and LH synthesis and release

Question 25

What contraindications are there for testosterone therapy?

Answer 25

• 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

Question 26

What is the most common side effect of testosterone therapy in men?

Answer 26

an increase in hemoglobin content

Question 27

What is the number one kind of hormone-producing pituitary adenoma?

Answer 27

prolactinoma

Question 28

Why is the prolactin axis unique compared to the other anterior pituitary hormones?

Answer 28

• 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

Question 29

Prolactinoma

Answer 29

• 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

Question 30

Cabergoline

Answer 30

• 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)

Question 31

Bromocriptine

Answer 31

• 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

Question 32

How do you expect someone with central diabetes insipidous to fair on a water deprivation test?

Answer 32

• 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

Question 33

What are the symptoms of vasopressin deficiency?

Answer 33

• thirst
• polydipsia
• polyuria