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