PITUITARY: JUST THE BASICS PART 2 THE PATIENT
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1 PITUITARY: JUST THE BASICS PART 2 THE PATIENT
2 DISCLOSURE Relevant relationships with commercial entities none Potential for conflicts of interest within this presentation none Steps taken to review and mitigate potential bias N/A
3 LEARNING OBJECTIVES This lecture is designed to meet the following end-of-week learning objectives: 1. Describe the tests of function of the pituitary, thyroid and adrenal glands 2. Describe the importance of dynamic testing for pituitary and adrenal disease (if it is low, stimulate it, if it is high, suppress it) 3. Describe the presentation of pituitary/thyroid/adrenal disease: Hyperfunction, hypo function, mixed hyper- and hypo-function, masses 4. Describe the role of imaging in endocrine disorders (pituitary MRI, Thyroid ultrasound, radioactive iodine, thyroid scan, adrenal CT or MRI)
4 MODULE OBJECTIVES By the end of this module, you should be able to: 1. Describe the clinical presentation of pituitary tumours, including: Mass effect Hyper-function Hypo-function 2. Describe investigation of pituitary tumors, including nonfunctional tumours and functional tumours (Prolactinoma, Acromegaly and Cushing s disease)
5 Pituitary The Master Gland: Sagittal (side) view of sella
6 Physiology of the Pituitary Master gland Each hormonal axis has its own unique functions and feedback loop control, disease presentations, investigations and treatments Anterior pituitary: 1. Growth hormone 2. Prolactin 3. TSH 4. ACTH 5. LH & FSH Posterior pituitary: 1. ADH 2. Oxytocin
7 PRINCIPLES USED TO DIAGNOSE PITUITARY DISORDERS 1. Focus on benign pituitary adenomas 2. Most are very small, and discovered incidentally 3. Large adenomas can cause problems: a. Overproduce hormone (can happen with small ones, too) b. Mass effect, including reduced pituitary function 4. When a hormone level is abnormal, this can be physiological or pathological. a. Pathological: i. Low and can t be stimulated ii. High and can t be suppressed
8 PRINCIPLES USED TO DIAGNOSE PITUITARY DISORDERS (for you to read later) 1. There are many kinds of pituitary disease processes, we will focus on the most common, pituitary adenomas (benign tumours arising from pituitary hormone-producing cells). 2. Most pituitary tumours are very small, and do not cause any symptoms, and are discovered incidentally when the brain is imaged for other reasons. 3. Pituitary tumors become problematic when they overproduce a pituitary hormone or grow large enough to have mass effect, including reducing the normal hormones produced in cells in the normal gland, headaches, cranial nerve dysfunction. 4. When a hormone level is abnormal, this can be physiological or pathological. It is pathological if it is low and can t be stimulated into the normal range or it is high and can t be suppressed into the normal range.
9 THREE PRESENTATION OF 1. Mass effect PITUITARY LESIONS 2. Hyperfunction 3. Hypofunction
10 THREE PRESENTATION OF PITUITARY LESIONS 1. Mass effect Can present with Headache Cranial nerve defects Hypopituitarism from stalk compression (and a rise in Prolactin Stalk effect ) See separate video Cranial nerve exam in pituitary disorders
11 MASS EFFECT: CORONAL VIEW Cr III, IV, V1, V2, VI Chiasm= Cr II V v Tumour V v Pituitary Cavernous Sinus (red) Internal carotid artery Sphenoid sinus Coronal (front) view of normal pituitary A pituitary adenoma
12 2. HYPERFUNCTION OF THREE AXES Prolactin GH ACTH
13 PROLACTIN HORMONE AXIS & FUNCTION Hypothalamus Hypothalamus GnRH + - Pituitary Pituitary + Prolactin LH, FSH + Milk Breast Ovaries/ Testes hypogonadism
14 PROLACTIN OVERPRODUCTION PROLACTINOMA PRESENTATION Presentation Baseline lab Rule out other causes for prolactin Suppression testing Galactorrhea Prolactin Pregnancy Not done Amenorrhea Breast feeding Infertility T4 Erectile dysfunction Hypogonadism Stalk effect Drugs Renal failure Liver failure
15 GROWTH HORMONE AXIS & FUNCTION
16 GH OVERPRODUCTION ACROMEGALY PRESENTATION
17 ACROMEGALY ( GH) Presentation Baseline lab Other causes for GH Suppression testing - Bone + tissue growth - Metabolic syndrome -Heart disease IGF-1 GH Almost always pituitary adenoma Glucose suppression test to suppress GH -Carpal tunnel syndrome -Sleep apnea -Osteoarthritis -Colon polyps
18 ACTH HORMONE AXIS & FUNCTION
19 ACTH OVERPRODUCTION CUSHING S DISEASE PRESENTATION Orth, Uptodate 2014, Cushing s clinical features
20 CUSHING S SYNDROME ( CORTISOL) - Rule out exogenous steroid use Presentation -Central obesity -Abnormal fat deposition (supraclavicular, dorsal, round face) -Metabolic syndrome -Bruising -Weakness -Osteoporosis Lab testing: (at least 2/3 below abn) 1. cortisol (in 24 hour urine collection) 2. midnight salivary cortisol 3. AbN dexamethasone suppression test Causes for cortisol (location of tumor) ACTH -pituitary -ectopic tumor (not in pituitary) ACTH - Adrenal
21 3. HYPOFUNCTION Order in which hormones are lost: Go-Look-For-The-Adenoma-Please GH-LH-FSH-TSH-ACTH-Prolactin Expect low pituitary and target organ hormones All pituitary hormones are tonically stimulated by hypothalamic hormones, except for Prolactin which is tonically suppressed.
22 HYPOFUNCTION Assess clinically for symptoms and signs of pituitary hormone deficiency: GH: short stature in childhood onset of disease LH + FSH: hypogonadism (erectile dysfunction, amenorrhea, loss of libido, decreased shaving) TSH: hypothyroidism (weight gain, cold intolerance, constipation, decreased mentation) ACTH: hypocortisolism (weight loss, hypotension, nausea + vomiting, weakness, fatigue) Measure baseline hormones: -8 AM cortisol, ACTH, stsh, free T4, GH, IGF-1, LH, FSH, estradiol or bioavailable testosterone, prolactin If low-normal, try to stimulate it (insulin tolerance test for ACTH and GH deficiency)
23 STIMULATION TESTING FOR HYPOPITUITARISM Insulin tolerance test: iv insulin given to induce hypoglycemia, which stimulates cortisol and GH Can also give GnRH to stimulate FSH and LH to determine if there is hypogonadism (this is usually obvious clinically, and unnecessary to do)
24 DIAGNOSE HYPOFUNCTION: If baseline hormone level is very low or if it is modestly low and does not respond appropriately (to target) in a stimulation test
25 PUTTING IT ALL TOGETHER A patient presents with a 1 cm pituitary tumour: 1. Assess for mass effect 2. Assess for hyperfunction 3. Assess for hypofunction
26 MODULE OBJECTIVES By now, you should be able to: 1. Describe the clinical presentation of pituitary tumours, including: Mass effect Hyper-function Hypo-function 2. Describe investigation of pituitary tumors, including nonfunctional tumours and functional tumours (Prolactinoma, Acromegaly and Cushing s disease)
27 Additional summary slides follow, for your reading.
28 PUTTING IT ALL TOGETHER 1. ASSESS FOR MASS EFFECT: Headache Cranial nerve exam Ophthalmologist + Visual field testing MRI of sella
29 PUTTING IT ALL TOGETHER 2. ASSESS FOR HYPERFUNCTION: Hormone History and physical exam Lab testing Treatment Prolactin Hypogonadism Galactorrhea, esp women Prolactin Dopamine agonist (rarely OR, radiation) GH Acromegaly IGF-1 screen (GH suppression test if hi IFG-1) Surgery Somatostatin agonist (rarely radiation) ACTH Cushing s If indicated: 1 mg DST 24 hr UFC MN salivary cortisol ACTH Surgery (rarely radiation, medication or bilateral adrenalectomy)
30 PUTTING IT ALL TOGETHER 3. ASSESS FOR HYPOFUNCTION Hormone GH History and physical exam Short stature child Not thriving adult Lab testing IGF-1 (GH with ITT) LH, FSH Hypogonadism LH, FSH Estradiol OR Bioavailable testosterone TSH Hypothyroidism stsh Free T4 ACTH Hypocortisolism ACTH 8 AM Cortisol (Cortisol with ITT) Prolactin Can t breastfeed Low prolactin Treatment GH (selective in adults) Estrogen/ Progesterone Testosterone Levo-thyroxine Hydrocortisone
31 Presentation Mass effect function (most have no function) function Diagnosis - Examine -prolactin -GH cranial nerves II-VI -visual field testing -MRI -ACTH/cortisol (Consider other causes for function) Measure baseline hormones Suppression testing - Stimulation test (insulin tolerance test) Treatment Drugs Surgery Radiation Drugs Surgery Radiation Hormone therapy (T4, cortisol, sex hormones, GH, ADH)
32 WHAT ABOUT THE POSTERIOR PITUITARY? ADH: Water conservation in kidney Can be disturbed with hypothalamic lesions of after transphenoidal surgery Deficiency: Central Diabetes insipidus See medskl - Polyuria Excess: Syndrome of Inappropriate ADH (SIADH) See Week 35 Oxytocin: no known clinical problems with excess or deficiency
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