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Flashcards in Anterior Pituitary - Maas & Auble Deck (43):

How does the hypothalamic-pituitary axis for prolactin release differ from most other pituitary hormones?

Whereas the other anterior pituitary hormones are mostly under direct contol of stimulating hypothalamic hormones (CRH for ACTH, GHRH for GH, etc.), prolactin is primarily under direct inhibitory control by dopamine release from the hypothalamus. Prolactin secretion is increased by a decrease in inhibitory dopamine.


What actions does prolactin have on breast tissue?

  • Breast differentiation
  • Duct prolfieration & branching
  • Glandular tissue development
  • Milk protein & lactogenic enzyme synthesis


Which dopamine receptor is primarily responsible for the inhibition of prolactin in the pituitary? What type of receptor protein is it?

D2, a GPCR


What is required for the diagnosis of Hyperprolactinemia?

single measurement of increased serum prolactin

 >250 ng/ml


Your patient has a prolactin level of 340 ng/ml. Before you consider pathological causes, what purely physiological mediators of prolactin levels should you first rule out as the cause?

  • Pregnancy
  • Lactation
  • Exercise
  • Sleep
  • Stress


In general, what types of drugs cause hyperprolactinemia?

Name some drugs in this class.

  • Dopamine antagonists (you're inhibiting the inhibitor!)
    • Receptor antagonists
      • Metoclopramide (used for GERD, nausea)
      • Risperidone (used for schizophrenia, bipolar)
      • Phenothiazines
      • Butyrophenones
    • Synthesis inhibitors
      • Methyldopa (antihypertensive)
  • Estrogens


If a tumor is indeed at fault, which tumor is most likely when a patient's prolactin level is:

  • Mild (25-100 ng/ml)?
  • Moderate (100-250 mg/ml)?
  • Severe (>250 mg/ml)?

  • Mild: Non-prolactin-secreting pituitary tumor with infundibular stalk compression
  • Moderate: Microprolactinoma
  • Severe: Prolactinoma


What effects would infundibular stalk compression cause on the release of:

  • ACTH
  • GH
  • LH & FSH
  • Prolactin

  • Decrease (inhibition of CRH transport to the pituitary)
  • Decrease (GHRH)
  • Decrease (GnRH)
  • Increase (inhibition of the inhibitory dopamine)


Excluding medications and tumors, what are some other pathological causes of hyperprolactinemia?

  • Sarcoidosis
  • Irradiation to the brain
  • Trauma
    • Accidental
    • Pituitary surgery
  • Lymphocytic hypophysitis (autoimmune)
  • Chronic Renal Failure or Cirrhosis (decreased clearance)


How might hyperprolactinemia present in women?

In men?

  • Women
    • Menstrual irregularities
    • Galactorrhea (50-80% of affected women)
    • Infertility
  • Men
    • Decreased libido
    • Erectile dysfunction
    • Galacorrhea (less common: 20-30% of affected men)
  • Hypogonadism in both sexes


Large pituitary tumors such as macroprolactinomas can cause what symptoms secondary to their mass effect?

  • Headaches & neurologic deficits
    • Cavernous sinus involvement
  • Vision changes
    • Optic chiasm compression


Why do young women typically present with microadenomas (incl. microprolactinoma) whereas older women more often present with macroprolactinomas?

(Hint: men also more often present with macroprolactinomas)

  • Young women usually present earlier due to work up of noted menstrual irregularities
  • Post-menopausal women (and men) will obviously not notice symptoms like this
    • Although, sometimes men will be diagnosed early following a presention of decreased libido and/or ED.


What drug class is used to treat hyperprolactinemia?

Name two specific drugs in this class.

Which is preferred, and why?

  • Dopamine agonists
    • Bromocriptine
    • Cabergoline
      • Preferred
      • Higher efficacy (for normalizing prolactin & shrinking tumor size)
      • Higher receptor affinity
      • Fewer side effects (more selective for D2 receptor)
      • Longer half-life (less frequent dosing)


What are side effects of dopamine agonists?

  • Nausea & Vomiting
  • Orthstatic hypotension
  • Dizziness
  • Nasal congestion

(N.B. Cabergoline is reported to cause cardiac valvulopathy in Parkinson's patients, but the drug is used at much higher doses in those patients)


When is Bromocriptine preffered over Cabergoline in the treatment of hyperprolactinemia, and why?

  • In pts undergoing fertility induction that also have hyperprolactinemia
  • As initial treatment for macroprolactinomas that have caused compromise of vision, neurologic status, or pituitary function
  • For safety reasons
    • Bromocriptine has a longer track record for these uses
    • Bromocriptine has a shorter half-life (easier to adjust & compensate for overdoses, I assume)


Which hormone(s) positively regulate(s) GH release from the pituitary?

Which hormone(s) negatively regulate(s) GH release from the pituitary?

Positive: GH

Negative: IGF-1 & Somatostatin


How does acromegaly present clinically?

[memorizing is probably low-yield, go for broad strokes]

A veritable constellation of symptoms:

  • Headache
  • Coarse facial features
    • Lips, nose, & tongue enlargement
    • Skull growth, esp. supraorbital ridges
    • Lower jaw growth
  • Cardiomyopathy, CVD, & HTN
  • Thickened skin
  • Myopathy
  • Increased sweating
  • Hand & feet enlargement
    • Arthropathy
    • Carpal tunnel syndrome
  • Impaired glucose tolerance --> T2DM
  • Hepatomegaly
  • Colon cancer


  1. What is typically measured to diagnose acromegaly?
  2. What confounds can interfere with this measurement?

  1. Serum IGF-1
    • Diagnostic in 99% of pts
    • Better than measuring GH
      • Longer t1/2
      • Less pulsatile
  2. Confounds:
    • Malnutrition
    • Acute illness
    • Celiac disease
    • Poorly controlled DM
    • Liver disease
    • Estrogen ingestion


You suspect your pt has acromegaly but he also has recently come down with the flu. The illness may interfere with IGF-1 levels. How else could you diagnose acromegaly then and there?

  • Oral glucose tolerance test
    • Give 100g glucose load & measure GH levels two hours later
    • Glucose normally supresses GH levels to <1 ng/ml within 2hrs
      • [This seems to fit with GH being greatest shortly after sleep onset - you're not eating!]
    • In acromegaly, GH levels may paradoxically increase, remain unchanged, or decrease but not to <1 ng/ml.


What non-pharmaceutical options are there for treating acromegaly? Are they effective?

  • Transsphenoidal pituitary surgery
    • Curative in 65-95% micro-, 40-60% macro-
  • Radiation therapy


What three drug classes are used to treat acromegaly? Name examples of each.

  • Somatostatin Receptor Ligands (SRLs)
    • Octreotide
    • Lanreotide
  • GH Receptor Antagonist
    • Pegvisomat
      • Blocks peripheral actions of GH (e.g. liver GH receptor)
  • Dopamine agonists - occasionally
    • Cabergoline
      • 30% of GH-secreting pituitary adenomas are plurihormal and also secrete prolactin


What type of receptor is the peripheral GH receptor?



There are many possible causes of panhypopituitarism / hypopituitarism.

Name as many as you can.

[I would suggest being familiar, not memorizing this point by point.]

  1. Mass legions
    • pituitary tumors, craniopharyngiomas, cysts, other tumors & cancers
  2. Treatment of the skull / brain adjacent to the pituitary
    • surgery, radiation, radiosurgery
  3. Infiltrative diseases
    • lymphocytic hypophysitis, hemochromatosis, sarcoidosis
  4. Traumatic
    • head injury or perinatal trauma
  5. Vascular
    • Sheehan's syndrome (post-partum), pituitary tumor apoplexy
  6. Medications
    • opiates, glucocorticoids, thyroxine, sex steroids
  7. Infections
    • Many
  8. Genetic
    • Combined or isolated defects
  9. Developmental
    • Ectopic pituitary, pituitary hypoplasia, midline cerebral/cranial malformations


Describe the clinical (lab) findings of panhypopituitarism.

  • ACTH deficiency or secondary adrenal insufficiency
  • TSH deficiency or seconary hypothyroidism
  • GH deficiency (in adult)
  • Prolactin deficiency
  • Gonadotropin deficiency or secondary hypogonadism

(Note that prolactin is also deficient, highlighting the decreased synthetic capability of the pituitary, as opposed to a blockade of transport from the hypothalamus (e.g. tumor), in which prolactin would increase due to loss of negative dopamine feedback.)


When trying to make a diagnosis of panhypopituitarism, what is the key finding regarding levels of pituitary hormones?

Pituitary hormone levels are low or innapropriately not elevated given the decreases in T4, cortisol, testosterone/estradiol, and IGF-1.


In panhypopituitarism, what drug is given to treat the deficiency in:

  1. Thyroid hormone?
  2. Cortisone?
  3. Female sex hormones?
  4. Male sex hormones?
  5. Growth hormone?

  1. Levothyroxine (T4)
  2. Hydrocortisone
  3. Estrogen and progesterone (if uterus present.)
  4. Testosterone
  5. recombinant Growth Hormone


When treating the thyroid deficiency of a pt with panhypopituitarism, what should you adjust the dosage of levothyroxine based on?

Dose according to free T4not TSH


What extra drug treatments are required for fertility in a man or woman with panhypopituitarism?

  • Female: Gonadotropins & other fertility drugs
  • Male: hCG injections 3x/week


What drug is used to treat mineralocorticoid deficiency in panhypopituitarism?

Trick question [sorry again] - no treatment required!

Mineralocortocoids are part of the RAAS system, which is not compromised in hypopituitarism (secondary adrenal insufficiency). Mineralocorticoid replacement would be required in a primary adrenal insufficiency (or other defect in RAAS).


Regarding rGH replacement therapy for hypopituitarism or isolated GH deficiency:

  1. How often is it given?
  2. What time of day?
  3. What route?
  4. What two factors is the dosing based upon?
  5. What should be monitered to determine any dose changes?

Daily subQ injection

  1. Once daily
  2. Evening, to mimic the normal diurnal pattern of GH release
  3. SubQ
  4. Dosing based on:
    • mg/kg/week
    • etiology of disease
  5. IGF-1 levels


Name four possible clinical signs of growth hormone deficiency in neonates.

  1. Jaundice
  2. Hypoglycemia
  3. Microphallus
  4. Traumatic delivery (contributing factor)


Name 7 possible clinical signs of GH deficiency in children (i.e., older than an infant).

  1. Propensity for hypoglycemia
  2. Increased fat
  3. High-pitched voice
  4. Microphallus
  5. Absent or delayed puberty in the adolescent
  6. Weight less affect than height
  7. Physical skull defects / midline craniofacial abnormalaties
    • Occasionally present
    • Cleft lip, cleft palate, single central incisor


What type of test is used to diagnose GH deficiency in children?

Can you name specific examples?

  • Stimulation tests
    • Exercise
    • Levodopa
    • Clonidine
    • Arginine HCl
    • Glucagon
    • GHRH
    • Insulin (rarely used any more - more dangerous, esp. in infants)


Who will require higher dosing of rGH: a child with a true growth hormone deficiency or a child with idiopathic short stature (ISS)?

ISS requires higher dose.

GH deficiency: body ready & able to respond to GH once it has some!

ISS: Some defect downstream of GH causes "resistance" to the hormone's effects.


Name two genetic disorders that can result in short stature despite adequate GH production.

  1. Turner's Syndrome (most often caused by monosomy X)
  2. Noonan's Syndrome (several signalling genes implicated; some yet unknown)


What specific structures within the cavernous sinus can be compromised by enlargement of the pituitary?

  • Internal carotid artery
  • CNs III, IV, V (V1 & V2), and VI


What should initial treatment be for a macroprolactinoma that has already caused compromise of vision, neurologic function, and pituitary function?

Dopamine agonists are still the favored initial treatment, not surgery.

They are effective in reducing prolactin and shrinking the tumor in >80% of pts.


Is it important to treat patients with a microprolactinoma even if they are asymptomatic?

No. Unless symtoms present (whether from prolactin effects or a tumor mass effect), treatment is usually not needed.


What is the major serum binding protein of IGF-1?



What are general metabolic effects of GH?

  • Antagonizes insulin
  • Increases lipolysis & FFA production
  • Increases protein synthesis


Name two symtoms of primary adrenal insufficiency that will not be present in secondary adrenal insufficiency. Why?

  • Hyperkalemia
    • Deficient mineralocortocoid activity results in decreased potassium excretion. Mineralocortocoid activity is preserved in secondary insufficiency.
  • Hyperpigmentation
    • Excessive ACTH stimulates melanocytes. ACTH is increased in primary insufficiency (loss of negative feedback) but is decreased in secondary insufficiency.


What symptoms of primary hypothyroidism are not present in secondar hypothyroidism?


Unlike adrenal insufficiency, priamry and secondary hypothyroidism are indistinguishable on the basis of clinical features alone. Labs are needed.


What are side effects of GH treatment in children?

S/E are fortunately rare, but can include:

  • SCFE
  • scoliosis
  • pseudotumor cerebri
  • snoring / OSA from tonsil grwoth
  • Cancer risk?
    • Debated. In practice, children with other dispositions for cancer are not recommended for GH therapy.

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