Anterior Pit (5/6) Flashcards

1
Q

what important shit sits around the anterior pituitary

A

common carotid

sphenoid sinus with CN III, IV, VI

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2
Q

What does the anterior pit secreate?

A

Prolactin

Growth hormone (GH)

Adrenocorticotropic hormone (ACTH)

Follicle stimulating hormone (FSH)

Luteinizing hormone (LH)

Thyroid‐stimulating hormone (TSH)

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3
Q

Prolactin synthesis and secretion is mainly under tonic inhibitory control by_____ which is made in the hypothalamus and it keeps prolactin at its basal level.

A

dopamine

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4
Q

Stimulators of _______ include reduced dopamine availability to the lactotroph, thyrotropin‐releasing hormone (TRH), estrogen, vasopressin, vasoactive intestinal polypeptide (VIP), oxytocin and epidermal growth factor.

A

prolactin synthesis and secretion

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5
Q

How is hyperprolactinemia diagnosed?

A

single measurement of serum prolactin and a level above the appropriate population reference range confirms the diagnosis.

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6
Q

A serum prolactin concentration of >250 ng/ml usually indicates the presence of a

A

prolactinoma (prolactin‐secreting pituitary tumor)

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7
Q

However, some drugs, including _____and _____ may increase prolactin to >200 ng/ml

A

metoclopramide and risperidone (dopamine antagonists),

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8
Q

What is the likely cause of mild/mod hyperprolactinemia in the 25-100ng/ml range?

A

in the presence of a larger pituitary mass, is more likely to be due to a nonprolactin‐secreting tumor with infundibular stalk compression and inhibition of dopamine transport to the lactotroph.

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9
Q

PHysiological causes of HYPERprolactinemia

A

Pregnancy, lactation, exercise, sleep and stree

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10
Q

Medications that cause hyperprolactinemia

A

Antihypertensives such as methyldopa

Estrogens

D2 dopamine receptor antagonists such as metoclopramide, domperidone Neuroleptics/antipsychotics such as phenothiazines, butyrophenones,risperidone also block dopamine receptors

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11
Q

Hyperprolactinemia can be a result of hypothalamic-pituitary stalk damage as a result of:

A

Infiltrative disorders (Sarcoidosis)

Irradiation to brain

Trauma with pituitary stalk section or pituitary surgery Tumors

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12
Q

Hyperprolactinemia due to pitutiary origin may result from

A

Prolactinomas

Macroadenoma (compression of infundibular stalk)

Lymphocytic hypophysitis (autoimmune)

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13
Q

Prolactinomas and hyperprolactinemia are more common in women with peak prevalence being between ___ years

A

25‐35

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14
Q

How do young menstrating women present with a prolactinoma?

A

young menstruating women present with menstrual irregularities, galactorrhea (occurs in 50‐80% of affected women) and infertility.

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15
Q

How do men present with hyperprolactinemia

A

Men may report a decrease in libido and erectile dysfunction as a result of hypogonadism, but galactorrhea is less common, occurring in approximately 20‐30% of affected men.

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16
Q

In hyperprolactinemia, The hypogonadism in men and decrease in menses in women are both caused by the hyperprolactinemia inhibiting the

A

pituitary gonadotropins, FSH and LH.

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17
Q

When prolactinoma is the cause of the hyperprolactinemia, women tend to present with microadenomas due to

A

the early presentation and work up of the menstrual irregularities

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18
Q

macroprolactinomas are more frequent in

A

men and postmenopausal women at presentation.

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19
Q

signs and symptoms of macroprolactinomas include

A

headaches, neurologic deficits due to cavernous sinus involvement and visions changes due to optic chiasm compression and cavernous sinus involvement

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20
Q

Main treatement for Hyperprolactinemia

A

Dopamine agonist to supress produciton of prolactin via D2 receptor

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21
Q

MOA of Cabergoline in tx of hyperprolactinemia

efficacy:

A

dompaine agonist

higher efficacy in normalizing prolactin levels and in shrinking tumor size and fewer side effects.

longer half-life (65 hours), higher affinity, and greater selectivity for the D2 receptor (approximately four times more potent) than bromocriptine

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22
Q

Side effects of Cabergoline

A

nausea, vomiting, orthostatic lightheadedness, dizziness and nasal congestion, but cabergoline has also been reported to cause a cardiac valvulopathy in Parkinson’s patients treated with much higher doses of.

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23
Q

Dopamine agonist recommended in patients undergoing fertility induction that also have hyperprolactinemia, because of its greater track record.

A

Bromocriptine:

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24
Q

Whats the half life of bromocriptine

A

Bromocriptine has a relatively short elimination half-life (between 2 and 8 hours) and requires frequent dosing.

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25
Q

What are the results of using bromocriptine in pt with prolactinoma?

A

Normalize prolactin, decrease tumor size and restore gonadal function in greater than 80% of patients with prolactinomas

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26
Q

Initial treatment for macroprolactinomas that have caused compromise of vision, neurologic deficits and pituitary function.

A

Bromocriptine

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27
Q

What two factors inhibit GH release?

What increaes it?

A

inhibited by IGF-1 and somatostatin

increased by GHRH

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28
Q

. GH stimulates _____ secretion by the liver which circulates in the blood attached to binding proteins

A

insulin‐like growth factor 1 (IGF‐1)

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29
Q

____and _____ are critical in determining longitudinal skeletal growth, as well as skeletal maturation and acquisition of bone mass and in adulthood, they are instrumental in the maintenance of skeletal architecture and bone mass

A

GH and IGF‐1

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30
Q

GH also has effects on carbohydrate, lipid and protein metabolism by :

A

antagonizing insulin action, increasing lipolysis and free fatty acid production and increasing protein synthesis.

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31
Q

e abnormal enlargement of the extremities of the skeleton and is caused by unrestrained hypersecretion of GH in adulthood

A

acromegaly

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32
Q

. In children, excessive GH secretion prior to closure of the epiphyseal growth plate leads to

A

gigantism or very tall stature

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33
Q

Acromegaly is always due to

A

due to a GH‐secreting pituitary tumor

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34
Q

Approximately, 30% of GH‐secreting pituitary adenomas are_____ and also secrete prolactin. The incidence of acromegaly is about 2‐4 per million with a mean age at diagnosis of 40‐50 years.

A

plurihormonal

35
Q

period from the earliest onset of symptoms and signs to diagnosis is 8‐10 years during which time many patients have been treated both medically and surgically for many of the metabolic abnormalities and morbidities caused by GH excess.

A

timeline for acromegaly

36
Q

common features of somatic changes we see with acromegaly

A

big hands/feet, prognathism or enlarged mandible, frontal bossing, malocculsion w/ spaced teeth, sleep apnea, skin tags and nevi, excess sweating, cardiomegaly, HTN

37
Q

Endocrin changes seen inpts with acromegaly

A

Menstrual abnormalities and male hypogonadism due to concomitant PRL production by tumor or tumor compression of gonadotrophs

Galactorrhea due to (a) concomitant PRL production by tumor or (b) direct GH stimulation of PRL‐ binding sites in the breast

Diabetes mellitus type 2/impaired glucose tolerance caused by direct anti‐insulin effects of GH.

38
Q

Measurement of______ can diagnose excess GH in 99% of patients with acromegaly.

A

serum IGF‐1

39
Q

IGF‐1 has a half life of 16 hours so a single measurement is more constant and accurate than a single measurement of GH due to

A

its very short half life and very pulsatile secretion.

40
Q

Conditions that can cause inaccurate low IGF‐1 levels include

A

malnutrition, acute illness, celiac disease, poorly controlled diabetes mellitus, liver disease, and estrogen ingestion.

41
Q

What is another test besides IGF-1 to diagnose GH excess

A

Oral glucose tolerance test, using a 100 gram glucose load, is another test used to diagnose GH excess

42
Q

whats the #1 tx for acromegaly?

A

transphenoid surgery to remove the tumor

Patients with intrasellar microadenomas have a 75‐95% cure rate with surgery. Even in patients with noninvasive macroadenomas surgical removal results in normalization of IGF‐1 in 40‐68% of patients

43
Q

How does radiation therapy work for pts with GH excess?

A

can decrease and normalize GH secreation; may take 10-20 yrs to achieve

has 60% in normalizing ; single dose gamma knife radiotherapy with 5 year remission rate

44
Q

What drug therapy is recommended for acromegaly?

A

somatostatin receptor ligands (SRLs); ocreotide and lanreotide

Cabergoline

Pegvisomat

45
Q

GH receptor antagonist used to tx acromegaly. Works by blocking peripheral action of GH (liver GH receptor)

A

Pegvisomant

46
Q

is indicated in patients who have persistent elevation in IGF‐1 with maximum doses of SRLs.

A

Pegvisomant

47
Q

. This drug is highly effective in the treatment of acromegaly and normalizes IGF‐1 levels in 97% of patients; however, transient elevation in liver function tests is seen in 25% and tumor growth is seen in <2% of patients treated with this drug.

A

Pegvisomant

48
Q

is the most efficacious of the dopamine agonist in acromegaly but it is very limited and is effective in less than 10% of patients.

A

Cabergoline

49
Q

In acromegaly these are indicated for first line treatment when there is low probability of surgical cure, after failed surgical cure of GH hypersecretion, before surgery to improve severe comorbidities that prevent or could complicate immediate surgery, and to provide GH and IGF‐1 control or partial control while waiting for radiotherapy to its maximum effect

A

Octreotide and lanreotide

50
Q

Receptor targets for treatment of acromegaly. Pituitary somatostatin receptor subtypes and D2 receptors and peripheral growth hormone (GH) receptors are targets for therapeutic ligands

A

targets for pituitary receptors

51
Q

results from the failure of one or more pituitary hormones to be produced or secreted from the anterior pituitary gland while panhypopituitarism is the deficiency of all anterior pituitary hormones

A

Hypopituitarism

52
Q

Mass lesions that can cause Panhyopituitarism/Hypopituitarism

A

such as pituitary tumors, craniopharyngiomas, cysts (Rathke’s cleft cyst), other brain tumors (meningiomas), pituitary carcinomas, metastatic tumors (breast, lung, colon)

53
Q

Treatment of sellar, parasellar and hypothalamic disease, such as pituitary/hypothalamic surgery, radiotherapy, radiosurgery (gamma knife) can lead to:

A

Panyhypopituitarism/Hypopituitarism

54
Q

other causes of Panhypopituitarism

A

Infiltrative disease, such as autoimmune (lymphocytic hypophysitis), hemochromatosis, sarcoidosis

Traumatic, such as head injury, perinatal trauma

Vascular, such as Sheehan’s syndrome, pituitary tumor apoplexy

Medications, such as opiates, pharmacologic glucocorticoid therapy, suppressive thyroxine therapy,sex steroid treatment

55
Q

Key clinical findings of Panhypopituitarism

A

ACTH deficiency or secondary adrenal insufficiency

TSH deficiency or secondary hypothyroidism

GH deficiency in adult

Prolactin deficiency

Gonadotropin deficiency of hypogonadotropic hypogonadism

56
Q

ACTH deficiency or secondary adrenal insufficiency

A

Unintentional weight loss, Generalized weakness, Lethargy and fatigue, Nausea/vomiting/anorexia, Abdominal pain, Diffuse arthralgias and myalgias, Orthostatic hypotension, Hyponatremia, Hypoglycemia

57
Q

TSH deficiency or secondary hypothyroidism causes:

A

Weight gain, Generalized weakness, Fatigue and lethargy, Diffuse arthralgias and myalgias, Cold intolerance, Constipation, Dry skin and hair, Diffuse edema with periorbital edema Bradycardia

58
Q

GH deficiency in adult

A

Abnormal body composition with increased visceral fat and decreased lean muscle mass, Psychological impairment with reduced energy, social isolation, emotional lability, depressed mood, Reduced muscle strength and exercise performance, Reduced bone mineralization, Abnormal lipid profile with elevated LDL and TG and decreased HDL

59
Q

When diagnosing panHYPOpituitarism, what do we order for Prolactin, TSH?

A

Prolactin: see basal prolactin level

TSH: see basal TSH and free T4: low T4 with low or inappropriately normal TSH

60
Q

ACTH in Panhypopituitarism:

A

cortisol 8AM fasting: insufficient if cortisol<3 mcg/dl

  • ACTH stimulation test: serum cortisol insufficiency if response <18 mcg/dl
  • Insulin tolerance test with serum measurement of cortisol at 0, 30, and 60 mins: insufficiency if serum cortisol resonpse is <18mcg/dl
61
Q

Testing for Panhypopituitarism: FSH/LH Males: 8AM fasting serum total testosterone, FSH, LH:

A

insufficiency if testosterone is below the normal range with low or inappropriately normal LH and FSH.

62
Q

Testing for Panhypopituitarism

In Females: Basal serum estradiol, FSH, LH: insufficiency if

A

estradiol is low with low or inappropriately normal FSH and LH.

63
Q

Hormone replacement recomended for low thyroid

A

TSH or thyroid is replaced with levothyroxine or T4, adjust dose according to free T4 and not TSH

64
Q

What do we do to tx panhypopituitarism from adrenal gland standpoint?

A

ACTH or cortisol is replaced with hydrocortisone 10 mg QAM and 5 mg QPM or prednisone 5‐7.5 mg QD, no mineralocorticoid is needed with secondary adrenal insufficiency

65
Q

What do you to do tx females with panhypopituitarism suffering from lack of Gonadotropins

A

Gonadotropins female is replaced with estrogen and progesterone (if uterus present), such as OCP, patch. Fertility will require fertility drugs, gonadotropins, for ovulation.

66
Q

What do you to do tx males with panhypopituitarism suffering from lack of Gonadotropins

A

Gonadotropins male is replaced with testosterone, such as injections, gel, patch forms. Fertility will require HCG injections IM 3 times per week.

67
Q

Newborn baby has jaundice, hypoglycemia, microphallus

these are all symptoms of:

A

GH deficiency in nenoate

68
Q

Propensity for hypoglycemia Increased fat High‐pitched voice Microphallus Absent or delayed puberty in the adolescent Weight less affected than height

all signs of

A

GH deficiency in children

69
Q

GH deficiency in children can be seen doing which type of test

A

often order combo of tests: see stuff like arginine,Levodopa, or insulin or clonidine

signlas for GH peak at sleep, exercise

70
Q

Recommended therapy for child with GH deficiency

A

e recombinant human growth hormone (rGH), which is given as a subcutaneous injection. It is typically given each evening to mimic the normal diurnal pattern of growth hormone release.

71
Q

How do you dose rGH for child with true GH deficiency

A

need much smaller doses of GH than a child with idiopathic short stature (ISS), and the dose is around 0.2‐0.3 mg/kg/week.

72
Q

How do we determine dose changes for rGH in GH deficienct children?

A

check IGF‐I (insulin‐like growth factor 1) levels to determine dose changes.

73
Q

is used therapeutically in children with short stature with growth hormone deficiency and short stature despite adequate GH production with other conditions including Turner’s syndrome, N

A

Growth hormone (hGH)

74
Q

a dopamine agonist, is used for the treatment of hyperprolactinemia, prolactin‐secreting adenomas, acromegaly and Parkinson’s disease.

A

Bromocriptine,

75
Q

is also a dopamine agonist used to treat hyperprolactinemic disorders.

A

Cabergoline

76
Q

somatostatin analogs used to treat acromegaly

A

Octreotide and lanreotideare

77
Q

is a GH receptor antagonist used for the treatment of acromegaly

A

Pegvisomant

78
Q

Pt has milky discharge from fluid, not pregnant, no recent deliveries.

get prolactin level: its at 1250 (normal is <23.3)

what is the next step?

A

MRI of pituitary

79
Q

What is the recommended treatement for prolactin secreating pituitary tumor?

A

For macro: start a dopamine agonist such as carbergoline

80
Q

What is the preferred D2 receptor agonist to use over bromocriptine bc has less side effects and better efficacy to normalize prolactin levels

A

cabergoline

81
Q

why do we see hypogonadism with hyperprolactinemia

A

dt its inhibitory effect on gonadotorpins

82
Q

What is a side effect with hGH injections that you need to be careful of?

A

headaches with nausea or vomitting

83
Q

in children tx for growth hormone deficiency, rhGH is given each night by subQ injeciton and you need to check______ to insure proper dosing

A

IGF-1

84
Q

Side effects of GH are rare and include:

A

slipped capital femoral epiphysis, scoliosis, psuedotumor cerebri, obstructive sleep apnea