Transcript Diabetes Insipidus by Suzette Grace Kho Medical Grandrounds 7

HONEY, I BLEW UP
THE KID!
A SUPER Sized Medical
Grand Rounds
Presentor: Suzette Grace R. Kho, M.D.
Resource Persons:
Eric Flores, M.D. (Neurosurgery)
Paolo Villanueva, M.D (Pathology)
Gerardo Beltran, M.D. (Radiology)
Teresa Sy-Ortin, M.D. (Radio-oncology)
Moderator: Thelma Crisostomo, M.D.
To present a case of a 17 year old
female with unusually tall stature
 To discuss differential diagnosis, & workup for patients presenting with pituitary
mass
 to discuss pathophysiology & treatment
options for patients presenting with
pituitary tumors

F.O.
 17 Female
 Filipino
 Cagayan de Oro
Chief Complaint:
Evaluation of Tall Stature
>
198 cm
191cm
185 cm
168 cm
154 cm
121 cm
95th %

3 mos PTA



CONSULT
(+) “dimming” of her peripheral
vision.
(+) difficulty guarding her
opponents, & would sometimes
miss catching a pass.
no consult was done until an
annual school PE
› Tall stature
› Delayed development of
secondary sexual
characteristcs
› Visual field abnormalities






(-) rashes, (-) skin pigmentation
(-) nocturia, (-) polyuria, (-) polydipsia
(-) palpitations, (-) tremors, (-) heat/ cold
intolerance, (-)weight gain/ weight loss
(-) chest pain , (-)no difficulty of breathing,
(-) lactation
(-) easy fatigability, (-) body weakness,
(-) tetany, (-) muscle cramps
(-) hirsutism
Delivered term via NSD to a 24 y/o G2P1
 Birth weight: 6 lbs.
 Birth length: claims to be within normal
 No delivery complications


unremarkable

unremarkable









Father- 5’4” (162.54 cm)
Mother- 5’3” (160 cm), menarche at age 12
*midparental height: 154.77cm
1 Sibling: Brother- 5’9” (175.26 cm)
tall relatives >182 cm ( 6’): mother side
-8 uncles-: 6’ to 6’2”
-1 male cousin: 6’1”
(+) thyroid disease- aunt
(+) HPN- father, uncle
(+) asthma- father and brother
(+) CVA- grandfather
(-) DM, (-) colon cancer
Conscious, coherent, ambulatory,
oriented to 3 spheres


Vital Signs:
BP 110/70 mmHg HR 84 bpm
RR 20 cpm
T 36.3°C
Anthropometrics
wt: 95.5kg
ht: 198cm
BMI:
24.1(overweight)



upper segment:
84.84 cm
lower segment:
113cm
U/L segment:
0.76
6’6
”
Anthropometrics
ht: 198cm
Arm span - 205.74 cm
Physical
Examination
(+) depressed anterior
(5.5 cm x 3.5cm) & posterior
(1.5cm x1.0cm) fontanelles
 no coarsening of features
 (+) slightly thickened &
widened nose and lips
 (+) gap between incisors,
with slight prominence of
jaw

Physical Examination
Lipomastia with no distinct glandular tissues
External genitalia: female
pubic hair, with no clitoral enlargement,
bright pink vaginal mucosa, no milky
secretions noted.
Physical
Examination


(+) prominent hands
and feet, with
thickening of the
soles of the foot
Full & equal pulse
Neurologic Examination
Awake, alert, oriented to 3 spheres
 Pupils 3-4mm ERTL, EOM full and equal, (+) ROR, (+)
visual field cuts
 Can smile, frown, clench teeth, tongue midline on
protrusion
 Can shrug shoulders
 MMT: 5/5 on all extremities
 Sensory: 100% intact
 No dysmetria, no dysdiadokinesia
 (-) Brudzinski’s (-) Kernig’s
 (-) Babinski
 DTR: ++

Salient Features
Depressed fontanelles
 slightly thickened &
widened nose and lips
 upper tooth gap with
slight prominence of
jaw
 Prepubertal Tanner
stage 1 breasts
 Tanner stage 3 pubic
hair
 Prominent hands and
feet

 17
year old female
 Tall stature
 Delayed puberty
 Headaches
 Visual field defect
Differentials
Tall Stature
Familial
Pituitary Mass
Chromosomal
Abnormalities
Pubertal Delay
Headache &
Visual Changes
Physiologic
Pathologic
Pituitary Mass
Chromosomal
Abnormalities
Astigmatism
Migraine
Intracranial
Tumor
Initial Impression
 Gigantism
probably secondary
to Growth hormone secreting
pituitary adenoma with
Hypogonadotrophic
Hypogonadism
Work Up
Clinical Features of
Gigantism/ Acromegaly
IGF-1 Level
Dx
excluded
Normal for Age &
Gender
Adequate GH
suppression
Elevated
Measure OGTT &
GH levels
Inadeguate /
no GH
suppression
Surgery
Assess
likelihood
of surgical
success
Medical
Piuitary Mass
Pituitary MRI
(Clinical features figure from Minkowski O. Ueber einen Fall von Akromegalie. Berliner Klinische
Wochenschrift 1887;21:371-374; from Melmed S. Medical progress: acromegaly. N Engl J Med
2006;355:2558-2573. Erratum in N Engl J Med 2007;356:879).
Work up
75g Oral Glucose Tolerance Test
TIME
(mins)
Growth FBS
Hormone
(n.v. 0-7)
IGF-1
(193-731
ng/ml)
0
203.229
90.98
1244
60 mins
208.948
109.17
120 mins
199.466
67.32
NONSUPPRESSION
MRI of Brain
(+)pituitary mass
 Referred to a neurosurgeon

› Transsphenoidal Surgery
GENETIC STUDY AUTOMATED PERIMETRY
VISUAL FIELD TEST
LEFT EYE
TEMPORAL
HEMIANOPSIA
RIGHT EYE
TEMPORAL
HEMIANOPSIA
WITH CENTRAL
SPARING
Hormones
9/09
F- Prolactin (3.6-18.9 ng/ml)
255.49
F- FSH (3.3-8.8 mlU/ml)
0.366
F- LH (0.6-6.2 mlU/ml)
0.001
27.346 (normal)
F- Testosterone
F- Estradiol
F-DHEAS (0.94-11.67 umol/L)
19.845 (premenarcheal)
10/16/09
8.484
Cortisol 8am (138-690 nmol/L)
9am
10/19/09
420.960
279.550
ACTH (<50 pg/ml)
10/16/09
15.231
TSH IRMA (0.27- 3.75)
FT4 (8.8- 33)
9/12/09
0.621
23.413
Pelvic Ultrasound

infantile uterus, with thin endometrium (3mm),
small left ovary , and right ovary not visualized.

Infantile
uterus, with
thin
endometrium
(3mm)
Small left
ovary, right
ovary not
visualized
Skeletal Survey
Bone Aging
Bone Mineral Density
NORMAL
SPINE
FEMORAL NECK
2 D Echocardiogram
Ultrasound of the Neck and
Thyroid Gland
Dec. 2, 2010: transnasal transphenoidal
resection of the pituitary mass
 Post op:
› (+) mild transient DI, treated with small
doses Desmopressin 100 mcg/tablet
› Hydrocortisone 100mg/IV was maintained
and tapered in 4 days. Transient sugar
elevations noted, given insulin injections.
› 7th HD: discharged, on Prednisone
7.5mg/tab (5mg- 0-2.5mg).

PATIENT: F.O. 17/F
SPECIMEN NO.: 10-SR-0282
IMMUNOHISTOCHEMICAL STAIN:
GROWTH HORMONE, POSITIVE (>90%)
IMMUNOHISTOCHEMICAL STAIN
PROLACTIN, POSITIVE (<5%)
Follow Up
75g Oral Glucose Tolerance Test
TIME
0
60
mins
120
mins
9/15/09
(Pre-op)
FBS
Growth
Hormone
(n.v. 0-7)
203.229
90.98
1/15/10
(Post-op)
FBS
Growth
Hormone
(n.v. 0-7)
378.709
93.19
208.948
109.17 415.996
109.17
199.466
67.32
83.7
NONSUPPRESSION
419.659
NONSUPPRESSION
IGF-1
9/11/09
(193-731 ng/ml) Pre-op
0
1244
1/15/10
Post-op
1075
Sex Hormones
9/16/09
Pre-op
1/20/10
Post -op
F-Prol (3.6- 18.9 ng/mL)
255.499
383.588
F-FSH (3.3-8.8 mIU/mL)
0.366
0.001
F-LH (0.6-6.2 mlU/ml)
0.001
0.018
Estradiol pg/ml
9/17/09
Pre-op
19.845
1/21/10
Post- op
19.496
(premenarcheal)
(premenarcheal)
Follow Up
Repeat MRI 3 mos. after surgery: mass
slightly
decreased
but
appears
unchanged
 April 29, 2010: Repeat transsphenoidal
surgery

Updates
9/16/09
1/20/10
5/19/10
(Baseline) 1st Post -op 2nd Post -op
F-Prol
(3.6-18.9 ng/ml)
F-FSH
(3.3-8.8 mlU/ml))
F-LH
(0.6-6.2 mlU/ml)
255.499
383.588
0.366
0.001
0.76
0.001
0.018
0.26
Updates
75g Oral Glucose Tolerance Test
9/15/09
BASELINE
1/15/10
1st Post-op
Growth
Hormone
(0-7)
378.709
FBS
0
FBS
Growth
Hormone
(0-7)
203.229
90.98
60 mins
208.948
415.996
109.1
7
83.7 256.873
120 mins 199.466
109.1
7
67.32
419.659
93.19
6/4/10
2nd Postop
Growth
Hormone
(0-7)
NONSUPPRESSION NONSUPPRESSION NONSUPPRESSION
Updates
Insulin
Growth
Like
Factor 1
0
9/11/09
1st
Pre
op
(193-731)
1/15/10
1st
Post
op
1244
1,075
4/15/10
2nd
Pre
op
1437
5/19/10
2nd
Post
op
(1mo)
>1600
7/16/10
2nd
Post
Op
(3 mos)
1429
CASE SUMMARY

17 year old female


› Tall stature
› Prominently enlarged
hands and feet
› Slightly widened and
thickened nose and lips
› Widened upper tooth gap
Delayed puberty
Tanner stage 1 breasts
tanner stage 3 pubic hair
Bitemporal Hemianopsia
MRI of the brain: (+)
pituitary mass
Histopathological &
Immunohistochemical
Findings: GH & Prolactin
Macroadenoma
Elevated
 GH levels
 IgF-1 level
 Prolactin level
 Prepubertal
 Estradiol
 FSH and LH level

Infantile uterus
Normal Karyotype 46 XX
Final Diagnosis

Gigantism secondary to
Growth Hormone and
Prolactin Co- Secreting
Pituitary Macroadenoma
with stalk compression
resulting in
hypogonadotrophic
hypogonadism, s/p
Transnasal Transphenoidal
Surgery (12/2/09 & 4/29/10)
The Pituitary Gland & Mass
Effects of Pituitary Tumor
COMPRESSION OF
PITUITARY STALK
BITEMPORAL
HEMIANOPSIA
HEADACHES
HYPERPROLACTINEMIA
HYPOPITUITARISM
Hypothalamic Pituitary Axis
Hypothalamus
Pituitary
Trophic H.
Target
Organ
In our patient..
HORMONE HYPERSECRETION
Growth Hormone Secreting Adenoma (>90%)
Prolactin Co-Secreting Adenoma (<5%)
(Mammasomatotrophs)
GIGANTISM
Combined GH and
Prolactin over-secretion
common in
early
childhood gigantism
Lafferty, A.R & Chrousos, G.P., Pituitary tumors in Children & Adolescents.
J. Clin. Endccinol. Metab. 1999.84:4317-4323.
GIGANTISM VS. ACROMEGALY
TIMING OF GH
EXCESS
During period of
active growth
Open epiphyseal plates
After epiphyseal
closure
INCIDENCE
Total cases reported
only in the hundreds
3- 4 cases/million
TALL STATURE
Cardinal feature
10% Cases
Identical twins, 22 years old, excess GH secretion
>98%
Melmed SM, ed. Acromegaly: A Comprehensive Guide to Diagnosis and
Treatment. East Hanover, NJ:Novartis; 2003.
Melmed S. Medical progress: acromegaly. N Engl J Med 2006;355:2558-2573.
Erratum in N Engl J Med 2007;356:879.
49
Clinical Features of Acromegaly
Melmed S. N Engl J Med 2006;355:2558-2573
Treatment Guidelines



Neurosurgery: TUMOR > 2cm =
REDUCED Success Rates
Medical Therapy
 Somatostatin Receptor
Ligands
 Dopamine Agonists
 GH Receptor Antagonist
Radiation Therapy
Mortality in Acromegaly
GH Level: most
impt. factor in
determining
survival in patients
with acromegaly
Adapted from Rajasoorya C, et al. Clin Endocrinol. 1994; 41: 95–102.
Updates




June 15, 2010: 10 days loading dose 100 mcg
Somatostatin SC q 8hrs was given, then
somatostatin 300mg/ IM once a month started
(+) headaches and dizziness
July 29, 2010: 2nd Post-op MRI showed further
decrease in the size of the pituitary mass
Scheduled to go to Boston this September to
seek further treatment at Massachusetts
General Hospital with pituitary expert, Dr. Anne
Klibanski
Summary





Pituitary tumors develop when specific types of
pituitary cells proliferate and oversecrete their
respective hormones.
Gigantism/ Acromegaly is a rare disorder
characterized by GH hypersecretion and
elevated IGF-1 levels
Almost all cases (98%), of acromegaly are
caused by a somatotrope adenoma
Early diagnosis and treatment is important to
prevent long term complications and mortality.
Controlling levels of GH in patients with
acromegaly improves survival
Thank you
and
Good Day!
:)
Genetically Predetermined
Height
 Calculate
Final Height prediction (midparental height)
› Girl
 In: (Father's Ht. - 5 + Mother's Ht.) / 2
 Cm: (Father's Ht. - 13 + Mother's Ht.) / 2
> F.O.
 In: (64- 5 + (63) = 122 /2= 61 = 5’1”
 Cm:(162.54-13 +(160))= 309.54 /2 =
154.77cm
1st TSS
12/2/09
2nd HD
12/3/09
am
3rd HD
12/3/09 12/4/09 12/5/09 12/6/09 12/7/09
night
3rd HD 4th HD 5th HD 6th HD 7th HD
RBS
108.24
160.98
229.15
111.68
139.19
Osmolality
Blood
(275-295)
296.0
309
308
302.0
302
303
297
Osmolality
Urine
(250-900)
1,036
75
106.9
Na (136-145)
BUN
Calculated
Osmolality
24 hr Intake
138
11.8
286
143
10.01
299
144
8.02
304
144
7.71
297
143
5.41
296
142
145
2580
11742
11742
5731
4520
6072
3600
24 hr Output
3350
9640
9640
8395
6990+
1x
7195
4400
TRANSSPHENOIDAL PITUITARY SURGERY: PRIMARY
INDICATIONS
1. Intolerance to
medical therapy
5. Resistance at
medical therapy
2. Pituitary
hemorrhage
6. Visual tract or CNS
compression
3. Relief of
compressive
hypopituitarism
4 .Personal choice
7. Tumor recurrence
after surgery or
radiation
8. Desire for
immediate
pregnancy with
macroadenoma