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Evaluation of theChild with Suspected Pituitary Disease

Craig Alter, MD University of Pennsylvania

Children’s Hospital of Philadelphia

What we will cover…

*What laboratory tests to order

*MRI: common pituitary findings

* Diabetes Insipidus

* Craniopharyngioma

* Prolactinoma

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Pituitary Hormones• LH, FSH

• TSH

• GH

• Prolactin

• ACTH

• ADH (Vasopressin)

• Oxytocin

Pituitary Labs

• LH, FSH: ultrasensitive or pediatric assay

testosterone, estradiol

• TSH: free-T4, TSH, not TSH alone

• GH: IGF-1, IGFBP3

• Prolactin may need serial dilutions

• ACTH 730-8am fasting cortisol

• ADH (Vasopressin):

fasting Ur Osm, Osm, Chem panel

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IGF-1

• 37 ng/ml (very low!)

MRI Findings:

* Mass in the pituitary

* Absent posterior pit bright spot

* Considerations:craniopharyngioma, Rathke’s cleft cyst, adenoma

Pituitary Diagnoses• Craniopharyngioma

• Rathke’s Cleft cyst

• Pars intermedia cyst

• Hamartoma

• Gem Cell tumors (germinoma)

• Histiocytosis

• Adenoma, Prolactinoma

• Optic nerve hypoplasia

• Ectopic Posterior Pituitary

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Pituitary Diagnoses• Craniopharyngioma: calcifications, CT can

help, benign, cysts can recur after surgery

• Rathke’s Cleft cyst

• Pars intermedia cyst: small, < 3 mm, benign

• Hamartoma: associated with precocity

• Gem Cell tumors (germinoma) - DI

• Histiocytosis (DI)

• Adenoma, Prolactinoma

• Optic nerve hypoplasia

Next patient• Growing poorly

• Delayed puberty

• Perhaps adrenal insufficiency symptoms

• Drinks a great deal, nocturia

• Breast discharge

• Fatigue

• Visual complaints, headaches

• Just get the MRI already!!

CaseDavid Ingelfinger

*14 6/12 male polydipsia/uria

*6 months increased thirst

*Up 9 times/night

*Urine: 8 liters/day

*Failed trial restriction

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Review of Systems DI

*Rare absentee from school

*Weight loss 117-->106 lbs

*Less appetite

*No headaches/visual complaints

Physical Examination DI

*Energetic,well appearing

*Growth normal

*Tanner 4, 12 ml testes

*Visual fields normal

Laboratory Workup

LabQuest

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Laboratory Workup DI

Sodium 142-146

T4 6.6 ug/dL TSH 4.4

IGF-1 403 ng/ml IGFBP3 4.6

Cortisol 19.5 ug/dL

Prolactin 36 ng/ml

Glucose 86 mg/dl

Water Deprivation

*12 hours:

*Sodium 150

*Serum Osm 308

*Urine Osm <225

*Urine Osm 513 (+vasopressin)

Gadolinium Contrast,to be or not to be?

Hypothalamus

Pit. Stalk

Pituitary

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Gadolinium Contrast,to be or not to be?

Gadolinium Contrast,to be !

MRI with Normal Pituitary

Infundibular stalk

Pituitary

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Normal Bright Spot

MRI with Thickened Pituitary Stalk

Thickened infundibular stalk

Pituitary

Initial MRI of DI patient

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MRI Results

*Loss of bright spot

*Fullness of Infundibular stalk

What next?

A) Follow-up...when?

B) MRI: repeat it?

C) Refer for biopsy?

D) Obtain a bone age?

DI in Childrenetiology (n=79)

* Idiopathic 52%

* Intracranial tumor 23%Germinoma 1/3Cranio 1/3Post-surg 1/3

* Histiocytosis 15%

* Familial 6%

* Post-trauma 3%

* Autoimmune 1%

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Diagnosis of DI Based on Ageat Presentation

Diagnosis of DI Based on Ageat Presentation

CNS Germinoma

* 7.8% of brain tumors in children

* 1/3

* 2.5 years

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CNS Germinoma

* 7.8% of brain tumors in children

* 1/3 present with diabetes insipidus

* 2.5 years - median time until Dx(after DI)

Normal Bright Spot on T1

MRI in DI:Loss of hyperintensity?

*Sensitivity: 94%(rest disappears in time)

*Specificity: 90% except under 2 mo old

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Normal Pituitary Stalk

*Normal Stalk 46%*Children with normal stalk:

Idiopathic 52%Histiocytosis 19%Familial 14%CNS malform 11%Germinoma 3%

Pituitary Stalk Thickening

*Stalk thickened 37%

*Children with thick stalk:Leger Maghnie

n=26 n=29

Idiopathic 65% 62%Histiocytosis 19% 17%Germinoma 15% 17%

Anterior Pituitary Disease?

*Some deficit 61%

*Of those w/ deficiency:GH deficiency 59%Hypothyroidism 18%Hypogonadism 24%Adrenal insuffic. 22%

*Prolactin > 20 30%

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SummaryDiagnosis of Germinoma

*Loss of bright spot --> not risk

*Stalk thickening --> 17% risk

*No thickening --> 3% risk

*Progress thickening --> risk

*Ant Pit Disease --> not risk

*CSF Positive for hCG --> risk

Diagnosis of GerminomaWhat is the median time

until Diagnosis?

*2.5 years

*1 year in the NEJM Study

==> frequent MRI indicated

ConclusionDI in Children

*1/3 germinoma present w/ DI

*Data show under 5 yr low risk

*MRI findings in DIloss of bright spotpituitary stalk thickening

*PST increases risk of tumorMRI needs f/u q3-6 mo.

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Tanner 4

MRI with Ectopic Posterior Pituitary

Ectopic Posterior Pituitary (EPP)

*DI not common

*Risk of Multiple Pituitary Hormone Disease (MPHD)

*Risk of Adult GHD

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Precocious Puberty

*Normal

*Hamartoma (neural cells, wrong location)

*Mass outside of the sella

Harmartoma

Understanding the MRI• Bright spot present? (absent in Central DI)

• Ectopic posterior pituitary

(GHD, panhypopit, no DI)

• Stalk thickened? (infiltrative disorders)

• Optic nerve compression?

• Cysts or tumors?

• Calcifications

• Pineal region (germinoma)

• Optic nerve hypoplasia, corpus callosum

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