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Anterior Pituitary Flashcards

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1
Q

What are the 3 lobes of the pituitary gland?

A
  • Adenohypophysis (anterior pituitary gland)
  • Neurohypophysis (posterior pituitary gland)
  • Intermediate
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2
Q

What is the size & location of the Pituitary Gland?

What is the role of the intermediate lobe?

A
  • 600 mg
  • Sits in the skull base in bony structure
    • Sella turcica
  • Intermediate Lobe
    • Regresses in humans (15 wks gestation)
    • Absent in adult normal pituitary gland
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3
Q

What is the role of the infundibular stalk with the Pituitary Gland?

A

portal plexus circulation

connects the hypothalamus to the pituitary gland

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4
Q

What is the Pituitary Gland surrounded by?

  • Superiorly
  • Both sides
A
  • Superiorly: optic chiasm
  • Both sides: cavernous sinuses
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5
Q

Cavernous sinuses each contain ____________.

A
  • ICA
  • CNs III, IV, VI
  • V1, V2
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6
Q

What hormones are secreted by the anterior pituitary gland?

A
  • Prolactin
  • Growth Hormone (GH)
  • Adrenocorticotrophic hormone (ACTH)
  • Follicle Stimulating Hormone (FSH)
  • Luteinizing Hormone (LH)
  • Thyroid-stimulating Hormone (TSH)
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7
Q

What 2 major peptide hormones are secreted by the posterior pituitary gland?

Synthesis & transport?

A
  • Hormones
    • AVP (vasopression) or anti-diuretic hormone
    • Oxytocin
  • Synthesized by SON & PVN of hypothalamus
  • Transported in posterior lobe (neurosecretrory granules) along _supraopticohypophyseal tract _
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8
Q

How does Dopamine regulate prolactin secretion?

A
  • Tonic inhibitory control of prolactin synthesis & secretion
  • Made in the hypothalamus
  • Keeps prolactin at a basal level
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9
Q

What are the stimulators of Prolactin synthesis & secretion? (7)

A
  1. Reduced dopamine availability to lactotroph
  2. Thyrotropin-releasing hormone (TRH)
  3. Estrogen
  4. Vasopressin
  5. Vasoactive Intestinal Polypeptide (VIP)
  6. Oxytocin
  7. Epidermal Growth Factor
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10
Q

What serum measurement of prolactin will confirm Hyperprolactinemia?

A
  • Serum prolactin >250 ng/ml
    • Prolactinoma** **(Prolactin-secreting pituitary tumor)
  • Serum prolactin >200 ng/ml
    • Metoclopramide, Risperidone (Dopamine antagonists)
  • Serum prolactin 100-250 ng/ml
    • Microprolactinomas
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11
Q

_____________ compression can cause Hyperprolactinemia.

A

Infundibular stalk compression

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12
Q

How does an infundibular stalk compression cause Hyperprolactinemia?

A
  • Mild/moderate hyperprolactinemia (25-100 ng/ml) in the presence of a large pituitary mass
  • Non-prolactin secreting tumor
  • Inhibition of dopamine transport
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13
Q

What are some physiological causes of Hyperprolactinemia?

A
  • Pregnancy
  • Lactation
  • Exercise
  • Sleep
  • Stress
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14
Q

What are the medications that cause Hyperprolactinemia?

A
  • Anti-hypertensives (methyldopa)
  • Estrogens
  • D2 dopamine receptor antagonists
    • Metoclopramide, domperidone
  • Neuroleptics/anti-psychotics
    • Phenothiazines, butyrophenones, risperidone
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15
Q

What are the pathological causes of Hyperprolactinemia?

A
  • Hypothalamic-pituitary stalk damage
    • Infiltrative disorders (sarcoidosis)
    • Irradiation to brain
    • Trauma w/ pituitary stalk section or surgery
    • Tumors
  • Pituitary
    • Prolactinomas
    • Macroadenoma (compression of infundibular stalk)
    • Lymphocytic hypophysitis (autoimmune)
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16
Q

What are the systemic disorders that cause Hyperprolactinemia?

A
  • Neurogenic from chest wall trauma, surgery, herpes zoster
    • Stimulation of afferent neural pathways
  • Chronic renal failure
    • Decreased metabolic breakdown of PRL
    • Increased production
  • Cirrhosis
  • Primary hypothyroidism
    • Stimulation of increased hypothalamic TRH
    • Stimulation of PRL
  • Polycystic ovarian disease
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17
Q

Hyperprolactinemias most commonly present in (men/women) ages ________YO.

Prolactinomas are rare in __________ & ___________.

A
  • Women
  • 25-35 YO
  • Childhood & adolescence
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18
Q

How does Hyperprolactinemia present in women?

A
  • Young menstruating women
  • **Menstrual irregularities **
    • ​Inhibition of FSH & LH
  • Galactorrhea (50-80%)
  • **Infertility **
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19
Q

How does Hyperprolactinemia present in men?

A
  • Decrease in libido
  • Erectile dysfunction (hypogonadism)
    • Inhibition of FSH & LH
  • Galactorrhea (20-30%)
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20
Q

Microadenomas are more common in (men/women).

Macroadenomas are more common in (men/women) and ________.

A
  • Microadenomas
    • Women
  • Macroadenomas
    • Men
    • **Post-menopausal women **
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21
Q

What are the symptoms of a Macroadenoma?

A
  • Headaches
  • Neurologic deficits (cavernous sinus)
  • Vision changes (optic chiasm compression)
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22
Q

How is Hyperprolactinemia typically treated?

What are some examples?

A
  • Dopamine agonists
    • Bromocriptine
    • **Cabergoline **
  • Activation of D2 receptors
  • Suppress prolactin production
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23
Q

What is the mechanism of Cabergoline?

Why is it the preferred dopamine agonist?

Study These Flashcards
A
  • Higher efficacy in normalizing prolactin levels
  • Shrinks tumor size
  • Fewer side effects
  • Longer t1/2 = 65 hrs
  • Higher affinity & greater selectivity for D2 receptor
  • 4X more potent than Bromocriptine
24
Q

What are the side effects of dopamine agonists? (Bromocriptine, Cabergoline)

Study These Flashcards
A
  • Nausea, vomiting
  • Orthostatic lightheadedness
  • Dizziness & nasal congestion
  • Cardiac valvulopathy in Parkinson’s patients (Cabergoline)
25
In what situation would **Bromocriptine** be preferred over Cabergoline? What are some of its properties?
**Patients undergoing fertility induction with hyperprolactinemia** t1/2 = 2-8 hrs requires frequent dosing
26
How are **Prolactinomas** treated?
* **Transsphenoidal (surgical) resection** * Patients who can't tolerate dopamine agonists * Patients who don't respond to medical treatment * **No treatment** * Asymptomatic microprolactinomas * **Radiation therapy ** * Patients who can't tolerate dopamine agonists * Tumor that don't regress * Surgical risk too high * Unresectable tumor
27
What is **Growth Hormone**?
* Single-chain polypeptide (191 aa) * Synthesized, stored & secreted by the anterior pituitary somatotrophs
28
How is Growth Hormone secretion regulated?
* Hypothalamic derived factors: **GHRH, SST** * GHRH stimulates somatotroph GH release * SST is the major GH inhibitory factor * GH stimulates **IGF-1** secretion by the liver --\> circulates in the blood attached to binding proteins * \>80% of IGF-1 is bound to **IGFBP-3**
29
How do **GH** & **IGF-1** affect the human skeleton & growth?
* Longitudinal skeletal growth * Skeletal maturation * Acquisition of bone mass * Maintenance of skeletal architecture & bone mass
30
How does Growth Hormone affect human metabolism?
* Effects on carbohydrate, lipid & protein metabolism * Antagonizes insulin action * Increases lipolysis & free fatty acid production * Increases protein synthesis
31
What is **Acromegaly**? What is it usually caused by?
* Abnormal enlargement of the extremities of the skeleton * 2-4 per million * Mean age of diagnosis: 40-50 YO * Almost always due to **GH-secreting pituitary tumor** * Plurihormonal (30%) * Secrete prolactin
32
What is the difference between Acromegaly development in adults & children?
* **Adults**: unrestrained hypersecretion of GH * **Children**: excessive GH secretion prior to closure of the epiphyseal growth plate (gigantism)
33
How does **Acromegaly** clinically present? What is the timeline of progression?
* Rate of change is **slow** **&** **insidious** * Disease present _8-10 yrs_ before diagnosis * Physical changes of the bone & soft tissue * Multiple endocrine & metabolic abnormalities
34
What are the **somatic changes** of Acromegaly?
* Enlargement of bones & soft tissue of hands & feet * Arthralgias of weight bearing joints (knees & hips) * Prognathism or enlargement of the mandible * Frontal bossing or prominent supraorbital ridge * Malocclusion & wide spacing of the teeth * Sleep apnea (50%) * Carpal tunnel syndrome & other peripheral neuropathies & paresthesias * Excessive sweating * Skin tags & nevi * Colon polyps & carcinoma (2.4:1 risk for colon cancer) * Cardiomegaly & cardiomyopathy * Hypertension * Visceromegaly (hepatomegaly, megacolon, thyromegaly)
35
What are the **endocrine-metabolic** changes of Acromegaly?
* **Menstrual abnormalities & male hypogonadism** * Concomitant PRL production by tumor or tumor compression of Gonadotrophs * Galactorrhea * Concomitant PRL production by tumor * Direct GH stimulation of PRL-binding sites in the breast * Type 2 DM/impaired glucose tolerance * Direct anti-insulin effects of GH
36
\_\_\_\_\_\_\_ & ________ are the diagnostic tests for Acromegaly.
**Serum IGF-1** **Oral glucose tolerance test **
37
How is **serum IGF-1** used to diagnose Acromegaly? Why is serum IGF-1 _preferred_ over serum GH?
* Diagnoses _excess GH_ (99% of patients) * **t1/2 = 16 hrs ** * Single measurement more constant & accurate than single measurement of GH * **Short t1/2** * **Pulstatile secretion** * Conditions that cause inaccurately low IGF-1 * Malnutrition * Acute illness * Celiac disease * Poorly controlled DM * Liver disease * Estrogen ingestion
38
How is the **oral glucose tolerance test** used to diagnose Acromegaly?
* 100 g glucose load * Normally, glucose suppresses GH levels * **\< 1 ng/ml by 2 hrs ** * In Acromegaly, GH levels paradoxically _increase_, remain _unchanged_ or _decrease_ (but not below ng/ml)
39
What are the **treatment** options for Acromegaly?
* **Transsphenoidal surgery** * **Radiation therapy** * **Drug therapy **
40
What is the effectiveness of **Transsphenoidal surgery** for Acromegaly?
* Primary therapy * **Cure rate proportional to tumor size ** * Intrasellar Microadenomas (75-95%) * Non-invasive Macroadenomas (40-68%) * 40-60% of tumors _not_ controlled by surgery alone * Cavernous sinus invasion * Intracapsular intraarachnoid invasion
41
What is the effectiveness of **radiation therapy** for Acromegaly?
* Takes **10-20 yrs** * Normalizes GH & IGF-1 levels \>60% * Max response takes 10-15 yrs * Focused single gamma knife radiotherapy * 5 yr remission rate = 29-60% * **Hypopituitarism** \>50% of patients within 5-10 yrs
42
What are the 3 drug therapies used for treatment of Acromegaly?
Dopamine agonists (Cabergoline) SST receptor ligands GH receptor antagonists
43
What are the **SRLs** used for Acromegaly? What are their indications? Side effects?
* **Octreotide, Lanreotide** * SST receptor subtypes 2, 5 * Indicated for 1st line * Low prob. of surgical cure * Failure surgical cure of GH hypersecretion * Before surgery to improve comorbidities * GH & IGF-1 control w/ radiotherapy * **Reduce GH & IGF-1 levels to normal** (40-65%) * **Shrinks tumor size** (50%) * Side effects * Diarrhea * Abdominal cramping * Flatulence * Cholelithiasis (15%)
44
What is the **GH receptor antagonist** used for Acromegaly? Mechanism? Effectiveness?
* **Pegvisomant** * Blocks peripheral action of GH through blockade of GH receptor (**liver**) * Indicated in patients w/ persistent elevation in IGF-1 on max doses of SRLs * Highly effective in acromegaly * **Normalizes IGF-1 (97%)** * Transient elevation in LFTs (25%) * Tumor growth (\<2%)
45
What is **Panhypopituitarism**?
Deficiency of **ALL** anterior pituitary hormones
46
Normal physiologic secretion of pituitary hormones relies on........ (3 things)
1. **Intact** **hypothalamic control** of pituitary function 2. **Transport** **of hypothalamic regulators** to the pituitary through the portal plexus circulation in the infundibular stalk 3. **Normal functioning** of the anterior pituitary hormone secreting cells
47
What are the **causes** of Panhypopituitarism?
* **Mass lesions** * Treatment of sellar, parasellar & hypothalamic disease * **Infiltrative disease** * **Traumatic** * **Vascular** * **Medications** * Infectious * **Genetic** * Developmental
48
What are the **clinical findings** of Panhypopituitarism?
* ACTH deficiency or secondary adrenal insufficiency * TSH deficiency or secondary hypothyroidism * GH deficiency in adult * Prolactin deficiency * Gonadotropin deficiency or hypogonadotropichypogonadism
49
What **diagnostic testing** is done for Panhypopituitarism?
* **Prolactin** * **TSH** * Basal TSH & free T4 * Low free T4 or inappropriately normal TSH * **ACTH** * Cortisol 8AM fasting (\<3 mcg/dl) * ACTH stimulation test (\<18 mcg/dl) * Insulin tolerance test (\<18 mcg/dl) * **FSH/LH** * _Males_: 8AM fasting serum total testosterone, FSH, LH * Insufficiency if testosterone \< normal w/ low or inappropriately normal FSH, LH * _Females_: Basal serum estradiol, FSH, LH * Insufficiency if estradiol is low w/ low or inappropriately normal FSH, LH * **GH** * Basal IGF-1 * Insulin tolerance test * GHRH-arginine stimulation test * Glucagon stimulation test
50
What types of **hormone replacement** are used for Panhypopituitarism?
* TSH or thyroid * **Levothyroxine** or T4 * ACTH or cortisol * **Hydrocortisone** * Gonadotrophs female * **Estrogen & progesterone** * Fertility requires gonadotropins * Gonadotrophs male * **Testosterone** * Fertility requires HCG injections * **Growth Hormone ** * Daily subq injection
51
What are the clinical signs of **Growth Hormone Deficiency** in a _neonate_?
* Jaundice * Hypoglycemia * Microphallus * Traumatic delivery (contributing factor)
52
What are the clinical signs of **Growth Hormone Deficiency** in a _child_?
* Propensity for hypoglycemia * Increased fat * High-pitched voice * Microphallus * Absent or delayed puberty in the adolescent * Weight less affected than height * Occasionally present * Physical defects of the skull * Midline craniofacial abnormalities (cleft lip & palate, single central incisor)
53
How is Growth Hormone Deficiency **diagnosed**?
* Exercise * Levodopa * Clonidine * **Arginine HCl** * **Insulin** * Glucagon * GHRH
54
What **drug therapy** is used to treat Growth Hormone Deficiency?
**recombinant human growth hormone (rGH)**
55
How is recombinant human growth hormone (**rGH**) administered?
* **Subq** injection each evening * Mimics normal diurnal pattern for GH release * **Dosing based on mg/kg/wk & diagnosis** * True GH deficiency \< idiopathic short stature * 0.2-0.3 mg/kg/wk * Check IGF-1 levels for dose changes
56
What are the _side effects_ of recombinant human growth hormone? (**rGH**)
* Slipped capital femoral epiphysis (SCFE) * Scoliosis * Psuedotumor cerebri * Snoring/sleep apnea from tonsil growth * Children at risk for cancers not recommended * Down Syndrome * Previous cancers

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