Pituitary 2 Flashcards
Definition of what?
◦Genetic tall stature
Constitutional tall stature
Child’s height is similar to his or her parents
taller than their peers
◦Have accelerated growth velocity
◦Moderately advanced bone age
Constitutional Tall Stature
What are the 2 genetic syndromes associated w/ tall stature?
- Klinefelter’s Syndrome
- Marfan’s Syndrome
Which genetic syndrome causing Tall Stature?
Most common cause of congenital hypogonadism
Results in “eunuchoidal” proportions (long arms and legs)
Learning disabilities, mainly in expressive language
Small testes and gynecomastia
2 or more X chromosomes present in male phenotypes
Klinefelter’s Syndrome
Which genetic syndrome causing Tall Stature?
◦- inherited autosomal dominant disorder - connective tissue disease
Tall stature
Long, thin fingers and hyperextensibility of joints
Marfan’s Syndrome
3 endocrine causes of Tall Stature
- Pituitary Gigantism (rare)
- Precocious Puberty
- Hyperthyroidism
Signs of what?
- GH excess
- Height exceeds 3-4 SDs from normal
- HA or visual field involvement
- Rapid growth rate, body proportional prior to epiphyseal fusion
- Excessive size for age
Pituitary Gigantism (rare)
- GH secreting pituitary adenoma/tumor
Which cause of Tall Stature?
◦Early tall stature due to early sex steroid secretion
◦Marked advancement of bone age
◦Greater incidence in girls or boys?
◦Early epiphyseal closure
◦Adult short stature
Precocious Puberty
- Girls
What are 4 causes of precocious puberty?
- Congenital adrenal hyperplasia,
- virilizing adrenal tumors,
- testicular and ovarian tumors,
- ovarian cysts
Which cause of tall stature?
◦Overproduction or over-treatment with exogenous thyroxine
◦Increased growth and advanced bone age
Hyperthyroidism
Is excess GH or PRL more common?
- PRL (prolactin)
- GH
Dx of pituitary gigantism
- Most children w/ tall stature DO NOT have pituitary gigantism (rare)
- r/o genetics cause, precocious puberty, hyperthyroidism
- Dysmorphic/disproportionate features/neurocog problems suggest what as the cause?
Chromosomal cause: Klinefelter’s Syndrome
Initial eval of Tall Stature to r/o Pituitary Gigantism consists of what? (5)
- bone age,
- thyroid function tests,
- sex steroid hormone concentrations,
- karyotype,
- GH-related studies
3 diagnostic components to dx pituitary gigantism
- IGF-1 levels
- GH suppression tests (OGTT)
- Radiographic imaging (MRI)
What is the GOLD STANDARD dx test to dx Pituitary Gigantism?
- What lab value has to be elevated to move onto this test?
- How does the test work?
- What is a “normal” result?
GH Suppression Tests (OGTT)
- Used if IGF-1 suggests GH excess
- Serum GH response to an oral glucose load
- Normal: GH concentration falls below tng/dL within 2 hours of glucose load.
What 2 structures are analyzed on radiographic imaging to dx Pituitary Gigantism?
What type of imaging?
MRI of hypothalamus & pituitary gland
Definition of what?
◦Excessive growth hormone (GH) after puberty
◦Mean age - 40-45 years
Diagnosis delayed due to slow progression of signs and symptoms
Acromegaly
What is the MC cause of Acromegaly?
GH secreting adenoma of pituitary
What are the somatic effects of Acromegaly?
Stimulation of growth of tissues
- Skin
- Connective tissue
- Cartilage
- Bone
- Viscera
What are the 2 metabolic effects of Acromegaly?
- Insulin antagonism
- Lipogenesis
Adenoma of pituitary causing Acromegaly may cause what 3 local sxs?
- HA
- Visual field defects (bitemporal hemianopsia)
- CN palsies
Clinical manifestations of Acromegaly
- Insidious onset
- SLOW progression
- Avg interval from onset of sxs –> until dx is usually how many years?
- At diagnosis, 75% have what??
- 60% have what sxs?
- 10% have what sxs?
- 12 year interval
- 75%: macroadenomas (10mm or greater)
- 60%: HA
- 10%: visual sxs
What type of growth associated w/ Acromegaly is described here?
- Enlarged jaw (macrognathia)
-
Enlarged, swollen hands and feet
- ↑ shoe and glove size, need to enlarge rings
-
Facial features
- Enlargement of nose and frontal bones
- Teeth become spread apart
Acral Overgrowth
What type of growth is described? (Acromegaly)
◦Synovial tissue/cartilage enlarge
◦Hypertrophic arthropathy of knees, ankles, hips, spine
◦Back pain and kyphosis
Articular Overgrowth
Acromegaly
- Bone density increases in what 2 structures?
- 3 results of CVD?
- Height changed how?
- Spine & hips
- HTN, LVH, cardiomyopathy
- Height NOT necessarily taller (depends on the onset of GH excess)
Sxs of acromegaly caused by what??
◦Women menstrual dysfunction, hot flashes and vaginal atrophy
◦Men erectile dysfunction, loss of libido, decreased facial hair growth and testicular atrophy
Decreased secretion of gonadotropins due to a Macroadenoma
(Pituitary Function messed up)
What skin/hair changes are associated w/ acromegaly??
◦Skin thickening and skin tags
◦Hyperhidrosis is common (~50%), often malodorous
◦Increased hair growth and hirsutism
(THICK, hairy, sweaty, smelly skin)
3 Soft Tissue clinical manifestations of acromegly
◦Macroglossia
◦Deepening of the voice
◦Paresthesias of the hands (CTS ~ 20%) = carpal tunnel syndrome
Acromegaly
- Macroglossia puts pts at risk for what??
- 50% develop this…
OSA
Acromegaly pts are at increased risk of what 3 tumors?
- Benign uterine tumors
- Colonic adenomatous polyps
- Adenocarcinoma of colon/stomach/esophagus/melanoma
(10% develop malignant tumors)
Acromegaly pts have enlargment of what organs? (5)
Visceral organs
- Thyroid
- Heart
- Liver
- Kidneys
- Prostate
“Thy heart lives kindly and proudly”
What are the 2 common laboratory abnormalities of Acromegaly??
- Hyperglycemia (25% w/ overt DM)
- Hyperprolactinemia (>200)
Acromegaly
- Mortality rate is 2-3X the expected rate, mostly due to what 2 conditions?
- Reduced overall survival by how many yrs on avg?
- CVD & Cancer
- 10 yrs
T/F
- Treatment of Acromegaly which lowers GH to normal levels DOES NOT return mortality rate to normal
False, tx which lowers GH to normal WILL return mortality rate to normal
What is the SINGLE BEST test for acromegaly??
Serum IGF-1 Concentration
What test has + results in over 85% of acromegaly pts?
(Do this test if IGF-1 is elevated and still have clinical suspicion for Acromegaly)
OGTT (Oral Glucose Tolerance Test)
- Negative/Normal result: GH falls to 2 or less within 2 hours after ingestion of glucose
- Positive/Abnormal result: GH values are >
What test would you do if IGF-1 was elevated and OGTT had inadequate suppression and you’re still suspicious for Acromegaly?
MRI of pituitary
- If normal: get Chest/Abd CT
- If + = GH secreting pituitary adenoma
What are the 3 goals of therapy for BOTH Pituitary Gigantism & Acromegaly
- Lower serum GH
- Get IGF-1 within reference range for age/sex of pt
- Identify/Remove Tumor surgically, destroy w/ raidation, or reduce w/ drug therapy
T/F
- Treatment of Pituitary Gigantism & Acromegaly often does NOT restore normal GH secretion
True
What are the 3 tx options for both Pituitary Gigantism & Acromegaly?
- Surgery (Transphenoidal) (TX OF CHOICE!!)
- Radiation (cranial)
-
Pharm:
- Bromocriptine,
- Octreotide,
- GH receptor antagonists,
- Combo therapy (Bromo+Octreotide in children)
Transphenoidal Surgery is Treatment of Choice for Pituitary Gigantism AND Acromegaly:
- Curative for micro/macro adenomas
- Complication/Recurrence rates are higher in adults or children??
- GH secretion falls to normal in 80% of pts w/ which type of adenoma? (better success)
- How soon after surgery do GH levels fall to normal??
- How soon do serum IGF-1 level fall to normal??
- CHILDREN
- Microadenomas (<10mm) = better success compared to macroadenomas (low success rate)
- GH: 1-2 hours
- IGF-1: 7-10 days
What can result from Cranial Radiation as an adjunctive therapy in treatment of PG & Acromegaly?
-
Children:
- delayed efficacy
- Panhypopituitarism
- Deficiencies of: GH, gonadotropin, thyrotropin
- Learning disabilities
- Emotional changes
- Obesity
(LEPOD)
Which pharm tx for PG & Acromegaly?
◦a dopamine analog, was the agent used most commonly until recently
Bromocriptine
Which pharm tx for PG & Acromegaly?
- somatostatin analog****
- Highly effective - both adults and children with GH excess - most common agent
- Subcutaneous injection or continuous infusion
Octreotide
Long Term Management of PG & Acromegaly consists of what 3 things & how often??
- Clinical exams
- Serum IGF-1
- OGTT
(Every 3-4 months)
Long Term Management of PG & Acromegaly
- Monitor for S/S of pituitary hormone deficiency how often??
- Gonadotropin deficiency - amenorrhea in women/androgen deficiency in men
- Secondary thyroid and adrenal insufficiency
- Measure serum levels of what 2 things?
- Annually
- Thyroxine & Cortisol
Long Term Management of PG & Acromegaly
- To monitor size of adenoma, an MRI should be repeated how often?
- What other assessment needs to be completed and how often?
- Repeat yearly for the first “several years” after surgery
- Visual Field Assessment (Semi-annually)
Systemic Evaluation of Long Term Management of pts/ w PG or Acromegaly:
- Colonoscopy how often/age?
- CV exam?
- 3-4 yr intervals in pts 50 y/o+
- Annual cardiovascular eval
Summary of PG and Acromegaly: 8 steps
- Good H&P
- Follow growth curves
- If suspicious for pathologic tall stature:
- Obtain bone age with wrist radiograph
- Rule out precocious puberty, hyperthyroidism, and Klinefelter’s or Marfan’s
- IGF-1
- Confirm with GH suppression test
- Refer to pediatric or adult endocrinology
