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“Simple can be
harder than
complex:
You have to work hard to
get your thinking clean to
make it simple. But it’s
worth it in the end
because once you get
there, you can move
mountains.”
- Steve Jobs
Friday, March 21, 14
Iris Thiele Isip Tan MD, MSc
Assoc. Prof. 4, UP College of Medicine
Chief, Medical Informatics Unit
GPs as
Pituitary
Stalkers
Pituitary
Pathologies
Simplified
David and Goliath by Robert Temple Ayres
Friday, March 21, 14
to be a
PituitaryStalker
How
optical_illusion_tshirt by Kevin
https://flic.kr/p/a573df
Remember by clsawyer
http://www.sxc.hu/photo/659706
Ask Remember Refer
Friday, March 21, 14
to be a
PituitaryStalker
How
“The world is full of obvious
things which nobody by any
chance ever observes.”
- Sherlock Holmes
optical_illusion_tshirt by Kevin
https://flic.kr/p/a573df
Have a
questioning
mind!
Ask
Friday, March 21, 14
David
and Goliath
Who was
the real
underdog?
David and Goliath by Robert Temple Ayres
Friday, March 21, 14
Did
Goliath
acromegaly
have
?
Friday, March 21, 14
David and Goliath
Painting by Giovan Francesco Nagli
Height “6 cubits and a
span” (2.5-3 meters)
Slow-moving and
ponderous
Goliath saw “sticks”
Stone sunk into forehead
Goliath fell forward
Did
Goliath
acromegaly
have
Friday, March 21, 14
38/F
previously healthy
3-month
history of
blurring
of vision
headache by beermug
http://www.sxc.hu/photo/1413980
Friday, March 21, 14
Optometrist or
ophthalmologist?
Prescribed
eye glasses
Progressed to
dimness of
vision
frame on eyechart by Brybs
http://www.sxc.hu/photo/1152188
Friday, March 21, 14
Diffuse throbbing
headaches
followed by
progressive
blurring
of vision
Family physician?
Internist?
Neurologist?
headache by beermug
http://www.sxc.hu/photo/1413980
Friday, March 21, 14
Menses stopped
6 mos ago
followed by the
headaches
Gynecologist?
No
galactorrhea
Endocrinologist?
headache by beermug
http://www.sxc.hu/photo/1413980
Friday, March 21, 14
Who makes the initial
diagnosis of a pituitary lesion?
Diagnostic
Source
Total percentage (n=404)Total percentage (n=404)Total percentage (n=404)Diagnostic
Source Prolactinoma Non-functioning Acromegaly
Internist/Family Med 16 23 39
Endocrinologist 34 14 25
Gynecologist 34 10 <1
Ophthalmologist/
Optometrist
6 25 6
Relatives/ self 2 1 6
Neurologist 0 3 5
Dentist 0 0 5
Other 8 24 14
Drange et al JCEM 85:168–174, 2000
Friday, March 21, 14
Pituitary adenomas
come to clinical attention
mass
effects
hormone
excess
hormone
insufficiency
Friday, March 21, 14
to be a
PituitaryStalker
How
optical_illusion_tshirt by Kevin
https://flic.kr/p/a573df
Remember by clsawyer
http://www.sxc.hu/photo/659706
Ask Remember
Illness
script
Friday, March 21, 14
Key Elements of the Clinical
Diagnostic Reasoning Process Bowen J. NEJM
2006;355:2217-2225
Patient’s story
Data acquisition
Accurate “problem representation”
Generation of hypothesis
Search for and selection of illness script
Diagnosis
Knowledge
Context
Experience
Friday, March 21, 14
Expert clinicians store and
recall knowledge as
diseases, conditions, or
syndromes - “illness
scripts” - that are
connected to problem
representations.
These representations trigger
clinical memory, permitting the
related knowledge to become
accessible for reasoning.
A room lamp without lampshade by Mattox
http://www.sxc.hu/photo/1120345
Bowen J. NEJM 2006;355:2217-2225
Friday, March 21, 14
Illness Script - Structure Bowen J. NEJM 2006;355:2217-2225
Predisposing
conditions
Pathophysiological
insult
Clinical
consequences
Rare
17% of population
Equal sex incidence
Incidence increases with age
Tumor growth
Compression of optic nerve
Extension to cavernous or sphenoid sinus
Compression of normal pituitary
Non-functioning
pituitary adenoma
Friday, March 21, 14
By OpenStax College [CC-BY-3.0
(http://creativecommons.org/licenses/by/3.0)], via Wikimedia Commons
andThe Pituitary
Optic Chiasm
Friday, March 21, 14
Image from http://www.medicinemcq.com/index.php/journals/sub_details/138/39/FMGE-MARCH-2012-ENT-AND-OPHTHALMOLOGY
andThe Pituitary
Cavernous Sinus
Friday, March 21, 14
Illness Script - Structure Bowen J. NEJM 2006;355:2217-2225
Predisposing
conditions
Pathophysiological
insult
Clinical
consequences
Rare
17% of population
Equal sex incidence
Incidence increases with age
Tumor growth
Compression of optic nerve
Extension to cavernous or sphenoid sinus
Compression of normal pituitary
Nonspecific headache
Visual disturbances (bitemporal hemianopsia)
Ophthalmoplegia, diplopia and/or ptosis
CSF rhinorrhea
Anterior pituitary failure (hypopituitarism)
Non-functioning
pituitary adenoma
Friday, March 21, 14
Image from http://www.medicinemcq.com/index.php/journals/sub_details/138/39/FMGE-MARCH-2012-ENT-AND-OPHTHALMOLOGY
Bitemporal
hemianopsia
Friday, March 21, 14
Illness Script - Structure Bowen J. NEJM 2006;355:2217-2225
Predisposing
conditions
Pathophysiological
insult
Clinical
consequences
Most common pituitary tumor
F:M ratio 10:1
Neoplastic transformation of anterior
pituitary lactrotrophs resulting in excess
synthesis and secretion of prolactin
Prolactinoma
Oligo- or amenorrhea
Galactorrhea
Erectile dysfunction or decreased libido
Hypopituitarism (compression from large tumor)
Friday, March 21, 14
Hypergonadotropic
hypogonadism
Ovarian failure
Hyper-
prolactinemia
galactorrhea
headache
amenorrhea
Pituitary
adenoma
visual
disturbances
Discriminating
feature
Defining
feature
Discriminating
feature
Discriminating
feature
Defining
feature
Hypo-
gonadotropic
hypogonadism
Friday, March 21, 14
Patient presenting with secondary amenorrhea;
negative pregnancy test
Check TSH and prolactin levels
Both
normal
Normal TSH
Abnormal prolactin
Progestogen challenge test
No withdrawal bleed
Estrogen/progestogen
challenge test
Withdrawal bleed
Normogonadotropic
hypogonadism
No withdrawal bleed
Outflow obstruction
Withdrawal bleed
Check FSH and LH
FSH >20 IU/L
LH >40 IU/L
Hypergonadotropic
hypogonadism
FSH & LH <5 IU/L
Perform MRI to evaluate
for pituitary tumor
Normal MRI:
hypogonadotropic hypogonadism
Normal prolactin
Abnormal TSH
Thyroid disease
Prolactin <100 ng/mL
(100 mcg/L)
Consider
other causes
Prolactin >100 ng/mL
Perform MRI to evaluate
for prolactinoma
Negative MRI
Friday, March 21, 14
What happens when
you can’t match an
illness script?
59/F with dizziness,
vomiting and
weakness ...
Rounadabout by ColinBroug
http://www.sxc.hu/photo/1265027
Friday, March 21, 14
Third time admitted
for vomiting, dizziness
and general weakness
Previous admissions
also with hypoglycemia
and pneumonia or UTI
Normal endoscopy
end to end ...
What to do?!
Photo by Ashley Webb
https://flic.kr/p/5u36oV
Friday, March 21, 14
Adrenal
insufficiency?!
31 years ago
Postpartum bleeding
needing BT
Delivered twins at home
Retained placenta
Screaming by ralaenin
http://www.sxc.hu/photo/579286
Friday, March 21, 14
Illness Script - Structure Bowen J. NEJM 2006;355:2217-2225
Predisposing
conditions
Pathophysiological
insult
Clinical
consequences
5.1 per 100,000 women
Severe postpartum vaginal bleeding
Severe hypotension or shock requiring fluid
replacement or blood transfusion
Sheehan’s
syndrome
Friday, March 21, 14
Friday, March 21, 14
Illness Script - Structure Bowen J. NEJM 2006;355:2217-2225
Predisposing
conditions
Pathophysiological
insult
Clinical
consequences
5.1 per 100,000 women (Iceland)
Severe postpartum vaginal bleeding
Severe hypotension or shock requiring fluid
replacement or blood transfusion
Pituitary enlargement
Lactotroph hyperplasia
Pituitary gland susceptible to ischemia
Postpartum pituitary necrosis
Failure of postpartum lactation
Failure to resume regular menses
Varying degrees of hypopituitarism
Empty sella on CT scan or MRI
Sheehan’s
syndrome
Friday, March 21, 14
Sheehan’s
Syndrome
Presentation
At ER following a
stressful event
Coma of hypothyroidism
Adrenal insufficiency
Hypoglycemia
Hyponatremia
http://www.sxc.hu/photo/65898Ozkan& Kolac, Neuroendocrinol Lett 2005;26(3):257-60
Friday, March 21, 14
GH deficiency
Reduced energy and vitality
Reduced muscle mass and
strength
Decreased sweating and impaired
thermogenesis
Increased central adiposity
Increased CV risk
Decreased BMD
Prabhakar & Shalet, Postgrad Med J 2006;82:259–66
Friday, March 21, 14
ACTH deficiency
Fatigue, weakness, anorexia,
weight loss
Nausea, vomiting, abdominal pain
Hypoglycemia
Circulatory collapse if acute onset
Loss of axillary and pubic hair in
women
Prabhakar & Shalet, Postgrad Med J 2006;82:259–66
Friday, March 21, 14
Gonadotrophin
deficiency
Men: erectile dysfunction, soft
testes, reduced muscle mass and
energy
Women: oligo/amenorrhea,
dyspareunia, breast atrophy
Both: loss of libido, flushes,
infertility, regression of sexual
characteristics, reduced BMD
Prabhakar & Shalet, Postgrad Med J 2006;82:259–66
Friday, March 21, 14
TSH deficiency
Fatigue, apathy, psychomotor
retardation
Cold intolerance, dry skin
Constipation
Weight gain
Prabhakar & Shalet, Postgrad Med J 2006;82:259–66
Friday, March 21, 14
45/M
referred to
surgeon for
colon CA
Referred by
surgeon
to me for coarse
facial features
http://www.cinemainsomnia.com/lobo-
loves-rondo-does-rondo-love-lobo/
Friday, March 21, 14
Illness Script - Structure Bowen J. NEJM 2006;355:2217-2225
Predisposing
conditions
Pathophysiological
insult
Clinical
consequences
40-70 cases per million population
Mean age of onset 30 y
Onset to diagnosis 5-15 y
Mean age at diagnosis:
40 y in men and 45 y in women
GH excess
GH-secreting pituitary adenomas
Inc incidence of colonic polyps & colon adenoCA,
diabetes, hypertension and CVD
Soft tissue swelling & enlargement of extremities
Increase in ring and/or shoe size
Hyperhidrosis
Coarsening of facial features
Prognathism, macroglossia
Acromegaly
Friday, March 21, 14
Rondo Hatton
American Actor
Acromegaly attributed to exposure
to German mustard gas attack in World War I
http://i1139.photobucket.com/albums/n545/travislouie37/Rondoisgoodwiththeladies.jpg
Friday, March 21, 14
Sheehan’s
syndrome
Non-functioning
adenoma
hypopituitarism
Functioning
Pituitary
adenoma
Discriminating
feature
Defining
feature
Discriminating
feature
Discriminating
feature
mass
effects
ACTH
TSH
Excess secretion
PRL
GH
Hormone
deficiency
Postpartum
hemorrhage
Defining
feature
Friday, March 21, 14
At rounds more than a decade ago with MALA ...
How much does a
human pituitary gland weigh?
Seagull in front of sea by cobrasoft
http://www.sxc.hu/photo/1437851
Friday, March 21, 14
“But what physician
has not had patients
who don’t make
any sense at all? To
tell the truth, they’re
our stock-in-trade.
We talk and write
about the ones we
can make sense of.”
- Walker Percy
Dr. House MD Caricature Hugh Laurie by Nelson Santos
https://flic.kr/p/46tXvx
Friday, March 21, 14
to be a
PituitaryStalker
How
optical_illusion_tshirt by Kevin
https://flic.kr/p/a573df
Remember by clsawyer
http://www.sxc.hu/photo/659706
Ask Remember Refer
Friday, March 21, 14
Thank You
@endocrine_witch
Friday, March 21, 14

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Pituitary Pathologies Simplified

  • 1. “Simple can be harder than complex: You have to work hard to get your thinking clean to make it simple. But it’s worth it in the end because once you get there, you can move mountains.” - Steve Jobs Friday, March 21, 14
  • 2. Iris Thiele Isip Tan MD, MSc Assoc. Prof. 4, UP College of Medicine Chief, Medical Informatics Unit GPs as Pituitary Stalkers Pituitary Pathologies Simplified David and Goliath by Robert Temple Ayres Friday, March 21, 14
  • 3. to be a PituitaryStalker How optical_illusion_tshirt by Kevin https://flic.kr/p/a573df Remember by clsawyer http://www.sxc.hu/photo/659706 Ask Remember Refer Friday, March 21, 14
  • 4. to be a PituitaryStalker How “The world is full of obvious things which nobody by any chance ever observes.” - Sherlock Holmes optical_illusion_tshirt by Kevin https://flic.kr/p/a573df Have a questioning mind! Ask Friday, March 21, 14
  • 5. David and Goliath Who was the real underdog? David and Goliath by Robert Temple Ayres Friday, March 21, 14
  • 7. David and Goliath Painting by Giovan Francesco Nagli Height “6 cubits and a span” (2.5-3 meters) Slow-moving and ponderous Goliath saw “sticks” Stone sunk into forehead Goliath fell forward Did Goliath acromegaly have Friday, March 21, 14
  • 8. 38/F previously healthy 3-month history of blurring of vision headache by beermug http://www.sxc.hu/photo/1413980 Friday, March 21, 14
  • 9. Optometrist or ophthalmologist? Prescribed eye glasses Progressed to dimness of vision frame on eyechart by Brybs http://www.sxc.hu/photo/1152188 Friday, March 21, 14
  • 10. Diffuse throbbing headaches followed by progressive blurring of vision Family physician? Internist? Neurologist? headache by beermug http://www.sxc.hu/photo/1413980 Friday, March 21, 14
  • 11. Menses stopped 6 mos ago followed by the headaches Gynecologist? No galactorrhea Endocrinologist? headache by beermug http://www.sxc.hu/photo/1413980 Friday, March 21, 14
  • 12. Who makes the initial diagnosis of a pituitary lesion? Diagnostic Source Total percentage (n=404)Total percentage (n=404)Total percentage (n=404)Diagnostic Source Prolactinoma Non-functioning Acromegaly Internist/Family Med 16 23 39 Endocrinologist 34 14 25 Gynecologist 34 10 <1 Ophthalmologist/ Optometrist 6 25 6 Relatives/ self 2 1 6 Neurologist 0 3 5 Dentist 0 0 5 Other 8 24 14 Drange et al JCEM 85:168–174, 2000 Friday, March 21, 14
  • 13. Pituitary adenomas come to clinical attention mass effects hormone excess hormone insufficiency Friday, March 21, 14
  • 14. to be a PituitaryStalker How optical_illusion_tshirt by Kevin https://flic.kr/p/a573df Remember by clsawyer http://www.sxc.hu/photo/659706 Ask Remember Illness script Friday, March 21, 14
  • 15. Key Elements of the Clinical Diagnostic Reasoning Process Bowen J. NEJM 2006;355:2217-2225 Patient’s story Data acquisition Accurate “problem representation” Generation of hypothesis Search for and selection of illness script Diagnosis Knowledge Context Experience Friday, March 21, 14
  • 16. Expert clinicians store and recall knowledge as diseases, conditions, or syndromes - “illness scripts” - that are connected to problem representations. These representations trigger clinical memory, permitting the related knowledge to become accessible for reasoning. A room lamp without lampshade by Mattox http://www.sxc.hu/photo/1120345 Bowen J. NEJM 2006;355:2217-2225 Friday, March 21, 14
  • 17. Illness Script - Structure Bowen J. NEJM 2006;355:2217-2225 Predisposing conditions Pathophysiological insult Clinical consequences Rare 17% of population Equal sex incidence Incidence increases with age Tumor growth Compression of optic nerve Extension to cavernous or sphenoid sinus Compression of normal pituitary Non-functioning pituitary adenoma Friday, March 21, 14
  • 18. By OpenStax College [CC-BY-3.0 (http://creativecommons.org/licenses/by/3.0)], via Wikimedia Commons andThe Pituitary Optic Chiasm Friday, March 21, 14
  • 20. Illness Script - Structure Bowen J. NEJM 2006;355:2217-2225 Predisposing conditions Pathophysiological insult Clinical consequences Rare 17% of population Equal sex incidence Incidence increases with age Tumor growth Compression of optic nerve Extension to cavernous or sphenoid sinus Compression of normal pituitary Nonspecific headache Visual disturbances (bitemporal hemianopsia) Ophthalmoplegia, diplopia and/or ptosis CSF rhinorrhea Anterior pituitary failure (hypopituitarism) Non-functioning pituitary adenoma Friday, March 21, 14
  • 22. Illness Script - Structure Bowen J. NEJM 2006;355:2217-2225 Predisposing conditions Pathophysiological insult Clinical consequences Most common pituitary tumor F:M ratio 10:1 Neoplastic transformation of anterior pituitary lactrotrophs resulting in excess synthesis and secretion of prolactin Prolactinoma Oligo- or amenorrhea Galactorrhea Erectile dysfunction or decreased libido Hypopituitarism (compression from large tumor) Friday, March 21, 14
  • 24. Patient presenting with secondary amenorrhea; negative pregnancy test Check TSH and prolactin levels Both normal Normal TSH Abnormal prolactin Progestogen challenge test No withdrawal bleed Estrogen/progestogen challenge test Withdrawal bleed Normogonadotropic hypogonadism No withdrawal bleed Outflow obstruction Withdrawal bleed Check FSH and LH FSH >20 IU/L LH >40 IU/L Hypergonadotropic hypogonadism FSH & LH <5 IU/L Perform MRI to evaluate for pituitary tumor Normal MRI: hypogonadotropic hypogonadism Normal prolactin Abnormal TSH Thyroid disease Prolactin <100 ng/mL (100 mcg/L) Consider other causes Prolactin >100 ng/mL Perform MRI to evaluate for prolactinoma Negative MRI Friday, March 21, 14
  • 25. What happens when you can’t match an illness script? 59/F with dizziness, vomiting and weakness ... Rounadabout by ColinBroug http://www.sxc.hu/photo/1265027 Friday, March 21, 14
  • 26. Third time admitted for vomiting, dizziness and general weakness Previous admissions also with hypoglycemia and pneumonia or UTI Normal endoscopy end to end ... What to do?! Photo by Ashley Webb https://flic.kr/p/5u36oV Friday, March 21, 14
  • 27. Adrenal insufficiency?! 31 years ago Postpartum bleeding needing BT Delivered twins at home Retained placenta Screaming by ralaenin http://www.sxc.hu/photo/579286 Friday, March 21, 14
  • 28. Illness Script - Structure Bowen J. NEJM 2006;355:2217-2225 Predisposing conditions Pathophysiological insult Clinical consequences 5.1 per 100,000 women Severe postpartum vaginal bleeding Severe hypotension or shock requiring fluid replacement or blood transfusion Sheehan’s syndrome Friday, March 21, 14
  • 30. Illness Script - Structure Bowen J. NEJM 2006;355:2217-2225 Predisposing conditions Pathophysiological insult Clinical consequences 5.1 per 100,000 women (Iceland) Severe postpartum vaginal bleeding Severe hypotension or shock requiring fluid replacement or blood transfusion Pituitary enlargement Lactotroph hyperplasia Pituitary gland susceptible to ischemia Postpartum pituitary necrosis Failure of postpartum lactation Failure to resume regular menses Varying degrees of hypopituitarism Empty sella on CT scan or MRI Sheehan’s syndrome Friday, March 21, 14
  • 31. Sheehan’s Syndrome Presentation At ER following a stressful event Coma of hypothyroidism Adrenal insufficiency Hypoglycemia Hyponatremia http://www.sxc.hu/photo/65898Ozkan& Kolac, Neuroendocrinol Lett 2005;26(3):257-60 Friday, March 21, 14
  • 32. GH deficiency Reduced energy and vitality Reduced muscle mass and strength Decreased sweating and impaired thermogenesis Increased central adiposity Increased CV risk Decreased BMD Prabhakar & Shalet, Postgrad Med J 2006;82:259–66 Friday, March 21, 14
  • 33. ACTH deficiency Fatigue, weakness, anorexia, weight loss Nausea, vomiting, abdominal pain Hypoglycemia Circulatory collapse if acute onset Loss of axillary and pubic hair in women Prabhakar & Shalet, Postgrad Med J 2006;82:259–66 Friday, March 21, 14
  • 34. Gonadotrophin deficiency Men: erectile dysfunction, soft testes, reduced muscle mass and energy Women: oligo/amenorrhea, dyspareunia, breast atrophy Both: loss of libido, flushes, infertility, regression of sexual characteristics, reduced BMD Prabhakar & Shalet, Postgrad Med J 2006;82:259–66 Friday, March 21, 14
  • 35. TSH deficiency Fatigue, apathy, psychomotor retardation Cold intolerance, dry skin Constipation Weight gain Prabhakar & Shalet, Postgrad Med J 2006;82:259–66 Friday, March 21, 14
  • 36. 45/M referred to surgeon for colon CA Referred by surgeon to me for coarse facial features http://www.cinemainsomnia.com/lobo- loves-rondo-does-rondo-love-lobo/ Friday, March 21, 14
  • 37. Illness Script - Structure Bowen J. NEJM 2006;355:2217-2225 Predisposing conditions Pathophysiological insult Clinical consequences 40-70 cases per million population Mean age of onset 30 y Onset to diagnosis 5-15 y Mean age at diagnosis: 40 y in men and 45 y in women GH excess GH-secreting pituitary adenomas Inc incidence of colonic polyps & colon adenoCA, diabetes, hypertension and CVD Soft tissue swelling & enlargement of extremities Increase in ring and/or shoe size Hyperhidrosis Coarsening of facial features Prognathism, macroglossia Acromegaly Friday, March 21, 14
  • 38. Rondo Hatton American Actor Acromegaly attributed to exposure to German mustard gas attack in World War I http://i1139.photobucket.com/albums/n545/travislouie37/Rondoisgoodwiththeladies.jpg Friday, March 21, 14
  • 40. At rounds more than a decade ago with MALA ... How much does a human pituitary gland weigh? Seagull in front of sea by cobrasoft http://www.sxc.hu/photo/1437851 Friday, March 21, 14
  • 41. “But what physician has not had patients who don’t make any sense at all? To tell the truth, they’re our stock-in-trade. We talk and write about the ones we can make sense of.” - Walker Percy Dr. House MD Caricature Hugh Laurie by Nelson Santos https://flic.kr/p/46tXvx Friday, March 21, 14
  • 42. to be a PituitaryStalker How optical_illusion_tshirt by Kevin https://flic.kr/p/a573df Remember by clsawyer http://www.sxc.hu/photo/659706 Ask Remember Refer Friday, March 21, 14