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Endocrinology and VHL: The adrenal and the pancreas

LAUREN FISHBEIN MD, PHDUNIVERSITY OF COLORADO SCHOOL OF MEDICINEDIVISION OF ENDOCRINOLOGY, METABOLISM AND DIABETESDIVISION OF BIOMEDICAL INFORMATICS AND PERSONALIZED MEDICINEOCTOBER 20, 2018

Overview

Definition of a hormone Adrenal gland Adrenal hormones Pancreas gland Pancreas hormones and enzymes

Endocrine Glands

Organs in our body that make hormones

https://s-media-cache-ak0.pinimg.com/736x/5e/eb/a4/5eeba4d996ec972d35980896fe5bb654.jpg

Master GlandMetabolismEnergyBP/HR

Food breakdown and metabolismSignals for energy usage and stores

EnergyBPMetabolism

Female hormones Male hormones

What is a hormone?

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What is a hormone?

Hormones are chemical messengers in the body Send messages about a particular function from

one cell to another

Liver

Receptor

Pancreas

Hormone

Can you name some hormones?

Common examples Thyroid hormone Estrogen Progesterone Testosterone FSH

Several other hormones come from the adrenal and pancreas glands

Adrenal gland

http://cf.ydcdn.net/1.0.1.66/images/main/A5adrenalgland.jpg

Adrenal Histology

http://district.bluegrass.kctcs.edu/shirley.whitescarver/BIO139Labhttp://dspace.udel.edu:8080/dspace/bitstream/19716/1826/2/cenamc1.GIF

1. Capsule2. zona

glomerulosa3. zona

fasciculata4. zona

reticularis 5. Adrenal

medulla

Medulla

cortex

fight or flight

aldosterone

glucocorticoids

androgens

adrenaline

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Adrenal Medulla

•Medulla is like a nerve ganglion and releases secretions (messages) directly into blood

http://www.studyinukraine.eu/spinal-cord-spinal-nerves-and-autonomic-nervous-system-with-figures/

Adrenal medulla hormones

(TH) (PNMT)

Rate limiting step Upregulated by cortisol

Also called adrenaline

Adrenaline(metanephrinescatecholamines)

Pheochromocytoma – leads to high blood pressure, rapid heart rate, sweating, headache, anxiety, tremors, increased blood sugar Some people with pheo have no symptoms

Flight or flight response

Pheochromocytoma (and Paraganglioma)

Pheochromocytomas (pheos) Tumors in the adrenal medulla Make adrenaline hormones About 20% of patients with VHL will develop

pheos

Paragangliomas Tumors in nerve bundles (ganglia) outside the

adrenal gland Similar to pheos Rare in patients with VHL

Petri et al British Journal of Surgery 2009

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Testing for pheochromocytoma

Blood test Plasma free metanephrines

24hr urine test Urine fractionated metanephrines

If found to have pheo, need pre-op blocking with special blood pressure medication called alpha blocker before surgery Blocks effects of high adrenaline

Ex: phenoxybenzamine, prazosin, doxazosinα-adrenergic receptor

VHL and Pheo

http://cf.ydcdn.net/1.0.1.66/images/main/A5adrenalgland.jpg

• VHL can be associated with bilateral pheochromocytomas

• “Can I survive with one adrenal gland?”

• What about no adrenal glands?

AldosteroneCortisolAndrogens (Testosterone)

Salt/water balanceControl BP

Steroid hormoneControls immune system,BP, metabolism, bone health, …

Male physical characteristics

aldosterone

cortisol

androgen

• Cortical sparing adrenalectomy sometimes used• We have medications to replace all of these hormones as needed

Adrenal Insufficiency

Caused by having no functional adrenal gland

Fludrocortisone (Florinef) Aldosterone replacement Salt/water balance hormone – maintains BP and

potassium/sodium levels Hydrocortisone/prednisone

Cortisol replacement BP/metabolism/blood sugar/other hormone Extra medication needed when sick or ill or before

surgery – “sick day rules”

aldosterone

cortisol

androgen

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VHL and the pancreas

VHL increases risk of several types of pancreatic masses and cysts Mass is solid Cyst is fluid filled Most will be benign

One type of mass seen is a pancreatic neuroendocrine tumor

Pancreatic Neuroendocrine Tumors (PNETs)

10-15% of all PNETs are associated with genetic syndromes ~9-17% of patients with VHL develop PNETs

Also seen in other syndromes Multiple Endocrine Neoplasia Type 1 (MEN1)Neurofibromatosis Type 1 (NF1)Tuberous Sclerosis Complex (TSC)

Pancreatic Neuroendocrine Tumors (PNETs)

Guidelines suggest removal of pancreatic masses over ~3cm in patients with VHL

The vast majority of PNETs in patients with VHL are benign and non-functional

Functional (F) vs Non-functional (NF)

F-PNETS Hormone elevated in blood + clinical syndrome

NF-PNETS No clinical syndrome even if hormone detectable

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Pancreas

http://biocrine.com/wp-content/uploads/2011/09/DAD2.pnghttp://quasargroupconsulting.com/anatomy/pancreaseCells.gif

Histology of pancreas

Exocrine pancreas

Endocrine pancreasIslet of Langerhans

Pancreas Hormones –Pancreas messengers

http://quasargroupconsulting.com/anatomy/pancreaseCells.gif

Exocrine pancreas –makes enzymes to digest food

http://www.animatedpancreaspatient.com/en-pancreas/view/m501-s4-exocrine-pancreatic-insufficiency-epi-slide-show

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Exocrine pancreas –makes enzymes to digest food

http://www.animatedpancreaspatient.com/en-pancreas/view/m501-s4-exocrine-pancreatic-insufficiency-epi-slide-show

Lack of nutrients for our body

Can cause bloating and diarrhea

Pancreas Hormones –Pancreas messengers

http://quasargroupconsulting.com/anatomy/pancreaseCells.gif

Insulin

Insulinoma– low blood sugar, confusion, vision changes, unusual behavior, rapid heart beat, sweating, shakiness, amnesia, eating every few hours, waking up at night to eat to avoid symptoms.

Liver

Receptor

Pancreas

Insulin

Muscle

Blood sugar

Blood sugar

Blood sugar

Blood sugar

Blood sugar

Blood sugar

Glucagon

Glucagonoma – blood sugar too high causing diabetes, weight loss, blood clots and a specific rash called necrolytic migratory erythema.

Liver

Receptor

Pancreas

Glucagon

Blood sugar

Blood sugar

Blood sugar

Blood sugar

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PancreasSomatostatin

Somatostatinoma – results in dysregulation of many endocrine hormones. Lowers insulin leading to diabetes. Slows GI motility which can lead to gallstones, intolerance to fat in the diet and leads to fatty diarrhea.

Receptor

Pancreas

Somatostatin

Nerve

glucagoninsulin

Pituitary picture from https://s-media-cache-ak0.pinimg.com/236x/3d/45/12/3d4512b044af3b0e5877a78499114d4e.jpg

Decrease acid Slow

motility Secrete pituitary

hormones

Vasoactive Intestinal Polypeptide(VIP)

VIPoma – causes huge amounts of very watery diarrhea leading to dehydration, low potassium and chloride

Liver

Receptor

Pancreas

VIP

glycogen

Energy

Pancreasbicarb

Majority of PNETs in VHL are non-functional

So why am I talking about the hormones?

A pancreas that is not functioning well or is absent due to surgery, may make too little hormone and enzymes We can replace these with medications

Abnormal functioning pancreas

Insulin is the main hormone of concern when absent Insulin deficiency causes diabetes mellitus We can replace insulin to control diabetes

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Insulin

Liver

Receptor

Pancreas

Insulin

Muscle

Blood sugar

Blood sugar

Blood sugar

Blood sugar

Blood sugar

Blood sugar

Abnormal functioning pancreas

Absent exocrine pancreas is another concern Absent enzymes cause bloating and discomfort

because food cannot be digested well We can control the symptoms with giving back the

enzymes before each meal

Exocrine pancreas –makes enzymes to digest food

http://www.animatedpancreaspatient.com/en-pancreas/view/m501-s4-exocrine-pancreatic-insufficiency-epi-slide-show

Summary

Definition of a hormone Adrenal gland Adrenal hormones Pancreas gland Pancreas hormones and enzymes

http://cf.ydcdn.net/1.0.1.66/images/main/A5adrenalgland.jpghttp://biocrine.com/wp-content/uploads/2011/09/DAD2.pnghttp://quasargroupconsulting.com/anatomy/pancreaseCells.gif

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Questions?