HONEY, I BLEW UP THE KID! A SUPER Sized Medical Grand Rounds
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Transcript of HONEY, I BLEW UP THE KID! A SUPER Sized Medical Grand Rounds
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, & work-up 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
121 cm
154 cm
168 cm
185 cm
191cm
198 cm
> 95th %
3 mos PTA (+) “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 abnormalitiesCONSULT
(-) 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 bpmRR 20 cpm T 36.3°C
Anthropometricswt: 95.5kg ht: 198cmBMI:
24.1(overweight)
upper segment: 84.84 cm
lower segment: 113cm
U/L segment: 0.76
6’6”
Anthropometrics
Arm span - 205.74 cm
ht: 198cm
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
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
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: ++
17 year old female
Tall stature Delayed puberty Headaches Visual field defect
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
Salient Features
DifferentialsTall Stature Pubertal
DelayHeadache &
Visual Changes
Familial Pituitary MassChromosomal Abnormalities
PhysiologicPathologicPituitary MassChromosomal Abnormalities
AstigmatismMigraineIntracranial Tumor
Initial Impression
Gigantism probably secondary to Growth hormone secreting pituitary adenoma with Hypogonadotrophic Hypogonadism
Work UpClinical Features of
Gigantism/ Acromegaly
IGF-1 Level
Normal for Age & Gender Elevated
Measure OGTT & GH levels
Adequate GH suppression
Inadeguate / no GH
suppression
Pituitary MRI
Dx excluded
Piuitary Mass
Assess likelihood of surgical success
Surgery
Medical
(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).
75g Oral Glucose Tolerance Test TIME (mins)
Growth Hormone(n.v. 0-7)
FBS IGF-1 (193-731 ng/ml)
0 203.229
90.98 1244
60 mins 208.948
109.17
120 mins
199.466
67.32
Work up
NONSUPPRESSION
MRI of Brain (+)pituitary mass Referred to a neurosurgeon
› Transsphenoidal Surgery
GENETIC STUDY AUTOMATED PERIMETRY
VISUAL FIELD TEST
LEFT EYE RIGHT EYETEMPORAL TEMPORAL HEMIANOPSIA 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
F- Testosterone 27.346 (normal)
F- Estradiol 19.845 (premenarcheal)
10/16/09 F-DHEAS (0.94-11.67 umol/L) 8.484
10/19/09Cortisol 8am (138-690 nmol/L) 420.960 9am 279.550
10/16/09ACTH (<50 pg/ml) 15.231
9/12/09TSH IRMA (0.27- 3.75) 0.621FT4 (8.8- 33) 23.413
Pelvic Ultrasound
Infantile uterus, with thin endometrium (3mm)
Small left ovary, right ovary not visualized
infantile uterus, with thin endometrium (3mm), small left ovary, and right ovary not visualized. infantile uterus, with thin endometrium (3mm), small left ovary, and right ovary not visualized.
Skeletal Survey
Bone Aging
Bone Mineral Density
SPINESPINE FEMORAL NECKFEMORAL NECK
NORMALNORMAL
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/FSPECIMEN NO.: 10-SR-0282
IMMUNOHISTOCHEMICAL STAIN: GROWTH HORMONE, POSITIVE (>90%)
IMMUNOHISTOCHEMICAL STAIN PROLACTIN, POSITIVE (<5%)
75g Oral Glucose Tolerance Test9/15/09(Pre-op)
1/15/10(Post-op)
TIME Growth Hormone (n.v. 0-7)
FBS Growth Hormone (n.v. 0-7)
FBS
0 203.229 90.98 378.709 93.19
60 mins
208.948 109.17
415.996 109.17
120 mins
199.466 67.32 419.659 83.7
Follow Up
NONSUPPRESSIONNONSUPPRESSION
IGF-1(193-731 ng/ml)
9/11/09Pre-op
1/15/10Post-op
0 1244 1075
Sex Hormones 9/16/09Pre-op
1/20/10Post -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
9/17/09Pre-op
1/21/10Post- op
Estradiol pg/ml 19.845 (premenarcheal)
19.496 (premenarcheal)
Follow Up Repeat MRI 3 mos. after surgery: mass
slightly decreased but appears unchanged
April 29, 2010: Repeat transsphenoidal surgery
9/16/09(Baseline)
1/20/101st Post -op
5/19/102nd Post -op
F-Prol (3.6-18.9 ng/ml)
255.499 383.588
F-FSH (3.3-8.8 mlU/ml))
0.366 0.001 0.76
F-LH (0.6-6.2 mlU/ml)
0.001 0.018 0.26
Updates
75g Oral Glucose Tolerance Test 9/15/09 BASELINE
1/15/10 1st Post-op
6/4/10 2nd Post-op
Growth Hormone (0-7)
FBS Growth Hormone (0-7)
FBS Growth Hormone (0-7)
0 203.229 90.98 378.709 93.19
60 mins 208.948 109.17
415.996 109.17
120 mins
199.466 67.32 419.659 83.7 256.873
Updates
NONSUPPRESSION NONSUPPRESSION NONSUPPRESSION
Insulin Growth Like Factor 1
9/11/091st Preop(193-731)
1/15/101st Postop
4/15/102nd Preop
5/19/102nd Postop(1mo)
7/16/102nd
PostOp
(3 mos)
0 1244 1,075 1437 >1600 1429
Updates
17 year old female› Tall stature› Prominently enlarged
hands and feet› Slightly widened and
thickened nose and lips› Widened upper tooth gap
Delayed pubertyTanner stage 1 breaststanner 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
CASE SUMMARY
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
BITEMPORAL HEMIANOPSIA
HEADACHES
COMPRESSION OF PITUITARY STALK
HYPERPROLACTINEMIA HYPOPITUITARISM
Hypothalamic Pituitary AxisHypothalamus
Pituitary
Trophic H.
Target Organ
In our patient..HORMONE HYPERSECRETION
Growth Hormone Secreting Adenoma (>90%)
Prolactin Co-Secreting Adenoma (<5%)
(Mammasomatotrophs)
GIGANTISM
Lafferty, A.R & Chrousos, G.P., Pituitary tumors in Children & Adolescents. J. Clin. Endccinol. Metab. 1999.84:4317-4323.
Combined GH and Prolactin over-secretion common inearly childhood gigantism
GIGANTISM VS. ACROMEGALY
TIMING OF GH EXCESS
During period of active growth
Open epiphyseal plates
After epiphyseal closure
INCIDENCETotal cases reported only in the hundreds
3- 4 cases/million
TALL STATURE Cardinal feature 10% Cases
Identical twins, 22 years old, excess GH secretion
49
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.
>98%
Clinical Features of Acromegaly
Melmed S. N Engl J Med 2006;355:2558-2573
Neurosurgery: TUMOR > 2cm = REDUCED Success Rates
Medical Therapy Somatostatin Receptor
Ligands Dopamine Agonists GH Receptor Antagonist
Radiation Therapy
Treatment Guidelines
Mortality in AcromegalyMortality in Acromegaly
Adapted from Rajasoorya C, et al. Clin Endocrinol. 1994; 41: 95–102.
GH Level: most impt. factor in determining
survival in patients with acromegaly
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 (mid-parental 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 12/3/09am
12/3/09 night
12/4/09 12/5/09 12/6/09 12/7/09
2nd HD 3rd HD 3rd HD 4th HD 5th HD 6th HD 7th HD
RBS 108.24 160.98 229.15 111.68 139.19 106.9
OsmolalityBlood (275-295)
296.0 309 308 302.0 302 303 297
OsmolalityUrine (250-900)
1,036 75
Na (136-145) 138 143 144 144 143 142 145BUN 11.8 10.01 8.02 7.71 5.41Calculated Osmolality
286 299 304 297 296
24 hr Intake 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
7. Tumor recurrence after surgery or radiation
4 .Personal choice 8. Desire for immediate pregnancy with macroadenoma