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

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…

One in 5 people in the general population have a pituitary adenoma ** Neurohypophysis ** • Most are non-functional • The most common clinically functioning pituitary adenomas are * prolactin producing adenomas. * * Adenohypophysis Figure: Transverse section of the pituitary in patient who died from non-pituitary cause.

Pituitary Sagittal view of sella http://www.endotext.org/chapter/radiology-of-the-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 Chiasm Pituitary Cn III, IV, V V Cavernous V1, V2, v v sinus VI Internal carotid Sphenoid artery sinus Coronal view of normal pituitary A pituitary adenoma

Mass Effect • Headache (h/a) • Cranial nerve II – Optic chiasm • Decreased visual acuity • Decreased colour vision • Visual field defect: bitemporal hemianopsia • RA PD • Pale optic disc • Cranial nerves III, IV, V 1 , V 2 , 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) Check ACTH • ↓ Cortisol suppressibility (1 mg DST) • Loss of diurnal variation ( ↑ midnight salivary cortisol)

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

Optic Chiasm: Bitemporal hemianopsia I am a good person and so are you I am the law I ccca adm the law We are the way http://pixgood.com/bitemporal-quadrantanopia.html

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

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

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

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?