Pituitary disease for GIM: Lessons I have learned Jeannette Goguen, - - PowerPoint PPT Presentation

Pituitary disease for GIM: Lessons I have learned

Jeannette Goguen, MD, FRCPC University of Toronto, St. Michael’s Hospital Canadian Society of Internal Medicine

Annual Meeting 2017 Toronto, ON

CSIM Annual Meeting 2017

Goguen: Pituitary disease for the General Internist: Lessons I have learned --- November 2, 2017

Learning Objectives: By the end of the talk, you should have:

• 1. A general internist approach to the person with suspected or known

pituitary disease

• 2. Knowledge of common pitfalls in the diagnosis of pituitary diseases—

a and how to avoid them!

The following presentation represents the views of the speaker at the time of the presentation. This information is meant for educational purposes, and should not replace other sourcesof information or your medical judgment.

CSIM Annual Meeting 2017

Conflict Disclosures

Definition: A Conflict of Interest may occur in situations where the personal and professional interests of individuals may have actual, potential or apparent influence over their judgment and actions.

I have no conflicts to declare I will discuss no off-label therapeutics

Goguen: Pituitary disease for the General Internist: Lessons I have learned --- November 2, 2017

Overview

• 1. First year medicine in 5 minutes
• 2. Practical lessons I have learned:
• Clinical presentation & lab testing

First year Medicine in 5 minutes…

• Most are non-functional
• The most common

clinically functioning pituitary adenomas are prolactin producing adenomas.

**

*

** Neurohypophysis

*

Figure: Transverse section of the pituitary in patient who died from non-pituitary cause.

*

Adenohypophysis

One in 5 people in the general population have a pituitary adenoma

http://www.endotext.org/chapter/radiology-of-the-pituitary/

Sagittal view of sella Pituitary

Three Presentations of Pituitary Tumours

• 1. Mass effect:

History, Cranial nerve exam, Visual fields, MRI

• 2. Hyperfunction, from most to least common:

nil > ↑Prolactin > ↑GH > ↑ACTH > ↑TSH 3. Hypofunction, Deficiency of pituitary hormone(s): Usually lost in this order: GH, then LH and FSH, TSH, ACTH, Prolactin

(“Go Look For The Adenoma, Please”)

Mass Effect: Pituitary adenoma

Coronal view of normal pituitary A pituitary adenoma

V v V v

Chiasm Pituitary

Sphenoid sinus

Cn III, IV, V1, V2, VI

Internal carotid artery Cavernous sinus

Mass Effect

• Headache (h/a)
• Cranial nerve II – Optic chiasm
• Decreased visual acuity
• Decreased colour vision
• Visual field defect: bitemporal hemianopsia
• RAPD
• Pale optic disc
• Cranial nerves III, IV, V1, V2, VI - Cavernous sinus
• Diplopia Diplopia
• Facial numbness
• Abnormal extraocular movements

Hyperfunction

• 1. Prolactinoma (excess prolactin)
• Assess clinically for symptoms and signs of ↑prolactin
• Galactorrhea
• Hypogonadism: amenorrhea, erectile dysfn, ↓ libido
• Measure prolactin
• R/O other causes of ↑ prolactin
• No suppression test available

Hyperfunction

• 2. Acromegaly (excess GH)
• Assess clinically for symptoms and signs of GH excess

(growth of tissues, metabolic effects)

• Measure baseline GH and IGF-1
• Try to suppress ↑ GH (75 g oral glucose suppression test)

Hyperfunction

• 3. Cushing’s disease (excess ACTH)
• Assess clinically for symptoms and signs of ↑ cortisol
• Catabolic effects
• Metabolic effects, fat distribution
• Psychiatric effects
• Measure:
• ↑ Cortisol production (UFC)
• ↓ Cortisol suppressibility (1 mg DST)
• Loss of diurnal variation (↑ midnight salivary cortisol)

Hyperfunction

• 3. Cushing’s disease (excess ACTH)
• Assess clinically for symptoms and signs of ↑ cortisol
• Catabolic effects
• Metabolic effects, fat distribution
• Psychiatric effects
• Measure:
• ↑ Cortisol production (UFC)
• ↓ Cortisol suppressibility (1 mg DST)
• Loss of diurnal variation (↑ midnight salivary cortisol)

Check ACTH

Hypofunction

• Assess clinically for symptoms and signs of pituitary hormone

deficiency:

• LH + FSH: hypogonadism
• TSH: hypothyroidism (weight gain, cold intolerance, constipation, ↓ mentation)
• ACTH: hypocortisolism (↓ weight, ↓ BP, nausea + vomiting, weakness, fatigue)
• Prolactin: cannot breastfeed
• Measure baseline hormones:
• LH, FSH, estradiol or bioavailable testosterone
• Prolactin
• sTSH, free T4
• 8 AM cortisol, ACTH
• GH, IGF-1
• If low-normal, try to stimulate it
• Insulin tolerance test for ACTH and GH deficiency
• ACTH stimulation test with caveats

Hypofunction

• Assess clinically for symptoms and signs of pituitary hormone

deficiency:

• LH + FSH: hypogonadism
• TSH: hypothyroidism (weight gain, cold intolerance, constipation, ↓ mentation)
• ACTH: hypocortisolism (↓ weight, ↓ BP, nausea + vomiting, weakness, fatigue)
• Prolactin: cannot breastfeed
• Measure baseline hormones:
• LH, FSH, estradiol or bioavailable testosterone
• Prolactin
• sTSH, free T4
• 8 AM cortisol, ACTH
• GH, IGF-1
• If low-normal, try to stimulate it
• Insulin tolerance test for ACTH and GH deficiency
• ACTH stimulation test with caveats

Hypofunction

• Assess clinically for symptoms and signs of pituitary hormone

deficiency:

• LH + FSH: hypogonadism
• TSH: hypothyroidism (weight gain, cold intolerance, constipation, ↓ mentation)
• ACTH: hypocortisolism (↓ weight, ↓ BP, nausea + vomiting, weakness, fatigue)
• Prolactin: cannot breastfeed
• Measure baseline hormones:
• LH, FSH, estradiol or bioavailable testosterone
• Prolactin
• sTSH, free T4
• 8 AM cortisol, ACTH
• GH, IGF-1
• If low-normal, try to stimulate it
• Insulin tolerance test for ACTH and GH deficiency
• ACTH stimulation test with caveats

Lessons I have learned…

• I. Mass effect

Case 1: What do you see?

If you see cavernous sinus neuropathy and sellar lesion, think outside of the box:

Pituitary adenoma

If you see cavernous sinus neuropathy and sellar lesion, think outside of the box:

Pituitary adenoma

Metastatic cancer Apoplexy Lymphoma Unrelated disorder (e.g., Myasthenia gravis) Very nasty Pituitary tumour

Optic Chiasm: Bitemporal hemianopsia

I am a good person and so are you

http://pixgood.com/bitemporal-quadrantanopia.html

I am the law I ccca adm the law We are the way

Inferior Quadrantanopsia

I ran all the way to the end of the field and I ran all the way to the end of the field and I ran all the way to the end of the field and I ran all the way to the end of the field and

European glaucoma society - eurgs.org

Case 2: What is the diagnosis?

• 19 year old woman with amenorrhea 5 months, galactorrhea

and headaches

• Not sexually active, no other medical conditions, no medications
• c/o visual problems
• O/E unremarkable

Lab testing

Hormone Lab result Normal range Prolactin 250 < 25 ug/L FSH 2 3-20 IU/L LH 1 2-56 IU/L Estradiol 5000 110-1600 pmol/L sTSH 2 0.5-5 mU/L Free T4 16 10-20 pmol/L 8 AM Cortisol 600 200-600 nmol/L ACTH 5 3-15 pmol/L GH 4 1-5 ug/L IGF-1 400 80-500 ug/L

Lab testing

Hormone Lab result Normal range Prolactin 250 < 25 ug/L FSH 2 3-20 IU/L LH 1 2-56 IU/L Estradiol 5000 110-1600 pmol/L sTSH 2 0.5-5 mU/L Free T4 16 10-20 pmol/L 8 AM Cortisol 600 200-600 nmol/L ACTH 5 3-15 pmol/L GH 4 1-5 ug/L IGF-1 400 80-500 ug/L

Elevated prolactin

Serri, O. et al. CMAJ 2003;169:575-581

Causes of hyperprolactinemia

Serri, O. et al. CMAJ 2003;169:575-581

Causes of hyperprolactinemia

Case 3

18 year old woman presents with weight gain, and heavy periods

• Screening prolactin done be her gynecologist
• 150 ug/L (normal < 25 ug/L)
• She is referred to the GIM clinic

Lab testing

Hormone Lab result Normal range Prolactin 150 < 25 ug/L FSH 2 3-20 IU/L LH 1 2-56 IU/L Estradiol 100 110-1600 pmol/L sTSH 120 0.5-5 mU/L Free T4 4 10-20 pmol/L 8 AM Cortisol 600 200-600 nmol/L ACTH 5 3-15 pmol/L GH 4 1-5 ug/L IGF-1 400 80-500 ug/L

Lab testing

Hormone Lab result Normal range Prolactin 150 < 25 ug/L FSH 2 3-20 IU/L LH 1 2-56 IU/L Estradiol 100 110-1600 pmol/L sTSH 120 0.5-5 mU/L Free T4 4 10-20 pmol/L 8 AM Cortisol 600 200-600 nmol/L ACTH 5 3-15 pmol/L GH 4 1-5 ug/L IGF-1 400 80-500 ug/L

Case 3: MRI before and after Rx

Acromegaly

Miller Clinical Endocrinology (2011) 75, 226–231

Acromegaly

Case 4

• AC 68 yo man, married, retired carpenter
• Medical consult pre-op (TURP)
• c/o 1 yr history of sinus type pains in the front of his

head, hoarse voice, and dry throat.

• Also complains (when you ask him) that he has had

to get his weddings rings enlarged.

• X-ray of his sinus revealed sellar enlargement

Typical hands

Hormone testing

• Screening:
• IGF-1 900 (normal 200-400)
• Confirmatory:
• 75 gram oral glucose stimulation test:

All GH levels over 10 (normal < 1 ug/L)

Case 4 MRI

What do you have to consider perioperatively?

Monitoring for complications of acromegaly

Disease-related Headache, fatigue, hyperhydrosis IGF-1 q 6 mo, suppressed GH q yr Metabolic DM, lipids, BP, Ca2+, BMD CVD LVH, CAD, 2D ECHO; Skeletal Arthritis, CTS, OP, jaw malocclusion Respiratory Sleep apnea GI Colon polyps GU Kidney stones, BPH Other Hypopituitarism, MNG Mass effect Visual field defect, MRI

Monitoring for complications of acromegaly

Disease-related Headache, fatigue, hyperhydrosis IGF-1 q 6 mo, suppressed GH q yr Metabolic DM, lipids, BP, Ca2+, BMD CVD LVH, CAD, 2D ECHO; Skeletal Arthritis, CTS, OP, jaw malocclusion Respiratory Sleep apnea GI Colon polyps GU Kidney stones, BPH Other Hypopituitarism, MNG Mass effect Visual field defect, MRI

Acromegaly

Case 5

• 48 year old woman complains of coarsening of her features
• Always tired
• New onset hypertension and T2DM: A1C is 12%

Lab tests:

• Screen for acromegaly: IGF-1 350 (normal 150-400)
• Now what?

What causes misleading acromegaly testing?

What causes misleading IGF-1 levels?

Falsely ↓ IGF-1 Falsely ⇡ IGF-1

Malnourished state Pregnancy Liver disease Hypothyroidism Poorly controlled diabetes

Falsely unsuppressed GH

Obesity Liver disease Renal disease Poorly controlled diabetes Estrogen Rx/Pregnancy

Cushing’s

When should you consider this diagnose?

Cushing’s

When should you consider this diagnose?

• Classic features
• Severe hypertension/hyperglycemia/hypokalemia/osteoporosis
• Adrenal Cushing’s:
• Adrenal incidentaloma
• Hypotension post adrenalectomy (unrecognized adrenal Cushing’s)

Internal medicine workup for Cushing’s

Nieman JCEM 93: 1526 –1540, 2008)

Internal medicine workup for Cushing’s

Differential for Cushing’s syndrome

• (Exogenous)
• ACTH-dependent
• Pituitary
• Ectopic
• ACTH independent
• Adrenal

Case 6

• 26 year old woman with 12 lbs weight gain for “no reason” that

she cannot shed, face is rounder

• Normal A1c, normal blood pressure
• Seen in GIM clinic
• 1 mg O/N DST plasma cortisol 350 (normal < 50)
• What is going on?

Case 7

• 78 year old woman with Parkinson’s disease, postural dizziness

and weight loss, not hyperpigmented

• 8 AM cortisol 64 nmol/L, ACTH 2 pmol/L
• Referred to endocrine: Does she have adrenal insufficiency?
• (Rest of pituitary panel is normal, normal electrolytes)
• What is going on?

Things that mess up cortisol testing

Falsely elevated Falsely lower Glucocorticoid therapy

(Cortef, Prednisone, Prednisolone, adrenal gland)

Glucocorticoid therapy

(e.g. Dex, Fluticasone)

Altered sleep-wake cycle Altered sleep-wake cycle ⇡ Cortisol binding globulin: Estrogen Rx, pregnancy ↓ Cortisol binding globulin (malnutrition) ⇡ Clearance of dexamethasone (in DST) Polyuria (Urine free cortisol) Pseudo-Cushings

(obesity, alcoholism, depression, severe stress)

Back to Case 6

• 26 year old woman with 12 lbs weight gain for “no reason” that

she cannot shed, face is rounder

• Normal A1c, normal blood pressure
• Seen in GIM clinic
• 1 mg O/N DST plasma cortisol 350 (normal < 50)
• What is going on?

Back to Case 7

• 78 year old woman with Parkinson’s disease, postural dizziness

and weight loss, not hyperpigmented

• 8 AM cortisol 64 nmol/L, ACTH 2 pmol/L
• Referred to endocrine: Does she have adrenal insufficiency?
• (Rest of pituitary panel is normal, normal electrolytes)
• What is going on?

Case 8: Worst headache of his life…

• 58 year old man, collapses with worse headache of his life
• Meningismus, mild fever
• ICU: shock, cultures negative
• Cranial nerve III palsy
• Labs: Na+ 114 mmol/L, K+ 4.0, creatinine 100, TSH 2
• ACTH stimulation test: baseline cortisol 100, stimulates to 600
• ne hour after ACTH given
• Too large for MRI scan
• What is going on? What urgencies may need to be addressed?

Case 8: Worst headache of his life…

• 58 year old man, collapses with worse headache of his life
• Meningismus, mild fever
• ICU: shock, cultures negative
• Cranial nerve III palsy
• CT scan negative, Too large for MRI scan
• Labs: Na+ 114 mmol/L, K+ 4.0, creatinine 100, TSH 2
• ACTH stimulation test: baseline cortisol 100, stimulates to 600
• ne hour after ACTH given
• What is going on? What urgencies may need to be addressed?

Case 8: Worst headache of his life…

• 58 year old man, collapses with worse headache of his life
• Meningismus, mild fever
• ICU: shock, cultures negative
• Cranial nerve III palsy
• CT scan negative, Too large for MRI scan
• Labs: Na+ 114, K+ 4.0, creatinine 100, TSH 2, glucose 3
• ACTH stimulation test: baseline cortisol 100, stimulates to 600
• ne hour after ACTH given
• What is going on? What urgencies may need to be addressed?

Case 8: Worst headache of his life…

• 58 year old man, collapses with worse headache of his life
• Meningismus, mild fever
• ICU: shock, cultures negative
• Cranial nerve III palsy
• CT scan negative, Too large for MRI scan
• Labs: Na+ 114 mmol/L, K+ 4.0, creatinine 100, TSH 2
• ACTH stimulation test: baseline cortisol 100, stimulates to 600
• ne hour after ACTH given
• What is going on? What urgencies need to be addressed?

Case 8: Worst headache of his life…

• Na+ 114 hypoadrenalism and hypothyroidism (need free T4!)
• K+ 4.0 normal in secondary hypoadrenalism
• Hypoglycemia  acute hypoadrenalism and GH deficiency
• ACTH stimulation test: baseline cortisol 100, stimulates to 600
• ne hour after ACTH given consistent with new secondary

hypoadrenalism

Case 8: Worst headache of his life…

• Na+ 114 hypoadrenalism and hypothyroidism (need free T4!)
• K+ 4.0 normal in secondary hypoadrenalism
• Hypoglycemia  acute hypoadrenalism and GH deficiency
• ACTH stimulation test: baseline cortisol 100, stimulates to 600
• ne hour after ACTH given consistent with new secondary

hypoadrenalism

Case 8: Worst headache of his life…

• Na+ 114 hypoadrenalism and hypothyroidism (need free T4!)
• K+ 4.0 normal in secondary hypoadrenalism
• Hypoglycemia  acute hypoadrenalism and GH deficiency
• ACTH stimulation test: baseline cortisol 100, stimulates to 600
• ne hour after ACTH given consistent with new secondary

hypoadrenalism

Case 8: Worst headache of his life…

• Na+ 114 hypoadrenalism and hypothyroidism (need free T4!)
• K+ 4.0 normal in secondary hypoadrenalism
• Hypoglycemia  acute hypoadrenalism and GH deficiency
• ACTH stimulation test: baseline cortisol 100, stimulates to 600
• ne hour after ACTH given consistent with new secondary

hypoadrenalism

Treatment

• 1. ECFV support
• 2. Glucose administration
• 3. Hydrocortisone 100 mg i.v. q 8 hours
• 4. Hyponatremia:
• Restrict free water
• May need hypertonic saline
• May need Desmopressin
• 5. Later: L-Thyroxine
• 6. Surgery for Cranial nerve II involvement

Fieseriu JCEM 101: 3888 –3921, 2016

Diabetes insipidus

When would you see this?

• Postop transsphenoidal surgery
• Known DI, gets sick and comes to ED
• Unknown DI polyuria and polydipsia or hypernatremia

What should you remember?

• Keep the DDAVP going
• Watch for free water excess being given monitor the sodium very

carefully

Conclusions…Lessons I have learned

• Mass effect = TROUBLE if III, IV, V1, V2, VI
• Prolactinoma = BROAD differential
• Acromegaly = Easy to MISS! COMPLICATIONS
• Cushing’s/Adrenal insufficiency = CHALLENGE

Watch out for false lab results!

• Apoplexy = Can KILL: hypotension, hyponatremia,

hypoglycemia Surgery for Optic nerve compression

• Diabetes insipidus = Watch those SODIUM LEVELS

Pale optic disc

What causes misleading prolactin levels?

Macroprolactin (F+) and Hook effect (F-)

Smith Nature Reviews Endocrinology 3, 279-289 (March 2007)

Case 9

• 56 year old woman, homemaker, with 5 mm pituitary lesion
• Feels totally well, unremarkable physical examination
• 8 AM cortisol 64 nmol/L, ACTH 2 pmol/L
• Rest of pituitary panel is normal:
• TSH 4, free T4 14
• LH 25, FSH 50, estradiol < 70
• GH 1, IGF-1 250
• Prolactin 9
• What is going on?