Lecture 17: Anterior Pituitary Disorders Flashcards
What artery supplies the anterior pituitary gland?
Superior hypophyseal artery
What are the 5 types of endocrine cells in the anterior pituitary? What do they secrete?
- Somatotrophs: GH
- Lactotrophs: LH
- Gonadotrophs: LH & FSH
- Corticotroph: ACTH
- Thyrotroph: TSH
How does a GH deficiency present in general?
Growth disorders in children
Abnormal body composition in adults
How does a Gonadotropin deficiency present?
Menstrual disorders and infertility in women.
Decreased sexual function, infertility, and loss of secondary sex characteristics in men.
How does a TSH deficiency present?
Hypothyroidism
How does an ACTH deficiency present?
Hypocortisolism
How does a Prolactin deficiency present?
Failure of lactation
What primarily inhibits prolactin?
Dopamine
How does prolactin inhibit itself?
Release of prolactin can cause a release of dopamine, so it is a negative feedback loop.
When is prolactin secretion highest?
non-REM sleep, usually 4-6am.
When are PRL levels the highest?
Pregnancy
10x increase
Declines rapidly within 2 weeks of parturition.
What keeps PRL levels elevated post pregnancy? How?
Breast-feeding.
The sucking causes a decrease in dopamine.
What hormone is responsible for the stimulation of milk release?
Oxytocin. PRL stimulates ADDITIONAL milk production.
What are the functions of PRL?
- Induce/maintain lactation
- Decrease reproductive function
- Suppress sex drive
How does PRL inhibit reproductive function?
Suppresses hypothalamic release of GnRH and pituitary gonadotropin secretion and impairs gonadal steroidogenesis.
What is the most common pituitary hormone hypersecretion syndrome?
Hyperprolactinemia in both sexes.
What is the MCC of elevated PRL levels > 200?
PRL-secreting pituitary adenomas.
What is the mnemonic for hyperprolactinemia etiologies?
PROLACTINS
* Pregnancy
* Renal failure
* OCPs
* Liver failure
* Adenoma
* Chest wall disease
* Thyroidal disease
* Infiltrative disease
* Nursing/nipple stimulation
* Stalk effect
What are the hallmark signs of hyperprolactinemia in women?
- Amenorrhea
- Galactorrhea (80% of women)
- Infertility
What is the hallmark sign of hyperprolactinemia in men?
Hypogonadotropic hypogonadism
What other significant structure is extremely close to the pituitary gland?
Optic chiasm
When is the ideal time to measure PRL levels?
Fasting morning levels
What kind of tests can we run to exclude other DDx for hyperprolactinemia?
- TSH/FT4 to r/o hypothyroidism
- hCG
- CMP
- Men: serum total and free testosterone, LH, and FSH.
- Women: serum estradiol, LH, and FSH
When is a MRI indicated for evaluating hyperprolactinemia?
If we have a PRL > 200 or unable to find another cause.
Cannot detect microadenomas.
How do we treat hyperprolactinemia?
- Normalizing PRL levels by finding the cause.
- Microprolactinemias can be treated with estrogen, estrogen/progesterone, or testosterone.
- Dopamine agonists
What is the general medication for hyperprolactinemia regardless of cause?
Dopamine agonists.
What are the two dopamine agonists?
- Cabergoline: long-acting
- Bromocriptine: short-acting (when you want to be pregnant)
What are the main SE of dopamine agonists?
- Constipation
- Nasal stuffiness/congestion
- Dry mouth
- Nightmares
- Insomnia
- Vertigo
What kind of patients do we need to be wary of when giving higher doses of cabergoline?
Parkinson’s. Risk of cardiac valve insufficiency.
How long do patients stay on dopamine agonists?
Usually a year.
Must resect adenoma for longer-term therapy.
Can you take dopamine agonists in pregnancy?
Yes if microadenoma.
Requires monitoring in macroadenomas if med stopped.
What is the only clinical manifestation of hypoprolactinemia?
Inability to lactate after delivery
What is sheehan’s syndrome?
Postpartum hypoprolactinemia due to necrosis of pituitary gland.
Often the result of severe hypotension or shock during delivery.
What are the causes of hypoprolactinemia?
- Sheehan’s syndrome
- Dopamine agonists
- Tumors
How do we treat hypoprolactinemia?
- Dopamine antagonists
- Surgery if tumor
What are GHIH, GH, and IGF-1?
- GHIH = Growth hormone inhibiting hormone (Somatostatin)
- GH = Growth hormone (Somatotropin)
- IGF-1 = Insulin like growth factor 1 (Somatomedin)
What hormone does growth hormone do the opposite effect of?
Insulin
What does GH act on that releases IGF-1?
Liver and other organs, resulting in skeletal growth and cell growth.
What is the most abundant anterior pituitary hormone?
GH
What two things control GH secretion?
GHRH
Somatostatin
When is GH secretion the greatest?
Nighttime
What increases GH levels?
- Sleep
- Stress
- Exercise
- Low BG levels
As GH levels increase, what happens to IGF-1 levels?
Liver will secrete more IGF-1.
What sex has higher IGF-1 levels?
Women
What can cause GH deficiency?
- Disruption of GH axis in either the hypothalamus or pituitary.
What are the main etiologies for acquired GH deficiency?
- Trauma
- Infections (encephalitis, meningitis)
- Cranial irradiation
What is the main cause of mortality of children with GH deficiency?
Other hormone deficiencies, usually because of the CV changes from an altered body composition and dyslipidemia.
How does isolated GH deficiency typically present?
- Short stature
- Micropenis
- Increased fat
- High-pitched voice
- Hypoglycemia
How can GH deficiency be inherited?
- Autosomal dominant
- Recessive
- X-linked
What can cause GH insensitivity?
Defects in GH receptor structure or signaling
What lab tests diagnose GH insensitivity?
- Normal/high GH levels
- Low IGF-1 levels
What is the main and only significant clinical manifestation of a GH deficiency?
Growth failure, which requires tracking of growth rate.
Use a growth chart!
What criteria prompts us to evaluate for possible GH deficiency?
- Short stature 2.5 SD below the mean
- Height velocity < 25th percentile
- Less severe short stature + growth failure without any other explanation.
- Evidence suggesting hypothalamic-pituitary dysfunction
- Evidence for deficits in other hypothalamic-pituitary hormones.
What are other causes of growth failure besides GH deficiency?
- Chronic systemic disease
- Hypothyroidism
- Turner syndrome
- Skeletal disorders
What lab tests should we order to help diagnose GH deficiency?
- GH stimulation test
- IGF-1
- IGFBP3 (binding protein 3), carries IGF-1
- Bone age
What makes measuring GH production difficult?
GH secretion being pulsatile, since it is highest during sleep.
How can we make our GH stimulation tests more useful?
Measuring IGF-1 and IGFBP3 also.
Explain the process of a GH stimulation test.
- Using either physiologic stimuli or pharmcologic stimuli
- Must perform 2 different stimulation tests that both show subnormal GH secretion.
- Must perform both after overnight fasts
- Positive test = minor increases in GH at most.
What imaging test could help us determine if there is a GH deficiency?
MRI to visualize the hypothalamus and pituitary.
CT of brain w/ contrast can screen for pituitary tumor.
What is the treatment for GH deficiency?
Recombinant GH (0.02-0.05mg/kg/day)) SC
What is the treatment for GH insensitivity?
IGF-1 to bypass GH receptors.
What usually causes GH deficiency in adults?
Hypothalamic or pituitary somatotrope damage.
What is the usual order of hormone loss with hypothalamic/pituitary damage?
GH => FSH/LH => TSH => ACTH
What are the clinical features of AGHD?
- Changes in body composition
- Lipid metabolism
- CV dysfunction
What does body composition change look like in AGHD?
- Reduced lean body mass
- Increased fat mass
- Increased waist-to-hip ratio
What chronic conditions can occur with AGHD?
- HLD
- LV dysfunction
- HTN
- Increased fractures
How do we test for AGHD?
Same as children. It is extremely rare though.
What risk factors would prompt us to evaluate for AGHD?
- Pituitary Surgery
- Pituitary/hypothalamic tumor or granulomas
- Hx of cranial irradiation
- Radiologic evaluation of pituitary lesion
- Childhood GH replacement therapy
- Unexplained low age and sex-match IGF-1 levels.
What are the CIs to treating AGHD?
- Active neoplasm
- Intracranial hypertension
- Uncontrolled diabetes + retinopathy
What is the dosing for recombinant GH for treating AGHD?
0.1-0.3 mg/d up to 1.25mg/d for IGF-1 level maintenance.
What should we monitor when administering recombinant human GH?
- Fundoscopic examinations for intracranial HTN
- Adults: IGF-1 every 1-2 months, then semiannually
- Children: Growth curve and PE with skeletal assessment every visit.
What SE should we counsel pts on/watch out for when giving rHGH?
- Fluid retention
- Joint pain
- CTS
- Myalgias
- Paresthesias
- Hyperglycemia
- DM
- HA
- Increased ICP
- HTN
- Tinnitus
- Slipped capital femoral epiphysis
What secretes GH from the anterior pituitary?
Somatotrophs
What hormone inhibits GH secretion from the anterior pituitary?
Somatostatin
What is the other name for IGF-1?
Somatomedin
What is the treatment for GHD?
Somatotropin
What is the cause of acromegaly/gigantism?
GH hypersecretion due to a somatotrope lesion usually.
Rarely an extrapituitary lesion.
Ectopic secretion has come from pancreatic, ovarian, lung, or hematopoeitic origins.
What is the MCC of excess GHRH-mediated acromegaly?
Chest or abdominal carcinoid tumor.
How does acral bony overgrowth typically appear?
GRADUAL
* Frontal bossing
* Increased hand and foot size
* Mandibular enlargement with prognathism
* Widened space between lower incisor teeth
What kind of soft tissue changes occur due to swelling?
- Heel pad thickness
- Increased shoe or glove size
- Ring tightening
- Coarse facial features
- Large fleshy nose
What organs are typically enlarged with acromegaly/gigantism?
- Cardiomegaly
- Macroglossia (big tongue)
- Thyromegaly
What are the predominant clinical concerns with patients who have acromegaly/gigantism?
- Cardiomyopathy with arrhythmias
- LVH
- Decreased diastolic function
- HTN
What other conditions can result from having acromegaly/gigantism?
- Sleep apnea
- DM
- Colon polyps
How much is lifespan generally reduced by excess GH levels?
10 years on average if left uncontrolled.
What confirms the diagnosis of acromegaly?
Failure of GH suppression to < 0.4 mg/L within 1-2 hours of an oral glucose load of 75g. High glucose should stimulate somatoSTATIN release.
What are the goals of treatment for acromegaly?
- Controlling GH and IGF-1 hypersecretion
- Ablate/arrest tumor growth
- Restore mortality rate to normal
- Preserve pituitary function
What is the preferred primary treatment for adenomas in acromegaly?
Transsphenoidal surgical resection for both micro and macroadenomas.
What is the adjuvant therapy for acromegaly?
External radiation therapy or high-energy stereotactic techniques
What is the pharmacotherapy for acromegaly?
- Somatostatin analogues
- Dopamine agonists
Both can be combined.
Which somatostatin analogue supresses gallbladder contractility?
Octreotide.
Suppresses postprandial gallbladder contractility and delays gallbladder emptying.
What is the most common presentation of adult hypopituitarism?
Hypogonadism.
How does hypogonadism present in females?
- Oligomenorrhea
- Amenorrhea
- Infertility
- Decreased vaginal secretions
- Decreased libido
- Osteoporosis
How does hypogonadism present in males?
- Decreased libido
- Impotency
- Infertility
- Decreased muscle mass
- Reduced beard/hair growth
What labs help us evaluate hypogonadism?
- Low gonadotropin levels with low sex hormone concentrations
- IV GnRH should stimulate LH/FSH, causing increased serum levels. Abnormal response shows abnormal pituitary function.
- MRI/other pituitary hormone tests
In primary hypogonadism, what levels of GnRH, LH, and FSH would I see?
High for all.
Gonads not responding.
In secondary hypogonadism, what levels of GnRH, LH, and FSH would I see?
Low for all.
Issue is in the hypothalamus/pituitary
For males, what lab tests help evaluate hypogonadism?
- Serum testosterone < 240
- Free testosterone < 35
- Serum LH and PRL levels
For females, what labs help evaluate hypogonadism?
- hCG (r/o pregnancy)
- Serum PRL
- Serum FSH and LH
- Serum TSH
For males, how do we treat hypogonadism?
- Testosterone replacement
- hCG (if infertile due to oligospermia)
- Leuprolide/GnRH analog (if intact pituitary)
- Clomiphene, stimluates pituitary gonadotropins.
For females, how do we treat hypogonadism?
- Cyclical replacement of estrogen and progesterone.
- For ovulation: human menopausal gonadotropin (hMG) or recombinant FSH/LH
- Pulsatile GnRH for hypothalamic infertility
When is ACTH secretion at its peak?
6AM
