10/24/2015 An Image Tells a Thousand Words1920s Vaudeville Medical - - PowerPoint PPT Presentation

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UCSF CME October 2015 S.Melmed

Medical Approach to Large Pituitary Masses

An Image Tells a Thousand Words……1920’s Vaudeville

“Lofty” Albert Kramer 1897-1976 height 2.69 m (8’ 9¾”) With brother-in-law “Seppetoni” Josef height 87 cm (2’ 10”)

Lateral Cephalometric Radiograph

Agrawal BMJ Case Rep. 2013

• 36-yr-old barber
• Clicking jaw symptoms of TMJ
• Had to enlarge his scissors

because fingers didn’t fit

• IGF-I 1600 ng/mL GH 14

ng/mL

Etiology of Pituitary Mass

Neoplastic Adenoma Meningioma, Germinoma Rathke’s cyst Craniopharyngioma Hypothalamic hamartoma, Gangliocytoma Metastases Lymphoma and leukemia Infiltrative / Inflammatory Hypophysitis Sarcoidosis Histiocytosis X Hemachromatosis Vascular Apoplexy Pregnancy-related Sickle cell disease Arteritis Infections Fungal Parasitic Pneumocystis TB

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IGF-1 1150 ng/ml

Image Challenge

• A. Craniopharyngioma
• B. Cushing disease
• C. Meningioma
• D. Prolactinoma
• E. Rathke cleft cyst

What is the most likely diagnosis in this 32-year-old man? Prolactinoma is the most common cause of a pituitary adenoma. This large tumor regressed substantially following cabergoline treatment .

Male Macroprolactinomas

Anwuzia-Iwegbu BMJ 2013 Ahmed NEJM 2010

Cabergoline-induced shrinkage

Giant pituitary adenoma

Fleseriu J Neurooncol 2006

PRL 103 ng/mL Stalk Compression?

PRL

Signal Antibody Capture Antibody

HOOK EFFECT

PRL on dilution: 13,000 ng/ml

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Prolactinoma: Cabergoline-induced pneumocephalus detected by brain CT

Machicado JCEM 2012

Bromocriptine-induced brainstem angulation with invasive prolactinoma

Lou JCEM 2013

CT shows bony destruction of clivus and skull base

Right ovary Left

• vary

Right ovary Van Wijk NEJM 2011

FSH-oma E2 23,501 pmol/l LH <0.1 IU/l FSH 27 IU/l

Hypo/hypergonadism ?

Newnham NEJM 2008

PITUICYTOMA Thyroid transcription factor 1 Amenorrhea, Abdominal Pain, and Weight Gain

Giant adenomas

Cappabianca Acta Neurochir, 2014

Sagittal

Sphenoid sinus Suprasellar extension

Coronal

Suprasellar vessel encroachment

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Non-functioning Adenomas: Recurrence-free Survival

Mayson, J Neurooncol, 2014 Losa, J Neurosurg, 2008

Invasion of neighboring structures

• rapid growth
• recurrence
• diameter >4 cm
• resistance to medical therapy
• extracranial metastasis (carcinoma)

Atypical Pituitary Adenomas

WHO 2004

Aggressive,invasive ,pleomorphic increased mitotic activity, Ki-67 >3% p53 immunoreactivity

ACTH p53 Ki-67

Zada J Neurosurg 2011

Silent Corticotroph Adenoma

Nonfunctioning Large/Invasive Cytologically Atypical Plurihormonal

PAS POMC ACTH

69 yr old man with acute food poisoning

In good health when eating breakfast at restaurant Stomach cramps, vomiting, bloody diarrhea, Severe headache acute bacterial enterocolitis Late p.m.: Diplopia Right ptosis Non-reactive pupils 3rd, 4th, 6th nerve palsies

Apoplexy

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Hypophysitis with stalk thickening

Coronal T1 post-contrast

M.Maya

Hypophysitis with stalk thickening

Sagittal T1 post contrast

M.Maya

Hypophysitis

Sci Trans Med 6(230):1-11, 2014

GH PRL TSH ACTH FSH S-100 Anti-CTL4

Sci Trans Med 6(230):1-11, 2014

Hypophysitis

Monocytes CD45 F4/80

CTLA-4 blocking AB Control Injections:

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Hypophysitis

J Clin Endocrinol Metab 99:4078, 2014

Pre-Rx Rx Rx Post-Rx

Survival

Hypophysitis positively predicts metastatic melanoma survival

100 80 60 40 Percent survival 10 20 30 40 50 60 70 No Hypophysitis Months after treatment initiation + Hypophysitis, p=0.05

Lessons learned………

Significance: All cancer patients receiving CTLA-4 blockers should be screened for pituitary dysfunction and hormone replacement initiated. Combination with PD-1 blockade may be an added risk factor. Hypophysitis may be a positive survival predictor

Obesity : Hypothalamic tumor

Müller Horm Res 2008

Giant craniopharyngioma

MRI T2 : hyperintense lesion All 3 cranial fossae Extending as low as C2 anterior to the brainstem.

Garg Ped Neurosurg 2013

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Adamantinomatous Craniopharyngioma Containing Teeth

Beaty N Engl J Med 2014.

Aggressive parasellar mass Intermittent Facial Flushing and Diarrhea

Mc Cormack NEJM 2014

Octreoscan: Chronic acromegaly Octreoscan MRI

Melmed, NEJM 322, 1990

Octreoscan: Pituitary Carcinoma

38-year-old female Post-GTT GH 27 ng/mL IGF-1 498 ng/mL S/P transsphenoidal surgery 5 years prior MRI nl

Greenman JCEM 1996

20 10 30 40 50 60 –30d –7d 3 h 9 h 18 h 40 h *A:V gradient 1:7 Surgery* GH (ng/mL)

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Melmed & Jameson Harrisons Internal Medicine 2015

May require disease- specific therapy

Non-secreting Pituitary Mass

Differential diagnosis by MRI and clinical features Dynamic pituitary reserve testing Non-functioning adenoma Microadenoma Macroadenoma MRI

Surgery Observe

Other sellar mass Surgery Histologic diagnosis MRI Exclude aneurysm

Trophic hormone testing and replacement Trophic hormone testing and replacement

Follow-up: MRI

Low risk of visual loss

Lawson JCEM 2008

Pituitary Parathyroid Pancreas

Pituitary Imaging………………

Melmed NEJM 1985

Galactorrhea Elevated GH and IGF1 Small pituitary gland

Ectopic GH

• 2
• 1

1 2 3 4 24 48 72 144 5 10 15 20 25 30 35 40 45 50

• 72

SERUM GH (ng/ml) hours *

TumorA/V

GH GRADIENT 34/368 * Aggressive GH-secreting tumor……………………….

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Reserves