Anterior Pituitary Flashcards
What are the 3 lobes of the pituitary gland?
- Adenohypophysis (anterior pituitary gland)
- Neurohypophysis (posterior pituitary gland)
- Intermediate
What is the size & location of the Pituitary Gland?
What is the role of the intermediate lobe?
- 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
What is the role of the infundibular stalk with the Pituitary Gland?
portal plexus circulation
connects the hypothalamus to the pituitary gland
What is the Pituitary Gland surrounded by?
- Superiorly
- Both sides
- Superiorly: optic chiasm
- Both sides: cavernous sinuses
Cavernous sinuses each contain ____________.
- ICA
- CNs III, IV, VI
- V1, V2
What hormones are secreted by the anterior pituitary gland?
- Prolactin
- Growth Hormone (GH)
- Adrenocorticotrophic hormone (ACTH)
- Follicle Stimulating Hormone (FSH)
- Luteinizing Hormone (LH)
- Thyroid-stimulating Hormone (TSH)
What 2 major peptide hormones are secreted by the posterior pituitary gland?
Synthesis & transport?
- Hormones
- AVP (vasopression) or anti-diuretic hormone
- Oxytocin
- Synthesized by SON & PVN of hypothalamus
- Transported in posterior lobe (neurosecretrory granules) along _supraopticohypophyseal tract _
How does Dopamine regulate prolactin secretion?
- Tonic inhibitory control of prolactin synthesis & secretion
- Made in the hypothalamus
- Keeps prolactin at a basal level
What are the stimulators of Prolactin synthesis & secretion? (7)
- Reduced dopamine availability to lactotroph
- Thyrotropin-releasing hormone (TRH)
- Estrogen
- Vasopressin
- Vasoactive Intestinal Polypeptide (VIP)
- Oxytocin
- Epidermal Growth Factor
What serum measurement of prolactin will confirm Hyperprolactinemia?
- 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
_____________ compression can cause Hyperprolactinemia.
Infundibular stalk compression
How does an infundibular stalk compression cause Hyperprolactinemia?
- Mild/moderate hyperprolactinemia (25-100 ng/ml) in the presence of a large pituitary mass
- Non-prolactin secreting tumor
- Inhibition of dopamine transport
What are some physiological causes of Hyperprolactinemia?
- Pregnancy
- Lactation
- Exercise
- Sleep
- Stress
What are the medications that cause Hyperprolactinemia?
- Anti-hypertensives (methyldopa)
- Estrogens
- D2 dopamine receptor antagonists
- Metoclopramide, domperidone
- Neuroleptics/anti-psychotics
- Phenothiazines, butyrophenones, risperidone
What are the pathological causes of Hyperprolactinemia?
-
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)
What are the systemic disorders that cause Hyperprolactinemia?
-
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
Hyperprolactinemias most commonly present in (men/women) ages ________YO.
Prolactinomas are rare in __________ & ___________.
- Women
- 25-35 YO
- Childhood & adolescence
How does Hyperprolactinemia present in women?
- Young menstruating women
- **Menstrual irregularities **
- Inhibition of FSH & LH
- Galactorrhea (50-80%)
- **Infertility **
How does Hyperprolactinemia present in men?
- Decrease in libido
-
Erectile dysfunction (hypogonadism)
- Inhibition of FSH & LH
- Galactorrhea (20-30%)
Microadenomas are more common in (men/women).
Macroadenomas are more common in (men/women) and ________.
- Microadenomas
- Women
- Macroadenomas
- Men
- **Post-menopausal women **
What are the symptoms of a Macroadenoma?
- Headaches
- Neurologic deficits (cavernous sinus)
- Vision changes (optic chiasm compression)
How is Hyperprolactinemia typically treated?
What are some examples?
- Dopamine agonists
- Bromocriptine
- **Cabergoline **
- Activation of D2 receptors
- Suppress prolactin production
What is the mechanism of Cabergoline?
Why is it the preferred dopamine agonist?
- 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
What are the side effects of dopamine agonists? (Bromocriptine, Cabergoline)
- Nausea, vomiting
- Orthostatic lightheadedness
- Dizziness & nasal congestion
- Cardiac valvulopathy in Parkinson’s patients (Cabergoline)
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
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
What is Growth Hormone?
- Single-chain polypeptide (191 aa)
- Synthesized, stored & secreted by the anterior pituitary somatotrophs
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
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
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
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
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)
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
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)
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
_______ & ________ are the diagnostic tests for Acromegaly.
Serum IGF-1
**Oral glucose tolerance test **
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
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)
What are the treatment options for Acromegaly?
- Transsphenoidal surgery
- Radiation therapy
- **Drug therapy **
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
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
What are the 3 drug therapies used for treatment of Acromegaly?
Dopamine agonists (Cabergoline)
SST receptor ligands
GH receptor antagonists
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%)
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%)
What is Panhypopituitarism?
Deficiency of ALL anterior pituitary hormones
Normal physiologic secretion of pituitary hormones relies on…….. (3 things)
- Intact hypothalamic control of pituitary function
- Transport of hypothalamic regulators to the pituitary through the portal plexus circulation in the infundibular stalk
- Normal functioning of the anterior pituitary hormone secreting cells
What are the causes of Panhypopituitarism?
- Mass lesions
- Treatment of sellar, parasellar & hypothalamic disease
- Infiltrative disease
- Traumatic
- Vascular
- Medications
- Infectious
- Genetic
- Developmental
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
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
-
Males: 8AM fasting serum total testosterone, FSH, LH
-
GH
- Basal IGF-1
- Insulin tolerance test
- GHRH-arginine stimulation test
- Glucagon stimulation test
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
What are the clinical signs of Growth Hormone Deficiency in a neonate?
- Jaundice
- Hypoglycemia
- Microphallus
- Traumatic delivery (contributing factor)
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)
How is Growth Hormone Deficiency diagnosed?
- Exercise
- Levodopa
- Clonidine
- Arginine HCl
- Insulin
- Glucagon
- GHRH
What drug therapy is used to treat Growth Hormone Deficiency?
recombinant human growth hormone (rGH)
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
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
